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Water clear cell adenoma of the parathyroid gland is a rare neoplasm composed of large clear cells with foamy cytoplasm and mild nuclear pleomorphism, compressing the residual nonneoplastic parathyroid tissue. The differential diagnosis includes a variety of neoplasms with clear cell features. In this article, we provide an overview of the entity with a historical perspective, in order to help pathologists in distinguishing it from other neoplasms in their daily practice.

We performed scintigraphy with technetium-99m-methoxyisobutylisonitrile (MIBI) in 10 patients with parathyroid adenoma (7 lesions) or hyperplasia (9 lesions). Correlation between an amount of accumulation of MIBI and histological types of the lesions were evaluated with special reference to an amount of oxyphilic cell in the lesions. Selected lesions were also evaluated for mitochondrial density by electromicroscopy and showed increased mitochondrial density in the oxyphilic cells. All lesions equal to or above 220 mg showed positive scintigraphic results despite differences in cell types. Undetected lesions were all equal to or below 100 mg. The scintigraphic results for 2 lesions with abundant oxyphilic cells were both positive although those for 11 lesions with abundant chief cells only 6 were positive, probably because these lesions were smaller in the hyperplasia group. In conclusion, MIBI uptake in parathyroid lesions was not dependent on the cell type but either on the size or functional state of the lesions.

The authors suggest a new method of biopsy of a seemingly normal human parathyroid gland during surgery for parathyroid adenoma. Such a method provides adequate surgical specimen to rule out a likely diffuse hyperplastic disease associated with the parathyroid adenoma, and for the ultrastructural study of the gland, without any risk of postoperative complication. In all patients, ultrastructural examination showed an abnormal cell population and signs of glandular atrophy as a consequence of the high level of serum calcium due to hormonal hyperfunction of the parathyroid adenoma.

We report a water-clear cell adenoma of the parathyroid gland, a lesion which to our knowledge has not been described previously. Like its rare but well-described hyperplastic counterpart, water-clear cell hyperplasia, this adenoma is composed of cells with abundant foamy-to-granular cytoplasm and mild nuclear pleomorphism. The cells form glandular structures and cell nests separated by fine fibrovascular septae. The tumor cells stain positively with anti-parathyroid hormone and show characteristic glassy and flocculate material by electron microscopy. Unlike water-clear cell hyperplasia, water-clear cell adenoma is a solitary lesion that compresses the residual nonneoplastic parathyroid gland.

Using a one-stage silver staining technique, nucleolar organizer regions (AgNORs) were studied in paraffin sections of parathyroid glands (and in two lymph node metastases) from patients operated upon because of hyperparathyroidism or thyroid disease. The parathyroids were microscopically differentiated into normal, hyperplastic, adenomatous and carcinomatous glands. AgNORs were observed as distinct black dots of varying size and somewhat varying configuration in the nuclei of all glands. The mean number of AgNORs in the hyperplastic and adenomatous glands was not significantly different from that in the normal glands, whereas the carcinomatous glands exhibited significantly increased mean AgNOR number. No evidence was obtained for a role of AgNOR counting in the differentiation between normal and hyperplastic or adenomatous parathyroids, but the results suggest a potential role of enumeration of AgNORs in the discrimination between benign and malignant parathyroid neoplasms.

Light and electron microscopic localization of parathyroid hormone (PTH) in human and bovine parathyroid tissue has been achieved using an indirect peroxidase labeled antibody method. Granular deposition of the reaction product was found throughout the chief cell cytoplasm. There was no nuclear staining. At the ultrastructural level, parathyroid hormone localized by this method appeared to be largely confined to the secretory granules in the cytoplasm of cells. Mitochondria and nuclei were free of reaction product. Aggregated sacs of granular endoplasmic reticulum were minimally reactive, and Golgi apparatuses did not show reaction product.

On the basis of the results of histological, histochemical, and electron microscopic studies of pathologically altered parathyroid glands (PTG) in primary and secondary (chronic renal insufficiency) hyperparathyrosis a classification of tumors of this organ is suggested. It takes into account the fact that PTG tumors have a complex histological structure and heterogeneous cellular composition: chief dark, chief clear, transitional oxiphilic, exiphilic, small (round), spindle cells, and C-cells with different structural and functional orientation. Staining with Sudan-III of frozen sections of PTG tissue in primary hyperparathyrosis may be recommended as an additional test for differential diagnosis between adenoma and hyperplasia taking into account that the cytoplasm of chief cells of adenoma contains Sudanophilic bodies, while the cytoplasm of small cells of adenoma and chief (dark and clear) cells of hyperplasid PTG does not. The appearance of C-cells in the thymus, thyroid glands and adenomatous PTG in primary hyperparathyrosis may be considered to be a compensatory-adaptative response to hypercalciemia. Formation of C-cell adenomatosis in a normal PTG combined with PTG adenoma indicates the activity of these glands.

Ultrastructural morphometry was performed on human parathyroid tissue from adenomas in chronic and acute (pernicious) hyperparathyroidism (HPT) including contralateral atrophic glands with the aim to compare the observed alterations with the corresponding clinico-functional findings. Quantitative assessment of various cell organelles, nucleus and cell perimeter revealed that significant correlations between ultrastructural features and laboratory parameters were only calculable by regarding extreme ranges of functional stages, i.e. adenomas of acute HPT (hyperparathyroid crisis) and contralateral atrophic glands. In chief cells of chronic HPT there was an inhomogeneity of measurements due to the disparate composition of the adenomatous tissue. Our results show that large complex lipid bodies and extensive accumulations of glycogen are valuable indicators of a functionally suppressed chief cell in atrophic parathyroid glands. An increased number of coated pits and vesicles is amongst other features (increase in size or number of Golgi apparatus, rough endoplasmic reticulum, mitochondria, nucleus and nucleolus as well as extension of the plasma membrane) characteristic of an endocrine stimulation.

Nuclear diameter was measured in 55 parathyroid chief-cell adenomas to determine its value in histological diagnosis and to assess its relationship to other features of primary hyperparathyroidism. Mean nuclear diameter for the whole group of adenomas was significantly greater than that for the accompanying normal glands. Mean nuclear diameter in individual adenomas was significantly greater than that in the accompanying normal gland in 27 out of 34 cases. Nuclear diameter was correlated with tumour weight and with plasma calcium but was not correlated with duration of history. It was significantly greater in the group of patients with overt bone disease than in those with kidney stones and in those with neither kidney stones nor overt bone disease. Assessment of nuclear diameter is of value in histological diagnosis of parathyroid adenoma. The rate of growth of the adenoma may be a factor determining nuclear diameter.

Oxyphil cells and oxyphil cell adenomas of parathyroid glands are, in most instances, regarded to be nonfunctioning. Although 21 cases of hyperparathyroidism associated with parathyroid oxyphil cell adenoma have been reported, secretion of hormone by these tumors has not been conclusively demonstrated. A parathyroid adenoma, diagnosed by light microscopy as oxyphil type, together with the results from ultrastructural and biochemical studies of the patient's adenomatous tissue, are reported here. The patient, a 64-year-old male, was found to have elevated serum calcium, low serum phosphorus, and elevated serum immunoreactive parathormone: findings consistent with hyperparathyroidism. After excision of two small normal-appearing glands and one greatly enlarged (1.9 g) parathyroid gland, those laboratory values returned to normal. Light microscopy of the enlarged parathyroid indicated that it consisted almost entirely of an oxyphil adenoma. Electron microscopy revealed that the adenoma was composed mainly of mitochondria-rich oxyphil cells but also of interspersed transitional oxyphil cells and rare scattered chief cells. Golgi zones, rough endoplasmic reticulum, and prosecretory and secretory-like granules were observed in some oxyphil cells, in most transitional oxyphil cells, and in the infrequent chief cells. Thus, many of these cells appear to contribute to the production and secretion of parathormone. Biochemical studies performed directly on the adenomatous tissue demonstrated that it was able to synthesize proparathormone and parathormone, although the proportion of hormonal peptide synthesis relative to that of the total protein synthesis in this tissue was much smaller (0.9%) than that found in normal parathyroid tissue (5.7%). There was a small increase in immunoreactive parathormone when the adenoma tissue was incubated in a low-calcium medium. These findings indicate that this oxyphil adenoma of the parathyroid gland synthesized and secreted parathormone, apparently to some extent autonomously, but suggest that its capacity to do so was largely dependent on its component of cells other than fully developed oxyphil cells, such as transitional oxyphil cells.

On the basis of studies of the histological structure of 7 parathyreoadenomas removed in connection with primary hyperparathyroidism three types of their structure (trabecular, acinose, and solid) were singled out. As to their cellular composition, the adenomas could be divided into clear-cell and dark-cell adenomas (of main cells), oxyphilic adenomas, and adenomas of C-cells. The same cells (predominantly main clear cells) were found in the 9 studied hyperplastic parathyroid glands. Certain differences between the ultrastructure of cells of parathyreoadenomas and that of the hyperplastic parathyroid glands were established.