Parathyroid adenomas represent a common endocrine problem, whereas parathyroid carcinomas are very rare tumors. With an estimated incidence of 0.015 per 100,000 population and an estimated prevalence of .005% in the United States, parathyroid cancer is one of the rarest of all human cancers.[1,2] In Europe, the United States, and Japan, parathyroid carcinoma has been estimated to cause hyperparathyroidism (HPT) in .017% to 5.2% of the cases; however, many series report this entity to account for less than 1% of patients with primary HPT.[1,3,4,5] The median age in most series is between 45 and 51 years. The ratio of affected women to men is 1:1 in contrast to primary HPT in which there is a significant female predominance (ratio of 3-4:1).
The etiology of parathyroid carcinoma is unknown; however, an increased risk of parathyroid cancer has been associated with multiple endocrine neoplasia 1 and with autosomal dominant familial isolated hyperparathyroidism.[6,7,8] Parathyroid cancer has also been associated with external radiation exposure; however, most reports describe an association between radiation and the more common parathyroid adenoma.[1,5]
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
Patients with stage I and II disease have an excellent prognosis, regardless of histology. A Children's Cancer Group study demonstrated that pulsed chemotherapy with cyclophosphamide,...
Parathyroid cancer typically runs an indolent, albeit tenacious, course because the tumor has a rather low malignant potential. At initial presentation, very few patients with parathyroid carcinoma have metastases either to regional lymph nodes (<5%) or distant sites (<2%). In the National Cancer Database series of 286 patients, only 16 (5.6%) had lymph node metastases noted at the time of initial surgery. A higher proportion of parathyroid cancers locally invade the thyroid gland, overlying strap muscles, recurrent laryngeal nerve, trachea, or esophagus. Some patients are not identified preoperatively or intraoperatively as having parathyroid carcinoma and undergo parathyroid procedures devised to treat parathyroid adenoma. Only after review of the postsurgical pathology, or when these patients experience local or distant recurrence, is a correct diagnosis of parathyroid carcinoma made. Parathyroid carcinoma tends to be localized in the inferior parathyroid glands; one series reported that the primary tumor originating in the inferior parathyroid glands was found in 15 of 19 cases involving local invasion.[9,10]
Approximately 40% to 60% of patients experience a postsurgical recurrence, typically in the range of 2 to 5 years after the initial resection.[11,12] In most cases, hypercalcemia precedes physical evidence of recurrent disease. (Refer to the PDQ summary on Hypercalcemia for more information.) The location of recurrence is typically regional, either in the tissues of the neck or in cervical lymph nodes, and accounts for approximately two thirds of recurrent cases. Often, local recurrences in the neck are difficult to identify because they may be small and multifocal, and they may involve scar tissue from a previous surgical procedure. Use of ultrasonography, sestamibi-thallium scanning, and positron emission tomography may help to identify difficult-to-detect recurrent disease.[14,15,16] In older studies, distant metastases were reported to occur in 25% of patients, primarily in the lungs but also in the bone and liver.[13,17] More recent series indicate that the incidence of recurrence may be higher, possibly because of more accurate pathologic diagnoses that exclude patients with atypical adenomas. Because of its low malignant potential, the morbidity and mortality associated with parathyroid cancer primarily result from the metabolic consequences of the disease and not directly from malignant growth.[9,17] In the National Cancer Database series of 286 patients, the 10-year survival rate was reported to be approximately 49%. A smaller series has reported a 10-year survival rate of 77%, which might be related to improvements in supportive medical care and in the prevention of fatal hypercalcemia.