pag. 216-318 - Siapec

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COMUNICAZIONI E POSTER
risultati instabili, mentre BAT26 è risultato stabile; complessivamente
il reperto è stato di alta instabilità (MSI-H). Questi risultati
hanno indirizzato alla ricerca della mutazione germinale.
L’analisi mutazionale in DHPLC non ha messo in evidenza
mutazioni puntiformi nei geni MSH2 ed MLH1. La successiva
analisi con multiplex ligation-dependent probe amplification
(MLPA) ha messo in evidenza la delezione completa del
gene MSH2. Le stesse analisi sono state poi effettuate su campioni
istologici e su sangue del padre e sono state osservate le
medesime alterazioni.
Conclusioni
Delezione completa di MSH2 è stata riscontrata nella nostra
casistica solamente in questa famiglia ed in un’altra con carcinoma
del colon destro a 36 aa. nel probando.
La rilevanza del caso è data dalla giovane età di insorgenza,
dalla situazione iniziale di apparente non-rischio famigliare,
dalla stabilità del microsatellite BAT26 e dal tipo infrequente
di mutazione riscontrata, cioè delezione completa del gene
MSH2.
Il dato di un’età così giovanile di insorgenza di carcinoma del
colon deve essere tenuto in considerazione nella valutazione
di tempi di sorveglianza colonscopica nelle famiglie
HNPCC.
Depletion of MTDNA limited to the external
layer of muscularis propria induces
gastrointestinal dysmotility in a MNGIE
patient
C. Giordano, M. Sebastiani, C. Travaglini, P. Sale, M.L.
Valentino * , V. Carelli * , G. d’Amati
Dipartimento di Medicina Sperimentale e Patologia, Università
di Roma “La Sapienza”; * Dipartimento di Scienze Neurologiche,
Università di Bologna
Introduction
Mitochondrial neurogastrointestinal encephalomyopathy
(MNGIE) is an autosomal recessive disease clinically defined
by severe gastrointestinal dysmotility, cachexia, ptosis,
ophthalmoparesis, peripheral neuropathy, white matter
changes in brain MRI, and mitochondrial abnormalities.
Loss-of-function mutations in thymidine phosphorylase (TP)
gene induce pathologic accumulations of thymidine and deoxyuridine,
which generate mtDNA defects (depletion, multiple
deletions and point mutations).
The origin of gastrointestinal dysmotility is currently unclear.
Material and methods
We present a detailed histological description of the gastrointestinal
tract of a patient carrying the homozygous TP
mutation 1443G > A and, by the mean of laser capture microdissection,
correlate the morphological findings with
mtDNA abnormalities.
Results
Small intestine showed marked atrophy of the external layer
of muscularis propria, with evidence of cytoplasmic vacuolization,
mitochondrial proliferation and nuclei with condensed
chromatin. In contrast, the internal layer and the
myenteric and submucosal plexi were unremarkable. Genetic
analysis revealed strikingly selective depletion of mtDNA
in the small intestine, compared to esophagus, stomach and
colon. Microdissection of the small intestine revealed depletion
of mtDNA only in the external layer of muscularis propria.
Interestingly, analysis of the gastrointestinal tract from
ten controls revealed a non-homogeneous distribution of
mtDNA content; the small intestine had the lowest levels of
mtDNA. Multiple deletions were detected only in the upper
esophagus and in skeletal muscle. Site-specific somatic point
mutations, mostly T > C transitions preceded by 5’poly-A sequences,
were detected at low abundance both in the muscle
and nervous tissue of the gastrointestinal tract.
Conclusions
We conclude that profound mtDNA depletion in the external
layer of muscularis propria is the major determinant for the
morphologic changes and indicates that visceral myopathy is
responsible for gastrointestinal dysmotility in this MNGIE
patient. Our results suggest that tissues with constitutively
low amounts of mtDNA may be more sensitive to defects of
thymidine phosphorylase.
Epstein-Barr virus infection in gastric
carcinomas with peritumoral neutrophil
infiltration
A. Ieni, G. Niedobitek * , T. Kirchner * , R.A. Caruso, C. Inferrera
Dipartimento di Patologia umana Messina; * Institute Of
Pathology, University Of Erlangen, Germany
The Epstein-Barr virus is a ubiquitous human herpesvirus
which establishes a life-long persistent infection of B-cells in
over 90% of the human adult population. The association of
Epstein-Barr virus (EBV) with a proportion of gastric carcinomas
is well established. We have recently identified tumour
infilration by neutrophils as a potential indicator of a
favourable prognosis in advanced gastric cancer (AGC). Here
we have tested the hypothesis that infiltration by neutrophils
may be related to EBV infection of the tumour cells.
Methods
One hundred cases of gastric carcinomas (50 carcinomas with
peritumoral neutrophil infiltration – 50 gastric adenocarcinomas
without stromal inflammatory reaction) were analysed by
in Situ Hybridization for the detection of the EBV-encoded
small nuclear RNAs (EBERs) 35S-labelled probes were employed
and bound probes were detected by autoradiography.
Results
In situ hybridization showed EBV infection of the tumour
cells in one case of neutrophil-rich gastric carcinoma and in
one case of ordinary carcinoma (2%). In one of these cases,
EBV infection was detected both in tumour tissue and in the
adjacent non-neoplastic mucosa. These data confirm that
Epstein-Barr virus infection is rarely associated with gastric
carcinoma and show that EBV is not preferentially found in
AGC with neutrophils. Furthermore we provide evidence of
viral infection of non-neoplastic gastric mucosa.
Congenital malignant peripheral nerve
sheath tumor of the small bowel
unassociated with von Recklinghausen’s
disease: a heretofore unreported occurrence
E. Kuhn, F. Pallotti, L. Runza, S. Carinelli
U.O. Anatomia Patologica, Ospedale Maggiore Policlinico
“Mangiagalli - Regina Elena”, Milano, Italia
Introduction
Malignant peripheral nerve sheath tumor (MPNST) in children
is uncommon, and is frequently associated with von