A Case Report of Metastatic Medullary Thyroid Carcinoma

Introduction:
Medullary thyroid carcinoma is rare condition representing 1-2% of thyroid cancers originating from parafollicular calcitonin producing cells. Mutations are either sporadic or hereditary, the latter of which is associated with MEN2A/B and RET germline mutations. In this report, we present a case of medullary thyroid carcinoma in an 80 year old male identified by an incidental ultrasound finding.

Case Description:
Patient is an 80 year old male who originally presented to an ophthalmologist with chief complaint of vision loss. Ophthalmologic evaluation was consistent with ocular vein occlusion. The patient was sent for a carotid doppler which revealed an incidental finding of a large thyroid nodule. Dedicated thyroid ultrasound measured the left sided thyroid nodule to be 4.5cm. FNA and tissue pathology was consistent with follicular neoplasm, Bethesda Category 5 tissue that was highly suspicious for malignancy. Thyroseq TM molecular analysis revealed a KRAS-G12R mutation and overexpression miR375 suggestive of medullary thyroid carcinoma. He was referred to ENT surgery and obtained preoperative urine metanephrines, PTH, CEA and Calcitonin. His CEA and Calcitonin were both elevated (183 ng/mL and 10,103 pg/mL respectively) with a normal PTH (55 pg/mL) and urine metanephrines (146 ug/mL). During planned total thyroidectomy via radical left neck dissection, patient had signal loss of the left vagus nerve. Unfortunately, the right thyroidectomy was aborted with plans for completion thyroidectomy after recovery of the vagus nerve. Post-operative pathology revealed a 5.5 cm medullary thyroid carcinoma confined to the thyroid with fifteen lymph nodes positive for metastatic disease. Oncologic workup consisted of PET CT which revealed multiple sites of intrathoracic hypermetabolism and hilar lymphadenopathy consistent with metastatic disease. Most concerning was involvement of the pleural surface. In addition, there was a residual nodule detected in the remnant right thyroid lobe. Due to the disease burden, however, the decision was ultimately to not pursue completion thyroidectomy. Biopsy of the hilar lymph nodes was performed via endobronchial ultrasound with transbronchial needle aspiration. Tissue analysis did not reveal malignant cells. Currently, he awaits an official tissue diagnosis which delays chemotherapy.

Discussion:
The ideal treatment of medullary thyroid carcinoma involves early identification and total thyroidectomy. As an adjunct in advanced disease, the approach to surgery can be a more palliative focus to preserve function rather than disease eradication. Identification of the mutations as sporadic or hereditary also guides treatment as nearly all hereditary MEN2A/B, and 50% of sporadic mutations are of the RET proto-oncogene. In sporadic mutations, 18-80% of carcinomas that lack RET mutations have mutations of HRAS, KRAS or NRAS. In the case presented, chemotherapy will begin once pending mutation analysis is received.