The etiology of parathyroid carcinoma remains unclear. The incidence of parathyroid carcinoma is equal between males and females, with a peak age of onset in the fifth decade, approximately 10 years

Figure 7-2. Neck dissection with parathyroid mass.

earlier than the peak onset for benign parathyroid disease.13 Like thyroid carcinoma in which external beam radiation is a clear predisposing event, there have been a few reports of parathyroid abnormalities developing after exposure to neck radiation, more often causing benign adenoma than parathyroid carcinoma.14,15

Given the rarity of the disease, little is known about the molecular pathogenesis. Parathyroid carcinoma is likely to follow the type of multistep carcinogenesis best described in colon cancer. It is quite likely that a series of mutations will confer a survival or growth advantage to a specific parathyroid cell and its clone of progenitor cells. The types of mutations that lead to this growth advantage include the ones that result in the overexpression of normal genes and of normal growth receptors to growth-stimulating factors. Other mutations can result in alterations in deoxyribonucleic acid (DNA) methylation, which, in turn, can alter the expression of key controlling genes, leading to reduced activity of genes responsible for the control of the growth of the cell.

Cyclin D1 (PRAD1) is an oncogene on chromosome 11q13 whose protein product, a cell-cycle regulator, is overexpressed in 18 to 40% of parathyroid adenomas1618 and in 66 to 91% of parathyroid carcinomas.16,18 In addition, a clonal chromosomal inversion has been observed in a small subset (5%) of parathyroid adenomas, resulting in the juxtaposition of the controlling region of the parathyroid hor mone gene (on chromosome 11p15) to the cyclin D1 oncogene (on 11q13).19,20 This rearrangement leads to the overexpression of cyclin D1, which results in increased cell proliferation. What is not clear is whether cyclin D1 is a causative factor in parathyroid disease, but it deserves further study as a potential therapeutic target.

RET-activating mutations, which account for tumor development through the uncontrolled activation of the receptor tyrosine kinase in multiple endocrine neoplasia (MEN) type II syndrome, are being considered as possibly involved in parathyroid tumorigenesis. The RET proto-oncogene is located on chromosome 10q11. Specific RET

Figure 7-3. Resected parathyroid carcinoma mass.

Figure 7-3. Resected parathyroid carcinoma mass.




Parathyroid Carcinoma



30 cases per year or < 0.5% of all cases of

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