A Young Male with Parafibromin-Deficient Parathyroid Carcinoma Due to a Rare Germline HRPT2/CDC73 Mutation

We describe a 25-year-old male with hyperparathyroidism presenting with a pathological fracture, brown tumors, hypercalcemia, and markedly elevated parathyroid hormone levels. There was no family history of hyperparathyroidism or jaw tumors. Surgical remo val revealed a single large tumor confirmed to be malignant. Immunohistochemical analysis revealed the absence of parafibromin and decreased APC (adenomatosis polyposis coli) expression. Genetic analysis revealed a rare germline nonsense mutation (R76X) in the parafibromin gene, HRPT2/CDC73. Parathy roid carcinoma should be suspected as a cause of hyperparathyroidism when clinical manifestations are severe, particularly in young individuals,<  59 years. Immunohistochemistry may lead to suspicion for a germline mutation as a significant contributor despite absence of a family history. The discovery of a germline mutation in parathyroid carcinoma alters the clinical management of the index case and that of family members. Long-term foll ow-up studies of such patients are necessary to develop evidence-based clinical guidelines.
Source: Endocrine Pathology - Category: Pathology Source Type: research