Thyroid Makes Three: Incidental Discovery of Medullary Thyroid Cancer

Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) arising from parafollicular or C cells and accounts for 3-4% of all thyroid cancers. MTC is either sporadic or familiar, with the sporadic form accounting for 75-80% of cases. The familial form is associated with germline mutations in the Rearranged during Transfection (RET) proto-oncogene. Most MTC cases are found during the evaluation of thyroid nodules. We report a case of incidentally discovered medullary thyroid cancer during the staging of a mucosa-associated lymphoid tissue (MALT) lymphoma of the bladder.

Case Description :

A 69-year-old male with a history of papillary urothelial carcinoma in 2015 was found to have a MALT lymphoma of the bladder during an asymptomatic routine screening cystoscopy. A staging positron emission tomography (PET) scan revealed an incidental right thyroid nodule with mild PET avidity. Thyroid ultrasound showed a TIRADS 4 right-sided 3.0 x 2.4 x 2.3 cm nodule. Fine needle aspiration (FNA) resulted with atypia of undetermined significance and molecular testing showed overexpression of microRNA 375, suggestive of MTC. The patient had a normal TSH 2.63 mcIU/mL (0.358-3.74), free T4 1.04 ng/dL (0.76-1.46), and CEA 1.0 ng/mL (0.0-3.0), with an elevated calcitonin 24.2 pg/mL (0.0-8.4). Genetic screening showed no mutations in exons 10, 11, 13, 14, 15, and 16 of the RET gene, indicating this was likely a sporadic case of MTC. Pheochromocytoma was ruled out and otolaryngology performed a total thyroidectomy with bilateral level VI/VII neck dissection. Pathology revealed a 3.1cm MTC with angio/lymphatic invasion, 5/5 lymph nodes positive for disease, and negative margins. Patient’s calcitonin was undetectable after eight weeks and follow-up ultrasound showed no disease.

Discussion :

Medullary thyroid cancer is an uncommon thyroid cancer usually discovered during the evaluation of solitary thyroid nodules or multinodular goiters. This case was found incidentally on a staging PET scan and utilized molecular testing of the FNA sample to make a diagnosis. This patient had three forms of primary cancers in the past 6 years and a strong family history of multiple malignancies. Review of current literature revealed no cases of MTC and MALT lymphoma, however a few cases noted other NETs occurring with MALT lymphoma and one case noted a patient with urothelial carcinoma and MTC. While no RET gene mutation was identified in this case, it is possible the combination could represent a new cancer syndrome or an undiscovered gene mutation. Further study is needed to determine if there is any link between urothelial carcinoma, MALT lymphoma, and medullary thyroid cancer.