Sinonasal Myxoma: A Distinct Entity or a Myxoid Variant of Desmoid Fibromatosis?

Sinonasal myxoma (SNM) is a rare benign mesenchymal tumor that arises in the sinonasal cavity or maxilla and almost exclusively affects young children. Currently, it is considered a specific entity, but its molecular characteristics have not been reported. Lesions diagnosed as SNM and odontogenic myxoma/fibromyxoma (OM/OFM) were identified from the participating institutions, and the clinicopathologic features were recorded. Immunohistochemistry for β-catenin was performed on all cases with available tissue. Next-generation sequencing (NGS) was performed on all SNM cases. Five patients with SNM were identified, including 3 boys and 2 girls with an age range of 20-36 months (mean: 26 months). The tumors were well-defined, centered in the maxillary sinus, surrounded by a rim of woven bone, and composed of a moderately cellular proliferation of spindle cells oriented in intersecting fascicles in a variably myxocollagenous stroma that contained extravasated erythrocytes. Histologically, the tumors resembled myxoid desmoid fibromatosis. Three tested cases showed nuclear expression of β-catenin. In 3 tumors, NGS revealed intragenic deletions of APC exons 5-6, 9 and 15, or 16, respectively, with concurrent loss of the other wild-type copy of APC, predicted to result in biallelic inactivation. The deletions were identical to those that occur in desmoid fibromatosis, and copy-number analysis raised the possibility that they were germline. In addition, one case showed possible deletion of APC exons 12-14, and another case exhibited a CTNNB1 p.S33C mutation. Ten patients with OM/OFM were identified, including 4 women and 6 men (mean age: 42 years). Seven tumors involved the mandible, and 3 the maxilla. Histologically, the tumors differed from SNM, and all cases lacked nuclear expression of β-catenin. These findings suggest that SNM represents a myxoid variant of desmoid fibromatosis that often arises in the maxilla. Because the APC alterations might be germline, genetic testing of the affected patients should be considered.