Sabato 27 ottobre 2012 - Pacini Editore

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I tumori neuroendocrini del pancreas
P. Capelli
Paper not received
Aspetti neuroendocrini di tumori nonneuroendocrini
M. Milione, P. Gasparini, A. Aiello, A. Testi, F. Perrone, F.
Melotti, S. Pilotti, G. Sozzi, G. Pelosi
Fondazione IRCCS Istituto Nazionale dei Tumori, Dipartimento di
Patologia Diagnostica e Laboratorio
Intraspinal Ewing’s sarcoma ES and/or primitive neuroectodermal
tumors (PNET) arise in the soft tissue. These pPNET
originate in the neural crest region and are considered a very
rare and aggressive neoplasm which develops locally in the
chest wall and lower extremities. Histologically, pPNETs
are composed of undifferentiated small round cells that may
form Homer Wright or Flexner–Wintersteiner rosettes and
perivascular pseudo-rosettes. Moreover, histological differentiation
of ES/pPNET from carcinoid tumor, small cell undifferentiated
carcinoma, neuroblastoma, rhabdomyosarcoma,
fibrosarcoma or malignant peripheral nerve sheath tumor, is a
diagnostic challenge due to similarity in histology and clinical
presentation among these tumors. An essential tool in diagnosing
ES/pPNET is immunohistochemistry (IHC). In particular
CD99 (MIC2), which recognizes a 30/32 kDa surface
glycoprotein a, is expressed in more than 90% of ES/pPNET
Also, CD99 expression may be seen in several tumors such
as malignant lymphoma, leukemia and small cell carcinoma
(Kushner BH, Riopel M, Menasc LP Lumadue JA).
Non-random chromosomal aberrations, in particular translocations,
often characterize a number of neoplasms including
bone and soft tissue tumors. ES/pPNET is a solid tumor
characterized by the presence of chromosomal translocations
involving the gene EWS, located at 22q12 and a gene of the
ETS family. In particular, 85% of cases possess the EWS-
FLI1 fusion protein created by a chromosomal translocation
t(12;22)(q24;q12), in which the DNA-binding domain of the
ETS transcripts fuses to the transactivation domain of FLI1.
However, EWS-FLI1 is not the only fusion transcript responsible
for ES/pPNET as the second most common partner gene
which forms a chimeric fusion with EWS is ERG, formed
by a chromosomal rearrangement t(22;21) (q22;q12) and accounting
for approximately 10% of cases. Other fusion genes
with EWS are less frequent but still present in ES/pPNET
are EWS-ETV1 t(7;22), EWS-ETV4 t(7;22), and EWS-FEV
t(2;22) (REF. Sankar et al).
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
Overall, in soft-tissue tumors, the incidence of ES/PNET is
of 4%. Literature describes the occurrence of pPNET anywhere
in the body, with the most affected site being thoracopulmonary,
followed by pelvis, retroperitoneum or abdomen,
limbs, neck and other unknown origins (Kushner et al).
Moreover, literature reports isolated cases of pPNET also in
pancreas, heart, kidney, ovary, uterus, testis, urinary bladder
and parotid gland (REF). The ileo-cecal site is an even rarer
location for this neoplasm and literature describes only single
case reports. Regardless the origin of this aggressive and rare
neoplasm, ES/pPNET has an overall unfavorable prognosis.
Unfortunately, despite the combined approaches used such as
therapy with surgery and chemotherapy with radiations, only
25% of patients with tumors greater than 5 cm were alive at
24 months. Moreover, molecular events of tumorigenisis in
ES/pPNETs are still poorly understood but critical in order
to identify novel molecular markers for new target therapy.
Yearly, our institution diagnoses about 100ES/pPNET cases
of different origin site. Interestingly, over the past year, we diagnosed
5 ES/pPNET cases with primary site in the ileo-cecal
region. We here describe how an accurate histological differentiation,
associated with IHC and molecular cytogenetic
characterization of the specimen, were able to give an accurate
diagnosis and prognosis.
Over the past 15 years we treated 5 patients with ES pNET
with a primary in the ileocecal region. Interestingly, all cases
presented a similar clinical presentation and identical morphologic
and immunophenotypical characterization.
Microscopically, the 5 specimens showed a sheet-like proliferation
of spindle-to-polygonal cells with large vesicular
nuclei with thin vascular stroma. Focally, the tumor formed
ribbon-like or rosette structures, with moderate mitosis (10/50
high-power field). Moreover, neither invasive growth nor
metastasis to lymph nodes was identified.
Prior to IHC, all cases were identified as poorly differentiated
epithelial neoplasm. In order to define the proper histotype a
series of antibodies, summarized in table 1, were utilized for
IHC. All five cases presented an identical IHC pattern: a) focal
positivity for the cytokeratin (CK) AE1/AE3, CAM 5.2,
synaptophisin (SYN), and chromogranin A (CgA); b) strongly
diffuse positivity for CD 117,vimentin,CD 99, FlI-1; c) negative
for epithelial membrane antigen (EMA), S100, leucocyte
common antigen (LCA), CD 34, smooth muscle actine
(SMA), carcinoembryonic antigen (CEA), desmin and WT-1
(C19 and C180). Proliferative index of neoplasia valued with
MIB-1/Ki-67 immunostaining was about 30%.
A molecular and molecular cytogenetics analysis, such as RT-
PCR, FISH, and SKY were performed as complementary tests
to IHC to better characterize the histotype.
In details no KIT mutations were found in any of the 5 cases,
therefore excluding the possibility of being a GIST. On the
other hand, FISH confirmed rearrangemnts of EWS for all
five cases, confirming the dignosis of a pNET.
Presentazione gruppo di studio GIPE
C. Capella
Paper not received