Parathyroid cancer pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]


On gross pathology, stony-hard mass with lobulations and a dense, fibrous, grayish-white capsule are characteristic findings of parathyroid cancer. On microscopic histopathological analysis, dense fibrous trabeculae, mitoses, and capsular invasions are characteristic findings of parathyroid cancer.


  • Parathyroid cancer typically runs an indolent course because the tumor has a rather low malignant potential.[1]
  • At initial presentation, very few patients with parathyroid carcinoma have metastases either to regional lymph nodes (<5%) or distant sites (<2%).
  • A higher proportion of parathyroid cancers may locally invade the thyroid gland, overlying strap muscles, recurrent laryngeal nerve, trachea, or esophagus. Parathyroid carcinoma tends to originate from 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.
  • Approximately 40% to 60% of patients experience a postsurgical recurrence, typically in the range of 2 to 5 years after the initial resection. In most cases, hypercalcemia precedes the evidence of recurrent disease on physical examination.
  • The location of recurrence is typically regional, either in the tissue of the neck or in the cervical lymph nodes, where these account for approximately two thirds of recurrent cancer cases.
  • Distant metastases were reported to occur in 25% of patients, which primarily occurs in the lungs, but may also occurs in the bone and liver. Serum parathyroid hormone levels may be 3 to 10 times above the upper limit of normal and hence cause nephrolithiasis or nephrocalcinosis.


  • HRPT2/CDC73 gene mutation is involved in the pathogenesis of parathyroid cancer.

Associated Conditions

Gross Pathology

  • Parathyroid carcinoma may be distinguished from adenomas by the stony-hard consistency and lobulation of parathyroid carcinoma.
  • In most series, the median maximal diameter of parathyroid carcinomas is between 3.0 cm and 3.5 cm compared with a diameter of approximately 1.5 cm for benign parathyroid adenomas.
  • In approximately 50% of the patients, the malignant tumor is surrounded by a dense, fibrous, grayish-white capsule that infiltrates adjacent tissues. The clinical features of parathyroid carcinoma are caused primarily by the effects of excessive secretion of parathormone (PTH) by the tumor rather than by the infiltration of vital organs by tumor cells.

Microscopic Pathology

  • Histopathologically, as with other endocrine neoplasms, the distinction between benign and malignant parathyroid tumors is a difficult process.
  • On microscopic histopathological analysis, dense fibrous trabeculae, trabecular growth patterns, and capsular invasions are characteristic findings of parathyroid carcinomas.
  • Capsular and vascular invasions appear to correlate best with the tumor recurrence.


  1. Parathyroid cancer. (2015). Accessed on December 29, 2015

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