Parathyroid Carcinoma

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com



Parathyroid Carcinoma
Parathyroid carcinoma accounts for 1% of the parathyroid gland tumors and almost always presents as primary hyperparathyroidism. The serum calcium level is very high in up to 65% of patients; however, there are cases when the calcium level is only mildly elevated or even normal.


Epidemiology and Etiology

In Europe, the United States, and Japan, parathyroid carcinoma has been estimated to cause hyperparathyroidism up to 5% of cases. The median age of patients is between 45 and 51 years. It affects both sexes equally, in contrast to primary hyperparathyroidism, in which there is a significant female predominance.

The etiology of parathyroid carcinoma is largely unknown. A causal relationship with prior neckirradiation is not apparent, as only 1.4% of patients have a history of neck irradiation. Parathyroid carcinoma can be associated with the hereditary hyperparathyroidism–jaw tumor syndrome with an incidence of 10% to 15%, which is due to an inactivating mutation of the CDC73 gene (formerly HRPT2) that encodes the parafibromin protein. In addition, somatic mutations of the HRPT2 gene have been demonstrated in sporadic parathyroid carcinomas (66% to 100%) but have not been seen with sporadic adenomas.

Parathyroid cancer has been occasionally reported in familial isolated hyperparathyroidism, MEN type 1 and MEN-2A syndromes.

Signs and Symptoms
Most patients with parathyroid cancer have symptomatic moderate to severe hypercalcemia (mean serum calcium level, 15 mg/dL) and high parathyroid hormone levels (5 to 10 times greater than the upper limits of normal). They often present with a palpable neck mass with possible recurrent laryngeal nerve palsy. Unlike benign hyperparathyroidism, renal and bone abnormalities are more common in patients with parathyroid cancer.

In hyperparathyroidism–jaw tumor syndrome, patients present in late adolescence or early adulthood with multigland cystic parathyroid adenomas that carry a high risk for carcinoma. Patients with this syndrome will have maxillary or mandibular ossifying fibromas (30% to 40%) or renal cysts or hamartomas (20%).

Rarely, nonfunctioning tumors may present as neck masses; their clinical course is similar to that of functioning tumors. Clinical concern about parathyroid cancer should be raised in the presence of a palpable neck mass and severe hypercalcemia, recurrent hyperparathyroidism, or associated vocal cord paralysis.

Parathyroid cancer usually has an indolent 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%).

Pathology
The principal features of parathyroid cancer include a trabecular pattern, mitotic figures, thick fibrous bands, and capsular or vascular invasion of disease. Other important features include lymphatic or hematogenous metastases and histologic evidence of tumor infiltration into the surrounding tissues (including macroscopic adherence or vocal cord paralysis).

Although cytologic evidence of mitoses is necessary to establish the diagnosis of carcinoma, mitotic activity alone is an unreliable indicator of malignancy. The loss of parafibromin staining on immunohistochemistry is 94.4% specific for parathyroid carcinoma.The only reliable microscopic finding of malignancy is invasion of surrounding structures or metastasis to lymph nodes or other organs.

Treatment
Surgical treatment of primary hyperparathyroidism
The diagnosis of parathyroid carcinoma is sometimes made during surgical exploration for primary hyperparathyroidism. Most surgeons advocate identification of all four parathyroid glands. In most cases, the upper glands can be found on the posterior aspect of the upper third of the thyroid lobe, just cephalad to the inferior thyroid artery and adjacent to the recurrent laryngeal nerve as it enters the larynx.

The inferior parathyroid glands are more variable in location. Most are found on the posterior or lateral aspect of the lower pole of the thyroid gland, but the inferior parathyroid glands may be ectopically placed in the superior or true mediastinum, often within the thymus. The inferior and, less commonly, superior glands can be found in an ectopic location in the upper or lateral neck, adjacent to the esophagus, or within the carotid sheath. Parathyroid carcinoma usually arises from the inferior glands.

Surgical exploration for primary hyperparathyroidism. Most cases of primary hyperparathyroidism are caused by a single hyperfunctioning parathyroid adenoma. If the surgeon finds one (or occasionally two) enlarged abnormal gland(s) and the remaining glands are normal, the enlarged gland should be removed.

If fo

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  Parathyroid Cancer