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Chondrosarcoma with Target-Like Chondrocytes: Update on Molecular Profiling and Specific Morphological Features
1Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, and Institute of Postgraduate Studies, Prague, Czech Republic.
Abstract:
This is the first histological and molecular analysis of two chondrosarcomas with target-like chondrocytes that were compared with a group of conventional chondrosarcomas and enchondromas. The unique histological feature of target-like chondrocytes is the presence of unusual hypertrophic eosinophilic APAS-positive perichondrocytic rings (baskets). In the sections stained with Safranin O/Fast green, the outer part of the ring was blue and the material in the lacunar space stained orange, similarly to intercellular regions. Immunohistochemical examination showed strong positivity for vimentin, factor XIIIa, cyclin D1, osteonectin, B-cell lymphoma 2 apoptosis regulator (Bcl-2), p53 and p16. The S-100 protein was positive in 25 % of neoplastic cells. Antibodies against GFAP, D2-40 (podoplanin), CD99, CKAE1.3 and CD10 exhibited weak focal positivity. Pericellular rings/baskets contained type VI collagen in their peripheral part, in contrast to the type II collagen in intercellular interterritorial spaces. Ultrastructural examination revealed that pericellular rings contained an intralacunar component composed of microfibrils with abundant admixture of aggregates of dense amorphous non-fibrillar material. The outer extralacunar zone was made up of a layer of condensed thin collagen fibrils with admixture of non-fibrillar dense material. NGS sequencing identified a fusion transcript involving fibronectin 1 (FN1) and fibroblast growth factor receptor 2 (FGFR2) at the RNA level. At the DNA level, no significant variant was revealed except for the presumably germline variant in the SPTA1 gene.
Insights
This study reveals unique chondrosarcoma features, identifying target-like chondrocytes with specific perichondrocytic rings. A novel FN1-FGFR2 fusion transcript was discovered in these rare bone tumors.
Area of Science:
- Oncology
- Histopathology
- Molecular Biology
Background:
- Chondrosarcomas are malignant tumors of cartilage.
- Target-like chondrocytes represent a rare histological subtype.
- Understanding their unique features is crucial for diagnosis and treatment.
Purpose of the Study:
- To perform the first histological and molecular analysis of chondrosarcomas with target-like chondrocytes.
- To compare these tumors with conventional chondrosarcomas and enchondromas.
- To identify the molecular underpinnings of this rare chondrosarcoma variant.
Main Methods:
- Histological and immunohistochemical analysis of tumor samples.
- Safranin O/Fast green staining for matrix components.
- Ultrastructural examination of pericellular structures.
- Next-generation sequencing (NGS) for molecular profiling.
Main Results:
- Target-like chondrocytes exhibit eosinophilic, APAS-positive perichondrocytic rings ('baskets').
- Immunohistochemistry showed positivity for vimentin, factor XIIIa, cyclin D1, osteonectin, Bcl-2, p53, and p16.
- Pericellular rings contained type VI collagen, distinct from intercellular type II collagen.
- NGS identified a novel FN1-FGFR2 fusion transcript at the RNA level.
Conclusions:
- Chondrosarcomas with target-like chondrocytes possess distinct histological and ultrastructural features.
- The identified FN1-FGFR2 fusion transcript may play a role in the pathogenesis of these rare tumors.
- Further research is warranted to elucidate the clinical significance of this finding.

