Hyperparathyroidism-Jaw Tumor Syndrome in a Patient With Colon Cancer: A Case Report

Background: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disease, caused by mutations in the CDC73 gene, characterized by parathyroid tumors in association with fibro-osseous lesions of the mandible or maxilla. The occurrence of renal cysts or tumors, uterine and thyroid tumors has been reported. The association with other neoplastic lesions has been described, but its meaning and frequency are not well established. Clinical Case: A 48-year-old Roma woman was admitted to our hospital due to severe abdominal pain and constipation. She had a past history of kidney stones with several episodes of acute renal colic and had been recently diagnosed with colon cancer. Her family history was positive for colon cancer. Disease staging suggested the presence of liver metastases and multiple lytic lesions of the axial skeleton, pelvis and femurs. Laboratory investigation disclosed high calcium levels (15 mg/dL) and cancer associated hypercalcemia was suspected. However, PTH was markedly elevated (2979 pg/mL), in favor of a parathormone dependent cause. Further imaging procedures showed a heterogeneous mass, posterior to the right thyroid lobe and bone lesions on the left mandible, likely to correspond to brown tumors. Once the hypercalcemia was controlled, she was submitted to parathyroidectomy and right thyroid lobectomy plus sigmoidectomy and liver biopsy. The histology revealed an atypical parathyroid adenoma with 3,5 cm and papillary thyroid cancer with 1,2 cm, as well as colon adenocarcinoma metastatic to the liver. Postoperatively, the patient developed a hungry bone syndrome needing adequate treatment. Two months after surgery, the patient initiated chemotherapy for colon cancer. Screening for germline mutations in the CDC73 gene (formerly HRPT2) was positive for a deletion (c.765_766delTG/p.Val256LysX10). Conclusions: Hypercalcemia in a patient with malignant disease may be independent of malignancy. In the patient presented herein her past history of kidney stones and the involvement of the mandible were highly suggestive of HPT-JT. Missing the diagnosis would negatively impact in the patient′s prognosis and in the management of her family. Further clinical and genetic studies are ongoing trying to clarify whether the patient has two inherited conditions or a phenotype of HPT-JT including colon cancer.