Association Between Parafibromin Expression and Presence of Brown Tumors and Jaw Tumors in Patients with Primary Hyperparathyroidism: Series of Cases with Review of the Literature

Abstract

Case series Patients: Male, 57-year-old • Male, 42-year-old • Female, 45-year-old • Male, 42-year-old Final Diagnosis: Brown tumor • hyperparathyroidism Symptoms: Brown tumor • hypercalcemia Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Rare disease Background: Brown and jaw tumors are rare entities of poorly understood etiology that are regarded as end-stage of bone remodeling in patients with long-lasting and chronic hyperparathyroidism. Jaw tumors are mainly diagnosed in jaw tumors syndrome (HPT-JT syndrome) and are caused by mutation in the CDC73 gene, encoding parafibromin, a tumor suppressing protein. The aim of this work is to present 4 cases of patients in whom the genetic mutation of the CDC73 gene and clinical presentation coexist in an unusual setting that has not yet been described. Case Reports: We present cases of 4 patients with primary hyperparathyroidism. Three were diagnosed with brown tumors (located in long bones, ribs, iliac, shoulders) and 1 with brown and jaw tumors. Expression of parafibromin in affected parathyroid tissues were analyzed. In patients without positive parafibromin staining, we searched for CDC73 mutation using next-generation sequencing. Parafibromin staining was positive in 1 patient with brown tumors and was negative in 2 individuals with brown tumors and 1 with brown and jaw tumors. CDC73 mutation was detected in two-thirds of patients (60%) with negative staining for parafibromin and brown tumors. MEN1 mutation was found in the patient with brown tumor and positive staining for parafibromin. Conclusions: Patients with hyperparathyroidism and coexistence of brown tumors or jaw tumors might have decreased expression of parafibromin in parathyroid adenoma tissue, which might be caused by CDC73 mutation and suggest a genetic predisposition. Further research on much larger study groups is needed.

Recurrent Primary Hyperparathyroidism in Hyperparathyroid Jaw Tumor Syndrome: A Case Report

“…The youngest female patient reported was 19 years old and presented with mandibular ossifying fibromas, while the youngest male patient reported was six years old and presented with multiple maxillary and mandibular ossifying fibromas [ 10 ]. The oldest reported female patient in our search was 52 years old with adenomyosis and the oldest reported male patient was 57 years old with brown tumors secondary to abnormal metabolism of the bone from HPT [ 11 , 12 ]. One case report described 13 family members with a pathologic mutation of the CDC73 gene and found the penetrance to be roughly 50% at 40 years of age [ 13 ].…”