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.

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 REPORT 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.

Treatment of pathological fractures due to brown tumours in a patient with hyperparathyroidism and lack of parafibromin expression - A case report.

Brown tumours, known also as osteitis fibrosa cystica, are benign osteolytic lesions found in 5-15% of patients with hyperparathyroidism, and commonly located in mandibles, the shafts of long bones, the pelvis or ribs. As they compromise bone strength, pathological fractures can be a typical effect of their presence; but given the complex nature of the disease process in this case, such fractures require an interdisciplinary approach directed at orthopaedic treatment, plus management of the underlying hyperparathyroidism. In this paper, we present the case of a 36-year-old female patient with bilateral anophthalmia, hyperparathyroidism and nephrolithiasis, in whom a fall led to her sustaining a pathological fracture of the proximal third of the femoral shaft in the place of an osteolytic lesion, as well as second pathological fracture of the left patella also changed by multiple examples of such lesions. Parathyroidectomy on account of adenoma had been performed 2 weeks prior to the trauma. The femoral shaft fracture was treated surgically, the patella fracture conservatively, and a sample brown tumour was found in tissue. As the parathyroid showed no parafibromin expression, a diagnosis of HPT-JT (hyperparathyroidism and jaw tumour) was arrived at, with this condition given as caused by CDC73 mutation. This disease is able to account for brown tumours, hyperparathyroidism, benign or malignant tumours of kidneys, intestinal tract, and lungs. The approach combining treatment of the fractures with intervention over the parathyroid adenoma proved a successful one, with complete bone union ensuing, and no relapse into hyperparathyroidism 2 years on from the surgery. This case indicates the importance of an interdisciplinary approach to the treatment of brown tumours, as well as the necessity for a diagnosis to be extended when incidental brown tumours are found.

Membranous glomerulonephritis - a common, unspecific pattern of glomerular injury.

Membranous nephropathy (MN) is a chronic form of glomerulonephritis, associated with the presence of immune complexes beneath the podocytes on the subepithelial region of glomerular capillaries. MN is not a disease entity but one of relatively common patterns of glomerular injury that may be a manifestation of primary renal autoimmunological reaction or may evolve as a phenomenon secondary to wide spectrum of systemic processes.