Synchronous triple thyroid neoplasms with unique molecular alterations: A rare case report

Abstract

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma are common subtypes of thyroid cancer, while hyalinizing trabecular tumor (HHT) of the thyroid is a rare peculiar type of follicular cell neoplasm. Although all three tumor types originate from thyroid follicular cells, the frequency of their co-presence in the same thyroid gland is unknown. Herein, we describe an extremely rare case with three types of concurrent thyroid neoplasms in one patient. This patient was a 60-year-old female who presented with large symptomatic multinodular goiter clinically. Fine needle aspiration of the right thyroid nodule showed atypia of undetermined significance. She then received total thyroidectomy. Microscopically, there were 3 types of tumors identified: multifocal (x4) PTC (largest focus 1.5 cm) with focal tall cell features, encapsulated angioinvasive oncocytic carcinoma (8.2 cm), and a small HHT (0.6 cm). The HHT was encapsulated, containing spindled to polygonal cells with oval to elongated nuclei arranged in a trabecular growth pattern. The PTC and oncocytic carcinoma were diagnosed by morphology only. The diagnosis of HHT was confirmed by immunohistochemistry showing the tumor cells to be positive for pan-cytokeratin, thyroglobulin, TTF-1, and PAX8, while negative for synaptophysin, chromogranin, and calcitonin. Next generation sequencing demonstrated different molecular alterations: BRAF V600E mutation in PTC; NRAS mutation in oncocytic carcinoma, and HRAS mutation in HHT. This is the first case report of triple thyroid neoplasms occurring synchronously in one patient. The unique genetic alteration of each individual tumor suggests different pathogenetic mechanisms.