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
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
Vol. 103 December 2011
318 Cytologic re-evaluation of negative effusions from patients with malignant
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
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
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
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,
343 Adenolipoma of the skin
S. Karoui, T. Badri, R. Benmously, E. Ben Brahim, A. Chadli-Debbiche, I. Mokhtar,
346 Adenomatous transformation in a giant solitary Peutz-Jeghers-type hamartomatous
F. Limaiem, S. Bouraoui, A. Lahmar, S. Jedidi, S. Aloui, S. Korbi, S. Mzabi
Aut. Trib. di Genova n. 75 del 22/06/1949
Società Italiana di Anatomia Patologica e Citopatologia Diagnostica,
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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 W.F. Grigioni, Bologna Governing Board
Marco Chilosi, Verona G. Inghirami, Torino SIAPEC-IAP
L. Leoncini, Siena President:
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C. Clemente, Milano Vol. 103 December 2011
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CONTENTS of help in the diagnostic work-up of patients with effusions suspi-
cious for mesothelioma.
Intra-operative frozen section technique for breast cancer:
The role of 2D bar code and electronic cross-matching end of an era
in the reduction of misidentification errors in a pathology
laboratory. A safety system assisted E. Manfrin, A. Remo, F. Falsirollo, G.P. Pollini, A. Parisi,
by the use of information technology A. Nottegar, F. Bonetti
G. Fabbretti Data on 2436 primary breast carcinomas diagnosed between 1992
and 2006 were collected to evaluate the rate of frozen section pro-
Introduction. Mismatching of patients and specimens can lead to cedures performed over time. Frozen section procedures performed
incorrect histopathological diagnoses. Most misidentification errors
to evaluate resection margins for conservative surgery or sentinel
in laboratories occur during the manual pre-laboratory and labora-
tory phases. In the past few years, we have examined this vital and node status were excluded. Over time, there was a decrease in the
challenging issue in our unit and introduced appropriate procedures. use of frozen sections indistinctly extended to all pT cancer catego-
Recently, we have paid special attention to the problem of speci- ries. The rate of cancers diagnosed with frozen sections was 51.2%
men mix-ups in the gross examination phase and the mismatching of in 1999, and 0% in 2005-2006. In the same period, the adoption
blocks and slides in the cutting phase. of cytology and core biopsy for breast cancer diagnosis increased
Objective. We have focused on the reduction of the potential sources from 40% in 1992 to more than 90% since 1999. In an audited
of mismatching of specimen containers, tissue blocks and slides, diagnostic activity on breast pathology, the routine use of frozen
focusing in particular on the most critical steps which are gross cut- sections on primary lesions was considered inappropriate, particu-
ting and preparation of microtome sections. larly in assessment of clinically non-palpable lesions, and should be
Design. A 2D bar code directly printed on the labels of specimen contain- limited to cases with inadequate pre-surgical sampling.
ers, 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.
The diagnostic accuracy of cervical biopsies in determining
Results. The present system permits full sample traceability from cervical lesions: an audit
the moment samples reach the laboratory to the issuing of the final J. Wang, M. El-Bahrawy
report. Indeed, the LIS records samples, blocks and slides in real time Objective. The present audit was carried out to assess the diag-
throughout the entire procedure, as well as the operator’s name, and nostic accuracy of cervical punch biopsy during colposcopy in
the date and time each individual procedure is done. This facilitates comparison with diagnosis from subsequent cone excision.
later monitoring of the entire workflow.
Design and setting. Retrospective analysis was performed by
Conclusions. The introduction of 2D bar code and electronic cross-
checking represents a crucial step in significantly increasing the safe examining the histopathology reports for paired cervical punch
management of cases and improving the quality of the entire work biopsies and cervical cone excisions for cases reported from April
process. 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
Cytologic re-evaluation of negative effusions from patients was instituted).
with malignant mesothelioma
Sample. 150 women had both cervical punch and cone biopsies
V. Ascoli, D. Bosco, C. Carnovale Scalzo performed in the 2004-2005 period, while 149 women had both
Background. Cytology is a controversial means of diagnosing biopsies performed in 2008.
malignant mesothelioma due to the high rates of negative sam- Main outcome measures and results. In 2004-5, the rate of con-
ples. The aim of the present study was to review effusions origi- sistent diagnosis was 68.7%, compared with 75.8% in 2008. This
nally reported as “negative” in patients with histologically-proven was due to a decrease in the rates of overdiagnosis (16.7% vs.
mesothelioma to evaluate possible pitfalls. 14.8%) and underdiagnosis (14.7% vs. 9.4%), which was statisti-
Methods. We reviewed the cytologic slides of 25 specimens cally significant. The sensitivity rates for 2004-5 and 2008 were
that refer to 15 epithelioid, 5 biphasic, 4 sarcomatoid and 1 well- 87.5% and 89.7%, and the specificity rates for the same periods
differentiated papillary mesotheliomas. For comparison, we also were 39.8% and 39.4% respectively.
reviewed 23 specimens from non-neoplastic conditions. For each Conclusions. This audit highlights the importance of planning
effusion, we evaluated the background and calculated a score con- patient management on the basis of co-ordinated information
sidering the following items: amount of mesothelial cells, archi- from smear results, history, colposcopy findings and cervical
tectural pattern and atypical features, and a revised diagnosis was biopsies. The introduction of specialist gynaecological histopa-
rendered. thology reporting has significantly improved the rates of consis-
Results. More than half of the effusions initially called “nega- tent diagnosis.
tive” (but mesothelioma by histology) were considered atypical/
suspicious (false-negative diagnosis); the remaining cases were “Combined” desmoplastic melanoma of the vulva with poor
true-negative or inadequate. Almost all effusions initially called clinical outcome
“negative” (but non-neoplastic by histology) were considered
negative. The only item that seems to discriminate between the G. Collina
two groups is atypia of mesothelial cells. Desmoplastic melanomas in an unusual variant of melanoma that
Conclusions. The present study has highlighted the following pit- usually occurs in sun-damaged skin of elderly people. Desmopla-
falls: (i) to report effusions devoid of mesothelial cells as negative sia may be the prominent features of the lesion or represent a por-
that instead should be reported as inadequate/non-diagnostic; (ii) tion of an otherwise non-desmoplastic melanoma; these latter are
to underestimate low cellular effusions containing atypical meso- called “combined” desmoplastic melanoma. Desmoplastic mela-
thelial cells or high cellular effusions containing bland mesothe- nomas of the vulva are rare. Herein, we report a case of “com-
lial cells with a morular pattern; (iii) to consider that an inflamma- bined” DM of the labia minor consisting of a superficial spitzoid
tory background may obscure a scant number of mesothelial cells. component and a deeper spindle desmoplastic component. Protein
A categorized system (inadequate (M1), negative (M2), atypical S-100 expression was ubiquitous, while MART-1 and HMB-45
(M3) and suspicious (M4)) for reporting effusion cytology may be were limited to the superficial spitzoid component and were nega-
tive in desmoplastic areas. Notably, the nodal metastasis retained eccrine sweat glands inside the fat proliferation. A 32-year-
the same biphasic pattern seen in the primary tumour. The patient old woman presented to our department with a slow-growing,
died of widespread metastatic disease 3 years after diagnosis. 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
Case reports in the periphery and centre of the nodule. These features were
suggestive of ALS.
Tuberculosis of superficial lymph nodes, a not so rare event ALS is a rare microscopic variant of cutaneous lipoma having
to consider in diagnosis. A case in an elderly male similar clinical features to lipoma. The most frequent locations
of this tumour are thighs (as in our patient), shoulders, chest
A. Merante, M.R. Ambrosio, B.J. Rocca, A.M. Condito, and arms. Histologically, the tumour is composed of lobulated
A. Ambrosio, M. Arvaniti, G. Ruotolo adipose tissue with larger and more prominent lobules than
Tuberculosis (TB) is still one of the most frequent infectious those in normal subcutaneous adipose tissue. A well-developed
diseases worldwide. Until the 1990s, Western European countries capsule may also be identified. Eccrine glands and ducts, without
showed a low frequency of TB infection, but the rise of immigration proliferative changes, are well-differentiated within the adipose
has led to a rapid increase in its occurrence. In the elderly, tissue.
TB is emerging as a significant health problem (age-related Differential diagnosis of adenolipoma includes the common
decline of the cell-mediated immunity, associated illnesses, use lipoma and its variants, skin tag and other hamartomatous lesions,
of immunosuppressive drugs, malnutrition, poor life conditions), such as nevus lipomatosus superficialis, and the lipomatous
although its detection and diagnosis is not easy also considering its variant of eccrine angiomatous hamartoma.
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 Adenomatous transformation in a giant solitary
lymphadenitis without pulmonary manifestations, the possibility Peutz-Jeghers-type hamartomatous polyp
of a TB aetiology is often not taken into consideration in the F. Limaiem, S. Bouraoui, A. Lahmar, S. Jedidi, S. Aloui,
differential diagnosis of lymphadenopathy, resulting in significant S. Korbi, S. Mzabi
delay of appropriate treatment. Solitary Peutz-Jeghers-type polyp is a rare hamartomatous polyp
Herein, we describe the case of a 78-year-old male with nocturnal without associated mucocutaneous pigmentation or a family his-
fever, weakness, night sweats, loss of weight and decay in general tory of Peutz-Jeghers Syndrome. It is usually encountered in the
condition. The patient had a past medical history of prostate small intestine, but rarely involves the rectum. A 27-year-old
adenocarcinoma treated with hormone therapy.The past medical previously healthy female patient presented with a two-month
history in association with clinical findings and laboratory data history of rectal bleeding. The patient had neither mucocu-
(anaemia, high titers of fibrinogen and reactive c-protein) led taneous pigmentation nor a family history of gastro-intestinal
to the suspect of metastatic adenocarcinoma. Only histological polyposis. Endoscopic examination revealed a solitary lobular
and molecular biology findings allowed us to make a correct polypoid lesion in the lower rectum. The polyp was sessile and
diagnosis of TB. 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
Adenolipoma of the skin
arborizing muscular network originating from the muscularis
S. Karoui, T. Badri, R. Benmously, E. Ben Brahim, mucosa, and was covered by well organized mucosa with sev-
A. Chadli-Debbiche, I. Mokhtar, S. Fenniche eral foci of dysplastic glands. The final pathological diagnosis
Adenolipoma of the skin (ALS) is an uncommon histological was solitary Peutz-Jeghers type hamartomatous polyp with ade-
variant of lipoma, characterized by the presence of normal nomatous transformation.
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
U.O. Anatomia Patologica e Citologia, Ospedale Infermi, Rimini, Italy
Mismatch errors • Risk management • 2D Barcode technology • Safety management of patient specimens
Introduction. Mismatching of patients and specimens can lead being used; in addition, the system performs an electronic cross-
to incorrect histopathological diagnoses. Most misidentification check of tissue blocks and slides, which is managed by the labora-
errors in laboratories occur during the manual pre-laboratory and tory information system.
laboratory phases. In the past few years, we have examined this Results. The present system permits full sample traceability
vital and challenging issue in our unit and introduced appropriate from the moment samples reach the laboratory to the issuing
procedures. Recently, we have paid special attention to the prob- of the final report. Indeed, the LIS records samples, blocks and
lem of specimen mix-ups in the gross examination phase and the slides in real time throughout the entire procedure, as well as
mismatching of blocks and slides in the cutting phase. the operator’s name, and the date and time each individual pro-
Objective. We have focused on the reduction of the potential cedure is done. This facilitates later monitoring of the entire
sources of mismatching of specimen containers, tissue blocks and workflow.
slides, focusing in particular on the most critical steps which are Conclusions. The introduction of 2D bar code and electronic
gross cutting and preparation of microtome sections. cross-checking represents a crucial step in significantly increas-
Design. A 2D bar code directly printed on the labels of specimen ing the safe management of cases and improving the quality of
containers, and directly printed onto cassettes and slides, is now the entire work process.
Introduction incorrectly-recorded laterality and anatomical sites.
Another two steps in the procedure that are particularly
Since the publication of “To err is human” in 1999 1, prone to error are the gross and cutting phases, which
substantial work has been done to reduce factors that are characterized by sample mix-ups and block and slide
contribute to errors in medical and surgical pathology mismatching errors.
practice. Procedures in the histopathology unit involve A significant reduction in the number of misidentifica-
multistep processes with several handoffs of materi- tion errors on accession was achieved in 2008 with the
als, which are all potential sources of error 2. Errors that elimination of handwritten requests and handwritten
may occur at any stage of processing vary in frequency, labels, and by the introduction of an order entry with
depending on the laboratory. Several papers have been electronic requests and labels. In addition, direct print-
published that analyze and propose solutions 3-5. Over ing of cassettes and slides by automatics printers inter-
the past five years, we have approached this challenging faced with the laboratory information system produced
issue in our laboratory, with particular focus on the pre- a considerable reduction in block and slide mismatching
laboratory and laboratory phases. errors.
The most critical step is the accession phase, which is However, data analysis in 2009 revealed continuing
characterized by incorrect patient identifications and block and slide mismatching. For this reason, at the be-
The author is grateful to the entire Pathology Unit Staff; particular Giovanna Fabbretti, U.O. Anatomia Patologica e Citologia,
thanks are given to Luigi Santucci, Director of the Information Ospedale Infermi, via Settembrini 2, 47900 Rimini, Italy - E-mail:
Technology Department, and to Francesco Graziani, Rina Velati email@example.com
and Carla Zucca of Dedalus SpA.
314 g. fabbretti
ginning of 2010, a 2D bar code was introduced, which Fig. 1. cassettes and slides with a directly printed 2D bar code
is directly printed onto container labels, cassettes and and accession code number. Slides also show readable text: name
of institution, type of stain (he: yellow slides and immunostains
slides, in order to reduce mismatching in the gross ex- for Ki-67, progesterone and oestrogen receptors: white charged
amination and cutting phases. This new technology is slides) name and surname of patient.
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.
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, Aus-
tralia), 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, Ban- matching of a block and its associated slides. It is im-
nockburn, IL) to handle cassette and slide printing case- possible for two identically identified blocks or slides to
by-case during the gross and cutting phases; this avoids exist. For example, if a slide is printed and then the same
the need for manual code transcription. All of the above slide is printed again, the first slide printed is identified
has been described in detail in a previous publication 6. in the 2D bar code as 11-I-13500A21 and the second one
Since 2010, the LIS has used a 2D bar code and has been 11-I-13500A22.
interfaced with both cassette and slides printers (a Lei- This is of fundamental importance and is a key point
ca printer in the Cytology Lab and Slide Mate printers regarding matching of blocks and slides.
[Thermo Fisher Scientific, Waltham, MA] at the Cutting Each workstation in our unit is equipped with a PC,
Station); the LIS also has been integrated with a Leica monitor and scanner. We have also equipped each cut-
BOND-III instrument, which fully automates immuno- ting station with small slide printers to avoid the need to
histochemistry work; 2D bar codes are directly printed preprint slides. The LIS manages each individual step
onto immunohistochemistry slides at the cutting station: via the 2D bar code regarding the processing of samples,
the BOND-III reads the 2D slide bar codes. Extensive blocks and slides by recording the name of the operator
bar code printing testing and validation for cassettes and and the date and time of the step; in this way, each single
slides was conducted by Leica, Thermo Fisher Scien- case is traceable during the entire work procedure.
tific and Dedalus, and for scanner configuration by the The LIS furthermore records any error or problem de-
Dedalus Company and Metrologic Instruments Inc. We tected at any stage in the workflow. This function is
chose the Metrologic MS1690 Focus, which is an om- quick and easy to access by using a keyboard; in this
nidirectional scanner capable of reading all standard 1D function, a list of predetermined parameters are dis-
and 2D bar codes. played: e.g. error or problem type, possible corrective
During set up, we carried out ping testing on cassettes action, date, time and operator. Cases where an error has
and slides. No input failure occurred. Bar code misread- been detected are marked by a special icon, so that the
ing may be caused by poor quality cassette and slide ma- pathologist is alerted and can check the validity of the
terials, which can cause variations in printing quality. corrective actions taken before diagnosis.
We always test any new material that will be used. Errors and problems are subdivided in the following
The following are printed on cassettes: the accession way: accession errors, specimen errors or problems, and
code (e.g. 11-I-11340), specimen container letter (e.g. misidentification during the processing procedure. Each
A, B, C), subpart block number (e.g. 1, 2) and a 2D bar subgroup is further divided into other sub-categories (e.g.
code, which includes a progressive printing number misidentification during gross examination, embedding,
(Fig. 1). cutting, etc.). This system permits rapid analysis of col-
The following is printed on the slides as human readable lected data. Once a month, a specially trained technical
text: accession code (e.g. 11-I-13800), patient name and staff member evaluates data trends.
surname, type of stain (e.g. HE, PAS), the name of our The unit’s workflow, which is bar code based, is de-
unit (Anat Pat, RN); in addition there is a 2D bar code, scribed in a consistent and easy-to-read manner.
which also encodes a progressive printing number. 1. Accession phase: after a double check to verify that
The progressive printing number, found in both slide data on the electronic request corresponds to that on
and cassette 2D bar codes, is essential for the univocal the medical report that accompanies specimens (e.g.
role of 2D bar coDe anD electronic croSS-matching in the reDuction of miSiDentification errorS 315
Fig. 2. Downloaded request form and adhesive labels attached to for sentinel lymph nodes, yellow for small biopsies,
specimen containers. above: patient data; middle: the two sub- blue for lymph nodes, pink for skin biopsies and
mitted specimens: 1) skin from the lumbo-sacral region; 2) skin green for surgical specimens), section number, and
from the patient’s hip and clinical information; below: the space
occupied by detached labels. the routine stains or immunostains, if provided. The
default setting may be modified at any time during
the process. Cassettes are directly printed (Leica Mi-
crosystems, Bannockburn, IL) case-by-case during
gross examination. The printing process is quick and
3. Tissue embedding phase: after processing each cas-
sette is read by the scanner before embedding the tis-
sue. 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 cas-
sette’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 scan-
ner. the liS displays all relevant information and shows a list of
bronchoscopy, endoscopic report, etc.), the case is embedded cassettes.
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 con-
tainers 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
2. Gross examination phase: the specimen containers
are moved to the gross bench for sectioning and re-
cording of macroscopic findings. Our LIS provides
many predetermined parameters for each anatomi-
cal site and each medical procedure; for example,
the topographic code (SNOMED), the number and
colour of the cassette (orange for urgent cases, white
Fig. 5. cutting station: the cassette is read by the scanner, the liS
shows all tissue block information (patient name and surname,
Fig. 3. an internal lab worksheet: accession number and 1-di- code number, tissue type, number of fragments, embedded
mensional bar code and adhesive labels for specimen containers status, operator and date) and the slide mate printer prints the
with a 2-dimensional bar code. relevant information on the slide.
316 g. fabbretti
ded in cassettes, the case status is changed from gross because the clinical information was not concordant
executed to embedded. The LIS sequentially shows a with histological appearance. In other cases, the slide
list of all embedded cassettes on the monitor in the samples clearly did not correspond with the anatomical
work session, and, if required, supplies a printed site indicated in the request when viewed under the mi-
list. croscope. Another particularly important result achieved
4. Cutting phase: just before cutting, the operator reads by the introduction of 2D bar coding is the introduction
the block’s bar code with the scanner, and the slide of automated tracing; it is now possible in real time, to
printer prints all the associated slides; after section trace a specimen container or missing block and locate
cutting (and only at this time - before it is picked it immediately.
up) the slide is read by the scanner. If the slide does Indeed, the LIS manages the workflow, step by step, re-
not match the block, a message error on the moni- cording the operator’s name, date and time of each single
tor alerts the operator (Fig. 5). The LIS displays the step. We are now able to know what is happening in real
changing status of the slide from requested to vali- time, and to take immediate action to locate a misplaced
dated only if the slide matches correctly. When all container or block.
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 Discussion
procedure, there is the final check before delivering
slides to the referring pathologist. Each slide is read The case-by-case direct printing of bar code numbers
by the scanner, and when all slides of a single case on cassettes and slides by automated printers managed
(routine stain, special stains and immunostains) are by the LIS prevents errors caused by handwritten labels
‘pinged’ the case is ready to be sent for medical ex- and by transcription. Checking correspondence between
amination. 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
Results therefore subject to error caused by fatigue and lack of
The results achieved have been particularly good and of Even if the mismatch rate was low in the gross exami-
significant importance. Since the introduction in 2010 nation and cutting phases, and in keeping with data re-
of 2D bar codes on container labels, we have not had a ported in recent literature 7, an error that mismatches a
single case of sample mix up in the gross examination slide to the wrong patient can have serious consequences
phase in a total of 26,964 histological cases. In the gross on clinical outcome.
examination phase, each case begins with a reading For this reason, we worked closely with the LIS provider
of the 2D bar code on the container label, and the LIS to design a system that would prevent this type of error.
makes it impossible for a code number that is different to The result is that we have up-graded our LIS with the
the case number in question to be printed on a cassette. introduction of 2D bar codes on labels of specimen con-
In contrast, in 2009 we had 10 errors in a total of 26,961 tainers, and direct printed on cassettes and slides. The
(0.03%) cases that involved mismatch of samples from biggest leap in improved quality was achieved by the
the same patient. introduction of electronic cross-match managed by LIS.
Additionally, in the cutting phase we have had no mis- Another important advance is that there is now sample
match since automatic cassette and slide cross checking traceability throughout the entire workflow.
was made possible by the introduction of 2D bar codes In a recent paper, Zarbo et al. 8 describes a workflow
in 2010 (26,964 histological cases; 80,571 tissue blocks). dependent on bar code reading and illustrates the use of
In contrast in the same period in 2009, we had 32 mis- traditional bar codes on specimen container labels, in
matches from a total of 26,961 cases (0.11%) (80,361 specific labels for slides and use 2D bar code only for
tissue blocks) caused by the transfer of sections from one cassettes.
block to a mismatched slide. Data analysis showed that Unfortunately, in their laboratory, electronic requests
mismatch errors were more or less equally distributed are not yet employed and cases are accessioned manu-
between routine cutting (14 cases) and re-cutting. There ally from handwritten requisitions, which are often in-
was a slightly greater error prevalence for re-cutting (18 complete and unclear, as noted by Dimenstein 9. The
cases), where the errors involved cases with similar code labelling of slides represents an additional manual step
numbers (e.g. 09-I-23715 and 09-I-23915); 12 of 18 er- that is time consuming, prone to error and finally more
rors involved specimens from different patients, and 4 of expensive than directly printing on them.
18 involved different specimens from the same patient. The electronic checking introduced in the cutting sta-
Of the 14 routine cutting mismatch errors, 10 involved tion overcomes the problem of operators failing to fol-
different patients. None of the errors for either the gross low standard procedures, which was an issue that Zarbo
examination or the cutting phase resulted in adverse con- emphasized in his report. The LIS prevents proceeding
sequences for the patient, as they were detected during to the next case and alerts the operator is procedures are
subsequent steps. The errors were noticed in some cases 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 317
read by the scanner, the case is not validated. The intro- procedure, and not later in the pathology lab by a member
duction of electronic cross checking of blocks and slides of administration or technical staff. During gross tissue
is an effective means of preventing inevitable human er- examination, LIS case data can be accessed by reading
rors in the cutting phase caused by fatigue, lack of con- the 2D bar code on container labels, avoiding mix-up of
centration and heavy workload. specimens; the direct printing of cassettes one case at a
During the development of this project, the only con- time avoids the need for them to be prepared in advance
cern was the possible increase in processing times. How- and eliminates the risk of confusing cassettes from dif-
ever, during the first three weeks after the adoption of ferent patients. The direct printing of slides, one block at
the new workflow we experienced only a small delay a time, at the moment of cutting of sections, eliminates
in slide delivery, which was caused by the need to train the need for labelling, which is a time consuming step.
all operators; such training is obviously necessary when More importantly, it also eliminates a potential source of
introducing new organizational procedures. All techni- error because traditional labelling is a manual procedure
cal staff have very positively accepted this new working that is visually checked. Furthermore, labelling is more
procedure. In addition, in recent years much has been expensive than direct printing of slides. The introduction
accomplished in training all operators in risk manage- of electronic cross-checking using 2D bar codes directly
ment, and on-going work has been done with the entire printed onto blocks and slides represents a very important
team to identify the causes of mismatching and improv- qualitative leap. In our experience, it represents the best
ing workflow. The knowledge of when, where and why method for avoiding block and slide mismatching.
misidentification errors occur, which is a fundamental The redesigned workflow with 2D bar codes has an-
prerequisite for their successful reduction, has been fa- other advantage: real time case traceability throughout
cilitated by the LIS, which allows quick, easy and com- the entire procedure. Gradually we redesigned the entire
plete error reporting at each step of the work flow, as workflow procedure over a period of years. The support
previously described. we received from top management was crucial for its
In summary, the work over the last few years has been success. In our experience, no single piece of technology
focused on simplifying workflow procedures as much as can eliminate errors in a complex system such as a pa-
possible by utilizing information technology, and the em- thology work flow composed of multiple handoffs. Each
ployment of bar coding to minimize operator caused error. laboratory has to consider the individual requirements of
The process was streamlined by eliminating some poten- their own workflow.
tially error prone procedures, most importantly eliminat- The LIS and bar code technology play a leading role in
ing manual accession input in the LIS by using a direct making the entire process far safer. However, there is
electronic request entry. It is important to note that in this also the need for standard operating procedures for each
manner, the patient and his or her samples are correctly step, accompanied by an efficient system of recording
identified at the time they are taken, in the place they are errors for every phase (pre-lab, lab and post-lab) and rig-
taken and by the clinician who performed the medical orous daily compliance with all procedures.
References gical pathology: an 18-mounth experience. Am J Clin Pathol
Kohn LT, Corrigan JM, Donaldson MS, eds. To err is human: 6
Fabbretti G. Risk management: correct patient and specimen iden-
building a safer health system. Washington, DC: National Acad- tification in a surgical pathology laboratory. The experience of
emies Press 1999. Infermi Hospital, Rimini, Italy. Pathologica 2010;102:96-101.
Nakhleh RE. Error reduction in surgical pathology. Arch Pathol 7
Nakhleh RE, Idowu MO, Souers RJ, et al. Mislabeling of cases,
Lab Med 2006;130:630-2. specimens, blocks, and slides: a college of American pathologists
Zarbo RJ, D’Angelo R. The Henry Ford Production System: effec- study of 136 institutions. Arch Pathol Lab Med 2011;135:969-74.
tive reduction of process defects and waste in surgical pathology. 8
Zarbo RJ, Tuthill JM, D’Angelo R, et al. The Henry Ford Produc-
Am J Clin Pathol 2007;128:1015-22. tion System: reduction of surgical pathology in process misidenti-
D’Angelo R, Zarbo RJ. The Henry ford Production System: mea- fication defects by bar code-specified work process standardisa-
sures of process defects and waste in surgical pathology. Am J tion. Am J Clin Pathol 2009;131:468-77.
Clin Pathol 2007;128:423-9. 9
Dimenstein IB. Letter to the Editor. Am J Clin Pathol
Layfield LJ, Anderson GM. Specimen labelling errors in sur- 2009;132:975-6.
Cytologic re-evaluation of negative effusions
from patients with malignant mesothelioma
V. ASCOLI, D. BOSCO, C. CARNOVALE SCALZO
Dipartimento di Scienze Radiologiche, Oncologiche e Anatomo-patologiche, Sapienza Università di Roma, Italy
Mesothelioma • Cytology • Serous effusion • Reactive mesothelium • Diagnostic pitfalls
Background. Cytology is a controversial means of diagnosing suspicious (false-negative diagnosis); the remaining cases were
malignant mesothelioma due to the high rates of negative sam- true-negative or inadequate. Almost all effusions initially called
ples. The aim of the present study was to review effusions origi- “negative” (but non-neoplastic by histology) were considered
nally reported as “negative” in patients with histologically-proven negative. The only item that seems to discriminate between the
mesothelioma to evaluate possible pitfalls. two groups is atypia of mesothelial cells.
Methods. We reviewed the cytologic slides of 25 specimens that Conclusions. The present study has highlighted the following pit-
refer to 15 epithelioid, 5 biphasic, 4 sarcomatoid and 1 well- falls: (i) to report effusions devoid of mesothelial cells as negative
differentiated papillary mesotheliomas. For comparison, we that instead should be reported as inadequate/non-diagnostic; (ii) to
also reviewed 23 specimens from non-neoplastic conditions. underestimate low cellular effusions containing atypical mesothelial
For each effusion, we evaluated the background and calculated cells or high cellular effusions containing bland mesothelial cells with
a score considering the following items: amount of mesothelial a morular pattern; (iii) to consider that an inflammatory background
cells, architectural pattern and atypical features, and a revised may obscure a scant number of mesothelial cells. A categorized sys-
diagnosis was rendered. tem (inadequate (M1), negative (M2), atypical (M3) and suspicious
Results. More than half of the effusions initially called “nega- (M4)) for reporting effusion cytology may be of help in the diagnos-
tive” (but mesothelioma by histology) were considered atypical/ tic 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
Since most malignant mesothelioma (MM) first present sample should be considered.
with a pleural/peritoneal effusion 1, cytologic analysis We present herein the experience of our laboratory on
represents the primary diagnostic approach. However, 25 cases of histologically-proven MM in which cyto-
cytologic diagnosis of MM is notoriously challenging logic diagnosis on effusions was originally reported
with a sensitivity ranging from 30% to 80% 1-4. This as negative for malignancy. Based on the re-examina-
variability mainly reflects the lack of experience of pa- tion of cytology specimens, we investigated the type
thologists with this rare malignancy and the complex- of errors, if any, and produced a scoring system that
ity in interpretation of the changes in mesothelial cells, might be helpful in detecting mesothelioma cells. For
the main pitfall being the resemblance of mesothelioma comparison, 23 negative effusions from histologically-
cells to normal or reactive mesothelial cells. The lack of demonstrated non-neoplastic conditions were also re-
a dedicated technical approach to the handling of effu- examined.
sions is also the source of errors such as improper collec-
tion and processing of effusions fluids 5.
The topic of whether cytology should be an acceptable Materials and methods
means of diagnosing MM is controversial 6, but a role for
cytology cannot be excluded, also because cytology may From a series of 109 histologically proven cases of MM
be the only source of pathological material available. (all with a previous effusion examined) that were diag-
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: firstname.lastname@example.org
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, from 1 to 7 points
multinucleation, atypical mitosis, macronucleoli,
cytomegalia, vacuolation of the cytoplasm, presence
of squamoid cells)
nosed in our institution (Azienda Ospedaliera Policlinico There were two main patterns: neutrophil plentiful
“Umberto I”, Roma) over a 9-year period, we retrieved (Fig. 1), and small lymphocyte plentiful (Fig. 2). In
25 cases in which the original cytology report was “nega- effusions with abundant neutrophils, there was also a
tive for malignancy”. Fourteen cases were first effusions large amount of fibrin and necrosis obscuring meso-
and 11 were recurrent effusions. The final histologic di- thelial cells, when present (Fig. 3).
agnosis was as follows: epithelioid MM (n = 15), well- • Mesothelial cells. In 6 specimens, mesothelial cells
differentiated papillary mesothelioma (n = 1), biphasic were absent (inadequate/non-diagnostic specimens);
MM (n = 5) and sarcomatoid MM (n = 4). Twenty-one in the other 19 specimens, mesothelial cells were
were MM of the pleura and 4 of the peritoneum. present (adequate specimens). Of these 19 adequate
Cytological material consisted of conventional smears specimens, 12 effusions were scarcely cellular and 7
stained with Papanicolaou and Giemsa stains. None of moderate-to-abundant cellular.
the 25 specimens had been processed by the cell block • Mesothelial architecture. Mesothelial cells were seen
technique. Also, immunocytochemistry had not been re- either as scattered single cells (n = 11, Figs. 1-4) or as an
quested. admixture of single and clustered cells (n = 8, Fig. 5).
The cytological slides were reviewed by the three • Mesothelial atypical features. Of the 19 adequate
coauthors who were non-blinded to the original di- specimens, 5 effusions showed mesothelial with no
agnosis, and the following cytological features were atypical features. The other 14 effusions showed
considered: 1) background, defined in terms of in-
flammatory cells (lymphocytes, neutrophils, mixed
inflammatory cells) and the presence of necrosis; Fig. 1. Single mesothelial cells surrounded by neutrophils; note
2) mesothelial cellularity, defined as absent, scarce, cytomegalia, multinucleation and prominent nucleoli. histology
revealed epithelial mesothelioma. cytodiagnosis on revision: m4/
moderate, and abundant; 3) mesothelial cell architec- suspicious.
ture, the arrangement of mesothelial cells in clusters/
morulae or as individual cells; 4) mesothelial atypi-
cal features, including anisonucleosis, atypical mi-
tosis, binucleation/multinucleation, macronucleoli,
cytomegalia, vacuolation of the cytoplasm and pres-
ence 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.
Group negative by cytology/mesothelioma by histology
The main features of cytological revision of the 25 MM
cases together with the corresponding histological sub-
types are reported in Table II, and in Figures 1-4.
• Background. All effusion samples were character-
ized by a variable amount of inflammatory cells.
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
Histologic Cytological revision Diagnosis on revision
Background Mesothelial cells
Inflammatory Amount Architecture Atypical Total
Cell Type features Score
epithelial lymphocytes 0 na na 0 inadequate/non-diagnostic (m1)
epithelial neutrophils 0 na na 0 inadequate/non-diagnostic (m1)
epithelial neutrophils 0 na na 0 inadequate/non-diagnostic (m1)
epithelial neutrophils 0 na na 0 inadequate/non-diagnostic (m1)
Sarcomatous lymphocytes 0 na na 0 inadequate/non-diagnostic (m1)
epithelial mixed 0 na na 0 inadequate/non-diagnostic (m1)
epithelial neutrophils/ 1 1 0 2 negative (m2)
epithelial mixed 1 1 0 2 negative (m2)
Sarcomatous neutrophils/ 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)
wDpm mixed 3 2 2 7 Suspicious (m4)
epithelial neutrophils 2 2 4 8 Suspicious (m4)
na = not applicable
wDpm = well-differentiated papillary mesothelioma
often multinucleation and macronucleoli and cyto- (n = 1), and with no atypical nuclear features. The back-
megalia (Figs. 1, 3), also in addition to vacuolation of ground of the smears was heavily inflammatory; often
the cytoplasm and squamoid cells (Fig. 4); the least there were granulocytes and also abundant necrosis. The
frequent atypical features were anisonucleosis and overall score was 2.
mitosis. M3-Atypical mesothelial cells of undetermined signifi-
Upon revision, we attributed the 25 effusions to 4 cat- cance. We included 8 effusions in this category charac-
egories: M1 (inadequate), M2 (negative), M3 (atypical) terized by scarce rather than moderate mesothelial cellu-
and M4 (suspicious). larity; mesothelial cells were seen as single cells (n = 6)
M1-Inadequate/non-diagnostic. We included 6 cases in more than in clusters (n = 2); mesothelial cells showed
this category that were completely devoid of mesothe- a few atypical nuclear features; the inflammatory back-
lial cells. The background of the smears was heavily in- ground was mainly represented by lymphocytes (Fig. 2).
flammatory (granulocytes or lymphocytes). The overall A single case included in this category was highly cel-
score was 0. lular, but anisonucleosis was the only atypical feature
M2-Negative. We included 5 cases with a low number of mesothelial cells. The overall score was between 3
of mesothelial cells lying singly (n = 4) or in clusters and 5.
cytologic re-evaluation of negative effuSionS from patientS with malignant meSothelioma 321
Fig. 2. Single atypical mesothelial cell surrounded by numerous Fig. 4. Single atypical mesothelial cells surrounded by abundant
lymphocytes. histology revealed biphasic mesothelioma. cytodi- inflammatory cells; note many orangiophilic squamoid cells. his-
agnosis on revision: m3/atypical. tology revealed epithelial mesothelioma. cytodiagnosis on revi-
Fig. 3. abundant necrosis, fibrin, inflammatory cells; there were
only very rare single atypical mesothelial cells. histology revealed
biphasic mesothelioma. cytodiagnosis on revision: m4/suspi-
Fig. 5. clusters of mesothelial cells with bland atypical features.
histology revealed epithelial mesothelioma. cytodiagnosis: on re-
M4-Suspicious mesothelial cells. We included 6 effu-
sions characterized by moderate/abundant mesothelial
cellularity; in all specimens, there were clusters of me-
sothelial 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 character-
ized by a variable amount of inflammatory cells.
• Mesothelial cells. In a single specimen, mesothelial
cells were absent (inadequate/non-diagnostic speci-
men); 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 Cytological revision Diagnosis on revision
Background Mesothelial cells
Inflammatory Amount Architecture Atypical Total Score
Cell Type features
no malignancy neutrophils 0 na na 0 inadequate/
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 atypi- cases. These effusions represent diagnostic errors (false-
cal features (n = 2). negative diagnoses) because they contained atypical me-
Upon revision, we attributed the 23 effusions to 2 cat- sothelial cells. When excluding 6 inadequate specimens
egories, M1 (inadequate) and M2 (negative). (24%), the remaining 5 cases (20%) were confirmed as
M1-Inadequate/non-diagnostic. We included a single negative for malignancy, and were not diagnostic errors
case in this category that was completely devoid of me- (true-negative diagnoses) by cytology.
sothelial cells. The background of the smears was heav- The scoring system is not particularly useful in sepa-
ily inflammatory (granulocytes). rating the effusions due to non-neoplastic conditions
M2-Negative. We included 22 cases with a moderate from effusions due to mesothelioma. However, there
number of mesothelial cells lying singly or in clusters is a bias of case selection in the MM group. In fact,
and with no atypical nuclear features or minimal atypi- effusions due to MM were cases were that had been
cal features. The background of the smears was inflam- called “negative” in earlier diagnosis; it is likely that
matory. The overall score was between 2 and 6. effusions containing clear-cut mesotheliomatous cells
would give a higher score. Architectural features seem
to be a non-informative variable, and the amount of
Discussion mesothelial cells does not discriminate between the
two groups; rather, it seems that more abundant meso-
Our results showed that the cytologic revision of speci- thelial cells characterize the “negative” effusions more
mens previously reported as negative (but mesothelioma than “false negative effusions” due to mesothelioma.
by histology) provided a different diagnosis in 56% of Atypical features are probably the most useful charac-
cytologic re-evaluation of negative effuSionS from patientS with malignant meSothelioma 323
teristics in the daily practice to discriminate between sediment); (iii) the absence of immunocytochemistry
the two groups. (because cell blocks are not routinely prepared in our
Based on our diagnosis on revision, we propose that laboratory in case of negative effusions).
effusions containing atypical mesothelial cells should Taking into account histology, effusions that also re-
be called at the very least “effusions containing atypi- mained negative on revision included three of four sar-
cal mesothelial cells of undetermined significance” comatous MM of the present series; this finding is not
(M3 category); those effusions containing abundant unexpected and is a well-know feature in the cytologic
mesothelial cells with a morular pattern with some literature (mesothelial cells are entrapped in the fibrous
atypical features should be called “suspicious for me- tissue). Among the suspicious/M4 effusions, there was
sothelioma” (M4 category). The M3/atypical and M4/ a case of well-differentiated peritoneal mesothelioma
suspicious effusions are at variance more on the basis (WDPM), which is an uncommon subtype of mesothe-
of the amount of mesothelial cells and on the basis of lioma characterized by superficial spreading of papillary
cell grouping, rather than on the number of atypical formations lined by bland epithelioid cells that can be a
nuclear features. We also propose, similar to thyroid/ source of false-negative cytologic diagnoses. However,
breast and cervical cytology, a system for reporting ef- this entity should be recognized by cytology in highly
fusion cytology that could be of help in the diagnostic cellular effusions and reliably be called suspicious for
work-up of fluids for mesothelioma: inadequate (M1), mesothelioma 8 9.
negative (M2), atypical (M3) and suspicious (M4), as
recently reported 3.
Although we are aware of the limits of cytology in di- Conclusions
agnosis of mesothelioma, and confirmed herein, the
present study has allowed us to focus on the follow- 1. More than half of effusions due to mesothelioma that
ing pitfalls: (i) To call negative those effusions that are were initially called “negative for malignancy” are
devoid of mesothelial cells; these effusions should be false-negatives on revision. The remaining cases are
called inadequate/unsatisfactory, non-diagnostic. Any either true negatives (very scarce cellularity) or inad-
specimen with no mesothelial cells to be evaluated equate (absence of mesothelial cells).
should be unsatisfactory for evaluation, as in thyroid 2. Cytology may aid in diagnosis in patients with epi-
and cervical cytology. (ii) To pay little attention to low thelioid and biphasic MM, but not in patients with
cellular effusions containing atypical mesothelial cells sarcomatoid MM.
dispersed as single cells. Several conditions limit exfo- 3. Obscuring inflammatory background (lymphocytes,
liation of diagnostic cells into effusions (recurrent ef- neutrophils) and necrosis may hamper diagnostic
fusions, non-epithelial mesothelioma). Any specimen evaluation of atypical mesothelial cells.
with abnormal cells should be satisfactory for evalu- 4. Currently, to limit the number of false-negative diag-
ation, as for cervical/thyroid cytology. In such cases, nosis, we ask clinicians to send the total amount of
a note should be added indicating that the presence of fluid that is actually collected to increase the amount
mesothelioma cannot be excluded. (iii) To not take into of cells. We carefully process effusion fluid to rou-
account high cellular effusions with a striking morular tinely prepare cell-blocks, as strongly recommended
pattern of mesothelial cells of bland appearance. An- by most experts.
other pitfall is the heavy inflammatory background that 5. As in thyroid/breast and cervical cytology, a catego-
may hamper the diagnosis by obscuring the scant num- rized system for reporting effusion cytology may be
ber of mesothelial cells. In the atypical/M3 category, of help in the diagnostic work-up of fluids for meso-
we noticed that inflammatory cells were mainly lym- thelioma (inadequate [M1], negative [M2], atypical
phocytes; interestingly, it is known that mesothelioma [M3] and suspicious [M4]).
can be heavily infiltrated with many immune effector 6. The scoring system adopted in this study (evaluating
cells, with T-lymphocytes constituting the major part the amount of mesothelial cells, architectural pattern
of inflammatory cells 7. Other factors (data not shown) and atypical features of mesothelial cells) is not par-
that may have contributed to the diagnostic pitfall are: ticularly useful in separating effusions due to non-
(i) the scarce amount of fluid examined respect to neoplastic conditions from those due to mesothe-
the amount of fluid evacuated implying hypocellular lioma; nevertheless, atypical features are probably
specimens; (ii) the improper specimen processing (ex- the most useful characteristics in the daily practice to
cess of blood and insufficient concentration of cellular discriminate between the two groups.
324 v. aScoli et al.
Whitaker D. The cytology of malignant mesothelioma. Cytopathol-
Di Bonito L, Falconieri G, Colautti I, et al. Cytopathology of ma- 6
Sheaff M. Should cytology be an acceptable means of diagnosing
lignant mesothelioma: a study of its patterns and histological bas-
malignant mesothelioma? Cytopathology 2010;22:3-4.
es. Diagn Cytopathol 1993;9:25-31.
Renshaw AA, Dean BR, Antman KH, et al. The role of cytologic
Hegmans JP, Hemmes A, Hammad H, et al. Mesothelioma envi-
evaluation of pleural fluid in the diagnosis of malignant mesothe- ronment comprises cytokines and T-regulatory cells that suppress
lioma. Chest 1997;111:106-9. immune responses. Eur Respir J 2006;27:1086-95.
Rakha EA, Patil S, Abdulla K, et al. The sensitivity of cytologic
Ikeda K, Suzuki T, Tate G, et al. Cytomorphologic features of
evaluation of pleural fluid in the diagnosis of malignant mesothe- well-differentiated papillary mesothelioma in peritoneal effusion:
lioma. Diagn Cytopathol 2010;38:874-9. a case report. Diagn Cytopathol 2008;36:512-5.
Sherman ME, Mark EJ. Effusion cytology in the diagnosis of 9
Haba T, Wakasa K, Sasaki M. Well-differentiated papillary
malignant epithelioid and biphasic pleural mesothelioma. Arch mesothelioma in the pelvic cavity. A case report. Acta Cytol
Pathol Lab Med 1990;114:845-51. 2003;47:88-92.
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
Frozen sections • Intraoperative diagnosis • Breast cancer • Core needle biopsy • Fine needle aspiration cytology
Data on 2436 primary breast carcinomas diagnosed between 1992 in 1999, and 0% in 2005-2006. In the same period, the adoption
and 2006 were collected to evaluate the rate of frozen section pro- of cytology and core biopsy for breast cancer diagnosis increased
cedures performed over time. Frozen section procedures performed from 40% in 1992 to more than 90% since 1999. In an audited
to evaluate resection margins for conservative surgery or sentinel diagnostic activity on breast pathology, the routine use of frozen
node status were excluded. Over time, there was a decrease in the sections on primary lesions was considered inappropriate, particu-
use of frozen sections indistinctly extended to all pT cancer catego- larly in assessment of clinically non-palpable lesions, and should be
ries. The rate of cancers diagnosed with frozen sections was 51.2% 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
The frozen section technique was first introduced by of resection margins 22-24 and status of sentinel lymph
Wilson in 1905 for intraoperative diagnosis of breast nodes 25-27.
carcinoma 1. In subsequent years, intraoperative frozen In the literature, only limited data have been collected
section examination was established as a reliable pro- with the aim of objectively defining the decreasing use
cedure for the rapid histologic evaluation of surgical of FS. The aim of the current study was to analyse the
breast specimens 2-6. Advances in radiology, pathology, frequency of FS utilization in primary breast cancer se-
surgical techniques, medical oncology and radiotherapy ries over a period of 15 years, and to evaluate the influ-
have changed the diagnostic and therapeutic approaches ence of clinical and pathological variables on results.
to breast cancer. Nowadays, different therapeutic strate-
gies to breast cancer are available and tailored treatment
for each individual patient is guided by detailed clinical Materials and methods
and pathological data available before surgery. Over the
years, the flow-chart referred to the assessment of breast Data on a large series of consecutive breast cancers, de-
lesions has been progressively shifted from intraopera- tected outside a screening program and surgically treated
tive procedures to pre-surgical diagnostic techniques, as in “G.B. Rossi” University Hospital in Verona between
imaging guided fine-needle aspiration cytology (FNAC) January 1992 to December 2006 were extracted from
and core needle biopsy (CNB) or vacuum-assisted gun files of the Breast Cancer Registry and the Department
needle biopsy (VAB) 7-13. The diffusion of mammogra- of Pathology of the same institution. The rate of breast
phy has increased the detection of small cancers (< 1 cm) cancers submitted to FS for intraoperative diagnostic
as well as proliferative, low grade atypical lesions for purpose were retrieved from computerized diagnostic
which intraoperative frozen sections (FS) should not be files of the Department of Pathology. Frozen section
considered mandatory 4-6 14-18. In this scenario, FS has lost procedures performed to evaluate resection margins for
its role as the first line diagnostic method guiding the conservative surgery or sentinel node status were ex-
surgical strategy on primary breast lesions 19-21 through cluded. According to the purpose of the present analysis,
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.
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 detec- cancers were submitted to FS, but in 2005 and 2006,
tion, “in situ” or invasive cancer histology, lesion size no primary breast lesion was assessed with FS (Fig. 2).
measured on the histological slide and expressed in pT The progressively decreasing use of FS began in the
category according to the American Joint Committee on middle of the 1990’s. At the beginning of the 2000’s,
Cancer (AJCC) 28. To match the number of cancers his- the requests for FS on primary breast lesions registered
tologically diagnosed and the number of needle biopsies a nearly vertical decrease (Fig. 2). The decreasing use
performed to gain a pre-surgical diagnosis, pathologi- of FS on primary breast cancers involved all pT cancer
cal files were also searched for pre-operative diagnostic categories (Fig. 3). From 1992 to 1999, the rate of can-
procedures performed on primary breast lesions during cers submitted to FS was significantly influenced by
the same period. 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
Between January, 1992 and December 2006, 2434 pri- cancers between 1992 and 2006.
mary breast cancers were collected at the Department Cancer series Frozen Section rate
of Pathology of the University of Verona (Tab. I). Inva- Year n. 2434 %
sive breast cancers accounted for 85.6% (2,084 cases) 1992 117 51.3
and “in situ” cancers for 13.5% (329 cases). In 0.9%
of cases, the invasive or “in situ” type was not speci- 1993 139 48.2
fied (21 cases). Over the years, the detection rate of 1994 105 48.5
invasive breast cancers smaller than 2 cm (pT1mic-a, 1995 125 44.0
pT1b, pT1c) showed a progressive increase balanced 1996 120 39.1
by the decreasing detection rate of cancers larger than
1997 155 29.0
2 cm (pT2+) (Fig. 1). Changes in the distribution in
the detection rate of breast cancer in favour of small 1998 195 25.6
lesions were observed during the middle of the 1990’s, 1999 175 22.8
but a higher detection rate was registered in 1999 and 2000 222 12.1
continued in subsequent years, favoured by the intro-
2001 207 1.0
duction of the breast cancer screening program and
more participation of women in non-organized mam- 2002 186 0.0
mography tests. From 1999, the detection rate of “in 2003 129 6.2
situ” carcinoma showed an increase that was almost 2004 162 3.7
always greater than 15% (Fig. 1). The rate of FS per- 2005 219 0
formed yearly on primary breast lesions progressively
decreased over time (Tab. I). In 1992, 50% of detected 2006 178 0
frozen SectionS for breaSt cancer DiagnoSiS 327
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 the needle sampling procedures performed. The rate of
less than 2.5% in all pT cancer categories (Fig. 4). cancers submitted to a pre-surgical sampling procedure,
Data on pre-surgical diagnostic procedures performed either FNAC and CNB, increased exponentially since
on surgically treated lesions were completely avail- 1995 (Fig. 5), which was balanced by the decreasing use
able for screen-detected breast cancers and have been of FS (Fig. 2).
previously published 10-11. All screen-detected breast
cancers were assessed with FNAC or CNB before sur-
gery. FNAC was adopted as a first-line method to obtain Discussion
cytological smears from suspicious lesions with an ac-
curacy that was well within the thresholds proposed by The results of the current study about the use of FS on
European guidelines for quality assurance in breast can- primary breast lesions during 15 years of surgical pa-
cer screening programmes 29. Briefly, the FNAC positive thology activity (1992-2006), have shown the progres-
predictive value for a malignant diagnosis was 99.3%, sive disuse of this technique in our institution. A rate as
the inadequate rate from cancer (IRc) was 2.4% and the high as 50% of primary breast cancers were submitted to
false-positive rate (FPR) was 0.5%. FS in 1992, but at present no cancers are assessed with
Data on pre-surgical sampling diagnostic procedures FS in an intraoperative setting (Tab. I).
performed on clinically detected cancers were avail- For many years, the diagnosis of breast cancer was guid-
able for about 60% of all cases for years between 1992 ed by the intraoperative assessment of suspicious lesions
and 1997, but for subsequent years (1998-2006) more by frozen sections. After long-lasting scientific discus-
of 90% of cases were furnished with information about sions 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 Screening programmes favour the detection of lower
which FS should be adopted 14 15 17 18 21 30-32. Trained person- graded, smaller sized breast cancers as well as pre-inva-
nel and accurate selection of lesions to be submitted to FS sive lesions and pure microcalcifications for which the
evaluation limited the false–negative rate to as less than 1%, feasibility of intraoperative consultation has been evalu-
and the number of deferred diagnoses to less than 5% 2 6 21. ated, but not routinely recommended 3 33. Studies sug-
The appropriateness of FS examination for diagnosis of gest that FS for these breast lesions may have a lower
mammographically-detected lesions has been subject of accuracy and may impair the results of definitive histol-
controversy, and most authors have concluded that frozen ogy from paraffin-embedded tissue due to freezing arte-
section examination should be limited to cases with distinct facts 14-17 34 35.
gross lesions larger 1.0 cm 16 17. As a consequence, the per- In the current cancer series, the beginning of the screen-
centage of breast specimens evaluated by frozen sections ing activity coincided with the growing detection of can-
has decreased over the years. A review of data from Ben cers smaller than 1 cm and the decreasing rate of cancers
Taub Hospital (Houston, USA) documented that, between larger than 2 cm (Fig. 1). However, only 8% of breast
1985 and 1995, 20% to 35% of all intraoperative consulta- cancers collected from 1999 to 2006 were screen-detect-
tions sent to frozen section analysis were from the breast, ed, and assume that the “positive” effect of screening
but this decreased to 4-8% in the 2000’s 21. programmes in stimulating women to perform mam-
In our institution, the decreasing use of FS, already de- mography examinations favoured the improved detec-
tectable in the middle of 1990’s, registered an accelera- tion of small breast cancers even in a female popula-
tion at the beginning of 2000’s in concomitance with the tion that was not invited to screening represents 92% of
beginning of screening programme activity (Fig. 2). 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.
frozen SectionS for breaSt cancer DiagnoSiS 329
smaller than 1 cm shifted from 12-18% between 1992 solved cases sent to FS. The type of breast lesion on
and 1996 to 20- 40% in subsequent years. mammograms or ultrasound (focal, parenchymal distor-
The growing number of small breast lesions may be a tion, calcifications) and the confidence of the radiolo-
cause of the reduced use of FS. The sensitivity of frozen gist or pathologist with a needle sampling technique are
section diagnoses of breast lesions after the introduction guiding the modality to obtain diagnostic samples from
of a national programme in mammographic screening breast lesions 8-10, reducing costs 13 and limiting the use
in Luxembourg dropped from 92.3% in 1990 to 87.6% of FS to those cases in which a pre-surgical diagnosis is
in 1998, the negative predictive value from 95.7% to not adequate.
88.3%, and invasive breast cancers ≤ 1 cm increased A preoperative core or fine-needle biopsy may eliminate
from 14.2% to 22.3% (p < 0.01). Breast frozen section unnecessary surgery and significantly reduce costs 38-40.
examinations in 1990 compared to those in 1998 de- The study of sentinel lymph node and schemes of neo-
clined from 70.7% to 62.2% 20. adjuvant chemotherapy that increase breast conserva-
Nevertheless, the decreasing use of FS is not completely tion surgery, disease-free and overall survival in patients
explained by the increased detection rate of small cancers with complete pathological response 41, favoured the
less than 1 cm. In current series, the decreasing rate of FS adoption of core needle biopsy for histological dem-
performed on primary breast cancers was observed in all onstration of breast carcinoma and for the assessment
pT cancer categories (Fig. 2). The comparison between of a biological cancer profile predictive of response to
the FS rate performed on breast cancers collected between medical therapy. In addition, preoperative diagnosis of
1992 and 1999 and the FS rate in cancer series between invasive breast cancer increases the likelihood of clean
2000 and 2006, stratified according to cancer size, high- margins at definitive surgery 38-40. This reduces the need
lights that in the 2000’s FS was exceptionally performed for a two-stage procedure and improves both surgical
for diagnostic purpose on primary breast cancers, what- and oncological outcomes 42 43.
ever the cancer size (Fig. 3). This is far more interesting Advances in surgical techniques, oncology, pathology,
for our analysis, especially if it is considered that in 2005 radiotherapy and radiology have influenced a new vi-
and 2006, on a total of 397 cancers, no FS was performed sion for treatment of breast cancer and reduced surgical
(Tab. I), even if 60% of detected cancers were larger than trauma. The current results confirm that drastic changes
1 cm and potentially amenable to FS (Fig. 1). have occurred in the management of breast lesions, with
The strictly adherence to guideline recommendations more patients evaluated in a pre-operative setting. After
favouring pre-surgical, image-guided needle assessment more than 100 years from its first adoption as a rapid
of breast suspicious lesions to avoid unnecessary sur- method for breast cancer diagnosis 1, the use of frozen
gery 29, aided the widespread adoption of FNAC, CNB sections is no longer considered for primary breast le-
and VAB to obtain a diagnosis on mammographically sions. In an audited diagnostic activity on breast pathol-
detected breast lesions 36. In a multidisciplinary approach ogy, the routine use of FS on primary lesions is inappro-
to breast lesions, biopsy techniques provided optimal di- priate, particularly in the assessment of clinically non-
agnostic accuracy with a sensitivity between 93% and palpable lesions. Its use should be limited to cases with
100% and a specificity between 98% and 100% 10 30-32, inadequate pre-surgical sampling quantified in no more
which undoubtedly influenced the reduction of unre- than 5% of surgically removed cancers 29.
Ciatto S, Houssami N, Ambrogetti D, et al. Accuracy and underes-
timation of malignancy of breast core needle biopsy: the Florence
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of 1,490 consecutive cases. Am J Surg Pathol 1995;19:1267-71. of the Verona mammographic breast cancer screening program
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The diagnostic accuracy of cervical biopsies
in determining cervical lesions: an audit
J. WANG, M. EL-BAHRAWY
Department of Histopathology, Hammersmith Hospital, Imperial College London, UK
Cervix • Biopsy • Colposcopy • Dysplasia • Cancer • Screening
Objective. The present audit was carried out to assess the diag- Main outcome measures and results. In 2004-5, the rate of con-
nostic accuracy of cervical punch biopsy during colposcopy in sistent diagnosis was 68.7%, compared with 75.8% in 2008. This
comparison with diagnosis from subsequent cone excision. was due to a decrease in the rates of overdiagnosis (16.7% vs.
Design and setting. Retrospective analysis was performed by 14.8%) and underdiagnosis (14.7% vs. 9.4%), which was statisti-
examining the histopathology reports for paired cervical punch cally significant. The sensitivity rates for 2004-5 and 2008 were
biopsies and cervical cone excisions for cases reported from April 87.5% and 89.7%, and the specificity rates for the same periods
2004 to March 2005 (when cervical biopsies and cones were were 39.8% and 39.4% respectively.
reported by general pathologists) and from January to December Conclusions. This audit highlights the importance of planning
2008 (when reporting by specialist gynaecological pathologists patient management on the basis of co-ordinated information
was instituted). from smear results, history, colposcopy findings and cervical
Sample. 150 women had both cervical punch and cone biopsies biopsies. The introduction of specialist gynaecological histopa-
performed in the 2004-2005 period, while 149 women had both thology reporting has significantly improved the rates of consis-
biopsies performed in 2008. tent diagnosis.
Introduction opsy, the patient then undergoes cervical cone or loop
In the UK, a cervical screening program has been imple- Therefore, accurate diagnosis on the biopsy taken at col-
mented since the 1980s, and the advantages of cervical poscopy is key in directing further management of the
screening are well documented, with a decrease in both patient. Despite the importance of this key step in the
incidence and mortality from cervical cancers. Despite patient pathway, there have been few studies examin-
its success, cervical screening by cytology is not always ing the reliability of cervical punch biopsies. One study
reliable. It has been established that the average screen- analysed 352 cases and showed that there was a concor-
ing sensitivity and specificity of cervical cytology is dance rate of only 66% between the histological diagno-
about 61-66% and 82-91%, respectively 1 2. However, a ses of punch biopsies and the results of the subsequent
positive cervical cytology result is only the first step in loop excision of the cervix 3. In another study of 107
the pathway towards definitive diagnosis and treatment cases, cervical punch biopsy was compared to cytology.
of a cervical lesion. The current practice in the UK is It was found that there was a consistency rate of 63%
that a patient with a cytology result confirming defi- between cervical punch biopsies and cones 4.
nite dyskaryosis or with repeated borderline change We investigated the accuracy of reporting of cervical bi-
requires referral to colposcopy. At colposcopy, the opsies taken at colposcopy, which would influence the
cervix is visualized and a punch biopsy is often taken subsequent management of patients. Moreover, the prac-
for histological examination. If high grade cervical tice of histopathologists as a whole is moving towards
intraepithelial neoplasia (CIN) or cervical glandular specialist reporting. It also remains to be seen if such a
intraepithelial neoplasia (CGIN) is confirmed on bi- move improves the accuracy of cervical punch biopsy
M. El-Bahrawy is grateful for support from the NIHR Biomedical Mona A. El-Bahrawy, Department of Histopathology, Imperial
Research Centre funding scheme. J. Wang receives funding from College London, Hammersmith Hospital, DuCane Road, London
the NIHR Clinical Lecturer scheme. W12 0NN UK - Tel. 020 8383 3442 - Fax 020 8383 8141 - E-mail:
332 J. wang, m. el-bahrawy
diagnosis. In this audit, we investigated the diagnostic of high-grade squamous intra-epithelial lesions (HSIL).
accuracy of cervical biopsies performed at a gynaeco- The same situation also applies for CIN2/3 and CGIN.
logical cancer centre. The accuracy of diagnosis in two However, CIN1 and human papilloma virus (HPV) in-
different periods was analysed, a period during which fections were categorized separately, despite the similar
the diagnosis of cervical biopsies and cones was done by management plans and the common Bethesda classifica-
general pathologists, and a period after specialist report- tion of low-grade SIL (LSIL). This is because these le-
ing by gynaecological histopathologists was instituted sions have previously had different management strate-
and the vast majority of cervical biopsies were reported gies in the UK. In addition, a diagnosis of CIN (difficult
by specialists. 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
Methods to grade) and a subsequent cone diagnosis of HPV only
or benign conditions was considered overdiagnosis.
Patients In addition to comparing the reporting accuracy be-
This is a retrospective study of histopathology reporting tween the two periods, the results were categorized into
on cervical punch biopsies and cones during two periods. whether the reporting of the cervical punch biopsy was
The earlier period was from 1 April 2004 to 31 March done by specialist gynaecological histopathologists, or
2005, and the later period was from 1 January 2008 to by general histopathologists.
31 December 2008. Only patients who had both a cervi-
cal biopsy and a subsequent cone biopsy reported at the
Department of Histopathology, Hammersmith Hospital, There have not been any previous publications that have
during the periods defined were included. dealt in detail with the problem of overdiagnosis or un-
derdiagnosis in cervical biopsies. However, Boonkilit et
Data collection al. have shown in their series that there is a concordance
For each pair of specimens, pathology reports were re- rate of 66% between cervical biopsy results and cones 3.
trieved and the following data collected: type of speci- For the purposes of the present audit, therefore, we have
men, consultant histopathologist (general or specialist) considered a consistent diagnosis rate of 60% to be ac-
reporting the case and diagnosis. In cases where the ceptable. Also, Thompson et al. have shown that there
diagnosis fell between two categories, the higher grade was a negative diagnosis in cone excisions of 28-68% 5.
diagnosis was recorded, as in most cases further man- Thus, an overdiagnosis rate of less than 25% was con-
agement would be based on the higher grade disease. sidered acceptable.
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 To determine if the number of consistent diagnoses and
diagnosis is CIN 1 and CGIN, the diagnosis was CGIN. the number of either over- or underdiagnoses were sig-
Based on the diagnoses of the biopsies and cones, each nificantly different between the two periods of reporting,
pair of specimens was categorized as having consistent a chi-square test was performed. A significant difference
diagnoses, overdiagnoses or underdiagnoses. Situations in reporting accuracy was if the p value was < 0.05.
of overdiagnosis and underdiagnosis are summarized in Finally, to calculate the sensitivity, specificity, positive
Table I. predictive value (PPV) and negative predictive value
For the audit purposes, since CIN2 and CIN3 are both (NPV) for the two reporting periods, each diagnosis was
high grade lesions which have similar management pro- categorized into positive results (high-grade lesions or
tocols, a biopsy of CIN2 with a subsequent cone excision higher, including CIN2, 3, CGIN and invasive cancer) or
showing CIN3, or vice versa, was classified as consistent negative results (low-grade or benign lesions, including
diagnosis. This is in line with the Bethesda classification CIN1, HPV, atypia or inflammation). This classification
was based on the management protocols for the diag-
nosis, with high-grade lesions being an indication for a
Tab. I. criteria for overdiagnosis and underdiagnosis.
cone excision. Biopsy samples which were CIN (diffi-
cult to grade) or inadequate were classified as consistent
cin2 or 3 cin1/hpv/benign conditions with the cone diagnosis (as described above).
cin1 hpv/benign conditions
cin (difficult to grade) hpv/benign conditions
cervical punch biopsy cone biopsy Cervical biopsy and cone results
cin1 cin2 or 3
From April 2004 to March 2005, a total of 744 cervi-
hpv cin 1, 2 or 3
cal punch biopsies were reported. Of these, 150 cervical
cin (any grade) invasive carcinoma biopsies had subsequent cone biopsies done in the same
benign conditions/atypia hpv/cin/invasive carcinoma 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
of patients having subsequent cone biopsies. The mean 2: the cervical punch biopsy showed no definite features of dys-
age of the patients for this period was 31 years (range plasia (c, X100) and the subsequent cone showed cin2 (D, X100).
In 2004-2005, the histological diagnoses of cervical bi-
opsies 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 in-
vasive 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.
Sensitivity and specificity of re-
For the reporting period 2004-5,
the sensitivity of the cervical bi-
opsy 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
Consistency of reporting
The results were categorized
into cervical biopsies that were
consistent with cone diagnosis,
overdiagnoses or underdiag-
noses. The results are shown in
Tables II, III and IV respective-
ly. There was an increase in the
percentage of consistent diagno-
ses in 2008 (75.8%) compared
with 2004 (68.7%), with de-
crease in both the incidences of
over- (14.8% vs 16.7%) and un-
derdiagnoses (9.4% vs 14.7%).
The results are presented in
Considering cases of overdiag-
nosis in the original cervical bi-
opsy, 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 J. wang, m. el-bahrawy
excision. For this subset, it was also found that there was sies reported by general pathologists in 2004-2005, the
a decrease from 15.3% in 2005 to 13.4% in 2008 (high- incidences of consistent diagnosis, overdiagnosis and
lighted in bold in Table III). underdiagnosis were 68.1%, 17.0% and 14.8%, respec-
In 2004-5, only 15 of 150 (10%) cases were reported by tively. In contrast, for biopsies undergoing specialist re-
specialist gynaecological pathologists. In contrast, 123 porting in 2008, the incidences of consistent diagnosis,
of 149 (83%) cases were reported by specialist patholo- overdiagnosis and underdiagnosis were 76.4%, 14.6%
gists in 2008. The results show that for the cervical biop- and 8.9%, respectively.
Tab. II. number of consistent diagnoses between cervical biopsies and cones.
Punch Biopsy Diagnosis Cone Diagnosis 2004 % of total 2008 % of total
cin1 cin1 5 3.3 4 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 others 7 4.7 3 2.0
cin 2/3 cgin (1) (2)
cgin cin2/3 (1)
cin(difficult to grade) cin2/3 (1) (1)
inadequate cin/inv (4)
total 103 68.7 113 75.8
naD: no abnormality detected; infl: inflammation; meta: metaplasia; inv: invasive carcinoma
Tab. III. number of overdiagnoses in cervical biopsies compared with cones.
Punch Biopsy Diagnosis Cone Diagnosis 2004 % of total 2008 % of total
cin2/3 cin1 17 11.3 16 10.7
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 0 0.0 1 0.7
total 25 16.7 22 14.8
naD: no abnormality detected; infl: inflammation; meta: metaplasia; inv: invasive carcinoma
Tab. IV. number of underdiagnoses in cervical biopsies compared with cones.
Punch Biopsy Diagnosis Cone Diagnosis 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 6 4.0 2 1.3
(cin1) (2) (1)
(cin2/3) (4) (1)
cin inv 4 2.7 0 0.0
naD/infl/meta cin/inv 5 3.3 4 2.7
(cin2/3) (2) (4)
naD/infl/meta hpv 1 0.7 1 0.7
total 22 14.7 14 9.4
naD: no abnormality detected; infl: inflammation; meta: metaplasia; inv: invasive carcinoma
DiagnoStic accuracy of cervical biopSieS 335
Statistical analysis the basis of smear results of high grade dyskaryosis, per-
To determine if there was a difference in the incidence sistent low grade dyskaryosis or a colposcopic impres-
of over- and underdiagnosis between the two periods sion of high grade lesion. This highlights the importance
of reporting, Pearson’s chi-square test was applied. A in which biopsy diagnoses are considered in context of
statistically significant improvement in the rate of over- the cervical smear and colposcopy results, thus leading
diagnosis was found cChi-square = 346, p = 0.03) and to a cone excision despite a negative or low grade bi-
underdiagnosis (chi-square = 375, p < 0.01). opsy, if indicated.
The overdiagnosis rate is considered more critical, as it
leads to cone excisions even if smear results and col-
Discussion poscopic impression are not consistent. In our study,
the rate of overdiagnoses of high grade lesions was de-
Cervical punch biopsy is an essential component in cervi- creased from 15% to 13% from the first to the second
cal screening, yet it has limitations despite targeted sam- period of study. This is significant, as cone excisions can
pling at colposcopy and care in specimen processing and be associated with complications (although rare), and
reporting. A previous study showed that 33% of directed hence should be avoided if not indicated.
biopsies did not detect the high-grade lesion found in the It must be stated that the discrepancy between punch
cone 6, while 40% of random biopsies were able to detect biopsy diagnosis and cone biopsy does not necessarily
high grade dysplasia. Assessment of cervical cone biop- imply an incorrect interpretation by the pathologist in all
sies also has its challenges. In one study, 99 negative cones cases. In some instances, the lesions are small and may
were reviewed and 21 cases were subsequently found to be totally removed by the biopsy, and hence may not be
be positive for dysplasia or malignancy 7. In another study, represented in the subsequent cone. Also, although very
of 95 negative cone biopsies 25 on subsequent review or informative and accurate in the majority of cases, cervi-
resectioning were found to have significant lesions 5. cal punch biopsies have their inherent limitations. It is
In this study, we investigated the accuracy of cervical possible that the biopsied part of the cervix at colposcopy
punch biopsy reporting, as compared with subsequent does not target the area of actual abnormality, and hence
diagnosis of cone excision specimens. We show that the dysplasia is not detected due to an erroneous site of
the rate of consistent diagnoses has increased from sampling. Improvements which may increase the accu-
2004 to 2008, from 68.7% to 75.8%. This was due to racy of the biopsy include four quadrant biopsies 9 and
a statistically significant decrease in both the rates of studying histological sections taken at multiple levels for
over- and underdiagnoses. The reason for this improve- thorough histological assessment 10. A fact that must also
ment is most likely due to a change in the practice of be acknowledged is that in some cases there is justifiable
reporting cervical biopsies, from that by general his- interobserver variability. Some biopsies are difficult to
topathologists in the general pool of specimens, to interpret due to being small, partially traumatised, poor-
specialist reporting by gynaecological histopatholo- ly orientated or even showing very subtle changes that
gists, which was the only change in laboratory practice require much experience and may well initiate interob-
between both periods. In a previous study examining server variability. Recent developments to improve the
positive cones to determine the accuracy of biopsies 8, diagnosis of cervical biopsies, as well as cervical smears,
of 355 biopsy-proven cases of dysplasia, 323 had a include HPV genotyping for high risk HPV subtypes
subsequent positive cone. With 22 negative cones, the and immunohistochemistry for p16INK4a 11 12. These
PPV was 91%. However, when only high grade lesions additional tests have been shown to aid in the diagno-
on pre-cone histology or cytology were analysed, 277 sis of CIN in equivocal and difficult cases. For example,
of 371 cases had a positive cone diagnosis, giving a p16INK4a has been shown to significantly improve the
sensitivity of 74.7%. Our current study therefore was interobserver agreement between pathologists for punch
comparable with a sensitivity of 89.7% and a PPV of biopsies 12.
83.9% with specialist reporting.
Two other previous studies compared the consistency be-
tween the pre-cone diagnosis and the cone excision. The Conclusion
consistency rate between cervical biopsy and cone exci-
sion pathological diagnoses was 66.2% in one study 3 In conclusion, the role of cervical biopsy is essential but
and 63% in another 4. Our study showed a comparable still has its limitations. As recommended by the National
consistency rate in the first period, but in the second Health Service (NHS) cervical screening programme, it
period where specialist reporting was implemented, the is essential that patient management is based on co-ordi-
rate was increased to over 75%. nated information of smear results, history, colposcopy
It is important to note that in our cohort cases with under- findings and cervical biopsy results. It is recommended
diagnosis still underwent cone biopsies, although these that these specimens are reported by specialist gynaeco-
diagnoses will not lead to a cone excision if considered logical pathologists, which have been shown to be ad-
in isolation. In these cases, the cone was performed on vantageous in increasing the diagnostic accuracy.
336 J. wang, m. el-bahrawy
Wentzensen N, Zuna RE, Sherman ME, et al. Accuracy of cervical
specimens obtained for biomarker studies in women with CIN3.
Coste J, Cochand-Priollet B, de Cremoux P, et al. Cross sectional Gynecol Oncol 2009;115:493-6.
study of conventional cervical smear, monolayer cytology, and hu- 7
Golbang P, Scurry J, de Jong S, et al. Investigation of 100 consecutive
man papillomavirus DNA testing for cervical cancer screening. negative cone biopsies. Br J Obstet Gynaecol 1997;104:100-4.
Spitzer M, Chernys AE, Shifrin A, et al. Indications for cone biopsy:
Kulasingam SL, Hughes JP, Kiviat NB, et al. Evaluation of human pathologic correlation. Am J Obstet Gynecol 1998;178(1 Pt 1):74-9.
papillomavirus testing in primary screening for cervical abnor-
malities: comparison of sensitivity, specificity, and frequency of
Cagle AJ, Hu SY, Sellors JW, et al. Use of an expanded gold stan-
referral. JAMA 2002;288:1749-57. dard to estimate the accuracy of colposcopy and visual inspection
with acetic acid. Int J Cancer 2010;126:156-61.
Boonlikit S, Asavapiriyanont S, Junghuttakarnsatit P, et al. Cor-
relation between colposcopically directed biopsy and large loop
Fadare O, Rodriguez R. Squamous dysplasia of the uterine cervix:
excision of the transformation zone and influence of age on the tissue sampling-related diagnostic considerations in 600 consecu-
outcome. J Med Assoc Thai 2006;89:299-305. tive biopsies. Int J Gynecol Pathol 2007;26:469-74.
Heatley MK, Bury JP. The correlation between the grade of dys- 11
Sigurdsson K, Taddeo FJ, Benediktsdottir KR, et al. HPV geno-
karyosis on cervical smear, grade of cervical intraepithelial neo- types in CIN 2-3 lesions and cervical cancer: a population-based
plasia (CIN) on punch biopsy and the final histological diagnosis study. Int J Cancer 2007;121: 2682-7.
on cone biopsies of the cervix. Cytopathology 1998;9:93-9. 12
Horn LC, Reichert A, Oster A, et al. Immunostaining for p16INK4a
Thompson AD, Duggan MA, Nation J, et al. Investigation of laser used as a conjunctive tool improves interobserver agreement of
cervical cone biopsies negative for premalignancy or malignancy. the histologic diagnosis of cervical intraepithelial neoplasia. Am J
J Low Genit Tract Dis 2002;6:84-91. Surg Pathol 2008;32:502-12.
“Combined” desmoplastic melanoma of the vulva
with poor clinical outcome
Unit of Anatomic Pathology, Department of Oncology, Maggiore Hospital, Bologna, Italy
Desmoplastic melanoma • “Combined” • Vulva • Immunohistochemistry • Protein S100
Desmoplastic melanomas in an unusual variant of melanoma superficial spitzoid component and a deeper spindle desmoplas-
that usually occurs in sun-damaged skin of elderly people. Des- tic component. Protein S-100 expression was ubiquitous, while
moplasia may be the prominent features of the lesion or rep- MART-1 and HMB-45 were limited to the superficial spitzoid
resent a portion of an otherwise non-desmoplastic melanoma; component and were negative in desmoplastic areas. Notably,
these latter are called “combined” desmoplastic melanoma. Des- the nodal metastasis retained the same biphasic pattern seen in
moplastic melanomas of the vulva are rare. Herein, we report the primary tumour. The patient died of widespread metastatic
a case of “combined” DM of the labia minor consisting of a disease 3 years after diagnosis.
Introduction Materials and methods
Melanoma represents the second most frequent malig- The excised material was fixed in 10% formalin and em-
nancy of the vulva. These neoplasms occur mostly in bedded in paraffin. Deparaffinized 5-µm-thick sections
post-menopausal women and are generally diagnosed were stained with haematoxylin and eosin. Immunohis-
when they ulcerate and discharge blood 1. Vulvar des- tochemistry was performed using the Ventana System
moplastic melanomas are uncommon, and only a few employing the following antibodies: protein S100 (Ven-
cases have been documented 1-4. Herein, we report a tana ready to use), MART-1 [Melan-A (A-103), Ventana
case of “combined” desmoplastic and spitzoid mela- ready to use], HMB-45 (Cell Marque ready to use), actin
noma. [muscle-specific (HHF35) Cell Marque ready to use].
Clinical history Results
A 73-year-old female sought medical attention for an A 0.3 cm punch biopsy showed a hyperplastic epider-
ulcerated nodule of the right labia major. A biopsy was mis with atypical melanocytes localized at the dermal-
performed and a diagnosis of melanoma was rendered. epidermal junction (Fig. 1). The upper dermis was in-
Two weeks later she underwent surgical excision. The filtrated by epithelioid and pleomorphic melanocytes.
skin ellipse measured 2.5 × 2 cm and was centred by Dilated capillaries reminiscent of Spitz lesion were also
a grey ulcerated nodule measuring 2 cm in diameter. present (Fig. 2). The skin ellipse showed a polypoid, ul-
Sentinel lymph node procedure was performed and a cerated and hypopigmented tumour (Fig. 3). The lesion
right inguinal lymph node was removed. The sentinel was composed of single or grouped melanocytes, which
lymph was metastatic. Complete inguinal lymphoad- reached the upper layer of the epidermis.
enectomy failed to show other metastases. The patient In the deeper part of the dermis, the epithelioid compo-
died of widespread metastatic disease 3 years after di- nent merged with spindle neoplastic cells interspersed
agnosis. among dense collagen bundles (Fig. 4) which represent-
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:
338 g. collina
Fig. 1. punch biopsy shows ulcerated and hyperplastic epidermis Fig. 4. in the deep part of the lesion, neoplastic melanocytes
and neoplastic cells expanding the superficial dermis, revealing oe- are spindled and immersed in a desmoplastic stroma, which
dema and dilated vessels. shows increased mucin.
Fig. 2. neoplastic melanocytes are either epithelioid either spin- Fig. 5. S100 protein diffusely stained neoplastic melanocytes in
dled. lymphocytes in groups and dilated vessels are also present both the epithelioid and spindle component in the desmoplastic
(left side). area.
Fig. 3. melanoma has polypoid conformation with dumbbell Fig. 6. Strong mart 1 immunostaining in the epithelioid superfi-
features and reaches the deep dermis almost approaching the cial melanocytes, while spindled melanocytes, including those of
sub-cutaneous fat. the desmoplastic area, were negative.
ed 40% of the entire lesion. Features of neurotropism spindle cells (Fig. 6), which were nonetheless faintly
and angiotropism were present. positive; HMB-45 stained only a few epithelioid mel-
Protein S100 was ubiquitous (Fig. 5), while MART-1 anocytes. Smooth muscle actin was negative.
strongly stained the epithelioid melanocytes of the spit- The micro-staging of this lesion showed it to fall into
zoid component of the upper part of the lesion that were the poor prognosis category (i.e. 5.7 mm in Breslow’s
almost negative in the desmoplastic areas except for rare thickness, ulceration and the number of mitosis was at
“combineD” DeSmoplaStic melanoma of the vulva with poor clinical outcome 339
Fig. 7. metastatic-inguinal-sentinel-lymph node: the biphasic or replacement nerve bundles typical of this melanoma
patter of primary lesion is also preserved in the metastasis, epi- subtype 6.
thelioid melanocytes are localized on the left, while the desmo- DM/neurotropic melanomas of the vulva are uncom-
plastic area is evident on the right.
mon, and similar to mucosal melanomas, have a dismal
We report a case of “combined” DM of the labia mi-
nor consisting of a superficial spitzoid component and a
deeper spindle desmoplastic component. S-100 expres-
sion was ubiquitous, while MART-1 and HMB-45 were
limited to the superficial spitzoid component and were
negative in desmoplastic areas. Notably, the nodal me-
tastasis 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 metasta-
ses 7. Complete lymphoadenectomy failed to show other
metastatic lymph nodes. The patient died 3 years later
due to widespread metastases.
least 6 per mm2). The lymph node showed metastatic There is still controversy on the prognosis of DM. Early
deposits composed of either spitzoid or desmoplastic ar- studies suggested an aggressive behaviour than conven-
eas (Fig 7). tional melanomas, while others documented DM with a
more favourable clinical course 5
Busam et al. 8 suggested that pure desmoplastic mela-
Discussion nomas thicker than 4 mm have a better prognosis when
compared with combined DM and conventional mela-
Desmoplastic melanoma (DM) is a rare variant of nomas of the same thickness. In their study, only 3 of
spindle cell melanoma that usually occurs in the sun- 26 patients with pure DM died of disease compared to
damaged skin of elderly patients. Conley et al. first de- the experience of their institution, where 25% of patients
scribed DM in 1971 as “a variant of spindle cell mela- died for thick conventional melanomas in 3 years. Our
noma which elicits the production of abundant colla- patient seems to confirm that thickness and the presence
gen” 5. Reed and Leonard further expanded the original of “combined” histological components represent valu-
description and documented the extensive infiltration able prognostic indicators of poor outcome.
Conley J, Lattes R, Orr W. Desmoplastic malignant melanoma (a
rare variant of spindle cell melanoma). Cancer 1971;28:914-36.
Byrne PR, Maiman M, Mikhail A, et al. Neurotropic desmoplastic mel- 6
Reed JG, Leonard DD. Neurotropic melanoma: a variant of des-
anoma: a rare vulvar malignancy. Gynecol Oncol 1995;56:289-93. moplastic melanoma. Am J Surg. Pathol 1979;3:301-11.
Warner TF, Hafez GR, Buchler DA. Neurotropic melanoma of the 7
de Almeida LS, Requena L, Rutten A, et al. Desmoplastic malig-
vulva. Cancer 1982;49:999-1004. nant melanoma : a clinicopathologic analysis of 113 cases. Am J
Mulvany NJ, Sykes P. Desmoplastic melanoma of the vulva. Pa- Dermatopathol 2008;30:207-15.
thology 1997;29:241-5. 8
Busam KJ, Mujumdar U, Hummer AJ, et al. Cutaneous desmo-
Rogers RS 3 , Gibson LE. Mucosal, genital, and unusual clinical
rd plastic melanoma: reappraisal of morphologic heterogeneity and
variants of melanoma. Mayo Clin Proc 1997;72:362-6. prognostic factors. Am J Surg Pathol 2004;28:1518-25.
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;
University “Magna Graecia” of Catanzaro, Italy; 4 Microbiology Section, University “Federico II”, Napoli, Italy
Tuberculosis • Mycobacterium • PCR
Tuberculosis (TB) is still one of the most frequent infectious dis- aetiology is often not taken into consideration in the differential
eases worldwide. Until the 1990s, Western European countries diagnosis of lymphadenopathy, resulting in significant delay of
showed a low frequency of TB infection, but the rise of immigra- appropriate treatment.
tion has led to a rapid increase in its occurrence. In the elderly, TB Herein, we describe the case of a 78-year-old male with nocturnal
is emerging as a significant health problem (age-related decline of fever, weakness, night sweats, loss of weight and decay in gen-
the cell-mediated immunity, associated illnesses, use of immuno- eral condition. The patient had a past medical history of prostate
suppressive drugs, malnutrition, poor life conditions), although its adenocarcinoma treated with hormone therapy. The past medical
detection and diagnosis is not easy also considering its subclinical history in association with clinical findings and laboratory data
presentation. Almost 70% of all TB infections in Italy are found (anaemia, high titers of fibrinogen and reactive C-protein) led to
in the lungs; 50% of the extrapulmonary infections affect lymph the suspect of metastatic adenocarcinoma. Only histological and
nodes. Due to the low incidence of superficial tuberculous lymph- molecular biology findings allowed us to make a correct diagnosis
adenitis without pulmonary manifestations, the possibility of a TB of TB.
Introduction numerous. It is well known that the age-related decline
of the cell-mediated immunity (thymus, lymph node
Tuberculosis (TB) is still one of the most frequently- and spleen involution) may cause reactivation of latent
occurring infectious diseases worldwide. According infections. Moreover, the presence of associated ill-
to the World Health Organization (WHO) 1, approxi- nesses such as diabetes mellitus, chronic renal failure,
mately one-third of the world’s population is current- diffuse parenchymal lung diseases, certain malignan-
ly infected with tubercle bacilli, while 8 million new cies, as well as the use of immunosuppressive drugs
cases of active disease develop each year and 3 million (e.g. corticosteroids), may further impair cell-mediated
patients die 2. Until the 1990s, Western European coun- immunity, increasing the risk of reactivation. Adverse
tries showed a rather low frequency of TB infection, social factors, such as malnutrition, poor living condi-
but the rise of immigration has led to a rapid increase tions as well as staying in nursing homes also affect the
in its occurrence 3. Furthermore, it is well known that elderly much more frequently than younger individu-
TB can be associated with diseases that depress the als 4 5. In the former, TB is not easy to detect and di-
immune system, such as leukaemia or HIV, affecting agnose because it does not manifest so clearly in these
specific age groups (infants, elderly). In the elderly, TB individuals. In fact, symptoms (loss of weight, night
is emerging as a significant health problem. It may be sweats, weakness, anorexia, mild fever) are often non-
either exogenous or endogenous in origin, with the lat- specific and may be attributed to age-related changes 6.
ter representing over 90% of cases and consisting of re- The presence of other chronic diseases may confuse the
activation of dormant disease in the lungs or elsewhere clinical picture, and often the patient is unable to give
in the body 4. Predisposing factors in the elderly are an accurate account of symptoms.
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@example.com
tuberculoSiS of Superficial lymph noDeS, a not So rare event to conSiDer in DiagnoSiS 341
Apart from general diagnostic problems, there are diffi- cay of general conditions, for a few weeks. The patient
culties regarding the recognition of TB affecting various suffered from chronic obstructive airway disease and
sites. In fact, almost 70% of all TB infections in Italy 7 cerebral vasculopathy. Moreover, he had a history of
are found in the lungs; of the remaining extrapulmonary prostatic adenocarcinoma treated with hormone thera-
infections, approximately 50% affect lymph nodes. Due py as well as a pacemaker. On physical examination,
to the low incidence of tuberculous lymphadenitis with- a swelling of a right laterocervical lymph node was
out pulmonary manifestations, the possibility of TB is observed. In particular, the node was tender, mobile
often not taken into consideration in the differential di- and painful with irregular borders. Blood pressure
agnosis of lymphadenopathy, resulting in a significant was 110/60 mmHg, heart rate 94 beats per min (bpm)
delay of appropriate treatment. and body temperature was 38.1°C. Laboratory data
Unfortunately, very little clinical data is available on revealed hyperleucocytosis (5.9 × 103/mm3) with ab-
the diagnosis and therapy of lymph node TB in Western solute neutrophilia (neutrophils 78.3%, lymphocytes
countries 8. However, owing to the immigration that has 13.3%), normochromic normocytic anaemia (haemo-
taken place over the last decades, there is a renewed in- globin 10.5 g/dl, mean corpuscular volume 88 μm3)
terest in the disease. with an increase of acute phase proteins (C-reactive
protein-PCR, procalcitonin, fibrinogen). To rule out
a metastatic adenocarcinoma of the prostate or lym-
Case report phoproliferative disorder, a lymph node ultrasound
imaging (US) of the neck and a whole body CT-scan
A 78-year-old male was admitted to the Geriatrics were performed. The US revealed an enlarged (7 cm
Unit of Catanzaro Hospital for the onset of nocturnal in maximum diameter), inhomogeneous lymph node
fever, weakness, night sweats, loss of weight and de- 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 pali-
saded 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 a. merante et al.
lous lymphadenopathy was suspected. Shortly after, a not decreased and accounts for almost 7.5% of all patients
Mendel-Mantoux test as well as sputum and urinalysis infected by mycobacterium tuberculosis. Nevertheless, it
were carried out with negative results. seems that tuberculous lymphadenopathy is not taken into
Histological and microbiological analyses of the lymph consideration in Western countries and diagnosis is per-
node were also conducted by US-guided fine-needle as- formed only by histological examination 12.
piration (FNA). One aliquot of FNA sample was fixed In the present case, the past medical history (prostatic
in 95% ethyl alcohol and stained by Giemsa for cyto- adenocarcinoma), in association with clinical findings
logic analysis. Immunohistochemistry for CKAE1/AE3 (fever associated with vague and non-specific symp-
and PSA was made. Another aliquot was used for mi- toms) and laboratory data (anaemia, high titres of fi-
croscopic detection of the microorganism using Ziehl- brinogen and PCR) led to the suspect of metastatic ad-
Neelsen (ZN) stain as well as agar and radioactive cul- enocarcinoma. Only histological and molecular biology
ture (BACTEC). To assess the genotype of the mycobac- findings allowed us to make a correct diagnosis. Dif-
terium, polymerase chain reaction (PCR) and the IS6110 ferential diagnosis of granulomatous lymphadenopathy
restriction-fragment-length-polymorphism (RFPL) were includes sarcoidosis (well-defined, non-caseating granu-
performed using standard methods 9. lomas with a ring of collagen), atypical mycobacterial
Lymph node architecture was effaced by the presence of infections (less granulomatous changes with more acute
large granulomas, sometimes confluent, with central necro- inflammation, sometimes with abscess formation and a
sis (Fig. 1a). A number of epithelioid cells (arranged in a histiocytic proliferation of spindle cells mimicking an
palisaded architecture), multinucleated giant cells of Lang- inflammatory pseudotumor), lepromatous lymphadenitis
hans type and, occasionally, foreign body type in between, (rare, non-caseating granulomas with numerous foamy
encircling caseosis and bordered by lymphocytes and plas- macrophages replacing the paracortical regions and con-
ma cells, were surrounded by thick fibrous layers (Fig. 1b). taining abundant intracellular organisms) and Hodgkin
CKAE1/AE3 and PSA were negative. ZN and PCR for lymphoma (non caseating granulomas in the paracorti-
mycobacterium tuberculosis were positive (Fig. 1c-d). cal areas, Reed-Stemberg and Hodgkin cells).
On the basis of the morphological and molecular biol-
ogy findings, a diagnosis of tuberculous lymphadenopa-
thy was made. Conclusion
Treatment with isoniazid, rifampicin and pyrazinamide
was established, according to the recommendations of It is important to bear in mind that TB infection, although
the American Thoracic Society 10, with immediate im- infrequent, may be the cause of a lymphadenopathy. In
provement of clinical conditions. One month later, the elderly patients, a delay in diagnosis represents a seri-
patient developed hepatotoxicity, and isoniazid and ri- ous problem since TB is curable only when treatment is
fampicin was replaced with rifabutin. established at an early stage 4.
The pathological examination of lymph nodes plays a criti-
cal role in diagnosis. In fact, although from a clinical view-
Discussion point there may be some confusion as to whether an enlarged
lymph node is due to TB or to other benign or malignant
TB remains one of the leading infectious diseases, caus- lymphadenopathies, the histological picture is characteristic
ing significant morbidity and mortality worldwide 11. Al- and diagnosis is readily established by biopsy examination
though the reporting of new TB infections has declined of the lymph node. Moreover, the demonstration of Koch’s
steadily over time, the frequency of lymph node TB has bacillus using Ziehl-Neelsen stain and PRC is definitive.
Ministero della Salute - DG della Prevenzione Sanitaria. Ufficio
V - Malattie Infettive e Profilassi Internazionale.
Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph 8
Cailhol J, Decludt B, Che D. Sociodemographic factors that con-
node tuberculosis in Northern Germany: a clinical review. Chest tribute to the development of extrapulmonary tuberculosis were
2002;121:1177-82. identified. J Clin Epidemiol 2005;58:1066-71.
Baussano I, Cazzadori A, Scardigli A, et al. Clinical and demo- 9
van Embden JD, Cave MD, Crawford JT, et al. Strain identifica-
graphic aspects of extrathoracic tuberculosis: experience of an tion of Mycobacterium tuberculosis by DNA fingerprinting: rec-
Italian university hospital. Int J Tuberc Lung Dis 2004;8:486-92. ommendations for a standardized methodology. J Clin Microbiol
Brudey K, Driscoll JR, Rigouts L, et al. Mycobacterium tubercu- 1993,31:406-9.
losis complex genetic diversity: mining the fourth international 10
Ramón-García S, Ng C, Anderson H, et al. Synergistic drug combi-
spoligotyping database (SpolDB4) for classification, population nations for tuberculosis therapy identified by a novel high through-
genetics and epidemiology. BMC Microbiol 2006,6:23. put screen. Antimicrob Agents Chemother 2011;55:3861-9.
Sood R. The problem of geriatric tuberculosis. Journal of Indian 11
World Health Organization. Global tuberculosis control: Surveil-
Academy of Clinical Medicine 2004;5:156-62. lance, Planning, Financing. Geneva, WHO Report; 2008.
Salvado M, Garcia-Vidal C, Pilar Vazquez P, et al. Mortality of 12
Montoro E, Rodriguez R. Global burden of tuberculosis. In:
Tubercolosis in very old people. J Am Geriatr Soc 2010;58:18-22. Palomino JC, Leão SC, Ritacco V, eds. Tuberculosis 2007,
Zevallos M, Justman JE. Tubercolosis in the elderly. Clin Geriatr from basic science to patient care. Kamps and Bourcillier 2007,
Med 2003;19:121-38. pp. 263-81.
Adenolipoma of the skin
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
Adenolipoma • Perisudoral lipoma • Eccrine glands • Lipoma • Skin
Adenolipoma of the skin (ALS) is an uncommon histological var- of this tumour are thighs (as in our patient), shoulders, chest and
iant of lipoma, characterized by the presence of normal eccrine arms. Histologically, the tumour is composed of lobulated adipose
sweat glands inside the fat proliferation. A 32-year-old woman tissue with larger and more prominent lobules than those in nor-
presented to our department with a slow-growing, painless sub- mal subcutaneous adipose tissue. A well-developed capsule may
cutaneous soft tumour located on the upper part of the right thigh. also be identified. Eccrine glands and ducts, without proliferative
Microscopically, there was lobulated adipose tissue proliferation changes, are well-differentiated within the adipose tissue.
with well-differentiated eccrine glands and ducts in the periphery Differential diagnosis of adenolipoma includes the common
and centre of the nodule. These features were suggestive of ALS. lipoma and its variants, skin tag and other hamartomatous lesions,
ALS is a rare microscopic variant of cutaneous lipoma having such as nevus lipomatosus superficialis, and the lipomatous vari-
similar clinical features to lipoma. The most frequent locations ant of eccrine angiomatous hamartoma.
Introduction Fig. 1. painless nodule on the right upper thigh.
Adenolipoma of the skin (ALS) is an uncommon histo-
logical 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.
A 32-year-old woman presented to our department with
a slow-growing, painless nodule on her thigh. Cutane-
ous 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 Discussion
nodule was composed of adipose tissue proliferation with
distinct lobulation within the tumour. Well-differentiated Several variants of lipoma were described according to
eccrine glands and ducts were seen in the periphery and their location and morphology. In a lipoma, the adipose
centre of the nodule. No capsule was seen and no architec- tissue may be associated with other proliferative or non-
tural or cytological alteration was noticed in these glands proliferative tissues, such as in angiolipoma and fibrol-
(Fig 2). These features were suggestive of ALS. ipoma 1.
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: firstname.lastname@example.org
344 S. Karoui et al.
Figs. 2A, B. well-differentiated eccrine glands and ducts, with-
thigh (especially its upper part) and buttock (n = 16). The
out proliferative changes, within the adipose tissue (haematoxy- other reported locations are: the shoulder region (n = 3),
lin and eosin, X40). abdomen (n = 2), periungual region (n = 2), female ex-
ternal genitalia (n = 2), axillary region (n = 1), lower lip
A (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 adi-
pose 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 precise-
ly locate eccrine glands within fragmented specimens.
B 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 ne-
vus 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 be-
cause of its superficial location that can lead to earlier
symptoms. A subcutaneous lipoma may have a hernia-
tion within the dermis. In this latter case, the eccrine
glands are compressed and displaced rather than incor-
In 1993, Hitchcock et al. described an entity of lipoma porated into the lesion as in ALS 2.
in a series of 9 patients that had never been reported pre- Skin tag with a fatty stroma is also a differential diagno-
viously. It was a rare microscopic variant of cutaneous sis. In this tumour, the eccrine glands are rather located
lipoma composed of large lobules of mature adipocytic on both sides of the pedicle rather than within the fatty
tissue admixed with eccrine ducts and glands. This tu- component 3.
mour was called “adenolipoma of the skin” 2. Nevus lipomatosus superficialis has a different clini-
Ait-Ourhrouil and Grosshans reported, in 1997, a sec- cal feature. It presents as congenital multiple papules or
ond series of 11 cases 3. They postulated that this lesion nodules. Microscopically, it shows ectopic adipose tis-
develops from the peripheral adipose tissue of eccrine sue with fibrous tissue in the papillary and reticular der-
glands and suggested the name perisudoral lipoma. In- mis. The density of the collagen bundles, the abundance
cluding our patient, the total number of ALS reported of fibroblasts and its vascularity are more prominent
cases, in the English and French literature is 31 (Tab. than in normal skin 2 11.
I) 2-10. The tumour often has the appearance of a usual Eccrine angiomatous hamartoma is usually an isolated
lipoma. Occasionally, the clinical presentation is sug- congenital lesion showing a preponderance of eccrine
gestive of skin tag, neurofibroma or a hamartomatous and vascular proliferation, which are absent in ALS 2 12.
lesion. The delay between tumour occurrence and the ALS is a fatty-tissue proliferation that includes and
first medical evaluation ranges from 6 months (in our moves the normal eccrine glands to the centre of the tu-
case) to more than 10 years 3 5. The average size calcu- mour. This glandular component does not show any pro-
lated from our literature review is 2.7 cm 2-10. There is liferative changes. Its location on the upper thigh, as in
a female preponderance (22:9), and the average age at our patient, may allow clinical suspicion of ALS which
diagnosis is 47.8 years 2-10. ALS is mainly located on the should be confirmed by histological findings.
aDenolipoma of the SKin 345
Tab. I. Summary of the reported cases of alS.
Reference Age (years) Sex Location Size Duration
hitchcock 1993 2 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
ait-ourhrouil 1997 3 63 f thigh 1 to 3 cm > 10 years
(average: 2.5 cm)
55 m Shoulder 5 years
71 m abdomen > 10 years
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 n/a
rongioletti 1997 4 41 f thigh 2.7 cm many years
25 f thigh 2 cm 5 years
chadli-Debbiche 2001 5 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
48 m periungual (great toe) 0.8 cm n/a
Del agua 2004 8
45 f thigh 2.5 cm n/a
antunez 2005 9 40 f axillary region 3.7 cm n/a
pantanowitz 2008 10
41 f left groin 1.5 cm many years
44 f right vulva 2 cm 4 years
present case 32 f upper thigh 3 cm 6 months
Richert B, André J, Choffray A, et al. Periungual lipoma: about
three cases. J Am Acad Dermatol 2004;51(Suppl 2):S91-3.
Abensour M, Jeandel C, Heid E. Lipomes et lipomatoses cutanés. 8
Atunez P, Santos-Briz A, Munoz E, et al. Cutaneous apocrine cys-
Ann Dermatol Venereol 1987;114:873-82. tic adenolipoma. Am J Dermatopathol 2005;27:240-2.
Hitchcock M, Hurt M, Santa Cruz D. Adenolipoma of the skin: a 9
Pantanowitz L, Henneberry J, Otis C, et al. Adenolipoma of the
report of nine cases. J Am Acad Dermatol 1993;29:82-5. external female genitalia. Int J Gynecol Pathol 2008;27:297-
Ait-Ourhrouil M, Grosshans E. Le lipome périsudoral. Ann Der- 300.
matol Venereol 1997:124;845-8. 10
Del Agua C, Felipo F. Adenolipoma of the skin. Dermatol Online J
Rongioletti F, Santa Cruz D. L’adénolipome cutané. Ann Derma- 2004;10:9.
tol Venereol 1997;124:855-6. 11
Dotz W, Prioleau PG. Nevus lipomatous cutaneus superficia-
Chadli-Debbiche A, Ben Brahim E, Mzabi-Regaya S. Le lipome lis: a light and electron microscopic study. Arch Dermatol
périsudoral: une observation confirmant cette nouvelle entité. Ann 1984;120:376.
Pathol 2001;21:289-90. 12
Donati P, Amantea A, Balus L. Eccrine angiomatous hamartoma:
Ide F, Mishima K, Saito I. Adenolipoma of the lip. Br J Derma- a lipomatous variant. J Cutan Pathol 1989;16:227-9.
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
Department of Pathology Mongi Slim Hospital, Sidi Daoued La Marsa (2046), Tunisia
Peutz-Jeghers-type polyp • Hamartoma • Adenomatous transformation • Rectum
Solitary Peutz-Jeghers-type polyp is a rare hamartomatous polyp lesion in the lower rectum. The polyp was sessile and measured
without associated mucocutaneous pigmentation or a family his- 15 cm in diameter. As histological examination of the biopsy
tory of Peutz-Jeghers Syndrome. It is usually encountered in the specimen was suggestive of adenoma, endoscopic polypectomy
small intestine, but rarely involves the rectum. A 27-year-old pre- was performed. Histologically, this polyp had an arborizing mus-
viously healthy female patient presented with a two-month his- cular network originating from the muscularis mucosa, and was
tory of rectal bleeding. The patient had neither mucocutaneous covered by well organized mucosa with several foci of dysplastic
pigmentation nor a family history of gastro-intestinal polyposis. glands. The final pathological diagnosis was solitary Peutz-Jegh-
Endoscopic examination revealed a solitary lobular polypoid ers type hamartomatous polyp with adenomatous transformation.
Introduction nation, the patient’s skin including the perioral area was
unremarkable and oral mucosa appeared normal. En-
Solitary Peutz-Jeghers-type polyps (PJP) are uncommon doscopic examination revealed a lobular and polypoid
hamartomatous lesions without associated mucocutane- lesion in the lower rectum measuring 15 cm in diam-
ous pigmentation or a family history of Peutz-Jeghers eter (Fig. 1). A biopsy of this polyp was performed and
Syndrome (PJS) 1 2. They are most frequently encountered histological examination revealed findings suggestive of
in the small intestine, but rarely involve the rectum. Al- an adenoma with low-grade intra-epithelial neoplasia.
though several cases of solitary PJP have been reported in Endoscopic resection of the entire polyp was performed.
the literature, it is still unclear whether solitary PJP repre- Histopathologically, the excised polyp had an arborizing
sents an incomplete form of PJS or a different entity 3. In muscular network originating from the muscularis mu-
this paper, the authors report a new case of solitary Peutz- cosa (Fig. 2) and was covered by well organized mucosa
Jeghers-type hamartomatous polyp with several foci of with hyperplastic (Fig. 3) and cystically dilated glands
glandular dysplasia revealed by rectal bleeding. To the (Fig. 4). Several foci of dysplastic glands displaying
best of our knowledge, only 31 cases (Tab. I) of color- low-grade intra-epithelial neoplasia were also identified
ectal solitary Peutz-Jeghers-type hamartomatous polyps (Fig. 5). Thorough and careful examination of differ-
have been published in the English language literature to ent sections of the entire polyp did not reveal any addi-
date, and adenomatous transformation has never been de- tional adenocarcinomatous foci. After endoscopic treat-
scribed in solitary rectal PJP before. ment, no concomitant lesions were found elsewhere. At
present, the patient is still on follow-up.
A 27-year-old previously healthy female patient with no
family history of gastro-intestinal polyposis, presented A Peutz-Jeghers polyp (PJP) in a patient without muco-
with a two-month history of rectal bleeding. On exami- cutaneous pigmentation or family history of PJS is called
Faten Limaiem, Department of Pathology, Mongi Slim Hospital-La
Marsa- Tunisia - Tel. +216 96 55 20 57 - E-mail: fatenlimaiem@
aDenomatouS tranSformation in a Solitary peutz-JegherS-type polyp 347
Fig. 1. endoscopic examination revealing a lobular rectal polyp. Fig. 3. cystically dilated glands were identified within the polyp.
(haematoxylin & eosin; original magnification x 25).
Fig. 4. hyperplastic glands composed of tall columnar absorp-
Fig. 2. arborizing network of smooth muscle and connective tive cells and goblet cells. (haematoxylin & eosin; original mag-
tissue surrounding abundant normal glands. (haematoxylin & nification x 25).
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 Fig. 5. foci of dysplastic glands were noticed within the polyp
(haematoxylin & eosin; original magnification x 25).
WHO criteria: (1) three or more histologically confirmed
PJPs; (2) any number of PJPs with a family history of
PJS; (3) characteristic, prominent, mucocutaneus pig-
mentations 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 al-
so 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-
348 f. limaiem et al.
Tab. I. cases of colorectal solitary peutz-Jeghers type polyps reported in the literature.
Author/year Number Age (years) Location Size (cm) Presentation Treatment
of cases sex
Suda 17 (1988) 20 mean age = colorectal na na na
handa 12 (1990) 1 na colon na na na
(1991) 1 na transverse colon na na na
muto 9 (1993) 1 na colon na na na
(1996) 1 64/m lower rectum 2x1.5 x 1.5 bloody stools transanal surgical
oncel 4 5 46/m Sigmoid 1.5 Screening endoscopic polypectomy
68/m Sigmoid 2.5 Screening endoscopic polypectomy
46/m Sigmoid 2 Screening endoscopic polypectomy
33/f Sigmoid 2 rectal bleeding endoscopic polypectomy
56/m cecum 2 Screening endoscopic polypectomy
Jaremko 19 (2005) 1 19/m Descending na colo-colonic Subtotal colectomy
itaba 20 (2009) 1 50/m Sigmoid 1.8 Screening endoscopic polypectomy
garces 21 (2011) 1 na rectum na na na
limaiem (2011) 1 27/f lower rectum 15 rectal bleeding endoscopic polypectomy
na: not available
type hamartomatous polyp of the rectum (Tab. I). The low malignant potential 11. However, some reports have
largest colorectal PJP reported in literature had a size of described areas of neoplastic change, such as adeno-
2.5 cm compared to 15 cm in our patient. Gastrointestinal matous or carcinomatous change in solitary PJP 9 12-14.
hamartomatous polyps in patients with PJS have a dis- Patients with PJS are at increased risk of developing
tinct histological appearance with interdigitating smooth both intestinal and extraintestinal malignancies. Since
muscle fibres forming a characteristic branching tree pat- solitary PJP are rare, it is not known whether there is
tern (arborization) 8. They display a frond-like elongated any increased risk for other malignancies, as observed
epithelial component and cystic gland dilatation extend- in PJS. In 50–94% of patients with PJS, a mutation of
ing into the sub-mucosa or muscularis propria. Peutz- the LKB1/STK11 gene is found. Conversely, no muta-
Jeghers-type polyps are histologically identical to those tion of the LKB1/STK11 gene was found in two cases
in Peutz-Jeghers syndrome, although some authors have of solitary PJP in which genotyping was carried out 15 16.
pointed out that solitary Peutz-Jeghers-type polyps tend Unfortunately, we were not able to carry out genotyping
to exhibit less branching of the muscularis mucosae than in our case.
in the familial form 9 10. In summary, a case of solitary Peutz-Jeghers-type polyp
The main difficulty in defining the true entity of these with adenomatous transformation is reported herein. Our
solitary hamartomatous polyps lies in the small number case is unique in that it is the largest solitary PJP report-
of published cases, some of which provide little clinical ed in literature involving the rectum which is an exceed-
information. Because of the absence of involved family ingly rare location. It is still unclear whether a solitary
members, the lack of mucocutaneous pigmentation char- Peutz-Jeghers polyp (PJP) is an incomplete form of PJS
acteristic of PJS and the presence of a solitary polyp, a or a separate entity. Whether there is an increased risk
solitary PJP might be a disease entity distinct from PJS. of cancer in patients with solitary Peutz-Jeghers-type
There is, however, controversy about the occurrence of polyps is uncertain, but periodic surveillance in young
solitary PJPs 1 5. In most case reports and series, clini- patients would seem appropriate 4. Available data are
cal and histological criteria were not fully documented extremely limited, and it is difficult to draw firm con-
and there was usually no extended follow-up 11. Hamar- clusions regarding management of patients with solitary
tomatous polyps are generally considered to have very polyps 5.
aDenomatouS tranSformation in a Solitary peutz-JegherS-type polyp 349
Burkart AL, Sheridan T, Lewin M, et al. Do sporadic Peutz-Jegh-
ers polyps exist? Experience of a large teaching hospital. Am J
Burkart AL, Sheridan T, Lewin M. Do sporadic Peutz-Jeghers Surg Pathol 2007;31:1209-14.
polyps exist? Experience of a large teaching hospital. Am J Surg 12
Handa Y, Masuda T, Tadokoro M, et al. A case of a solitary Peutz-
Pathol 2007;31:1209-14. Jeghers type polyp of the colon accompanying adenomatous ele-
Acea Nebril B, Taboada Filgueira L, Parajó Calvo A. Solitary ments. Saitama-ken Igakkai Zasshi 1990;24:1476-8.
hamartomatous duodenal polyp; a different entity: report of a case 13
Nakayama H, Fujii M, Kimura A, et al. A solitary Peutz-Jeghers-
and review of the literature. Surg Today 1993;23:1074-77.
type hamartomatous polyp of the rectum: report of a case and re-
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350 pathologica 2011;103:350-356
Index Volume 103, No. 1-6
Issue 1 S. Squillaci, R. Marchione, M. Piccolomini
February 2011 40 An unusual case of signet ring cell adenocarcinoma
of the prostate
ORIGINAL ARTICLE L. Reggiani Bonetti, M. Lupi, E. Stauder,
1 Realistic technician staffing requirements in S. Bergamini, M. Scuri, A. Maiorana
a histopathology laboratory via an innovative 43 Subcutaneous Ewing sarcoma/PNET as a second
workload method cancer in a previously irradiated young patient.
M. Bergamaschi, G. Coccini An uncommon type of post-irradiation soft tissue
ANATOMY FOR HISTOPATHOLOGISTS M. Bruno, G.I. D’Antona, G. Vita, G. Perrone,
4 Muscle spindle and Pacinian corpuscle: conceptions, F. Fiordelisi, M. Bisceglia
misconceptions, and the far-fetched hypothesis of an 46 Nodular extramedullary hematopoiesis involving the
experienced surgical pathologist adrenal gland.
M. Bisceglia, S. Bisceglia, M.L. Bisceglia An uncommon cause of adrenal “incidentaloma”
M. Salemme, R. Rodella, S. Fisogni, F. Facchetti
CASE REPORTS 50 Ductal carcinoma of the prostate metastatic to the
8 Long pedunculated colonic polyp with skin
diverticulosis: case report and review of the literature G. Collina, C. Reggiani, G. Carboni
M.R. Ambrosio, B.J. Rocca, A. Ginori, A. Barone, M.
Onorati, S. Lazzi LETTER TO THE EDITOR-IN-CHIEF
11 Amniotc band syndrome: a case report 52 Needle core biopsy should replace fine needle
A.M. Buccoliero, F. Castiglione, F. Garbini, aspiration cytology in ultrasound-guided sampling of
D. Moncini, E. Lapi, E. Agostini, P. Fiorini, G.L. Taddei breast lesions
14 Partial nodal involvement by marginal zone B. Brancato, M. Scialpi, T. Pusiol, M.G. Zorzi,
lymphoma. Use of IGK gene rearrangement analysis D. Morichetti, F. Piscioli
in diagnostic work-up
A. Gazzola, E. Sabattini, C. Mannu, F. Bacci,
C.A. Sagramoso sacchetti, P. Artioli, L. Chilli, Issue 3
G. Da Pozzo, M. Piccioli, B. Falini, S.A. Pileri, June 2011
19 Morphological analysis of three extrathoracic ORIGINAL ARTICLES
bronchogenic cysts simulating neoplasms 53 Autoptic and echocardiographic findings in
M. Lupi, L. Reggiani bonetti, E. Stauder, S. Bettelli, seven foetuses with congenital heart anomalies,
A. Maiorana lung lobation defects and normal visceroatrial
22 Renal leiomyoma arrangement
N. Mashali, A.T. Awad, G. Trevisan, M. El-bahrawy F. Angiero, V. Fesslova, T. Rizzuti, M. Stefani
25 Melanoma of the nipple. An additional case 61 Solitary extramedullary plasmacytoma of the thyroid
V. Mourmouras, M.R. Ambrosio, M. Onorati, gland associated with multinodular goiter: case
B.J. Rocca, N. Di mari, F. De luca, C. Miracco 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
Issue 2 64 Sebaceous carcinoma of the vulva: critical approach
April 2011 to grading and review of the literature
T. Pusiol, D. Morichetti, M.G. Zorzi
27 Teaching anatomical pathology in the undergraduate CASE REPORTS
curriculum in Medicine: the experience of ‘C 68 Pleomorphic giant cell ductal carcinoma of the
Course’, Sapienza University, Rome breast
P. Gallo, G. D’Amati, C. Di Gioia, C. Giordano D. Tacchini, M.G. Mastrogiulio, L. Vassallo,
CASE REPORTS 71 A solitary pilar leiomyoma of the trunk
32 Cystic sebaceous lymphadenoma of the parotid R. Benmously-Mlika, F. Ishak, S. Ben Jennet,
gland: case report and review of the literature H. Hammami, T. Badri, I. Mokhtar, S. Fenniche
inDeX volume 103, no. 1-6 351
73 Malignant proliferating trichilemmal cyst of the CASE REPORTS
scalp: histological aspects and nosology 299 Histogenetic and taxonomic considerations
A. Khaled, M. Kourda, B. Fazaa, J. Kourda, on a case of post-traumatic bizarre parosteal
S. Ben Jilani, M. Ridha Kamoun, R. Zermani osteochondromatous proliferation (BPOP)
M. Filotico, A. Altavilla, S. Carluccio
LETTER TO THE EDITOR-IN-CHIEF 304 Reactive pseudo-glandular mesothelial hyperplasia
77 Reliability of K-ras mutational analysis on in testis tunica vaginalis: a case report
cytological samples from metastatic colorectal N. Di Naro, G. Puliga, L. Olla, G.A. Tolu
cancer 307 Incidental finding of peripheral B-cell non-
C. Bozzetti, F.V. Negri, N. Naldi, R. Nizzoli, Hodgkin lymphoma, lymphocytic/CLL type, of the
B. Bortesi, V. Zobbi, C. Azzoni, E.M. Silini, gallbladder in a patient with chronic cholecystitis
A. Ardizzoni H. Imenpour, M. Castagnola, G. De Silva, S. Zupo,
M. Truini, E. Merlo, L. Anselmi
311 Nodular hidradenoma in a 19-year-old woman
Issue 4 R. Benmously-Mlika, M. Jones, H. Hammami,
August 2011 N. Labbene, A. Debbiche, I. Mokhtar, S. Fenniche
ATTI DI CONGRESSO
79 Congresso Nazionale SIAPEC-IAP Issue 6
Palermo, 27-29 Ottobre 2011 Decmber 2011
Issue 5 313 The role of 2D bar code and electronic cross-
October 2011 matching in the reduction of misidentification errors
in a pathology laboratory. A safety system assisted
ORIGINAL ARTICLES by the use of information technology
271 Primary synovial sarcoma of the kidney. A case G. Fabbretti
report with pathologic appraisal investigation and 318 Cytologic re-evaluation of negative effusions from
literature review patients with malignant mesothelioma
A. Pitino, S. Squillaci, C. Spairani, M.F. Cosimi, V. Ascoli, D. Bosco, C. Carnovale Scalzo
E. Feyles, D. Ricci, F. Bardari, M. Graziano, 325 Intra-operative frozen section technique for breast
F. Morabito, F. Cesarani, M. Garruso, M. Belletti, cancer: end of an era
K. Beierl, K.M. Murphy E. Manfrin, A. Remo, F. Falsirollo, G.P. Pollini,
279 Oncocytic carcinoma of the parotid gland: case A. Parisi, A. Nottegar, F. Bonetti
report and review of the literature 331 The diagnostic accuracy of cervical biopsies in
T. Pusiol, D. Morichetti, M.G. Zorzi determining cervical lesions: an audit
J. Wang, M. El-Bahrawy
SPECIAL ARTICLE 337 “Combined” desmoplastic melanoma of the vulva
290 Epidemiological changes in breast tumours in Italy: with poor clinical outcome
the IMPACT study on mammographic screening G. Collina
Impact Working Group CASE REPORTS
340 Tuberculosis of superficial lymph nodes, a not so
GUIDELINES AND CHECK LISTS rare event to consider in diagnosis. A case in an
294 Breast cancer and primary systemic therapy. elderly male
Results of the Consensus Meeting on the A. Merante, M.R. Ambrosio, B.J. Rocca,
recommendations for pathological examination and A.M. Condito, A. Ambrosio, M. Arvaniti, G. Ruotolo
histological report of breast cancer specimens in 343 Adenolipoma of the skin
the Marche Region S. Karoui, T. Badri, R. Benmously, E. Ben Brahim,
A. Santinelli, M. De Nictolis, V. Mambelli, A. Chadli-Debbiche, I. Mokhtar, S. Fenniche
R. Ranaldi, I. Bearzi, N. Battelli, C. Mariotti, 346 Adenomatous transformation in a giant solitary
L. Fabbietti, S. Baldassarre, G.M. Giuseppetti, Peutz-Jeghers-type hamartomatous polyp
G. Fabris F. Limaiem, S. Bouraoui, A. Lahmar, S. Jedidi,
S. Aloui, S. Korbi, S. Mzabi
352 author inDeX
Abbona G.C., 143, 201 Bar E., 151 Bono F., 162 Carboni G., 50
Acconcia A., 240 Barbagli L., 190 Bono L., 139, 212 Cardone C., 181
Achille G., 187 Barbareschi M., 140, 157, 171, 215, 216 Bonzanini M., 80 Carducci A., 265
Adami G., 158 Barbato A., 140 Bordoni A., 163 Carella R., 157, 171
Addati T., 150, 187, 226 Barberis M., 125, 156, 219 Bortesi B., 77 Carlà T.G., 234
Afeltra A., 138 Barbiano di Belgiojoso G., 214 Bortul M., 148 Carli F., 221
Agostinelli C., 119, 168 Barbieri D., 153 Borzillo A., 248 Carluccio S., 299
Agostini E., 11 Barbieri P., 201 Borzomati D., 165, 193, 194, 229 Carnovale Scalzo C., 318
Al Omoush T., 148 Bardari F., 271 Bosco A., 165 Carolei D., 246
Alabiso O., 156 Barnabei A., 202 Bosco D., 318 Carolina A.F., 199
Alaggio R., 165, 186 Barollo S., 189 Bosi A., 179 Carosi I., 177, 207, 239
Albertoni L., 236 Baron L., 147 Bosisio F.M., 161, 223, 231 Carosi M., 202, 232, 251
Alesiani F., 197 Barone A., 8, 195, 211, 230 Botta C., 147 Carrieri G., 170
Alessandrini L., 147, 225 Barreca A., 162 Botta G., 135, 205 Carroccio A., 164
Allegra E., 247 Barresi G., 187, 231 Botti G., 107, 110, 136, 140, 144, 146, Carru C., 152
Allegrini S., 156, 192, 261 Barresi V., 187, 231 153, 164, 217, 218, 239, 240, 241, Caruso C., 138
Allia E., 100, 253 Bartoletti R., 266 245, 263, 264 Caruso F., 129
Alò P.L., 170, 176, 188 Bartolommei S., 265 Bouraoui S., 346 Caruso R., 233, 238
Aloui S., 346 Bartoloni G., 96 Bove G., 239 Caruso S., 214
Altavilla A., 299 Battaglia A., 228 Boveri E., 197 Casadio C., 157
Altomare V., 229 Battaglia G., 235 Bovo G., 161, 162, 243 Cascone P., 141
Amato M., 161, 165 Battelli N., 294 Bozzetti C., 77 Casini B., 217, 232
Amato T., 195 Battolla E., 160 Braccischi A., 169, 184, 229 Casoria A., 245
Ambrosio A., 230, 260, 340 Bearzi I., 294 Bragantini E., 171, 216 Casorzo L., 147, 259
Ambrosio M.R., 8, 25, 124, 181, 190, Becchina G., 94, 167, 194, 241 Brancato B., 52 Cassina E., 231
195, 210, 211, 212, 230, 238, 260, Bega O., 255 Brandi M.L., 213 Cassoni P., 162, 228
265, 340 Beierl K., 271 Brazzarola P., 144 Castagnola M., 307
Amico P., 165 Belardinelli V., 147, 225 Bresaola E., 157 Castellano I., 100, 228
Amore F., 165 Bellan C., 195, 210, 230, 238 Brisigotti M., 175, 216 Castiglia M., 182, 190
Amoroso A., 138 Bellavia T., 203 Brollo A., 158 Castiglione F., 11, 155, 205
Ancona E., 161, 235 Bellei E., 169 Brunelli C., 193, 194 Castrista M., 239
Andreini L., 216 Belletti M., 271 Brunelli F., 146 Cataldo I., 192, 237
Andreozzi A., 147 Bellevicine C., 145, 173, 190, 200, Brunelli M., 139, 204, 213, 216, 217 Catalucci A., 186, 208
Andronico G., 203 202, 243 Brunello E., 204, 216, 217 Catarini M., 197
Angelucci D., 172 Bellini R., 261 Bruno M., 43 Cattoretti G., 161, 162, 231
Angiero F., 53 Bellis D., 143, 159, 201 Bruzzone M., 250 Cavalli T., 213
Annaratone L., 221 Bellisano G., 62 Buccoliero A.M., 11, 155 Cavani A., 229
Anniciello A., 140 Belluso D., 159 Buffa C., 144 Cavazza A., 111, 157
Anniciello A.M., 107, 140 Belmonte B., 142, 177, 182 Bufo P., 144, 171, 185, 188, 240, 246, Cavedon E., 189
Anselmi L., 307 Beltrami V.R.L., 135, 205, 260 247, 262 Cè S., 248
Anselmi M., 208 Ben Brahim E., 343 Buglioni S., 148, 217 Ceciliani E., 252
Antinori S., 112, 113 Ben Jennet S., 71 Buonaguro F.M., 83 Centrone M., 150, 187
Antona J., 156, 192 Ben Jilani S., 73 Buonaguro L., 83 Cerasola G., 203
Antonelli M., 96 Ben-Dor D., 177 Burgio U., 199 Cernic S., 158
Antonini D., 159 Benerini Gatta L., 215, 261 Burioni R., 113 Cerrone M., 107, 110, 140, 146, 217,
Anzalone R., 145 Benevolo M., 234, 251 Butera D., 150 218, 241, 245, 263, 264
Apicella P., 146 Benmously R., 343 Buttitta F., 126, 155, 158, 203 Certo G., 219, 236, 253
Appetecchia M., 202 Benmously-Mlika R., 71, 311 Cesarani F., 271
Aprile G., 163 Bensi T., 201 Cabibi D., 142, 177, 182, 190, 218, 236 Cesarini E., 150
Aquino G., 110, 164, 171, 245, 246, 263 Beretta Anguissola G., 188 Cacciatore M., 164, 167, 197 Cesinaro A.M., 180
Aragona F., 177, 182 Bergamaschi M., 1, 174 Cadei M., 131, 215, 261 Chadli-Debbiche A., 343
Arborea G., 202, 206, 245, 249, 255 Bergamini S., 40, 169 Cagiano S., 144, 185, 246, 247 Chella A., 155, 203
Arcaini L., 196, 197 Bertazzoni G., 265 Cai T., 266 Chiapparini L., 157
Arcuri P., 190 Bertolaso A., 200 Caldara A., 215 Chiaramonte A., 195
Ardizzoni A., 77 Bertolotti A., 261 Caldarella A., 146 Chiarello G., 152, 154, 189, 251
Arena R., 210 Betta P.G., 201 Callea M., 161, 165 Chicchinelli N., 140
Arena V., 135, 148, 149, 214 Bettelli S., 19, 180, 215 Caltabiano R., 98, 186, 247, 261 Chilli L., 14
Arisio R., 100 Biancalani M., 146, 174 Calvaruso M., 164, 167, 197 Chilosi M., 144, 191, 200, 204, 213,
Arnoffi J., 232 Bianchi G., 169 Calvisi G., 135, 143 216, 217
Arrigoni C.V., 231 Bianchi P., 175 Camerlingo R., 217 Chiusa L., 100, 162, 228
Artioli P., 14 Bianchi S., 146 Campaner M., 258 Cianci R., 138
Arvaniti M., 340 Bianco M., 206, 207 Campisi V., 232 Cicchinelli I., 135, 143
Ascierto P., 140 Biasi O., 219 Canciglia R., 194 Cimino G., 195
Ascoli V., 318 Biggeri A., 228 Candia S., 148 Cimmino A., 137, 168, 202, 208, 245
Asioli S., 166 Bisceglia M., 4, 43, 177, 182, 183, 186, Canessa P.A., 160 Cintorino M., 211, 212, 265
Asselti M., 225, 226, 237 195, 206, 207, 216, 249 Cannata N., 238 Cirese V., 116
Avallone A., 240 Bisceglia M.L., 4 Cannizzaro C., 139, 213 Citraro L., 200
Awad A.T., 22 Bisceglia S., 4 Cantaloni C., 140, 157, 215 Ciuffetelli V., 175, 263
Azzolina V., 210 Boccardo S., 166, 221 Cantile M., 107, 110, 140, 146, 164, Claudio B., 217
Azzoni C., 77 Boccuzzo G., 225 217, 218, 239, 240, 241, 245, 263, Clemente C., 105
Bogina G., 99, 217 264 Clemente R., 236
Bacci F., 14, 119 Boldorini R., 156, 192, 261, 262 Capano R., 239, 240, 241 Coccia A., 253
Bacigalupo A., 179 Bollito E., 128 Capella S., 159 Coccini G., 1
Bacigalupo B., 160 Bolner A., 171 Capelli P., 191, 192 Coccini G., 174
Badri T., 71, 343 Bombonato M., 232 Caponio M.A., 150 Cocuzza S., 261
Baffa R., 235 Bonanni B., 219 Caporalini C., 204, 205 Colantoni A., 159
Bagnoli A., 175 Bonanno A., 233 Cappadona S., 228 Colao A., 202
Baldassarre S., 294 Bonanno E., 148, 159 Cappellesso R., 232 Colasante A., 172, 259
Baldelli R., 202 Bondi A., 87, 130 Cappello F., 145 Colato C., 144, 178
Baldini D., 148 Bonello L., 162 Capulli M., 186 Coletti G., 175, 263
Balistreri M., 161, 189, 235 Bonetti F., 216, 217, 220, 325 Caraglia M., 263 Colli S., 160, 166, 221
Balmativola D., 221 Bonifacio D., 79 Caramella D., 137 Collina F., 146, 217, 218
Balzarini P., 215, 261 Bonifacio M., 200 Carbone A., 149 Collina G., 50, 337
author inDeX 353
Colombo M.P., 197 Dell’Orto P., 156 Ferretti M., 252 Giantomassi F., 197
Colombo P., 223 Dell’Osa E., 198 Ferretti S., 88 Giardina C., 222
Colonna A., 158 Della Pace L., 239, 256 Ferro A., 215 Giardini R., 114
Colonna P., 200 Delrio P., 240 Ferro P., 160, 166, 221 Giarnieri E., 154
Comin C.E., 155, 204, 205 De Maglio G., 182, 216 Ferrone S., 107 Gigante A., 138, 211
Condito A.M., 340 Demarchi A., 264 Fesslova V., 53 Gigantino V., 263, 264
Conte P.F., 215 Denti A.M., 157 Feyles E., 271 Giglio A., 234
Contini M., 152 Dessanti P., 166 Fiaccavento R., 135 Gilioli E., 204
Convertino C., 148 Di Bella C., 223 Fiandrino G., 122 Gillio Tos A., 253
Coppola R., 161, 165, 193, 194, 229 Di Bello C., 162 Ficarra G., 215 Ginori A., 8, 68, 211
Corini F., 169, 184, 229, 243, 245 Di Bonito L., 79, 148 Ficarra V., 139 Gioioso A., 150
Cormio L., 170 Di Bonito M., 146, 217, 218 Ficial M., 213 Giordano C., 27
Corrao S., 145 Di Carlo A., 234 Filardo A., 254 Giordano T., 238
Corrente A., 255 Di Clemente D., 202, 206, 245, 249, Filotico M., 299 Giotta F., 225, 226
Corsi F., 239 255 Fiordelisi F., 43, 216 Giovagnini G., 175
Cosci E., 230 Di Clemente L., 263 Fiore G., 168, 206, 245, 249 Giovagnoli M.R., 82, 154
Cosimi M.F., 271 Di Cristofano C., 148 Fiorentino M., 128 Girardi G., 205, 260
Cossu-Rocca P., 152 Di Domenico M., 185 Fiorini P., 11 Girelli M.E., 189
Costa A., 238 Di Filippo F., 217 Fiorito C., 253 Girlando S., 171, 215
Costantini B., 197 Di Francesco A., 225 Fisogni S., 46 Girolomoni G., 178
Costanza G., 203 Di Gioia C., 27 Floccari F., 234 Giudici F., 79, 148, 213
Costarelli L., 148 Di Gregorio C., 231 Flora M., 147 Giuffra V., 137, 209
Covelli C., 249 Di Leo A., 228 Florena A.M., 164, 167, 197 Giuffrè G., 85
Covello R., 202 Di Lorenzo, I., 251 Floridi D., 205 Giuliani M., 234
Coverlizza S., 264 Di Lorito A., 172, 198, 200, 259 Foltran L., 163 Giuliani S., 140
Crescenzi A., 148 Di Marco F., 199 Fondi C., 179 Giunchi F., 128
Crippa S., 163, 233 Di Mari N., 25 Fontana V., 160 Giurato E., 186
Crisafulli C., 233 Di Matteo F.M., 193, 194 Fontecchio G., 137, 209 Giuseppetti G.M., 294
Crisman G., 135, 143, 146, 175, 196, Di Nardo P., 135 Fornaciari A., 137 Giusiani S., 137
234, 263, 266 Di Naro N., 62, 304 Fornaciari G., 137, 138, 209 Gobbo S., 139, 191, 192, 213, 216
Croce A., 159, 172, 200 Di Stasio E., 135 Fornari A., 128 Gomes V., 148
Croce C.M., 235 Di Tonno C., 157 Foscolo A.M., 254 Gorji N., 166
Crocetti E., 146 Diamanti L., 169, 184, 229 Francavilla S., 263 Goteri G., 197, 252
Crucitti P., 87, 161 Dimitri L., 239 Franceschini M.C., 160, 166, 221 Grammatica L., 187
Cuorvo L., 215 Dinelli M.E., 161, 162 Francesconi A., 202, 232 Grandi C., 171
Curcio E., 163 Diodoro M., 232 Francia di Celle P., 162 Grasso M.A., 207
Curcio M.P., 110 Discepoli S., 146, 266 Franco C., 122 Gravina G.L., 138, 209
Curti T., 266 Doglioni C., 112 Franco G., 197 Graziano M., 271
Dominici M., 215 Franco R., 107, 110, 136, 140, 144, 171, Graziano P., 157
D’Agruma L., 183 Donà M.G., 234, 251 185, 227, 239, 245, 263, 264 Greco M., 195
D’Alterio C., 239 Donadio M., 228 Franco V., 142, 164, 167, 236 Greco P., 87, 165
D’Amati G., 27, 148 Donnini I., 179 Frattini M., 156, 163, 233 Greggi S., 153
D’Amuri A., 234 Doring C., 196 Frossi B., 164, 197 Gri G., 164
D’Angelo A., 169, 184, 229 Fulcheri E., 250, 257 Grigolato P.G., 131, 215, 261
D’Angelo G., 172 Eccher A., 204 Fulciniti F., 140, 150 Grillo L.R., 148
D’Angelo P., 199 Eccher C., 215 Fumagalli C., 156, 219 Grimaldi B., 138
D’Angelo V., 207 Egarter-Vigl E., 258 Fusi C., 179 Grottola A., 265
D’Antona G.I., 43 El-Bahrawy M., 22, 331 Guadagno E., 189
D’Antuono T., 158 Epifani A., 234 Gaeta L.M., 194, 229 Guarneri V., 215
D’Armiento M., 93 Esposito A., 129, 134 Galardi F., 228 Guarnotta C., 142, 164, 167, 190, 197
D’Eredità G., 222 Galasso M., 235 Guerrieri A.M., 222
D’Urso P.I., 137, 208 Faa G., 62 Galletta F., 164 Guetti L., 155, 158, 203
Da Pozzo G., 14 Fabbietti L., 294 Galliani C., 182, 186, 249 Gugliotta P., 147
Dal Mas A., 148 Fabbretti G., 175, 313 Galliani C.A., 206 Guidi S., 179
Dal Santo M., 131 Fabbro M., 232 Galliani M., 211 Gulino A., 167
Dalla Palma P., 80, 118, 140, 171, 215, Fabris G., 294 Galligioni E., 215 Gurrera A., 186
216 Facchetti F., 46, 123, 168 Gallo D., 154 Gustinelli A., 262
Danza K., 227 Facchini G., 263 Gallo E., 217 Gustinucci D., 150
Daprile R., 220, 225, 227, 237 Facciolo F., 202 Gallo P., 27 Guzzardo V., 161, 225
David S., 145 Fadda G., 81, 152, 154, 189, 251 Galuppini F., 189 Guzzetti S., 220
De Bernard M., 235 Faggiano A., 202 Galzio R.J., 208
De Carolis S., 251 Falconieri G., 163, 216 Gambacorta M., 232 Hammami H., 71, 311
De Chiara A., 164 Falini B., 14, 119 Ganau M., 62 Hansmann M.L., 196
De Giorgi V., 142 Falsirollo F., 325 Gandolfo S., 170, 172 Hartmann S., 196
De Luca C., 202 Fara D., 263 Garbini F., 11 Hofmann W.P., 196
De Luca F., 25, 212 Fara Tanjona H., 156 Garofalo A., 232 Huhtamo E., 261
De Luca N., 177 Faraggiana T., 138, 211 Garruso M., 271
De Maglio G., 147, 158, 163 Farina M., 107, 140 Gaudio F., 202, 245 Iaccarino A., 190
De Marco L., 253 Farinati F., 236 Gazzola A., 14 Iannucci A., 204
De Miglio M.R., 152 Farinetti A., 180, 248, 265 Genderini F., 214 Icardi M., 201
De Murtas F., 239, 245 Farruggia P., 199 Genovese F., 94, 167, 194, 241 Ieni A., 187
De Nictolis M., 294 Fasanella S., 140 Genta R.M., 236 Ientile D., 238, 255
De Pangher Manzini V., 158 Fasola G., 158, 163 Gentile R., 90, 166, 191 Ilardi G., 141, 180, 240, 246, 248
De Pellegrin A., 79, 148 Fassan M., 86, 161, 189, 235, 236 Gessi M., 97 Imenpour H., 307
De Rosa G., 141, 144, 180, 190, 240, Fassina A., 125, 232 Ghiringhello B., 253, 260 Impara G., 234
246, 248 Fazaa B., 73 Giacalone B., 94, 167 Imperiale D., 144
De Rosa N., 200 Fazioli F., 164 Giacomelli L., 161, 225 Inghirami G., 119, 162, 167
De Salvo L., 217 Fedele F., 233 Giallombardo D., 182, 190, 236, 242 Ingravallo G., 137, 168, 202, 208, 222
De Santis R., 249 Fedeli F., 160, 166, 221 Giammaresi C., 139, 212 Intrieri T., 146
De Silva G., 307 Federico S., 253 Gianatti A., 147 Ioli A., 175
Deambrogio C., 253 Felicioni L., 155, 158, 203 Giannakakis K., 138, 211 Ionna F., 245
Debbiche A., 311 Fenniche S., 71, 331, 343 Giannatempo G., 195 Iop A., 158
Del Conte A., 158 Fenocchio D., 220 Giannatiempo R., 176, 185, 227, 239, Ishak F., 71
Del Vecchio M., 169, 184, 229 Ferdeghini M., 144 264 Isimbaldi G., 231
Del Vecchio M.T., 190, 210, 230 Feriozzi S., 211 Giannini A., 146, 228
Del Vescovo V., 157 Ferraiuolo P., 140 Giannone A.G., 218 Jaffrain-Rea M.L., 208
Delfino C., 179 Ferrantelli A., 139, 211, 212 Giannone G., 150, 187, 225 Jedidi S., 346
Dell’Antonio A., 148 Ferraris A.M., 221 Gianquinto D., 221 Jones M., 311
354 author inDeX
Kacerovská D., 259 Manini C., 151, 253, 264 Miracco C., 25 Ozben T., 169
Karoui S., 343 Manna A., 140 Miraglia M.C., 242
Kasal A., 258 Mannella E., 266 Miranda G., 209 Pacella E., 257
Kazakov D., 259 Mannone T., 114 Mittica G., 228 Pacenti L., 190
Khaled A., 73 Mannu C., 14 Mokhtar I., 71, 311, 343 Paci E., 146
Korbi S., 346 Mannucci S., 210 Molinari F., 233 Paganotti A., 156, 192
Kourda J., 73 Manta C., 160 Molinaro L., 162, 222 Pagliarulo M., 234
Kourda M., 73 Manzotti M., 156 Molo S., 122 Paglierani M., 142, 147
Kuppers R., 196 Marampon F., 138, 186, 209 Monari E., 169 Pagni F., 223
Marandino F., 217 Moncelsi S., 152, 251 Palamara G., 234
La Mantia E., 110, 136 Marasà L., 199, 211 Moncini D., 11 Palatini J., 235
La Rocca G., 145 Marasà S., 203, 242 Mondaini N., 266 Palazzoni G., 214
Labate A., 219, 236, 253 Marasco A., 254 Monego G., 135 Palermo A., 188
Labbene N., 311 Marazzi F., 214 Monga G., 156 Palma F., 187
Lagrasta C., 147 Marchelle G., 147, 225 Monticelli A., 185, 227, 239, 264 Palumbieri G., 246, 257
Lahmar A., 346 Marchesini G., 252 Montironi P.L., 151 Palumbo M., 206, 245, 255
Lai M.L., 62 Marchetti A., 109, 155, 158, 203 Montironi R., 128 Palummo N., 210
Lambertenghi D., 228 Marchiò C., 221, 228 Montrone T., 202, 206, 222, 245, 249, Panniello G., 177
Lanzafame S., 186, 261 Marchione M., 228, 248 255 Pannone G., 144, 171, 185, 188, 240,
Lapi E., 11 Marchione R., 32 Morabito F., 271 246, 247, 262
Larato C., 253 Marcolini L., 191, 192, 220, 237 Morassi F., 154 Papagerakis P., 262
Lastilla G., 182 Margiotta D., 138 Moretto D., 234 Papagerakis S., 262
Latini A., 234 Margiotta M., 175 Morichetti D., 52, 64, 141, 180, 181, Papaleo N., 151
Lattanzio G., 198, 200 Mariani M., 197 222, 258, 279 Papotti M., 128, 157
Lauricella C., 232 Mariani N., 201 Morosetti M., 211 Pappalettera F., 170
Lazzi S., 8, 124, 181, 195, 230, 238 Mariani S., 162 Mosca A., 139 Para P., 175
Leardo T., 253 Maricosu E., 152 Mottolese M., 148, 217 Paradiso A., 148, 220, 227, 237
Leocata P., 135, 143, 146, 175, 196, Marinelli C., 198 Mourmouras V., 25, 181, 238, 260 Parafioriti A., 182
234, 263, 266 Maringhini S., 210 Mucilli F., 155, 158, 203 Parente P., 235
Leonardi E., 147, 215 Mariotti C., 294 Munari E., 200, 213 Parenti R., 186
Leonardo E., 148 Marra F., 146 Mura A., 152 Parisi A., 144, 191, 192, 220, 237, 325
Leoncini L., 124, 195 Marra L., 185, 217, 240, 263, 264 Murari R., 176, 188 Parracino T., 206
Leone B.E., 223 Marsico A., 170, 172 Muroni M.R., 152 Parravicini C., 112
Leone G., 259, 261 Martellani F., 79, 148 Murphy K.M., 271 Pasqualini F., 177
Leoni P., 197 Martignoni G., 139, 204, 213, 216, 217 Musa M., 159 Pasquinelli G., 183
Lepanto D., 219 Martin V., 163 Muscarella L., 183 Pasquini P., 148
Li Cavoli G., 139, 211, 212 Martinesi M., 266 Muscatiello N., 166 Passamonti B., 150
Libener R., 201 Maruzzi M., 206 Mustacchi G., 148 Passantino R., 139, 211, 212
Liberati M., 259 Marzano A.L., 225, 226 Muti P., 148 Paulli M., 122, 196
Libretti L., 231 Marzi S., 186, 208 Mzabi S., 346 Pazzagli M., 142
Liguori G., 107, 110, 146, 164, 217, 218 Mascolo M., 141, 180, 246, 248 Pecciarini L., 147
Limaiem F., 346 Mashali N., 22 Nagar C., 94, 167, 194, 241 Pecorari M., 265
Liotta R., 191 Masiero E., 158, 163 Naldi N., 77 Pederzoli A., 175
Liuzzi M., 222 Massa P., 254 Nania A., 238 Pedica F., 191, 192
Lo Cunsolo C., 147 Massarelli G., 152, 168 Nanni N., 265 Pedicillo M.C., 247
Lo Mele M., 147, 225 Massi D., 106, 142, 179 Nannini R., 216 Pedretti P., 179
Loda M., 128 Mastrogiulio M.G., 211, 230, 238 Napoli A., 222 Pedron S., 217
Lomazzo G., 135 Mastrogiulio M.G., 68 Napoli P., 238 Pelella A., 239, 240
Longhi E., 112 Mataca E., 153 Nasorri F., 229 Pelizzo M.R., 189
Longo F., 165, 245 Materazzi S., 179 Nassini R., 179 Pellegrini W., 168
Lora V., 178 Matter M., 136 Natale G., 144 Pellis G., 148
Lorenzi L., 168 Mattioli E., 226 Navone R., 170, 172 Pelosi G., 125, 157
Losito N.S., 153 Mattoni M., 171, 185, 188, 246, 247, Nebuloni M., 177, 214 Penitente E., 172, 198, 259
Losito S., 245 262 Negri F.V., 77 Pennacchia I., 135, 149, 214
Lotta R., 166 Maura E., 170 Negri G., 154, 258 Pennelli G., 189, 236
Lucchini C., 220 Mazza S., 151 Nesi G., 213, 266 Pensiero V., 138
Lucchini V., 231 Mazzer M., 163 Nicastro A., 176, 185, 227, 239, 264 Pentenero M., 170, 172
Luchini C., 191, 192 Mazzitelli R., 236 Nicola M., 122 Pepe P., 127
Lucioni M., 122, 196 Mazzola S., 151 Nicolini M., 175 Pepi M., 155, 213
Ludwig K., 161 Mazzon E., 219, 236, 253 Nirchio V., 166, 170, 239, 256 Perdonà S., 263
Luparia P., 253 Mazzucchelli L., 163, 233 Nitti D., 236 Pericoli M.N., 148
Lupi M., 19, 40, 248 Menia E., 154 Nizzoli R., 77 Perracchio L., 148, 232
Lupo C., 133 Menis J., 158 Nocita A., 151, 254 Perrone G., 43, 161, 165, 193, 194, 229
Lusiardi M., 157 Mennilli S., 134 Nogales F.F., 152 Pescarmona E., 202, 217, 232, 251
Lutrino S., 163 Merante A., 260, 340 Noto S., 170 Pessina S., 156
Mercurio C., 209 Nottegar A., 204, 216, 217, 325 Petitti T., 211
Macario M., 220 Merlo E., 307 Novara G., 139 Petroni S., 150, 225, 226
Macciocu E., 154 Mescoli C., 236 Novelli L., 155, 204, 205 Pettinato G., 145
Macilotti M., 140 Mesiti M., 219 Nozzoli C., 179 Peveling-Oberhag J., 196
Macor P., 167 Messerini L., 155, 204, 205 Nucifora M., 233 Piacentini F., 215
Macrì L., 220, 221 Messina V., 238 Nugnes L., 176, 185, 227, 239, 264 Pica E., 176
Maglione A., 176, 185, 227, 239, 264 Mezzapelle R., 156, 192 Piccaluga P.P., 14, 119, 167, 197
Magro G., 101, 165, 186, 259, 261 Mezzaroba N., 167 Oackman C., 228 Piccioli M., 14
Maio V., 179 Mian C., 189 Ober E., 79, 148 Piccioni D., 175
Maione M.P., 176, 185, 227, 239, 264 Miani L., 252 Olianas R., 152 Piccolomini M., 32, 228, 248
Maiorana A., 19, 40, 169, 180, 215, 248 Micali S., 169 Olla L., 62, 304 Pietribiasi F., 101
Maiorano E., 202 Michal M., 259 Onetti Muda A., 138, 161, 165, 193, Pignata S., 153, 263
Malapelle U., 145, 200, 202, 243 Micheletti M., 170 194, 211, 229 Piiper A., 196
Malatesta S., 155, 158, 172, 198, 200, Micheli F., 173 Onorati M., 8, 25, 181, 190, 195, 210, Pilato B., 226
203, 259 Micheli P., 173 211, 212, 230, 238, 260, 265 Pileri S.A., 14, 119, 167, 168
Maletta F., 220, 253 Migaldi M., 180, 248, 265 Opocher G., 189 Pili F., 152
Malfettone A., 220, 227, 237 Miglio U., 156, 192 Oppressore D., 176, 185, 227, 239, 264 Pimpinelli F., 234
Mambelli V., 169, 184, 229, 245, 294 Miglionico L., 249 Oranges T., 179 Pimpinelli N., 179
Mamo M., 236 Migliore M., 186 Orecchia S., 201 Pinzani P., 142
Manfrin E., 216, 217, 220, 237, 325 Mignogna C., 103, 238, 255 Orlando E., 203, 242 Pioner R., 258
Mangerini R., 221 Mikuz G., 128 Orvieto E., 147, 225 Pirozzi G., 217, 241
Mangia A., 220, 227, 237 Mirabella A., 136 Ottelli Zoletti F., 228 Pisano C., 153
Mangiapia M., 200 Mirabella C., 170 Ottoveggio G., 94, 167, 194, 241 Piscioli F., 52, 141
author inDeX 355
Piscuoglio S., 136 Rostan I., 170, 172 Sibau A., 158 Unti E., 145, 199, 210, 241, 251
Pistillo M.P., 160, 166, 221 Rotellini M., 155, 204, 205 Silini E.M., 77 Uras M.G., 152
Pitino A., 271 Rotolo U., 139, 211, 212 Silvano Costa S., 153 Urbani V., 209
Pizzamiglio S., 148 Rubini V., 150 Silvestrini M., 171 Urso C., 146
Pizzi G., 254 Ruco L., 148 Simoncelli S., 215
Pizzi M., 161, 189, 235, 236 Rudà R., 228 Simone G., 150, 187, 220, 225, 226, Vago G., 214
Pizzolitto S., 158, 163 Rugge M., 86, 147, 161, 189, 225, 227, 237 Vairo M., 182
Polci R., 211 235, 236 Simonetti A., 228 Valduga F., 171
Pollini G.P., 325 Ruisi R., 251 Simoni A., 266 Valentino A., 203, 242
Poloni A., 197 Ruol A., 161 Sivori M., 160 Vandone A., 100
Ponte R., 257 Ruotolo G., 260, 340 Sollima L., 135, 143 Vanoni V., 171
Ponz de Leon M., 231 Russo A., 176, 185, 217, 227, 239, 264 Somma A., 189 Vanzati A., 243
Popescu O., 150, 226 Russo D., 173, 177 Somma P., 173 Varone V., 145, 173, 243
Porta C., 139 Russo L., 239, 264 Spagnoli L.G., 159 Vasquez E., 247, 259
Possanzini P., 156, 219 Russo S., 187, 202 Spairani C., 271 Vassallo L., 68, 211
Postiglione M., 176, 185, 227, 239, 264 Sparano L., 136 Vassarotto E., 225
Potortì I., 191 Sabatini A.M., 265 Spina D., 195 Vazzana N., 198
Pozzilli P., 188 Sabattini E., 14, 119 Spirito A., 206 Vecchio F.M., 149, 214
Prestipino J., 101 Sabbatini R., 252 Spoladore C., 225 Vecchio G.M., 165, 186
Priano R., 175 Sabino A., 165 Squillaci S., 32, 228, 248, 254, 271 Vecchione M.L., 141, 246, 248
Privitera E., 147 Saccardi R., 179 Staffolani M., 252 Veggiani C., 156, 192, 262
Pucillo C., 164, 197 Sacchini, A., 265 Staiano M., 150 Vellone V.G., 152, 154, 189, 251
Pugliese F., 138, 211 Sacco O., 107 Staibano S., 106, 141, 180, 240, 246, Ventura L., 137, 138, 186, 208, 209
Puliga G., 62, 304 Sagramoso Sacchetti C.A., 14 248 Venturoli S., 153
Pusiol T., 52, 64, 141, 180, 181, 222, Salatiello M., 202 Stauder E., 19, 40 Verderio P., 148
258, 279 Salemme M., 46 Stefani M., 53 Verdun di Cantogno L., 147
Puzzo L., 247 Salvatore C., 220, 227 Steinmeyer A., 266 Vermi W., 123
Salvatorelli L., 165, 186 Stigliano V., 232 Vezzosi V., 146
Quero C., 187, 225 Salvi S., 147, 166, 221 Stio M., 266 Viale G., 100
Salvianti F., 142 Stramazzotti D., 197, 252 Vianello F., 189
Rabitti C., 193 Salvio M., 201 Stufano V., 156 Viberti L., 85, 143, 201, 220
Raffaelli M., 189 Salvioni D., 223 Sulfaro S., 158 Vigani A., 160
Ragazzini T., 130 Sampaoli I., 175 Sullo L., 170 Vigevani E., 158
Ramieri M.T., 148, 176, 188 Sanchez Mete L., 232 Vigliar E., 173, 243
Ranaldi R., 294 Sangaletti S., 197 Taborro R., 184, 245 Vigna S., 147
Rappa F., 145 Sangapur R., 225 Tacchini D., 238 Villani E., 234
Rattotti S., 196 Sanguedolce F., 188, 247, 262 Tacchini D., 68 Villari N., 137
Ravanini P., 261 Santantonio R., 258 Taddei G.L., 11, 155 Vindigni C., 195
Re P., 201 Santi R., 213, 266 Taglieri D.M., 219, 236, 253 Viola P., 155, 158, 172, 198, 200, 203,
Re R., 197 Santinelli A., 147, 294 Tallarico E., 151, 254 259
Realdon S., 235 Santini D., 229 Tallarigo F., 151, 228, 248, 254 Visca P., 202
Reggiani Bonetti L., 19, 40, 169, 180, Santonastaso C., 241 Tallini G., 147 Vita G., 43
215, 231, 248, 265 Santopietro R., 181, 230, 238 Tancredi G., 205 Vitale A., 214
Reggiani C., 50 Santoro A., 144, 171, 185, 188, 189, Taraglio S., 144 Vitale A.R., 266
Reitano R., 170 240, 246, 247, 262 Tarquini E., 251 Vitale R., 248
Relli V., 136, 140 Sapia M.C., 210 Tasso G., 177 Vitarelli E., 231
Remo A., 220, 325 Sapino A., 100, 147, 162, 220, 221, Tatangelo F., 239, 240, 241 Vitiello A., 137
Resta L., 137, 206, 208, 245, 249, 255 228, 253 Tavani E., 114 Vitolo D., 148
Riboni R., 122 Saponaro C., 220, 227, 237 Tempia Valenta G., 172 Vittoria E., 217
Ribotta M., 135, 205, 260 Sarnelli G.C., 201 Terracciano L., 89, 136 Vocaturo A., 234, 251
Ricci A., 186 Sartore Bianchi A., 232 Terrenato I., 148, 217 Vocaturo G., 251
Ricci D., 271 Sartori M., 192 Testi R., 144 Volinia S., 235
Ricci M., 216 Satarpia L., 228 Tolu G.A., 62, 304 Volpe A., 159
Ricci R., 214 Scacchi C., 157 Tomasi A., 169
Ricco R., 168, 202 Scaffa C., 153 Tommasi S., 226 Wang J., 331
Rider-Stark J., 128 Scaglione, G., 167 Tondat F., 162
Ridha Kamoun M., 73 Scala C., 250 Tonelli F., 213 Zacchi A., 79, 148
Ridolfo A.L., 112 Scala S., 239 Tonello C., 112 Zagami M., 229
Righi A., 259 Scamarcio R., 168 Tonini G., 229 Zagarrigo C., 139
Righi D., 161, 194 Scambia G., 152, 251 Toppino D., 162 Zamboni G., 191, 217
Rinaudo C., 159 Scaramuzzino F., 190, 230 Torelli L., 79, 148 Zamò A., 200
Riotta S., 255 Scarcella S.V., 137, 208 Tornesello M.L., 83 Zamparese R., 169, 184, 229, 243, 245
Rivasi F., 153, 261, 262 Scarpino S., 148 Tornillo L., 91, 136 Zanatta L., 147
Rizzi C., 158 Scatena C., 142 Torrisi A., 186, 259 Zanconati F., 79, 148
Rizzuti T., 53 Schillaci L., 177 Tortorella S., 247, 262 Zandonà L., 148
Rocca B.J., 8, 25, 124, 181, 190, 195, Schillaci O., 142, 182 Tortorici C., 139, 212 Zanellato E., 163, 233
210, 211, 212, 230, 238, 260, 265, Schmidt A., 196 Tosoni A., 214 Zangrandi A., 147
340 Schurfeld K., 124 Tralongo V., 94, 167, 194, 241 Zanin T., 133
Rocco G., 136 Scialpi M., 52 Trapani F., 136 Zaninotto G., 161, 235
Rodella R., 46 Sciarrotta M.G., 155, 158, 203 Trappolini S., 197 Zannoni G.F., 102, 152, 154, 189, 251
Rodolico V., 182 Scibetta N., 145, 199, 210, 241, 251 Treves C., 266 Zanus G., 232
Rollo F., 234, 251 Scimeca M., 159 Trevisan G., 22 Zarrelli N., 249
Romanelli D., 163 Scivetti A., 206 Tricarico F., 166 Zawada L., 214
Romano A., 79, 148 Scognamiglio G., 107, 136, 140, 146, Tricarico N., 177 Zeppa P., 243
Romano M.F., 180 153, 218 Trincheri N.F., 201 Zermani R., 73
Romano S., 180 Scrima M., 110 Triolo R., 215 Zeuzem S., 196
Romeo G., 138 Scuri M., 40 Tripodi S., 190, 210, 211, 212, 230, 265 Zinellu A., 152
Roncalli M., 92 Segala D., 139, 204, 213 Tripodo C., 164, 167, 197 Zito Marino F., 110
Roncella S., 160, 166, 221 Senatore S.A., 234 Trizzino A., 199 Zizzi A., 197
Ronchetti L., 234 Senetta R., 228 Trodella L., 229 Zobbi V., 77
Ronco G., 253 Sentinelli S., 232 Trombatore M., 182, 190, 236 Zolfanelli F., 146
Rosa M., 211 Serra A., 261 Trombetta I., 209 Zorzi M.G., 52, 64, 141, 180, 181, 222,
Rosai J., 182 Serriello I., 211 Troncone G., 125, 145, 173, 189, 190, 258, 279
Rossano V., 151 Servino L., 261 200, 202, 243 Zuccotti G.F., 205, 260
Rossi Degl’Innocenti D., 155 Setta S., 172 Truglia M.C., 228 Zuegel U., 266
Rossi E.D., 81, 152, 154, 189, 251 Sgambato A., 180, 248, 265 Truini M., 166, 221, 307 Zummo G., 145
Rossi G., 109, 136, 157 Sgariglia R., 243 Tuccari G., 187 Zupo S., 307
Rossi R., 137, 208 Siano M., 141, 180, 240, 246, 248
356 Key worDS inDeX
Key words index
2D Barcode technology 313 G O
Gallbladder lymphoma 307 Ovary 19
A Giant cells 68
Adenolipoma 343 P
Adenomatous transformation 346 H Pacinian Corpuscle 4
Adnexal tumour 311 Hamartoma 346 Pathological examination 294
Adrenal 19 Hashimoto’s disease 61 PCR 340
Adrenal gland 46 Hereditary spherocytosis 46 Perineurium 4
Amniotc band syndrome 11 Hidradenoma 311 Peripheral neuroectodermal tumor 43
Apocrine 311 Histogenesis 32 Perisudoral lipoma 343
Autoptic examination 53 Histological report 294 Personnel workload 1
Histopathology laboratory 1 Peutz-Jeghers-type polyp 346
Hodgkin’s disease 43 Pilar leiomyoma 71
B Hyperplasia 304 Post-irradiation sarcoma 43
Biopsy 331 Prenatal diagnosis 53
Bizarre paraosteal chondromatous Primary systemic therapy 294
proliferations (BPOP) 299 I Prostate 40, 50
Breast 68 IGK 14 Protein S100 337
Breast cancer 294, 325 Immunohistochemistry 25, 279, 337
Bronchogenic cyst 19 Incidentaloma 46 R
Intraoperative diagnosis 325 Reactive mesothelium 318
C Renal neoplasms 271
Cancer 331 K Retroperitoneum 19
CD 138 61 Kappa chains 61 Risk management 313
Cervix 331 Kidney 22
Cleft palate 11 K-ras 77
Clinical governance 1 S
Colonic polyp 8 Safety management of patient
Colorectal cancer 77 L specimens 313
Colposcopy 331 Leiomyoma 22 Salivary gland cancer 279
Combined 337 Lip 11 Screening 331
Congenital heart anomalies 53 Lipoma 343 Sebaceous carcinoma 64
Core needle biopsy 325 Lung lobation defects 53 Sebaceous lymphadenoma 32
Cytology 318 Lymphoma 307 Sebaceous neoplasm 64
Second cancer 43
Serous effusion 318
D M Signet ring cell 40
Desmoplastic melanoma 337 Malignant oncocytoma 279 Skin 343
Diagnostic pitfalls 318 Malignant proliferating trichilemmal Skin metastases 50
Differential diagnosis 68, 271 cyst 73 Smooth muscle tumour 71
Diverticular polyps 8 Malignant proliferating trichilemmal Solitary extramedullary plasmacytoma 61
Diverticulosis 8 tumour 73 Stomach 19
Ductal carcinoma 50, 68 Mammography 52 Synovial sarcoma 271
Dysplasia 331 Medical Education 27 SYT/SSX gene fusion 271
Meningoencephalocele 11 T
E Mesothelial 304 Teaching Anatomical Pathology 27
Eccrine glands 343 Mesothelioma 318 Technician 1
Efficiency 1 Mismatch errors 313 Thyroid gland 61
Ewing’s sarcoma 43 Molecular biology 14 Tuberculosis 340
Extracardiac anomalies 53 Multinodular goiter 61 Tumour 22
Extramedullary hematopoiesis 46 Muscle Spindle 4 Tunica vaginalis 304
Extranodal lymphoma 307 Mycobacterium 340
F N Undergraduate curriculum in Medicine 27
Fine needle aspiration biopsy 77 Needle core biopsy 52
Fine needle aspiration cytology 52, 325 Neoadjuvant chemotherapy 294
Foetal echocardiography 53 Nipple 25 V
Frozen sections 325 Nodal marginal zone lymphoma 14 Vulva 337
Nose 11 Vulva cancer 64
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