Clinicopathological and molecular features of biphenotypic sinonasal sarcoma

Abstract

Objective: To study the clinicopathologic features, immunophenotype, molecular genetics and differential diagnosis of biphenotypic sinonasal sarcoma (BSNS), and to evaluate the role of PAX3 and PAX8 immunohistochemical (IHC) antibodies in the diagnosis of BSNS. Methods: Nasal sinus spindle cell tumors surgically treated at the Jinling Hospital from 2000 to 2019 were collected, including three cases of BSNS, 10 cases of acinar rhabdomyosarcoma, eight cases of schwannoma, five cases of hemangiopericytoma, three cases of fibrosarcoma, and one case of triton tumor. The cases were evaluated by histology, IHC by EnVision for PAX3 and PAX 8 (including PAX8 murine monoclonal antibody, clone number OTI6H8, hereinafter referred to as PAX8-OTI6H8 antibody; PAX8 rabbit monoclonal antibody, clone number EP298, hereinafter referred to as PAX8-EP298 antibody) molecular genetic tests. Results: All three BSNS patients were elderly women with clinical manifestations of nasal congestion and bleeding. Imaging showed a soft tissue density shadow of the nasal cavity and sinuses with bone destruction. The boundaries of tumors which were covered with ciliated columnar epithelium were unclear, and mucosal invasion and squamous metaplasia could be seen. Tumor cells were spindle-shaped, arranged in a bundle-like, braided arrangement, with little cellular atypia and occasional atypical mitotic figures. The tumoral interstitial vessels were mostly thin-walled, some showing staghorn-like changes. There was focal striated muscle differentiation in two cases, and bone invasion was seen in two cases. IHC staining showed that all three cases of BSNS expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. All eight cases of schwannoma, five cases of hemangiopericytoma, and one case of triton tumor did not express PAX3, PAX8-OTI6H8 or PAX8-EP298. Eight of the ten cases of alveolar rhabdomyosarcoma expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. Three cases of fibrosarcoma showed weak PAX3 and PAX8-OTI6H8 expression, but there was no PAX8-EP298 expression. FISH detection showed that PAX3 break apart in the tumor cells from all three patients (four specimens). Conclusions: BSNS is a distinct sinonasal low grade malignancy with dual differentiation which could be readily confused with a variety of spindle cell tumors encountered in the sinonasal cavity. The molecular genetics of PAX3 gene break is the gold standard for diagnosis of this tumor. IHC marker monoclonal PAX3 is 100% expressed in BSNS, while the specificity is limited. PAX8-OTI6H8 is also expressed in BSNS due to the cross reaction with PAX3 antibody, while PAX8-EP298 is all negative for these tumors.