Background: The thyroid gland is a treasure trove of pathology ranging from the benign to the overtly malignant. Both neoplastic and nonneoplastic thyroid lesions can exhibit oncocytic change. Here we present an overview of cytologic and histopathologic findings encountered in these oncocytic neoplasms with a focus on the molecular aspects that drive their tumorigenesis. Summary: Oncocytic change is unique to a subset of thyroid lesions ranging from nonneoplastic nodular hyperplasia to high-grade malignancy. It can also be encountered in non-follicular-derived neoplasms as well as in the adjacent parathyroid glands. At the genetic level, these lesions demonstrate a different genetic signature from classic follicular-derived lesions, often involving alterations of mitochondrial genes. Key Messages: Oncocytic change can be seen in nonneoplastic and neoplastic thyroid pathology. Rarely, oncocytic change can be seen in medullary thyroid carcinoma and certain subtypes of papillary thyroid carcinoma as well as the parathyroid gland. Oncocytic neoplasms of the thyroid harbor molecular alterations often involving mitochondrial genes, which is distinct from other thyroid neoplasia.

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