Mystery Case of Parathyroid Carcinoma Masquerading as a Thyroid Nodule

Abstract

Introduction: Parathyroid carcinoma is a rare malignancy with a prevalence of 0.005%. Patients typically present with symptoms of hypercalcemia and elevated parathyroid hormone (PTH) levels. Non-functional parathyroid carcinoma presenting with neck pain and normal calcium is a unique and challenging entity. We describe a challenging case of normocalcemic parathyroid carcinoma presenting as neck pain. Case Description: A 59-year old woman with a history of asthma, type 2 diabetes, and tobacco use presented with neck pain and swelling worsening over months. On physical exam, she was noted to have right-sided thyroid mass. CT scan of the neck showed an enlarged thyroid gland with a 1.6 cm nodule with evidence of the trachea’s compression. Subsequent thyroid US revealed a 2.1 cm dominant solid, hypoechoic nodule in the right thyroid lobe. Initial testing revealed normal calcium levels; however, PTH level was not available. FNA of the nodule was non-diagnostic with subsequent repeat FNA interpreted as benign mass. Due to suspicious imaging features and significant neck discomfort, she underwent right hemithyroidectomy. During the surgery, the nodule was noted to be invasive with evidence of extrathyroidal extension. Postoperatively calcium was 8.9 mg/dl (8.6–10.4 mg/dl), ionized calcium 4.7 mg/dl (4.8–5.6mg/dl), PTH 48 pg/mL (14–64 pg/ml), and vitamin D25OH 48 ng/dL (30-100ng/dl). TSH was mildly elevated at 4.59 uIU/ml (0.27–4.2 uIU/ml) with free T4 of 1.09 ng/dl (0.93–1.70ng/dl). The preliminary pathology report described follicular thyroid carcinoma; however, immunostains failed to confirm primary thyroid cancer. The lesion was negative for TTF-1, PAX8, TG, CEA, calcitonin, chromogranin, and synaptophysin. The tumor was strongly positive for GATA3, PTH and positive in nuclear staining for parafibroma. The specimen was evaluated by two pathologists who favored the diagnosis of parathyroid carcinoma. A separate incidental microscopic 4mm papillary thyroid carcinoma (PTC) was found and tested positive for BRAF mutation. Genetic testing for CDC73 was negative. PET scan showed increased uptake in the right thyroid bed. Given microscopic PTC and mildly elevated TSH, she was started on levothyroxine. The patient recovered successfully after the surgery with the resolution of symptoms. She was evaluated by an oncologist, and adjuvant radiation therapy was recommended. Conclusion: Non-functional parathyroid carcinoma is a unique entity, and its diagnosis may be delayed given an atypical presentation and normal endocrine function. Differentiation between nonfunctioning parathyroid carcinoma, parathyroid adenoma, and thyroid disease based on location and proximity to the thyroid may be challenging. Although concomitant thyroid disease is not uncommon, synchronous thyroid cancer is very rare.