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

FR-P-174
MPGN-like glomerulonephritis with intracapillary IgM thrombi in
Waldenström’s macroglobulinemia
D . Kratochvil 1 , K . Amann 2 , H . Bruck 1 , M . Büttner 2
1 University Hospital Essen, Internal Medicine, Essen, 2 University Hospital
Erlangen, Institute of Pathology, Erlangen
Aims. Lymphoproliferative disorders causing paraproteinemia can be
associated with various kidney injuries. In the context of a case report
earlier reports in literature and differential diagnoses of IgM-associated
glomerulonephritides (GN) are discussed.
Methods. Case report including the results of clinical, light microscopical,
immunohistochemical and electron microscopical investigations.
Literature search and discussion of earlier descriptions of glomerular
monoclonal IgM deposits in lymphoproliferative diseases.
Results. A 73-year-old female patient with a history of rheumathoid arthritis
and Waldenström’s disease was admitted to hospital for acute renal
failure with a mild proteinuria and hematuria. An MPGN-like GN
with intracapillary IgM thrombi was diagnosed. The patient reported
episodes of palpable purpura reminiscent of cryoglobulinemia. Despite
repeated analyses, however, no cryoglobulines could be detected. The renal
function recovered before the beginning of the immuno-modulatory
therapy.
Conclusions. In contrast to M. Waldenström-associated GN described
by Maroger-Morel in the present case a prominent glomerular hypercellularity
was found. A strict distinction between cryoglobulinemic and
non-cryoglobulinemic GN appears difficult taking previous reports in
literature into account.
FR-P-175
c-Met in undifferentiated pleomorphic sarcomas and fibroblastic/
myofibroblastic tumors
C . Wölfel1 , T . Knösel1 , T . Liehr2 , S . Hauke3 , A . Altendorf Hofmann4 , D . Katenkamp1
, I . Petersen1 1 2 Jena University Hospital, Institute of Pathology, Jena, Jena University Hospital,
Institute of Human Genetics, Jena, 3ZytoVision GmbH, Bremerhaven,
4Jena University Hospital, Department of General Surgery, Jena
Aims. Undifferentiated, pleomorphic sarcomas (UPS), formerly known
as malignant, fibrous histiocytoma (MFH) are defined as a group of
high-grade sarcomas in which any attempt to disclose their line of differentiation
has failed. These undifferentiated, pleomorphic sarcomas tend
to occur in the extremities of elderly patients as a deep-seated, enlarging
mass. The tumors frequently show an aggressive, rapid growth which
contrast with the limited therapeutic options consisting mainly of surgery
and radiotherapy while chemotherapy is usually not effective. c-MET
inhibition is recently evolving as a promising new target in cancer therapy.
C-Met is a proto-oncogene that encodes the hepatocyte growth factor
receptor which possesses tyrosine-kinase activity. An abnormal c-Met
activation in cancer triggers tumor growth, angiogenesis and encourage
metastasis leading to a poor prognosis for the patient. We aimed to analyze
the gene in soft tissue tumors.
Methods. The tumor collective consisted of 327 fibroblastic/myofibroblastic
tumors including 203 undifferentiated, pleomorphic sarcomas, 42 low
grade sarcomas and 82 pseudosarcomatous tumors of the fasciitis family.
It was analysed for c-Met expression by immunohistochemistry and c-
Met amplification by FISH. This was done on TMA sections (3 µm). One
TMA of fasciitis nodularis tissues was used as control. For immunhistochemistry
we applied a polyclonal rabbit anti-c-Met antibody with the
dilution 1:50 at pH 6.1. Furthermore, we used FISH probes located at the
c-Met region at chromosome 7q31.3 and as reference centromere probes
for chromosome 7. The slides were evaluated by fluorescence microscopy.
Results. Immunohistochemically, we found 53 sarcomas (16%) with a
high c-Met expression. In contrast, the fasciitis cases revealed no or only
low expression in all cases. For FISH analyses, 105 samples could so far
be investigated. They showed chromosomal aberrations in 37 cases (39%).
Many cases carried a polysomy of chromosome 7. In addition, 9 cases
(8.6%) revealed a selective amplification of the c-Met locus which, however,
was only rarely associated with a clear-cut c-met overexpression.
Conclusions. Conclusion: c-MET may represent an interesting therapeutic
target in a subset of undifferentiated pleomorphic sarcoma which
needs further evaluation.
FR-P-176
Cement spacers with MicroSilver (Bio-Gate) show decreasing
inflammation without hints for detrimental effects in histological
study of periprosthetic membranes
S . Söder1 , T . Bechert2 , P . Steinrücke2 , R . Ascherl3 , A . Hartmann1 1 2 Erlangen-Nürnberg, Institute of Pathology, Erlangen, Bio-Gate AG, Nürnberg,
3Klinik für Wechselendoprothetik, Chemnitz
Aims. Following hip replacement an infection rate of 2% was observed in
this procedure. So far Gentamycin-spacers are commonly used to control
periprosthetic infections. However especially in the presence of multiresistant
bacteria like MRSA they are often only of limited effect. Silver
has already proven to be effective in vitro. In a randomized prospective
clinical study by Bio-Gate AG, Gentamycin-spacers with additional
Microsilver component were compared with conventional Gentamycinspacers.
In addition to a comprehensive panel of clinical and microbiological
tests the periprosthetic membranes were studied histologically.
Methods. We received blinded samples from 17 different patients with
hip implant infections. Each patient received 2-stage revisions with
2 different cement spacers (Gentamycin and Gentamycin with added
Microsilver) following a randomization. Specimens were formalin fixed,
paraffin embedded, sectioned and hematoxylin-eosin stained.
Results. No silver particles could be identified in any sample, even
though occasionally wear particles were found in both groups. There was
no indication of allergic or toxic effects in the histological examination.
Typically a decline in inflammation was found in the course of the treatment.
Periprosthetic membranes from spacers with added Microsilver
showed typically a stronger or at least equal reduction in inflammation
than spacers with Gentamycin alone.
Conclusions. Histological examination gave no hints for adverse effects of
adding Microsilver to conventional spacers which is in accordance with
preliminary in vitro and animal studies. Furthermore a stronger effect
on inflammation activity was observed.
FR-P-177
GNAS1 mutations in tumorigenesis
B . Walther1 , I . Walther2 , Y . Chen1 , I . Petersen1 1 2 Jena University Hospital, Jena University Hospital, Institute of Pathology
Aims. The GNAS-1 gene is located on chromosome 20 and encodes for
the alpha-subunit of ubiquitary existing stimulatory G-proteins. The two
mutation hotspots R201H and R201C were evaluated which consists of
the replacement of arginine by histidine or cysteine, respectively. These
mutations have been previously reported in intramuscular myxomas representing
benign soft tissue tumors that are often found in near-trunk
muscle tissue of women. Furthermore, the McCune Albright syndrome
(MAS) being characterized by Café-au-lait spots, precocious puberty,
polyostotic fibrous dysplasia (FD) and other endocrine abnormalities is
related to GNAS-1 mutations. In MAS, thyroid adenomas and carcinomas,
adrenocortical hyperplasia and adenomas and pituitary tumors do
occur. Moreover mutations were detected in isolated fibrous dysplasia
(FD) or in combination with intramuscular myxomas in the context of
the so called Mazabraud’s syndrome. The aim of the study was to evaluate
the prevalence of these mutations in intramuscular myxomas and to
verify the usefulness of mutations analysis in the differential diagnosis of
soft tissue and bone lesions.
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