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

DO-080
DOG1: an immunohistochemical marker for neoplastic chondroblasts
in chondroblastoma
H . Akpalo 1 , C . Lange 2 , J . Zustin 1
1 University Medical Center Hamburg-Eppendorf, Institute of Pathology,
Hamburg, 2 University Medical Center Hamburg-Eppendorf, Clinic for Stem
Cell Transplantation, Hamburg
Aims. Chondroblastoma represents less than 1% of all primary bone tumors
and typically presents in the epiphysis of long bones of young patients.
The tumor is composed of cartilaginous and osseous matrix along
with cellular portions with polygonal chondroblasts with indented nuclei
and scattered osteoclast-type multinucleated cells. In the current study,
we wished to investigate the expression of several established immunohistochemical
markers in the cellular portions of chondroblastomas.
Methods. Nine chondroblastomas, seven chondromyxoid fibromas, five
giant cell tumors of bone and tissues from five fetal femoral bone endings
were analyzed using immunohistochemical antibodies (CD34, SMA,
DOG1, CD117, and CD163).
Results. The cellular areas of chondroblastoma cases contained nests of
DOG1+ SMA+ CD117− CD34− chondroblasts, a phenotype that was not
detected in chondromyxoid fibroma cases or in giant cell tumors. The
remaining chondroblasts showed only low expression of DOG1 or negative
reaction. Furthermore, numerous CD163+ macrophages were detected
in all tumors which were analyzed in our study: chondroblastomas,
chondromyxoid fibromas and giant cell tumors.
Conclusions. We described membranous DOG1+ chondroblasts located
within cellular portions of chondroblastoma along with CD163+ macrophages
and multinucleated osteoclastic giant cells. Therefore, chondroblastoma
can be added to the tumors that are usually positive for DOG1,
alongside GIST, rare solid-pseudopapillary neoplasms of the pancreas as
well as exceptional mesenchymal tumors including peritoneal leiomyomatosis,
uterine type retroperitneal leiomyoma, and synovial sarcoma.
DO-081
Bone erosion and inflammation – polymorphonuclear neutrophils
promote generation of osteoclasts in osteomyelitis patients
M .M . Gaida1 , B . Mayer2 , S . Stegmaier2 , P . Schirmacher1 , C . Wagner3 ,
G .M . Hänsch2 1 2 University of Heidelberg, Institute of Pathology, Heidelberg, University
of Heidelberg, Institute of Immunology, Heidelberg, 3BG Trauma Center
Ludwigshafen, Ludwigshafen
Aims. Chronic and persistent inflammatory processes in the proximity of
bones may lead to severe bone erosion, requiring the amputation of the
respective limb. Aim of the present study was to elucidate the process of
bone erosion in the context of inflammation.
Methods. To explore the relationship between inflammation and bone
erosion, biopsies of patients with osteomyelitis due to arterial occlusive
disease or to diabetes mellitus were examined (n=31) and the inflammatory
infiltrate, bone erosion and infiltration of osteoclasts were quantified.
In parallel, interleukin (IL)-8-induced differentiation of CD14+
monocytes derived from the peripheral blood of healthy individuals
to osteoclasts was tested in vitro. The cells were cultivated with monocyte
colony stimulating factor (M-CSF) and IL-8, and for comparison
with the well established osteoclast-inducing receptor activator of Nf κ
B ligand (RANKL). To verify the activity of newly generated osteoclasts
the ability to degrade ivory slices was tested. The classical pathway of
the osteoclastogenesis (NFATc1 and c-fos) was explored by Western blot
analysis of isolated cytoplasmic and nuclear proteins after stimulating
the isolated monocytes with IL-8.
Results. In tissue sections of osteomyelitis patients, in areas of bone destruction,
the number of osteoclasts correlated significantly with the
extent of the leukocytic infiltrate, particularly with the number of polymorphonuclear
neutrophils (PMN). PMN recovered from the infec-
ted sites showed characteristics of activation and produced interleukin
(IL)-8. CD14 + monocytes derived from the peripheral blood of healthy
individuals were cultivated with (M-CSF) and IL-8, and within 3 days,
a translocation of the transcription factor NFATc1 into the nucleus was
seen, as begin of the differentiation into osteoclasts. By 10 to 20 days,
multinucleated cells with the typical osteoclast morphology appeared
which expressed tartrate-resistant acid phosphatase (TRAP) and cathepsin
K. Moreover, these cells were able to resorb bone.
Conclusions. In patients with persistent inflammatory disease and loss of
bone, the abundance of PMN in areas of bone resorption correlated with
the number of osteoclasts. Since activated PMN are known to produce
IL-8, which is able to induce osteoclast formation, we propose that PMN
promote bone destruction by local generation of osteoclasts and thus
provide a link between the inflammation and bone erosion.
DO-082
High IGF2 and FGFR3 are associated with tumor progression in
pleomorphic undifferentiated sarcomas, but EGFR and FGFR3
mutations are a rare event
K . Rüping1 , D . Katenkamp1 , Y . Chen1 , A . Altendorf Hofmann2 , U . Settmacher2 ,
I . Petersen1 , T . Knösel1 1 2 Friedrich-Schiller University, Institute of Pathology, Jena, Friedrich-Schiller
University, Department of General, Visceral und Vascular Surgery, Jena
Aims. Pleomorphic undifferentiated sarcoma (formerly known as malignant
fibrous histiocytoma, MFH) is meanwhile recognized as a morphological
growth pattern shared by a wide variety of poorly differentiated
malignant neoplasms, which include specific subtypes of pleomorphic
sarcomas. Nevertheless prognostic and therapeutic options in these tumors
are urgently needed.
Methods. 327 fibroblastic/myofibroblastic differentiated tumors consisted
of 203 pleomorphic undifferentiated sarcomas, 42 low grade sarcomas
(10 low grade fibromyxoid sarcoma, 32 low grade myofibroblastic
sarcomas) and 82 pseudosarcomatous tumors of the fasciitis family were
analyzed immunohistochemically and correlated with clinicopathological
parameters. Additionally mutational analysis was performed on high
expressed specimens of EGFR and FGFR3.
Results. High expression was found in PDGFRA (45%), PDGFRB (35%),
EGFR (3.4%), TFE (30%), KDR (1.5%), IGF2 (68%), FGFR1 (6.5%) and
FGFR3 (52%). High expression of IGF2 and FGFR3 was significantly
correlated with higher tumor grading (low versus high, p5 cm, p