Diagnostic Dilemma Involving a Rare Case of a CDC73 Parafibromin-Deficient Parathyroid Adenoma

Primary hyperparathyroidism (PHPT) is most commonly caused by sporadic parathyroid adenomas, although 10% of cases have an underlying genetic condition which is important to diagnose to facilitate appropriate long-term follow-up, and personal and family screening.

We present a 38-year-old Caucasian male, with no prior medical or family history, with severe symptomatic hypercalcemia due to PHPT with corrected calcium of 3.48 mmol/L (2.1-2.6) and parathyroid hormone level of 46 pmol/L (2.0-9.3). Localization studies subsequently revealed a large cystic parathyroid mass adjacent to the left inferior thyroid pole. Subsequently, he had a left inferior parathyroidectomy, and his histopathology and immunohistochemistry demonstrated a parafibromin-deficient atypical parathyroid tumor. Given the immunohistochemistry findings, screening tests for other manifestations of hyperparathyroidism jaw tumor (HPT-JT) syndrome in the jaw and kidneys were performed and were unremarkable. Germline testing with multiplex ligation-dependent probe amplification studies showed no pathologic mutation in the CDC73 gene.

The negative immunostaining for parafibromin in our patient is associated with HPT-JT syndrome, though germline testing has shown no pathologic mutation in the CDC73 gene. Given that our patient has only manifested with an atypical parafibromin-deficient parathyroid adenoma, we encounter a diagnostic dilemma on whether our patient has HPT-JT syndrome or familial isolated primary hyperparathyroidism, which is less commonly associated with CDC73 mutations.

In cases suspicious for HPT-JT syndrome, it is important to arrange follow-up for recurrent PHPT and other manifestations of HPT-JT syndrome, as patients with familial isolated PHPT can be reclassified as having HPT-JT syndrome.