Rare Finding of Parathyroid Carcinoma in Setting of MEN2A and Metastatic Medullary Thyroid Cancer

Multiple Endocrine Neoplasia Type 2A (MEN2A), in addition to Medullary Thyroid Cancer (MTC), may include Pheochromocytomas and/or parathyroid adenomas. Here we present a case of MEN2A with Metastatic MTC with a rare finding of parathyroid carcinoma.

Case Description:

A 45-year-old female with medical history significant for Multinodular Goiter, Hyperparathyroidism, and Hypercalcemia. She presented for initial evaluation due to family history of Medullary Thyroid Cancer (MTC). Her mother’s diagnosis occurred in her 30’s with liver metastasis. While her sister died at the age of 35, from Metastatic MTC in the setting of MEN2A. Of note, our patient’s family lineage includes two cousins who married, and could be the source of the mutation. Our patient was asymptomatic at the time of initial presentation. Thyroid US was significant for 5 nodules, 3 of which had suspicious features of hypoechogenicity, calcifications and internal vascularity. Biopsy returned as Bethesda category IV consistent with medullary thyroid carcinoma. CT chest/abdomen/pelvis revealed upper mediastinal lymphadenopathy, and a non-specific 18 mm left adrenal mass. Labs revealed a Calcitonin level of 15630 (normal < 10 pg/ml), PTH level of 121(normal 10-55 pg/ml), and a CEA level of 387 (normal 0-2.5 ng/ml). Additional labs ruled out hormone secretion of the adrenal nodule. On genetic testing, patient was found to be heterozygous for p.C634Y mutation, a DNA sequence change from G to A at nucleotide position c.1901 in exon 11 of the RET gene. Commonly this is associated with MEN2A and familial MTC. She underwent a total thyroidectomy with neck dissection and parathyroidectomy. Final pathology confirmed metastatic medullary thyroid carcinoma with rare finding of parathyroid carcinoma. Post-operatively, patient was treated with Levothyroxine, Calcium carbonate and Calcitriol. Unfortunately, post operatively her CEA and Calcitonin remained high, 130 and 5775, respectively. PET scan revealed bilateral hypermetabolic cervical lymphadenopathy concerning for metastatic disease, left axillary lymphadenopathy and left adrenal mass. Patient underwent additional neck dissection, started Retevmo, and is currently under consideration for left adrenal nodule resection.

Discussion:

This case demonstrates an unusual, and rare finding of parathyroid carcinoma. Majority of patients with MEN2A have medullary thyroid carcinoma, pheochromocytoma and a parathyroid adenoma. Parathyroid carcinoma has an incidence of less than one percent of all cases of primary hyperparathyroidism and usually presents with a significant parathyroid hormone elevation. Along with being one of the overall rarest cancers, it is the single rarest endocrine malignancy.