JAZF1/PHF1 Rearrangement in Primary Ossifying Sarcomas of the Heart: A Novel Gene Fusion
John K Schoolmeester, Andrew L Folpe, William R Sukov, Jennelle C Hodge, Joseph J Maleszewski. Mayo Clinic, Rochester, MN
Background: Primary cardiac sarcomas represent a diverse group of malignancies, the majority of which lack recurrent translocations. Of the described translocation-associated cardiac sarcomas, synovial sarcoma is most common, with isolated reported cases of infantile fibrosarcoma, alveolar soft part sarcoma and low-grade fibromyxoid sarcoma.
Design: As part of a clinical validation for break apart strategy JAZF1 and PHF1 fluorescence in situ hybridization (FISH) probes, we identified a pulmonary metastasis that showed rearrangement of both loci. This lesion was from an unusual, distinctive ossifying cardiac sarcoma. Retrospective review of institutional cardiac sarcomas with ossification identified two additional cases. Histologic sections from all three cases were reviewed and corresponding formalin-fixed, paraffin-embedded tissue was tested for JAZF1 and PHF1 gene rearrangements. Cases showing rearrangement of both were then tested for JAZF1/PHF1 fusion using a dual-color, double fusion FISH probe.
Results: The tumors occurred in 1 man and 2 women, with age at presentation ranging from 59 to 70 years (mean 65.6 years). Tumors arose in the inferoseptal left and right ventricles (1 case) and left atrium (2 cases) and ranged from 6.8 to 10.0 cm (mean 8.3 cm). The tumor from the original patient showed a distinctive morphology including monomorphic cells, nuclear palisading and ossifying “amianthoid fiber-like” collagen. FISH confirmed JAZF1 and PHF1 gene rearrangements and JAZF1/PHF1 fusion. The remaining 2 cases showed a more pleomorphic infiltrate with areas of ossification, consistent with osteogenic sarcoma of the heart. These tumors were negative for JAZF1 and PHF1 rearrangements. All patients died of disease.
Conclusions: To the best of our knowledge, this represents the first example of a non-endometrial stromal neoplasm demonstrating a JAZF1 gene rearrangement. Given the patient's male sex, the tumor's distinctive morphology, the presence of a JAZF1/PHF1 gene fusion, and the absence of similar rearrangements in conventional cardiac osteosarcomas, this may represent a new entity among cardiac sarcomas, however confirmation of this hypothesis requires evaluation of additional similar cases.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 46, Wednesday Morning