MON-760 An Extremely Rare Case of Nonfunctioning Parathyroid Carcinoma

Abstract Disclosure: L.M. Santos: None. L. Figueiredo: None. G.O. Martins: None. L.A. Alvares: None. J.V. Lima: None. T.W. Melero: None. M. Galvão Silva: None. N. Scalissi: None. Introduction: Parathyroid carcinoma is a rare endocrine malignancy, accounting for less than 1% of primary hyperparathyroidism cases. It is typically associated with severe hypercalcemia and elevated PTH levels. However, nonfunctioning parathyroid carcinoma, which lacks significant biochemical alterations, is even rarer and presents a diagnostic challenge. Due to its aggressive nature, early identification and surgical management are crucial for improving patient outcomes. Objective: To report a rare case of nonfunctioning parathyroid carcinoma and discuss its clinical presentation, diagnostic challenges, genetic findings, and therapeutic approach based on a multidisciplinary evaluation. Methods: A retrospective review was conducted on a patient diagnosed with nonfunctioning parathyroid carcinoma. Clinical, laboratory, imaging, histopathological, and genetic data, as well as follow-up evaluations, were analyzed to assess disease progression and treatment response. Case Report: A 53-year-old female was referred for evaluation of a progressively enlarging anterior cervical mass over six months. She denied symptoms of hypo/hyperthyroidism, cervical compression, flushing, or gastrointestinal disturbances. Initial tests showed normal thyroid function, calcitonin, and CEA levels; calcium levels were not assessed. Fine-needle aspiration (FNA) biopsy revealed Bethesda II in the left thyroid lobe, suggesting atypia of undetermined significance. A neck CT scan showed heterogeneous enlargement of the left thyroid lobe extending into the superior mediastinum. The patient underwent total thyroidectomy, and histopathological examination revealed a 9.5 cm, 131 g parathyroid carcinoma with clear cell predominance, capsular, muscular, and vascular invasion, and Ki-67 = 30%, with positive RCC, CK7, CK20, AE1/AE3, chromogranin, and GATA3 markers. Genetic analysis identified a variant of uncertain significance (VUS) in SDHA (PM2, PP3) and another VUS in GCM2 (PP3), with no well-defined pathogenic mechanism. No CDC73 mutations were found. The patient later developed tumor regrowth, with a parathyroid scintigraphy scan revealing nodular radiotracer hyperconcentration in the right cervical region (3.3 × 2.5 cm). A second surgery was performed with expanded margins and lymph node dissection. Despite tumor progression, she did not develop hypercalcemia or elevated PTH levels. She is currently undergoing radiotherapy and remains free of distant metastases. Conclusion: This case highlights the importance of histopathological evaluation, immunohistochemical markers, and genetic analysis in differentiating it from other thyroid and parathyroid lesions. The presence of VUS in SDHA and GCM2 suggests a need for further investigation into their role in tumorigenesis. The absence of CDC73 mutations implies alternative molecular pathways. Presentation: Monday, July 14, 2025