96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
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Abstracts<br />
nal lymph nodes and splenomegaly. Investigation for TCR gamma gene<br />
rearrangement revealed the presence of a dominant amplificate. After<br />
8 cycles of standard cytotoxic chemotherapy according to the CHOP regimen<br />
a complete remission was achieved. Eleven years later, the patient<br />
presented with cervical and axillary lymphadenopathy and splenomegaly.<br />
Histological and immunohistological examination of an excised<br />
lymph node revealed a T-cell lymphoma with the characteristic features<br />
of AITL. Clonality analysis for TCR gamma chain genes revealed a clonal<br />
population with a different amplificate size that those from the initial<br />
manifestation.<br />
Conclusions. To our knowledge, this is the longest recurrence free period<br />
in AITL reported so far. Most interestingly the patient exhibited a novel<br />
T-cell clone at relapse not identifiable even among the minor clones at<br />
initial presentation.<br />
FR-P-153<br />
Severe central nervous system (CNS) graft versus host disease<br />
(GVHD) in a patient without any other GvHD symptoms after<br />
allogeneic stem cell transplantation<br />
C . Schra<strong>der</strong>1 , R . Stingele2 , W . Brück3 , I . Metz3 , C . Riedel4 , N . Schub1 , A . Humpe1 ,<br />
T . Valerius1 , G . Deuschel2 , M . Gramatzki1 , A . Günther1 1 2 2 University Hospital of Kiel, nd Department of Medicine, Kiel, UKSH, Campus<br />
Kiel, Department of Neurology, 3University of Göttingen, Department of<br />
Pathology, 4UKSH, Campus Kiel, Department of Neuroradiology<br />
Aims. Although graft versus horst disease (GvHD) is the most relevant<br />
complication of allogeneic stem cell transplantation (SCT), it rarely affects<br />
the central nervous system. Recently, a consensus conference proposed<br />
criteria of diagnosis for cerebral GvHD including the obligatory<br />
manifestation of chronic GvHD at other organs [Grauer et al., Brain, 133:<br />
2852, 2010]. We observed a 41-year-old women, who developed spastic<br />
paralysis and fell into coma 2.5 years after having an allogeneic peripheral<br />
blood stem cell stem cell transplantation (PBSCT) for acute myeloblastic<br />
leukemia from an unrelated HLA 9/10-matched donor. The patient<br />
presented with a history of several month of headache supposed to<br />
be caused by migraine. She had a history of acute GvHD stage III (skin<br />
and intestinal) but no signs of chronic GvHD. In addition she had no<br />
history of an independent autoimmunopathy or migraine prior to SCT.<br />
Methods. MRI scan was performed, cerebrospinal fluid was analyzed to<br />
exclude CNS relapse and infectious agents, and finally CNS biopsy was<br />
obtained by open brain surgery.<br />
Results. MRI scan showed disseminated severe leucencephalopathy without<br />
established sign of CNS relapse, lymphoma or typical infection. The<br />
cerebrospinal fluid analysis was normal. Toxoplasmosis and viral infection<br />
such as HSV, VZV, ADV, EBV, cmV, HHV-6 and HIV was excluded<br />
by PCR. The blood lymphocyte subset showed lymphopenia, however<br />
with normal CD4/CD8 ratio. Finally CNS biopsy revealed T-cells close<br />
to blood vessels – a pattern typical for cerebral GvHD. Immunosuppressive<br />
treatment was started with high dose steroids in combination with<br />
mycophenolatmofetil (MMF). She recovered rapidly and became completely<br />
awake within one week. After 9 months of immunosuppression<br />
the patient is competent in activities of daily living.<br />
Conclusions. GVHD of the central nervous system (CNS) is a rare disease<br />
after allogeneic stem cell transplantation. The absence of lymphocytes in<br />
the cerebrospinal fluid and normal CD4/CD8 ratio in peripheral blood<br />
does not exclude GvHD of the CNS. CNS biopsy should be consi<strong>der</strong>ed<br />
to confirm the diagnosis. This case demonstrates that CNS involvement<br />
can be the only manifestation of chronic GvHD. Immunosuppressive<br />
therapy may provide an impressive benefit in these patients.<br />
132 | Der Pathologe · Supplement 1 · 2012<br />
FR-P-154<br />
Tuberculous lymphadenitis and mycobacterium-negative granulomatous<br />
disease in patients receiving Imatinib mesylate (Glivec)<br />
treatment for gastrointestinal stromal tumors (GIST)<br />
A . Agaimy1 , A . Stegmann2 , A . Mackensen3 , N . Meidenbauer3 1Friedrich-Alexan<strong>der</strong> University of Erlangen, Institute of Pathology, Erlangen,<br />
2Friedrich-Alexan<strong>der</strong> University of Erlangen, Department of otorhinolaryngology,<br />
head and neck surgery, Erlangen, 3Friedrich-Alexan<strong>der</strong> University of<br />
Erlangen, Medical Clinic 5 , Erlangen<br />
Aims. Imatinib mesylate (IM) represents the standard treatment for patients<br />
with BCR-ABL-positive chronic myelogenous leukemia (CML) and<br />
is the first line adjuvant and palliative treatment modality for those with<br />
disseminated or inoperable gastrointestinal stromal tumor (GIST). IM is<br />
not known to be associated with an elevated risk for tuberculosis, since<br />
only five patients have been reported to date who developed tuberculosis<br />
during or after IM treatment for cmL (n=4) and GIST (n=1).<br />
Methods. We describe our experience with 3 patients (45–79 yrs of age)<br />
who developed necrotizing (caseating) granulomatous disease during<br />
IM treatment for GIST. Mean duration of treatment with Imatinib was<br />
9.5 (range: 9–48) months.<br />
Results. In 3 patients, enlarged lymph nodes with increased metabolism<br />
in Fludoxyglucose-Positron emission tomography (FDG-PET)-computer<br />
tomography-examinations were detected and resected. Affected sites<br />
were subcarinal/mediastinal (1), mediastinal/supraclavicular (1) and periparotideal<br />
cervical (1) lymph nodes. Histologic examination revealed<br />
necrotizing granulomatous disease suggestive of infection with M. tuberculosis<br />
or sarcoidosis. Sputum examination was negative for acid fast<br />
bacilli in all patients and DNA was negative for M. tuberculosis and other<br />
mycobacteria in two cases. However, M. tuberculosis was detected by<br />
PCR in the lymph node of one patient who was then successfully treated<br />
by antituberculous agents. All other patients received no anti-tuberculous<br />
therapy and were on complete response or stable neoplastic disease<br />
without evidence of progressive lymphadenopathy or lung lesions suggestive<br />
of active tuberculosis. Leucocyte and lymphocyte counts have<br />
been within normal limits throughout treatment with IM.<br />
Conclusions. Our observations un<strong>der</strong>line the necessity to sample enlarged<br />
or metabolic active lymph nodes developing during IM treatment<br />
for timely diagnosis and appropriate treatment of these rare complications.<br />
Follow up without treatment is safe for lesions without detection of<br />
M. tuberculosis by PCR. More studies are needed to clarify the potential<br />
causal relationship to IM treatment and to sufficiently explore the pathogenesis<br />
of lesions that were negative for M. tuberculosis.<br />
FR-P-155<br />
Therapeutic Polo-like kinase 1 inhibition results in mitotic arrest<br />
and subsequent cell death of leukemic cells in acute myeloid<br />
leukemia<br />
C . Münch1 , A .M . May1 , A .V . Pfister1 , K . Thurig1 , M . Lübbert2 , R . Wäsch2 ,<br />
T . Taube3 , S . Lassmann1 , M . Werner1 1 2 University Freiburg Medical Center, Institute of Pathology, Freiburg, University<br />
Freiburg Medical Center, Department of Hematology and Oncology,<br />
Freiburg, 3Boehringer Ingelheim Pharma GmbH & Co . KG, Clinical Research<br />
Aims. The mitotic kinase Polo-like kinase 1 (Plk1) is an important cell<br />
cycle regulator which is frequently overexpressed in acute myeloid leukaemia<br />
(AML). Our previous examination of AML blasts in pre- and posttreatment<br />
bone marrow biopsies of AML patients treated with the small<br />
molecule PLK1 inhibitor BI2536 revealed an increase of aberrant mitotic<br />
figures and apoptotic cells 24 hours after administration. The aim of<br />
this study was to extend this examination by investigating the effects of<br />
therapeutic PLK1 inhibition on AML cell lines and lymphoblastoid cell<br />
lines (LCLs) from healthy controls.<br />
Methods. Five AML cell lines (HL-60, KG1, OCIM2, NB4 and THP1)<br />
and two LCLs (LCL1 and LCL2) were cultured for 24 and 48 hours with