SUN-814 - Parathyroid Carcinoma Masquerading as Recurrent Adenoma: The Diagnostic Challenge of Ultra-Long Latency Recurrence

Introduction:
Parathyroid carcinoma (PC) accounts for < 1% of primary hyperparathyroidism (PHPT) cases. Most recurrences occur within 2–5 years and recurrence after >15 years is exceedingly rare. We report a case of PC presenting more than 15 years after initial parathyroidectomy for presumed adenoma, highlighting diagnostic features that should prompt early suspicion for malignancy.

Case Presentation:
A 41-year-old man presented with polydipsia and polyuria and was found to have severe hypercalcemia (calcium 14 mg/dL) with markedly elevated parathyroid hormone (PTH 527 pg/mL). This occurred over 15 years after parathyroidectomy at age 26 for presumed adenoma, following more than a decade of biochemical remission. The degree of hypercalcemia and PTH elevation was disproportionate to benign recurrence and raised concern for malignancy despite benign-appearing imaging. Ultrasound demonstrated a 1.7-cm hypoechoic lesion posterior to the left thyroid, with concordant delayed uptake on sestamibi scan.

Given extreme biochemical severity and young age at initial diagnosis, cinacalcet was initiated preoperatively. Surgical re-exploration revealed a firm, infiltrative left superior parathyroid mass, and en bloc resection with left thyroid lobectomy was performed. PTH declined from 527 pg/mL preoperatively to 3.6 pg/mL postoperatively, with normalization of calcium to 8.6 mg/dL. The patient developed hungry bone syndrome requiring calcium and calcitriol supplementation.

Pathology revealed a 1.7-cm hypercellular parathyroid neoplasm with thick fibrous bands, infiltrative growth into surrounding tissue, possible vascular invasion, scattered mitoses, Ki-67 approximately 5%, and loss of nuclear parafibromin expression, confirming parathyroid carcinoma. At 3-month follow-up, the patient remained in biochemical remission. Multidisciplinary tumor board recommended active surveillance which was supported by favorable prognostic features including complete resection, biochemical cure, Ki-67 < 10%, and N0 stage.

Discussion:
This case illustrates an exceptionally delayed presentation of parathyroid carcinoma, suggesting that the original lesion diagnosed as adenoma in a patient younger than 30 years likely represented unrecognized malignancy. Extreme biochemical severity, young-onset primary hyperparathyroidism, and recurrence after prolonged biochemical remission should heighten suspicion for carcinoma, even when localization studies appear benign. In patients with confirmed parathyroid carcinoma, germline CDC73 testing is recommended due to implications for recurrence risk and systemic surveillance. Extended follow-up data demonstrate that over one-third of recurrences occur beyond 10 years after surgery, underscoring the necessity for prolonged, often lifelong, biochemical surveillance with serial calcium and parathyroid hormone monitoring following resection.