Parathyroid glands are small oval structures on the posterior aspect of the thyroid gland. In the majority of cases, there are four glands arranged in two pairs, upper and lower pair, corresponding to the different origin. In rare cases, more than four parathyroid glands are identified.

Each gland is approximately 4mm each in size and 40-60 grams in weight. The cells of parathyroid gland (mainly chief cells) secrete parathyroid hormone involved in metabolism of calcium. Other cell types include oxyphil cells and rare water-clear cells. The amount of adipose tissue in parathyroid stroma increases after puberty reaching approximately 40% in the adult person.

Parathyroid hyperplasia is an increase in parenchymal mass of multiple parathyroid glands. This can happen with or without clinical stimulus for increased gland function (secondary vs. primary hyperplasia).

Hyperplasia can be sporadic or familial (MEN1, MEN2a or isolated familial hyperparathyroidism). This is an intrinsic abnormality of the parathyroid glands.

Secondary hyperplasia occurs when there is a clinical stimulus to the parathyroid gland to increase PTH secretion, such as in cases of chronic renal failure and vitamin D deficiency.

The increased mass of parathyroid cells result in an increase of parathyroid hormone secretion and hyperparathyroidism, which is also classified as primary, secondary or tertiary.

Familial cases of primary hyperplasia result in chief cell hyperplasia. Usually all glands are enlarged, however the size difference between glands may be present. Other cell types may be present, and the pattern of hyperplasia may be diffuse or nodular. There is an increase in parenchymal cells arranged in sheets, cords or acini, and decrease in stromal fat. Mitoses are rare, and there are no atypical mitoses. Chief cells are positive for PTH, parafibromin, keratin, and chromogranin, and negative for TTF1 and thyroglobulin. Secondary chief cell hyperplasia has similar histological appearance and clinical correlation is required for the diagnosis.

Water-clear cell hyperplasia is not familial, and the incidence is very low.

Differential diagnosis is parathyroid adenoma which is almost always solitary, and has a rim of normal or atrophic parathyroid tissue at the periphery. Clinical-pathological correlation is essential for diagnosis.

Parathyroid lesions also need to be differentiated from normal or neoplastic thyroid and metastatic disease, such as renal cell carcinoma.