a case report - Pacini Editore

pathologica 2008;100:1
Ed i t o r i a lE
Nel 2008 la Rivista Pathologica
compie 100 anni di pubblicazione
Durante questo lungo periodo la Rivista ha accompagnato
l’attività dei Patologi italiani fornendo informazioni
scientifiche e contribuendo alla creazione di una
Società Scientifica coesa e molto produttiva quale è la
SIAPEC-IAP.
In corrispondenza di questa importante ricorrenza il
Direttivo della SIAPEC-IAP, raccogliendo la richiesta
di numerosi Soci, ha voluto proporre un rinnovamento
per rilanciare Pathologica a livello nazionale ed internazionale,
introducendo significative modifiche che
consentano un incremento della qualità e la quantità dei
contributi scientifici.
Nell’individuare le innovazioni proposte da Roberto
Fiocca, Direttore Scientifico, e da Marco Chilosi (che
subentrerà nella Direzione Scientifica di Pathologica) si
è tenuto conto delle molteplici aspettative ed esigenze
dei Soci, dell’evoluzione delle tecnologie, del crescente
impatto della Patologia italiana a livello scientifico internazionale
nonché di favorire una maggiore collocazione
“mediterranea” della Rivista.
Le innovazioni comprendono:
Lingua
La Rivista pubblicherà solamente articoli in lingua
inglese. L’attuale opzione “lingua italiana / lingua inglese”
si è dimostrata infatti limitativa sulla quantità
e qualità dei contributi scientifici e sulla loro visibilità
internazionale. La pubblicazione in lingua inglese consentirà
di estendere le aree di affluenza a livello europeo
ed extraeuropeo. Sarà disponibile un servizio di editing,
a carico della Società Scientifica, per incrementare la
qualità dei lavori pubblicati da ricercatori non di madre
lingua inglese.
È prevista comunque la pubblicazione di numeri speciali
(in particolare gli atti di convegni e congressi organizzati
dalla Società) e di inserti di carattere normativo
o prettamente organizzativo in lingua italiana.
Pubblicazione online
La Rivista sarà pubblicata in versione cartacea ed in
versione online, accessibile su PubMed gratuitamente.
Questa innovazione, che ha ricevuto il generoso assenso
del Direttivo SIAPEC-IAP, è un servizio importante
per i lettori di Pathologica, e potrà garantire un’elevata
visibilità internazionale a quanti vorranno pubblicare su
Pathologica.
Segreteria Editoriale
La Segreteria Editoriale sarà riorganizzata centralizzando
presso la Pacini Editore (Pisa) il sistema di ricezione
e revisione dei manoscritti (esclusivamente via internet).
Questa innovazione consentirà di snellire e rendere più
efficaci i processi di revisione e di editing con notevole
ridimensionamento dei tempi di pubblicazione.
Siamo fiduciosi che queste innovazioni saranno apprezzate
dai Soci di SIAPEC-IAP e consentiranno a Pathologica
di affrontare con rinnovata energia le sfide di un
nuovo secolo di attività scientifica.
Roberto Fiocca
Marco Chilosi
Oscar Nappi (past-President)
Gianluigi Taddei (President)

pathologica 2008;100:2
Ed i t o r i a l
In 2008, Pathologica celebrates
its 100 th year of publication
During the last century, the Journal has accompanied
the activity of Italian pathologists, providing scientific
information and contributing substantially to the
creation of a solid and productive scientific society,
the SIAPEC-IAP. In celebration of this milestone, the
directing members of the SIAPEC-IAP, following the
requests of many members, have decided to renew
Pathologica at the national and international level by
significantly modifying both the quality and quantity of
scientific contributions.
The changes proposed by Roberto Fiocca (Scientific
Director) and Marco Chilosi (who will take over as new
Scientific Director) have considered the needs and expectations
of the members of SIAPEC-IAP, continually
evolving technologies and the increasingly important
impact of Italian pathologists at the international level,
in addition to the desire to give the journal a more Mediterranean
viewpoint.
The innovations include:
Language
Pathologica will be published exclusively in English.
The current option of English or Italian poses limits on
the quality and quantity of scientific contributions, and
international visibility. The publication of all articles in
English will allow more ample diffusion on a European
and extra-European level. All contributions will now
be copyedited in order to improve the overall quality of
publications submitted by non-native English speakers.
Nonetheless, special issues (e.g. abstract books from
meetings and congresses organised by the SIAPEC-
IAP), normatives and organisational material will continue
to be published in Italian.
Publication online
While the Journal will continue to be published in a printed
version, it will also be offered online and can be accessed
freely through PubMed. This advance was openly
welcomed by the directing members of the SIAPEC-IAP,
and is viewed as an important service for our readership.
It will also guarantee more international visibility for
those considering publication in Pathologica.
Publisher
Publishing will be reorganised using Pacini Editore,
located in Pisa, and manuscripts will be submitted and
revised exclusively via Internet. This innovation will
considerably increase the efficiency of all phases of
the publication process, and will considerably reduce
publication times.
We are confident that these changes will be greatly appreciated
by all members of the SIAPEC-IAP, which
will allow Pathologica to face the scientific challenges
of the next 100 years with renewed energy.
Roberto Fiocca
Marco Chilosi
Oscar Nappi (past-President)
Gianluigi Taddei (President)

PATHOLOGICA 2008;100:3-5
EDITORIAL
Genomic pathology for genomic biology
Patologia genomica per biologia genomica
R.D. CARDIFF
Center for Comparative Medicine and Department of Pathology and Laboratory Medicine, University of California, Davis CA
Tremendous advances in our understanding of the mammalian
genome have led to new enthusiasm for molecular-based
medicine. Indeed, genomic biology is now the
driving force in health sciences and medical research,
and meetings are convened to discuss the topic of
“Genomic Medicine”. New Institutes and Centers have
proliferated to take advantage of the technology. But,
in their euphoria, have the new “genomic biologists”
forgotten pathology, the study of disease? Or, has pathology
forgotten them? More cynically, do molecular
biologists truly believe that their technology can replace
the pathologist with machines? In their ignorance, their
technology is underserved.
Is this “disconnect” based on arrogance or ignorance?
The ignorance is evident in the current enthusiasm for
creating more mutant mice. The animal houses in Universities
are already overflowing with mice 1 . Now, a
new international consortium is intent on knocking out
the entire mouse genome, thus creating, gene by gene,
thousands of new mutant mouse strains. This program
is certain to establish the experimental mouse resources
that can potentially form the basis for understanding the
genetic and molecular biology of disease. Enthusiastic
planners, in some countries, indicate that they are prepared
to study the diseases in these mice. The question is
whether pathology is prepared for Genomic Biology 2 ?
Genome-based biology, founded initially on the mouse
and eventually on humans, will require comparative pathologists
who can recognize the gross and microscopic
patterns of disease in both species and who can integrate
the disease patterns with the genomic changes 2 . In the
past, comparative pathologists have served as the gatekeepers
of disease models, validating the similarity to,
or divergence from, human diseases. Now they will be
asked to recognize the sometimes subtle histopathological
variations related to minor changes in the genome.
Historically, the ancients recognized no difference
between healing animals or man and most “healers”
treated both 3 . Later, interested observers frequently
Acknowledgments
The Author appreciates the numerous suggestions and editorial
comments from the members of the Academy of Genomic Pathology
that served as the foundation for this essay.
used animals for experimental observation of anatomy,
physiology and pathology. When unable to dissect human
cadavers, they resorted to animals, leading to numerous
erroneous assumptions about human anatomy.
Two examples are the bicornuate uterus of the cow
and the spiral intestine of the pig, both of which are
frequently found in medieval depictions of human anatomy.
In fact, it has been said that veterinary medicine
was based on observation and facts during eras when
human medicine was based on theory and incantations.
With high economic and sometimes spiritual value, animals
were the leading resource for the study of biology
and pathology.
Modern comparative pathology originated with Rudolph
Virchow, the “Founder of Modern Pathology”,
who stated that “there is little difference” between diseases
in animals and in man 2 . The theme was taken up
by William Osler, the “Founder of Modern Medicine”,
who started a Veterinary College at McGill and is given
credit for coining the term “one medicine”. Interestingly,
Osler is also considered by many as the “Founder
of Veterinary Pathology”. Sadly, we lost the enthusiasm
exhibited by our predecessors.
Regrettably, the disciplines of medical and veterinary
pathology have drifted apart, leaving the field of comparative
pathology to a dedicated few. As documented
elsewhere, neither group of pathologists is training
protégées for the modern form of comparative pathology,
Genomic Pathology 2 . This form of pathology
requires an appreciation of the effects of molecular
changes on the pathobiology of the individual. In some
countries, veterinary pathologists are almost extinct.
Pathology training in veterinary medicine emphasizes
exotic and domestic animals. Laboratory animal training
is targeted to assist in board certification. While in high
demand in industry, the majority of veterinary pathologists
are reduced to mind-numbing, high throughput
toxicological screening in the business environment.
Pathology training in human medicine also emphasizes
Correspondence
R.D. Cardiff, Center for Comparative Medicine and Department
of Pathology and Laboratory Medicine, University of California,
Davis, CA 95616 USA - E-mail: rdcardiff@ucdavis.edu

4
high-throughput diagnosis that merely demands pattern
recognition, leaving little time for the appreciation of
the natural history or molecular biology of disease. Very
few medical training programs offer exposure to veterinary
pathologists or to animal diseases. The same can be
said of veterinary programs.
The development of genetic engineering in the mouse
has created an opportunity to test molecular-based
hypotheses on living mammals 2 . The study of these
animals is critical to achieving progress in human medicine.
Investigators now can control the mouse genome
by targeting, inserting or deleting specific genes, and
even controlling the temporal expression of genes. As a
result, the mouse has become the surrogate for human
disease. The optimism of current knock-out projects is
based on these genetically manipulated mice. The proposed
programs offer to knock-out the entire mouse genome,
ultimately creating between 10,000 and 200,000
new strains of mice.
Therefore, genetic manipulation targeting rodents now
enters the mix. Scientists can test their favorite molecule
in the context of a living mammal. They can separate
and isolate variables experimentally. They can study the
natural history of the disease from origin to the ultimate
consequence. Genomic biologists truly need the pathologists
they previously ignored. Workforce studies in the
United States and Europe have documented a shortage
of qualified, experienced mouse pathologists 1 2 (http://
www.prime-eu.org/D02). The question is: Who is going
to identify, classify and study the genome-based
diseases in the new generations of mice 1 2 4 ?
Our lack of preparation in pathology, unfortunately, has
left the majority of North American and European research
scientists without comparative pathologists who
are qualified to examine the diseases in their molecularly-manipulated
mice. This shortage has led to what has
been, somewhat sarcastically, called “Do-it-Yourself”
pathology 2 , performed by untrained and under-trained
investigators with little access to widely dispersed and
qualified pathologists. Do-it-Yourself pathology has led
to the publication of a number of serious errors. Normal
organs such as nipples and preputial glands have been described
as neoplasms. Neuroendocrine tumors have been
misdiagnosed as adenocarcinomas. Misuse of terminology
by well-intended but inexperienced investigators has
become another problem 2 5 6 . Unfortunately, the already
lengthy list of published errors continues to grow.
As a result of the genomic revolution, we are entering
an exciting period where comparative, Genomic
Pathologists will be in great demand. Imagine the exciting
opportunities when every slide examined reveals
pathologic phenomena never previously observed. Examples
from our own cases involve the recognition that
different genes cause different and unique microscopic
mammary tumor phenotypes in genetically engineered
R.D. CARDIFF
mice (GEM) 7-9 . These GEM tumors are unique and
quite different from the spontaneous tumors observed in
mammary tumor virus-infected mice. The identification
of unique genotype-specific “signature” phenotypes was
reinforced by the observation that tumors resulting from
activations of whole pathways could share one or more
phenotypic features. The concepts in mammary gland
pathology are applicable to tumors in other organs 7 .
Some mice develop tumors that are exact histological
phenocopies of human cancer. The unique genotyperelated
phenotypes observed in mice will soon be the
basis for modern pathology. These genotype-phenotype
correlations are the basis for Genomic Pathology.
What is the pathology of the future? The new pathology
will require integration of evidence from diverse
“-omic” sources with the natural history of disease and
the microscopic changes. The various “-omics” are subheadings
under the general heading of genomics 10 . The
next generation of pathologists will need to understand
how genes and their products affect the disease processes.
They will be the Genomic Pathologists.
However, experienced genomic pathologists are so
widely dispersed that our medical and veterinary training
programs lack faculty capable of teaching the subject
matter. Without rapid identification and deployment
of the available resources, the current scientific community
will continue to be subject to serious errors. The
pathological conditions of the numerous new mouse
strains will continue to be misinterpreted and chaos
shall reign.
How can the current generation of pathologists prepare
itself and the next generation of pathologists? Modern
dilemmas require modern solutions. We have proposed
that those interested and qualified genomic pathologists
join together in an International Academy of Genomic
Pathology 1 2 . Such a group will become a society of
like-minded people who will share experiences and
teach each other the nuances of our discipline. The
group can be geographically dispersed but remain connected
through the modern marvel of communications,
the Internet. Existing technology permits whole slide
imaging that can be placed on the Internet to be shared
and annotated. Since whole slide images can be viewed
at any magnification anywhere on the slide, they are like
meeting with your friends, colleagues and students over
a multi-headed microscope.
Further, the gathering of people with mutual interests represents
an educational opportunity for the next generation.
If we can meet and discuss cases, certainly our students can
do likewise. The Academy of Genomic Pathology can become
the faculty of an international university that teaches
the principles of our discipline. We invite like-minded
pathologists to join us in sharing experiences and opinions.
We invite the yet unskilled to attend our courses to learn
from the very best. It will be a great adventure.

GENOMIC PATHOLOGY FOR GENOMIC BIOLOGY
References
1 Barthold SW, Borowsky AD, Brayton C. From whence will they
come? – A perspective on the acute shortage of pathologists in
biomedical research. J Vet Diagn Invest 2007;19:455-6.
2 Cardiff RD, Ward JM, Barthold SW. One medicine-One pathology:
Are veterinary and medical pathology prepared? Lab Invest
2008 (in press).
3 Schwabe CW. Cattle, priests, and progress in medicine. Minneapolis:
Univ of Minnesota Press 1978.
4 Cardiff RD. Pathologists needed to cope with mutant mice. Nature
2007;447:528.
5 Cardiff RD, Rosner A, Hogarth MA, Galvez JJ, Borowsky AD,
Gregg JP. Validation: the new challenge for pathology. Toxicol
Pathol 2004;32(Suppl 1):31-9.
6 Lensch MW, Ince TA. The terminology of teratocarcinomas and
teratomas. Nat Biotechnol 2007;25:1211.
7 Cardiff RD, Munn RJ, Galvez JJ. The tumor pathology of genetically
engineered mice: a new approach to molecular pathology.
In: Fox JG, Davisson MT, Quimby FW, Barthold SW, Newcomer
CE, Smith AL, eds. The mouse in biomedical research: experimental
biology and oncology. Second Ed. New York: Elsevier, Inc
2006, p. 581-622.
8 Cardiff RD, Sinn E, Muller W, Leder P. Transgenic oncogene
mice. Tumor phenotype predicts genotype. Am J Pathol
1991;139:495-501.
9 Rosner A, Miyoshi K, Landesman-Bollag E, Xu X, Seldin DC,
Moser AR, et al. Pathway pathology: histological differences
between ErbB/Ras and Wnt pathway transgenic mammary tumors.
Am J Pathol 2002;161:1087-97.
10 Barthold SW. “Muromics”: genomics from the perspective of the
laboratory mouse. Comp Med 2002;52:206-23.
5

PATHOLOGICA 2008;100:6-8
CASE REPORT
Smooth muscle differentiation in ovarian
granulosa-cell tumours: a new case report
Differenziazione del muscolo liscio in tumori ovarici a cellule della granulosa:
un nuovo caso clinico
Introduction
I. ABBES, K. MRAD, M. DRISS, S. SASSI, R. DHOUIB, K. BEN ROMDHANE
Department of Cytology and Surgical Pathology, Salah Azaiez Institute, Bab Saadoun, 1006 Tunis, Tunisia
Various types of metaplasia have been demonstrated
within normal and hyperplastic ovarian stroma as well
as in ovarian tumours, including osseous, fat, decidual
and smooth muscle metaplasia 1 . Muscle fibres have been
identified on ultrastructural examination within the normal
theca externa of the follicles and cortical stroma 2-4 .
Smooth muscle differentiation has been also described in
some ovarian tumours such as granulosa-cell tumours of
both juvenile and adult types 3 4 . This type of metaplasia
is often under-recognized and has been described only
rarely. Its frequency has been estimated to be around 1.5
among all ovarian metaplasia 4 .
Case report
Key words
Granulosa-cell tumor • Smooth muscle metaplasia • Ovary
Summary
Smooth muscle differentiation in stromal ovarian tissue has rarely
been described in normal and tumoural ovaries, especially in
granulosa-cell tumours.
A moderately differentiated adult granulosa-cell tumour in an 83year-old-woman
is reported. Tumoural stroma included clusters
of regular smooth muscle cells stained positively for smooth
muscle actin.
The presence of smooth muscle differentiation in an ovarian
granulosa-cell tumour should be taken into consideration during
diagnosis.
An 83-year-old woman presented with a 1-year history
of a painful latero-uterine mass. Ultrasonographic examination
revealed the presence of abundant acites associated
with a heterogeneous right ovarian tumour pre-
Parole chiave
Tumore a cellule della granulosa • Metaplasia del muscolo liscio •
Ovaio
Riassunto
Raramente è stato descritto muscolo liscio differenziato in tessuto
ovarico stromale di ovaie normali o tumorali, specialmente
nei tumori a cellule della granulosa.
Riportiamo il caso di un tumore a cellule della granulosa
dell’adulto in una donna di 83 anni. Lo stroma del tumore conteneva
grappoli di cellule proprie del muscolo liscio positivamente
colorate per l’actina del muscolo liscio.
Durante la diagnosi sarebbe da tenere in considerazione la
presenza di muscolo liscio differenziato in un tumore ovarico a
cellule della granulosa.
senting both solid and cystic components. The patient
underwent hysterectomy and died immediately after
intervention due to a pulmonary vascular embolism.
Gross examination of the surgical specimen revealed an
encapsulated ovarian tumour measuring 30 x 15 x 13
cm with a smooth and lobulated surface. Its sectioned
surface was yellow to tan with an admixture of cystic
and solid hemorrhagic areas.
The contralateral ovary and the 2 fallopian tubes were
macroscopically normal.
Microscopically, there was an ovarian tumoural proliferation
arranged into cords and trabeculae in a background
of cellular stroma (Fig. 1). The tumoural cells presented
a scant cytoplasm and a round to ovoid nucleus with fine
chromatin and a longitudinal groove. Mitotic activity
was estimated at 5 per 10 high power fields. Tumoural
stroma included long fascicles of spindled cells with
eosinophilic cytoplasm and elongated nuclei with cigarshaped
ends (Fig. 2). These cells were immunoreactive
for smooth muscle actin (Fig. 3).
The contralateral ovary and the 2 fallopian tubes were
free of tumoural invasion.
Correspondence
Dr Imen Abbes, Department of Cytology and Surgical Pathology,
Salah Azaiez Institute, Bab Saadoun, 1006 Tunis, Tunisia
- Tel. +216 22 589364 - Fax +216 71 571380 - E-mail: imen.
abbes@rns.tn

SMOOTH MUSCLE DIFFERENTIATION IN OVARIAN GRANULOSA-CELL TUMOURS
Fig. 1. Tumoural proliferation arranged into cords and trabeculae
in a background of cellular stroma (haematoxylin and eosin, x 40).
Fig. 2. Clusters of smooth muscle cells within stroma (haematoxylin
and eosin, x 400).
Fig. 3. Spindle cells stained with antibodies against smooth muscle
actin (visualisation with 3,3’-Diaminobenzidine, x 400).
Discussion
This case highlights the possible existence of stromal
smooth muscle differentiation within a granulosa-cell
tumour, which may cause diagnostic difficulties. In fact,
due to a biphasic cellular pattern, granulosa-cell tumours
may be misdiagnosed as carcinosarcoma, poorly differentiated
carcinoma or Sertoli-Leydig cell tumours.
The presence of stromal smooth muscle actin immunostaining
favours a diagnosis of granulosa-cell tumour
over that of Sertoli-Leydig cell tumour.
Furthermore, in contrast to both carcinosarcoma and
poorly differentiated carcinoma, granulosa-cell tumours
do not show cyto-nuclear atypia, and the tumour cells
are often immunoreactive for inhibin 5-10 .
It should be pointed out that a wide variety of primary
and metastatic ovarian tumours may contain significant
numbers of positively staining luteinized cells for inhibin
8 . Accordingly, careful examination should be made
in the interpretation of inhibin positive cells.
Smooth muscle differentiation was originally described
using light microscopy in normal ovarian stroma 2 11 .
More recently, it has been confirmed by ultrastructural
and immunohistochemical analyses 3 12 . Smooth muscle
fibres are reportedly located in the theca externa of
secondary follicles and in deep cortical stroma, theoretically
accounting for the contractile properties of perifollicular
ovarian stroma 3-5 .
On the other hand, the absence of smooth muscle actin
in the normal outer ovarian cortex and theca interna,
as well as in stromal hyperplasia, suggests that sex
hormones may have no role in the genesis of smooth
muscle metaplasia 2 .
Doss et al. 4 reported that smooth muscle metaplasia
may occur as a response to the presence of a coexistent
physiologic or pathologic process. Pathologic ovarian
lesions include ovarian endometriosis, hyperthecosis,
massive ovarian oedema, mucinous cystadenomas, thecomas,
Brenner tumours and granulosa-cell tumour of
both juvenile and adult types 3 4 .
In conclusion, the present case report draws attention
to the pitfalls encountered in histological diagnosis of
granulosa-cell tumours due to the possible existence of
stromal smooth muscle differentiation.
7

8
References
1 Kurman RJ. Blaustein’s pathology of the female genital tract. New
York: Springer 2001.
2 Okamura H, Virutamasen P, Wright KH, Wallach EE. Ovarian
smooth muscle in the human being, rabbit and cat. Am J Obstet
Gynecol 1972;112:183-91.
3 Santini D, Ceccareli C, Leone O, Pasquinelli G, Piane S, Marabini
A, et al. Smooth muscle differentiation in normal human ovaries,
ovarian stromal hyperplasia and ovarian granulosa-stromal cells
tumors. Mod Pathol 1995;8:25-30.
4 Doss BJ, Wanek SM, Jacques SM, Qurashi F, Ramirez NC,
Lawrence WD. Ovarian smooth muscle metaplasia: an uncommon
and possibly under recognized entity. Int J Gynecol Pathol
1999;18:58-62.
5 Costa MJ, De Rose PB, Roth LM, Brescia RJ, Zaloudek CJ, Cohen
C. Immunohistochemical phenotype of ovarian granulosa cell
tumors: absence of epithelial membrane antigen has diagnostic
value. Hum Pathol 1994;25:60-6.
6 Rishi M, Howard LN, Bratthauer GL, Tavassoli FA. Use of monoclonal
antibody against human inhibin as a marker for sex cordstromal
tumors of the ovary. Am J Surg Pathol 1997;21:583-9.
I. ABBES ET AL.
7 Aguirre P, Thor AD, Scully RE. Ovarian endometrioid carcinoma
resembling sex cord-stromal tumors. An immunohistochemical
study. Int J Gynecol Pathol 1989;8:364-73.
8 Hldebrandt RH, Rouse DV, Longacre TA. Value of inhibin in the
identification of granulosa cell tumors of the ovary. Hum Pathol
1997;28:1387-95.
9 Costa MJ, Ames PF, Walls J, Roth LM. Inhibin immunohistochemistry
applied to ovarian neoplasms: a novel, effective, diagnostic
tool. Hum Pathol 1997;28:1247-54.
10 Otis CN, Powell JL, Barbuto D, Carcangiu ML. Intermediate filamentous
proteins in adult granulosa cell tumors. An immunohistochemical
study of 25 cases. Am J Surg Pathol 1992;16:962-8.
11 Czernobilsky B, Moll R, Levy R, Franke WW. Co-expression
of cytokeratin and vimentin filaments in mesothelial, granulosa
and rete ovarii cells of the human ovary. Eur J Cell Biol
1985;37:175-90.
12 Czernobilsky B, Shezen E, Lifschitz-Mercer B, Fogel M, Luzon
A, Jacob N, et al. Alpha smooth muscle actin (α SM actin) in normal
human ovaries, in ovarian stromal hyperplasia and in ovarian
neoplasms. Virch Archiv B Cell Pathol 1989;57:55-61.

PATHOLOGICA 2008;100:9-12
CASO CLINICO
Carcinoma squamoso in situ insorto su teratoma cistico
maturo ovarico
Squamous cell carcinoma in situ arising in ovarian mature cystic teratoma
A. GURRERA, F. BRANCATO, L. PUZZO, G. MAGRO, P. GRECO
Dip. “G.F. Ingrassia”, Anatomia Patologica, Azienda Ospedaliera-Universitaria Policlinico “G. Rodolico”, Catania
Parole chiave
Carcinoma squamoso • In situ • Teratoma cistico maturo
Riassunto
Il teratoma cistico maturo è una neoplasia quasi sempre benigna,
ma nel 2% dei casi può andare incontro a degenerazione maligna
di una delle sue componenti. Sebbene vari tipi di carcinoma
possono insorgere nel contesto di un teratoma maturo, la trasformazione
maligna interessa più frequentemente, nell’80% dei
casi, la componente squamosa con l’insorgenza di un carcinoma
squamoso invasivo. Nonostante l’alta incidenza di carcinoma
squamoso, sorprendentemente, il riscontro di carcinoma squamoso
in situ è eccezionale; solo rari casi sono riportati in letteratura.
Descriviamo un caso di carcinoma squamoso in situ insorto su di
un teratoma cistico maturo senza componente invasiva.
Introduzione
Il teratoma cistico maturo o cisti dermoide, caratterizzato
dalla predominanza di tessuto maturo di derivazione
ectodermica, è la forma più comune di teratoma ovarico
e rappresenta circa il 20% di tutte le neoplasie ovariche.
È quasi sempre benigno, ma nel 2% dei casi si può
riscontrare la trasformazione maligna di una delle sue
componenti. La frequenza di degenerazione maligna aumenta
con l’età con una media dell’1,8%. In questi casi
la prognosi dipende dallo stadio ed è scarsa nei casi estesi
oltre l’ovaio. La componente che più frequentemente
va incontro a degenerazione, in circa l’80% dei casi, è
quella squamosa con l’insorgenza di un carcinoma squamoso
invasivo, mentre solo raramente è stato riportato
in letteratura il carcinoma squamoso in situ. Tuttavia, altri
tumori possono insorgere nel contesto di un teratoma
cistico maturo: carcinoidi, carcinoma indifferenziato a
piccole cellule, carcinomi tiroidei, carcinomi basocellulari,
carcinomi annessiali, vari tipi di adenocarcinoma,
eventualmente associati alla componente squamosa
Key words
Squamous cell carcinoma • In situ • Mature cystic teratoma
Summary
Mature cystic teratoma is a benign neoplasm, but malignant
transformation of one component may occur in 2% of cases.
Although very different types of carcinomas may be arise from
mature cystic teratoma, invasive squamous cell carcinoma is the
most frequent type of malignancy found, comprising about 80%
of all malignancies arising from dermoid tumours. Although
invasive squamous cell carcinoma is relatively frequent, it is
surprising that so few cases of squamous cell carcinoma in situ
in mature cystic teratoma have been reported. We describe a case
of squamous cell carcinoma in mature cystic teratoma without
an invasive component.
(carcinomi adeno-squamosi), carcinomi mucoepidermoidi,
melanomi e vari tipi di sarcomi, leiomiosarcomi,
condrosarcomi e angiosarcomi.
Viene descritto un caso di carcinoma squamoso in situ
insorto su cisti dermoide dell’ovaio.
Caso clinico
Una donna di 48 anni presentava una tumefazione pelvica,
in sede annessiale destra che all’esame TC appariva
ipodensa, delle dimensioni di circa 20 cm. Fu eseguita
una istero-annessiectomia bilaterale.
ESAME MACROSCOPICO
L’esame macroscopico evidenziava nell’ovaio destro
una neoformazione cistica delle dimensioni di 20 x 17 x
12 cm a superficie esterna liscia e regolare con reticolo
vascolare evidente; al taglio era presente abbondante
materiale pilo-sebaceo; la superficie interna non mostrava
aree nodulari protrudenti in cavità e appariva in
Corrispondenza
Dott.ssa Alessandra Gurrera, Dip. “G.F. Ingrassia”, Anatomia
Patologica, Azienda Ospedaliera-Universitaria Policlinico “G.
Rodolico”, via S. Sofia 87, 95123 Catania, Italia - Tel. +39 095
3782030 - Fax +39 095 3782023 - E-mail: gurrera@policlinico.
unict.it

10
gran parte liscia e regolare, ad eccezione di un’area di
circa 5 cm che si presentava irregolare e ricoperta da
fini granulazioni; nella spessore della parete era incuneato
un abbozzo dentale. Nulla da rilevare nell’ovaio
sinistro. L’utero presentava tre leiomiomi, intramurali e
sottosierosi, endometrio lievemente ispessito; la cervice
non mostrava lesioni macroscopicamente evidenti.
ESAME MICROSCOPICO
L’esame istologico rivelava un teratoma cistico maturo
monodermico costituito esclusivamente da componente
ectodermica (cisti dermoide) nell’ovaio destro. La cisti
era rivestita da epitelio squamoso cheratinizzante con
riconoscibili strutture annessiali pilosebacee; l’area
irregolare descritta macroscopicamente appariva disepitelizzata
e sostituita da flogosi cronica granulomatosa
con istiociti e cellule giganti plurinucleate tipo corpo
estraneo frammiste a strutture pilari, nel cui contesto
si riconosceva epitelio cheratinizzante residuo (Fig. 1).
Nel contesto della flogosi granulomatosa, come reperto
inusuale, si reperiva un focolaio di circa 1 cm di carcinoma
squamoso in situ (Fig. 2) caratterizzato da disor-
Fig. 1. Teratoma cistico rivestito da epitelio squamoso cheratinizzante
maturo alternato ad aree disepitelizzate rivestite da flogosi
granulomatosa.
Fig. 2. Focolaio di carcinoma squamoso in situ nel contesto di
flogosi granulomatosa.
A. GURRERA ET AL.
dine cito-architetturale con stratificazione dell’epitelio,
atipie cito-nucleari e mitosi (Figg. 3A e 3B). Un esteso
ricampionamento dell’area nodulare non evidenziava
altre aree di carcinoma squamoso in situ, né alcuna
componente invasiva. Non era presente inoltre alcuna
componente epiteliale cilindrica, né mesodermica. Non
si evidenziava alcun focolaio di endometriosi. L’utero
presentava leiomiomi, iperplasia ghiandolare complessa
atipica dell’endometrio e cervicite cronica cistica
papillare.
IMMUNOISTOCHIMICA
Sulle sezioni del carcinoma squamoso in situ venivano
effettuate indagini immunoistochimiche per la determinazione
delle citocheratine 10 e 18 e per la proteina
p16 per dimostrare l’eventuale origine dal rivestimento
epidermico o da aree di metaplasia della lesione; queste
davano esito negativo.
Discussione
La maggior parte dei carcinomi squamosi primitivi
dell’ovaio insorge nel contesto di una cisti dermoide,
presentandosi generalmente sottoforma di un nodulo
intramurale che protrude all’interno della cavità cistica,
talvolta associato ad aree di emorragia o necrosi, o come
ispessimento della parete, raramente come aree a superficie
irregolare. I rimanenti o insorgono nel contesto di
endometriosi per trasformazione neoplastica squamosa
della componente endometrioide, o nel contesto di un
tumore di Brenner oppure fanno parte di un tumore
misto mesodermico. Esistono infine dei rari carcinomi
squamosi che si presentano in forma pura; l’istogenesi
di quest’ultimo gruppo è poco chiara.
La degenerazione maligna di un teratoma cistico maturo
è rara, potendosi verificare nel 2% dei casi 1 2 . Fattori di
rischio includono l’età (> 45 anni), le dimensioni (> 10
cm) ed elevati livelli di SCC-antigene (> 2,5 ng/mL).
Sebbene vari tipi di carcinoma possono insorgere in una
cisti dermoide, quali vari tipi di adenocarcinoma, derivati
sia dall’epitelio bronchiale che gastro-intestinale,
carcinoidi, carcinoma indifferenziato a piccole cellule,
carcinomi tiroidei, carcinomi basocellulari, carcinomi
annessiali, carcinomi mucoepidermoidi, melanomi 3 e
vari tipi di sarcomi, leiomiosarcomi, condrosarcomi e
angiosarcomi, la componente che più frequentemente
va incontro a degenerazione maligna, in circa l’80% dei
casi, è quella squamosa con l’insorgenza di un carcinoma
squamoso invasivo; in letteratura ne sono descritti
diversi casi 4 5 . Istologicamente possono presentare diversi
pattern: papillare o polipoide, cistico con aree di
necrosi, talvolta di tipo comedonico, verrucoso, infiltrativo,
insulare e sarcomatoide. Talvolta, la componente
squamosa può essere frammista ad elementi ghiandolari
con aspetti di carcinoma adenosquamoso. La prognosi
del carcinoma squamoso invasivo insorto su cisti dermoide
dipende dallo stadio con una sopravvivenza a
5 anni del 50%, 25%, 12% e 0% rispettivamente negli

CARCINOMA SQUAMOSO IN SITU INSORTO SU TERATOMA CISTICO MATURO OVARICO
Fig. 3. (A) Carcinoma in situ, con stratificazione dell’epitelio, atipie cito-nucleari e mitosi (B).
A B
stadi I, II, III e IV; altri fattori prognostici includono il
grading tumorale, il pattern di crescita, la rottura capsulare
e l’invasione vascolare 5 .
Nonostante il carcinoma squamoso invasivo sia la forma
di tumore maligno più frequentemente riscontrato
nel contesto di cisti dermoide 1 2 , il carcinoma squamoso
in situ, sia puro che associato alla componente invasiva
6 7 , è raro; in letteratura sono descritti solo 11 casi
di carcinoma squamoso in situ puro 8-15 (Tab. I); in due
di questi casi è stata anche segnalata l’associazione con
un adenocarcinoma endometrioide 11 14 , ma tale reperto
sembra essere occasionale; in un altro, è stata riportata
una associazione con un leiomiosarcoma 12 . Nel caso
da noi descritto era presente una iperplasia complessa
atipica dell’endometrio.
Per spiegare la bassa incidenza del carcinoma squamoso
in situ su teratoma cistico maturo si può ipotizzare
che o il carcinoma invasivo si sviluppa indipendentemente
da lesioni precursori o la sua bassa incidenza
è solo espressione di un insufficiente campionamento
della lesione.
In letteratura non esistono dati che spiegherebbero
l’eventuale differenza biologica tra il carcinoma
squamoso insorto in un teratoma cistico maturo
e quello insorto in altre sedi, compresa la cervice
uterina, pertanto, la sua origine è da attribuire, ed è
preceduta da aree di displasia e di carcinoma in situ
insorte dal rivestimento epidermico 4 14 , che può essere
di tipo maturo e immaturo 16 , o più frequentemente
da aree di metaplasia dell’epitelio colonnare, ciliato
e non 14 17 18 . La prima ipotesi sarebbe supportata dal
riscontro di aree di carcinoma in situ in continuità
con l’epitelio epidermico, anche se nei casi descritti
in letteratura aree di transizione sono descritte solo
raramente 4 14 , e dalla positività immunoistochimica
per la citocheratina 10. L’origine dall’epitelio metaplasico
può essere invece dimostrata dal riscontro di
epitelio colonnare residuo e dalla positività immunoistochimica
per la citocheratina 18 18 ; alcuni studi
11
hanno però evidenziato che solo la componente invasiva
esprime la positività per la citocheratina, mentre
le lesioni displastiche/in situ risultano negative 18 .
Inoltre, studi di citometria a flusso hanno dimostrato
che il carcinoma squamoso in situ insorto su di un
teratoma cistico maturo presenta una perdita della
aneuploidia analoga a quella delle lesioni displastiche
di altro grado e dei carcinomi in situ della cervice,
confermando, quindi, la loro analogia 11 . Nel caso da
noi descritto il carcinoma in situ appariva separato
Tab. I. Carcinoma squamoso in situ in teratoma cistico maturo.
Anno Autori N. casi Carcinoma
in situ
Comp.
invasiva
1956 Peterson 2 * *
1958 Marcial 1 *
1972 Klionsky
et al.
1
1983 Maeyama 1 * *
1989 Peuchmaur
et al.
1991 Tobon et al. 1 *
1993 Tyagi et al. 1 *
1994 Kuwashima
et al.
1995 Fujiit et al. 1 *
1996 Pins et al. 3 *
2002 Dadhval
et al.
2007 Gurrera
et al.
1
1
1
1
*
*
*
*
*

12
dall’epidermide circostante senza aree di transizione,
alternato a tessuto granulomatoso, morfologicamente
ricordava il carcinoma squamoso insorto su epitelio
metaplasico, ma non era presente epitelio cilindrico
residuo; inoltre le colorazioni immunoistochimiche
per le citocheratine 10 e 18 risultavano negative. Non
era possibile pertanto dimostrare con certezza l’origine
della neoplasia.
Conclusioni
Considerando che la storia naturale del carcinoma
squamoso insorto su cisti dermoide è simile a quella
Bibliografia
1 Scully RE, Young RH, Clement PB. Atlas of Tumor Pathology
Third Series. Tumors of the ovary, maldeveloped gonads, falloppian
tube, and broad ligament. Washington: American Registry of
Pathology 1996.
2 Nogales F, Talerman A, Kubik-Huch RA, Tavassoli FA, Devouassoux-Shisheboran
M. Germ cell Tumours. In: Tavassoli FA,
Devilee P, eds. Pathology and Genetics. Tumors of the breast and
female organs. Lyon: IARC Press 2000, p. 163-79.
3 Davis GL. Malignant melanoma arising in mature cystic teratoma
(dermoid cyst). Report of two cases and literature analysis. Int J
Gynecol Pathol 1996;15:356-62.
4 Tangjitgamol S, Manusirivithaya S, Sheanakul C, Leelahakorn
S, Thawaramara T, Jesadapatarakul S. Squamous cell carcinoma
arising from dermoid cyst: case reports and review of literature.
Int J Gynecol Cancer 2003;13:558-63.
5 Dos Santos L, Mok E, Iasonos A, Park K, Soslow R, Aghajanian
C, et al. Squamous cell carcinoma arising in mature cystic
teratoma of the ovary: A case series and review of the literature.
Ginecologic Oncol 2007; (in press).
6 Peterson WF, et al. Epidermoid carcinoma arising in a benign
cystic teratoma: report of 15 cases. Am J Obstet Ginec
1956;71:173-89.
7 Maeyama M, Miyazaki K, Oka M, Higashi K, Nakayama M,
Iwamasa T. Malignant degeneration of benign cystic teratoma
of the bilateral avaries: adenosquamous carcinoma in the right
tumor and squamous carcinoma in the left tumor. Nippon Sanka
Fujinka Gakkai Zasshi 1983;35:331-4.
8 Marcial-Rojas RA, Medina R. Cystic teratomas of the ovary. A
clinical and pathological analysis of 268 tumors. Arch Pathol
1958;66:577-89.
9 Klionsky BL, Nickens OJ, Amortegui AJ. Squamous cell carcinoma
in situ arising in adult cystic teratoma of the ovary. Arch
Path 1972;93:161-3.
A. GURRERA ET AL.
dei carcinomi squamosi insorti in altra sede, la forma
invasiva è verosimilmente preceduta da lesioni displastiche
e da carcinoma in situ; probabilmente, la bassa
incidenza del carcinoma squamoso in situ su teratoma
cistico maturo è da attribuire al fatto che questa lesione
spesso possa sfuggire ad una osservazione macroscopica
e che solo un campionamento esteso e meticoloso
possa svelarla. Nel caso da noi descritto, non era presente
alcuna lesione nodulare, o aree di ispessimento
della parete, ma solo un’area di disepitelizzazione della
parete cistica; istologicamente, il focolaio di carcinoma
squamoso in situ veniva riscontrato frammisto a tessuto
granulomatoso e svelato con un campionamento esteso
della lesione.
10 Peuchmaur M, Reynes M. Squamous cell carcinoma in situ
developing in dermoid cyst of the ovary: report of a case with
laminin immunohistochemical staining demonstrating basement
membrane integrity. Pathol Res Pract 1989;185:251-4.
11 Tobon H, Surti U, Naus GJ, Hoffner L, Hemphill RW. Squamous
cell carcinoma in situ arising in an ovarian mature cystic
teratoma. Report of one case with histopathologic, cytogenetic,
and flow cytometric DNA content analysis. Arch Pathol Lab Med
1991;115:172-4.
12 Tyagi SP, Maheshwari V, Tyagi N, Tewari K. Double malignancy
in a benign cystic teratoma of the ovary (a case report). Indian J
Cancer 1993;30:140-2.
13 Kuwashima Y, Uehara T, Kishi K, Nishimura T, Shiromizu K,
Matsuzawa M, et al. Malignant squamous cell elements in the
ovarian cancer: report of 5 cases and review of the literature. In
vivo 1994;8:1063-6.
14 Pins MR, Young RH, Daly WJ, Scully RE. Primary squamous
cell carcinoma of ovary. Report of 37 cases. Am J Surg Pathol
1996;20:823-33.
15 Dadhwal V, Sarkar SK, Arora V, Mittal S. Squamous cell carcinoma
in situ arising in mature cystic teratoma. Indian J Pathol
Microbiol 2002;45:345-6.
16 Czernobilsky B, Lifschitz-Mercer B, Luzon A, Jacob N, Benhur
H, Gorbacz S, et al. Cytokeratin patterns in the epidermis
of human ovarian mature cystic teratoma. Hum Pathol
1989;20:185-92.
17 Hirakawa T, Tsuneyoshi M, Enjoji M. Squamous cell carcinoma
arising in mature cystic teratoma of the ovary. Clinicopathologic
and topographic analysis. Am J Surg Pathol 1989;13:397-405.
18 Iwasa A, Oda Y, Kaneki E, Ohishi Y, Kurihara S, Yamada T, et
al. Squamous cell carcinoma arising in mature teratoma of the
ovary: an immunohistochemical analysis of its tumorigenesis.
Histopathology 2007;51:98-104.

PATHOLOGICA 2008;100:18-20
CASE REPORT
Collision epithelial and stromal tumours
of the stomach: a case report
Concomitanza di tumore epiteliale e tumore stromale dello stomaco: un caso clinico
A. TRABELSI, W. STITA, M. MOKNI, T. YACOUBI, S. MESTIRI, S. YAHYAOUI SADOK KORBI
Department of Pathology, CHU Farhat Hached, Sousse, Tunisia
Key words
Collision tumour • Stomach • Stromal tumour • Carcinoma
Summary
Collision epithelial and stromal tumours of the stomach are uncommon,
and only a few cases have been reported in the literature.
We describe a new case of a 54-year-old man who presented
with bloody emesis. An oesophagogastroduodenoscopy revealed
a stomach induration, and preoperative histological diagnosis
was signet ring carcinoma. Total gastrectomy was performed
and histological examination revealed a gastric collision tumour
composed of gastrointestinal stromal tumour intermixed with a
primary signet ring carcinoma. The neoplastic cells of the gastrointestinal
stromal tumour were diffusely positive for CD117,
while the signet ring cells were positive for cytokeratin. There
was no transition between the two components.
Introduction
The synchronous development of epithelial and stromal
tumours has been reported only rarely in the
literature 1-5 . We describe a new case of a 54-year-old
man who presented with bloody emesis. Histological
examination revealed a gastric signet-ring carcinoma
admixed with benign stromal tumour.
Methods
Specimens were fixed in 4% formaldehyde. Sections
were stained with haematoxylin and eosin. Gastric carcinoma
was classified according to Lauren’s criteria 6 .
The stromal component was classified according to the
WHO classification 3 .
Parole chiave
Tumori concomitanti • Stomaco • Tumore stromale • Carcinoma
Riassunto
La concomitanza di tumore epiteliale e tumore stromale è rara,
in letteratura sono stati riportati solo pochi casi. Descriviamo
il caso di un uomo di 54 anni che aveva presentato emesi
con sangue. L’esofagogastroduodenoscopia aveva rilevato un
indurimento dello stomaco, la diagnosi istologica preoperatoria
era di carcinoma a cellule ad anello con castone. Fu eseguita
una gastrectomia totale e l’esame istologico rivelò una concomitanza
di tumori gastrici composta da un tumore stromale
gastrointestinale mescolato a un carcinoma primitivo a cellule
ad anello con castone. Le cellule tumorali del tumore stromale
gastrointestinale erano diffusamente positive per CD117, mentre
le cellule ad anello con castone erano positive per citocheratina.
Non c’era transizione tra le due componenti.
Case report
A 54-year-old man presented with bloody emesis for
two weeks. An oesophagogastroduodenoscopy revealed
an induration that occupied the entire stomach; preoperative
histological diagnosis was signet ring carcinoma.
A total gastrectomy was performed. Macroscopic
appearance revealed diffuse thickening of the gastric
wall. Microscopic examination showed signet-ring cells
invading the entire gastric wall (fundus and antrum),
which extended to the surgical margin. In the fundus,
an occult benign submucosal stromal measuring 10 mm
was found, composed of sheets of spindle cells without
atypia or mitoses (Fig. 1). These cells were diffusely
positive for C-kit (CD117) (Fig. 2) and Cytokeratine
(Fig. 3), and negative for CD34, S100 protein and
smooth muscle actin. There was no transition between
the two components. In no-neoplastic gastric mucosa,
active chronic gastritis was detected and Helicobacter
pylori were observed. Five of 7 perigastric lymph nodes
were positive for metastatic carcinoma.
Correspondence
Amel Trabelsi, Department of Pathology, CHU Farhat Hached,
Sousse, Tunisia - Tel. +216 98 931610 - E-mail: trabelsiamel@
yahoo.fr

COLLISION EPITHELIAL AND STROMAL TUMOURS OF THE STOMACH
Tab. I. Synchronous occurrence of stomach epithelial and stromal tumours in the literature.
Author, year N. of cases Histologic subtype
Maiorana et al, 2000 6 5 cases stromal tumour + adenocarcinoma and 1 case stromal tumour + carcinoid
Andea et al., 2001 1 Stromal tumour + carcinoid
Liu et al., 2002 1 Stromal tumour + adenocarcinoma
Kaffes et al., 2002 1 Stromal tumour + adenocacinoma + MALT lymphoma
Bircan et al., 2004 2 Stromal tumour + adenocarcinoma
Discussion
The synchronous occurrence of epithelial and stromal
tumours in the stomach is uncommon 1-5 ; few cases have
described the simultaneous development of stromal
tumour with adenocarcinoma or carcinoids 1-5 (Tab. I).
Collision tumours of gastric carcinoma and stromal
neoplasms are extremely rare and to our knowledge,
this is only the second case reported. As with our case,
there was no transition between the different components
of the tumour in the other case reported 3 . In our
case, the stromal tumour was occult on pathologic
examination.
The admixture of gastric epithelial and stromal
tumours raises the question of whether such an occurrence
is a simple coincidence or whether the two
lesions were influenced by the same unknown carcinogen,
inducing the development of tumours of different
histological subtypes (epithelial and stromal)
in the same organ 2 7 8 .
Because of the rarity of gastric collision tumours, it is
difficult to determine their biologic behaviour 7 . In our
case, the stromal tumour was benign, and the carcinoma
had a larger impact on prognosis because of perigastric
lymph node metastasis.
Fig. 1. Spindle cell tumour intermixed with signet ring cell carcinoma
(haematoxylin and eosin, x100).
Fig. 2. Spindle cells are immunoreactive to c-Kit (x400).
Fig. 3. Signet ring cells are positive for cytokeratin (x400).
Conclusion
19
Gastric collision epithelial and stromal tumours are
extremely rare; more cases will have to be evaluated to
better understand their pathogenesis.

20
References
1 Maiorana A, Fante R, Maria Cexnaro A, Adriana Fauo R. Synchronous
occurance of epithelial and stromal tumors in the stomach.
Arch Pathol Lab Med 2000;124:682-6.
2 Andea AA, Lucas C, Cheng JD, Adsay NV. Synchronous occurrence
of epithelial and stromal tumors in the stomach. Arch Pahol
Lab Med 2001;125:318-9.
3 Liu SW, Chen GH, Hsieh PP. Collision tumor of the stomach: a
case report of mixed gastrointestinal stromal tumor and adenocarcinoma.
J Clin Gastroenterol 2002;35:332-4.
4 Kaffes A, Hughes L, Hollinshead J, Katelaris P. Synchronous
primary adenocarcinoma, mucosa-associated lymphoid tissue
lymphoma and a stromal tumor in a Helicobacter pylori-infected
stomach. J Gastroenterol Hepatol 2002;17:1033-6.
A. TRABELSI ET AL.
5 Bircan S, Candir O, Aydin S, Baspinar S, Bulbul M, Kapucuoglu
N, et al. Turk J Gastroenterol 2004;15:187-91.
6 Lauren P. The two histoogical main types of gastric carcinoma:
diffuse and so-called intestinal-type carcinoma: an attempt at
a histo-clinical classification. Acta Pathol Microbiol Scand
1965;64:31-49.
7 Liu S-W, Chen GH, Hsieh P-P. Collision tumor of the stomach. A
case report of mixed gastrointestinal stromal tumor and adenocarcinoma.
J Clin Gastroenterol 2002;35:332-4.
8 Cohen A, Geller SA, Horowitz Toth LS, Werther JL. Experimental
models for gastric leiomyosarcoma: the effects of N-methyl-
N-nitro-N-nitro-sognanidine in combination with stress, aspirin,
orsodiom Taurocholate. Cancer 1984;53:1088-92.

PATHOLOGICA 2008;100:21-24
CASO CLINICO
Sarcoma mieloide in leiomioma del miometrio
Myeloid sarcoma in uterine leiomyoma
F. PAGNI, F. BONO, C. DI BELLA, E. GALBIATI, A. FARAVELLI
Ospedale Civile Vimercate, Presidio di Desio-Università Milano-Bicocca, Desio (MI)
Parole chiave
Sarcoma mieloide • Leiomioma • Leucemia mieloide • Sarcoma
granulocitico • MPO
Riassunto
In questo report presentiamo il caso di una donna di 44 anni con
sanguinamento vaginale da due settimane. L’esame ginecologico
aveva rilevato la presenza di una neoformazione polipoide nella
cavità endometriale con diametro massimo di 4 cm. L’esame
istologico aveva rivelato un leiomioma classico infiltrato da una
altra neoplasia monomorfa , altamente indifferenziata.
L’analisi immunoistochimica aveva rilevato una reazione negativa
per citocheratina, CD10, inibina, CD99, CD20, CD3, TdT
e CD34, e una positività per CD45, MPO, CD68 e CD117. Fu
fatta diagnosi di sarcoma mieloide in leiomioma del miometrio.
I giorni seguenti la paziente aveva mostrato l’inizio di una leucemia
mieloide M5a. Quaranta giorni dopo la diagnosi la paziente
è morta per le complicanze legate all’immunodeficienza causata
dalla terapia. Questo caso sottolinea l’importanza di considerare
un sarcoma mieloide nella diagnosi differenziale di tumori indifferenziati
che insorgano in un sito extramidollare, specialmente
quando l’ordinario pannello anticorpale rivela negatività per i
marker epiteliali, mesenchimali e linfoidi, al fine di evitare errori
e permettere un ottimale management terapeutico.
Introduzione
Presentiamo in questo report un caso atipico di sarcoma
mieloide, una neoplasia altamente maligna composta da
elementi mieloidi maturi ed immaturi che proliferano in
sito anatomico diverso dal midollo osseo. Questa rara
neoplasia coinvolge maggiormente le ossa del cranio,
lo sterno, le coste, le vertebre, la cute, i linfonodi, i seni
paranasali, l’intestino ma rare sono le localizzazioni
nel distretto ginecologico riportate in letteratura 1 2 e, in
particolare, è del tutto eccezionale la segnalazione di
sarcoma mieloide insorto in concomitanza con patologia
benigna miometriale come invece descriviamo in questo
caso peculiare. Per le caratteristiche di estrema immaturità
degli elementi neoplastici, che possono sviare il patologo
nella diagnosi differenziale e per le conseguenze
Key words
Myeloid sarcoma • Leiomyoma • Myeloid leukemia • Granulocytic
sarcoma • MPO
Summary
In this case report we present a 44-year-old woman with a
2-weekhistory of vaginal bleeding. Gynaecological examination
revealed the presence of a polypoid neoformation in
the endometrial cavity with a maximum diameter of 4 cm.
Histological analysis showed a classic leiomyoma infiltrated
by a second monomorphic, highly undifferentiated neoplasia.
Immunohistochemical analysis revealed a negative reaction for
cytokeratin, CD10, inhibin, CD99, CD20, CD3, TdT and CD34,
and positivity for CD45, MPO, CD68 and CD117. A diagnosis
of myeloid sarcoma in myometrial leiomyoma was made. The
following days the patient showed the onset of an acute myeloid
leukaemia M5a. Forty days after diagnosis the patient died for
complications related to immunodeficiency caused by therapy.
Especially when a common antibody panel reveals negativity
for epithelial, mesenchymal and lymphoid markers, this case
underlines the importance of considering myeloid sarcoma in
differential diagnosis of undifferentiated tumours arising in an
extramedullary site in order to avoid errors and permit optimal
therapeutic management.
decisive che un pronto riconoscimento di questa lesione
ha sull’outcome dei pazienti, questo lavoro evidenzia
l’importanza di utilizzare un pannello immunoistochimico
minimo che comprenda marker di derivazione
mielo-monocitaria soprattutto qualora i pannelli immunoistochimici
di base risultino negativi nei confronti di
antigeni epiteliali, mesenchimali e linfoidi nel contesto
di una neoplasia maligna indifferenziata con sospetto
morfologico di origine mieloide.
Materiali e metodi
Gli anticorpi utilizzati nella definizione immunoistochimica
della lesione in esame sono stati: CD3 (Policlonal,
histoline), CD 10 (56C6, NovoCastra), CD20 (L26,
Corrispondenza
Dott. Fabio Pagni, Ospedale Civile Vimercate, Presidio di Desio-
Università “Bicocca”, via Mazzini 1, Desio (MI), Italia - Tel. +39
338 1833651 - E-mail: petala.83@tiscali.it

22
Histoline), CD34 (QBE nd/10, BioOptyca), CD45-LCA
(2B11, Dako), CD68 (PG-M1, Dako) CD79a (JCB117,
Dako), CD117 (policlonal, Dako), CK pool (AE1-AE3,
Dako), Chromogranine-A (Policlonal, Histoline), Ki67
(MIB1, Dako), Inhibin (R1, BioOptyca), MPO (policlonal,
Dako), Synaptophysine (Policlonal, Histoline),
NSE (BBS/NC, Dako), CD99 (HO 36-1,1 NovoCastra),
alfa smooth-muscle actin (1A4, BioOptyca).
Risultati e discussione
PRESENTAZIONE CLINICA
Una donna di 44 anni di età si presentava all’attenzione
del ginecologo per irregolare sanguinamento vaginale
da circa 2 settimane. L’esame ecografico della cavità
uterina rivelava la presenza di una neoformazione aggettante
nel lume endometriale e misurante 4 cm di diametro
massimo. Un emocromo di routine pre-operatorio
non evidenziava alterazioni di rilievo del quadro ematologico
con GB 3.700/mm 3 (61% neutrofili, 22% linfociti,
9% monociti, 3% eosinofili), piastrine 148.000/mm 3 ,
GR 4.280.000/mm 3 , Hb 10 g/dl. La paziente veniva
quindi sottoposta all’exeresi chirurgica della formazione
polipoide.
ESAME ISTOPATOLOGICO
L’esame istologico della lesione rivelava in prima
istanza la presenza di un leiomioma sottomucoso (Fig.
1). Tuttavia, nel contesto del leiomioma sottomucoso,
a maggior ingrandimento (Fig. 2), si evidenziava la
presenza di una proliferazione neoplastica sincrona
con caratteri di crescita infiltrativi ed arrecante diffusi
fenomeni di aggressione delle strutture ghiandolari
endometriali limitrofe e del miometrio. La neoplasia
presentava elementi altamente indifferenziati ed era
costituita da cellule monomorfe, di media-grande taglia,
atipiche, con abbondante rima citoplasmatica eosinofila
Fig. 1. Evidenza di leiomioma sottomucoso della cavità endometriale
(H&E, 2x).
F. PAGNI ET AL.
Fig. 2. Infiltrazione delle ghiandole endometriali da parte di
popolazione neoplastica maligna, indifferenziata, altamente monomorfa
(H&E, 10x).
periferica e con nucleo irregolare, talora indentato, con
cromatina dispersa e uno o due nucleoli. Erano inoltre
presenti frequenti mitosi atipiche (Fig. 3). L’indice di
proliferazione cellulare valutato con Mib1 era pari circa
Fig. 3. Le cellule neoplastiche mostrano abbondante citoplasma,
nucleo ovalare, nucleoli incospicui e numerose figure mitotiche
(H&E, 20x) – inset 3: all’interno della neoplasia rari elementi mieloidi
maturi sono evidenti ad alto ingrandimento (H&E, 40x).

SARCOMA MIELOIDE IN LEIOMIOMA DEL MIOMETRIO
all’80%. La definizione immunofenotipica della lesione
rivelava negatività delle cellule neoplastiche per CK
AE1/AE3 escludendo almeno in prima battuta un carcinoma
indifferenziato dell’endometrio. La successiva
ipotesi diagnostica era volta ad un sarcoma dello stroma
endometriale ma le colorazioni negative per CD10 e
inibina la escludevano. Inoltre la negatività per CD20,
CD3 escludevano un linfoma non Hodgkin a cellule B
mature, quella per TDT una forma a precursori e quella
di CD138 una neoplasia a differenziazione plasmacellulare.
Il campione risultava inoltre non immunoreattivo
per marker di derivazione neuroendocrina come sinaptofisina
e cromogranina A. Negativa anche la colorazione
per CD99, parametro importante, soprattutto volto
all’esclusione in età giovanile del sarcoma di Ewing e
di PNET. In questo senso va anche ricordato che CD99
può essere positivo nel 50% dei sarcomi mieloidi e in altre
neoplasie ematologiche, causando possibili problemi
diagnostici 3 . α-actina muscolare liscia rivelava il controllo
positivo interno negli elementi leiomiomatosi ma
la negatività nelle cellule tumorali maligne era completa.
Come quella per CD34, positivo nel controllo interno
delle strutture endoteliali, ma negativo nelle cellule
tumorali. Nell’ottica della diagnosi finale la negatività
di CD34 complicava ulteriormente la possibilità di una
neoplasia mieloide trattandosi di marker diffusamente
espresso in neoplasie ematologiche blastiche. La chiave
di risoluzione del quesito diagnostico derivò da una
debole positività per CD 45/LCA (Fig. 4a). Questa positività,
associata ad un’attenta rivalutazione del quadro
morfologico in ematossilina-eosina, che evidenziava la
rara presenza di elementi granulocitari maturi nel centro
della lesione, talora esprimenti granuli citoplasmatici
di possibile derivazione mieloide (Fig. 3-inset), impose
l’effettuazione di colorazioni immunoistochimiche
di conferma in questa direzione diagnostica. MPO e
CD117 (Fig. 4b, c) dimostrarono una diffusa reattività
Fig. 4a. debole positività per CD45/LCA; punto di partenza per la
corretta diagnosi (CD45/LCA, 10x); 4b: Punto fondamentale della
diagnosi: positività di MPO (20x); 4c: CD117 come marker mieloide
rivela la natura delle cellule neoplastiche (CD117/Ckit, 40x); 4d:
Positività focale per CD68 (CD68PGM-1, 20x).
23
nella popolazione tumorale accertando l’origine mieloide
del sarcoma. Una debole positività era inoltre
reperibile per CD68PGM1 (Fig. 4d) anche se si deve
ammettere che parte della positività era da attribuirsi ad
elementi istiocitari reattivi frammisti alle cellule neoplastiche.
L’esame istopatologico definitivo era dunque
compatibile con sarcoma mieloide in leiomioma del
miometrio.
Conclusione clinica
Circa due settimane dopo l’effettuazione della miomectomia
la paziente sviluppò anche nel sangue periferico i segni
di una leucemia mieloide acuta M5a (WHO, 2001).
Questo evento è peraltro possibile sia in simultaneità che
in epoca metacrona rispetto all’insorgenza di un sarcoma
mieloide 4 . La paziente fu immediatamente posta in terapia
per LMA secondo GIMEMA EORTC ma durante il
regime di condizionamento in previsione del trapianto di
midollo sviluppò quadro di shock settico ed exitus. Nonostante
l’esito infausto sottolineiamo con questo lavoro
la portata clinica di una diagnosi corretta di questa entità
patologica specialmente per le conseguenze critiche che
possono derivare, come già evidenziato in letteratura,
da una percorso diagnostico tardivo 5-7 in particolare
quando, come in questo caso, la neoplasia anticipa la
comparsa di una leucosi acuta periferica o quando viene
ad insorgere in sito francamente atipico come il distretto
ginecologico. Si sottolinea inoltre dal punto di vista
anatomopatologico l’importanza di un pannello minimo
immunoistochimico che comprenda CD34, MPO,
CD117 e CD68 per evidenziare l’origine mieloide di un
clone neoplastico indifferenziato, specialmente quando
sviluppatosi in sede extramidollare e qualora, in prima
battuta, risultino negativi i più comuni marker di origine
epiteliale, linfoide e mesenchimale. Il sarcoma mieloide
infatti può essere variabilmente costituito da una quota
di mieloblasti, promielociti ed elementi granulocitari
maturi come già proposto dalla classificazione WHO
2001. Da quest’aspetto morfologico derivano tre categorie
classificative: blastica, immatura e differenziata.
Una recente review 8 ha peraltro evidenziato l’assenza di
significato clinico-prognostico di questa classificazione
sottolineando invece la sempre maggiore importanza di
detezione di alterazioni molecolari con tecniche citogenetiche
come FISH per rilevare la presenza di aberrazioni
cromosomiche con incidenza preferenziale nel cluster
dei geni sui cromosomi 8 e 11 9 . Le conseguenze della
detezione di queste mutazioni potrebbero avere inoltre
possibili implicazioni terapeutiche nel futuro prossimo.
Attualmente la prognosi di queste lesioni è peraltro
ancora molto infausta peggiorando quella del quadro
mieloide associato. In questo senso, come questo caso
permette di evidenziare, la presenza di un clone mieloide
maligno in un sito extramidollare come l’utero trasforma
quest’ultimo in un “santuario farmacologico” rendendo
imperativo il prima possibile l’isterectomia come trattamento
elettivo complementare.

24
Bibliografia
1 Oliva E, Ferry JA, Young RH, Prat J, Srigley JR, Scully RE. Granulocytic
sarcoma of the female genital tract: a clinicopathologic
study of 11 cases. Am J Surg Pathol 1997;21:1156-65.
2 Garcia MG, Deavers MT, Knoblock RJ, Chen W. Myeloid sarcoma
involving the gynaecologic tract: a report of 11 cases an
review of the literature. Am J Clin Pathol 2006;125:783-90.
3 Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and Genetics.
Tumours of haematopoietic lymphoid tissues. Lyon: IARC
Press 2001, p. 104-5.
4 Glaser C, Michelon B, Peltier JY, Duboucher C, Bernheim A,
Perie G. Pre-leukemic granulocytic sarcoma of the uterus. Report
of a case. Ann Pathol 1998;18:187-91.
5 Breccia M, Mandelli F, Petti MC, D’Andrea M, Pescarmona E,
Pileri SA. Clinico-pathological characteristics of myeloid sarco-
F. PAGNI ET AL.
ma at diagnosis and during follow-up: report of 12 cases from a
singleinstitution. Leuk Res 2004;28:1165-9.
6 Kamble R, Kochupillai V, Sharma A, Kumar L, Thulkar S, Sharma
MC, et al. Granulocytic sarcoma of uterine cervix as presentation
of acute myeloid leukaemia: a case report and review of
literature. J Obstet Gynaecol Res 1997;23:261-6.
7 Yamauchi K, Yasuda M. Isolated extramedullary relapse of acute
myelogenous leukemia as a uterine granulocytic sarcoma in ana
allogenic hematopoietic stem cell transplantation recipient. Yonsei
Med J 2004;30;45:330 e segg.
8 Pileri SA, Ascani S, Campidelli C, Bacci F. Myeloid sarcoma: clinico-pathologic,
phenotypic and cytogenetic analysis of 92 adult
patients. Leukemia 2007;21:340-50.
9 Pullarkat V, Veliz L, Chang K, Mohrbacher A, Teotico AL.
Therapy – related mixed-lineage leukaemia translocation – positive,
monoblastic myeloid sarcoma of the uterus. J Clin Pathol
2007;60:562-4.

PATHOLOGICA 2008;100:25-30
CASE REPORT
Glomus tumour of the lung:
case report and literature review
Tumore glomico polmonare: caso clinico e revisione della letteratura
M.E. FILICE, M. LUCCHI * , B. LOGGINI, A. MUSSI * , G. FONTANINI
Dipartimento di Chirurgia, Sezione di Anatomia Patologica; * Dipartimento CardioToracico, Sezione di Chirurgia Toracica,
Università di Pisa
Key words
Glomus tumours • Pulmonary tumours • Immunohistochemistry
Summary
Glomus tumours are uncommon neoplasms usually arising in the
dermis and subcutaneous tissues where glomus bodies are generally
found. Occasionally glomus tumours can occur in extracutaneous
sites such as the gastrointestinal tract, bone, genitourinary
system and respiratory tract. Primary pulmonary glomus tumours
are very rare (only 17 cases reported in the literature), and are
often confused with other solid neoplasms such as carcinoids,
hemangiopericytomas and tumours belonging to the family of
Ewing’s sarcoma/primitive neuroectodermal tumours. We present
a case of a primary pulmonary glomus tumour originating in
the right main bronchus with focal invasion of the submucosa in a
69-year-old man. Histological and immunohistochemical features
are reported. The current literature is briefly reviewed, with special
attention to differential diagnosis and malignancy criteria.
Introduction
Glomus tumours originate from glomus cells, which
form glomus bodies and are involved in thermoregulation.
They are relatively frequent in the dermis and subcutaneous
tissues, but are extremely rare in deeper tissues
1 . Because of their rarity, primary visceral glomus
tumours are often confused with carcinoids, hemangiopericytomas,
smooth muscle neoplasms, primitive
neuroectodermal tumours (PNETs), paragangliomas
and other solid tumours. Differential diagnosis is based
on morphological and immunohistochemical features.
To date, only 17 primary pulmonary cases have been
reported in the literature (11 benign, 4 malignant and
2 with local infiltration) 2-12 . In this report we present a
case of primary pulmonary glomus tumour originating
in the right main bronchus.
Parole chiave
Tumore glomico • Neoplasie polmonari • Immunoistochimica
Riassunto
I tumori glomici sono neoplasie rare che originano generalmente
a livello del derma e del tessuto sottocutaneo, dove
abitualmente sono localizzati i corpuscoli glomici. Raramente
si possono trovare anche in sedi extracutanee, come il tratto
gastroenterico, l’osso, il tratto genitourinario e l’albero respiratorio.
I tumori glomici polmonari primitivi sono molto rari
(solo 17 casi attualmente riportati in letteratura) e vanno posti
in diagnosi differenziale con altre neoplasie quali i carcinoidi,
gli emangiopericitomi e le neoplasie della famiglia Sarcoma di
Ewing/Primitive NeuroEctodermal Tumors. Presentiamo un caso
di tumore glomico polmonare primitivo originato a livello del
bronco principale destro in un uomo di 69 anni, con descrizione
degli aspetti istologici ed immunoistochimici. Il tutto è corredato
da una revisione della letteratura con particolare attenzione alla
diagnosi differenziale e ai criteri di malignità.
Clinical history
A 69-year-old man with haemoptysis underwent a chest
x-ray that was negative for pleuro-pulmonary disease.
At bronchoscopy, a hypervascularised polypoid vegetation
that nearly completely occluded the right main
bronchus was found (Fig. 1). A biopsy specimen revealed
an angiomatous, benign neoformation. A chest
CT showed an endobronchial tumour, highlighted by
contrast media, and without any spread outside the
bronchial tree. Through a posterolateral thoracotomy
a sleeve resection of the right main bronchus was performed,
without parenchymal resection. The post-operative
course was uneventful.
Correspondence
Prof.ssa Gabriella Fontanini, Dipartimento di Chirurgia, Divisione
di Anatomia Patologica, Università di Pisa, via Roma 57,
56126, Pisa, Italia - Tel. +39 050 992983 - Fax +39 050 992942
- E-mail: g.fontanini@med.unipi.it

26
Fig. 1. Bronchoscopic image showing the endobronchial lesion in
the right main bronchus.
Materials and methods
Macroscopically, a soft endoluminal lesion, with a
uniform grey-white cut surface of 2 x 1.5 x 1 cm, was
detected; paraffin sections were prepared according to
standard procedures and stained with haematoxylin and
eosin
Immunohistochemical staining was performed using
monoclonal antibodies against smooth muscle actin
(Dako ® ; 1:30; no heat induced epitope retrieval – HIER),
vimentin (Ventana ® ; ready to use; HIER), CD56 (Ventana
® ; ready to use; HIER), synaptophysin (Ventana ® ;
ready to use; HIER), pan-cytokeratin (Ventana ® ; ready
to use; enzyme digest), thyroid transcription factor-1
(TTF-1) (Dako ® ; 1:30; HIER and Amplified), epithelial
membrane antigen (EMA) (Ventana ® ; ready to use; no
HIER), chromogranin A (Ventana ® ; ready to use; no
HIER) and factor-VIII related antigen (Ventana ® ; ready
to use; no HIER), all performed with the Ventana ®
Medical System, according to standard procedures.
Results
Histologically, the lesion was constituted of closely
apposed epithelioid round cells with scanty eosinophilic
cytoplasm. Nuclei were round or oval, with dispersed
chromatin and poor mitotic activity (Fig. 2A).
Supporting stroma consisted of delicate fibrovascular
septa, with occasional dilatated vessels. The lesion
showed a prevalently submucosal location with focal
infiltrative behaviour through the bronchial cartilage.
No lymph node dissemination was present in the 8
nodes examined. The lesion showed positivity for
M.E. FILICE ET AL.
smooth muscle actin and a typical cytoplasmic positivity
pattern for vimentin; all others markers were
negative (Fig. 2B, C, D).
Discussion
Glomus tumours originate from glomus cells. They are
modified smooth muscle cells forming glomus bodies, a
specialised form of arteriovenous anastomosis involved
in thermal regulation, located in the reticularis stratum
of the dermis 1 .Tumours arising from glomus cells are
relatively frequent in the skin and in superficial soft tissues,
but are very rare in deeper tissues and in visceral
organs, such as the stomach, rectum, heart, uterus, mediastinum
and lung 10 .
Histologically, glomus tumours are subdivided into
three types: common, glomangioma and glomangiomyoma,
depending on the prevalence of glomus cells,
vessels or smooth muscle cells, respectively 1 5 .
The histologic features of pulmonary glomus tumours
are the same as those of other sites. Macroscopic features
include a nodular configuration, with a uniform
grey-white or yellow cut surface. Microscopically,
these lesions are constituted of compact polygonal or
round cells that are closely apposed. Nuclei are round
or oval with dispersed chromatin, scarce or absent
mitotic activity, and little or no pleomorphism; scant
cytoplasm is amphophilic or eosinophilic. Supporting
stroma consists of delicate septa. In the “glomangioma”
pole of the spectrum, dilatated vascular spaces are
evident in the lesion 1 .
Glomus tumours show strong cytoplasmic positivity
for smooth-muscle and muscle-specific actin, mild to
moderate cytoplasmic positivity for vimentin and inconsistent
positivity for desmin. All cases reported in
the literature present a typical pseudomembranous pattern
of positivity for collagen IV, consisting of a strong
pericellular staining. Neuroendocrine, epithelial, neural
and histiocytic markers are usually negative.
Ultrastructurally, glomus cells have features of smooth
muscle cells: a polygonal shape with a round central
nucleus and prominent nucleolus, a cytoplasm containing
numerous thin microfilaments and rare pinocytotic
vesicles, but no neurosecretory granulus 1 5 13 .
The clinical presentation of the tumour depends on its
localization. Pulmonary glomus tumours, when symptomatic,
are usually associated with chest pain, cough,
fever (obstructive pneumonia), dyspnea, and pneumothorax;
hoarseness and dysphagia are characteristic of
the malignant variants 5 .
To date, 17 cases of primitive glomus tumours have been
reported arising from the tracheo-broncheal three (Tab.
I). The large majority of patients were adults (range 20-
73 years), with only one child (9 years). Twelve patients
were male and 5 were female. Twelve tumours arose
in the lung parenchyma, 4 in the bronchi and 1 in the
trachea. Histology revealed 11 glomus and 4 glomangiosarcoma
types; 2 cases showed local infiltration. For

GLOMUS TUMOUR OF THE LUNG
Fig. 2. (A) H&E section (20x) showing typical glomus cells with a characteristic perinuclear halo; (B) tumour cells show strong positivity for
actin smooth muscle (40x); (C) tumour cells are negative for F-VIII, which stains blood vessels (20x); (D) positivity for Vimentin (40x).
A B
C D
the majority of the cases, immunohistochemistry was
available with positivity for smooth muscle actin and
vimentin, while cytokeratins, neuroendocrine markers
and vascular markers were all negative 2-12 .
Pulmonary primary glomus tumours are rare lesions.
The differential diagnosis includes carcinoids, hemangiopericytoma,
smooth muscle neoplasms, PNETs,
paraganglioma and metastases. In all the cases morphological
and immunohistochemical characteristics are the
basis for differential diagnosis.
Pulmonary typical carcinoids are usually composed of
uniform groups of cells sustained by a fibrovascular
stroma with small centrally placed nuclei and eosinophilic
or amphophilic granular cytoplasm 14 . They
appear cytologically similar to glomus tumours, but
the cells of the latter present a finer chromatin pattern
and do not show an organoid arrangement of tumour
cells 5 9 . Immunohistochemical features distinguish
the two neoplasms: carcinoids show a neuroendocrine
phenotype with chromogranin A, synaptophisin and
neuron-specific enolase positivity 14 ; most carcinoid
27
tumours stain for cytokeratin, although 20% may be
keratin negative 15 .
A typical architectural vascular pattern, associated
with a monomorphous population of mesenchymal
cells, defines hemangiopericytoma occurring in the
lung. The vessels form a continuous ramifying vascular
network that has a “staghorn” configuration
and a striking variation in calibre 1 . Glomus tumours
can present a hemangiopericytomatous vascular pattern,
with prominent “staghorn-type” vessels; however
spindle cells with elongated nuclei are observed in
hemangiopericytoma tumour cells, in contrast to the
epithelioid round central nuclei of glomus neoplastic
cells 5 9 . Immunohistochemistry is very useful for distinguishing
the two types of tumours: hemangiopericytomas
usually express vimentin and CD34, and only
rarely actin and desmin 1 .
Extraskeletal Ewing’s sarcomas/primitive neuroectodermal
tumours may also be confused with glomus
tumours. The ES/PNET family usually occurs in adolescent
or young adults, although PNETs may arise in

28
Tab. I. Clinical features and immunophenotype compared to other cases reported in the literature.
CLINICAL FEATURES IMMUNOHISTOCHEMICAL MARKERS
Synaptophisin CD34 Factor
VIII
Chromogranin
A
vimentin desmin CK
cocktail
MS
Actin
author age sex diagnosis location SM
Actin
67 M glomus tumor left lower lobe * * * * * * * * *
Tang
(1978)
34 M glomus tumor right upper lobe * * * * * * * * *
Alt
(1983)
50 M glomus tumor right lung * * * * * * * * *
Koss
(1998)
41 M glomus tumor right lower lobe * * * * * * * * *
Koss
(1998)
20 M glomus tumor left mainstem + + + + - - - * *
bronchus
65 F glomus tumor right lung + + * - - - * - *
Gaertner
(2000)
Gaertner
(2000)
40 M glomus tumor right lower lobe + + + - - - - - *
Gaertner
(2000)
69 M glomangiosarcoma right upper lobe + + + - - - - - -
Gaertner
(2000)
73 M glomus tumor trachea * + * * - - - * -
29 F glomus tumor left main
* * + * - - * * *
bronchus
53 M glomangiosarcoma right lower lobe + + + * - - * * *
38 M glomangiosarcoma lung + + + * - * * * *
Gowan
(2001)
Yilmaz
(2002)
Hishida
(2003)
Folpe
(2001)
9 F glomangiosarcoma lung + + + * - * * * *
Folpe
(2001)
+ * + + - - - - *
right mainstem
bronchus
29 M glomus tumor with
atypical features
+ * + * - - - - *
37 M glomus tumor right bronchus
intermedius
Zhang
(2003)
De Weerdt
(2004)
62 F glomus tumor left lower lobe * * * * * * * * *
Sousa
(2006)
M.E. FILICE ET AL.
56 F glomangiomyoma right lower lobe * * * * * * * * *
Katabami
(2006)
(plus sign) positive staining, (minus sign) negative staining, * immunohistochemistry not available

GLOMUS TUMOUR OF THE LUNG
Tab. II. Immunophenotype of the glomus tumour in the present
study.
Antibody staining
SM Actin +
Vimentin +
CD56 -
Synaptophisin -
CK cocktail -
TTF1 -
EMA -
Chromogranin A -
Factor VIII -
(plus sign) positive staining, (minus sign) negative staining
older patients; however, ES and PNET have rarely been
described in the lung. For both ES and PNET, immunohistochemistry
is very useful: CD99 is usually positive
in contrast to glomus tumours 1 .
Among small round cells tumours, mediastinal paraganglioma
1 , alveolar rhabdomyosarcoma 1 and neuroblastoma
1 should also be excluded. In all of these cases immunohistochemical
and histochemical analyses are mandatory.
Other rare tumours can be considered for differential diagnosis,
such as solitary fibrous tumour, an uncommon
spindle-cell mesenchymal tumour that often presents a
prominent hemangiopericytoma-like vascular pattern.
Usually these tumours arise in the visceral pleura, but
may also originate in the lung parenchyma. They are
well circumscribed and often pedunculated. These lesions
stain typically with CD34 and bcl-2, and are negative
for keratins 15 .
Clear cell tumours are benign tumours probably arising
from perivascular epithelioid cells. The abundant
cytoplasmatic glycogen contained in the neoplastic cells
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2 Tang CK, Toker C, Foris NP, Trump BF. Glomangioma of the
lung. Am J Surg Pathol 1978;2:103-9.
3 Alt B, Huffer WE, Belchis DA. A vascular lesion with smooth
muscle differentiation presenting as a coin lesion in the lung:
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4 Koss M, Hochholzer L, Moran C. Primary pulmonary glomus
tumor: a clinicopathologic and immunohistochemical study of two
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5 Gaertner EM, Steinberg DM, Huber M, Hayashi T, Tsuda N,
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29
stains with periodic acid-Schiff (PAS). Tumours stain
also for HMB45 and are negative for keratins 15 .
The patient’s clinical history must be always evaluatedin
order to exclude metastatic lesions.
The majority of glomus tumours are benign. Only a
few cases of malignancy, associated with local invasion,
widespread metastases and exitus of the patients,
have been reported 1 5 16 17 . Atypical glomus tumours are
classified as infiltrative glomus tumours, glomangiosarcoma
arising from a glomus tumour, and de novo
glomangiosarcoma 9 17 . Currently, universally accepted
criteria for distinguishing benign from malignant visceral
glomus tumours are not available due to the small number
of cases reported. Folpe et al. 18 , in 2001, proposed a reclassification
of malignancy criteria for glomus tumours
after a review of 52 cases. All glomus tumours with
atypical features were subdivided into four categories
described below.
– Malignant glomus tumours (reserved for lesions with
a marked risk of metastasis): tumours with deep location
and a diameter greater than 2 cm, or atypical
mitotic figures, or a combination of moderate to high
nuclear grade and mitotic activity (5 mitoses x 50
high power fields [HPF]);
– Glomus tumours of uncertain malignant potential:
tumours with superficial location, associated with
high mitotic rate (> 5/50 HPF) or large size only or
deep location only;
– Symplastic glomus tumours: lesions with marked
nuclear atypia as their only unusual feature;
– Glomangiomatosis: diffusely infiltrating neoplasms,
similar to some vascular tumours and malformations,
probably the glomoid counterpart of angiomatosis;
this is a rare variant, with only 5% of glomus
tumours having atypical features; may be more frequent
during childhood 1 .
The rarity of these tumours makes it difficult to predict
prognosis. Of the malignant cases previously described
in the literature, one treated with surgery and chemotherapy
had a fatal outcome because of widespread
metastasis 17 months after surgery 5 8 16 . Therefore, close
follow-up is recommended.
6 Gowan RT, Shamji FM, Perkins DG, Maziak DE. Glomus tumor
of the trachea. Ann Thorac Surg 2001;72:598-600.
7 Yilmaz A, Bayramgurler B, Aksoy F, Yagci Tuncer L, Selvi A,
Uzman Ö. Pulmonary glomus tumor: a case initially diagnosed as
carcinoid tumor. Respirology 2002;7:369-71.
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the lung. Pathol Int 2003;53:632-6.
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12 Katabami M, Okamoto K, Ito K, Kimura K, Kaji H. Bronchogenic

30
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2001;25:1-12.

PATHOLOGICA 2008;100:31-35
CASE REPORT
Renal epithelioid angiomyolipoma:
a case report and literature review
Angiomiolipoma renale a cellule epiteliodi:
un caso clinico e revisione della letteratura
F. LIMAÏEM, A. MEKNI, I. CHELLY, Y. NOUIRA * , B. KHADIJA, S. HAOUET, N. KCHIR, A. HORCHANI * , Z. MONCEF
Department of Pathology, Hospital La Rabta, 1007 Bab Saadoun Tunis; * Department of Urology, Hospital La Rabta, 1007 Bab
Saadoun Tunis
Key words
Angiomyolipoma epithelioid cells • Kidney • Immunohistochemistry
Summary
Background
Renal epithelioid angiomyolipoma is a recently recognized variant
of angiomyolipoma, closely simulating renal cell carcinoma
both clinically and histologically. Only a relatively small number
of cases of epithelioid angiomyolipoma of the kidney have been
reported.
Aim
To highlight clinicopathological features of this rare tumour.
Observation
We report herein a new case of renal epithelioid angiomyolipoma
in a 38-year-old male with no stigmata of tuberous sclerosis.
The tumour was composed of diffuse sheets of epithelioid cells,
small numbers of adipocytes and occasional blood vessels. Immunohistochemically,
neoplastic cells were immunoreactive for
HMB-45, but negative for cytokeratin. The patient showed no
evidence of recurrence or metastatic disease one year after radical
nephrectomy.
Conclusions
Epithelioid angiomyolipoma may be locally aggressive and can
metastasise; therefore, long-term post-operative follow-up is
mandatory.
Introduction
Renal epithelioid angiomyolipoma (EAML) is a rare,
potentially malignant mesenchymal neoplasm, characterised
by proliferation of predominantly epithelioid
cells displaying positive immunoreactivity for melanoma
and smooth muscle markers. Although diagnosis
of angiomyolipoma (AML) is usually straightforward,
the epithelioid variant can clinically and pathologically
Parole chiave
Angiomiolipoma a cellule epiteliodi • Rene • Immunoistochimica
Riassunto
Premessa
L’angiomiolipoma renale a cellule epitelioidi è una variante
recentemente riconosciuta di angiomiolipoma, che simula da
vicino il carcinoma renale sia clinicamente che istologicamente.
È stato riportato solo un numero relativamente esiguo di casi di
angiomiolipoma a cellule epitelioidi del rene.
Scopo
Dare rilievo alle caratteristiche clinicopatologiche di questo
raro tumore.
Osservazioni
Qui riportiamo un nuovo caso di angiomiolipoma epitelioide
renale in un maschio di 38 anni senza stigmate di sclerosi
tuberosa. Il tumore era composto da diffusi strati di cellule
epitelioidi, un piccolo numero di adipociti e da occasionali vasi
sanguigni. All’immunoistochimica, le cellule neoplastiche erano
immunoreattive per HBM-45, ma negative per citocheratina. Un
anno dopo una nefrectomia radicale, il paziente non mostrava
evidenza di recidive di malattia o di metastasi.
Conclusioni
L’angiomiolipoma epitelioide può essere localmente aggressivo
e può metastatizzare; perciò, è obbligatorio un follow-up postoperatorio
a lungo termine.
resemble carcinoma, often generating diagnostic problems.
Only a limited number of reports of EAML are
present in the literature. Herein, we report herein a new
case of renal EAML which clinically and pathologically
mimicked renal cell carcinoma; we also highlight the
pathological and immunohistochemical profile of renal
EAML with a review of the current literature.
Correspondence
Faten Limaïem, 4, impasse Tarek Ibn Zied Mutuelleville, Tunis
1082, Tunisia - Tel. +216 96 552057 - E-mail: fatenlimaiem@
yahoo.fr

32
Case report
A 38-year-old previously healthy man with no stigmata
of tuberous sclerosis, presented with a 3-month history
of right lumbar pain. Physical examination revealed a
non-tender, non-distended abdomen. Abdominal ultrasonography
showed a hyperechoic round lesion involving
the upper pole of the right kidney devoid of fat
density. Computed tomography (CT) scan demonstrated
a heterogeneous enhancing mass suggestive of renal
cell carcinoma. Laboratory tests were within normal
limits. The patient underwent right radical nephrectomy.
Grossly, the tumour was well circumscribed, measuring
9 cm in diameter. Its cut surface was solid and whitish,
with focal yellowish areas. No extension into the
renal pelvis or capsule was observed. Microscopically,
the tumour was composed of densely packed epithelioid
cells arranged in sheets, solid islands and cords
with occasional adipocytes and scattered thick-walled
blood vessels (Fig. 1). Most epithelioid cells showed
a vesicular nucleus with a centrally located nucleolus,
and a very abundant and finely granular eosinophilic
or clear cytoplasm (Fig. 2). Mitotic figures were rare
(less than 1 per 10 high power fields). Nuclear pleomorphism
and necrosis were absent. No capsular, vascular
or lymphatic invasion was seen. The surrounding renal
parenchyma was unremarkable. Immunohistochemical
analysis was performed using the avidin-biotin complex
technique with antibodies against HMB-45, vimentin
and cytokeratin. Tumour cells were positive for HMB-
45 (Fig. 3) and negative for cytokeratin and vimentin.
The confirmed pathological diagnosis was epithelioid
angiomyolipoma. The patient had an uneventful recovery
and is symptom free one year post-operatively with
no evidence of recurrence or metastasis.
Fig. 1. The tumour is composed of densely packed epithelioid
cells arranged in sheets intermingled with adipocytes and thickwalled
blood vessels (haematoxylin and eosin, original magnification
x 100).
Discussion
F. LIMAÏEM ET AL.
Fig. 2. Epithelioid tumour cells showing abundant and granular
cytoplasm with occasional mitotic figures (arrow) (haematoxylin
and eosin, original magnification x 400).
Fig. 3. Positive immunostaining of tumour cells with HMB 45
(haematoxylin and eosin, original magnification x 400).
Epithelioid angiomyolipoma is a recently identified
variant of angiomyolipoma characterised by proliferation
of predominantly epithelioid smooth muscle cells
and producing an appearance distinctly different from
angiomyolipoma. Only a relatively small number of
cases of renal EAML have been reported (Tab. I). However,
because it may be frequently misdiagnosed as renal
cell carcinoma, this tumour might be more frequent than
reported in the literature. More than 50% of patients with
EAML have a history of tuberous sclerosis with a significantly
higher association than classic AML 1 . Both sexes
are equally affected, and the mean age at diagnosis is 38
years 1 . Although its aetiology and pathogenesis have not
been fully elucidated, EAML has recently been shown to
be clonal. Both immunohistochemical and ultrastructural
studies have supported the histogenesis from a single

RENAL EPITHELIOID ANGIOMYOLIPOMA
Tab. I. Renal epithelioid angiomyolipoma: review of the literature 1 2 6 10-27 .
Authors/year Age/sex TS Size (cm) Treatment Follow-up
Hartwick (1989) 2 cases (NA) - NA N NA
Ferry (1991) 49/F - 15 N Dead
Ashfaq (1993) 2 cases (NA) - 15 N NA
- 20 N NA
Mai (1996) 40/M - 15 RN 9 months
Eble (1997) 43/F + 10.2 PN 69 months
38/F - 10 N Lost to follow-up
20/F - 16 N 66 months
30/F - 13 N NA
48/M - 5.5 RN NA
Martignoni (1998) 60/M - 6 N Dead
36/F - 8 N 26 months
31/M - 10 N 10 months
Pea (1998) 18/F + NA N NA
24/F + N Dead 12 months
29/M + N Dead 18 months
Al-Saleem (1998) 21/F + NA RN Dead
Moch (1998) 19/M - NA RN NA
Delgado (1998) 6/F + 20 RN NED at 8 years
12/M - 15 RN NED at 7 years
34/M - 4.5 RN NED at 4 years
37/M - 3 RN NED at 1 year
16/F - 6 RN NA
L’Hostis (1999) 72/F - 9 NA DOD (24 months)
Christiano (1999) 42/M - 20.5 RN AWD
Mojica (2000) NA - NA NA NA
Cibas (2001) 49/M - NA PN Liver metastases
3 years AWD
Yip (2001) 75/M - 20 RN DWD
Radin (2001) 21/M + NA RN NA
Mai (2001) 47/M - NA N Recurrence 9 months
Mene (2001) NA + NA N NA
Yamamoto (2002) NA - NA RN Dead of metastasis (3
months)
Hino (2002) 34/M + NA RN Hepatic & peritoneal
Metastases (11 years)
Kawaguchi (2002) 28/F + NA RN Dead
Ong (2003) 74/F - 9 N NA
Marcus (2005) 42/F - 9.5 RN 2 months
Ma (2005) 44/F + 22 RN 17 months
Svec (2005) 47/F - 4.2 NA NA
Hung (2005) 17/F - 16 RN 12 months
Morioka (2006) 62/F - 20 RN 21 months
Park (2007) 69/M - 13 N NA
37/F + 4 PN NA
45/F - 1.4 PN NA
46/F - 17 N NA
Present case
AML: angiomyolipoma
AWD: alive with disease
DOD: dead of disease
EAML: epithelioid angiomyolipoma
N: nephrectomy
NA: not available
NED: no evidence of disease
PN: partial nephrectomy
RN: radical nephrectomy
TS: tuberous sclerosis
38/M - 9 RN 3 months
33

34
cell, specifically the perivascular epithelioid cell. It therefore
belongs to the family of the perivascular epithelioid
cell tumours (PEComas) 2 3 . Patients with renal EAML
are often symptomatic presenting with lumbar pain.
Laboratory tests are usually within normal limits; however,
a unique case of a renal EAML associated with
elevated serum prolactin levels has been reported in a
42-year-old woman 4 . Imaging findings closely mimic
renal cell carcinoma because of the paucity of adipose
tissue, as in our patient 5 .
Macroscopically, EAML are usually large with infiltrative
growth and a grey-tan white, brown or haemorrhagic
appearance. Necrosis may also be present 1 .
Microscopically, this variant often poses diagnostic
problems because the adipose tissue and tortuous thickwalled
blood vessels are not evident, in contrast to
conventional angiomyolipoma. EAML is characterised
by proliferation of predominantly epithelioid cells arranged
in sheets, often with perivascular cuffing of
epithelioid cells. The latter may surround blood vessels
and have thus been labelled perivascular epithelioid
cells (PEC). Tumour cells are round to polygonal with
abundant granular cytoplasm and enlarged vesicular
nuclei containing prominent nucleoli 1 . Multinucleated
and enlarged ganglion-like cells may be present.
A population of short spindle cells is seen in many
tumours, which may also display nuclear anaplasia, mitotic
activity, vascular invasion, necrosis and infiltration
of the perirenal fat. Haemorrhage is often prominent. A
few cases have focal areas of classic AML. Variations
in histology include variable admixtures of clear cells
although occasionally they may predominate, as in the
present case 1 .
EAML displays positive immunoreactivity for melanocytic
markers (HMB-45, HMB-50, Melan A) with
variable expression of smooth muscle markers (SMA,
muscle specific actin). Allelic losses of the short arm of
chromosome 16 have been observed in areas of classic,
epithelioid and sarcomatoid AML, indicating the clonality
of all these tumours 1 6 . P53 mutations have also been
References
1 Eble JN, Sauter G, Epstein JL, Sesterhenn IA. World Health
Organisation of Tumours. Pathology and genetics of tumours of
the urinary system and male genital organs. Lyon: IARC Press
2004.
2 Ong A, Pinto P, Kim F, Kavoussi L. Recurrent renal epithelioid
angiomyolipoma. Urology 2003;61:1035iii-1035v.
3 Belanger EC, Dhamanaskar PK, Mai KT. Epithelioid angiomyolipoma
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4 Quek ML, Soni RA, Hsu J, Skinner DG. Renal epithelioid
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6 Ma L, Kowalski D, Javed K, Hui P. Atypical angiomyolipoma of
F. LIMAÏEM ET AL.
detected in EAML, but not in classic AML, suggesting
an important role in the malignant transformation of the
tumour 6 . Histologically, the lesions most commonly
confused with renal EAML are renal cell carcinoma,
oncocytoma, medullary carcinoma and renal sarcomas.
Immunohistochemistry is particularly useful for distinguishing
EAML from renal cell carcinoma. The latter
is immunoreactive with cytokeratins and epithelial
membrane antigen, which is not observed in EAML.
In contrast to EAML, which consists of cells showing
diffuse cytoplasmic acidophilia and pleomorphic nuclei,
oncocytomas are composed of cells with acidophilic
granular cytoplasm and regular nuclei. Furthermore,
oncocytoma differ from EAML in their architectural
pattern and immunophenotypic profiles characterised
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membrane antigen and their lack of staining with
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arranged in solid nests or irregular tubules, and microcystic
or reticular growth is common. Careful attention
to these architectural characteristics, coupled with clinical
features, readily distinguishes medullary carcinoma
from renal EAML. Moreover, large cells resembling
ganglion cells and multinucleate giant cells, which are
generally present in renal EAML, are not features of
medullary carcinoma.
Owing to the frequent ambiguity of the preoperative
diagnosis and the potentially aggressive clinical
course of these tumours, surgical resection remains the
mainstay therapy. For patients with metastases or local
recurrence, renal EAML has been reported to respond
to doxorubicin 7 8 . Approximately one-third of patients
with renal EAML present with lymph node, lung, liver
or spinal cord metastases 9 . No prognostic parameters
have been reported, but the presence within the tumour
of necrosis, mitosis, nuclear anaplasia, and extrarenal
dissemination appear to be correlated with a poorer
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malignancy in AML is distant metastases (mainly lung
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8 Meng YH, Pei F, Lu P, Yu JY, Zheng J. Epithelioid angiomyolipoma
of kidney: clinicopathologic study of two cases and review
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Wani Y. Monotypic epithelioid angiomyolipoma of the kidney: A
case report. Int J Urol 2006;13:1240-2.
11 Park HK, Zhang S, Wong MK, Kim HL. Clinical presentation of
epithelioid angiomyolipoma. Int J Urol 2007;14:21-5.
12 Hino A, Hirokawa M, Takamura K, Sano T. Imprint cytology of
epithelioid angiomyolipoma in a patient with tuberous sclerosis. A
case report. Acta Cytol 2002;46:545-9.

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in a patient with tuberous sclerosis. J Comput Assist Tomogr
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14 Kawaguchi K, Oda Y, Nakanishi K, Saito K, Tamiya T, Nakahara
S, et al. Malignant transformation of renal angiomyolipoma: a
case report. Am J Surg Pathol 2002;26:523-9.
15 Hung MS, Hueimei J, Chang CP, Tai HL. Massive epithelioid
angiomyolipoma of the kidney in a young girl. Int J Urol
2005;12:998-1000.
16 Svec A, Velenska Z. Renal epithelioid angiomyolipoma a close
mimic of renal cell carcinoma. Report of a case and review of the
literature. Pathol Res Pract 2005;200:851-6.
17 Mai KT, Parkins DG, Collins JP. Epithelioid cell variant of renal
angiomyolipoma. Histopathology 1996;28:277-80.
18 Pea M, Bonetti F, Martignoni G, Henske EP, Manfrin E, Colato
C, et al. Apparent renal cell carcinomas in tuberous sclerosis are
heterogeneous. Am J Surg Pathol 1998;22:180-7.
19 Christiano AP, Yang X, Gerber GS. Malignant transformation of
renal angiomyolipoma. J Urol 1999;161:1900-1.
20 Martignoni G, Pea M, Rigaud G, Manfrin E, Colato C. Renal
angiomyolipoma with epithelioid sarcomatous transformation and
metastases. Am J Surg Pathol 2000;24:889-94.
35
21 Cibas ES, Goss GA, Kulke MH, Demetri GD, Fletcher CD. Malignant
epithelioid angiomyolipoma of the kidney. A case report and
review of the literature. Am J Surg Pathol 2001;25:121-6.
22 L’Hostis H, Deminiere C, Ferriere JM, Coindre JM. Renal
angiomyolipoma. A clinicopathologic, immunohistochemical,
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1999;23:1011-20.
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of the kidney, brain, and soft tissues in children and
young adults with the tuberous sclerosis complex. Cancer
1998;83:2208-16.
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1989;2:39A.
26 Ashfaq R, Weinberg AG, Albores-Saavedra J. Renal angiomyolipomas
and HMB 45 reactivity. Cancer 1993;71:3091-7.
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Rapidly progressive malignant epithelioid angiomyolipoma of the
kidney. J Urol 2002;168:190-1.

PATHOLOGICA 2008;100:36-40
CASO CLINICO
Angiolipoleiomioma cutaneo: segnalazione di un caso
e revisione della letteratura
Cutaneous angiolipoleiomyoma: a case report and literature review
S. SQUILLACI, R. MARCHIONE, C. SPAIRANI, M. SOCCIO * , F. TALLARIGO **
Unità Operativa di Anatomia Patologica, Ospedale di Vallecamonica, Esine, Brescia; * Divisione di Chirurgia, Ospedale di Vallecamonica,
Esine, Brescia; ** Unità Operativa di Anatomia Patologica, Ospedale “S. Giovanni di Dio”, Crotone
Parole chiave
Angiomiolipoma • Neoplasie cutanee • Angiolipoleiomioma
Riassunto
Gli Autori descrivono un caso raro di angiolipoleiomioma (ALL)
cutaneo ad insorgenza acrale e riassumono la letteratura sull’argomento.
Il paziente, maschio di 62 anni, presentava un nodulo
asintomatico, a lenta e progressiva crescita, del diametro di 2,2
cm, nel sottocute del polpaccio sinistro. Dieci mesi dopo l’escissione
chirurgica della neoformazione, il paziente sta bene ed è
libero da malattia.
Istologicamente la lesione, ben delimitata, risultava costituita da
tre componenti fra loro frammiste: aree di tessuto adiposo maturo
alternate a fascicoli di cellule fusate con citoplasma eosinofilo e
numerosi canali vascolari ad architettura variabile. All’indagine
immunoistochimica, la componente cellulare fusata della lesione
risultava positiva per vimentina e actina muscolo liscio, negativa
per proteina S-100, HMB45, MART1 e recettori estro-progestinici.
Viene anche discussa la diagnosi differenziale tra angiolipoleiomioma
ed altre neoplasie benigne, quali l’angioleiomioma e
l’angiomiolipoma sottocutaneo.
Introduzione
L’angiomiolipoma (AML) è un tumore mesenchimale
benigno costituito da tessuto adiposo maturo e tessuto
muscolare liscio intimamente compenetrati da una ricca
componente vascolare. È una neoplasia rara, dell’età
adulta. Più frequentemente si localizza nel rene dove
rappresenta lo 0,7-3% di tutti i tumori renali e si associa
spesso con la sclerosi tuberosa e più raramente con
altri disordini quali la malattia policistica dell’adulto, la
neurofibromatosi di tipo I e la sindrome di von Hippel-
Lindau 1 2 . Recentemente questo tipo di neoplasia viene
identificato con frequenza sempre maggiore anche in
siti extrarenali. Per entità clinico-patologiche morfologicamente
similari, con esclusivo coinvolgimento
Key words
Angiomyolipoma • Skin neoplasms • Angiolipoleiomyoma
Summary
The Authors describe a rare case of cutaneous angiolipoleiomyoma
in an acral location together with a brief literature review.
A 62-year-old male presented with a slow-growing asymptomatic
nodule, 2.2 cm in diameter, located in the subcutaneous tissue
of the left calf. Ten months after surgical excision, the patient is
alive and free of disease.
Histologically, the lesion was well-circumscribed and contained
three components: areas of mature fat tissue were intermingled
with cellular areas of spindle eosinophilic cells, reminiscent of
smooth muscle cells, and a complex mixture of vessels of different
types and sizes.Immunohistochemically, the cellular spindle
component was positive for vimentin and smooth muscle actin,
and negative for S-100, HMB-45, MART-1 and oestrogen and
progesterone receptors.
The Authors discuss differential diagnosis with other benign
lesions such as angioleiomyoma and subcutaneous angiomyolipoma.
cutaneo e sottocutaneo e immunoprofilo divergente per
negatività ai marcatori melanocitari, è stata opportunamente
e pertinentemente proposta l’etichetta di angiolipoleiomiomi
(ALL) 3-5 . In questo lavoro viene segnalato
un caso di ALL cutaneo con revisione della casistica
sull’argomento e ne vengono analizzati i problemi di
diagnosi differenziale, tenendo conto delle indicazioni
della recente letteratura.
Caso clinico
Paziente di sesso maschile di 62 anni con anamnesi
patologica remota positiva per epatite C, in regime di ricovero
presso la Divisione di Chirurgia dell’Ospedale di
Corrispondenza
Dott. Salvatore Squillaci, Unità Operativa di Anatomia Patologica,
Ospedale di Vallecamonica, via Manzoni 142, 25040 Esine
(BS), Italia - Tel. +39 0364 369256 - Fax +39 0364 369257 - Email:
anapat@ospedalevallecamonica.it

ANGIOLIPOLEIOMIOMA CUTANEO
Vallecamonica per il trattamento resettivo transuretrale
di un quadro di ipertrofia prostatica, riferisce ai sanitari
la presenza di una neoformazione intradermica a livello
della gamba sinistra a contatto con il ventre posteriore
del muscolo gastrocnemio. La lesione presente da 12
anni, non dolente, aveva subito un lento e progressivo
aumento di volume nel tempo, raggiungendo le dimensioni
di un uovo di quaglia. Il paziente non presentava
lesioni in altre parti del corpo e non riferiva segni di
altre malattie. All’esame obiettivo, la lesione appariva
come un nodulo di forma rotondeggiante di circa 2 cm
di diametro, ricoperto da cute leggermente sollevata e
di colore rosa-porpora. Alla palpazione risultava ben
delimitata, di consistenza duro-elastica e mobile rispetto
ai piani profondi e superficiali. L’esame clinico
orientava verso un lipoma. La lesione veniva asportata
chirurgicamente e risultava facilmente enucleabile. A 10
mesi dall’intervento il paziente è in buona salute e non
presenta segni di recidiva.
Materiali e metodi
Le sezioni istologiche di routine sono state ottenute da
blocchetti di tessuto fissato in formalina tamponata al
10% ed incluso in paraffina. I preparati istologici così
ottenuti sono stati colorati con ematossilina-eosina ed
orceina per le fibre elastiche. Le analisi immunoistochimiche
sono state condotte per vimentina (V9, Novocastra,
prediluito), actina muscolo liscio (Neomarkers, clone
1A4, 1:100), recettori progestinici (PG) (Biogenex,
PR88, prediluito), recettori estrogenici (ER) (Zymed,
6F11, prediluito), HMB-45 (Enzo Diagnostic, HMB 45,
prediluito), MART1 (Dako, clone A-103, 1:50), proteina
S-100 (Biogenex, 15E2E2, prediluito).
Risultati
Macroscopicamente il nodulo, unico, di cm 2,2 x 1,4 x
0,7, di forma rotondeggiante, di colore grigio-giallastro
e consistenza duro-elastica, ha un aspetto uniforme,
piuttosto omogeneo e appare discretamente delimitato
(Fig. 1).
La neoformazione interessa il tessuto sottocutaneo;
l’epidermide e il derma risultano indenni. Il quadro
istologico è caratterizzato dalla presenza di fasci di
tessuto muscolare liscio maturo commisti con tessuto
adiposo (Fig. 2). La componente adiposa è composta
da adipociti maturi tra loro omogenei e con piccoli nuclei
eccentrici. I vasi sanguigni intimamente frammisti
alla trama muscolo-adiposa sono di forma e calibro
altamente variabili; alcuni di essi ectasici, con lume a
“corna d’alce” e parete sottile, che si alternano ad altri
con parete muscolare spessa e lume di foggia rotonda o
ristretto, oblungo e deformato (Fig. 3). La colorazione
istochimica per orceina rivela la scarsa ed irregolare
rappresentazione della lamina elastica nei vasi a parete
ispessita, alcuni dei quali ne risultano privi (Fig. 4). Le
Fig. 1. Visione panoramica del nodulo che mostra contorni netti
e appare costituito da aree adipose alternate ad aree cellulate.
Fig. 2. Aree solide a struttura fascicolata composte da elementi
con citoplasma ampio, eosinofilo e nucleo allungato “a sigaro”
(EE, 100X).
37
cellule muscolari lisce tendono a sfumare impercettibilmente
con lo strato muscolare esterno dei vasi. Sono
presenti alcuni linfociti spesso aggregati e rari mastociti,
specie in sede perivascolare. Il lume dei vasi non risulta
trombizzato. Non sono presenti emorragie, necrosi,
calcificazioni. Non si rilevano atipie cellulari né figure
mitotiche. Alla periferia della neoformazione è presente

38
Fig. 3. Le aree cellulate appaiono costituite da fasci disordinati
di cellule fusate in continuità con le pareti dei vasi e commiste a
lobuli di tessuto adiposo (EE, 100X).
Fig. 4. Alcuni vasi a parete spessa appaiono del tutto privi di
lamina elastica (Orceina, 200X).
un sottile e discontinuo rivestimento capsulare connettivale
risparmiato dalla proliferazione tumorale.
Le indagini immunoistochimiche evidenziano positività
per vimentina in tutte le aree, per actina muscolo-liscio
lungo le pareti ispessite dei vasi e nella componente
muscolare e negatività per ER, PgR, HMB-45, MART-1
e proteina S-100 (quest’ultima presenta focalmente una
debole positività degli adipociti) (Fig. 5).
Discussione
L’AML è la più frequente neoplasia mesenchimale del
rene. Considerato fino a poco tempo fa un amartoma di
recente ne è stata dimostrata la natura neoplastica (clonalità
evidenziata dalla inattivazione di tipo non random
del cromosoma X). L’AML renale si presenta in forma
sporadica (poco più del 50% dei casi) ovvero in asso-
S. SQUILLACI ET AL.
Fig. 5. La componente a cellule fusate appare intensamente positiva
all’actina muscolo liscio (Dako EnVision, 200X).
ciazione con il complesso della sclerosi tuberosa (TSC)
in circa un terzo dei pazienti. La TSC è una facomatosi
(sindrome familiare neurocutanea) con doppia marcatura
genetica: 9q34 e 16p13 (geni TSC1 e TSC2) 4 .
Lesioni morfologicamente indistinguibili dall’AML renale
sono riportate in altre sedi seppure con minore frequenza:
sono stati descritti casi a livello retroperitoneale,
nel fegato, nella milza, nei linfonodi, nel polmone,
nella parete addominale, nel cuore, nel mediastino, nel
funicolo spermatico, nella salpinge, nell’utero e nella
parete vaginale, nel pene, nelle cavità nasale e orale e
nella galea capitis 6 7 .
L’ALL cutaneo, pur in presenza di evidenti similarità
istomorfologiche, differisce per molte caratteristiche
dall’AML renale 1-6 8-10 . È una lesione rara, descritta
per la prima volta da Argenyi et al. 11 nel 1986 come
angiomiolipoma cutaneo. Da allora hanno fatto seguito
sporadiche segnalazioni, tanto che nel mondo sono
stati 24 i casi a tutt’oggi pubblicati 1-4 6-15 . Le principali
caratteristiche cliniche dei casi descritti sono riassunte
in Tabella I. L’ALL cutaneo si presenta di solito in
soggetti di età adulta, con picco nella V e VI decade
di vita. L’età media alla diagnosi è di 51 anni, con un
range compreso tra 16 e 77 anni (1-4,6-15). Predilige
il sesso maschile (con un rapporto maschi: femmine di
3:1) 1-4 6-15 . Non sono descritti casi in età pediatrica o associati
a sclerosi tuberosa e ad altre sindromi familiari.
La neoformazione è sempre situata nel derma profondo
e/o nel sottocute con dimensioni comprese tra 0,4 e 4
cm 1 2 4 6 8-12 14 . Dall’analisi dei casi (compreso il nostro)
riportati in letteratura risulta che il distretto della testa
è la sede più colpita seguita dalle regioni acrali con il
maggior numero dei casi riscontrati all’orecchio e ai
tegumenti periauricolari 1-4 6-15 . La presentazione clinica
è aspecifica in forma di massa palpabile, non dolente e
spesso mobile sui piani profondi; il decorso è piuttosto
lento e graduale con un intervallo pre-operatorio che
può raggiungere i 40 anni 1-3 6-9 11-14 .

ANGIOLIPOLEIOMIOMA CUTANEO
Tab. I. Caratteristiche cliniche dei 25 casi di angiolipoleiomioma cutaneo descritti in letteratura.
Autore Età Sesso Dimensioni
(cm)
Sede Tempo
intercorso tra
esordio del
tumore e Ch.
Diagnosi clinica
Argenyi et al. 11 67 M 1 Elice orecchio dx 40 anni Cisti epidermoidale
Fitzpatrick et al. 3* 77 M NR NR Lipoma vs. cisti
Fitzpatrick et al. 3* 63 M NR 6 mesi GCTTS ** vs. ganglio
tenosinoviale
Fitzpatrick et al. 3* 50 M NR NR Massa
Fitzpatrick et al. 3* 59 F NR NR Nodulo
Fitzpatrick et al. 3* 52 M NR 1 anno Lipoma
Fitzpatrick et al. 3* 33 M NR 3 anni Cisti epidermoidale
Fitzpatrick et al. 3 * 48 M NR 2 mesi Lipoma
Fitzpatrick et al. 3* 39 M NR NR Nodulo sottocutaneo
Mehregan et al. 15 49 M NR Elice orecchio dx NR Cisti epidermoidale
Rodriguez-Fernandez
et al. 14
58 M 4 Gomito 15 anni NR
Van-Bernal et al. 6 49 M 2 Lobulo orecchio dx 5 anni Tumore vascolare
Buyukbabani et al. 9 38 M 2,5 Solco retroauricolare dx 10 anni NR
Buyukbabani et al. 9 36 M 1,5 Naso 3 anni NR
Obata et al. 7 54 F NR Faccia laterale sx
del naso
Lin et al. 8 65 F 2 Area pre-auricolare sx 10 anni NR
Tsuruta et al. 13 75 M NR Faccia laterale sx
del naso
5 anni Lipoma vs. emangioma
10 anni Lipoma
Beer et al. 1 43 M 0,4 Orecchio sx 6 mesi NR
Beer et al. 1 56 M 0,6 Mento Parecchi anni NR
Beer et al. 1 44 F 0,5 Orecchio sx 3 mesi Cisti epidermoidale
Hatori et al. 10 38 M 4 Ginocchio 5 anni Sarcoma
Del Sordo et al. 12 58 M 2 Padiglione orecchio dx. 3 anni Lesione angiomatosa
Makino et al. 4 16 F 2,5 Gluteo dx NR Emangioma
Debloom et al. 2 50 F 3 Coscia 5 anni Lipoma, cisti
epidermoidale,
angiolipoma
Squillaci et al. 62 M 2,2 Polpaccio sx 12 anni Lipoma
* 3 casi erano insorti al capo (naso, orecchio dx, solco retroauricolare dx), 4 agli arti superiori (2 ai gomiti e 2 al IV e V dito mano dx), 1 agli arti inferiori
(alluce piede dx); ** GCTTS = tumore a cellule giganti delle guaine tendinee; M = maschio; F = femmina; NR = non riportato; Ch = intervento chirurgico;
sx = sinistro; dx = destro
Le diagnosi cliniche poste più frequentemente sono state:
cisti epidermoidale, lipoma ed emangioma 1-4 6 7 11-13 15 . Altre
patologie che sul piano clinico possono entrare nella
diagnosi differenziale con l’ALL, qualora insorgente alle
39
dita, sono il tumore a cellule giganti della guaina tendinea
e il ganglio tenosinoviale 3 . Nel nostro caso viene formulata
diagnosi clinica di sospetto lipoma.

40
Le tecniche di immagini convenzionali quali la TAC e
la RM forniscono quadri non specifici e non indicativi
di ALL 4 7 10 . Infatti, aspetti di buona circoscrizione e
ipointensità in T1 con aree granulari di iperintensità in
T2 evidenziabili alla RM non sono elementi sufficienti
per una diagnosi conclusiva di natura della lesione 4 7 . In
un caso viene effettuata una biopsia incisionale pre-operatoria
da cui risulta la diagnosi di sospetto sarcoma 10 .
L’escissione chirurgica completa della lesione appare il
trattamento di scelta. Tutti i pazienti riportati fino ad ora
in letteratura, compreso il nostro, hanno goduto di un
andamento clinico benigno 1-4 6-8 10-14 . Due recidive locali
sono state descritte in un solo caso, verosimilmente conseguenti
a mancata radicalizzazione chirurgica 9 .
L’aspetto istologico dell’ALL con la peculiare commistione
di vasi, tessuto adiposo e tessuto muscolare liscio, ne
consente una diagnosi agevole nella maggior parte dei casi.
Un aspetto interessante, osservato in una segnalazione,
è la presenza di cellule multinucleate con nuclei polimorfi
e bizzarri nella componente mioide 14 . Queste alterazioni
citologiche rappresentano aspetti degenerativi, benigni,
analogamente a quanto si osserva in altre lesioni 14 . Tuttavia
la loro presenza può porre problemi di diagnosi differenziale
con il lipoma pleomorfo. Le cellule plurinucleate
di quest’ultima lesione (c.d. floret cells) sono adipociti e
presentano citoplasma vacuolizzato e positività immunoistochimica
alla proteina S-100 14 . Un’altra lesione che più
frequentemente può entrare in diagnosi differenziale con
l’ALL è l’angiolipoma, se presenta fibrosi perivascolare
ed interstiziale 3 5 6 8-10 12 15 . L’assenza di una componente
muscolare liscia e la struttura a parete sottile dei vasi,
con frequenti trombi di fibrina intraluminali, sono caratteristiche
morfologiche che consentono un corretto
riconoscimento 5 .
I casi di miolipoma sono distinguibili dall’ALL per
l’assenza della tipica componente artero-venosa 6 12 .
Ma forse i problemi più complessi di diagnosi diffe-
Bibliografia
1 Beer TW. Cutaneous Angiomyolipomas are HMB-45 negative, not
associated with tuberous sclerosis, and should be considered as
angioleiomyomas with fat. Am J Dermatopathol 2005;27:418-21.
2 Debloom JR, Friedrichs A, Swick BL, Whitaker DC. Management
of cutaneous angiomyolipoma and its association with tuberous
sclerosis. J Dermatol 2006;33:783-6.
3 Fitzpatrick JE, Mellette JR, Hwang RJ, Golitz LE, Zaim MT,
Clemons D. Cutaneous angiolipoleiomyoma. J Am Acad Dermatol
1990;23:1093-8.
4 Makino E, Yamada J, Tada J, Arata J, Iwatsuki K. Cutaneous
angiolipoleiomyoma. J Am Acad Dermatol 2006;54:167-71.
5 Mentzel T. Cutaneous lipomatous neoplasms. Sem Diagn Pathol
2001;18:250-7.
6 Van-Bernal JF, Mira C. Cutaneous angiomyolipoma. J Cutan
Pathol 1996;23:364-8.
7 Obata C, Murakami Y, Furue M, Kiryu H. Cutaneous angiomyolipoma.
Dermatology 2001;203:268-70.
8 Lin SJ, Chiu HC. An asymptomatic preauricular subcutaneous
nodule in a 65-year-old woman. Arch Dermatol 2003;139:382-6.
9 Buyukbabani N, Tetikkurt S, Ozturk S. Cutaneous angiomyoli-
S. SQUILLACI ET AL.
renziale si pongono con l’angioleiomioma (leiomioma
vascolare) e con l’angiomiolipoma sottocutaneo sporadico
1-3 5 6 8-12 15 16 .
All’interno di un angioleiomioma possono essere presenti
aree di tessuto adiposo come ben evidenziato da
Hachisuga et al. 17 che hanno notato la presenza di adipociti
maturi in 16 casi su 562 esaminati; tuttavia questa
entità si differenzia per un minor grado di “lipidizzazione”
1 3 5-7 11 12 15 17 . È possibile che l’ALL cutaneo possa
essere l’espressione terminale di un percorso patologico
partito da un angioleiomioma successivamente andato
incontro nel tempo a sostituzione adiposa, forse causata
da ripetuti traumatismi 1 7 12 . L’ipotesi istogenetica alternativa
sull’ALL cutaneo è che si tratti di un processo
amartomatoso 9 15 .
Una ulteriore lesione cutanea, recentemente descritta
(2007) da Magro e Lanzafame 16 come angiomiolipoma
(AML) sottocutaneo sporadico, presenta evidente somiglianza
morfologica con l’ALL ma diverge da esso
per la presenza di cellule epitelioidi eosinofile, la positività
all’HMB-45 ed ai recettori per estrogeni e progesterone.
Nel nostro caso, la negatività per i marcatori
melanocitari è ulteriormente avvalorata dall’assenza di
immunoreattività per il MART-1 con ciò sottolineando
la differenza immunofenotipica tra l’ALL e altre forme
di AML renale e cutaneo.
In conclusione, con questo lavoro abbiamo cercato sia
di offrire una revisione dei dati pubblicati nel mondo
su ALL cutaneo, che di definire gli aspetti clinico-patologici
di questa entità. Tale lesione è spesso riportata
in letteratura come AML cutaneo, termine che a nostro
avviso dovrebbe essere esclusivamente utilizzato per tumori,
istologicamente simili, derivati dalla proliferazione
delle cellule epitelioidi perivascolari (PEC). È importante
che il patologo riconosca l’ALL e lo differenzi da
queste forme neoplastiche che potrebbero rappresentare
una spia morfologica di un grave disordine genetico 16 .
poma: report of two cases with emphasis on HMB-45 utility. J Eur
Acad Dermatol 1998;11:151-4.
10 Hatori M, Watanabe M, Kokubun S. Angiomyolipoma in the knee.
A case report. Ups J Med Sci 2005;110:245-9.
11 Argenyi ZB, Piette WW, Goeken JA. Cutaneous angiomyolipoma.
A light-microscopic, immunohistochemical, and electron-microscopic
study (abstract). J Cutan Pathol 1986;13:434.
12 Del Sordo R, Colella R, Leite S, Sidoni A. Angiomiolipoma cutaneo:
descrizione di un caso e revisione della letteratura. Pathologica
2005;97:137-40.
13 Tsuruta D, Maekawa N, Ishii M. Cutaneous angiomyolipoma.
Dermatology 2004;208:231-2.
14 Rodriguez-Fernandez A, Caro-Mancilla A. Cutaneous angiomyolipoma
with pleomorphic changes. J Am Acad Dermatol
1993;29:115-6.
15 Mehregan DA, Mehregan DR, Mehregan AH. Angiomyolipoma. J
Am Acad Dermatol 1992;27:331-3.
16 Magro G, Lanzafame S. Sporadic subcutaneous angiomyolipoma
with expression of estrogen and progesterone receptors. Virchows
Arch 2007;450:123-5.
17 Hachisuga T, Hashimoto H, Enjoji M. Angioleiomyoma: a clinicopathologic
reappraisal of 562 cases. Cancer 1984;54:126-30.

PATHOLOGICA 2008;100:41-42
CASE REPORT
Aneurysmal bone cyst of the parietal bone. Case report
Cisti aneurismatica dell’osso parietale: caso clinico
S. ULIVIERI, G. OLIVERI, C. MIRACCO *
Dipartimento di Neurochirurgia, Ospedale “Santa Maria alle Scotte”, Siena; * Dipartimento di Patologia,
Ospedale “Santa Maria alle Scotte”, Siena
Key words
Aneurysmal bone cyst • Bone tumour • Surgery
Summary
Aneurysmal bone cyst is a benign lesion of unknown pathogenesis
seen more often in vertebrae and flat bones, and less commonly
in the shaft of long bones. Skull involvement is rare and
accounts for only 3-6% cases 1 , generally in the first three decades
of life. Histologically, the lesion is characterised by the presence
of multiple localisations, filled with venous blood and lined by
spindle-shaped fibroblasts with scattered multinucleated giant
cells and stromal cells. An unusual case of aneurismal bone cyst
of the parietal bone is reported.
Introduction
Aneurysmal bone cysts (ABC) are lytic, expansile,
non-neoplastic bone lesions consisting of multiple thinwalled,
cystic cavities containing blood. Three to 6%
of ABS occur in the skull convexity, whereas the skull
base is an unusual site. ABC have been reported at various
locations in the calvarium and skull base, including
the occipital bone, the frontal bone and, less frequently,
the parietal bone. Hypotheses regarding its pathogenesis
include vascular anomalies of bone, reaction to intramedullary
haemorrhage, or a primary neoplastic bone
lesion; local trauma prior to the development of ABC
has also been reported 2 . Some bony lesions, such as
fibrous dysplasia or chondroblastoma, have been found
in association with ABC. These may have preceded the
appearance of the lesion, predisposing its development.
Materials and methods
Aneurysmal bone cyst of a skull bone is a rare entity and
occurs mainly in the first 3 decades of life; diagnosis
and treatment are discussed.
Parole chiave
Cisti aneurismatica • Tumore osseo • Chirurgia
Riassunto
La cisti aneurismatica ossea è una neoplasia benigna ad eziogenesi
sconosciuta, con localizzazione cranica rara (solo nel 3-6%
dei casi) e di più frequente riscontro nelle prime tre decadi di
vita. Ben riconoscibile istologicamente con peculiari caratteristiche,
riportiamo un caso giunto alla nostra osservazione di cisti
aneurismatica in sede parietale.
Case report
A 61-year-old woman presented with a slow-growing
mass on the right side and a history of headache lasting
a few months. Upon admission, neurological examination
revealed no neurological deficits, and blood routine
investigations were within normal limits. Radiographs
of the skull in lateral and anteroposterior views revealed
expansion, sclerosis and thickening of the frontal and
parietal bone. CT scans showed an osteolytic lesion in
the right parietal region with inhomogeneous content
with solid and calcified cystic components (Fig. 1); MRI
confirmed that there was no infiltration of the dura. The
tumour was excised through a right fronto-parietal flap
with a large craniotomy following acrylic cranioplasty.
On histopathologic examination, large vascular spaces
separated by fibrous septa containing spindly and ovoid
stromal and multinucleated giant cells were visible;
inflammatory cells, haemosiderin and granulation tissue
were seen in the stroma (Fig. 2). The post-operative
course was uneventful and patient was discharged after
5 days.
Correspondence
Dott. Simone Ulivieri, Dipartimento di Neurochirurgia, Ospedale
“Santa Maria alle Scotte”, 53100 Siena, Italia - E-mail: simone.
ulivieri@tiscali.it

42
Fig. 1. CT scans showing an osteolytic lesion in the right parietal
region with inhomogeneous content with solid and calcified
cystic components.
Discussion
Aneurysmal bone cyst belongs to the group of benign
fibro-osseous lesions that also includes fibrous dysplasia,
ossifying fibroma, cementifying fibroma and benign osteoblastoma
3 . Jaffe and Lichtenstein 4 coined the term in 1942
to describe an atypical bone lesion with a vascular lining
and a characteristic “soap bubble” radiologic picture of expanded
bone. A review of the published literatureafter 1960
revealed 44 cases of ABC involving the skull, of which only
4 cases involved the parietal bone 5-8 . The lesion is more
common in women than men, and in young individuals in
References
1 Giovanni L, Maurizio F, Mario S. Angiography and computerized
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4 Jaffe HL, Lichtenstein L. Solitary unicameral bone cyst with emphasis
on the roentgen picture, the pathologic appearance and the
pathogenesis. Arch Surg 1942;44:1004-102.
S. ULIVIERI ET AL.
Fig. 2. Histopathologic examination: large vascular spaces separated
by fibrous septa containing spindly and ovoid stromal and
multinucleated giant cells were visible; inflammatory cells, haemosiderin
and granulation tissue were seen in the stroma.
the first three decades of life Radiography usually shows an
expansile cystic lesion with a honeycomb appearance; CT
studies can delineate the bone architecture of the tumour,
with a thin cortex of newly formed bone surrounding the
mass with contents of heterogeneous densities. MRI shows
a high signal intensity within the lesion, suggesting previous
clot formation and a low intensity peripheral rim suggesting
bone encapsulation. Histological examination shows bloodfilled
spaces surrounded by compressed fibrous tissue rather
than endothelium. Multinucleated giant cells of the osteoclast
type throughout the fibrous stroma are also common.
Haemosiderin laden macrophages and new bone formation
is found within the stromal matrix.
The treatment of choice for these lesions is total excision.
Long-term outcome, without the necessity of adjuvant
therapy (radiation therapy or chemotherapy), while simple
curettage or partial resection has a high recurrence rate 9 .
5 Alessio L, Iob I, Mottaran R, Salar G, Fiore D. Aneurysmal cysts
of the fronto-parietal bone. Riv Neurol 1989;59:53-7.
6 Oki S, Shima T, Uozumi T. Aneurysmal bone cyst of the skull – a
case report. No Shinkei Geka 1978;6:1197-201.
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with fibrous dysplasia of the parietal bone. Report of two cases. J
Neurosurg 1986;64:331-5.
8 Cacdac MA, Malis LI, Anderson PJ. Aneurysmal parietal bone
cyst. Case report. J Neurosurg 1972;37:237-41.
9 El Deeb M, Sedano HO, Waite DE. Aneurysmal bone cyst of the
jaws. Report of a case associated with fibrous dysplasia and review
of literature. Int J Oral Surg 1980;9:301-11.