96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

Abstracts
FR-003
Glucagon cell adenomatosis: a novel multifocal neuroendocrine
neoplasia restricted to the dorsal pancreas anlage
M . Anlauf 1 , P . Gerlach 1 , S . Schinner 2 , M . Schott 2 , M . Krausch 3 , K . Cupisti 3 , R .S .
Lanzmann 4 , C . Antke 5 , S . Schulz 6 , G . Klöppel 7 , H .E . Gabbert 1 , W .T . Knoefel 3 ,
W .A . Scherbaum 2
1 Institute of Pathology, University of Düsseldorf, 2 Department of Endocrinology,
Diabetes and Rheumatology, University of Düsseldorf, 3 Department of
General-, Visceral- and Pediatric Surgery, University of Düsseldorf, 4 Institute
of Diagnostic and Interventional Radiology, University of Düsseldorf,
5 Department of Nuclear Medicine, University of Düsseldorf, 6 Institute of
Pharmacology and Toxicology, University of Jena, 7 Institute of Pathology,
Technical University of München
Aims. Based on observations in four patients, glucagon cell adenomatosis
(GCA) has recently been proposed as a novel multifocal neuroendocrine
tumor disease of the pancreas.
Methods. We report on a 58-year-old patient treated by duodenopancreatectomy
who showed distinct features of GCA. In order to study the
tumor development and distribution the entire pancreas was embedded
and systematically analyzed.
Results. The patient presented with recent onset non-insulin-requiring
diabetes and abdominal discomfort. On CT the pancreas showed multiple
tumors and diffuse nodular enlargement corresponding to the
SPECT scintigraphy. The imaging findings were more pronounced in the
pancreatic body and tail than in the head. Pathology analysis revealed
12 neuroendocrine macrotumors and more than 10,000 microadenomas
mainly composed of glucagon cells. Metastases were not detected. The
nontumorous parenchyma revealed a ubiquitous glucagon cell hyperplasia
at the expense of the other endocrine islet cell types. These findings
were restricted to the body, tail and the upper portions of the pancreatic
head. The lower portion of the head of the pancreas that corresponds to
the ventral pancreas anlage had a normal appearance.
Conclusions. GCA is a novel multifocal neuroendocrine neoplastic disease
that is restricted to the dorsal pancreas anlage.
FR-004
Genetic alterations in glucagon cell adenomatosis
T . Henopp1 , M . Anlauf2 , S . Biskup3 , G . Klöppel4 , B . Sipos1 1University Hospital Tübingen, Institute for Pathology and Neuropathology,
Tübingen, 2University Hospital Düsseldorf, Institute for Pathology, Düsseldorf,
3Center for Genomics and Transcriptomics, Tübingen, 4Technische Universität München, Institute of Pathology, München
Aims. Glucagon cell adenomatosis (GCA) was recently recognized by us
as a multifocal neoplastic disease of the endocrine pancreas unrelated to
MEN1. Multiple micro- and a few macrotumors are found on the background
of a hyperplasia of glucagon cells. The disease may cause unspecific
abdominal symptoms and only rarely a glucagonoma syndrome.
Recently a mutation in the glucagon receptor (GCGR) gene was described
in one GCA patient. The aim is to investigate GCGR gene changes in
five patients with GCA.
Methods. Paraffin embedded and formalin fixed pancreatic tissues from
five patients showing multiple microadenomas and in three cases also
macroadenomas of glucagon cells were macro- or microdissected. The
extracted DNA was sequenced and the GCGR gene analysed for mutations.
Results. Sequencing of the GCGR gene revealed germline mutations in
three out of five patients. One patient shows two different heterozygous
point mutations in the hyperplastic alpha cells as well as in the non-tumorous
tissue leading to two premature stop codons. One patient harbors
a homozygous stop mutation. The third patient shows two homozygous
missense mutations of the GCGR gene that most likely also led to a
dysfunction of the GCGR. In the two other patients no germ line mutati-
48 | Der Pathologe · Supplement 1 · 2012
ons of the GCGR gene were detected. These variants were not identified
in healthy subjects.
Conclusions. The finding of germ line and somatic “loss of function” mutations
of the GCGR gene in three of five patients with GCA suggests that
a change in the signalling function of the GCGR may cause glucagon cell
adenomatosis via glucagon cell hyperplasia.
FR-005
Proliferative activity is not associated with tumor aggressiveness
in ileal neuroendocrine tumors
T . Henopp1 , J . Sperveslage1 , M . Anlauf2 , G . Klöppel3 , B . Neumayer1 ,
C .P . Gerlach2 , P . Rexin4 , T .M . Gress5 , R . Moll4 , B . Sipos1 1University Hospital Tübingen, Institute for Pathology and Neuropathology,
Tübingen, 2University Hospital Düsseldorf, Institute for Pathology, Düsseldorf,
3Technische Universität München, Institute of Pathology, München,
4University Hospital Giessen and Marburg, Institute for Pathology, Marburg,
5University Hospital Giessen and Marburg, Department of Internal Medicine,
Marburg
Aims. The accuracy of the new WHO grading system for neuroendocrine
neoplasms, which is based on proliferative activity, has not yet been
validated for ileal neuroendocrine tumors (iNETs). Aim of this study is
to analyse the proliferation rates in primary iNETS, lymph node and distant
metastases in order to determine the prognostic power of grade 1
and grade 2 categories in the WHO 2010 classification.
Methods. 64 primary iNETs, 35 matched node metastases and 20 distant
metastases were analysed for proliferation rate (Mib1, Phospho H3) using
automated image analysis assessing the maximum (hot spot) and overall
proliferative activity. Proliferation rates were compared in different
prognostic relevant cohorts (N0M0, N1M0 and N1M1).
Results. The maximum Mib1 proliferative rates were: 0.6% (range 0.27–
2.78) for N0M0, 0.77% (range 0.03–2.94) for N1M0 and 1.02% (range
0.2–12.17) for N1M1 primary iNETs. Corresponding node metastases
(0.66%; range 0.02–3.38) and distant metastases (0.83%, range 0.01–10.94)
showed comparable proliferative rates like primary iNETs. The number
of grade 1 and grade 2 iNETs was not different in the three cohorts.
Primary iNETs of N1M0 (2 cm; range 1–4.8) and N1M1 (1.95 cm; range
0.4–5) cohorts were significantly larger than N0M0 tumors (0.2 cm; range
0.2–1.6).
Conclusions. Grade 1 and grade 2 categories in the WHO classification
2010 do not have discriminatory power regarding prognosis for iNETs.
In fact, tumor spread is independent of proliferative activity in iNETs.
FR-006
Comprehensive assessment of Merkel cell polyomavirus in Merkel
cell carcinomas: fluorescence in situ hybridization versus qPCR?
A . Haugg1 , D . Rennspiess1 , A . zur Hausen1 , E .-J . Speel1 , G . Cathomas2 ,
J . Becker3 , D . Schrama3 1Maastricht University Medical Center, Department of Pathology, Maastricht,
Netherlands, 2Kantonsspital Liestal, Institute of Pathology, Switzerland,
3Medical University of Graz, Division of General Dermatology Department of
Dermatology, Graz, Austria
Aims. Merkel cell polyoma virus (MCPyV) is detected in 80% of Merkel
cell carcinomas (MCC). The clonal integration and tumor specific mutations
in the large T Antigen (LTAg) gene identify MCPyV as a novel
human tumor virus. To date the relationship between the viral presence
and cancer induction, development or clinical prognosis is discussed
controversially. Yet almost all studies are based on quantitative virus
detection, i.e. PCR or qPCR. Here we aimed to gain information about
the quality of the viral presence on the single cell level in the histomorphological
context.