High-Grade Transformation of Low-Grade Biphenotypic Sinonasal Sarcoma: A Morphological, Immunohistochemical, and Molecular Study

Objective: Biphenotypic sinonasal sarcoma (BSNS) is a recently described distinct spindle cell sarcoma with neural and myogenic differentiation which arises exclusively in the sinonasal region. Previously, these tumors were diagnosed as other (low-grade) mesenchymal tumors: nerve sheath tumors, fibrosarcoma, malignant peripheral nerve sheath tumors (MPNST), myofibrosarcoma, monophasic synovial sarcoma (SS). By immunohistochemistry, BSNS characteristically express S100 and smooth muscle actin (SMA) and/ or muscle specific actin (MSA). Its identification as a separate entity was supported by the presence of a distinctive genetic signature t(2;4) resulting in fusion of PAX3 gene, which behaves as regulator of neural crest and myogenic differentiation, with a variety of fusion partners. The most frequent translocation partner is MAML3 (mastermind like transcriptional cofactor 3).

Herein, we describe the clinicopathologic features and gene fusion status of one case of recurrent BSNS and its reclassification from synovial sarcoma diagnosis rendered at initial presentation.

Method and Results: A 66-year-old man presented with swelling of left eyelid, vertical diplopia and purulent nasal discharge. Pertinent history was a bifrontal craniotomy and trans-nasal approach performed 15 years before, for resection of a low-grade spindle cell mesenchymal tumor of left sinonasal cavity extending to the anterior skull base and left orbital wall. The original diagnosis was synovial sarcoma; with post-operative IMRT and chemotherapy.

The patient was followed up in the HN survivorship clinic with no evidence of disease.

Current MRI showed left supraorbital mass with intracranial extension, suspicious for recurrence. IR biopsy confirmed recurrence of spindle cell mesenchymal tumor, and a left orbital craniotomy was done for resection of the orbital tumor. The recurrence displayed geographical necrosis, increased proliferation rate (K_i-67~70%) and brisk mitotic count (25 MF/1 mm2), bone invasion- morphological features warranting a higher-grade sarcoma. Immunophenotypically, there was patchy expression of SMA and S100, and mosaic expression of H3K27me (partial loss). A comprehensive next generation sequencing performed to test for the presence of rearrangement in 138 target genes identified PAX3-MAML3 fusion. NGS retrospectively identified the same fusion in the original sarcoma- as molecular signature of BSNS. NGS and FISH studies did not support the original diagnosis of synovial sarcoma (absence of SS18-SSX2 fusion transcript and no rearrangement for SS18(SYT). The sarcoma was reclassified as BSNS, recurrent, with higher grade transformation. While the morphology, phenotype and molecular signature were in keeping with BSNS, the tumor showed biological progression toward a high-grade sarcoma (akin to MPNST).

The patient underwent reirradiation, SBRT, 5 fractions. Ten months postsurgery, surveillance MRIs confirmed NED, with stable postoperative changes.

Conclusion: High-grade transformation of low-grade BSNS has not been described /published so far. High-grade transformation in our case was not appreciated at the time of initial diagnosis, and it occurred in the local recurrence 15 years after. Awareness of this BSNS entity and recognition of high-grade features are important, as despite PAX3-MAML3 abnormality, it shows high-grade features which may indicate more aggressive behavior.

Due to an impression of a relatively indolent clinical course, the recognition of BSNS is of paramount importance to facilitate proper clinical management.

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Artikel online veröffentlicht:
15. Februar 2022