Case of Concurrent MTC and PTC in a Patient with a Germline RET Mutation.

Abstract

Dear Editor, It is well known that medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) have different histogeneses, the former being of neuroectodermal and the latter of endodermal origin. The simultaneous occurrence of these two tumors is a rare phenomenon, observed either as a mixed tumor (dual differentiation) or as a concurrent/collision tumor (spatially different tumors with well-defined components) [1]. We describe a case of concurrent MTC and PTC in a patient with a RET proto-oncogene germline mutation. A 63-year-old male, with type 2 DM, stage III chronic kidney disease (CKD), and hypertension, without prior history of head and neck radiation or family history of endocrine disease, was evaluated for an asymptomatic goiter. Thyroid ultrasound revealed a 0.6× 0.9×1.2 cm solid hypoechoic nodule with microcalcification in the right superior thyroid lobe. Fine needle aspiration biopsy (FNAB) was suspicious for medullary neoplasm. Calcitonin was high (175 pg/ml) and carcinoembryogenic antigen (CEA) was normal (3.3 ng/ml). Urine catecholamines and metanephrines were normal. He underwent total thyroidectomy and central lymph node dissection. There was a 0.5×0.7×1.5 cm MTC in the right lobe with capsular invasion without extra-thyroidal extension or perineural invasion. 1/5 level VI lymph nodes was positive for metastatic disease. The tumor cells were positive for calcitonin, CEA, and thyroid transcription factor-1 (TTF-1) and negative for thyroglobulin. C-cell hyperplasia was present (Fig. 1). A spatially distinct 0.4-cm second tumor was identified in the right lobe, focally invading the perithyroid fibroadipose tissue suggestive of extrathyroidal extension. The tumor cells were positive for cytokeratin-19 (CK19) and galectin and negative for calcitonin, consistent with micro-PTC (Fig. 2). Baseline and stimulated thyroglobulin were undetectable. Whole body scan showed two small foci of faint activity in the thyroid bed. RET proto-oncogene germline genetic testing was positive for Y791F (Tyr791Phe) in exon 13. This mutation is associated with low penetrance and less aggressive MTC. Somatic BRAF was not identified in either PTC or MTC tumors (Fig. 3a, b). The PTC tissue was negative for RET/PTC1 and RET/PTC3 rearrangements. CT scan of the chest, neck, and abdomen revealed multiple normal appearing cervical and mediastinal lymph nodes. A left adrenal adenoma measuring 1.9 cm was noted. Salivary cortisol, plasma aldosterone, and plasma renin activity were normal which suggested a non-functioning adrenal adenoma. Secondary hyperparathyroidism was attributed to vitamin D deficiency and CKD and was treated with vitamin D and calcium. Stage III MTC (pT1bN1aM0) and an * Robert J. Anderson Robert.Anderson4@va.gov