Oncocytic Thyroid Tumours With Pathogenic FLCN Mutations Mimic Oncocytic Papillary Thyroid Carcinoma on Fine-Needle Aspiration.

Abstract

Background: Thyroid tumours occur in patients with Birt-Hogg-Dubé syndrome (BHD), a condition caused by germline alterations in the FLCN gene that confers an increased cancer risk. Somatic FLCN mutations may also contribute to tumorigenesis. In this study, we present the first description of the cytopathology of two thyroid tumours evaluated by fine-needle aspiration (FNA) and harbouring pathogenic FLCN mutations.

Methods: We encountered two patients with oncocytic thyroid tumours in which comprehensive next-generation sequencing (NGS) identified pathogenic FLCN mutations. We present the FNA cytologic findings and corresponding histopathology, and discuss the diagnostic challenges posed by the FNAs, one of which was initially confounded by negative preoperative molecular testing.

Results: Both patients were middle-aged females. Patient 1 had an incidental thyroid nodule and a history of BHD. FNA of a TI-RADS 5 mass was diagnosed as suspicious for papillary thyroid carcinoma (PTC), Bethesda V, leading to total thyroidectomy. Patient 2 presented with a palpable nodule. Compressive symptoms prompted lobectomy, revealing an angioinvasive oncocytic carcinoma. Subsequent FNA findings of a metastasis cytologically resembled oncocytic PTC; however, it was correctly diagnosed as oncocytic carcinoma after correlation with prior histologic findings. Expanded NGS testing facilitated the final diagnosis of FLCN-mutated oncocytic adenoma in Patient 1 and high-grade differentiated oncocytic carcinoma in Patient 2.

Conclusion: Thyroid tumours harbouring FLCN mutations with oncocytic features may mimic PTC cytologically. Although rare, correct diagnosis of these tumours is essential to ensure appropriate treatment. For early detection, patients with BHD may benefit from thyroid ultrasound surveillance.