Parathyroid adenomas may be associated with multiple neuroendocrine neoplasia (MEN 1 and MEN 2A) syndromes (refer Chapter 1, Table 1.1).

Several imaging modalities are used to localize parathyroid gland lesions. These include ultrasonography, CT scanning, MRI, thallium substation scanning, and the recent technetium-99m sestamibi imaging. Ultrasonography is the most frequently used modality for primary hyperparathyroidism. A normal parathyroid gland is typically not seen with ultrasound. A parathyroid adenoma or a carcinoma is seen as a round, elliptical, or oblong hypoechoic mass. These may contain cysts and calcifications. Hyperplastic glands are usually much smaller than adenomas. Ultrasound cannot localize ectopic parathyroids. Thyroid nodules or lymph nodes may be mislabeled as parathyroids.

Parathyroid adenoma involves a single gland. A typical parathyroid adenoma is a thinly encapsulated, tan to reddish-brown neoplasm, homogeneous in consistence with a smooth external surface. Adenomas vary considerably in size and shape. They may be round, ellipsoid, bean or kidney shaped, or flattened and elongated (Fig. 9.2). Larger adenomas may undergo cystic change and may yield fluid contents at fine needle aspiration (FNA) biopsy. Histologically, adenomas are encapsulated neoplasms with compressed normal parenchyma outside the capsule. The growth pattern consists of closely packed chief cells arranged in anastomosing cords, nests, glandular formations, and sheets separated by a delicate network of sinusoids (Fig. 9.3). The dominant cell type is chief cells, often larger than their normal counterpart. The cell outlines are indistinct. Their cytoplasm ranges from faintly eosinophilic to clear and contains abundant glycogen deposits. The nuclei are round and central with dense chromatin and occasional nucleoli. A few cells may contain large, hyperchromatic nuclei.

The adenomas frequently contain cystic structures, which may be empty or filled with PAS-positive, eosinophilic, homogeneous material that strongly resembles colloid. The cells contain glycogen and fat. Argyrophilic granules in the cytoplasm of adenoma cells have been described.

The cells of parathyroid adenoma exhibit positive reactivity to parathyroid hormone, chromogranin A, and low molecular weight cytokeratin and negative reactivity to calcitonin, thyroglobulin, and vimentin.

Specimens for the cytologic diagnosis mostly represent fine needle biopsies of the suspected, enlarged parathyroid glands. Not uncommonly, the aspirates are submitted as thyroid FNA biopsies. The aspirate is variably cellular consisting of a large population of small round to cuboidal epithelial cells displayed singly, in loosely cohesive groups, or in thick syncytial type tissue fragments with or without various architectural configurations (Figs. 9.4,9.5,9.6,9.7 and 9.8). They may be monolayered (two-dimensional, Fig. 9.6E), trabecular (Figs. 9.6B and 9.7C), with branching and interdigitating to enclose spaces (Figs. 9.5B,D and 9.6B), or follicular (Figs. 9.4C and 9.6C) or may appear papillary-like with complex branching and frayed edges (Fig. 9.7D). Frequently, the extreme crowding and overlapping of nuclei within a tissue fragment result in a three-dimensional pattern (Figs. 9.4A and 9.7C). Another characteristic feature of parathyroid adenomas is the branching network of capillaries. The neoplastic cells are often seen along the capillaries (Fig. 9.7C; see Fig. 9.12C). The parathyroid adenoma cells are round to cuboidal, slightly smaller than normal thyroid follicular cells, measuring 6 to 7 mm in diameter. Their nuclei are round and uniform, containing coarsely granular chromatin (salt-pepper type) and micronucleoli. Nuclear pleomorphism is occasionally




present. Nuclear molding has been described as a “hitherto unreported diagnostic feature” but has not been documented by others. The parathyroid chief cells have scanty, pale cytoplasm with ill-defined cell borders and are frequently displayed as stripped nuclei, presenting a lymphocyte-like pattern (Fig. 9.6B). Occasionally single vacuoles are noted within the cytoplasm. The oncocytic cells contain appreciable amounts of granular cytoplasm and morphologically resemble Hürthle cells of the thyroid but for their smaller size. Although a monomorphic cellular pattern is commonly seen in adenomas, pleomorphic size and shapes may occasionally be encountered.