Primary squamous cell carcinoma of thyroid with a novel BRAF mutation and High PDL-1 expression: A case report with treatment implications and review of literature

Primary squamous cell carcinoma of thyroid (SCC-T) is an extremely rare, aggressive neoplasm with median survival of 9 months. Pure squamous morphology with absence of other cell types is required for diagnosis of SCC-T. Clinically, SCC-T behaves like anaplastic thyroid carcinoma (ATC) showing rapid growth, and extra thyroidal extension. We report a 91-year-old woman presenting with an enlarging thyroid mass and accompanying dysphagia and hoarseness. Fine needle aspiration revealed hypercellular specimen with large, pleomorphic, malignant cells. Intraoperative assessment revealed an inoperable tumor involving both thyroid lobes and extensively infiltrating surrounding soft tissues. A subtotal thyroidectomy was performed. Histology revealed squamous cell carcinoma replacing native thyroid tissue and infiltrating adjacent skeletal muscle. Lymphovascular and perineural invasion were present. Immunohistochemistry showed tumor cells positive for CK5-p40, Pax-8, TTF-1 and negative for thyroglobulin. P53 expression by IHC was high and Ki-67 proliferation index was > 90 %. (Next generation sequencing revealed a novel BRAF mutation (BRAF c.1799 T > A; 1801_1812del) along with TP53 and TERT mutations. PDL-1 immunohistochemistry showed positive expression in tumor cells (>80%), making patient also amenable to anti-PDL-1 immunotherapy. Patient was treated with BRAF inhibitor therapy with initial relief but eventually was put on hospice care due to increasing intolerance to therapy. This case represents a rare thyroid malignancy with a unique molecular signature consisting of a novel BRAF mutation [previously not described in SCC-T or ATC], associated with TERT-TP53 mutations. Further, importance of PDL-1 testing as a prognostic marker and as a guide to immunotherapy in refractory tumors is discussed.