Journal of the Italian Society of Anatomic Pathology and Diagnostic

Transcript

Cited in Index Medicus/MEDLINE, BIOSIS Previews, SCOPUS
Journal of the Italian Society of Anatomic Pathology
and Diagnostic Cytopathology,
Italian Division of the International Academy of Pathology
ORIGINAL ARTICLES
313 The role of 2D bar code and electronic cross-matching in the reduction
of misidentification errors in a pathology laboratory. A safety system assisted
by the use of information technology
G. Fabbretti
318 Cytologic re-evaluation of negative effusions from patients with malignant
mesothelioma
V. Ascoli, D. Bosco, C. Carnovale Scalzo
325 Intra-operative frozen section technique for breast cancer: end of an era
E. Manfrin, A. Remo, F. Falsirollo, G.P. Pollini, A. Parisi, A. Nottegar, F. Bonetti
Periodico bimestrale – POSTE ITALIANE SPA - Spedizione in Abbonamento Postale - D.L. 353/2003 conv. in L. 27/02/2004 n° 46 art. 1, comma 1, DCB PISA
Aut. Trib. di Genova n. 75 del 22/06/1949
331 The diagnostic accuracy of cervical biopsies in determining cervical lesions: an audit
J. Wang, M. El-Bahrawy
337 “Combined” desmoplastic melanoma of the vulva with poor clinical outcome
G. Collina
CASE REPORTS
340 Tuberculosis of superficial lymph nodes, a not so rare event to consider in diagnosis.
A case in an elderly male
A. Merante, M.R. Ambrosio, B.J. Rocca, A.M. Condito, A. Ambrosio, M. Arvaniti,
G. Ruotolo
343 Adenolipoma of the skin
S. Karoui, T. Badri, R. Benmously, E. Ben Brahim, A. Chadli-Debbiche, I. Mokhtar,
S. Fenniche
346 Adenomatous transformation in a giant solitary Peutz-Jeghers-type hamartomatous
polyp
F. Limaiem, S. Bouraoui, A. Lahmar, S. Jedidi, S. Aloui, S. Korbi, S. Mzabi
Società Italiana di Anatomia Patologica e Citopatologia Diagnostica,
Divisione Italiana della International Academy of Pathology
Vol. 103 December 2011
Materiale destinato esclusivamente ai Professionisti Sanitari
Ventana BenchMark ULTRA
Qualsiasi Test in qualsiasi momento
P
Processazione multi-modale
P
Accesso continuo e random
P
Flusso di lavoro continuo
P
Processazione delle urgenze (STATs)
P
Connettività bidirezionale LIS/VANTAGE
Roche Diagnostics SpA
Roche Tissue Diagnostics
Viale G.B. Stucchi, 110
20900 Monza (MB)
www.roche.it
Cited in Index Medicus/MEDLINE, BIOSIS Previews, SCOPUS
Journal of the Italian Society of Anatomic Pathology
and Diagnostic Cytopathology,
Italian Division of the International Academy of Pathology
Editor-in-Chief
Marco Chilosi, Verona
Associate Editor
Roberto Fiocca, Genova
Managing Editor
Roberto Bandelloni, Genova
Scientific Board
R. Alaggio, Padova
G. Angeli, Vercelli
M. Barbareschi, Trento
G. Barresi, Messina
C.A. Beltrami, Udine
G. Bevilacqua, Pisa
M. Bisceglia, S. Giovanni R.
A. Bondi, Bologna
F. Bonetti, Verona
C. Bordi, Parma
A.M. Buccoliero, Firenze
G.P. Bulfamante, Milano
G. Bussolati, Torino
A. Cavazza, Reggio Emilia
G. Cenacchi, Bologna
P. Ceppa, Genova
C. Clemente, Milano
M. Colecchia, Milano
G. Collina, Bologna
P. Cossu-Rocca, Sassari
P. Dalla Palma, Trento
G. De Rosa, Napoli
A.P. Dei Tos, Treviso
L. Di Bonito, Trieste
C. Doglioni, Milano
V. Eusebi, Bologna
G. Faa, Cagliari
F. Facchetti, Brescia
G. Fadda, Roma
G. Fornaciari, Pisa
M.P. Foschini, Bologna
F. Fraggetta, Catania
E. Fulcheri, Genova
P. Gallo, Roma
F. Giangaspero, Roma
W.F. Grigioni, Bologna
G. Inghirami, Torino
L. Leoncini, Siena
M. Lestani, Arzignano
G. Magro, Catania
A. Maiorana, Modena
E. Maiorano, Bari
A. Marchetti, Chieti
D. Massi, Firenze
M. Melato, Trieste
F. Menestrina, Verona
G. Monga, Novara
R. Montironi, Ancona
B. Murer, Mestre
V. Ninfo, Padova
M. Papotti, Torino
M. Paulli, Pavia
G. Pelosi, Milano
G. Pettinato, Napoli
S. Pileri, Bologna
R. Pisa, Roma
M.R. Raspollini, Firenze
L. Resta, Bari
G. Rindi, Parma
M. Risio, Torino
A. Rizzo, Palermo
J. Rosai, Milano
G. Rossi, Modena
L. Ruco, Roma
M. Rugge, Padova
M. Santucci, Firenze
A. Scarpa, Verona
A. Sidoni, Perugia
G. Stanta, Trieste
G. Tallini, Bologna
G. Thiene, Padova
P. Tosi, Siena
M. Truini, Genova
V. Villanacci, Brescia
G. Zamboni, Verona
G.F. Zannoni, Roma
Editorial Secretariat
G. Martignoni, Verona
M. Brunelli, Verona
Società Italiana di Anatomia Patologica e Citopatologia Diagnostica,
Divisione Italiana della International Academy of Pathology
Governing Board
SIAPEC-IAP
President:
C. Clemente, Milano
Vice President:
G. De Rosa, Napoli
General Secretary:
A. Sapino, Torino
Past President:
G.L. Taddei, Firenze
Members:
A. Bondi, Bologna
P. Dalla Palma, Trento
A. Fassina, Padova
R. Fiocca, Genova
D. Ientile, Palermo
L. Resta, Bari
L. Ruco, Roma
M. Santucci, Firenze
G. Zamboni, Verona
Associate Members
Representative:
T. Zanin, Genova
Copyright
Società Italiana di Anatomia
Patologica e Citopatologia
Diagnostica, Divisione
Italiana della International
Academy of Pathology
Publisher
Pacini Editore S.p.A.
Via Gherardesca, 1
56121 Pisa, Italy
Tel. +39 050 313011
Fax +39 050 3130300
[email protected]
www.pacinimedicina.it
Vol. 103 December 2011
Information for Authors including editorial standards
for the preparation of manuscripts
Pathologica is intended to provide a medium for the communication of
results and ideas in the field of morphological research on human diseases
in general and on human pathology in particular. The Journal welcomes
contributions concerned with experimental morphology, ultrastructural
research, immunocytochemical analysis, and molecular biology. Reports
of work in other fields relevant to the understanding of human pathology
may be submitted as well as papers on the application of new methods and
techniques in pathology. The official language of the journal is English.
Authors are invited to submit manuscripts according to the following
instructions by E-mail to:
[email protected], [email protected]
Lisa Andreazzi - Editorial Office
Pathologica - c/o Pacini Editore S.p.A.
Via Gherardesca 1, 56121 Pisa, Italy - Tel. +39 050 3130285
The files containing the article, illustrations and tables must be sent
in attachment and the following statement of Authors must also be
enclosed: separate letter, signed by every Author, stating that the
submitted material has not been previously published, and is not
under consideration (as a whole or partly) elsewhere, that its content
corresponds to the regulations currently in force regarding ethics
research and that copyright is transferred to the Publisher in case of
publication. If an experiment on humans is described, a statement must
be included that the work was performed in accordance to the principles
of the Declaration of Helsinki (1975, rev. 2000) and Authors must
state that they have obtained the informed consent of patients for their
participation in the experiments and for the reproduction of photographs.
As regards the studies performed on laboratory animals, Authors must
state that the relevant national laws or institutional guidelines have been
observed. The Authors are solely responsible for the statements made in
their article. Authors must also declare if they got funds, or other forms
of personal or institutional financing from Companies whose products
are mentioned in the article.
Editorial standards for the preparation of manuscripts
The article, exclusively in English, should be saved in .RTF format. Do
not use, under any circumstances, graphical layout programmes such as
Publisher™, Pagemaker™, Quark X-press™, Adobe Indesign™. Do not
format the text in any way (avoid styles, borders, shading …); use only
character styles such as italics, bold, underlined. Do not send the text in
PDF. Text and individual tables must be stored in separate files.
When submitting a manuscript Authors should consider the following
points/items:
a) Title of the work.
b) Names of the Authors and Institute or Organization to which each
Author belongs.
c) Section in which the Authors intend the article to be published
(although the final decision rests with the Editor-in-Chief).
d) Name, address, telephone number and E-mail address of the Author to
whom correspondence and galley proofs should be sent.
e) 3-5 key words.
f) Abstract, less than 250 words and subdivided into the following
sections: Introduction, Method(s), Results, Discussion. In the
Introduction section, the aim (or the aims) of the article must be
clearly summarised (i.e., the hypothesis Authors want to verify);
in the Method(s) section, the Authors must report the context of
the study, the number and the kind of subjects under analysis,
the kind of treatment and statistical analysis used. In the Results
section Authors must report the results of the study and of the
statistical analysis. In the Discussion section Authors must report
the significance of the results with regard to clinical implications.
g) References must be limited to the most essential and relevant, identified
in the text by Arabic numbers and listed at the end of the manuscript in
the order in which they are cited. The format of the references should
conform with the examples provided in N Engl J Med 1997;336:30915. The first three authors must be indicated, followed by “et al”.
Journals should be cited according to the abbreviations reported on
Pubmed. Examples of correct format for bibliographic citations:
Journal articles: Jones SJ, Boyede A. Some morphological observations on osteoclasts. Cell Tissue Res 1977;185:387-97.
Books: Taussig MJ. Processes in pathology and microbiology. Oxford: Blackwell 1984.
Chapters from books: Vaughan MK. Pineal peptides: an overview. In:
Reiter RJ, ed. The pineal gland. New York: Raven 1984, pp. 39-81.
h) Acknowledgements and information on grants or any other forms of
financial support must be cited at the end of the references.
i) Notes to the text, indicated by an asterisk or similar symbol, should be
shown at the bottom of the page.
Tables must be limited in number (the same data should not be presented
twice, in both text and tables), typewritten one to a page, and numbered
consecutively with Roman numbers.
Illustrations: Send illustrations in separate files from text and tables.
Software and format: preferably send images in .TIFF or .EPS format,
resolution at least 300 dpi (100 x 150 mm). Other possible formats: .JPEG,
.PDF, .PPT (Powerpoint files). Please do not include, when possibile,
illustrations in .DOC files. Insert an extension that identifies the file format
(example: .Tif; .Eps).
Drugs should be referred to by their chemical name; the commercial name
should be used only when absolutely unavoidable (capitalizing the first
letter of the product name and giving the name of the pharmaceutical firm
manufacturing the drug, town and country).
The editorial office accepts only papers that have been prepared in strict
conformity with the general and specific editorial standards for each
survey. The acceptance of the papers is subject to a critical revision by
experts in the field, to the implementation of any changes requested, and
to the final decision of the Editor-in-Chief.
Authors are required to correct and return (within 3 days of their mailing)
only the first set of galley proofs of their paper. Authors may order reprints,
at the moment they return the corrected proofs by filling in the reprint
order form enclosed with the proofs.
Applications for advertisement space should be directed to:
Pathologica - Pacini Editore S.p.A., Via Gherardesca, 56121 Pisa, Italy
Tel. +39 050 3130217 - Fax +39 050 3130300
E-mail: [email protected]
Subscription information
Pathologica publishes six issues per year. The annual subscription rates
for non-members are as follows:
Italy € 105,00; all other countries € 115,00. This issue € 20,00 for Italy,
€ 25,00 abroad.
Subscription orders and enquiries should be sent to: Pathologica - Pacini
Editore S.p.A. - Via Gherardesca, 56121 Pisa, Italy E-mail: [email protected] - On line subscriptions: www.pacinimedicina.it
Subscribers’ data are treated in accordance with the provisions of
the Legislative Decree, 30 June 2003, n. 196 – by means of computers
operated by personnel, specifically responsible. These data are used by
the Publisher to mail this publication. In accordance with Article 7 of the
Legislative Decree n. 196/2003, subscribers can, at any time, view, change
or delete their personal data or withdraw their use by writing to Pacini
Editore S.p.A. - Via A. Gherardesca 1, 56121 Pisa, Italy.
Photocopies, for personal use, are permitted within the limits of 15% of
each publication by following payment to SIAE of the charge due, article
68, paragraphs 4 and 5 of the Law April 22, 1941, n. 633. Reproductions
for professional or commercial use or for any other other purpose other
than personal use can be made following a written request and specific
authorization in writing from AIDRO, Corso di Porta Romana, 108, 20122
Milan, Italy ([email protected] – www.aidro.org).
The Publisher remains at the complete disposal of those with rights whom
it was impossible to contact, and for any omissions.
Journal printed with total chlorine free paper and water varnishing.
Printed by Pacini Editore, Pisa, Italy - February 2012
CONTENTS
of help in the diagnostic work-up of patients with effusions suspicious for mesothelioma.
Original articles
The role of 2D bar code and electronic cross-matching
in the reduction of misidentification errors in a pathology
laboratory. A safety system assisted
G. Fabbretti
Introduction. Mismatching of patients and specimens can lead to
incorrect histopathological diagnoses. Most misidentification errors
in laboratories occur during the manual pre-laboratory and laboratory phases. In the past few years, we have examined this vital and
challenging issue in our unit and introduced appropriate procedures.
Recently, we have paid special attention to the problem of specimen mix-ups in the gross examination phase and the mismatching of
blocks and slides in the cutting phase.
Objective. We have focused on the reduction of the potential sources
of mismatching of specimen containers, tissue blocks and slides,
focusing in particular on the most critical steps which are gross cutting and preparation of microtome sections.
Design. A 2D bar code directly printed on the labels of specimen containers, and directly printed onto cassettes and slides, is now being used; in
addition, the system performs an electronic cross-check of tissue blocks
and slides, which is managed by the laboratory information system.
Results. The present system permits full sample traceability from
the moment samples reach the laboratory to the issuing of the final
report. Indeed, the LIS records samples, blocks and slides in real time
throughout the entire procedure, as well as the operator’s name, and
the date and time each individual procedure is done. This facilitates
later monitoring of the entire workflow.
Conclusions. The introduction of 2D bar code and electronic crosschecking represents a crucial step in significantly increasing the safe
management of cases and improving the quality of the entire work
process.
Cytologic re-evaluation of negative effusions from patients
with malignant mesothelioma
Background. Cytology is a controversial means of diagnosing
malignant mesothelioma due to the high rates of negative samples. The aim of the present study was to review effusions originally reported as “negative” in patients with histologically-proven
mesothelioma to evaluate possible pitfalls.
Methods. We reviewed the cytologic slides of 25 specimens
that refer to 15 epithelioid, 5 biphasic, 4 sarcomatoid and 1 welldifferentiated papillary mesotheliomas. For comparison, we also
reviewed 23 specimens from non-neoplastic conditions. For each
effusion, we evaluated the background and calculated a score considering the following items: amount of mesothelial cells, architectural pattern and atypical features, and a revised diagnosis was
rendered.
Results. More than half of the effusions initially called “negative” (but mesothelioma by histology) were considered atypical/
suspicious (false-negative diagnosis); the remaining cases were
true-negative or inadequate. Almost all effusions initially called
“negative” (but non-neoplastic by histology) were considered
negative. The only item that seems to discriminate between the
two groups is atypia of mesothelial cells.
Conclusions. The present study has highlighted the following pitfalls: (i) to report effusions devoid of mesothelial cells as negative
that instead should be reported as inadequate/non-diagnostic; (ii)
to underestimate low cellular effusions containing atypical mesothelial cells or high cellular effusions containing bland mesothelial cells with a morular pattern; (iii) to consider that an inflammatory background may obscure a scant number of mesothelial cells.
A categorized system (inadequate (M1), negative (M2), atypical
(M3) and suspicious (M4)) for reporting effusion cytology may be
Intra-operative frozen section technique for breast cancer:
end of an era
E. Manfrin, A. Remo, F. Falsirollo, G.P. Pollini, A. Parisi,
A. Nottegar, F. Bonetti
Data on 2436 primary breast carcinomas diagnosed between 1992
and 2006 were collected to evaluate the rate of frozen section procedures performed over time. Frozen section procedures performed
to evaluate resection margins for conservative surgery or sentinel
node status were excluded. Over time, there was a decrease in the
use of frozen sections indistinctly extended to all pT cancer categories. The rate of cancers diagnosed with frozen sections was 51.2%
in 1999, and 0% in 2005-2006. In the same period, the adoption
of cytology and core biopsy for breast cancer diagnosis increased
from 40% in 1992 to more than 90% since 1999. In an audited
diagnostic activity on breast pathology, the routine use of frozen
sections on primary lesions was considered inappropriate, particularly in assessment of clinically non-palpable lesions, and should be
limited to cases with inadequate pre-surgical sampling.
The diagnostic accuracy of cervical biopsies in determining
cervical lesions: an audit
Objective. The present audit was carried out to assess the diagnostic accuracy of cervical punch biopsy during colposcopy in
comparison with diagnosis from subsequent cone excision.
Design and setting. Retrospective analysis was performed by
examining the histopathology reports for paired cervical punch
biopsies and cervical cone excisions for cases reported from April
2004 to March 2005 (when cervical biopsies and cones were
reported by general pathologists) and from January to December
2008 (when reporting by specialist gynaecological pathologists
was instituted).
Sample. 150 women had both cervical punch and cone biopsies
performed in the 2004-2005 period, while 149 women had both
biopsies performed in 2008.
Main outcome measures and results. In 2004-5, the rate of consistent diagnosis was 68.7%, compared with 75.8% in 2008. This
was due to a decrease in the rates of overdiagnosis (16.7% vs.
14.8%) and underdiagnosis (14.7% vs. 9.4%), which was statistically significant. The sensitivity rates for 2004-5 and 2008 were
87.5% and 89.7%, and the specificity rates for the same periods
were 39.8% and 39.4% respectively.
Conclusions. This audit highlights the importance of planning
patient management on the basis of co-ordinated information
from smear results, history, colposcopy findings and cervical
biopsies. The introduction of specialist gynaecological histopathology reporting has significantly improved the rates of consistent diagnosis.
“Combined” desmoplastic melanoma of the vulva with poor
clinical outcome
G. Collina
Desmoplastic melanomas in an unusual variant of melanoma that
usually occurs in sun-damaged skin of elderly people. Desmoplasia may be the prominent features of the lesion or represent a portion of an otherwise non-desmoplastic melanoma; these latter are
called “combined” desmoplastic melanoma. Desmoplastic melanomas of the vulva are rare. Herein, we report a case of “combined” DM of the labia minor consisting of a superficial spitzoid
component and a deeper spindle desmoplastic component. Protein
S-100 expression was ubiquitous, while MART-1 and HMB-45
were limited to the superficial spitzoid component and were nega-
tive in desmoplastic areas. Notably, the nodal metastasis retained
the same biphasic pattern seen in the primary tumour. The patient
died of widespread metastatic disease 3 years after diagnosis.
Case reports
Tuberculosis of superficial lymph nodes, a not so rare event
to consider in diagnosis. A case in an elderly male
A. Merante, M.R. Ambrosio, B.J. Rocca, A.M. Condito,
A. Ambrosio, M. Arvaniti, G. Ruotolo
Tuberculosis (TB) is still one of the most frequent infectious
diseases worldwide. Until the 1990s, Western European countries
showed a low frequency of TB infection, but the rise of immigration
has led to a rapid increase in its occurrence. In the elderly,
TB is emerging as a significant health problem (age-related
decline of the cell-mediated immunity, associated illnesses, use
of immunosuppressive drugs, malnutrition, poor life conditions),
although its detection and diagnosis is not easy also considering its
subclinical presentation. Almost 70% of all TB infections in Italy
are found in the lungs; 50% of the extrapulmonary infections affect
lymph nodes. Due to the low incidence of superficial tuberculous
lymphadenitis without pulmonary manifestations, the possibility
of a TB aetiology is often not taken into consideration in the
differential diagnosis of lymphadenopathy, resulting in significant
delay of appropriate treatment.
Herein, we describe the case of a 78-year-old male with nocturnal
fever, weakness, night sweats, loss of weight and decay in general
condition. The patient had a past medical history of prostate
adenocarcinoma treated with hormone therapy.The past medical
history in association with clinical findings and laboratory data
(anaemia, high titers of fibrinogen and reactive c-protein) led
to the suspect of metastatic adenocarcinoma. Only histological
and molecular biology findings allowed us to make a correct
diagnosis of TB.
Adenolipoma of the skin
S. Karoui, T. Badri, R. Benmously, E. Ben Brahim,
A. Chadli-Debbiche, I. Mokhtar, S. Fenniche
Adenolipoma of the skin (ALS) is an uncommon histological
variant of lipoma, characterized by the presence of normal
eccrine sweat glands inside the fat proliferation. A 32-yearold woman presented to our department with a slow-growing,
painless subcutaneous soft tumour located on the upper part of the
right thigh. Microscopically, there was lobulated adipose tissue
proliferation with well-differentiated eccrine glands and ducts
in the periphery and centre of the nodule. These features were
suggestive of ALS.
ALS is a rare microscopic variant of cutaneous lipoma having
similar clinical features to lipoma. The most frequent locations
of this tumour are thighs (as in our patient), shoulders, chest
and arms. Histologically, the tumour is composed of lobulated
adipose tissue with larger and more prominent lobules than
those in normal subcutaneous adipose tissue. A well-developed
capsule may also be identified. Eccrine glands and ducts, without
proliferative changes, are well-differentiated within the adipose
tissue.
Differential diagnosis of adenolipoma includes the common
lipoma and its variants, skin tag and other hamartomatous lesions,
such as nevus lipomatosus superficialis, and the lipomatous
variant of eccrine angiomatous hamartoma.
Adenomatous transformation in a giant solitary
Peutz-Jeghers-type hamartomatous polyp
F. Limaiem, S. Bouraoui, A. Lahmar, S. Jedidi, S. Aloui,
S. Korbi, S. Mzabi
Solitary Peutz-Jeghers-type polyp is a rare hamartomatous polyp
without associated mucocutaneous pigmentation or a family history of Peutz-Jeghers Syndrome. It is usually encountered in the
small intestine, but rarely involves the rectum. A 27-year-old
previously healthy female patient presented with a two-month
history of rectal bleeding. The patient had neither mucocutaneous pigmentation nor a family history of gastro-intestinal
polyposis. Endoscopic examination revealed a solitary lobular
polypoid lesion in the lower rectum. The polyp was sessile and
measured 15 cm in diameter. As histological examination of
the biopsy specimen was suggestive of adenoma, endoscopic
polypectomy was performed. Histologically, this polyp had an
arborizing muscular network originating from the muscularis
mucosa, and was covered by well organized mucosa with several foci of dysplastic glands. The final pathological diagnosis
was solitary Peutz-Jeghers type hamartomatous polyp with adenomatous transformation.
pathologica 2011;103:313-317
Original article
The role of 2D bar code and electronic cross-matching
in the reduction of misidentification errors
in a pathology laboratory. A safety system assisted
G. Fabbretti
U.O. Anatomia Patologica e Citologia, Ospedale Infermi, Rimini, Italy
Key words
Mismatch errors • Risk management • 2D Barcode technology • Safety management of patient specimens
Summary
Introduction. Mismatching of patients and specimens can lead
to incorrect histopathological diagnoses. Most misidentification
errors in laboratories occur during the manual pre-laboratory and
laboratory phases. In the past few years, we have examined this
vital and challenging issue in our unit and introduced appropriate
procedures. Recently, we have paid special attention to the problem of specimen mix-ups in the gross examination phase and the
mismatching of blocks and slides in the cutting phase.
Objective. We have focused on the reduction of the potential
sources of mismatching of specimen containers, tissue blocks and
slides, focusing in particular on the most critical steps which are
gross cutting and preparation of microtome sections.
Design. A 2D bar code directly printed on the labels of specimen
containers, and directly printed onto cassettes and slides, is now
being used; in addition, the system performs an electronic crosscheck of tissue blocks and slides, which is managed by the laboratory information system.
Results. The present system permits full sample traceability
from the moment samples reach the laboratory to the issuing
of the final report. Indeed, the LIS records samples, blocks and
slides in real time throughout the entire procedure, as well as
the operator’s name, and the date and time each individual procedure is done. This facilitates later monitoring of the entire
workflow.
Conclusions. The introduction of 2D bar code and electronic
cross-checking represents a crucial step in significantly increasing the safe management of cases and improving the quality of
the entire work process.
Introduction
incorrectly-recorded laterality and anatomical sites.
Another two steps in the procedure that are particularly
prone to error are the gross and cutting phases, which
are characterized by sample mix-ups and block and slide
mismatching errors.
A significant reduction in the number of misidentification errors on accession was achieved in 2008 with the
elimination of handwritten requests and handwritten
labels, and by the introduction of an order entry with
electronic requests and labels. In addition, direct printing of cassettes and slides by automatics printers interfaced with the laboratory information system produced
a considerable reduction in block and slide mismatching
errors.
However, data analysis in 2009 revealed continuing
block and slide mismatching. For this reason, at the be-
Since the publication of “To err is human” in 1999 1,
substantial work has been done to reduce factors that
contribute to errors in medical and surgical pathology
practice. Procedures in the histopathology unit involve
multistep processes with several handoffs of materials, which are all potential sources of error 2. Errors that
may occur at any stage of processing vary in frequency,
depending on the laboratory. Several papers have been
published that analyze and propose solutions 3-5. Over
the past five years, we have approached this challenging
issue in our laboratory, with particular focus on the prelaboratory and laboratory phases.
The most critical step is the accession phase, which is
characterized by incorrect patient identifications and
Acknowledgements
Correspondence
The author is grateful to the entire Pathology Unit Staff; particular
thanks are given to Luigi Santucci, Director of the Information
Technology Department, and to Francesco Graziani, Rina Velati
and Carla Zucca of Dedalus SpA.
Giovanna Fabbretti, U.O. Anatomia Patologica e Citologia,
Ospedale Infermi, via Settembrini 2, 47900 Rimini, Italy - E-mail:
[email protected]
314
ginning of 2010, a 2D bar code was introduced, which
is directly printed onto container labels, cassettes and
slides, in order to reduce mismatching in the gross examination and cutting phases. This new technology is
also an effective means of improving sample traceability
during the workflow.
The purpose of the present work is to discuss the highly
reliable work procedure we have developed, which fully
utilizes the benefits of information technology.
g. fabbretti
Fig. 1. Cassettes and slides with a directly printed 2D bar code
and accession code number. Slides also show readable text: name
of institution, type of stain (HE: yellow slides and immunostains
for Ki-67, progesterone and oestrogen receptors: white charged
slides) name and surname of patient.
Materials and methods
The entire process was reorganised in May 2008 when
a new laboratory information system (LIS, Armonia
Dedalus, SpA, Italy) was integrated with the Hospital
Information System (HIS; Trak-care, Traksystem, Australia), with an HL7 interface for receiving orders from
physicians through HIS order entry. This eliminated the
need for handwritten requests and handwritten container
labels. At the same time, the LIS was interfaced with the
cassette and slide printers (Leica Microsystems, Bannockburn, IL) to handle cassette and slide printing caseby-case during the gross and cutting phases; this avoids
the need for manual code transcription. All of the above
has been described in detail in a previous publication 6.
Since 2010, the LIS has used a 2D bar code and has been
interfaced with both cassette and slides printers (a Leica printer in the Cytology Lab and Slide Mate printers
[Thermo Fisher Scientific, Waltham, MA] at the Cutting
Station); the LIS also has been integrated with a Leica
BOND-III instrument, which fully automates immunohistochemistry work; 2D bar codes are directly printed
onto immunohistochemistry slides at the cutting station:
the BOND-III reads the 2D slide bar codes. Extensive
bar code printing testing and validation for cassettes and
slides was conducted by Leica, Thermo Fisher Scientific and Dedalus, and for scanner configuration by the
Dedalus Company and Metrologic Instruments Inc. We
chose the Metrologic MS1690 Focus, which is an omnidirectional scanner capable of reading all standard 1D
and 2D bar codes.
During set up, we carried out ping testing on cassettes
and slides. No input failure occurred. Bar code misreading may be caused by poor quality cassette and slide materials, which can cause variations in printing quality.
We always test any new material that will be used.
The following are printed on cassettes: the accession
code (e.g. 11-I-11340), specimen container letter (e.g.
A, B, C), subpart block number (e.g. 1, 2) and a 2D bar
code, which includes a progressive printing number
(Fig. 1).
The following is printed on the slides as human readable
text: accession code (e.g. 11-I-13800), patient name and
surname, type of stain (e.g. HE, PAS), the name of our
unit (Anat Pat, RN); in addition there is a 2D bar code,
which also encodes a progressive printing number.
The progressive printing number, found in both slide
and cassette 2D bar codes, is essential for the univocal
matching of a block and its associated slides. It is impossible for two identically identified blocks or slides to
exist. For example, if a slide is printed and then the same
slide is printed again, the first slide printed is identified
in the 2D bar code as 11-I-13500A21 and the second one
11-I-13500A22.
This is of fundamental importance and is a key point
regarding matching of blocks and slides.
Each workstation in our unit is equipped with a PC,
monitor and scanner. We have also equipped each cutting station with small slide printers to avoid the need to
preprint slides. The LIS manages each individual step
via the 2D bar code regarding the processing of samples,
blocks and slides by recording the name of the operator
and the date and time of the step; in this way, each single
case is traceable during the entire work procedure.
The LIS furthermore records any error or problem detected at any stage in the workflow. This function is
quick and easy to access by using a keyboard; in this
function, a list of predetermined parameters are displayed: e.g. error or problem type, possible corrective
action, date, time and operator. Cases where an error has
been detected are marked by a special icon, so that the
pathologist is alerted and can check the validity of the
corrective actions taken before diagnosis.
Errors and problems are subdivided in the following
way: accession errors, specimen errors or problems, and
misidentification during the processing procedure. Each
subgroup is further divided into other sub-categories (e.g.
misidentification during gross examination, embedding,
cutting, etc.). This system permits rapid analysis of collected data. Once a month, a specially trained technical
staff member evaluates data trends.
The unit’s workflow, which is bar code based, is described in a consistent and easy-to-read manner.
1. Accession phase: after a double check to verify that
data on the electronic request corresponds to that on
the medical report that accompanies specimens (e.g.
Role of 2D bar code and electronic cross-matching in the reduction of misidentification errors
Fig. 2. Downloaded request form and adhesive labels attached to
specimen containers. Above: patient data; middle: the two submitted specimens: 1) skin from the lumbo-sacral region; 2) skin
from the patient’s hip and clinical information; below: the space
occupied by detached labels.
bronchoscopy, endoscopic report, etc.), the case is
entered into the LIS by scanning a bar code on the
paper copy of the electronic request, determining
the recovery of the request from HIS (Fig. 2). The
LIS provides a lab worksheet with number (e.g.
11-I-14500) both as readable text and as a bar code
(Fig. 3), and also provides labels for specimen containers in readable text as well as a 2D bar code.
Once a misidentification error is detected, the case
is rejected and it will be processed after the error has
been corrected.
2. Gross examination phase: the specimen containers
are moved to the gross bench for sectioning and recording of macroscopic findings. Our LIS provides
many predetermined parameters for each anatomical site and each medical procedure; for example,
the topographic code (SNOMED), the number and
colour of the cassette (orange for urgent cases, white
Fig. 3. An internal lab worksheet: accession number and 1-dimensional bar code and adhesive labels for specimen containers
with a 2-dimensional bar code.
315
for sentinel lymph nodes, yellow for small biopsies,
blue for lymph nodes, pink for skin biopsies and
green for surgical specimens), section number, and
the routine stains or immunostains, if provided. The
default setting may be modified at any time during
the process. Cassettes are directly printed (Leica Microsystems, Bannockburn, IL) case-by-case during
gross examination. The printing process is quick and
easy.
3. Tissue embedding phase: after processing each cassette is read by the scanner before embedding the tissue. The LIS displays the following: code number,
tissue type, fragment number and notes, if recorded
during gross examination, including operator name,
date, time and status (Fig. 4); after reading, the cassette’s status is changed from processing to executed.
When all samples related to a single case are embed-
Fig. 4. Tissue embedding station: the cassette is read by the scanner. The LIS displays all relevant information and shows a list of
embedded cassettes.
Fig. 5. Cutting station: the cassette is read by the scanner, the LIS
shows all tissue block information (patient name and surname,
code number, tissue type, number of fragments, embedded
status, operator and date) and the slide Mate printer prints the
relevant information on the slide.
316
ded in cassettes, the case status is changed from gross
executed to embedded. The LIS sequentially shows a
list of all embedded cassettes on the monitor in the
work session, and, if required, supplies a printed
list.
4. Cutting phase: just before cutting, the operator reads
the block’s bar code with the scanner, and the slide
printer prints all the associated slides; after section
cutting (and only at this time - before it is picked
up) the slide is read by the scanner. If the slide does
not match the block, a message error on the monitor alerts the operator (Fig. 5). The LIS displays the
changing status of the slide from requested to validated only if the slide matches correctly. When all
slides related to a single case are validated, the case’s
status is changed from embedded to cut.
5. Checkout phase: at the end of the entire work flow
procedure, there is the final check before delivering
slides to the referring pathologist. Each slide is read
by the scanner, and when all slides of a single case
(routine stain, special stains and immunostains) are
‘pinged’ the case is ready to be sent for medical examination.
Results
The results achieved have been particularly good and of
significant importance. Since the introduction in 2010
of 2D bar codes on container labels, we have not had a
single case of sample mix up in the gross examination
phase in a total of 26,964 histological cases. In the gross
examination phase, each case begins with a reading
of the 2D bar code on the container label, and the LIS
makes it impossible for a code number that is different to
the case number in question to be printed on a cassette.
In contrast, in 2009 we had 10 errors in a total of 26,961
(0.03%) cases that involved mismatch of samples from
the same patient.
Additionally, in the cutting phase we have had no mismatch since automatic cassette and slide cross checking
was made possible by the introduction of 2D bar codes
in 2010 (26,964 histological cases; 80,571 tissue blocks).
In contrast in the same period in 2009, we had 32 mismatches from a total of 26,961 cases (0.11%) (80,361
tissue blocks) caused by the transfer of sections from one
block to a mismatched slide. Data analysis showed that
mismatch errors were more or less equally distributed
between routine cutting (14 cases) and re-cutting. There
was a slightly greater error prevalence for re-cutting (18
cases), where the errors involved cases with similar code
numbers (e.g. 09-I-23715 and 09-I-23915); 12 of 18 errors involved specimens from different patients, and 4 of
18 involved different specimens from the same patient.
Of the 14 routine cutting mismatch errors, 10 involved
different patients. None of the errors for either the gross
examination or the cutting phase resulted in adverse consequences for the patient, as they were detected during
subsequent steps. The errors were noticed in some cases
g. fabbretti
because the clinical information was not concordant
with histological appearance. In other cases, the slide
samples clearly did not correspond with the anatomical
site indicated in the request when viewed under the microscope. Another particularly important result achieved
by the introduction of 2D bar coding is the introduction
of automated tracing; it is now possible in real time, to
trace a specimen container or missing block and locate
it immediately.
Indeed, the LIS manages the workflow, step by step, recording the operator’s name, date and time of each single
step. We are now able to know what is happening in real
time, and to take immediate action to locate a misplaced
container or block.
Discussion
The case-by-case direct printing of bar code numbers
on cassettes and slides by automated printers managed
by the LIS prevents errors caused by handwritten labels
and by transcription. Checking correspondence between
the code number on container labels and the cassette at
the gross station and between block and the slide at the
cutting station was previously done visually and was
therefore subject to error caused by fatigue and lack of
concentration.
Even if the mismatch rate was low in the gross examination and cutting phases, and in keeping with data reported in recent literature 7, an error that mismatches a
slide to the wrong patient can have serious consequences
on clinical outcome.
For this reason, we worked closely with the LIS provider
to design a system that would prevent this type of error.
The result is that we have up-graded our LIS with the
introduction of 2D bar codes on labels of specimen containers, and direct printed on cassettes and slides. The
biggest leap in improved quality was achieved by the
introduction of electronic cross-match managed by LIS.
Another important advance is that there is now sample
traceability throughout the entire workflow.
In a recent paper, Zarbo et al. 8 describes a workflow
dependent on bar code reading and illustrates the use of
traditional bar codes on specimen container labels, in
specific labels for slides and use 2D bar code only for
cassettes.
Unfortunately, in their laboratory, electronic requests
are not yet employed and cases are accessioned manually from handwritten requisitions, which are often incomplete and unclear, as noted by Dimenstein 9. The
labelling of slides represents an additional manual step
that is time consuming, prone to error and finally more
expensive than directly printing on them.
The electronic checking introduced in the cutting station overcomes the problem of operators failing to follow standard procedures, which was an issue that Zarbo
emphasized in his report. The LIS prevents proceeding
to the next case and alerts the operator is procedures are
not followed. Furthermore, if the slide’s bar code is not
Role of 2D bar code and electronic cross-matching in the reduction of misidentification errors
read by the scanner, the case is not validated. The introduction of electronic cross checking of blocks and slides
is an effective means of preventing inevitable human errors in the cutting phase caused by fatigue, lack of concentration and heavy workload.
During the development of this project, the only concern was the possible increase in processing times. However, during the first three weeks after the adoption of
the new workflow we experienced only a small delay
in slide delivery, which was caused by the need to train
all operators; such training is obviously necessary when
introducing new organizational procedures. All technical staff have very positively accepted this new working
procedure. In addition, in recent years much has been
accomplished in training all operators in risk management, and on-going work has been done with the entire
team to identify the causes of mismatching and improving workflow. The knowledge of when, where and why
misidentification errors occur, which is a fundamental
prerequisite for their successful reduction, has been facilitated by the LIS, which allows quick, easy and complete error reporting at each step of the work flow, as
previously described.
In summary, the work over the last few years has been
focused on simplifying workflow procedures as much as
possible by utilizing information technology, and the employment of bar coding to minimize operator caused error.
The process was streamlined by eliminating some potentially error prone procedures, most importantly eliminating manual accession input in the LIS by using a direct
electronic request entry. It is important to note that in this
manner, the patient and his or her samples are correctly
identified at the time they are taken, in the place they are
taken and by the clinician who performed the medical
procedure, and not later in the pathology lab by a member
of administration or technical staff. During gross tissue
examination, LIS case data can be accessed by reading
the 2D bar code on container labels, avoiding mix-up of
specimens; the direct printing of cassettes one case at a
time avoids the need for them to be prepared in advance
and eliminates the risk of confusing cassettes from different patients. The direct printing of slides, one block at
a time, at the moment of cutting of sections, eliminates
the need for labelling, which is a time consuming step.
More importantly, it also eliminates a potential source of
error because traditional labelling is a manual procedure
that is visually checked. Furthermore, labelling is more
expensive than direct printing of slides. The introduction
of electronic cross-checking using 2D bar codes directly
printed onto blocks and slides represents a very important
qualitative leap. In our experience, it represents the best
method for avoiding block and slide mismatching.
The redesigned workflow with 2D bar codes has another advantage: real time case traceability throughout
the entire procedure. Gradually we redesigned the entire
workflow procedure over a period of years. The support
we received from top management was crucial for its
success. In our experience, no single piece of technology
can eliminate errors in a complex system such as a pathology work flow composed of multiple handoffs. Each
laboratory has to consider the individual requirements of
their own workflow.
The LIS and bar code technology play a leading role in
making the entire process far safer. However, there is
also the need for standard operating procedures for each
step, accompanied by an efficient system of recording
errors for every phase (pre-lab, lab and post-lab) and rigorous daily compliance with all procedures.
References
1
Kohn LT, Corrigan JM, Donaldson MS, eds. To err is human:
building a safer health system. Washington, DC: National Academies Press 1999.
2
Nakhleh RE. Error reduction in surgical pathology. Arch Pathol
Lab Med 2006;130:630-2.
3
Zarbo RJ, D’Angelo R. The Henry Ford Production System: effective reduction of process defects and waste in surgical pathology.
Am J Clin Pathol 2007;128:1015-22.
4
D’Angelo R, Zarbo RJ. The Henry ford Production System: measures of process defects and waste in surgical pathology. Am J
Clin Pathol 2007;128:423-9.
5
Layfield LJ, Anderson GM. Specimen labelling errors in sur-
317
gical pathology: an 18-mounth experience. Am J Clin Pathol
2010;134:466-70.
6
Fabbretti G. Risk management: correct patient and specimen identification in a surgical pathology laboratory. The experience of
Infermi Hospital, Rimini, Italy. Pathologica 2010;102:96-101.
7
Nakhleh RE, Idowu MO, Souers RJ, et al. Mislabeling of cases,
specimens, blocks, and slides: a college of American pathologists
study of 136 institutions. Arch Pathol Lab Med 2011;135:969-74.
8
Zarbo RJ, Tuthill JM, D’Angelo R, et al. The Henry Ford Production System: reduction of surgical pathology in process misidentification defects by bar code-specified work process standardisation. Am J Clin Pathol 2009;131:468-77.
9
Dimenstein IB. Letter to the Editor. Am J Clin Pathol
2009;132:975-6.
pathologica 2011;103:318-324
Original article
Cytologic re-evaluation of negative effusions
from patients with malignant mesothelioma
Dipartimento di Scienze Radiologiche, Oncologiche e Anatomo-patologiche, Sapienza Università di Roma, Italy
Key words
Mesothelioma • Cytology • Serous effusion • Reactive mesothelium • Diagnostic pitfalls
Summary
Background. Cytology is a controversial means of diagnosing
malignant mesothelioma due to the high rates of negative samples. The aim of the present study was to review effusions originally reported as “negative” in patients with histologically-proven
mesothelioma to evaluate possible pitfalls.
Methods. We reviewed the cytologic slides of 25 specimens that
refer to 15 epithelioid, 5 biphasic, 4 sarcomatoid and 1 welldifferentiated papillary mesotheliomas. For comparison, we
also reviewed 23 specimens from non-neoplastic conditions.
For each effusion, we evaluated the background and calculated
a score considering the following items: amount of mesothelial
cells, architectural pattern and atypical features, and a revised
diagnosis was rendered.
Results. More than half of the effusions initially called “negative” (but mesothelioma by histology) were considered atypical/
suspicious (false-negative diagnosis); the remaining cases were
true-negative or inadequate. Almost all effusions initially called
“negative” (but non-neoplastic by histology) were considered
negative. The only item that seems to discriminate between the
two groups is atypia of mesothelial cells.
Conclusions. The present study has highlighted the following pitfalls: (i) to report effusions devoid of mesothelial cells as negative
that instead should be reported as inadequate/non-diagnostic; (ii) to
underestimate low cellular effusions containing atypical mesothelial
cells or high cellular effusions containing bland mesothelial cells with
a morular pattern; (iii) to consider that an inflammatory background
may obscure a scant number of mesothelial cells. A categorized system (inadequate (M1), negative (M2), atypical (M3) and suspicious
(M4)) for reporting effusion cytology may be of help in the diagnostic work-up of patients with effusions suspicious for mesothelioma.
Introduction
Therefore, any information that could lend support to
the possibility to suspect a diagnosis of MM in a fluid
sample should be considered.
We present herein the experience of our laboratory on
25 cases of histologically-proven MM in which cytologic diagnosis on effusions was originally reported
as negative for malignancy. Based on the re-examination of cytology specimens, we investigated the type
of errors, if any, and produced a scoring system that
might be helpful in detecting mesothelioma cells. For
comparison, 23 negative effusions from histologicallydemonstrated non-neoplastic conditions were also reexamined.
Since most malignant mesothelioma (MM) first present
with a pleural/peritoneal effusion 1, cytologic analysis
represents the primary diagnostic approach. However,
cytologic diagnosis of MM is notoriously challenging
with a sensitivity ranging from 30% to 80% 1-4. This
variability mainly reflects the lack of experience of pathologists with this rare malignancy and the complexity in interpretation of the changes in mesothelial cells,
the main pitfall being the resemblance of mesothelioma
cells to normal or reactive mesothelial cells. The lack of
a dedicated technical approach to the handling of effusions is also the source of errors such as improper collection and processing of effusions fluids 5.
The topic of whether cytology should be an acceptable
means of diagnosing MM is controversial 6, but a role for
cytology cannot be excluded, also because cytology may
be the only source of pathological material available.
From a series of 109 histologically proven cases of MM
(all with a previous effusion examined) that were diag-
Correspondence
Valeria Ascoli, Dipartimento di Scienze Radiologiche, Oncologiche
e Anatomo-patologiche, Sapienza Università di Roma, viale Regina
Elena 324, 00161 Roma, Italy - Tel. +39 06 44703550 - Fax
+39 06 49973376 - E-mail: e-mail: [email protected]
Cytologic re-evaluation of negative effusions from patients with malignant mesothelioma
319
Tab. I. Scoring system.
Cytological features
Score
1.
Mesothelial cellularity
From 0 to 3 points (0 = absent, 1 = scarce, 2 = moderate,
3 = abundant)
2.
Architecture of mesothelial cells
From 1 to 2 points (1 = single, 2 = single & clusters)
3.
Atypical features of mesothelial cells (anisonucleosis,
multinucleation, atypical mitosis, macronucleoli,
cytomegalia, vacuolation of the cytoplasm, presence
of squamoid cells)
From 1 to 7 points
nosed in our institution (Azienda Ospedaliera Policlinico
“Umberto I”, Roma) over a 9-year period, we retrieved
25 cases in which the original cytology report was “negative for malignancy”. Fourteen cases were first effusions
and 11 were recurrent effusions. The final histologic diagnosis was as follows: epithelioid MM (n = 15), welldifferentiated papillary mesothelioma (n = 1), biphasic
MM (n = 5) and sarcomatoid MM (n = 4). Twenty-one
were MM of the pleura and 4 of the peritoneum.
Cytological material consisted of conventional smears
stained with Papanicolaou and Giemsa stains. None of
the 25 specimens had been processed by the cell block
technique. Also, immunocytochemistry had not been requested.
The cytological slides were reviewed by the three
coauthors who were non-blinded to the original diagnosis, and the following cytological features were
considered: 1) background, defined in terms of inflammatory cells (lymphocytes, neutrophils, mixed
inflammatory cells) and the presence of necrosis;
2) mesothelial cellularity, defined as absent, scarce,
moderate, and abundant; 3) mesothelial cell architecture, the arrangement of mesothelial cells in clusters/
morulae or as individual cells; 4) mesothelial atypical features, including anisonucleosis, atypical mitosis, binucleation/multinucleation, macronucleoli,
cytomegalia, vacuolation of the cytoplasm and presence of squamoid cells.
We calculated a score for each effusion considering the
amount of mesothelial cells, architecture of mesothelial
cells and number of atypical features (Tab. I). Based on
morphological features and taking into account the total
score, we formulated a revision diagnosis. To verify the
performance of the scoring system, we also reviewed 23
effusion specimens from histologically-demonstrated
non-neoplastic pleural conditions.
Results
Cytological revision
Group negative by cytology/mesothelioma by histology
The main features of cytological revision of the 25 MM
cases together with the corresponding histological subtypes are reported in Table II, and in Figures 1-4.
• Background. All effusion samples were characterized by a variable amount of inflammatory cells.
There were two main patterns: neutrophil plentiful
(Fig. 1), and small lymphocyte plentiful (Fig. 2). In
effusions with abundant neutrophils, there was also a
large amount of fibrin and necrosis obscuring mesothelial cells, when present (Fig. 3).
• Mesothelial cells. In 6 specimens, mesothelial cells
were absent (inadequate/non-diagnostic specimens);
in the other 19 specimens, mesothelial cells were
present (adequate specimens). Of these 19 adequate
specimens, 12 effusions were scarcely cellular and 7
moderate-to-abundant cellular.
• Mesothelial architecture. Mesothelial cells were seen
either as scattered single cells (n = 11, Figs. 1-4) or as an
admixture of single and clustered cells (n = 8, Fig. 5).
• Mesothelial atypical features. Of the 19 adequate
specimens, 5 effusions showed mesothelial with no
atypical features. The other 14 effusions showed
Fig. 1. Single mesothelial cells surrounded by neutrophils; note
cytomegalia, multinucleation and prominent nucleoli. Histology
revealed epithelial mesothelioma. Cytodiagnosis on revision: M4/
suspicious.
320
V. Ascoli et al.
Tab. II. Revision of 25 effusions with an original cytologic diagnosis of “negative for malignancy” and a final histologic diagnosis of “malignant
mesothelioma”.
Histologic
subtype
Background
Diagnosis on revision
Mesothelial cells
Inflammatory
Cell Type
Amount
Architecture
Atypical
features
Total
Score
Epithelial
Lymphocytes
0
NA
NA
0
Inadequate/non-diagnostic (M1)
Epithelial
Neutrophils
0
NA
NA
0
Epithelial
Neutrophils
0
NA
NA
0
Epithelial
Neutrophils
0
NA
NA
0
Sarcomatous
Lymphocytes
0
NA
NA
0
Epithelial
Mixed
0
NA
NA
0
Epithelial
Neutrophils/
Necrosis
1
1
0
2
Negative (M2)
Epithelial
Mixed
1
1
0
2
Negative (M2)
Neutrophils/
Necrosis
1
1
0
2
Negative (M2)
Sarcomatous
Mixed
1
1
0
2
Negative (M2)
Sarcomatous
Lymphocytes
1
1
0
2
Negative (M2)
Biphasic
Lymphocytes
1
1
1
3
Atypical (M3)
Epithelial
Lymphocytes
1
1
1
3
Atypical (M3)
Epithelial
Lymphocytes
1
1
2
4
Atypical (M3)
Biphasic
Lymphocytes
1
1
2
4
Atypical (M3)
Biphasic
Lymphocytes
2
2
1
5
Atypical (M3)
Epithelial
Lymphocytes
2
1
2
5
Atypical (M3)
Epithelial
Lymphocytes
1
2
2
5
Atypical (M3)
Biphasic
Lymphocytes
1
1
3
5
Atypical (M3)
Epithelial
Mixed
2
2
2
6
Suspicious (M4)
Biphasic
Lymphocytes
1
2
3
6
Suspicious (M4)
Epithelial
Mixed
2
2
2
6
Suspicious (M4)
Epithelial
Mixed/Necrosis
2
2
2
6
Suspicious (M4)
Mixed
3
2
2
7
Suspicious (M4)
Neutrophils
2
2
4
8
Suspicious (M4)
Sarcomatous
WDPM
Epithelial
NA = not applicable
WDPM = well-differentiated papillary mesothelioma
often multinucleation and macronucleoli and cytomegalia (Figs. 1, 3), also in addition to vacuolation of
the cytoplasm and squamoid cells (Fig. 4); the least
frequent atypical features were anisonucleosis and
mitosis.
Upon revision, we attributed the 25 effusions to 4 categories: M1 (inadequate), M2 (negative), M3 (atypical)
and M4 (suspicious).
M1-Inadequate/non-diagnostic. We included 6 cases in
this category that were completely devoid of mesothelial cells. The background of the smears was heavily inflammatory (granulocytes or lymphocytes). The overall
score was 0.
M2-Negative. We included 5 cases with a low number
of mesothelial cells lying singly (n = 4) or in clusters
(n = 1), and with no atypical nuclear features. The background of the smears was heavily inflammatory; often
there were granulocytes and also abundant necrosis. The
overall score was 2.
M3-Atypical mesothelial cells of undetermined significance. We included 8 effusions in this category characterized by scarce rather than moderate mesothelial cellularity; mesothelial cells were seen as single cells (n = 6)
more than in clusters (n = 2); mesothelial cells showed
a few atypical nuclear features; the inflammatory background was mainly represented by lymphocytes (Fig. 2).
A single case included in this category was highly cellular, but anisonucleosis was the only atypical feature
of mesothelial cells. The overall score was between 3
and 5.
Fig. 2. Single atypical mesothelial cell surrounded by numerous
lymphocytes. Histology revealed biphasic mesothelioma. Cytodiagnosis on revision: M3/atypical.
321
Fig. 4. Single atypical mesothelial cells surrounded by abundant
inflammatory cells; note many orangiophilic squamoid cells. Histology revealed epithelial mesothelioma. Cytodiagnosis on revision: M4/suspicious.
Fig. 3. Abundant necrosis, fibrin, inflammatory cells; there were
only very rare single atypical mesothelial cells. Histology revealed
biphasic mesothelioma. Cytodiagnosis on revision: M4/suspicious.
Fig. 5. Clusters of mesothelial cells with bland atypical features.
Histology revealed epithelial mesothelioma. Cytodiagnosis: on revision M4/suspicious.
M4-Suspicious mesothelial cells. We included 6 effusions characterized by moderate/abundant mesothelial
cellularity; in all specimens, there were clusters of mesothelial cells (Fig. 5); the number of nuclear atypical
features was variable. The overall score was > 5.
Group negative by cytology/negative by histology
The main features of the cytological revision of the 23
non-neoplastic cases are reported in Table III.
• Background. All effusion samples were characterized by a variable amount of inflammatory cells.
• Mesothelial cells. In a single specimen, mesothelial
cells were absent (inadequate/non-diagnostic specimen); most other specimens contained a moderate
amount of mesothelial cells.
• Mesothelial architecture. Mesothelial cells were seen
either as scattered single cells or as an admixture of
single and clustered cells.
• Mesothelial atypical features. Of the 22 adequate
specimens, effusions showed no atypical features
322
V. Ascoli et al.
Tab. III. Revision of 23 effusions with an original cytologic diagnosis of “negative for malignancy” and a final histologic diagnosis of “benign
hyperplasia of mesothelial cells/no evidence of malignancy”.
Histology
Background
Diagnosis on revision
Mesothelial cells
Inflammatory
Cell Type
Amount
Architecture
Atypical
features
Total Score
No malignancy
Neutrophils
0
NA
NA
0
Inadequate/
non-diagnostic (M1)
No malignancy
Mixed
1
1
0
2
Negative (M2)
No malignancy
Lymphocytes
1
1
0
2
Negative (M2)
No malignancy
Mixed
1
1
0
2
Negative (M2)
No malignancy
Mixed
1
1
0
2
Negative (M2)
No malignancy
Lymphocytes
2
1
0
3
Negative (M2)
No malignancy
Mixed
1
1
1
3
Negative (M2)
No malignancy
Mixed
2
2
0
4
Negative (M2)
No malignancy
Mixed
2
1
1
4
Negative (M2)
No malignancy
Mixed
3
1
1
5
Negative (M2)
No malignancy
Mixed
2
2
1
5
Negative (M2)
No malignancy
Lymphocytes
2
2
1
5
Negative (M2)
No malignancy
Mixed
2
2
1
5
Negative (M2)
No malignancy
Lymphocytes
2
2
1
5
Negative (M2)
No malignancy
Lymphocytes
2
2
1
5
Negative (M2)
No malignancy
Lymphocytes
2
2
1
5
Negative (M2)
No malignancy
Lymphocytes
2
2
1
5
Negative (M2)
No malignancy
Lymphocytes
2
2
1
5
Negative (M2)
No malignancy
Mixed
2
2
1
6
Negative (M2)
No malignancy
Lymphocytes
2
2
2
6
Negative (M2)
No malignancy
Lymphocytes
3
2
1
6
Negative (M2)
No malignancy
Lymphocytes
3
2
1
6
Negative (M2)
No malignancy
Mixed
2
2
2
6
Negative (M2)
NA: not applicable.
(n = 6), a single atypical feature (n = 14) or two atypical features (n = 2).
Upon revision, we attributed the 23 effusions to 2 categories, M1 (inadequate) and M2 (negative).
M1-Inadequate/non-diagnostic. We included a single
case in this category that was completely devoid of mesothelial cells. The background of the smears was heavily inflammatory (granulocytes).
M2-Negative. We included 22 cases with a moderate
number of mesothelial cells lying singly or in clusters
and with no atypical nuclear features or minimal atypical features. The background of the smears was inflammatory. The overall score was between 2 and 6.
Discussion
Our results showed that the cytologic revision of specimens previously reported as negative (but mesothelioma
by histology) provided a different diagnosis in 56% of
cases. These effusions represent diagnostic errors (falsenegative diagnoses) because they contained atypical mesothelial cells. When excluding 6 inadequate specimens
(24%), the remaining 5 cases (20%) were confirmed as
negative for malignancy, and were not diagnostic errors
(true-negative diagnoses) by cytology.
The scoring system is not particularly useful in separating the effusions due to non-neoplastic conditions
from effusions due to mesothelioma. However, there
is a bias of case selection in the MM group. In fact,
effusions due to MM were cases were that had been
called “negative” in earlier diagnosis; it is likely that
effusions containing clear-cut mesotheliomatous cells
would give a higher score. Architectural features seem
to be a non-informative variable, and the amount of
mesothelial cells does not discriminate between the
two groups; rather, it seems that more abundant mesothelial cells characterize the “negative” effusions more
than “false negative effusions” due to mesothelioma.
Atypical features are probably the most useful charac-
teristics in the daily practice to discriminate between
the two groups.
Based on our diagnosis on revision, we propose that
effusions containing atypical mesothelial cells should
be called at the very least “effusions containing atypical mesothelial cells of undetermined significance”
(M3 category); those effusions containing abundant
mesothelial cells with a morular pattern with some
atypical features should be called “suspicious for mesothelioma” (M4 category). The M3/atypical and M4/
suspicious effusions are at variance more on the basis
of the amount of mesothelial cells and on the basis of
cell grouping, rather than on the number of atypical
nuclear features. We also propose, similar to thyroid/
breast and cervical cytology, a system for reporting effusion cytology that could be of help in the diagnostic
work-up of fluids for mesothelioma: inadequate (M1),
negative (M2), atypical (M3) and suspicious (M4), as
recently reported 3.
Although we are aware of the limits of cytology in diagnosis of mesothelioma, and confirmed herein, the
present study has allowed us to focus on the following pitfalls: (i) To call negative those effusions that are
devoid of mesothelial cells; these effusions should be
called inadequate/unsatisfactory, non-diagnostic. Any
specimen with no mesothelial cells to be evaluated
should be unsatisfactory for evaluation, as in thyroid
and cervical cytology. (ii) To pay little attention to low
cellular effusions containing atypical mesothelial cells
dispersed as single cells. Several conditions limit exfoliation of diagnostic cells into effusions (recurrent effusions, non-epithelial mesothelioma). Any specimen
with abnormal cells should be satisfactory for evaluation, as for cervical/thyroid cytology. In such cases,
a note should be added indicating that the presence of
mesothelioma cannot be excluded. (iii) To not take into
account high cellular effusions with a striking morular
pattern of mesothelial cells of bland appearance. Another pitfall is the heavy inflammatory background that
may hamper the diagnosis by obscuring the scant number of mesothelial cells. In the atypical/M3 category,
we noticed that inflammatory cells were mainly lymphocytes; interestingly, it is known that mesothelioma
can be heavily infiltrated with many immune effector
cells, with T-lymphocytes constituting the major part
of inflammatory cells 7. Other factors (data not shown)
that may have contributed to the diagnostic pitfall are:
(i) the scarce amount of fluid examined respect to
the amount of fluid evacuated implying hypocellular
specimens; (ii) the improper specimen processing (excess of blood and insufficient concentration of cellular
323
sediment); (iii) the absence of immunocytochemistry
(because cell blocks are not routinely prepared in our
laboratory in case of negative effusions).
Taking into account histology, effusions that also remained negative on revision included three of four sarcomatous MM of the present series; this finding is not
unexpected and is a well-know feature in the cytologic
literature (mesothelial cells are entrapped in the fibrous
tissue). Among the suspicious/M4 effusions, there was
a case of well-differentiated peritoneal mesothelioma
(WDPM), which is an uncommon subtype of mesothelioma characterized by superficial spreading of papillary
formations lined by bland epithelioid cells that can be a
source of false-negative cytologic diagnoses. However,
this entity should be recognized by cytology in highly
cellular effusions and reliably be called suspicious for
mesothelioma 8 9.
Conclusions
1. More than half of effusions due to mesothelioma that
were initially called “negative for malignancy” are
false-negatives on revision. The remaining cases are
either true negatives (very scarce cellularity) or inadequate (absence of mesothelial cells).
2. Cytology may aid in diagnosis in patients with epithelioid and biphasic MM, but not in patients with
sarcomatoid MM.
3. Obscuring inflammatory background (lymphocytes,
neutrophils) and necrosis may hamper diagnostic
evaluation of atypical mesothelial cells.
4. Currently, to limit the number of false-negative diagnosis, we ask clinicians to send the total amount of
fluid that is actually collected to increase the amount
of cells. We carefully process effusion fluid to routinely prepare cell-blocks, as strongly recommended
by most experts.
5. As in thyroid/breast and cervical cytology, a categorized system for reporting effusion cytology may be
of help in the diagnostic work-up of fluids for mesothelioma (inadequate [M1], negative [M2], atypical
[M3] and suspicious [M4]).
6. The scoring system adopted in this study (evaluating
the amount of mesothelial cells, architectural pattern
and atypical features of mesothelial cells) is not particularly useful in separating effusions due to nonneoplastic conditions from those due to mesothelioma; nevertheless, atypical features are probably
the most useful characteristics in the daily practice to
discriminate between the two groups.
324
References
V. Ascoli et al.
5
Whitaker D. The cytology of malignant mesothelioma. Cytopathology 2000;11:139-51.
6
Sheaff M. Should cytology be an acceptable means of diagnosing
malignant mesothelioma? Cytopathology 2010;22:3-4.
7
Hegmans JP, Hemmes A, Hammad H, et al. Mesothelioma environment comprises cytokines and T-regulatory cells that suppress
immune responses. Eur Respir J 2006;27:1086-95.
1
Di Bonito L, Falconieri G, Colautti I, et al. Cytopathology of malignant mesothelioma: a study of its patterns and histological bases. Diagn Cytopathol 1993;9:25-31.
2
Renshaw AA, Dean BR, Antman KH, et al. The role of cytologic
evaluation of pleural fluid in the diagnosis of malignant mesothelioma. Chest 1997;111:106-9.
3
Rakha EA, Patil S, Abdulla K, et al. The sensitivity of cytologic
evaluation of pleural fluid in the diagnosis of malignant mesothelioma. Diagn Cytopathol 2010;38:874-9.
8
Ikeda K, Suzuki T, Tate G, et al. Cytomorphologic features of
well-differentiated papillary mesothelioma in peritoneal effusion:
a case report. Diagn Cytopathol 2008;36:512-5.
4
Sherman ME, Mark EJ. Effusion cytology in the diagnosis of
malignant epithelioid and biphasic pleural mesothelioma. Arch
Pathol Lab Med 1990;114:845-51.
9
Haba T, Wakasa K, Sasaki M. Well-differentiated papillary
mesothelioma in the pelvic cavity. A case report. Acta Cytol
2003;47:88-92.
pathologica 2011;103:325-330
Original article
Intra-operative frozen section technique
for breast cancer: end of an era
E. Manfrin, A. Remo*, F. Falsirollo, G.P. Pollini**, A. Parisi, A. Nottegar, F. Bonetti
Department of Pathology and Diagnosis, Section of Surgical Pathology, G.B. Rossi Hospital, University of Verona; * Surgical Pathology
Unit, Mater Salutis Hospital, ULSS21, Legnago (VR); ** Department of Surgery, G.B. Rossi Hospital, University of Verona, Italy
Key words
Frozen sections • Intraoperative diagnosis • Breast cancer • Core needle biopsy • Fine needle aspiration cytology
Summary
Data on 2436 primary breast carcinomas diagnosed between 1992
and 2006 were collected to evaluate the rate of frozen section procedures performed over time. Frozen section procedures performed
to evaluate resection margins for conservative surgery or sentinel
node status were excluded. Over time, there was a decrease in the
use of frozen sections indistinctly extended to all pT cancer categories. The rate of cancers diagnosed with frozen sections was 51.2%
in 1999, and 0% in 2005-2006. In the same period, the adoption
of cytology and core biopsy for breast cancer diagnosis increased
from 40% in 1992 to more than 90% since 1999. In an audited
diagnostic activity on breast pathology, the routine use of frozen
sections on primary lesions was considered inappropriate, particularly in assessment of clinically non-palpable lesions, and should be
limited to cases with inadequate pre-surgical sampling.
Introduction
intraoperative assessment of a suspicious breast lesion,
while an important role is still reserved to the evaluation
of resection margins 22-24 and status of sentinel lymph
nodes 25-27.
In the literature, only limited data have been collected
with the aim of objectively defining the decreasing use
of FS. The aim of the current study was to analyse the
frequency of FS utilization in primary breast cancer series over a period of 15 years, and to evaluate the influence of clinical and pathological variables on results.
The frozen section technique was first introduced by
Wilson in 1905 for intraoperative diagnosis of breast
carcinoma 1. In subsequent years, intraoperative frozen
section examination was established as a reliable procedure for the rapid histologic evaluation of surgical
breast specimens 2-6. Advances in radiology, pathology,
surgical techniques, medical oncology and radiotherapy
have changed the diagnostic and therapeutic approaches
to breast cancer. Nowadays, different therapeutic strategies to breast cancer are available and tailored treatment
for each individual patient is guided by detailed clinical
and pathological data available before surgery. Over the
years, the flow-chart referred to the assessment of breast
lesions has been progressively shifted from intraoperative procedures to pre-surgical diagnostic techniques, as
imaging guided fine-needle aspiration cytology (FNAC)
and core needle biopsy (CNB) or vacuum-assisted gun
needle biopsy (VAB) 7-13. The diffusion of mammography has increased the detection of small cancers (< 1 cm)
as well as proliferative, low grade atypical lesions for
which intraoperative frozen sections (FS) should not be
considered mandatory 4-6 14-18. In this scenario, FS has lost
its role as the first line diagnostic method guiding the
surgical strategy on primary breast lesions 19-21 through
Data on a large series of consecutive breast cancers, detected outside a screening program and surgically treated
in “G.B. Rossi” University Hospital in Verona between
January 1992 to December 2006 were extracted from
files of the Breast Cancer Registry and the Department
of Pathology of the same institution. The rate of breast
cancers submitted to FS for intraoperative diagnostic
purpose were retrieved from computerized diagnostic
files of the Department of Pathology. Frozen section
procedures performed to evaluate resection margins for
conservative surgery or sentinel node status were excluded. According to the purpose of the present analysis,
Correspondence
Erminia Manfrin, Department of Pathology and Diagnosis,
University of Verona, piazzale L.A. Scuro, 37134 Verona, Italy Tel. +39 045 8124810 - Fax +39 045 8027136 - E-mail: erminia.
[email protected]
326
E. Manfrin et al.
Fig. 1. Distribution of the breast cancer detection rate according to pT classification and year of detection.
cancers were stratified according to the year of detection, “in situ” or invasive cancer histology, lesion size
measured on the histological slide and expressed in pT
category according to the American Joint Committee on
Cancer (AJCC) 28. To match the number of cancers histologically diagnosed and the number of needle biopsies
performed to gain a pre-surgical diagnosis, pathological files were also searched for pre-operative diagnostic
procedures performed on primary breast lesions during
the same period.
Results
Between January, 1992 and December 2006, 2434 primary breast cancers were collected at the Department
of Pathology of the University of Verona (Tab. I). Invasive breast cancers accounted for 85.6% (2,084 cases)
and “in situ” cancers for 13.5% (329 cases). In 0.9%
of cases, the invasive or “in situ” type was not specified (21 cases). Over the years, the detection rate of
invasive breast cancers smaller than 2 cm (pT1mic-a,
pT1b, pT1c) showed a progressive increase balanced
by the decreasing detection rate of cancers larger than
2 cm (pT2+) (Fig. 1). Changes in the distribution in
the detection rate of breast cancer in favour of small
lesions were observed during the middle of the 1990’s,
but a higher detection rate was registered in 1999 and
continued in subsequent years, favoured by the introduction of the breast cancer screening program and
more participation of women in non-organized mammography tests. From 1999, the detection rate of “in
situ” carcinoma showed an increase that was almost
always greater than 15% (Fig. 1). The rate of FS performed yearly on primary breast lesions progressively
decreased over time (Tab. I). In 1992, 50% of detected
cancers were submitted to FS, but in 2005 and 2006,
no primary breast lesion was assessed with FS (Fig. 2).
The progressively decreasing use of FS began in the
middle of the 1990’s. At the beginning of the 2000’s,
the requests for FS on primary breast lesions registered
a nearly vertical decrease (Fig. 2). The decreasing use
of FS on primary breast cancers involved all pT cancer
categories (Fig. 3). From 1992 to 1999, the rate of cancers submitted to FS was significantly influenced by
cancer size with more FS performed on cancers larger
than 1 cm (FS rate in pT1c cancers: 40%; FS rate in
Tab. I. Frozen section procedures performed on 2434 primary breast
cancers between 1992 and 2006.
Cancer series
Frozen Section rate
Year
n. 2434
%
1992
117
51.3
1993
139
48.2
1994
105
48.5
1995
125
44.0
1996
120
39.1
1997
155
29.0
1998
195
25.6
1999
175
22.8
2000
222
12.1
2001
207
1.0
2002
186
0.0
2003
129
6.2
2004
162
3.7
2005
219
0
2006
178
0
327
Frozen sections for breast cancer diagnosis
Fig. 2. Yearly rate of breast cancers submitted to frozen section analysis between 1992 and 2006 in our institution.
pT2+ cancers: 48.7%). In the 2000’s, the FS rate was
less than 2.5% in all pT cancer categories (Fig. 4).
Data on pre-surgical diagnostic procedures performed
on surgically treated lesions were completely available for screen-detected breast cancers and have been
previously published 10-11. All screen-detected breast
cancers were assessed with FNAC or CNB before surgery. FNAC was adopted as a first-line method to obtain
cytological smears from suspicious lesions with an accuracy that was well within the thresholds proposed by
European guidelines for quality assurance in breast cancer screening programmes 29. Briefly, the FNAC positive
predictive value for a malignant diagnosis was 99.3%,
the inadequate rate from cancer (IRc) was 2.4% and the
false-positive rate (FPR) was 0.5%.
Data on pre-surgical sampling diagnostic procedures
performed on clinically detected cancers were available for about 60% of all cases for years between 1992
and 1997, but for subsequent years (1998-2006) more
of 90% of cases were furnished with information about
the needle sampling procedures performed. The rate of
cancers submitted to a pre-surgical sampling procedure,
either FNAC and CNB, increased exponentially since
1995 (Fig. 5), which was balanced by the decreasing use
of FS (Fig. 2).
Discussion
The results of the current study about the use of FS on
primary breast lesions during 15 years of surgical pathology activity (1992-2006), have shown the progressive disuse of this technique in our institution. A rate as
high as 50% of primary breast cancers were submitted to
FS in 1992, but at present no cancers are assessed with
FS in an intraoperative setting (Tab. I).
For many years, the diagnosis of breast cancer was guided by the intraoperative assessment of suspicious lesions
by frozen sections. After long-lasting scientific discussions about accuracy of FS on breast lesions, pathologists
Fig. 3. Rate of breast cancers submitted yearly to frozen section analysis according to cancer size.
328
E. Manfrin et al.
Fig. 4. Rate of cancers submitted to frozen section analysis according to cancer size in the 1990’s (blue column) and 2000’s (pink column).
achieved an overall agreement on the appropriate setting in
which FS should be adopted 14 15 17 18 21 30-32. Trained personnel and accurate selection of lesions to be submitted to FS
evaluation limited the false–negative rate to as less than 1%,
and the number of deferred diagnoses to less than 5% 2 6 21.
The appropriateness of FS examination for diagnosis of
mammographically-detected lesions has been subject of
controversy, and most authors have concluded that frozen
section examination should be limited to cases with distinct
gross lesions larger 1.0 cm 16 17. As a consequence, the percentage of breast specimens evaluated by frozen sections
has decreased over the years. A review of data from Ben
Taub Hospital (Houston, USA) documented that, between
1985 and 1995, 20% to 35% of all intraoperative consultations sent to frozen section analysis were from the breast,
but this decreased to 4-8% in the 2000’s 21.
In our institution, the decreasing use of FS, already detectable in the middle of 1990’s, registered an acceleration at the beginning of 2000’s in concomitance with the
beginning of screening programme activity (Fig. 2).
Screening programmes favour the detection of lower
graded, smaller sized breast cancers as well as pre-invasive lesions and pure microcalcifications for which the
feasibility of intraoperative consultation has been evaluated, but not routinely recommended 3 33. Studies suggest that FS for these breast lesions may have a lower
accuracy and may impair the results of definitive histology from paraffin-embedded tissue due to freezing artefacts 14-17 34 35.
In the current cancer series, the beginning of the screening activity coincided with the growing detection of cancers smaller than 1 cm and the decreasing rate of cancers
larger than 2 cm (Fig. 1). However, only 8% of breast
cancers collected from 1999 to 2006 were screen-detected, and assume that the “positive” effect of screening
programmes in stimulating women to perform mammography examinations favoured the improved detection of small breast cancers even in a female population that was not invited to screening represents 92% of
the current series. The overall detection rate for cancers
Fig. 5. Rate of breast cancer submitted yearly to pre-surgical needle sampling between 1992 and 2006 in our institution.
329
Frozen sections for breast cancer diagnosis
smaller than 1 cm shifted from 12-18% between 1992
and 1996 to 20- 40% in subsequent years.
The growing number of small breast lesions may be a
cause of the reduced use of FS. The sensitivity of frozen
section diagnoses of breast lesions after the introduction
of a national programme in mammographic screening
in Luxembourg dropped from 92.3% in 1990 to 87.6%
in 1998, the negative predictive value from 95.7% to
88.3%, and invasive breast cancers ≤ 1 cm increased
from 14.2% to 22.3% (p < 0.01). Breast frozen section
examinations in 1990 compared to those in 1998 declined from 70.7% to 62.2% 20.
Nevertheless, the decreasing use of FS is not completely
explained by the increased detection rate of small cancers
less than 1 cm. In current series, the decreasing rate of FS
performed on primary breast cancers was observed in all
pT cancer categories (Fig. 2). The comparison between
the FS rate performed on breast cancers collected between
1992 and 1999 and the FS rate in cancer series between
2000 and 2006, stratified according to cancer size, highlights that in the 2000’s FS was exceptionally performed
for diagnostic purpose on primary breast cancers, whatever the cancer size (Fig. 3). This is far more interesting
for our analysis, especially if it is considered that in 2005
and 2006, on a total of 397 cancers, no FS was performed
(Tab. I), even if 60% of detected cancers were larger than
1 cm and potentially amenable to FS (Fig. 1).
The strictly adherence to guideline recommendations
favouring pre-surgical, image-guided needle assessment
of breast suspicious lesions to avoid unnecessary surgery 29, aided the widespread adoption of FNAC, CNB
and VAB to obtain a diagnosis on mammographically
detected breast lesions 36. In a multidisciplinary approach
to breast lesions, biopsy techniques provided optimal diagnostic accuracy with a sensitivity between 93% and
100% and a specificity between 98% and 100% 10 30-32,
which undoubtedly influenced the reduction of unre-
solved cases sent to FS. The type of breast lesion on
mammograms or ultrasound (focal, parenchymal distortion, calcifications) and the confidence of the radiologist or pathologist with a needle sampling technique are
guiding the modality to obtain diagnostic samples from
breast lesions 8-10, reducing costs 13 and limiting the use
of FS to those cases in which a pre-surgical diagnosis is
not adequate.
A preoperative core or fine-needle biopsy may eliminate
unnecessary surgery and significantly reduce costs 38-40.
The study of sentinel lymph node and schemes of neoadjuvant chemotherapy that increase breast conservation surgery, disease-free and overall survival in patients
with complete pathological response 41, favoured the
adoption of core needle biopsy for histological demonstration of breast carcinoma and for the assessment
of a biological cancer profile predictive of response to
medical therapy. In addition, preoperative diagnosis of
invasive breast cancer increases the likelihood of clean
margins at definitive surgery 38-40. This reduces the need
for a two-stage procedure and improves both surgical
and oncological outcomes 42 43.
Advances in surgical techniques, oncology, pathology,
radiotherapy and radiology have influenced a new vision for treatment of breast cancer and reduced surgical
trauma. The current results confirm that drastic changes
have occurred in the management of breast lesions, with
more patients evaluated in a pre-operative setting. After
more than 100 years from its first adoption as a rapid
method for breast cancer diagnosis 1, the use of frozen
sections is no longer considered for primary breast lesions. In an audited diagnostic activity on breast pathology, the routine use of FS on primary lesions is inappropriate, particularly in the assessment of clinically nonpalpable lesions. Its use should be limited to cases with
inadequate pre-surgical sampling quantified in no more
than 5% of surgically removed cancers 29.
References
8
Ciatto S, Houssami N, Ambrogetti D, et al. Accuracy and underestimation of malignancy of breast core needle biopsy: the Florence
experience of over 4000 consecutive biopsies. Breast Cancer Res
Treat 2007;101:291-7.
1
Wilson LB. A method for the rapid preparation of fresh tissue for
the microscope. JAMA 1905;45:1737.
2
Bianchi S, Palli D, Ciatto S, et al. Accuracy and reliability of frozen section diagnosis in a series of 672 non-palpable breast lesions. Am J Clin Pathol 1995;103:199-205.
9
Lieske B, Ravichandran D, Wright D. Role of fine-needle aspiration cytology and core biopsy in the preoperative diagnosis of
screen-detected breast carcinoma. Br J Cancer 2006;95:62-6.
3
Ferreiro JA, Gisvold JJ, Bostwick DG. Accuracy of frozen-section
diagnosis of mammographically directed breast biopsies. Results
of 1,490 consecutive cases. Am J Surg Pathol 1995;19:1267-71.
10
4
Fessia L, Ghiringhello B, Arisio R, et al. Accuracy of frozen section
diagnosis in breast cancer detection. A review of 4436 biopsies and
comparison with cytodiagnosis. Pathol Res Pract 1984;179:61-6.
Manfrin E, Mariotto R, Remo A, et al. Is there still a role for fineneedle aspiration cytology in breast cancer screening? Experience
of the Verona mammographic breast cancer screening program
with real-time integrated radiopathologic activity (1999-2004).
Cancer Cytopathol 2008;144:74-82.
11
Manfrin E, Falsirollo F, Remo A, et al. Cancer size, histotype, and
cellular grade may limit the success of fine-needle aspiration cytology for screen-detected breast carcinoma. Cancer Cytopathol
2009;117:491-9.
5
Niu Y, Fu XL, Yu Y, et al. Intra-operative frozen section diagnosis of breast lesions: a retrospective analysis of 13,243 Chinese
patients. Chin Med J (Engl) 2007;120:630-5.
6
Rosen PP. Frozen section diagnosis of breast lesions. Recent experience with 556 consecutive biopsies. Ann Surg 1978;187:17-9.
12
Mariotto R, Brancato B, Bonetti F, et al. Real-time reading in
mammography breast screening. Radiol Med 2007;112:287-303.
7
Berner A, Davidson B, Sigstad E, et al. Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions. Diagn
Cytopathol 2003;29:344-8.
13
Nasuti JF, Gupta PK, Baloch ZW. Diagnostic value and cost-effectiveness of on-site evaluation of fine-needle aspiration specimens:
review of 5,688 cases. Diagn Cytopathol 2002;27:1-4.
330
14
Immediate management of mammographically detected breast lesions. Association of Directors of Anatomic and Surgical Pathology. Am J Surg Pathol 1993;17:850-1.
15
Cheng L, Al-Kaisi NK, Liu AY, et al. The results of intraoperative consultations in 181 ductal carcinomas in situ of the breast.
Cancer 1997;80:75-9.
16
17
Fechner RE Frozen section examination of breast biopsies. Practice parameter. Am J Clin Pathol 1995;103:6-7.
Niemann TH, Lucas JG, Marsh WL Jr. To freeze or not to freeze. A
comparison of methods for the handling of breast biopsies with no
palpable abnormality. Am J Clin Pathol 1996;106:225-8.
18
Oberman HA. A modest proposal. Am J Surg Pathol 1992;16:69-70.
19
Scheiden R, Sand J, Tanous AM, et al. Consequences of a National
Mammography Screening Program on diagnostic procedures and
tumor sizes in breast cancer. A retrospective study of 1540 cases
diagnosed and histologically confirmed between 1995 and 1997.
Pathol Res Pract 2001;197:467-74.
E. Manfrin et al.
30
Caya JG, Robinson TM. Accuracy and reliability of frozen section
diagnosis. Am J Clin Pathol 1995;104:358-60.
31
Cserni G. Pitfalls in frozen section interpretation: a retrospective
study of palpable breast tumors. Tumori 1999;85:15-8.
32
Speights VO Jr. Evaluation of frozen sections in grossly benign
breast biopsies. Mod Pathol 1994;7:762-5.
33
Dorel-Le Theo M, Dales JF, Garcia S, et al. Accuracy of intraoperative frozen section diagnosis in non palpable breast lesions: a
series of 791 cases. Bull Cancer 2003;90:357-62.
34
Riedl O, Fitzal F, Mader N, et al. Intraoperative frozen section
analysis for breast-conserving therapy in 1016 patients with breast
cancer. Eur J Surg Oncol 2009;35:264-70.
35
Tinnemans TGM, Wobbes TH, Holland R, et al. Mammographic
and histologic correlation of non-palpable lesions of the breast
and reliability of frozen section diagnosis. Surg Gynecol Obstet
1987;165;523-9.
20
Scheiden R, Sand J, Tanous AM, et al. Accuracy of frozen section diagnoses of breast lesions after introduction of a national programme
in mammographic screening. Histopathology 2001;39:74-84.
36
Bruening W, Fontanarosa J, Tipton K, et al. Systematic review:
comparative effectiveness of core-needle and open surgical biopsy
to diagnose breast lesions. Ann Intern Med 2010;152:238-46.
21
Laucirica R. Intraoperative assessment of the breast: guidelines
and potential pitfalls. Arch Pathol Lab Med 2005;129:1565-74.
37
22
Chagpar A, Yen T, Sahin A, Hunt KK, et al. Intraoperative margin
assessment reduces reexcision rates in patients with ductal carcinoma in situ treated with breast-conserving surgery. Am J Surg
2003;186:371-7.
Bulgaresi P, Cariaggi P, Ciatto S, et al. Positive predictive
value of breast fine needle aspiration cytology (FNAC) in combination with clinical and imaging findings: a series of 2334
subjects with abnormal cytology. Breast Cancer Res Treat
2006;97:319-21.
38
23
Fleming FJ, Hill AD, Mc Dermott EW, et al. Intraoperative margin assessment and re-excision rate in breast conserving surgery.
Eur J Surg Oncol 2004;30:233-7.
White RR, Halperin TJ, Olson JA, et al. Impact of core-needle
breast biopsy on the surgical management of mammographic abnormalities. Ann Surg 2001;233:769-77.
39
24
Jensen JA. Breast cancer: should we investigate margins or redesign the surgical approach? J Am Coll Surg 2010;210:1012.
25
Jensen AJ, Naik AM, Pommier RF, et al. Factors influencing accuracy of axillary sentinel lymph node frozen section for breast
cancer. Am J Surg 2010;199:629-35.
Cox CE, Reintgen DS, Nicosia SV, et al. Analysis of residual cancer after diagnostic breast biopsy: an argument for fine-needle
aspiration cytology. Ann Surg Oncol 1995;2:201-6.
40
26
Gipponi M, Bassetti C, Canavese G, et al. Sentinel lymph node as
a new marker for therapeutic planning in breast cancer patients. J
Surg Oncol 2004;85:102-11.
King TA, Cederbom GJ, Champaign JL, et al. A core breast biopsy diagnosis of invasive carcinoma allows for definitive surgical
treatment planning. Am J Surg 1998;176:497-501.
41
van der Hage JA, van de Velde CJ, Julien JP, et al. Preoperative
chemotherapy in primary operable breast cancer: results from the
European Organization for Research and Treatment of Cancer
trial 10902. J Clin Oncol 2001;19:4224-37.
42
Spivack B, Khanna MM, Tafra L, et al. Margin status and local recurrence after breast-conserving surgery. Arch Surg
1994;129:952-7.
43
Wazer DE, DiPetrillo T, Schmidt-Ullrich R, et al. Factors influencing cosmetic outcome and complication risk after conservative
surgery and radiotherapy for early-stage breast carcinoma. J Clin
Oncol 1992;10: 356-363.
27
Liu LC, Lang JE, Lu Y, et al. Intraoperative frozen section analysis
of sentinel lymph nodes in breast cancer patients: a meta-analysis
and single-institution experience. Cancer 2011;15;117:250-8.
28
Greene FL, Page DL, Fleming ID, et al. AJCC Cancer staging
handbook. New York: Springer-Verlag 2002.
29
Perry N, Broeders M, de Wolf C, et al. European Guidelines for
Quality Assurance in Breast Cancer Screening and Diagnosis. 4th
ed. Luxembourg: Office for Official Publications of the European
Communities 2006.
pathologica 2011;103:331-336
Original article
The diagnostic accuracy of cervical biopsies
in determining cervical lesions: an audit
Department of Histopathology, Hammersmith Hospital, Imperial College London, UK
Key words
Cervix • Biopsy • Colposcopy • Dysplasia • Cancer • Screening
Summary
Objective. The present audit was carried out to assess the diagnostic accuracy of cervical punch biopsy during colposcopy in
comparison with diagnosis from subsequent cone excision.
Design and setting. Retrospective analysis was performed by
examining the histopathology reports for paired cervical punch
biopsies and cervical cone excisions for cases reported from April
2004 to March 2005 (when cervical biopsies and cones were
reported by general pathologists) and from January to December
2008 (when reporting by specialist gynaecological pathologists
was instituted).
Sample. 150 women had both cervical punch and cone biopsies
performed in the 2004-2005 period, while 149 women had both
biopsies performed in 2008.
Main outcome measures and results. In 2004-5, the rate of consistent diagnosis was 68.7%, compared with 75.8% in 2008. This
was due to a decrease in the rates of overdiagnosis (16.7% vs.
14.8%) and underdiagnosis (14.7% vs. 9.4%), which was statistically significant. The sensitivity rates for 2004-5 and 2008 were
87.5% and 89.7%, and the specificity rates for the same periods
were 39.8% and 39.4% respectively.
Conclusions. This audit highlights the importance of planning
patient management on the basis of co-ordinated information
from smear results, history, colposcopy findings and cervical
biopsies. The introduction of specialist gynaecological histopathology reporting has significantly improved the rates of consistent diagnosis.
Introduction
opsy, the patient then undergoes cervical cone or loop
excision.
Therefore, accurate diagnosis on the biopsy taken at colposcopy is key in directing further management of the
patient. Despite the importance of this key step in the
patient pathway, there have been few studies examining the reliability of cervical punch biopsies. One study
analysed 352 cases and showed that there was a concordance rate of only 66% between the histological diagnoses of punch biopsies and the results of the subsequent
loop excision of the cervix 3. In another study of 107
cases, cervical punch biopsy was compared to cytology.
It was found that there was a consistency rate of 63%
between cervical punch biopsies and cones 4.
We investigated the accuracy of reporting of cervical biopsies taken at colposcopy, which would influence the
subsequent management of patients. Moreover, the practice of histopathologists as a whole is moving towards
specialist reporting. It also remains to be seen if such a
move improves the accuracy of cervical punch biopsy
In the UK, a cervical screening program has been implemented since the 1980s, and the advantages of cervical
screening are well documented, with a decrease in both
incidence and mortality from cervical cancers. Despite
its success, cervical screening by cytology is not always
reliable. It has been established that the average screening sensitivity and specificity of cervical cytology is
about 61-66% and 82-91%, respectively 1 2. However, a
positive cervical cytology result is only the first step in
the pathway towards definitive diagnosis and treatment
of a cervical lesion. The current practice in the UK is
that a patient with a cytology result confirming definite dyskaryosis or with repeated borderline change
requires referral to colposcopy. At colposcopy, the
cervix is visualized and a punch biopsy is often taken
for histological examination. If high grade cervical
intraepithelial neoplasia (CIN) or cervical glandular
intraepithelial neoplasia (CGIN) is confirmed on bi-
Acknowledgements
Correspondence
M. El-Bahrawy is grateful for support from the NIHR Biomedical
Research Centre funding scheme. J. Wang receives funding from
the NIHR Clinical Lecturer scheme.
Mona A. El-Bahrawy, Department of Histopathology, Imperial
College London, Hammersmith Hospital, DuCane Road, London
W12 0NN UK - Tel. 020 8383 3442 - Fax 020 8383 8141 - E-mail:
[email protected]
332
diagnosis. In this audit, we investigated the diagnostic
accuracy of cervical biopsies performed at a gynaecological cancer centre. The accuracy of diagnosis in two
different periods was analysed, a period during which
the diagnosis of cervical biopsies and cones was done by
general pathologists, and a period after specialist reporting by gynaecological histopathologists was instituted
and the vast majority of cervical biopsies were reported
by specialists.
Methods
Patients
This is a retrospective study of histopathology reporting
on cervical punch biopsies and cones during two periods.
The earlier period was from 1 April 2004 to 31 March
2005, and the later period was from 1 January 2008 to
31 December 2008. Only patients who had both a cervical biopsy and a subsequent cone biopsy reported at the
Department of Histopathology, Hammersmith Hospital,
during the periods defined were included.
Data collection
For each pair of specimens, pathology reports were retrieved and the following data collected: type of specimen, consultant histopathologist (general or specialist)
reporting the case and diagnosis. In cases where the
diagnosis fell between two categories, the higher grade
diagnosis was recorded, as in most cases further management would be based on the higher grade disease.
As examples, for the purpose of this audit in a punch
biopsy reported as showing CIN 2-3, the diagnosis was
considered as CIN 3 and for a punch biopsy where the
diagnosis is CIN 1 and CGIN, the diagnosis was CGIN.
Based on the diagnoses of the biopsies and cones, each
pair of specimens was categorized as having consistent
diagnoses, overdiagnoses or underdiagnoses. Situations
of overdiagnosis and underdiagnosis are summarized in
Table I.
For the audit purposes, since CIN2 and CIN3 are both
high grade lesions which have similar management protocols, a biopsy of CIN2 with a subsequent cone excision
showing CIN3, or vice versa, was classified as consistent
diagnosis. This is in line with the Bethesda classification
Tab. I. Criteria for overdiagnosis and underdiagnosis.
Overdiagnosis Criteria
CIN2 or 3
CIN1
CIN (difficult to grade)
Underdiagnosis Criteria
Cervical punch biopsy
CIN1
HPV
CIN (any grade)
Benign conditions/atypia
CIN1/HPV/benign conditions
HPV/benign conditions
HPV/benign conditions
of high-grade squamous intra-epithelial lesions (HSIL).
The same situation also applies for CIN2/3 and CGIN.
However, CIN1 and human papilloma virus (HPV) infections were categorized separately, despite the similar
management plans and the common Bethesda classification of low-grade SIL (LSIL). This is because these lesions have previously had different management strategies in the UK. In addition, a diagnosis of CIN (difficult
to grade) or an inadequate sample at cervical biopsy was
deemed to be consistent with any CIN grade in the cone
excision. However, a biopsy diagnosis of CIN (difficult
to grade) and a subsequent cone diagnosis of HPV only
or benign conditions was considered overdiagnosis.
In addition to comparing the reporting accuracy between the two periods, the results were categorized into
whether the reporting of the cervical punch biopsy was
done by specialist gynaecological histopathologists, or
by general histopathologists.
Standards
There have not been any previous publications that have
dealt in detail with the problem of overdiagnosis or underdiagnosis in cervical biopsies. However, Boonkilit et
al. have shown in their series that there is a concordance
rate of 66% between cervical biopsy results and cones 3.
For the purposes of the present audit, therefore, we have
considered a consistent diagnosis rate of 60% to be acceptable. Also, Thompson et al. have shown that there
was a negative diagnosis in cone excisions of 28-68% 5.
Thus, an overdiagnosis rate of less than 25% was considered acceptable.
Statistical analysis
To determine if the number of consistent diagnoses and
the number of either over- or underdiagnoses were significantly different between the two periods of reporting,
a chi-square test was performed. A significant difference
in reporting accuracy was if the p value was < 0.05.
Finally, to calculate the sensitivity, specificity, positive
predictive value (PPV) and negative predictive value
(NPV) for the two reporting periods, each diagnosis was
categorized into positive results (high-grade lesions or
higher, including CIN2, 3, CGIN and invasive cancer) or
negative results (low-grade or benign lesions, including
CIN1, HPV, atypia or inflammation). This classification
was based on the management protocols for the diagnosis, with high-grade lesions being an indication for a
cone excision. Biopsy samples which were CIN (difficult to grade) or inadequate were classified as consistent
with the cone diagnosis (as described above).
Results
Cone biopsy
CIN2 or 3
CIN 1, 2 or 3
Invasive carcinoma
HPV/CIN/invasive carcinoma
Cervical biopsy and cone results
From April 2004 to March 2005, a total of 744 cervical punch biopsies were reported. Of these, 150 cervical
biopsies had subsequent cone biopsies done in the same
period. The mean age of patients was 32 years (range
Diagnostic accuracy of cervical biopsies
333
21-77 years). In 2008 (January to December), the total
Fig. 1. Case 1: Cervical punch biopsy showed CIN3 (A, X100), and
number of cervical punch biopsies was 514, with 149
the subsequent cone only showed inflammation (B, X100). Case
2: The cervical punch biopsy showed no definite features of dysof patients having subsequent cone biopsies. The mean
plasia (C, X100) and the subsequent cone showed CIN2 (D, X100).
age of the patients for this period was 31 years (range
23-70).
In 2004-2005, the histological diagnoses of cervical biopsies were 13 CIN1, 64 CIN2, 42 CIN3, 2 CIN difficult
to grade, 5 CGIN, 5 invasive carcinoma, 6 HPV and 13
benign lesion (e.g. cervicitis). Among the cone biopsies,
there were 27 CIN1, 45 CIN2, 50 CIN3, 4 CGIN, 10
invasive carcinoma, 7 HPV and 7 benign lesion. The
percentages of high-grade lesions diagnosed by cervical
biopsies and at cone excision were 78.7% and 72.7%,
respectively. Figure 1 shows examples of the different
diagnoses in cervical punch and cone biopsies.
In 2008, among the cervical biopsies, there were 13 CIN1,
89 CIN2, 29 CIN3, 1 CIN difficult to grade, 2 CGIN, 3 invasive carcinoma, 2 HPV and 10 benign. Among the cone
biopsies, there were 21 CIN1, 65 CIN2, 45 CIN3, 2 CGIN,
3 invasive, 2 HPV and 10 benign lesion. The percentages
of high-grade lesions diagnosed
by cervical biopsies and at cone
Fig. 2. (A) Rates of over- and under- and correct diagnosis in the years 2004-5 and 2008. (B)
excision were 83.2% and 77.2%,
Sensitivities, specificities, PPV and NPV in both periods.
respectively.
Sensitivity and specificity of reporting
For the reporting period 2004-5,
the sensitivity of the cervical biopsy was 87.5%, the specificity
was 39.5%, the PPV was 81.0%
and the NPV was 51.7%. In
2008, the respective values were
89.7%, 39.4%, 83.9% and 52%.
The results are shown in Figure
2A.
Consistency of reporting
The results were categorized
into cervical biopsies that were
consistent with cone diagnosis,
overdiagnoses or underdiagnoses. The results are shown in
Tables II, III and IV respectively. There was an increase in the
percentage of consistent diagnoses in 2008 (75.8%) compared
with 2004 (68.7%), with decrease in both the incidences of
over- (14.8% vs 16.7%) and underdiagnoses (9.4% vs 14.7%).
The results are presented in
Figure 2B.
Considering cases of overdiagnosis in the original cervical biopsy, an important subset were
those diagnosed as high grade
lesions on the cervical biopsy,
but subsequently found to be low
grade or benign lesions on cone
334
excision. For this subset, it was also found that there was
a decrease from 15.3% in 2005 to 13.4% in 2008 (highlighted in bold in Table III).
In 2004-5, only 15 of 150 (10%) cases were reported by
specialist gynaecological pathologists. In contrast, 123
of 149 (83%) cases were reported by specialist pathologists in 2008. The results show that for the cervical biop-
sies reported by general pathologists in 2004-2005, the
incidences of consistent diagnosis, overdiagnosis and
underdiagnosis were 68.1%, 17.0% and 14.8%, respectively. In contrast, for biopsies undergoing specialist reporting in 2008, the incidences of consistent diagnosis,
overdiagnosis and underdiagnosis were 76.4%, 14.6%
and 8.9%, respectively.
Tab. II. Number of consistent diagnoses between cervical biopsies and cones.
Punch Biopsy Diagnosis Cone Diagnosis
2004
% of total
2008
CIN1
CIN1
5
3.3
4
% of total
2.7
CIN2
CIN2
45
30.0
70
47.0
CIN3
CIN3
35
23.3
27
18.1
INV
INV
5
3.3
3
2.0
CGIN
CGIN
3
2.0
1
0.7
NAD/INFL/META
NAD/INFL/META
3
2.0
5
3.4
Others
CIN 2/3
CGIN
CIN(difficult to grade)
Inadequate
Total
Others
CGIN
CIN2/3
CIN2/3
CIN/INV
7
(1)
(1)
(1)
(4)
103
4.7
3
(2)
2.0
(1)
68.7
113
75.8
% of total
11.3
2008
16
% of total
10.7
NAD: No abnormality detected; INFL: Inflammation; META: Metaplasia; INV: Invasive carcinoma
Tab. III. Number of overdiagnoses in cervical biopsies compared with cones.
CIN2/3
CIN1
2004
17
CIN2/3
HPV
3
2.0
0
0.0
CIN2/3
NAD/INFL/META
3
2.0
4
2.7
CIN3
CIN2
0
0.0
0
0.0
CIN1
HPV
1
0.7
1
0.7
CIN (difficult to grade)
HPV
1
0.7
0
0.0
CIN1
Atypia
Total
0
0.0
1
0.7
25
16.7
22
14.8
Tab. IV. Number of underdiagnoses in cervical biopsies compared with cones.
2004
% of total
2008
% of total
CIN1
CIN2/3
6
4.0
7
4.7
CIN2
CIN3
0
0.0
0
0.0
HPV
CIN
(CIN1)
(CIN2/3)
INV
6
(2)
(4)
4
(3)
(1)
5
(1)
(2)
(2)
1
4.0
1.3
2.7
2
(1)
(1)
0
3.3
4
2.7
0.7
1
0.7
22
14.7
14
9.4
CIN
(CIN3)
(CIN1)
NAD/INFL/META
NAD/INFL/META
Atypia
Total
CIN/INV
(INV)
(CIN2/3)
(CIN1)
HPV
0.0
(4)
335
Diagnostic accuracy of cervical biopsies
Statistical analysis
To determine if there was a difference in the incidence
of over- and underdiagnosis between the two periods
of reporting, Pearson’s chi-square test was applied. A
statistically significant improvement in the rate of overdiagnosis was found cChi-square = 346, p = 0.03) and
underdiagnosis (chi-square = 375, p < 0.01).
Discussion
Cervical punch biopsy is an essential component in cervical screening, yet it has limitations despite targeted sampling at colposcopy and care in specimen processing and
reporting. A previous study showed that 33% of directed
biopsies did not detect the high-grade lesion found in the
cone 6, while 40% of random biopsies were able to detect
high grade dysplasia. Assessment of cervical cone biopsies also has its challenges. In one study, 99 negative cones
were reviewed and 21 cases were subsequently found to
be positive for dysplasia or malignancy 7. In another study,
of 95 negative cone biopsies 25 on subsequent review or
resectioning were found to have significant lesions 5.
In this study, we investigated the accuracy of cervical
punch biopsy reporting, as compared with subsequent
diagnosis of cone excision specimens. We show that
the rate of consistent diagnoses has increased from
2004 to 2008, from 68.7% to 75.8%. This was due to
a statistically significant decrease in both the rates of
over- and underdiagnoses. The reason for this improvement is most likely due to a change in the practice of
reporting cervical biopsies, from that by general histopathologists in the general pool of specimens, to
specialist reporting by gynaecological histopathologists, which was the only change in laboratory practice
between both periods. In a previous study examining
positive cones to determine the accuracy of biopsies 8,
of 355 biopsy-proven cases of dysplasia, 323 had a
subsequent positive cone. With 22 negative cones, the
PPV was 91%. However, when only high grade lesions
on pre-cone histology or cytology were analysed, 277
of 371 cases had a positive cone diagnosis, giving a
sensitivity of 74.7%. Our current study therefore was
comparable with a sensitivity of 89.7% and a PPV of
83.9% with specialist reporting.
Two other previous studies compared the consistency between the pre-cone diagnosis and the cone excision. The
consistency rate between cervical biopsy and cone excision pathological diagnoses was 66.2% in one study 3
and 63% in another 4. Our study showed a comparable
consistency rate in the first period, but in the second
period where specialist reporting was implemented, the
rate was increased to over 75%.
It is important to note that in our cohort cases with underdiagnosis still underwent cone biopsies, although these
diagnoses will not lead to a cone excision if considered
in isolation. In these cases, the cone was performed on
the basis of smear results of high grade dyskaryosis, persistent low grade dyskaryosis or a colposcopic impression of high grade lesion. This highlights the importance
in which biopsy diagnoses are considered in context of
the cervical smear and colposcopy results, thus leading
to a cone excision despite a negative or low grade biopsy, if indicated.
The overdiagnosis rate is considered more critical, as it
leads to cone excisions even if smear results and colposcopic impression are not consistent. In our study,
the rate of overdiagnoses of high grade lesions was decreased from 15% to 13% from the first to the second
period of study. This is significant, as cone excisions can
be associated with complications (although rare), and
hence should be avoided if not indicated.
It must be stated that the discrepancy between punch
biopsy diagnosis and cone biopsy does not necessarily
imply an incorrect interpretation by the pathologist in all
cases. In some instances, the lesions are small and may
be totally removed by the biopsy, and hence may not be
represented in the subsequent cone. Also, although very
informative and accurate in the majority of cases, cervical punch biopsies have their inherent limitations. It is
possible that the biopsied part of the cervix at colposcopy
does not target the area of actual abnormality, and hence
the dysplasia is not detected due to an erroneous site of
sampling. Improvements which may increase the accuracy of the biopsy include four quadrant biopsies 9 and
studying histological sections taken at multiple levels for
thorough histological assessment 10. A fact that must also
be acknowledged is that in some cases there is justifiable
interobserver variability. Some biopsies are difficult to
interpret due to being small, partially traumatised, poorly orientated or even showing very subtle changes that
require much experience and may well initiate interobserver variability. Recent developments to improve the
diagnosis of cervical biopsies, as well as cervical smears,
include HPV genotyping for high risk HPV subtypes
and immunohistochemistry for p16INK4a 11 12. These
additional tests have been shown to aid in the diagnosis of CIN in equivocal and difficult cases. For example,
p16INK4a has been shown to significantly improve the
interobserver agreement between pathologists for punch
biopsies 12.
Conclusion
In conclusion, the role of cervical biopsy is essential but
still has its limitations. As recommended by the National
Health Service (NHS) cervical screening programme, it
is essential that patient management is based on co-ordinated information of smear results, history, colposcopy
findings and cervical biopsy results. It is recommended
that these specimens are reported by specialist gynaecological pathologists, which have been shown to be advantageous in increasing the diagnostic accuracy.
336
References
1
2
3
Coste J, Cochand-Priollet B, de Cremoux P, et al. Cross sectional
study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening.
BMJ 2003;326:733.
Kulasingam SL, Hughes JP, Kiviat NB, et al. Evaluation of human
papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of
referral. JAMA 2002;288:1749-57.
Boonlikit S, Asavapiriyanont S, Junghuttakarnsatit P, et al. Correlation between colposcopically directed biopsy and large loop
excision of the transformation zone and influence of age on the
outcome. J Med Assoc Thai 2006;89:299-305.
4
Heatley MK, Bury JP. The correlation between the grade of dyskaryosis on cervical smear, grade of cervical intraepithelial neoplasia (CIN) on punch biopsy and the final histological diagnosis
on cone biopsies of the cervix. Cytopathology 1998;9:93-9.
5
Thompson AD, Duggan MA, Nation J, et al. Investigation of laser
cervical cone biopsies negative for premalignancy or malignancy.
J Low Genit Tract Dis 2002;6:84-91.
Wentzensen N, Zuna RE, Sherman ME, et al. Accuracy of cervical
specimens obtained for biomarker studies in women with CIN3.
Gynecol Oncol 2009;115:493-6.
6
Golbang P, Scurry J, de Jong S, et al. Investigation of 100 consecutive
negative cone biopsies. Br J Obstet Gynaecol 1997;104:100-4.
7
Spitzer M, Chernys AE, Shifrin A, et al. Indications for cone biopsy:
pathologic correlation. Am J Obstet Gynecol 1998;178(1 Pt 1):74-9.
8
Cagle AJ, Hu SY, Sellors JW, et al. Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection
with acetic acid. Int J Cancer 2010;126:156-61.
9
Fadare O, Rodriguez R. Squamous dysplasia of the uterine cervix:
tissue sampling-related diagnostic considerations in 600 consecutive biopsies. Int J Gynecol Pathol 2007;26:469-74.
10
11
Sigurdsson K, Taddeo FJ, Benediktsdottir KR, et al. HPV genotypes in CIN 2-3 lesions and cervical cancer: a population-based
study. Int J Cancer 2007;121: 2682-7.
Horn LC, Reichert A, Oster A, et al. Immunostaining for p16INK4a
used as a conjunctive tool improves interobserver agreement of
the histologic diagnosis of cervical intraepithelial neoplasia. Am J
Surg Pathol 2008;32:502-12.
12
pathologica 2011;103:337-339
Original article
“Combined” desmoplastic melanoma of the vulva
with poor clinical outcome
G. Collina
Unit of Anatomic Pathology, Department of Oncology, Maggiore Hospital, Bologna, Italy
Key words
Desmoplastic melanoma • “Combined” • Vulva • Immunohistochemistry • Protein S100
Summary
Desmoplastic melanomas in an unusual variant of melanoma
that usually occurs in sun-damaged skin of elderly people. Desmoplasia may be the prominent features of the lesion or represent a portion of an otherwise non-desmoplastic melanoma;
these latter are called “combined” desmoplastic melanoma. Desmoplastic melanomas of the vulva are rare. Herein, we report
a case of “combined” DM of the labia minor consisting of a
superficial spitzoid component and a deeper spindle desmoplastic component. Protein S-100 expression was ubiquitous, while
MART-1 and HMB-45 were limited to the superficial spitzoid
component and were negative in desmoplastic areas. Notably,
the nodal metastasis retained the same biphasic pattern seen in
the primary tumour. The patient died of widespread metastatic
disease 3 years after diagnosis.
Introduction
Melanoma represents the second most frequent malignancy of the vulva. These neoplasms occur mostly in
post-menopausal women and are generally diagnosed
when they ulcerate and discharge blood 1. Vulvar desmoplastic melanomas are uncommon, and only a few
cases have been documented 1-4. Herein, we report a
case of “combined” desmoplastic and spitzoid melanoma.
The excised material was fixed in 10% formalin and embedded in paraffin. Deparaffinized 5-µm-thick sections
were stained with haematoxylin and eosin. Immunohistochemistry was performed using the Ventana System
employing the following antibodies: protein S100 (Ventana ready to use), MART-1 [Melan-A (A-103), Ventana
ready to use], HMB-45 (Cell Marque ready to use), actin
[muscle-specific (HHF35) Cell Marque ready to use].
Clinical history
Results
A 73-year-old female sought medical attention for an
ulcerated nodule of the right labia major. A biopsy was
performed and a diagnosis of melanoma was rendered.
Two weeks later she underwent surgical excision. The
skin ellipse measured 2.5 × 2 cm and was centred by
a grey ulcerated nodule measuring 2 cm in diameter.
Sentinel lymph node procedure was performed and a
right inguinal lymph node was removed. The sentinel
lymph was metastatic. Complete inguinal lymphoadenectomy failed to show other metastases. The patient
died of widespread metastatic disease 3 years after diagnosis.
A 0.3 cm punch biopsy showed a hyperplastic epidermis with atypical melanocytes localized at the dermalepidermal junction (Fig. 1). The upper dermis was infiltrated by epithelioid and pleomorphic melanocytes.
Dilated capillaries reminiscent of Spitz lesion were also
present (Fig. 2). The skin ellipse showed a polypoid, ulcerated and hypopigmented tumour (Fig. 3). The lesion
was composed of single or grouped melanocytes, which
reached the upper layer of the epidermis.
In the deeper part of the dermis, the epithelioid component merged with spindle neoplastic cells interspersed
among dense collagen bundles (Fig. 4) which represent-
Correspondence
Guido Collina, Unit of Anatomic Pathology, Department of
Oncology, Maggiore Hospital, l.go B. Nigrisoli 2, 40133 Bologna,
Italy - Tel. +39 051 6478908 - Fax +39 051 6478660 - E-mail:
[email protected]
338
G. Collina
Fig. 1. Punch biopsy shows ulcerated and hyperplastic epidermis
and neoplastic cells expanding the superficial dermis, revealing oedema and dilated vessels.
Fig. 4. In the deep part of the lesion, neoplastic melanocytes
are spindled and immersed in a desmoplastic stroma, which
shows increased mucin.
Fig. 2. Neoplastic melanocytes are either epithelioid either spindled. Lymphocytes in groups and dilated vessels are also present
(left side).
Fig. 5. S100 protein diffusely stained neoplastic melanocytes in
both the epithelioid and spindle component in the desmoplastic
area.
Fig. 3. Melanoma has polypoid conformation with dumbbell
features and reaches the deep dermis almost approaching the
sub-cutaneous fat.
Fig. 6. Strong MART 1 immunostaining in the epithelioid superficial melanocytes, while spindled melanocytes, including those of
the desmoplastic area, were negative.
ed 40% of the entire lesion. Features of neurotropism
and angiotropism were present.
Protein S100 was ubiquitous (Fig. 5), while MART-1
strongly stained the epithelioid melanocytes of the spitzoid component of the upper part of the lesion that were
almost negative in the desmoplastic areas except for rare
spindle cells (Fig. 6), which were nonetheless faintly
positive; HMB-45 stained only a few epithelioid melanocytes. Smooth muscle actin was negative.
The micro-staging of this lesion showed it to fall into
the poor prognosis category (i.e. 5.7 mm in Breslow’s
thickness, ulceration and the number of mitosis was at
339
“Combined” desmoplastic melanoma of the vulva with poor clinical outcome
Fig. 7. Metastatic-inguinal-sentinel-lymph node: the biphasic
patter of primary lesion is also preserved in the metastasis, epithelioid melanocytes are localized on the left, while the desmoplastic area is evident on the right.
least 6 per mm2). The lymph node showed metastatic
deposits composed of either spitzoid or desmoplastic areas (Fig 7).
Discussion
Desmoplastic melanoma (DM) is a rare variant of
spindle cell melanoma that usually occurs in the sundamaged skin of elderly patients. Conley et al. first described DM in 1971 as “a variant of spindle cell melanoma which elicits the production of abundant collagen” 5. Reed and Leonard further expanded the original
description and documented the extensive infiltration
References
1
Byrne PR, Maiman M, Mikhail A, et al. Neurotropic desmoplastic melanoma: a rare vulvar malignancy. Gynecol Oncol 1995;56:289-93.
2
Warner TF, Hafez GR, Buchler DA. Neurotropic melanoma of the
vulva. Cancer 1982;49:999-1004.
3
Mulvany NJ, Sykes P. Desmoplastic melanoma of the vulva. Pathology 1997;29:241-5.
4
Rogers RS 3 , Gibson LE. Mucosal, genital, and unusual clinical
variants of melanoma. Mayo Clin Proc 1997;72:362-6.
rd
or replacement nerve bundles typical of this melanoma
subtype 6.
DM/neurotropic melanomas of the vulva are uncommon, and similar to mucosal melanomas, have a dismal
prognosis 4.
We report a case of “combined” DM of the labia minor consisting of a superficial spitzoid component and a
deeper spindle desmoplastic component. S-100 expression was ubiquitous, while MART-1 and HMB-45 were
limited to the superficial spitzoid component and were
negative in desmoplastic areas. Notably, the nodal metastasis retained the same biphasic pattern seen in the
primary tumour. This is infrequent considering that in a
series of 55 DM only 2% showed lymph-node metastases 7. Complete lymphoadenectomy failed to show other
metastatic lymph nodes. The patient died 3 years later
due to widespread metastases.
There is still controversy on the prognosis of DM. Early
studies suggested an aggressive behaviour than conventional melanomas, while others documented DM with a
more favourable clinical course 5
Busam et al. 8 suggested that pure desmoplastic melanomas thicker than 4 mm have a better prognosis when
compared with combined DM and conventional melanomas of the same thickness. In their study, only 3 of
26 patients with pure DM died of disease compared to
the experience of their institution, where 25% of patients
died for thick conventional melanomas in 3 years. Our
patient seems to confirm that thickness and the presence
of “combined” histological components represent valuable prognostic indicators of poor outcome.
5
Conley J, Lattes R, Orr W. Desmoplastic malignant melanoma (a
rare variant of spindle cell melanoma). Cancer 1971;28:914-36.
6
Reed JG, Leonard DD. Neurotropic melanoma: a variant of desmoplastic melanoma. Am J Surg. Pathol 1979;3:301-11.
7
de Almeida LS, Requena L, Rutten A, et al. Desmoplastic malignant melanoma : a clinicopathologic analysis of 113 cases. Am J
Dermatopathol 2008;30:207-15.
8
Busam KJ, Mujumdar U, Hummer AJ, et al. Cutaneous desmoplastic melanoma: reappraisal of morphologic heterogeneity and
prognostic factors. Am J Surg Pathol 2004;28:1518-25.
pathologica 2011;103:340-342
Case report
Tuberculosis of superficial lymph nodes, a not so rare
event to consider in diagnosis. A case in an elderly male
A. Merante, M.R. Ambrosio1, B.J. Rocca1, A.M. Condito2, A. Ambrosio3, M. Arvaniti4, G. Ruotolo
Head Physician Geriatric Unit, “Pugliese-Ciaccio” Hospital, Catanzaro, Italy; 1 Department of Human Pathology and Oncology,
Pathological Anatomy Section, University of Siena, Italy; 2 Emergency Medicine Unit, “Pugliese-Ciaccio” Hospital, Catanzaro, Italy;
3 University “Magna Graecia” of Catanzaro, Italy; 4 Microbiology Section, University “Federico II”, Napoli, Italy
Key words
Tuberculosis • Mycobacterium • PCR
Summary
Tuberculosis (TB) is still one of the most frequent infectious diseases worldwide. Until the 1990s, Western European countries
showed a low frequency of TB infection, but the rise of immigration has led to a rapid increase in its occurrence. In the elderly, TB
is emerging as a significant health problem (age-related decline of
the cell-mediated immunity, associated illnesses, use of immunosuppressive drugs, malnutrition, poor life conditions), although its
detection and diagnosis is not easy also considering its subclinical
presentation. Almost 70% of all TB infections in Italy are found
in the lungs; 50% of the extrapulmonary infections affect lymph
nodes. Due to the low incidence of superficial tuberculous lymphadenitis without pulmonary manifestations, the possibility of a TB
aetiology is often not taken into consideration in the differential
diagnosis of lymphadenopathy, resulting in significant delay of
appropriate treatment.
Herein, we describe the case of a 78-year-old male with nocturnal
fever, weakness, night sweats, loss of weight and decay in general condition. The patient had a past medical history of prostate
adenocarcinoma treated with hormone therapy. The past medical
history in association with clinical findings and laboratory data
(anaemia, high titers of fibrinogen and reactive C-protein) led to
the suspect of metastatic adenocarcinoma. Only histological and
molecular biology findings allowed us to make a correct diagnosis
of TB.
Introduction
numerous. It is well known that the age-related decline
of the cell-mediated immunity (thymus, lymph node
and spleen involution) may cause reactivation of latent
infections. Moreover, the presence of associated illnesses such as diabetes mellitus, chronic renal failure,
diffuse parenchymal lung diseases, certain malignancies, as well as the use of immunosuppressive drugs
(e.g. corticosteroids), may further impair cell-mediated
immunity, increasing the risk of reactivation. Adverse
social factors, such as malnutrition, poor living conditions as well as staying in nursing homes also affect the
elderly much more frequently than younger individuals 4 5. In the former, TB is not easy to detect and diagnose because it does not manifest so clearly in these
individuals. In fact, symptoms (loss of weight, night
sweats, weakness, anorexia, mild fever) are often nonspecific and may be attributed to age-related changes 6.
The presence of other chronic diseases may confuse the
clinical picture, and often the patient is unable to give
an accurate account of symptoms.
Tuberculosis (TB) is still one of the most frequentlyoccurring infectious diseases worldwide. According
to the World Health Organization (WHO) 1, approximately one-third of the world’s population is currently infected with tubercle bacilli, while 8 million new
cases of active disease develop each year and 3 million
patients die 2. Until the 1990s, Western European countries showed a rather low frequency of TB infection,
but the rise of immigration has led to a rapid increase
in its occurrence 3. Furthermore, it is well known that
TB can be associated with diseases that depress the
immune system, such as leukaemia or HIV, affecting
specific age groups (infants, elderly). In the elderly, TB
is emerging as a significant health problem. It may be
either exogenous or endogenous in origin, with the latter representing over 90% of cases and consisting of reactivation of dormant disease in the lungs or elsewhere
in the body 4. Predisposing factors in the elderly are
Correspondence
Maria Raffaella Ambrosio, Department of Human Pathology and
Oncology, Pathological Anatomy Section, University of Siena, via
delle Scotte 6, 53100 Siena, Italy - Tel. +39 0577 233236 - Fax
+39 0577 233235 - E-mail: [email protected]
Tuberculosis of superficial lymph nodes, a not so rare event to consider in diagnosis
Apart from general diagnostic problems, there are difficulties regarding the recognition of TB affecting various
sites. In fact, almost 70% of all TB infections in Italy 7
are found in the lungs; of the remaining extrapulmonary
infections, approximately 50% affect lymph nodes. Due
to the low incidence of tuberculous lymphadenitis without pulmonary manifestations, the possibility of TB is
often not taken into consideration in the differential diagnosis of lymphadenopathy, resulting in a significant
delay of appropriate treatment.
Unfortunately, very little clinical data is available on
the diagnosis and therapy of lymph node TB in Western
countries 8. However, owing to the immigration that has
taken place over the last decades, there is a renewed interest in the disease.
Case report
A 78-year-old male was admitted to the Geriatrics
Unit of Catanzaro Hospital for the onset of nocturnal
fever, weakness, night sweats, loss of weight and de-
341
cay of general conditions, for a few weeks. The patient
suffered from chronic obstructive airway disease and
cerebral vasculopathy. Moreover, he had a history of
prostatic adenocarcinoma treated with hormone therapy as well as a pacemaker. On physical examination,
a swelling of a right laterocervical lymph node was
observed. In particular, the node was tender, mobile
and painful with irregular borders. Blood pressure
was 110/60 mmHg, heart rate 94 beats per min (bpm)
and body temperature was 38.1°C. Laboratory data
revealed hyperleucocytosis (5.9 × 103/mm3) with absolute neutrophilia (neutrophils 78.3%, lymphocytes
13.3%), normochromic normocytic anaemia (haemoglobin 10.5 g/dl, mean corpuscular volume 88 μm3)
with an increase of acute phase proteins (C-reactive
protein-PCR, procalcitonin, fibrinogen). To rule out
a metastatic adenocarcinoma of the prostate or lymphoproliferative disorder, a lymph node ultrasound
imaging (US) of the neck and a whole body CT-scan
were performed. The US revealed an enlarged (7 cm
in maximum diameter), inhomogeneous lymph node
with a hyperechoic centre, and on this basis, tubercu-
Fig. 1. Effacement of lymph node architecture by large granulomas, with central necrosis, surrounded by epithelioid giant cells in a palisaded arrangement (a, haematoxylin-eosin [H&E], original magnification [OM] 10x); the giant cells show large, clear, slightly reticulated,
C-shaped nuclei (b, H&E OM 20x). Positivity for Ziehl-Neelsen stain (c, ZN OM 20x) and PCR for mycobacterium tuberculosis (d).
342
lous lymphadenopathy was suspected. Shortly after, a
Mendel-Mantoux test as well as sputum and urinalysis
were carried out with negative results.
Histological and microbiological analyses of the lymph
node were also conducted by US-guided fine-needle aspiration (FNA). One aliquot of FNA sample was fixed
in 95% ethyl alcohol and stained by Giemsa for cytologic analysis. Immunohistochemistry for CKAE1/AE3
and PSA was made. Another aliquot was used for microscopic detection of the microorganism using ZiehlNeelsen (ZN) stain as well as agar and radioactive culture (BACTEC). To assess the genotype of the mycobacterium, polymerase chain reaction (PCR) and the IS6110
restriction-fragment-length-polymorphism (RFPL) were
performed using standard methods 9.
Lymph node architecture was effaced by the presence of
large granulomas, sometimes confluent, with central necrosis (Fig. 1a). A number of epithelioid cells (arranged in a
palisaded architecture), multinucleated giant cells of Langhans type and, occasionally, foreign body type in between,
encircling caseosis and bordered by lymphocytes and plasma cells, were surrounded by thick fibrous layers (Fig. 1b).
CKAE1/AE3 and PSA were negative. ZN and PCR for
mycobacterium tuberculosis were positive (Fig. 1c-d).
On the basis of the morphological and molecular biology findings, a diagnosis of tuberculous lymphadenopathy was made.
Treatment with isoniazid, rifampicin and pyrazinamide
was established, according to the recommendations of
the American Thoracic Society 10, with immediate improvement of clinical conditions. One month later, the
patient developed hepatotoxicity, and isoniazid and rifampicin was replaced with rifabutin.
Discussion
TB remains one of the leading infectious diseases, causing significant morbidity and mortality worldwide 11. Although the reporting of new TB infections has declined
steadily over time, the frequency of lymph node TB has
References
1
Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph
node tuberculosis in Northern Germany: a clinical review. Chest
2002;121:1177-82.
2
Baussano I, Cazzadori A, Scardigli A, et al. Clinical and demographic aspects of extrathoracic tuberculosis: experience of an
Italian university hospital. Int J Tuberc Lung Dis 2004;8:486-92.
3
Brudey K, Driscoll JR, Rigouts L, et al. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international
spoligotyping database (SpolDB4) for classification, population
genetics and epidemiology. BMC Microbiol 2006,6:23.
4
Sood R. The problem of geriatric tuberculosis. Journal of Indian
Academy of Clinical Medicine 2004;5:156-62.
5
Salvado M, Garcia-Vidal C, Pilar Vazquez P, et al. Mortality of
Tubercolosis in very old people. J Am Geriatr Soc 2010;58:18-22.
6
Zevallos M, Justman JE. Tubercolosis in the elderly. Clin Geriatr
Med 2003;19:121-38.
A. Merante et al.
not decreased and accounts for almost 7.5% of all patients
infected by mycobacterium tuberculosis. Nevertheless, it
seems that tuberculous lymphadenopathy is not taken into
consideration in Western countries and diagnosis is performed only by histological examination 12.
In the present case, the past medical history (prostatic
adenocarcinoma), in association with clinical findings
(fever associated with vague and non-specific symptoms) and laboratory data (anaemia, high titres of fibrinogen and PCR) led to the suspect of metastatic adenocarcinoma. Only histological and molecular biology
findings allowed us to make a correct diagnosis. Differential diagnosis of granulomatous lymphadenopathy
includes sarcoidosis (well-defined, non-caseating granulomas with a ring of collagen), atypical mycobacterial
infections (less granulomatous changes with more acute
inflammation, sometimes with abscess formation and a
histiocytic proliferation of spindle cells mimicking an
inflammatory pseudotumor), lepromatous lymphadenitis
(rare, non-caseating granulomas with numerous foamy
macrophages replacing the paracortical regions and containing abundant intracellular organisms) and Hodgkin
lymphoma (non caseating granulomas in the paracortical areas, Reed-Stemberg and Hodgkin cells).
Conclusion
It is important to bear in mind that TB infection, although
infrequent, may be the cause of a lymphadenopathy. In
elderly patients, a delay in diagnosis represents a serious problem since TB is curable only when treatment is
established at an early stage 4.
The pathological examination of lymph nodes plays a critical role in diagnosis. In fact, although from a clinical viewpoint there may be some confusion as to whether an enlarged
lymph node is due to TB or to other benign or malignant
lymphadenopathies, the histological picture is characteristic
and diagnosis is readily established by biopsy examination
of the lymph node. Moreover, the demonstration of Koch’s
bacillus using Ziehl-Neelsen stain and PRC is definitive.
7
Ministero della Salute - DG della Prevenzione Sanitaria. Ufficio
V - Malattie Infettive e Profilassi Internazionale.
8
Cailhol J, Decludt B, Che D. Sociodemographic factors that contribute to the development of extrapulmonary tuberculosis were
identified. J Clin Epidemiol 2005;58:1066-71.
9
van Embden JD, Cave MD, Crawford JT, et al. Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol
1993,31:406-9.
10
Ramón-García S, Ng C, Anderson H, et al. Synergistic drug combinations for tuberculosis therapy identified by a novel high throughput screen. Antimicrob Agents Chemother 2011;55:3861-9.
11
World Health Organization. Global tuberculosis control: Surveillance, Planning, Financing. Geneva, WHO Report; 2008.
12
Montoro E, Rodriguez R. Global burden of tuberculosis. In:
Palomino JC, Leão SC, Ritacco V, eds. Tuberculosis 2007,
from basic science to patient care. Kamps and Bourcillier 2007,
pp. 263-81.
pathologica 2011;103:343-345
Case report
S. Karoui, T. Badri, R. Benmously, E. Ben Brahim*, A. Chadli-Debbiche*, I. Mokhtar, S. Fenniche
Department of Dermatology, Habib Thameur Hospital, Faculty of Medicine, University of Tunis El Manar; * Department of Pathology,
Habib Thameur Hospital, Faculty of Medicine, University of Tunis El Manar, Tunisia
Key words
Adenolipoma • Perisudoral lipoma • Eccrine glands • Lipoma • Skin
Summary
Adenolipoma of the skin (ALS) is an uncommon histological variant of lipoma, characterized by the presence of normal eccrine
sweat glands inside the fat proliferation. A 32-year-old woman
presented to our department with a slow-growing, painless subcutaneous soft tumour located on the upper part of the right thigh.
Microscopically, there was lobulated adipose tissue proliferation
with well-differentiated eccrine glands and ducts in the periphery
and centre of the nodule. These features were suggestive of ALS.
ALS is a rare microscopic variant of cutaneous lipoma having
similar clinical features to lipoma. The most frequent locations
Introduction
of this tumour are thighs (as in our patient), shoulders, chest and
arms. Histologically, the tumour is composed of lobulated adipose
tissue with larger and more prominent lobules than those in normal subcutaneous adipose tissue. A well-developed capsule may
also be identified. Eccrine glands and ducts, without proliferative
changes, are well-differentiated within the adipose tissue.
Differential diagnosis of adenolipoma includes the common
lipoma and its variants, skin tag and other hamartomatous lesions,
such as nevus lipomatosus superficialis, and the lipomatous variant of eccrine angiomatous hamartoma.
Fig. 1. Painless nodule on the right upper thigh.
Adenolipoma of the skin (ALS) is an uncommon histological variant of lipoma characterized by the presence
of normal eccrine sweat glands inside a fat proliferation.
We report a new case with a review the literature.
Case report
A 32-year-old woman presented to our department with
a slow-growing, painless nodule on her thigh. Cutaneous examination showed a subcutaneous soft tumour of
1.5 cm in diameter located on the upper part of the right
thigh. The lesion was covered by an erythematous skin,
with no palpable thrill (Fig. 1). A diagnosis of lipoma
was suspected. Surgical excision of the tumour and the
overlying skin was performed.
Gross examination revealed a soft, yellow, lobulated mass
measuring 3 cm in greatest diameter. Microscopically, the
nodule was composed of adipose tissue proliferation with
distinct lobulation within the tumour. Well-differentiated
eccrine glands and ducts were seen in the periphery and
centre of the nodule. No capsule was seen and no architectural or cytological alteration was noticed in these glands
(Fig 2). These features were suggestive of ALS.
Discussion
Several variants of lipoma were described according to
their location and morphology. In a lipoma, the adipose
tissue may be associated with other proliferative or nonproliferative tissues, such as in angiolipoma and fibrolipoma 1.
Correspondence
Talel Badri, Department of Dermatology, Habib Thameur Hospital,
8, rue Ali Ben Ayed, 1008 Tunis, Tunisia - Tel. +216 98 829300 Fax +216 71 399115 - E-mail: [email protected]
344
Figs. 2A, B. Well-differentiated eccrine glands and ducts, without proliferative changes, within the adipose tissue (haematoxylin and eosin, X40).
A
B
In 1993, Hitchcock et al. described an entity of lipoma
in a series of 9 patients that had never been reported previously. It was a rare microscopic variant of cutaneous
lipoma composed of large lobules of mature adipocytic
tissue admixed with eccrine ducts and glands. This tumour was called “adenolipoma of the skin” 2.
Ait-Ourhrouil and Grosshans reported, in 1997, a second series of 11 cases 3. They postulated that this lesion
develops from the peripheral adipose tissue of eccrine
glands and suggested the name perisudoral lipoma. Including our patient, the total number of ALS reported
cases, in the English and French literature is 31 (Tab.
I) 2-10. The tumour often has the appearance of a usual
lipoma. Occasionally, the clinical presentation is suggestive of skin tag, neurofibroma or a hamartomatous
lesion. The delay between tumour occurrence and the
first medical evaluation ranges from 6 months (in our
case) to more than 10 years 3 5. The average size calculated from our literature review is 2.7 cm 2-10. There is
a female preponderance (22:9), and the average age at
diagnosis is 47.8 years 2-10. ALS is mainly located on the
s. karoui et al.
thigh (especially its upper part) and buttock (n = 16). The
other reported locations are: the shoulder region (n = 3),
abdomen (n = 2), periungual region (n = 2), female external genitalia (n = 2), axillary region (n = 1), lower lip
(n = 1), supraclavicular region (n = 1), arm (n = 1), hip
(n = 1) and breast (n = 1) 2-10.
Histologically, the tumour is composed of lobulated adipose tissue with larger and more prominent lobules than
those in normal subcutaneous adipose tissue. Unlike our
patient, a well-developed capsule may also be identified.
Eccrine glands and ducts, without proliferative changes,
are well-differentiated within adipose tissue 2 3. Only one
case of ALS with apocrine glandular cystic component
has been reported in a 40-year-old female patient with an
axillary tumour 8.
The frequency of adenolipoma might be underestimated,
especially when sectioning of lesions can miss the few
glandular components or when it is impossible to precisely locate eccrine glands within fragmented specimens.
When the eccrine glands have a peripheral location in
specimens, it may be also difficult to affirm whether the
glands are within the tumour or are contained in adjacent
normal structures 2 4.
The histological differential diagnosis of adenolipoma
includes common lipoma and its variants, skin tag, also
in addition to other hamartomatous lesions, such as nevus lipomatosus superficialis and the lipomatous variant
of eccrine angiomatous hamartoma 11 12.
Adenolipoma usually has a similar clinical presentation
to common lipoma. The size of adenolipoma appears to
be smaller than that of common lipomas, probably because of its superficial location that can lead to earlier
symptoms. A subcutaneous lipoma may have a herniation within the dermis. In this latter case, the eccrine
glands are compressed and displaced rather than incorporated into the lesion as in ALS 2.
Skin tag with a fatty stroma is also a differential diagnosis. In this tumour, the eccrine glands are rather located
on both sides of the pedicle rather than within the fatty
component 3.
Nevus lipomatosus superficialis has a different clinical feature. It presents as congenital multiple papules or
nodules. Microscopically, it shows ectopic adipose tissue with fibrous tissue in the papillary and reticular dermis. The density of the collagen bundles, the abundance
of fibroblasts and its vascularity are more prominent
than in normal skin 2 11.
Eccrine angiomatous hamartoma is usually an isolated
congenital lesion showing a preponderance of eccrine
and vascular proliferation, which are absent in ALS 2 12.
ALS is a fatty-tissue proliferation that includes and
moves the normal eccrine glands to the centre of the tumour. This glandular component does not show any proliferative changes. Its location on the upper thigh, as in
our patient, may allow clinical suspicion of ALS which
should be confirmed by histological findings.
345
Tab. I. Summary of the reported cases of ALS.
Reference
Hitchcock 1993 2
Ait-Ourhrouil 1997 3
Rongioletti 1997 4
Age (years)
Sex
Location
Size
Duration
25
M
Arm
1 cm
N/A
61
M
Thigh
N/A
44
F
Shoulder
6 cm
33
F
Supraclavicular
1.5 cm
37
M
Shoulder
4 cm
39
F
Thigh
0.8 cm
52
F
Thigh
1.5 cm
25
F
Thigh
4.4 cm
75
M
Thigh
4 cm
63
F
Thigh
55
M
Shoulder
1 to 3 cm
(average: 2.5 cm)
71
M
Abdomen
61
F
Buttock
2 years
44
F
Buttock
Many years
49
F
Hip
Many years
61
M
Thigh
2 years
63
F
Breast
Many years
48
F
Thigh
Many years
54
F
Thigh
Many years
48
M
Abdomen
41
F
Thigh
2.7 cm
N/A
Many years
25
F
Thigh
2 cm
5 years
34
F
Thigh
8 cm
11 years
Ide 2003 6
57
F
Lower lip
2 cm
3 years
Bichert 2004 7
67
F
Periungual (middle finger)
N/A
Many years
Periungual (great toe)
0.8 cm
N/A
48
M
8
45
F
Thigh
2.5 cm
N/A
Antunez 2005 9
40
F
Axillary region
3.7 cm
N/A
Pantanowitz 2008
Present case
10
41
F
Left groin
1.5 cm
Many years
44
F
Right vulva
2 cm
4 years
32
F
Upper thigh
3 cm
6 months
References
Richert B, André J, Choffray A, et al. Periungual lipoma: about
three cases. J Am Acad Dermatol 2004;51(Suppl 2):S91-3.
7
1
Abensour M, Jeandel C, Heid E. Lipomes et lipomatoses cutanés.
Ann Dermatol Venereol 1987;114:873-82.
2
Hitchcock M, Hurt M, Santa Cruz D. Adenolipoma of the skin: a
report of nine cases. J Am Acad Dermatol 1993;29:82-5.
3
Ait-Ourhrouil M, Grosshans E. Le lipome périsudoral. Ann Dermatol Venereol 1997:124;845-8.
10
4
Rongioletti F, Santa Cruz D. L’adénolipome cutané. Ann Dermatol Venereol 1997;124:855-6.
11
Chadli-Debbiche A, Ben Brahim E, Mzabi-Regaya S. Le lipome
périsudoral: une observation confirmant cette nouvelle entité. Ann
Pathol 2001;21:289-90.
12
6
5 years
> 10 years
Chadli-Debbiche 2001 5
Del Agua 2004
5
> 10 years
Ide F, Mishima K, Saito I. Adenolipoma of the lip. Br J Dermatol 2003;148:606-7.
Atunez P, Santos-Briz A, Munoz E, et al. Cutaneous apocrine cystic adenolipoma. Am J Dermatopathol 2005;27:240-2.
8
9
Pantanowitz L, Henneberry J, Otis C, et al. Adenolipoma of the
external female genitalia. Int J Gynecol Pathol 2008;27:297300.
Del Agua C, Felipo F. Adenolipoma of the skin. Dermatol Online J
2004;10:9.
Dotz W, Prioleau PG. Nevus lipomatous cutaneus superficialis: a light and electron microscopic study. Arch Dermatol
1984;120:376.
Donati P, Amantea A, Balus L. Eccrine angiomatous hamartoma:
a lipomatous variant. J Cutan Pathol 1989;16:227-9.
pathologica 2011;103:346-349
Case report
Adenomatous transformation in a giant solitary
F. LIMAIEM, S. BOURAOUI, A. LAHMAR, S. JEDIDI, S. ALOUI, S. Korbi, S. MZABI
Department of Pathology Mongi Slim Hospital, Sidi Daoued La Marsa (2046), Tunisia
Key words
Peutz-Jeghers-type polyp • Hamartoma • Adenomatous transformation • Rectum
Summary
Solitary Peutz-Jeghers-type polyp is a rare hamartomatous polyp
without associated mucocutaneous pigmentation or a family history of Peutz-Jeghers Syndrome. It is usually encountered in the
small intestine, but rarely involves the rectum. A 27-year-old previously healthy female patient presented with a two-month history of rectal bleeding. The patient had neither mucocutaneous
pigmentation nor a family history of gastro-intestinal polyposis.
Endoscopic examination revealed a solitary lobular polypoid
lesion in the lower rectum. The polyp was sessile and measured
15 cm in diameter. As histological examination of the biopsy
specimen was suggestive of adenoma, endoscopic polypectomy
was performed. Histologically, this polyp had an arborizing muscular network originating from the muscularis mucosa, and was
covered by well organized mucosa with several foci of dysplastic
glands. The final pathological diagnosis was solitary Peutz-Jeghers type hamartomatous polyp with adenomatous transformation.
Introduction
nation, the patient’s skin including the perioral area was
unremarkable and oral mucosa appeared normal. Endoscopic examination revealed a lobular and polypoid
lesion in the lower rectum measuring 15 cm in diameter (Fig. 1). A biopsy of this polyp was performed and
histological examination revealed findings suggestive of
an adenoma with low-grade intra-epithelial neoplasia.
Endoscopic resection of the entire polyp was performed.
Histopathologically, the excised polyp had an arborizing
muscular network originating from the muscularis mucosa (Fig. 2) and was covered by well organized mucosa
with hyperplastic (Fig. 3) and cystically dilated glands
(Fig. 4). Several foci of dysplastic glands displaying
low-grade intra-epithelial neoplasia were also identified
(Fig. 5). Thorough and careful examination of different sections of the entire polyp did not reveal any additional adenocarcinomatous foci. After endoscopic treatment, no concomitant lesions were found elsewhere. At
present, the patient is still on follow-up.
Solitary Peutz-Jeghers-type polyps (PJP) are uncommon
hamartomatous lesions without associated mucocutaneous pigmentation or a family history of Peutz-Jeghers
Syndrome (PJS) 1 2. They are most frequently encountered
in the small intestine, but rarely involve the rectum. Although several cases of solitary PJP have been reported in
the literature, it is still unclear whether solitary PJP represents an incomplete form of PJS or a different entity 3. In
this paper, the authors report a new case of solitary PeutzJeghers-type hamartomatous polyp with several foci of
glandular dysplasia revealed by rectal bleeding. To the
best of our knowledge, only 31 cases (Tab. I) of colorectal solitary Peutz-Jeghers-type hamartomatous polyps
have been published in the English language literature to
date, and adenomatous transformation has never been described in solitary rectal PJP before.
Clinical history
A 27-year-old previously healthy female patient with no
family history of gastro-intestinal polyposis, presented
with a two-month history of rectal bleeding. On exami-
Discussion
A Peutz-Jeghers polyp (PJP) in a patient without mucocutaneous pigmentation or family history of PJS is called
Correspondence
Faten Limaiem, Department of Pathology, Mongi Slim Hospital-La
Marsa- Tunisia - Tel. +216 96 55 20 57 - E-mail: fatenlimaiem@
yahoo.fr
Adenomatous transformation in a solitary Peutz-Jeghers-type polyp
Fig. 1. Endoscopic examination revealing a lobular rectal polyp.
Fig. 2. Arborizing network of smooth muscle and connective
tissue surrounding abundant normal glands. (haematoxylin &
eosin; original magnification x 10).
an isolated or solitary PJP 4. Whenever a PJP is found, it
is important to rule out a diagnosis of PJS on the basis of
WHO criteria: (1) three or more histologically confirmed
PJPs; (2) any number of PJPs with a family history of
PJS; (3) characteristic, prominent, mucocutaneus pigmentations with a family history of PJS; (4) any number
of PJPs and characteristic, prominent, mucocutaneous
pigmentation 3. In our case, histological examination
showed the characteristic features of PJP, but the patient
did not fulfil WHO criteria for PJS diagnosis (negative
family history for PJS and absence of mucocutaneous
pigmentation), and was therefore considered to have a
solitary PJP. Solitary Peutz-Jeghers polyps are extremely
rare, with an estimated incidence of 1:120,000 5. They
are found most frequently in the small intestine, but also occur in the large bowel and stomach 6 7. A Medline
search of the English language literature revealed only
three well-documented cases of solitary Peutz-Jeghers-
347
Fig. 3. Cystically dilated glands were identified within the polyp.
(haematoxylin & eosin; original magnification x 25).
Fig. 4. Hyperplastic glands composed of tall columnar absorptive cells and goblet cells. (haematoxylin & eosin; original magnification x 25).
Fig. 5. Foci of dysplastic glands were noticed within the polyp
(haematoxylin & eosin; original magnification x 25).
348
F. limaiem et al.
Tab. I. Cases of colorectal solitary Peutz-Jeghers type polyps reported in the literature.
Author/year
Number
of cases
Age (years)
sex
Location
Size (cm)
Presentation
Treatment
Suda 17 (1988)
20
Mean age =
55.1 years
Males: 74%
Colorectal
NA
NA
NA
Handa 12 (1990)
1
NA
Colon
NA
NA
NA
1
NA
Transverse colon
NA
NA
NA
1
NA
Colon
NA
NA
NA
1
64/M
Lower rectum
2x1.5 x 1.5
Bloody stools
Transanal surgical
resection
5
46/M
Sigmoid
1.5
Screening
Endoscopic polypectomy
68/M
Sigmoid
2.5
Screening
46/M
Sigmoid
2
Screening
Yamanaka
18
(1991)
Muto 9 (1993)
Nakayama
13
(1996)
Oncel 4
(2003)
33/F
Sigmoid
2
Rectal bleeding
56/M
Cecum
2
Screening
1
19/M
Descending
colon
NA
Colo-colonic
intussusception
Subtotal colectomy
Itaba 20 (2009)
1
50/M
Sigmoid
1.8
Screening
Garces 21 (2011)
1
NA
Rectum
NA
NA
NA
Limaiem (2011)
1
27/F
Lower rectum
15
Rectal bleeding
Jaremko 19 (2005)
NA: not available
type hamartomatous polyp of the rectum (Tab. I). The
largest colorectal PJP reported in literature had a size of
2.5 cm compared to 15 cm in our patient. Gastrointestinal
hamartomatous polyps in patients with PJS have a distinct histological appearance with interdigitating smooth
muscle fibres forming a characteristic branching tree pattern (arborization) 8. They display a frond-like elongated
epithelial component and cystic gland dilatation extending into the sub-mucosa or muscularis propria. PeutzJeghers-type polyps are histologically identical to those
in Peutz-Jeghers syndrome, although some authors have
pointed out that solitary Peutz-Jeghers-type polyps tend
to exhibit less branching of the muscularis mucosae than
in the familial form 9 10.
The main difficulty in defining the true entity of these
solitary hamartomatous polyps lies in the small number
of published cases, some of which provide little clinical
information. Because of the absence of involved family
members, the lack of mucocutaneous pigmentation characteristic of PJS and the presence of a solitary polyp, a
solitary PJP might be a disease entity distinct from PJS.
There is, however, controversy about the occurrence of
solitary PJPs 1 5. In most case reports and series, clinical and histological criteria were not fully documented
and there was usually no extended follow-up 11. Hamartomatous polyps are generally considered to have very
low malignant potential 11. However, some reports have
described areas of neoplastic change, such as adenomatous or carcinomatous change in solitary PJP 9 12-14.
Patients with PJS are at increased risk of developing
both intestinal and extraintestinal malignancies. Since
solitary PJP are rare, it is not known whether there is
any increased risk for other malignancies, as observed
in PJS. In 50–94% of patients with PJS, a mutation of
the LKB1/STK11 gene is found. Conversely, no mutation of the LKB1/STK11 gene was found in two cases
of solitary PJP in which genotyping was carried out 15 16.
Unfortunately, we were not able to carry out genotyping
in our case.
In summary, a case of solitary Peutz-Jeghers-type polyp
with adenomatous transformation is reported herein. Our
case is unique in that it is the largest solitary PJP reported in literature involving the rectum which is an exceedingly rare location. It is still unclear whether a solitary
Peutz-Jeghers polyp (PJP) is an incomplete form of PJS
or a separate entity. Whether there is an increased risk
of cancer in patients with solitary Peutz-Jeghers-type
polyps is uncertain, but periodic surveillance in young
patients would seem appropriate 4. Available data are
extremely limited, and it is difficult to draw firm conclusions regarding management of patients with solitary
polyps 5.
349
Adenomatous transformation in a solitary Peutz-Jeghers-type polyp
References
Burkart AL, Sheridan T, Lewin M. Do sporadic Peutz-Jeghers
polyps exist? Experience of a large teaching hospital. Am J Surg
Pathol 2007;31:1209-14.
12
Acea Nebril B, Taboada Filgueira L, Parajó Calvo A. Solitary
hamartomatous duodenal polyp; a different entity: report of a case
and review of the literature. Surg Today 1993;23:1074-77.
13
1
2
3
4
5
Ter Borg PP, Westenend PP, Hesp FW. A solitary Peutz-Jeghers type polyp in the jejunum of a 19 year-old male. Cases J
2008;1:68.
Oncel M, Remzi FH, Church JM, Goldblum JR, et al. Course and
follow-up of solitary Peutz-Jeghers polyps: a case series. Int J Colorectal Dis 2003;18:33-5.
Kitaoka F, Shiogama T, Mizutani A, et al. A solitary Peutz-Jeghers-type hamartomatous polyp in the duodenum. A case report including results of mutation analysis. Digestion 2004;69:79-82.
6
Decosse JJ. Polyps, polyposis, and benign tumors. In: Zuidema
GD, Condon RE, eds. Shackelford’s surgery of the alimentary
tract. Vol IV, 4th edn. Philadelphia: Saunders 1996, pp. 114-123.
7
Church JM. Other polyposis syndromes. Semin Colon Rectal Surg
1995;6:61-6.
8
Schreibman IR, Baker M, Amos C, et al. The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol 2005;100:476-90.
9
Burkart AL, Sheridan T, Lewin M, et al. Do sporadic Peutz-Jeghers polyps exist? Experience of a large teaching hospital. Am J
Surg Pathol 2007;31:1209-14.
11
Muto T. Polyp and polyposis of large bowel. Tokyo: Igaku-Shoin
Ltd. 1993, pp. ll9-120.
10
Yamanaka K, Sekoguchi T, Miyahara S, et al. Incomplete type
Peutz-Jeghers syndrome with a solitary polyp in the transverse
colon, report of a case. To Cho 1991;26: 1173-6.
Handa Y, Masuda T, Tadokoro M, et al. A case of a solitary PeutzJeghers type polyp of the colon accompanying adenomatous elements. Saitama-ken Igakkai Zasshi 1990;24:1476-8.
Nakayama H, Fujii M, Kimura A, et al. A solitary Peutz-Jegherstype hamartomatous polyp of the rectum: report of a case and review of the literature. Jpn J Clin Oncol 1996;26:273-6.
Suzuki S, Hirasaki S, Ikeda F, et al. Three cases of solitary PeutzJeghers-type hamartomatous polyp in the duodenum. World J Gastroenterol 2008;14:944-7.
14
Mc Garrity TJ, Kulin HE, Zaino RJ. Peutz-Jeghers syndrome. Am
J Gastroenterol 2000;95:596-604.
15
Retrosi G, Nanni L, Vecchio FM, et al. Solitary Peutz-Jeghers polyp in a pediatric patient. Case Rep Gastroenterol 2010;18:452-6.
16
17
Suda T, Watanabe H, Hatayama K, et al. Peutz-Jeghers syndrome.
Rinsho Kagaku 1988;1A:332-40.
18
Yamanaka K, Sekoguchi T, Miyahara S, et al. Incomplete type
Peutz-Jeghers syndrome with a solitary polyp in the transverse
colon, report of a case. To Cho 1991;26:1173-6.
Jaremko JL, Rawat B. Colo-colonic intussusception caused by a
solitary Peutz-Jeghers polyp. Br J Radiol. 2005;78:1047-9.
19
Itaba S, Iboshi Y, Nakamura K, et al. Education and imaging. Gastrointestinal: Solitary Peutz-Jeghers-type hamartoma of the colon.
J Gastroenterol Hepatol 2009;24:498.
20
21
Garces M, García-Granero E, Faiz O, et al. Ultralow anterior resection for prolapsed giant solitary rectal polyp of Peutz-Jeghers
type. Am Surg 2011;77:501-2.
350
pathologica 2011;103:350-356
Index Volume 103, No. 1-6
Issue 1
February 2011
40
ORIGINAL ARTICLE
1
Realistic technician staffing requirements in
a histopathology laboratory via an innovative
workload method
M. Bergamaschi, G. Coccini
ANATOMY FOR HISTOPATHOLOGISTS
4
Muscle spindle and Pacinian corpuscle: conceptions,
misconceptions, and the far-fetched hypothesis of an
experienced surgical pathologist
M. Bisceglia, S. Bisceglia, M.L. Bisceglia
CASE REPORTS
8
Long pedunculated colonic polyp with
diverticulosis: case report and review of the literature
M.R. Ambrosio, B.J. Rocca, A. Ginori, A. Barone, M.
Onorati, S. Lazzi
11 Amniotc band syndrome: a case report
A.M. Buccoliero, F. Castiglione, F. Garbini,
D. Moncini, E. Lapi, E. Agostini, P. Fiorini, G.L. Taddei
14 Partial nodal involvement by marginal zone
lymphoma. Use of IGK gene rearrangement analysis
in diagnostic work-up
A. Gazzola, E. Sabattini, C. Mannu, F. Bacci,
C.A. Sagramoso sacchetti, P. Artioli, L. Chilli,
G. Da Pozzo, M. Piccioli, B. Falini, S.A. Pileri,
P.P. Piccaluga
19 Morphological analysis of three extrathoracic
bronchogenic cysts simulating neoplasms
M. Lupi, L. Reggiani bonetti, E. Stauder, S. Bettelli,
A. Maiorana
22 Renal leiomyoma
N. Mashali, A.T. Awad, G. Trevisan, M. El-bahrawy
25 Melanoma of the nipple. An additional case
V. Mourmouras, M.R. Ambrosio, M. Onorati,
B.J. Rocca, N. Di mari, F. De luca, C. Miracco
Issue 2
April 2011
ORIGINAL ARTICLE
27 Teaching anatomical pathology in the undergraduate
curriculum in Medicine: the experience of ‘C
Course’, Sapienza University, Rome
P. Gallo, G. D’Amati, C. Di Gioia, C. Giordano
CASE REPORTS
32 Cystic sebaceous lymphadenoma of the parotid
gland: case report and review of the literature
43
46
50
S. Squillaci, R. Marchione, M. Piccolomini
An unusual case of signet ring cell adenocarcinoma
of the prostate
L. Reggiani Bonetti, M. Lupi, E. Stauder,
S. Bergamini, M. Scuri, A. Maiorana
Subcutaneous Ewing sarcoma/PNET as a second
cancer in a previously irradiated young patient.
An uncommon type of post-irradiation soft tissue
sarcoma
M. Bruno, G.I. D’Antona, G. Vita, G. Perrone,
F. Fiordelisi, M. Bisceglia
Nodular extramedullary hematopoiesis involving the
adrenal gland.
An uncommon cause of adrenal “incidentaloma”
M. Salemme, R. Rodella, S. Fisogni, F. Facchetti
Ductal carcinoma of the prostate metastatic to the
skin
G. Collina, C. Reggiani, G. Carboni
LETTER TO THE EDITOR-IN-CHIEF
52 Needle core biopsy should replace fine needle
aspiration cytology in ultrasound-guided sampling of
breast lesions
B. Brancato, M. Scialpi, T. Pusiol, M.G. Zorzi,
D. Morichetti, F. Piscioli
Issue 3
June 2011
ORIGINAL ARTICLES
53 Autoptic and echocardiographic findings in
seven foetuses with congenital heart anomalies,
lung lobation defects and normal visceroatrial
arrangement
F. Angiero, V. Fesslova, T. Rizzuti, M. Stefani
61 Solitary extramedullary plasmacytoma of the thyroid
gland associated with multinodular goiter: case
report and review of the literature
G. Puliga, L. Olla, G. Bellisano, N. Di Naro,
M. Ganau, M.L. Lai, G. Faa, G.A. Tolu
64 Sebaceous carcinoma of the vulva: critical approach
to grading and review of the literature
T. Pusiol, D. Morichetti, M.G. Zorzi
CASE REPORTS
68 Pleomorphic giant cell ductal carcinoma of the
breast
D. Tacchini, M.G. Mastrogiulio, L. Vassallo,
A. Ginori
71 A solitary pilar leiomyoma of the trunk
R. Benmously-Mlika, F. Ishak, S. Ben Jennet,
H. Hammami, T. Badri, I. Mokhtar, S. Fenniche
351
Index volume 103, no. 1-6
73
Malignant proliferating trichilemmal cyst of the
scalp: histological aspects and nosology
A. Khaled, M. Kourda, B. Fazaa, J. Kourda,
S. Ben Jilani, M. Ridha Kamoun, R. Zermani
Issue 4
August 2011
CASE REPORTS
299 Histogenetic and taxonomic considerations
on a case of post-traumatic bizarre parosteal
osteochondromatous proliferation (BPOP)
M. Filotico, A. Altavilla, S. Carluccio
304 Reactive pseudo-glandular mesothelial hyperplasia
in testis tunica vaginalis: a case report
N. Di Naro, G. Puliga, L. Olla, G.A. Tolu
307 Incidental finding of peripheral B-cell nonHodgkin lymphoma, lymphocytic/CLL type, of the
gallbladder in a patient with chronic cholecystitis
H. Imenpour, M. Castagnola, G. De Silva, S. Zupo,
M. Truini, E. Merlo, L. Anselmi
311 Nodular hidradenoma in a 19-year-old woman
R. Benmously-Mlika, M. Jones, H. Hammami,
N. Labbene, A. Debbiche, I. Mokhtar, S. Fenniche
ATTI DI CONGRESSO
79 Congresso Nazionale SIAPEC-IAP
Palermo, 27-29 Ottobre 2011
Issue 6
Decmber 2011
LETTER TO THE EDITOR-IN-CHIEF
77 Reliability of K-ras mutational analysis on
cytological samples from metastatic colorectal
cancer
C. Bozzetti, F.V. Negri, N. Naldi, R. Nizzoli,
B. Bortesi, V. Zobbi, C. Azzoni, E.M. Silini,
A. Ardizzoni
Issue 5
October 2011
ORIGINAL ARTICLES
271 Primary synovial sarcoma of the kidney. A case
report with pathologic appraisal investigation and
literature review
A. Pitino, S. Squillaci, C. Spairani, M.F. Cosimi,
E. Feyles, D. Ricci, F. Bardari, M. Graziano,
F. Morabito, F. Cesarani, M. Garruso, M. Belletti,
K. Beierl, K.M. Murphy
279 Oncocytic carcinoma of the parotid gland: case
report and review of the literature
T. Pusiol, D. Morichetti, M.G. Zorzi
SPECIAL ARTICLE
290 Epidemiological changes in breast tumours in Italy:
the IMPACT study on mammographic screening
programmes
Impact Working Group
GUIDELINES AND CHECK LISTS
294 Breast cancer and primary systemic therapy.
Results of the Consensus Meeting on the
recommendations for pathological examination and
histological report of breast cancer specimens in
the Marche Region
A. Santinelli, M. De Nictolis, V. Mambelli,
R. Ranaldi, I. Bearzi, N. Battelli, C. Mariotti,
L. Fabbietti, S. Baldassarre, G.M. Giuseppetti,
G. Fabris
ORIGINAL ARTICLES
313 The role of 2D bar code and electronic crossmatching in the reduction of misidentification errors
in a pathology laboratory. A safety system assisted
G. Fabbretti
318 Cytologic re-evaluation of negative effusions from
patients with malignant mesothelioma
325 Intra-operative frozen section technique for breast
cancer: end of an era
E. Manfrin, A. Remo, F. Falsirollo, G.P. Pollini,
A. Parisi, A. Nottegar, F. Bonetti
331 The diagnostic accuracy of cervical biopsies in
determining cervical lesions: an audit
337 “Combined” desmoplastic melanoma of the vulva
with poor clinical outcome
G. Collina
CASE REPORTS
340 Tuberculosis of superficial lymph nodes, a not so
rare event to consider in diagnosis. A case in an
elderly male
A. Merante, M.R. Ambrosio, B.J. Rocca,
A.M. Condito, A. Ambrosio, M. Arvaniti, G. Ruotolo
343 Adenolipoma of the skin
S. Karoui, T. Badri, R. Benmously, E. Ben Brahim,
A. Chadli-Debbiche, I. Mokhtar, S. Fenniche
346 Adenomatous transformation in a giant solitary
F. Limaiem, S. Bouraoui, A. Lahmar, S. Jedidi,
S. Aloui, S. Korbi, S. Mzabi
352
Author index
Author Index
Abbona G.C., 143, 201
Acconcia A., 240
Achille G., 187
Adami G., 158
Addati T., 150, 187, 226
Afeltra A., 138
Agostinelli C., 119, 168
Agostini E., 11
Al Omoush T., 148
Alabiso O., 156
Alaggio R., 165, 186
Albertoni L., 236
Alesiani F., 197
Alessandrini L., 147, 225
Allegra E., 247
Allegrini S., 156, 192, 261
Allia E., 100, 253
Alò P.L., 170, 176, 188
Aloui S., 346
Altavilla A., 299
Altomare V., 229
Amato M., 161, 165
Amato T., 195
Ambrosio A., 230, 260, 340
Ambrosio M.R., 8, 25, 124, 181, 190,
195, 210, 211, 212, 230, 238, 260,
265, 340
Amico P., 165
Amore F., 165
Amoroso A., 138
Ancona E., 161, 235
Andreini L., 216
Andreozzi A., 147
Andronico G., 203
Angelucci D., 172
Angiero F., 53
Annaratone L., 221
Anniciello A., 140
Anniciello A.M., 107, 140
Anselmi L., 307
Anselmi M., 208
Antinori S., 112, 113
Antona J., 156, 192
Antonelli M., 96
Antonini D., 159
Anzalone R., 145
Apicella P., 146
Appetecchia M., 202
Aprile G., 163
Aquino G., 110, 164, 171, 245, 246, 263
Aragona F., 177, 182
Arborea G., 202, 206, 245, 249, 255
Arcaini L., 196, 197
Arcuri P., 190
Ardizzoni A., 77
Arena R., 210
Arena V., 135, 148, 149, 214
Arisio R., 100
Arnoffi J., 232
Arrigoni C.V., 231
Artioli P., 14
Arvaniti M., 340
Ascierto P., 140
Ascoli V., 318
Asioli S., 166
Asselti M., 225, 226, 237
Avallone A., 240
Awad A.T., 22
Azzolina V., 210
Azzoni C., 77
Bacci F., 14, 119
Bacigalupo A., 179
Bacigalupo B., 160
Badri T., 71, 343
Baffa R., 235
Bagnoli A., 175
Baldassarre S., 294
Baldelli R., 202
Baldini D., 148
Balistreri M., 161, 189, 235
Balmativola D., 221
Balzarini P., 215, 261
Bar E., 151
Barbagli L., 190
Barbareschi M., 140, 157, 171, 215, 216
Barbato A., 140
Barberis M., 125, 156, 219
Barbiano di Belgiojoso G., 214
Barbieri D., 153
Barbieri P., 201
Bardari F., 271
Barnabei A., 202
Barollo S., 189
Baron L., 147
Barone A., 8, 195, 211, 230
Barreca A., 162
Barresi G., 187, 231
Barresi V., 187, 231
Bartoletti R., 266
Bartolommei S., 265
Bartoloni G., 96
Battaglia A., 228
Battaglia G., 235
Battelli N., 294
Battolla E., 160
Bearzi I., 294
Becchina G., 94, 167, 194, 241
Bega O., 255
Beierl K., 271
Belardinelli V., 147, 225
Bellan C., 195, 210, 230, 238
Bellavia T., 203
Bellei E., 169
Belletti M., 271
Bellevicine C., 145, 173, 190, 200,
202, 243
Bellini R., 261
Bellis D., 143, 159, 201
Bellisano G., 62
Belluso D., 159
Belmonte B., 142, 177, 182
Beltrami V.R.L., 135, 205, 260
Ben Brahim E., 343
Ben Jennet S., 71
Ben Jilani S., 73
Ben-Dor D., 177
Benerini Gatta L., 215, 261
Benevolo M., 234, 251
Benmously R., 343
Benmously-Mlika R., 71, 311
Bensi T., 201
Beretta Anguissola G., 188
Bergamaschi M., 1, 174
Bergamini S., 40, 169
Bertazzoni G., 265
Bertolaso A., 200
Bertolotti A., 261
Betta P.G., 201
Bettelli S., 19, 180, 215
Biancalani M., 146, 174
Bianchi G., 169
Bianchi P., 175
Bianchi S., 146
Bianco M., 206, 207
Biasi O., 219
Biggeri A., 228
Bisceglia M., 4, 43, 177, 182, 183, 186,
195, 206, 207, 216, 249
Bisceglia M.L., 4
Bisceglia S., 4
Boccardo S., 166, 221
Boccuzzo G., 225
Bogina G., 99, 217
Boldorini R., 156, 192, 261, 262
Bollito E., 128
Bolner A., 171
Bombonato M., 232
Bonanni B., 219
Bonanno A., 233
Bonanno E., 148, 159
Bondi A., 87, 130
Bonello L., 162
Bonetti F., 216, 217, 220, 325
Bonifacio D., 79
Bonifacio M., 200
Bono F., 162
Bono L., 139, 212
Bonzanini M., 80
Bordoni A., 163
Bortesi B., 77
Bortul M., 148
Borzillo A., 248
Borzomati D., 165, 193, 194, 229
Bosco A., 165
Bosco D., 318
Bosi A., 179
Bosisio F.M., 161, 223, 231
Botta C., 147
Botta G., 135, 205
Botti G., 107, 110, 136, 140, 144, 146,
153, 164, 217, 218, 239, 240, 241,
245, 263, 264
Bouraoui S., 346
Bove G., 239
Boveri E., 197
Bovo G., 161, 162, 243
Bozzetti C., 77
Braccischi A., 169, 184, 229
Bragantini E., 171, 216
Brancato B., 52
Brandi M.L., 213
Brazzarola P., 144
Bresaola E., 157
Brisigotti M., 175, 216
Brollo A., 158
Brunelli C., 193, 194
Brunelli F., 146
Brunelli M., 139, 204, 213, 216, 217
Brunello E., 204, 216, 217
Bruno M., 43
Bruzzone M., 250
Buccoliero A.M., 11, 155
Buffa C., 144
Bufo P., 144, 171, 185, 188, 240, 246,
247, 262
Buglioni S., 148, 217
Buonaguro F.M., 83
Buonaguro L., 83
Burgio U., 199
Burioni R., 113
Butera D., 150
Buttitta F., 126, 155, 158, 203
Cabibi D., 142, 177, 182, 190, 218, 236
Cacciatore M., 164, 167, 197
Cadei M., 131, 215, 261
Cagiano S., 144, 185, 246, 247
Cai T., 266
Caldara A., 215
Caldarella A., 146
Callea M., 161, 165
Caltabiano R., 98, 186, 247, 261
Calvaruso M., 164, 167, 197
Calvisi G., 135, 143
Camerlingo R., 217
Campaner M., 258
Campisi V., 232
Canciglia R., 194
Candia S., 148
Canessa P.A., 160
Cannata N., 238
Cannizzaro C., 139, 213
Cantaloni C., 140, 157, 215
Cantile M., 107, 110, 140, 146, 164,
217, 218, 239, 240, 241, 245, 263,
264
Capano R., 239, 240, 241
Capella S., 159
Capelli P., 191, 192
Caponio M.A., 150
Caporalini C., 204, 205
Cappadona S., 228
Cappellesso R., 232
Cappello F., 145
Capulli M., 186
Caraglia M., 263
Caramella D., 137
Carbone A., 149
Carboni G., 50
Cardone C., 181
Carducci A., 265
Carella R., 157, 171
Carlà T.G., 234
Carli F., 221
Carluccio S., 299
Carnovale Scalzo C., 318
Carolei D., 246
Carolina A.F., 199
Carosi I., 177, 207, 239
Carosi M., 202, 232, 251
Carrieri G., 170
Carroccio A., 164
Carru C., 152
Caruso C., 138
Caruso F., 129
Caruso R., 233, 238
Caruso S., 214
Casadio C., 157
Cascone P., 141
Casini B., 217, 232
Casoria A., 245
Casorzo L., 147, 259
Cassina E., 231
Cassoni P., 162, 228
Castagnola M., 307
Castellano I., 100, 228
Castiglia M., 182, 190
Castiglione F., 11, 155, 205
Castrista M., 239
Cataldo I., 192, 237
Catalucci A., 186, 208
Catarini M., 197
Cattoretti G., 161, 162, 231
Cavalli T., 213
Cavani A., 229
Cavazza A., 111, 157
Cavedon E., 189
Cè S., 248
Ceciliani E., 252
Centrone M., 150, 187
Cerasola G., 203
Cernic S., 158
Cerrone M., 107, 110, 140, 146, 217,
218, 241, 245, 263, 264
Certo G., 219, 236, 253
Cesarani F., 271
Cesarini E., 150
Cesinaro A.M., 180
Chadli-Debbiche A., 343
Chella A., 155, 203
Chiapparini L., 157
Chiaramonte A., 195
Chiarello G., 152, 154, 189, 251
Chicchinelli N., 140
Chilli L., 14
Chilosi M., 144, 191, 200, 204, 213,
216, 217
Chiusa L., 100, 162, 228
Cianci R., 138
Cicchinelli I., 135, 143
Cimino G., 195
Cimmino A., 137, 168, 202, 208, 245
Cintorino M., 211, 212, 265
Cirese V., 116
Citraro L., 200
Ciuffetelli V., 175, 263
Claudio B., 217
Clemente C., 105
Clemente R., 236
Coccia A., 253
Coccini G., 1
Coccini G., 174
Cocuzza S., 261
Colantoni A., 159
Colao A., 202
Colasante A., 172, 259
Colato C., 144, 178
Coletti G., 175, 263
Colli S., 160, 166, 221
Collina F., 146, 217, 218
Collina G., 50, 337
353
Author index
Colombo M.P., 197
Colombo P., 223
Colonna A., 158
Colonna P., 200
Comin C.E., 155, 204, 205
Condito A.M., 340
Conte P.F., 215
Contini M., 152
Convertino C., 148
Coppola R., 161, 165, 193, 194, 229
Corini F., 169, 184, 229, 243, 245
Cormio L., 170
Corrao S., 145
Corrente A., 255
Corsi F., 239
Cosci E., 230
Cosimi M.F., 271
Cossu-Rocca P., 152
Costa A., 238
Costantini B., 197
Costanza G., 203
Costarelli L., 148
Covelli C., 249
Covello R., 202
Coverlizza S., 264
Crescenzi A., 148
Crippa S., 163, 233
Crisafulli C., 233
Crisman G., 135, 143, 146, 175, 196,
234, 263, 266
Croce A., 159, 172, 200
Croce C.M., 235
Crocetti E., 146
Crucitti P., 87, 161
Cuorvo L., 215
Curcio E., 163
Curcio M.P., 110
Curti T., 266
D’Agruma L., 183
D’Alterio C., 239
D’Amati G., 27, 148
D’Amuri A., 234
D’Angelo A., 169, 184, 229
D’Angelo G., 172
D’Angelo P., 199
D’Angelo V., 207
D’Antona G.I., 43
D’Antuono T., 158
D’Armiento M., 93
D’Eredità G., 222
D’Urso P.I., 137, 208
Da Pozzo G., 14
Dal Mas A., 148
Dal Santo M., 131
Dalla Palma P., 80, 118, 140, 171, 215,
216
Danza K., 227
Daprile R., 220, 225, 227, 237
David S., 145
De Bernard M., 235
De Carolis S., 251
De Chiara A., 164
De Giorgi V., 142
De Luca C., 202
De Luca F., 25, 212
De Luca N., 177
De Maglio G., 147, 158, 163
De Marco L., 253
De Miglio M.R., 152
De Murtas F., 239, 245
De Nictolis M., 294
De Pangher Manzini V., 158
De Pellegrin A., 79, 148
De Rosa G., 141, 144, 180, 190, 240,
246, 248
De Rosa N., 200
De Salvo L., 217
De Santis R., 249
De Silva G., 307
Deambrogio C., 253
Debbiche A., 311
Del Conte A., 158
Del Vecchio M., 169, 184, 229
Del Vecchio M.T., 190, 210, 230
Del Vescovo V., 157
Delfino C., 179
Dell’Antonio A., 148
Dell’Orto P., 156
Dell’Osa E., 198
Della Pace L., 239, 256
Delrio P., 240
De Maglio G., 182, 216
Demarchi A., 264
Denti A.M., 157
Dessanti P., 166
Di Bella C., 223
Di Bello C., 162
Di Bonito L., 79, 148
Di Bonito M., 146, 217, 218
Di Carlo A., 234
Di Clemente D., 202, 206, 245, 249,
255
Di Clemente L., 263
Di Cristofano C., 148
Di Domenico M., 185
Di Filippo F., 217
Di Francesco A., 225
Di Gioia C., 27
Di Gregorio C., 231
Di Leo A., 228
Di Lorenzo, I., 251
Di Lorito A., 172, 198, 200, 259
Di Marco F., 199
Di Mari N., 25
Di Matteo F.M., 193, 194
Di Nardo P., 135
Di Naro N., 62, 304
Di Stasio E., 135
Di Tonno C., 157
Diamanti L., 169, 184, 229
Dimitri L., 239
Dinelli M.E., 161, 162
Diodoro M., 232
Discepoli S., 146, 266
Doglioni C., 112
Dominici M., 215
Donà M.G., 234, 251
Donadio M., 228
Donnini I., 179
Doring C., 196
Eccher A., 204
Eccher C., 215
Egarter-Vigl E., 258
El-Bahrawy M., 22, 331
Epifani A., 234
Esposito A., 129, 134
Faa G., 62
Fabbietti L., 294
Fabbretti G., 175, 313
Fabbro M., 232
Fabris G., 294
Facchetti F., 46, 123, 168
Facchini G., 263
Facciolo F., 202
Fadda G., 81, 152, 154, 189, 251
Faggiano A., 202
Falconieri G., 163, 216
Falini B., 14, 119
Falsirollo F., 325
Fara D., 263
Fara Tanjona H., 156
Faraggiana T., 138, 211
Farina M., 107, 140
Farinati F., 236
Farinetti A., 180, 248, 265
Farruggia P., 199
Fasanella S., 140
Fasola G., 158, 163
Fassan M., 86, 161, 189, 235, 236
Fassina A., 125, 232
Fazaa B., 73
Fazioli F., 164
Fedele F., 233
Fedeli F., 160, 166, 221
Federico S., 253
Felicioni L., 155, 158, 203
Fenniche S., 71, 331, 343
Fenocchio D., 220
Ferdeghini M., 144
Feriozzi S., 211
Ferraiuolo P., 140
Ferrantelli A., 139, 211, 212
Ferraris A.M., 221
Ferretti M., 252
Ferretti S., 88
Ferro A., 215
Ferro P., 160, 166, 221
Ferrone S., 107
Fesslova V., 53
Feyles E., 271
Fiaccavento R., 135
Fiandrino G., 122
Ficarra G., 215
Ficarra V., 139
Ficial M., 213
Filardo A., 254
Filotico M., 299
Fiordelisi F., 43, 216
Fiore G., 168, 206, 245, 249
Fiorentino M., 128
Fiorini P., 11
Fiorito C., 253
Fisogni S., 46
Floccari F., 234
Flora M., 147
Florena A.M., 164, 167, 197
Floridi D., 205
Foltran L., 163
Fondi C., 179
Fontana V., 160
Fontecchio G., 137, 209
Fornaciari A., 137
Fornaciari G., 137, 138, 209
Fornari A., 128
Foscolo A.M., 254
Francavilla S., 263
Franceschini M.C., 160, 166, 221
Francesconi A., 202, 232
Francia di Celle P., 162
Franco C., 122
Franco G., 197
Franco R., 107, 110, 136, 140, 144, 171,
185, 227, 239, 245, 263, 264
Franco V., 142, 164, 167, 236
Frattini M., 156, 163, 233
Frossi B., 164, 197
Fulcheri E., 250, 257
Fulciniti F., 140, 150
Fumagalli C., 156, 219
Fusi C., 179
Gaeta L.M., 194, 229
Galardi F., 228
Galasso M., 235
Galletta F., 164
Galliani C., 182, 186, 249
Galliani C.A., 206
Galliani M., 211
Galligioni E., 215
Gallo D., 154
Gallo E., 217
Gallo P., 27
Galuppini F., 189
Galzio R.J., 208
Gambacorta M., 232
Ganau M., 62
Gandolfo S., 170, 172
Garbini F., 11
Garofalo A., 232
Garruso M., 271
Gaudio F., 202, 245
Gazzola A., 14
Genderini F., 214
Genovese F., 94, 167, 194, 241
Genta R.M., 236
Gentile R., 90, 166, 191
Gessi M., 97
Ghiringhello B., 253, 260
Giacalone B., 94, 167
Giacomelli L., 161, 225
Giallombardo D., 182, 190, 236, 242
Giammaresi C., 139, 212
Gianatti A., 147
Giannakakis K., 138, 211
Giannatempo G., 195
Giannatiempo R., 176, 185, 227, 239,
264
Giannini A., 146, 228
Giannone A.G., 218
Giannone G., 150, 187, 225
Gianquinto D., 221
Giantomassi F., 197
Giardina C., 222
Giardini R., 114
Giarnieri E., 154
Gigante A., 138, 211
Gigantino V., 263, 264
Giglio A., 234
Gilioli E., 204
Gillio Tos A., 253
Ginori A., 8, 68, 211
Gioioso A., 150
Giordano C., 27
Giordano T., 238
Giotta F., 225, 226
Giovagnini G., 175
Giovagnoli M.R., 82, 154
Girardi G., 205, 260
Girelli M.E., 189
Girlando S., 171, 215
Girolomoni G., 178
Giudici F., 79, 148, 213
Giuffra V., 137, 209
Giuffrè G., 85
Giuliani M., 234
Giuliani S., 140
Giunchi F., 128
Giurato E., 186
Giuseppetti G.M., 294
Giusiani S., 137
Gobbo S., 139, 191, 192, 213, 216
Gomes V., 148
Gorji N., 166
Goteri G., 197, 252
Grammatica L., 187
Grandi C., 171
Grasso M.A., 207
Gravina G.L., 138, 209
Graziano M., 271
Graziano P., 157
Greco M., 195
Greco P., 87, 165
Greggi S., 153
Gri G., 164
Grigolato P.G., 131, 215, 261
Grillo L.R., 148
Grimaldi B., 138
Grottola A., 265
Guadagno E., 189
Guarneri V., 215
Guarnotta C., 142, 164, 167, 190, 197
Guerrieri A.M., 222
Guetti L., 155, 158, 203
Gugliotta P., 147
Guidi S., 179
Gulino A., 167
Gurrera A., 186
Gustinelli A., 262
Gustinucci D., 150
Guzzardo V., 161, 225
Guzzetti S., 220
Hammami H., 71, 311
Hansmann M.L., 196
Hartmann S., 196
Hofmann W.P., 196
Huhtamo E., 261
Iaccarino A., 190
Iannucci A., 204
Icardi M., 201
Ieni A., 187
Ientile D., 238, 255
Ilardi G., 141, 180, 240, 246, 248
Imenpour H., 307
Impara G., 234
Imperiale D., 144
Inghirami G., 119, 162, 167
Ingravallo G., 137, 168, 202, 208, 222
Intrieri T., 146
Ioli A., 175
Ionna F., 245
Iop A., 158
Ishak F., 71
Isimbaldi G., 231
Jaffrain-Rea M.L., 208
Jedidi S., 346
Jones M., 311
354
Kacerovská D., 259
Karoui S., 343
Kasal A., 258
Kazakov D., 259
Khaled A., 73
Korbi S., 346
Kourda J., 73
Kourda M., 73
Kuppers R., 196
La Mantia E., 110, 136
La Rocca G., 145
Labate A., 219, 236, 253
Labbene N., 311
Lagrasta C., 147
Lahmar A., 346
Lai M.L., 62
Lambertenghi D., 228
Lanzafame S., 186, 261
Lapi E., 11
Larato C., 253
Lastilla G., 182
Latini A., 234
Lattanzio G., 198, 200
Lauricella C., 232
Lazzi S., 8, 124, 181, 195, 230, 238
Leardo T., 253
Leocata P., 135, 143, 146, 175, 196,
234, 263, 266
Leonardi E., 147, 215
Leonardo E., 148
Leoncini L., 124, 195
Leone B.E., 223
Leone G., 259, 261
Leoni P., 197
Lepanto D., 219
Li Cavoli G., 139, 211, 212
Libener R., 201
Liberati M., 259
Libretti L., 231
Liguori G., 107, 110, 146, 164, 217, 218
Limaiem F., 346
Liotta R., 191
Liuzzi M., 222
Lo Cunsolo C., 147
Lo Mele M., 147, 225
Loda M., 128
Lomazzo G., 135
Longhi E., 112
Longo F., 165, 245
Lora V., 178
Lorenzi L., 168
Losito N.S., 153
Losito S., 245
Lotta R., 166
Lucchini C., 220
Lucchini V., 231
Luchini C., 191, 192
Lucioni M., 122, 196
Ludwig K., 161
Luparia P., 253
Lupi M., 19, 40, 248
Lupo C., 133
Lusiardi M., 157
Lutrino S., 163
Macario M., 220
Macciocu E., 154
Macilotti M., 140
Macor P., 167
Macrì L., 220, 221
Maglione A., 176, 185, 227, 239, 264
Magro G., 101, 165, 186, 259, 261
Maio V., 179
Maione M.P., 176, 185, 227, 239, 264
Maiorana A., 19, 40, 169, 180, 215, 248
Maiorano E., 202
Malapelle U., 145, 200, 202, 243
Malatesta S., 155, 158, 172, 198, 200,
203, 259
Maletta F., 220, 253
Malfettone A., 220, 227, 237
Mambelli V., 169, 184, 229, 245, 294
Mamo M., 236
Manfrin E., 216, 217, 220, 237, 325
Mangerini R., 221
Mangia A., 220, 227, 237
Mangiapia M., 200
Author index
Manini C., 151, 253, 264
Manna A., 140
Mannella E., 266
Mannone T., 114
Mannu C., 14
Mannucci S., 210
Manta C., 160
Manzotti M., 156
Marampon F., 138, 186, 209
Marandino F., 217
Marasà L., 199, 211
Marasà S., 203, 242
Marasco A., 254
Marazzi F., 214
Marchelle G., 147, 225
Marchesini G., 252
Marchetti A., 109, 155, 158, 203
Marchiò C., 221, 228
Marchione M., 228, 248
Marchione R., 32
Marcolini L., 191, 192, 220, 237
Margiotta D., 138
Margiotta M., 175
Mariani M., 197
Mariani N., 201
Mariani S., 162
Maricosu E., 152
Marinelli C., 198
Maringhini S., 210
Mariotti C., 294
Marra F., 146
Marra L., 185, 217, 240, 263, 264
Marsico A., 170, 172
Martellani F., 79, 148
Martignoni G., 139, 204, 213, 216, 217
Martin V., 163
Martinesi M., 266
Maruzzi M., 206
Marzano A.L., 225, 226
Marzi S., 186, 208
Mascolo M., 141, 180, 246, 248
Mashali N., 22
Masiero E., 158, 163
Massa P., 254
Massarelli G., 152, 168
Massi D., 106, 142, 179
Mastrogiulio M.G., 211, 230, 238
Mastrogiulio M.G., 68
Mataca E., 153
Materazzi S., 179
Matter M., 136
Mattioli E., 226
Mattoni M., 171, 185, 188, 246, 247,
262
Maura E., 170
Mazza S., 151
Mazzer M., 163
Mazzitelli R., 236
Mazzola S., 151
Mazzon E., 219, 236, 253
Mazzucchelli L., 163, 233
Menia E., 154
Menis J., 158
Mennilli S., 134
Merante A., 260, 340
Mercurio C., 209
Merlo E., 307
Mescoli C., 236
Mesiti M., 219
Messerini L., 155, 204, 205
Messina V., 238
Mezzapelle R., 156, 192
Mezzaroba N., 167
Mian C., 189
Miani L., 252
Micali S., 169
Michal M., 259
Micheletti M., 170
Micheli F., 173
Micheli P., 173
Migaldi M., 180, 248, 265
Miglio U., 156, 192
Miglionico L., 249
Migliore M., 186
Mignogna C., 103, 238, 255
Mikuz G., 128
Mirabella A., 136
Mirabella C., 170
Miracco C., 25
Miraglia M.C., 242
Miranda G., 209
Mittica G., 228
Mokhtar I., 71, 311, 343
Molinari F., 233
Molinaro L., 162, 222
Molo S., 122
Monari E., 169
Moncelsi S., 152, 251
Moncini D., 11
Mondaini N., 266
Monego G., 135
Monga G., 156
Monticelli A., 185, 227, 239, 264
Montironi P.L., 151
Montironi R., 128
Montrone T., 202, 206, 222, 245, 249,
255
Morabito F., 271
Morassi F., 154
Moretto D., 234
Morichetti D., 52, 64, 141, 180, 181,
222, 258, 279
Morosetti M., 211
Mosca A., 139
Mottolese M., 148, 217
Mourmouras V., 25, 181, 238, 260
Mucilli F., 155, 158, 203
Munari E., 200, 213
Mura A., 152
Murari R., 176, 188
Muroni M.R., 152
Murphy K.M., 271
Musa M., 159
Muscarella L., 183
Muscatiello N., 166
Mustacchi G., 148
Muti P., 148
Mzabi S., 346
Nagar C., 94, 167, 194, 241
Naldi N., 77
Nania A., 238
Nanni N., 265
Nannini R., 216
Napoli A., 222
Napoli P., 238
Nasorri F., 229
Nassini R., 179
Natale G., 144
Navone R., 170, 172
Nebuloni M., 177, 214
Negri F.V., 77
Negri G., 154, 258
Nesi G., 213, 266
Nicastro A., 176, 185, 227, 239, 264
Nicola M., 122
Nicolini M., 175
Nirchio V., 166, 170, 239, 256
Nitti D., 236
Nizzoli R., 77
Nocita A., 151, 254
Nogales F.F., 152
Noto S., 170
Nottegar A., 204, 216, 217, 325
Novara G., 139
Novelli L., 155, 204, 205
Nozzoli C., 179
Nucifora M., 233
Nugnes L., 176, 185, 227, 239, 264
Oackman C., 228
Ober E., 79, 148
Olianas R., 152
Olla L., 62, 304
Onetti Muda A., 138, 161, 165, 193,
194, 211, 229
Onorati M., 8, 25, 181, 190, 195, 210,
211, 212, 230, 238, 260, 265
Opocher G., 189
Oppressore D., 176, 185, 227, 239, 264
Oranges T., 179
Orecchia S., 201
Orlando E., 203, 242
Orvieto E., 147, 225
Ottelli Zoletti F., 228
Ottoveggio G., 94, 167, 194, 241
Ozben T., 169
Pacella E., 257
Pacenti L., 190
Paci E., 146
Paganotti A., 156, 192
Pagliarulo M., 234
Paglierani M., 142, 147
Pagni F., 223
Palamara G., 234
Palatini J., 235
Palazzoni G., 214
Palermo A., 188
Palma F., 187
Palumbieri G., 246, 257
Palumbo M., 206, 245, 255
Palummo N., 210
Panniello G., 177
Pannone G., 144, 171, 185, 188, 240,
246, 247, 262
Papagerakis P., 262
Papagerakis S., 262
Papaleo N., 151
Papotti M., 128, 157
Pappalettera F., 170
Para P., 175
Paradiso A., 148, 220, 227, 237
Parafioriti A., 182
Parente P., 235
Parenti R., 186
Parisi A., 144, 191, 192, 220, 237, 325
Parracino T., 206
Parravicini C., 112
Pasqualini F., 177
Pasquinelli G., 183
Pasquini P., 148
Passamonti B., 150
Passantino R., 139, 211, 212
Paulli M., 122, 196
Pazzagli M., 142
Pecciarini L., 147
Pecorari M., 265
Pederzoli A., 175
Pedica F., 191, 192
Pedicillo M.C., 247
Pedretti P., 179
Pedron S., 217
Pelella A., 239, 240
Pelizzo M.R., 189
Pellegrini W., 168
Pellis G., 148
Pelosi G., 125, 157
Penitente E., 172, 198, 259
Pennacchia I., 135, 149, 214
Pennelli G., 189, 236
Pensiero V., 138
Pentenero M., 170, 172
Pepe P., 127
Pepi M., 155, 213
Perdonà S., 263
Pericoli M.N., 148
Perracchio L., 148, 232
Perrone G., 43, 161, 165, 193, 194, 229
Pescarmona E., 202, 217, 232, 251
Pessina S., 156
Petitti T., 211
Petroni S., 150, 225, 226
Pettinato G., 145
Peveling-Oberhag J., 196
Piacentini F., 215
Pica E., 176
Piccaluga P.P., 14, 119, 167, 197
Piccioli M., 14
Piccioni D., 175
Piccolomini M., 32, 228, 248
Pietribiasi F., 101
Pignata S., 153, 263
Piiper A., 196
Pilato B., 226
Pileri S.A., 14, 119, 167, 168
Pili F., 152
Pimpinelli F., 234
Pimpinelli N., 179
Pinzani P., 142
Pioner R., 258
Pirozzi G., 217, 241
Pisano C., 153
Piscioli F., 52, 141
355
Author index
Piscuoglio S., 136
Pistillo M.P., 160, 166, 221
Pitino A., 271
Pizzamiglio S., 148
Pizzi G., 254
Pizzi M., 161, 189, 235, 236
Pizzolitto S., 158, 163
Polci R., 211
Pollini G.P., 325
Poloni A., 197
Ponte R., 257
Ponz de Leon M., 231
Popescu O., 150, 226
Porta C., 139
Possanzini P., 156, 219
Postiglione M., 176, 185, 227, 239, 264
Potortì I., 191
Pozzilli P., 188
Prestipino J., 101
Priano R., 175
Privitera E., 147
Pucillo C., 164, 197
Pugliese F., 138, 211
Puliga G., 62, 304
Pusiol T., 52, 64, 141, 180, 181, 222,
258, 279
Puzzo L., 247
Quero C., 187, 225
Rabitti C., 193
Raffaelli M., 189
Ragazzini T., 130
Ramieri M.T., 148, 176, 188
Ranaldi R., 294
Rappa F., 145
Rattotti S., 196
Ravanini P., 261
Re P., 201
Re R., 197
Realdon S., 235
Reggiani Bonetti L., 19, 40, 169, 180,
215, 231, 248, 265
Reggiani C., 50
Reitano R., 170
Relli V., 136, 140
Remo A., 220, 325
Resta L., 137, 206, 208, 245, 249, 255
Riboni R., 122
Ribotta M., 135, 205, 260
Ricci A., 186
Ricci D., 271
Ricci M., 216
Ricci R., 214
Ricco R., 168, 202
Rider-Stark J., 128
Ridha Kamoun M., 73
Ridolfo A.L., 112
Righi A., 259
Righi D., 161, 194
Rinaudo C., 159
Riotta S., 255
Rivasi F., 153, 261, 262
Rizzi C., 158
Rizzuti T., 53
Rocca B.J., 8, 25, 124, 181, 190, 195,
210, 211, 212, 230, 238, 260, 265,
340
Rocco G., 136
Rodella R., 46
Rodolico V., 182
Rollo F., 234, 251
Romanelli D., 163
Romano A., 79, 148
Romano M.F., 180
Romano S., 180
Romeo G., 138
Roncalli M., 92
Roncella S., 160, 166, 221
Ronchetti L., 234
Ronco G., 253
Rosa M., 211
Rosai J., 182
Rossano V., 151
Rossi Degl’Innocenti D., 155
Rossi E.D., 81, 152, 154, 189, 251
Rossi G., 109, 136, 157
Rossi R., 137, 208
Rostan I., 170, 172
Rotellini M., 155, 204, 205
Rotolo U., 139, 211, 212
Rubini V., 150
Ruco L., 148
Rudà R., 228
Rugge M., 86, 147, 161, 189, 225,
235, 236
Ruisi R., 251
Ruol A., 161
Ruotolo G., 260, 340
Russo A., 176, 185, 217, 227, 239, 264
Russo D., 173, 177
Russo L., 239, 264
Russo S., 187, 202
Sabatini A.M., 265
Sabattini E., 14, 119
Sabbatini R., 252
Sabino A., 165
Saccardi R., 179
Sacchini, A., 265
Sacco O., 107
Sagramoso Sacchetti C.A., 14
Salatiello M., 202
Salemme M., 46
Salvatore C., 220, 227
Salvatorelli L., 165, 186
Salvi S., 147, 166, 221
Salvianti F., 142
Salvio M., 201
Salvioni D., 223
Sampaoli I., 175
Sanchez Mete L., 232
Sangaletti S., 197
Sangapur R., 225
Sanguedolce F., 188, 247, 262
Santantonio R., 258
Santi R., 213, 266
Santinelli A., 147, 294
Santini D., 229
Santonastaso C., 241
Santopietro R., 181, 230, 238
Santoro A., 144, 171, 185, 188, 189,
240, 246, 247, 262
Sapia M.C., 210
Sapino A., 100, 147, 162, 220, 221,
228, 253
Saponaro C., 220, 227, 237
Sarnelli G.C., 201
Sartore Bianchi A., 232
Sartori M., 192
Satarpia L., 228
Scacchi C., 157
Scaffa C., 153
Scaglione, G., 167
Scala C., 250
Scala S., 239
Scamarcio R., 168
Scambia G., 152, 251
Scaramuzzino F., 190, 230
Scarcella S.V., 137, 208
Scarpino S., 148
Scatena C., 142
Schillaci L., 177
Schillaci O., 142, 182
Schmidt A., 196
Schurfeld K., 124
Scialpi M., 52
Sciarrotta M.G., 155, 158, 203
Scibetta N., 145, 199, 210, 241, 251
Scimeca M., 159
Scivetti A., 206
Scognamiglio G., 107, 136, 140, 146,
153, 218
Scrima M., 110
Scuri M., 40
Segala D., 139, 204, 213
Senatore S.A., 234
Senetta R., 228
Sentinelli S., 232
Serra A., 261
Serriello I., 211
Servino L., 261
Setta S., 172
Sgambato A., 180, 248, 265
Sgariglia R., 243
Siano M., 141, 180, 240, 246, 248
Sibau A., 158
Silini E.M., 77
Silvano Costa S., 153
Silvestrini M., 171
Simoncelli S., 215
Simone G., 150, 187, 220, 225, 226,
227, 237
Simonetti A., 228
Simoni A., 266
Sivori M., 160
Sollima L., 135, 143
Somma A., 189
Somma P., 173
Spagnoli L.G., 159
Spairani C., 271
Sparano L., 136
Spina D., 195
Spirito A., 206
Spoladore C., 225
Squillaci S., 32, 228, 248, 254, 271
Staffolani M., 252
Staiano M., 150
Staibano S., 106, 141, 180, 240, 246,
248
Stauder E., 19, 40
Stefani M., 53
Steinmeyer A., 266
Stigliano V., 232
Stio M., 266
Stramazzotti D., 197, 252
Stufano V., 156
Sulfaro S., 158
Sullo L., 170
Taborro R., 184, 245
Tacchini D., 238
Tacchini D., 68
Taddei G.L., 11, 155
Taglieri D.M., 219, 236, 253
Tallarico E., 151, 254
Tallarigo F., 151, 228, 248, 254
Tallini G., 147
Tancredi G., 205
Taraglio S., 144
Tarquini E., 251
Tasso G., 177
Tatangelo F., 239, 240, 241
Tavani E., 114
Tempia Valenta G., 172
Terracciano L., 89, 136
Terrenato I., 148, 217
Testi R., 144
Tolu G.A., 62, 304
Tomasi A., 169
Tommasi S., 226
Tondat F., 162
Tonelli F., 213
Tonello C., 112
Tonini G., 229
Toppino D., 162
Torelli L., 79, 148
Tornesello M.L., 83
Tornillo L., 91, 136
Torrisi A., 186, 259
Tortorella S., 247, 262
Tortorici C., 139, 212
Tosoni A., 214
Tralongo V., 94, 167, 194, 241
Trapani F., 136
Trappolini S., 197
Treves C., 266
Trevisan G., 22
Tricarico F., 166
Tricarico N., 177
Trincheri N.F., 201
Triolo R., 215
Tripodi S., 190, 210, 211, 212, 230, 265
Tripodo C., 164, 167, 197
Trizzino A., 199
Trodella L., 229
Trombatore M., 182, 190, 236
Trombetta I., 209
Troncone G., 125, 145, 173, 189, 190,
200, 202, 243
Truglia M.C., 228
Truini M., 166, 221, 307
Tuccari G., 187
Unti E., 145, 199, 210, 241, 251
Uras M.G., 152
Urbani V., 209
Urso C., 146
Vago G., 214
Vairo M., 182
Valduga F., 171
Valentino A., 203, 242
Vandone A., 100
Vanoni V., 171
Vanzati A., 243
Varone V., 145, 173, 243
Vasquez E., 247, 259
Vassallo L., 68, 211
Vassarotto E., 225
Vazzana N., 198
Vecchio F.M., 149, 214
Vecchio G.M., 165, 186
Vecchione M.L., 141, 246, 248
Veggiani C., 156, 192, 262
Vellone V.G., 152, 154, 189, 251
Ventura L., 137, 138, 186, 208, 209
Venturoli S., 153
Verderio P., 148
Verdun di Cantogno L., 147
Vermi W., 123
Vezzosi V., 146
Viale G., 100
Vianello F., 189
Viberti L., 85, 143, 201, 220
Vigani A., 160
Vigevani E., 158
Vigliar E., 173, 243
Vigna S., 147
Villani E., 234
Villari N., 137
Vindigni C., 195
Viola P., 155, 158, 172, 198, 200, 203,
259
Visca P., 202
Vita G., 43
Vitale A., 214
Vitale A.R., 266
Vitale R., 248
Vitarelli E., 231
Vitiello A., 137
Vitolo D., 148
Vittoria E., 217
Vocaturo A., 234, 251
Vocaturo G., 251
Volinia S., 235
Volpe A., 159
Wang J., 331
Zacchi A., 79, 148
Zagami M., 229
Zagarrigo C., 139
Zamboni G., 191, 217
Zamò A., 200
Zamparese R., 169, 184, 229, 243, 245
Zanatta L., 147
Zanconati F., 79, 148
Zandonà L., 148
Zanellato E., 163, 233
Zangrandi A., 147
Zanin T., 133
Zaninotto G., 161, 235
Zannoni G.F., 102, 152, 154, 189, 251
Zanus G., 232
Zarrelli N., 249
Zawada L., 214
Zeppa P., 243
Zermani R., 73
Zeuzem S., 196
Zinellu A., 152
Zito Marino F., 110
Zizzi A., 197
Zobbi V., 77
Zolfanelli F., 146
Zorzi M.G., 52, 64, 141, 180, 181, 222,
258, 279
Zuccotti G.F., 205, 260
Zuegel U., 266
Zummo G., 145
Zupo S., 307
356
key words index
Key words index
2D Barcode technology
313
A
Adenocarcinoma
Adenolipoma
Adenomatous transformation
Adnexal tumour
Adrenal
Adrenal gland
Amniotc band syndrome
Apocrine
Autoptic examination
40
343
346
311
19
46
11
311
53
B
Biopsy
331
Bizarre paraosteal chondromatous
proliferations (BPOP)
299
Breast
68
Breast cancer
294, 325
Bronchogenic cyst
19
C
Cancer
CD 138
Cervix
Cleft palate
Clinical governance
Colonic polyp
Colorectal cancer
Colposcopy
Combined
Congenital heart anomalies
Core needle biopsy
Cytology
D
Desmoplastic melanoma
Diagnostic pitfalls
Differential diagnosis
Diverticular polyps
Diverticulosis
Ductal carcinoma
Dysplasia
E
Eccrine glands
Efficiency
Ewing’s sarcoma
Extracardiac anomalies
Extramedullary hematopoiesis
Extranodal lymphoma
F
Fine needle aspiration biopsy
Fine needle aspiration cytology
Foetal echocardiography
Frozen sections
331
61
331
11
1
8
77
331
337
53
325
318
337
318
68, 271
8
8
50, 68
331
343
1
43
53
46
307
77
52, 325
53
325
G
Gallbladder lymphoma
Giant cells
307
68
H
Hamartoma
Hashimoto’s disease
Hereditary spherocytosis
Hidradenoma
Histogenesis
Histological report
Histopathology laboratory
Hodgkin’s disease
Hyperplasia
I
IGK
Immunohistochemistry
Incidentaloma
Intraoperative diagnosis
346
61
46
311
32
294
1
43
304
14
25, 279, 337
46
325
K
Kappa chains
Kidney
K-ras
L
Leiomyoma
Lip
Lipoma
Lung lobation defects
Lymphoma
M
Malignant oncocytoma
Malignant proliferating trichilemmal
cyst
Malignant proliferating trichilemmal
tumour
Mammography
Medical Education
Melanoma
Meningoencephalocele
Mesothelial
Mesothelioma
Mismatch errors
Molecular biology
Multinodular goiter
Muscle Spindle
Mycobacterium
N
Needle core biopsy
Neoadjuvant chemotherapy
Nipple
Nodal marginal zone lymphoma
Nose
61
22
77
22
11
343
53
307
279
73
73
52
27
25
11
304
318
313
14
61
4
340
O
Ovary
19
P
Pacinian Corpuscle
4
Pathological examination
294
PCR
340
Perineurium
4
Peripheral neuroectodermal tumor
43
Perisudoral lipoma
343
Personnel workload
1
Peutz-Jeghers-type polyp
346
Pilar leiomyoma
71
Post-irradiation sarcoma
43
Prenatal diagnosis
53
Primary systemic therapy
294
Prostate
40, 50
Protein S100
337
R
Reactive mesothelium
Rectum
Renal neoplasms
Retroperitoneum
Risk management
318
346
271
19
313
S
Safety management of patient
specimens
313
Salivary gland cancer
279
Screening
331
Sebaceous carcinoma
64
Sebaceous lymphadenoma
32
Sebaceous neoplasm
64
Second cancer
43
Serous effusion
318
Signet ring cell
40
Skin
343
Skin metastases
50
Smooth muscle tumour
71
Solitary extramedullary plasmacytoma 61
Stomach
19
Synovial sarcoma
271
SYT/SSX gene fusion
271
T
Teaching Anatomical Pathology
Technician
Thyroid gland
Tuberculosis
Tumour
Tunica vaginalis
27
1
61
340
22
304
U
Undergraduate curriculum in Medicine 27
52
294
25
14
11
V
Vulva
Vulva cancer
337
64
Il sito her2testing.it si arricchisce di una nuova e importante sezione interamente dedicata
alla corretta determinazione dello stato di HER2 nel carcinoma mammario.
Una sezione accessibile sempre dal sito www.her2testing.it che fornirà al patologo
contenuti e risorse utili dedicate all’esecuzione e interpretazione del test HER2 nel
carcinoma mammario, con le sue specifiche caratteristiche e differenze rispetto al
carcinoma gastrico.
Una serie di contenuti formativi e interattivi che aiuteranno il patologo ad
approfondire la letteratura scientifica di riferimento e le linee guida nazionali e
internazionali, e perfezionare la pratica clinica.
brochure
breast:Layout
23-01-2012
15:54 di
Pagina
La struttura
del sito1consentirà
al patologo
avere1accesso
alle sezioni teoriche
e pratiche che, come per la sezione dedicata al carcinoma gastrico e della giunzione
gastroesofagea, saranno divise in:
st i n g
.it
2
HER
testing
Breast and
Gastric Cancer
www
.
2 te
Area formazione su HER2 sezione dedicata alla pratica clinica, con esercizi
r
interattivi sull’assegnazione dello score HER2 e gli interventi audio video
he
della rubrica Incontra l’esperto, con testimonianze degli esperti membri
del Board scientifico.
Saperne di più su HER2 sezione dedicata all’approfondimento
della teoria, contenente guide illustrate, filmati con i commenti degli
Opinion leader internazionali di riferimento, le pubblicazioni fondamentali
della letteratura scientifica nazionale e internazionale.
La sezione dedicata al carcinoma gastrico e della giunzione gastroesofagea è sempre attiva
per questadel
nuova
sezione
al carcinoma
eAnche
a disposizione
patologo
e sidedicata
arricchisce
di nuovi e mammario
interessanti aggiornamenti.
sono previsti aggiornamenti periodici e costanti per garantire al patologo
la possibilità
di avere
disposizione
un che
sito vanno
sempreadpiù
ricco di contenuti
Oltre
alle nuove
letturea ed
esercitazioni
implementare
le sezioni
e risorse
utili alla pratica
clinica.
Area
Formazione
su HER2
e Saperne di più su HER2 sono disponibili online:
UPDATE
�Un link diretto per accedere alla
La
FAD è online!
2
Clicchi qui
per accedere
direttamente
al corso
FAD HER2 testing nel carcinoma gastrico
HER
testing
e della giunzione gastroesofagea
La sezione dedicata al carcinoma gastrico e della giunzione gastroesofagea è sempre attiva
da Congressi
e Webcast:
è stato pubblicato
e a News
disposizione
del patologo
e si arricchisce
di nuovi e interessanti aggiornamenti.
nella sezione dedicata agli appuntamenti congressuali
ilOltre
webcast
del Simposio
Medicina
personalizzata:
alla nuove
letture ed
esercitazioni
che vanno ad implementare le sezioni
dalla
malattia
HER2
positiva
al
melanoma
Area formazione su HER2 e Saperne di più su HER2 sono disponibili su HER2:
che si è svolto a il 28 ottobre 2011 a Palermo
Un link
direttoCongresso
per accedere
alla FAD HER2 nel carcinoma
durante
l’ultimo
Siapec
gastrico e della giunzione gastroesofagea
nel carcinoma gastrico
e della giunzione
gastroesofagea
�
News da Congressi e Webcast: è stato pubblicato nella sezione
dedicata agli appuntamenti congressuali il webcast del Simposio Medicina personalizzata: dalla malattia
HER2 positiva al melanoma che si è svolto a il 28 ottobre 2011 a Palermo durante l’ultimo Congresso Siapec
Impegnata per un ambiente migliore, Roche utilizza carta riciclata
CellPrep è un sistema
che appone cellule esfoliative
su vetrino in un’area circolare di 20 mm,
disponendole in monostrato
e mantenendo integri gli aggregati cellulari
Sistema automatico a
passaggio singolo
Trasporto e caricamento
automatico della membrana
filtrante
“Surely Speedy Solution”
Sistema dotato di schermo
LCD per un facile utilizzo

Journal of the Italian Society of Anatomic Pathology and Diagnostic

Transcript

Documenti analoghi

EXTRA-PROJECTED IMPLANTS AS AN ALTERNATIVE SURGICAL

[Prenatal diagnosis of congenital diaphragmatic hernia: an update]

United against breast cancer - Information from

Donation American Cancer Society April2013

Breast Cancer - Metodo di Bella

Advanced International Breast Cancer Course

Early detection through mammography

Cranio-cervical necrotizing fascitiis

Validation of Dermoscopy as a Real

Breast carcinoma metastases in paranasal sinuses, a rare

original article - Scienza in Rete

Peritoneal mesothelioma in a case of inguinal hernia. A review of

4th I-DSD Symposium - Scottish Transgender Alliance