The normal parenchymal content of adult parathyroid tissue is half stroma and fat and half chief cells (Figure 5-1). In children, the parenchyma is almost entirely composed of chief cells. The size of parathyroid adenomas tends to correlate with the severity of hypercalcemia. These adenomas are hypercellular and usually devoid of stromal fat (Figure 5-2). A thin compressed rim of normal tissue may be identified. Oncocytic and water clear cells may also be present. Parenchymal cells are arranged in solid sheets, cords, tubular structures, or micro-cytic formations, and the admixture of stromal and adipose elements varies with age and function. The parenchyma-to-stroma ratio is used as an indicator for a normocellular or hypercellular gland. The median ratio is about 50%. In abnormal glands, stromal fat is scant. Molecular studies have established that parathyroid adenomas are clonal proliferations. The cells are larger than normal, and the nuclei show hyperchromasia and atypia and have an increased deoxyribonucleic acid (DNA) content.8

Primary parathyroid hyperplasia results from an increase in chief cells, oncocytic cells, transitional oncocytic cell mixtures, and stromal elements in the absence of a known stimulus. Grossly and microscopically, parathyroid hyperplasia does not differ from adenomatous disease, although adenomas are more likely to have a compressed rim of normal parathyroid tissue. The surgeon can usually determine whether a parathyroid gland is normal or hyperplastic because hyperplastic or adenomatous glands are darker, firmer, and larger.

PHPT can be caused by three different pathologic lesions: adenoma, hyperplasia, or carcinoma. An adenoma is a benign neoplasm composed of chief cells, transitional oncocytic cells, or a mixture of these cell types. Adenomas, macroscopically enlarged glands, are responsible for approximately 80% of cases of PHPT and usually affect a single gland (Figure 5-3). By definition, the other glands are normal or atrophic. PHPT is associated with the dominantly inherited MEN types I and II.

For distinction between parathyroid hyperplasia and a parathyroid adenoma, the gross appearance

Figure 5-1. Normal parathyroid parenchyma is half stroma and A rim of compressed normal tissue can be identified (hematoxylin half chief cells (hematoxylin and eosin; x25 original magnification). and eosin; x25 original magnification).

of the glands at the time of surgery is of utmost importance. Hyperplasia, by definition, involves all of the parathyroid glands. Most adenomas involve a single gland, whereas some patients may have enlargement of two or three parathyroid glands with one normal gland (double and triple adenomas). The diagnosis is based on the combination of gross features and histologic parameters but mostly on the finding of one or more normal parathyroid glands. Because it is impossible to distinguish between a hyperplastic or adenomatous gland histologically, some experts use the term multiple abnormal parathyroid glands rather than hyperplasia. The surgeon should know that when there is more than one abnormal parathyroid gland, all glands should be considered abnormal unless proven otherwise.

Parathyroid carcinoma is responsible for 1% of cases of PHPT. It is usually a slow-growing neoplasm of parenchymal cells. It will be discussed in further chapters. Other rare parathyroid tumors include lipoadenomas and carcinosarcomas.

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