Malignant Neoplasms of the Parathyroid Gland

Clinical Features

Parathyroid carcinoma affects fewer than 1/1,000,000 population per year, develops in all ages, although more frequently in older adults (mean 6th decade) and up to a decade earlier than adenoma. There is no sex bias, distinctly different from the marked female predominance in patients with parathyroid adenoma. Japanese and Italian patients show a higher incidence of carcinoma than other races.

The clinical features are due primarily to the effects of excessive parathyroid hormone (PTH) secretion and hypercalcemia. Laboratory values of greater than 1,000 ng/L for PTH and greater than 16 mg/dL for serum calcium are very concerning for parathyroid carcinoma. The nonspecific symptoms (weakness, fatigue, anorexia, weight loss, nausea, polyuria, polydipsia) overlap with adenoma, but excessively high serum calcium levels (>16 mg/dL) are associated with nephrolithiasis, renal insufficiency, and bone “brown tumors.” Concurrent bone disease and kidney stones are more common in patients with carcinoma than adenoma. A palpable neck mass (in up to 75% of patients) suggests carcinoma and is often difficult to remove at surgery due to adherence to the soft tissues, nerves (recurrent laryngeal nerve involvement gives hoarseness), and/or thyroid gland. Carcinoma may develop in any parathyroid gland but is slightly more common in the lower parathyroid glands.

Most cases are sporadic, with only a small subset associated with familial disease forms. There are recurrent losses of chromosome 13q, the same region known to contain the retinoblastoma (RB1) and BRCA2 tumor suppressor genes. A genomic region frequently lost in parathyroid adenomas is 11q, the location of MEN1 , but it is almost never identified in carcinoma, supporting the contention that parathyroid carcinomas arise de novo rather than from preexisting adenomas. Carcinoma is a component of HPT-JT syndrome, where it is identified in approximately 15% of patients. Carcinomas are rarely associated with prior irradiation, renal failure, and celiac disease. Radiographic studies are usually unreliable in separating adenoma from carcinoma but can aid in planning surgery.

Pathologic Features