Case of the Week

Next generation sequencing of this tumor identified a FN1::TEK gene fusion. Fusions of FN1 with various receptor tyrosine kinase genes (including TEK, FGFR2, FGFR1, MERTK and NTRK1 have been observed in calcified chondroid mesenchymal neoplasms.

This is a newly recognized group of benign soft‑tissue tumors termed calcified chondroid mesenchymal neoplasms (CCMN). These tumors most often arise in the temporomandibular joint and distal extremities, show nodular/lobular growth of polygonal to stellate cells in a chondroid matrix, and frequently contain grungy or lace‑like (chondroblastoma‑like) calcifications, sometimes with CPPD crystal deposition and focal tenosynovial giant cell tumor (TGCT)-like features. Using targeted RNA sequencing, these tumors harbor recurrent FN1-receptor tyrosine kinase gene fusions in most cases, most commonly FN1::FGFR2, but also FN1::FGFR1 and novel fusions involving MERTK, NTRK1, and TEK, supporting a shared molecular pathogenesis. Although these lesions overlap morphologically with chondroblastoma‑like soft tissue chondroma, chondroid TGCT, and tumoral pseudogout, their distinctive fusion profile and expanded morphologic spectrum justify recognition as a separate diagnostic category with generally indolent behavior after excision.

Reference:

Liu YJ, Wang W, Yeh J, et al. Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including FGFR2, FGFR1, MERTK, NTRK1, and TEK: a molecular and clinicopathologic analysis. Mod Pathol. 2021 Jul;34(7):1373-1383.