Nonneoplastic Conditions

Primary chief cell hyperplasia: usually accounts for 10% of cases of primary hyperparathyroidism but is also seen against a background of secondary hyperparathyroidism. About 25% of cases of primary chief cell hyperplasia are familial and arise in Multiple Endocrine Neoplasia syndromes 1 and 2 or as an isolated familial form, but most are sporadic. The four parathyroid glands are symmetrically enlarged in around 50% of patients while the asymmetric enlargement of the remainder mimics parathyroid adenoma (pseudoadenomatous hyperplasia). Microscopically, the glands contain numerous chief cells in diffuse sheets or as nodules with oncocytes; transitional forms also present. Mitotic figures may be present. Intraglandular adipocyte numbers are usually much reduced, although rarely the fat cells may be abundant (lipohyperplasia). Cystic change may occur in very large glands. Distinction from adenoma formation can be difficult but the enlargement of multiple glands is usually diagnostic.

Primary clear cell hyperplasia: the four parathyroid glands are markedly enlarged, particularly the superior glands. The chief cells are arranged in small nests and have profoundly clear cytoplasm ("water-clear" cells). There is usually marked hypercalcaemia but water-clear cell hyperplasia is not MEN-associated.

Secondary parathyroid hyperplasia: very similar appearances to primary chief cell hyperplasia but there tends to be symmetrical enlargement, particularly in the early stages. Early changes include loss of the intraglandular adipocytes with conspicuous nests of chief cells but in longstanding cases the glands usually have a marked nodular pattern. Oncocytes may be prominent in established cases; cystic change and fibrosis may develop.

Cysts: usually arise due to degenerative changes in an adenoma or hyperplastic parathyroid gland but some are developmental anomalies of the third and fourth branchial arches. Cystic degeneration in an adenomatous or hyperplastic gland is usually associated with hyperparathyroidism; typical chief cells line the fibrous wall of the cyst. Developmental cysts tend not to be functional and are usually associated with the inferior parathyroid glands; these cysts are lined by respiratory or cuboidal epithelium with parathyroid cells in the fibrous wall.

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