Water-clear Cells Research Articles

Impact of Histological Subtypes on Preoperative Localization of Parathyroid Adenomas

Introduction: Parathyroid scintigraphy and ultrasonography are the primary imaging methods used for localizing parathyroid adenomas. However, there remains a risk of missed or failed localization. This study aims to investigate the relationship between clinical and pathological findings in patients with parathyroid adenoma, focusing on the causes behind missed adenomas and localization failures. Patients and Methods: We analyzed the demographic, clinical, laboratory, and radiological data of patients who underwent surgery for primary hyperparathyroidism due to adenomas. Additionally, we reassessed the adenomas' pathologic characteristics, including size, weight, dominant cell type, and the percentage of oxyphilic cells. Results: A total of 115 patients were studied, with dominant cell types distributed as follows: 83 (71.6%) conventional chief cells, 15 (12.9%) water-clear cells, and 17 (14.7%) oxyphilic cells. The average percentage of oxyphilic cells was 21.15%. The localization rate via ultrasonography was significantly lower in the water-clear cell group (p < 0.05). While not statistically significant, the localization success using scintigraphy was lower in the oxyphilic cell group compared to others (58.8% vs. 80.7% and 86.7%). Our findings suggest that histological subtypes of parathyroid adenomas, particularly dominant cell content, may affect preoperative localization success. Conclusion: Missed parathyroid adenomas may be attributed to their histological subtypes and dominant cell composition. These factors could influence the accuracy of preoperative localization with ultrasonography and scintigraphy.

Brief review of parathyroid adenoma; problems caused by water clear cells

Water clear cells; they can be seen in many tumors such as germ cell tumors, kidney tumors, lymphomas, sarcomas, thymic carcinomas, parathyroid carcinomas, paraganglioma. They may be primary or may occur as a result of metastatic conditions. Therefore, histopathologically differential diagnosis may be difficult or confusing. Clinical findings, radiological findings and histopathological evaluation may be required for differential diagnosis. 
 Here, as immunohistochemically; a case with parathormone, CD10 positive and synaptophysin negative and CD10 positivity in the area where clear cells are dominant is presented.
 The case was reported as water clear cell (WCC) component dominant parathyroid adenoma with clinical, biochemical, radiological evaluation and histopathology and the differential diagnosis is discussed.

Primary hyperparathyroidism caused by enormous unilateral water-clear cell parathyroid hyperplasia

BackgroundParathyroid water-clear cell hyperplasia (WCCH) and water-clear cell adenoma (WCCA) are rare causes of primary hyperparathyroidism. The frequency of WCCH seems to be less than 1% of all primary hyperplasia.Case presentationWe report a 53-year-old woman with a large unilateral water clear cell parathyroid hyperplasia associated with primary hyperparathyroidism and severe osteoporosis. Ultrasonography showed a 5.4 cm multilobulated hypoechoic well defined mass localized in the lower half of the left thyroid lobe. Technetium sestamibi scanning showed a persistent very large area of increased activity possibly corresponding to a left inferior double parathyroid adenoma. At surgery, two large merged lobulated parathyroid glands were removed from the left superior and inferior aspects of the adjacent thyroid extending to the sub-clavicular area. Histopathology showed polygonal hyperplastic vacuolated cells with abundant water clear cytoplasm. The lesion had lack of capsule or rim of parathyroid tissue and immunohistochemistry was positive for PTH staining. These findings were consistent with diffused water clear cell hyperplasia. After parathyroidectomy, iPTH and calcium levels dropped immediately.ConclusionThe clinical presentation of the patients with water clear cells parathyroid content and hyperparathyroidism is indistinguishable from that of the more common causes of primary hyperparathyroidism of adenoma or hyperplasia and the diagnosis is made only on pathological examination. In conclusion, the distinction of water clear cell hyperplasia from water clear cell adenoma can be challenging in many cases, although clinically significant as far as treatment and follow-up.

Water Clear Parathyroid Adenoma: A report of 2 cases

Hyperparathyroidism occurs mainly due to parathyroid hyperplasia, adenoma and rarely carcinoma. Most of the adenomas are composed of chief cells. Water clear cell adenoma are a rare phenomenon. We are sharing two cases of parathyroid adenomas composed entirely of water clear cells and requires high degree to suspicion to identify them as they have low endocrinological activity. DOI: 10.21276/APALM.1074

Water Clear Cell Parathyroid Adenoma: Case Report and Literature Review

Water clear cell parathyroid adenoma is a rare cause of primary hyperparathyroidism. In this rare disease entity, normal parathyroid tissue is replaced with growth of water-clear cells, instead of the chief cell hyperplasia associated with the majority of parathyroid adenomas. We present the case of a water clear cell parathyroid adenoma in a 54 year old woman with symptomatic hypercalcemia, as well as a review of the literature on this rare disease. This constitutes the 17th reported case of water clear cell parathyroid adenoma.

Water-clear cell adenoma associated with primary hyperparathyroidism: report of a case

We report a case of water-clear cell adenoma associated with primary hyperparathyroidism. A 59-year-old woman with a history of renal stones and bone fracture was referred for investigation of hypercalcemia and an elevated serum parathyroid hormone level. Skeletal X-rays showed osteopenia and ultrasound showed enlarged tumors in both sides of the inferior thyroid region. Computed tomography demonstrated a tumor in the posterior aspect of the left thyroid lobe but no lesion in the right aspect of the neck. Grossly, we found a 500 mg left lower parathyroid gland (PTG) and a 100 mg right lower PTG. Histologically, the left lower PTG comprised mainly water-clear cells (WCCs) containing numerous vacuoles. Chief cells were dispersed among the WCCs, but the right lower PTG showed normal parathyroid tissue. Several investigators have speculated that WCCs are derived from chief cells, and we diagnosed WCC adenoma. Following this case report, we review the relevant literature.

Frozen Section of Thyroid and Parathyroid Specimens

To the Editor.—We read with great interest the recent article by Drs Anton and Wheeler1 describing the role of frozen section in the evaluation of thyroid and parathyroid specimens, and we were pleased to see their emphasis on the use of preoperative fine needle aspiration and intraoperative cytologic preparations to guide the surgical management of these lesions. There are, however, a few points that we feel deserve further comment.The authors suggest that the distinction between a thyroid adenoma and an adenomatous nodule represents a pathologic diagnostic dilemma; however, in our opinion, this is misleading because both lesions are benign and will be managed similarly. Furthermore, the pathologic distinction between hyperplastic thyroid nodules, so-called adenomatous nodules, and thyroid adenomas has been shown in many cases to be unreliable as supported by the finding that, even in multinodular goiters, more than 60% of nodules are monoclonal proliferations.2With regard to the hyalinizing trabecular adenoma, the authors do not mention that a small subset of these tumors has been shown to have metastatic potential and hence the preferred term used by the World Health Organization, hyalinizing trabecular tumor. Molecular studies indicate that hyalinizing trabecular tumors share some of the molecular changes seen in papillary thyroid carcinomas such as the RET/PTC gene rearrangement, and thus these tumors may in fact represent an indolent variant of papillary carcinoma rather than a separate entity.3With respect to the parathyroid glands, we would stress that an experienced parathyroid (endocrine) surgeon very seldom needs to call for a frozen section to identify the tissue as parathyroid. At the Massachusetts General Hospital, the extent to which our 4 endocrine surgeons performing these operations use the frozen section for the purpose of identifying tissue as parathyroid is estimated to be less than 1% of cases, and usually only when there has been a previous thyroid or parathyroid operation. Frozen sections are predominantly used for distinguishing normal from abnormal glands (ie, to distinguish an adenoma or a double adenoma from primary chief cell hyperplasia).Although not mentioned by the authors, in our experience, the use of an intraoperative fat stain for evaluating intracellular and extracellular fat is helpful for distinguishing normal from abnormal parathyroid tissue. This is particularly true in children in whom stromal fat is sparse or absent or in very small biopsies in which the stromal fat is irregularly distributed. In fact, at our institution, frozen section examination of extremely small samples of normal parathyroid glands of less than 1 to 2 mm is easily done and very informative, especially in conjunction with use of a fat stain. In addition, our surgeons often apply the intraoperative parathyroid assay in conjunction with a single frozen section, and, in our hands, this has proven very successful.Finally, we would like to point out that the normal parathyroid glands do not technically contain water clear cells. Water clear cells have a specific ultrastructure, with a cytoplasm filled with enlarged vacuoles thought to represent abnormal secretory vesicles not found in the vacuolated chief cells of the normal gland.45 Water clear cells are only present in water clear hyperplasia and water clear adenomas, whereas the glycogen-rich chief cell is a normal variant of the chief cell secretory cycle.The authors have no relevant financial interest in the products or companies described in this letter.

Ultrastructure of the water-clear cell in the parathyroid gland of SAMP6 mice

Although the parathyroid water-clear cell is very rare, it has clinical significance because of its association with parathyroid hyperplasia or adenoma. SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal model for senile osteoporosis. We investigated the morphology of the parathyroid glands in SAMP6 and age-matched normal mouse SAMR1. The parathyroid water-clear cells, which contained numerous vacuoles and the crystalloid inclusions, were found in SAMP6 mice at 5, 8 and 12 months of age. It was noted that the number of water-clear cells increased with aging, which are fairly consistent with the change of the serum parathyroid hormone (PTH) level. We did not find any water-clear cells in the parathyroid glands of SAMR1 mice. The existence of water-clear cells may represent hyperfunction of the parathyroid glands in SAMP6.

Intrathyroidal water-clear cell parathyroid adenoma: A case report

Adenomas of the parathyroid gland, the majority of which contain mixed cell populations, are the most frequent cause of primary hyperparathyroidism. Parathyroid adenomas composed exclusively of water-clear cells are exceptionally rare. Until now, only 2 cases have been reported in English literature. We report a water-clear cell adenoma of the parathyroid gland in an intrathyroidal position, which has not been described previously according to our knowledge. HUM PATHOL 32:889-892. Copyright © 2001 by W.B. Saunders Company

Synchronous water-clear cell double parathyroid adenomas a hitherto uncharacterized entity?

Water-clear cell hyperplasia is a rare but well-documented cause of primary hyperparathyroidism. Parathyroid adenomas of the water-clear cell type are exceptionally rare, and only 2 cases have been reported. We describe a patient with synchronous water-clear cell double parathyroid adenomas, an entity that has not previously been reported. In our case, the enlarged superior parathyroid glands were completely replaced by water-clear cells, with only a minute rim of extracapsular, histologically unremarkable parathyroid tissue. The inferior parathyroid glands were grossly unremarkable, and incisional biopsy specimens were histologically normal (no foci of water-clear cells were identified). The findings in this case are most consistent with the diagnosis of double adenomas of the water-clear cell type. We acknowledge that despite molecular proof of monoclonality of the 2 lesions, it is not possible to entirely exclude the possibility that this unusual case could be due to asymmetric hyperplasia.

Parvalbumin is expressed in normal and pathological human parathyroid glands.

The parathyroid glands are of major importance in calcium homeostasis. Small changes in the plasma calcium (Ca2+) concentration induce rapid changes in parathyroid hormone (PTH) secretion to maintain the extracellular Ca2+ levels within the physiological range. Extracellular Ca2+ concentration is continuously measured by a G-protein-coupled Ca2+-sensing receptor, which influences the expression and secretion of PTH. The mechanism of signal transduction from receptor sensing to PTH secretion is not well understood, but changes in PTH secretion are tightly linked to changes in the cytosolic Ca2+ concentration. Using immunohistochemistry and Western blot analysis, we detected the EF Ca2+ binding protein parvalbumin (PV) in normal and in hyperplastic and adenomatous human parathyroid glands. The strongest PV signal was present in chief cells and water clear cells, whereas in oxyphilic cells only a weak signal was observed. Immunohistochemistry and in situ hybridization of the PTH indicated a co-localization of PV and PTH in the same cell types. Because changes in the cytosolic Ca2+ concentration are believed to influence the process of PTH secretion, a possible role of PV as a modulator of this Ca2+ signaling is envisaged.

Fine structure of the parathyroid and ultimobranchial glands of the snake, Elaphe quadrivirgata.

The ultrastructure of the parathyroid gland and ultimobranchial gland of the snake, Elaphe quadrivirgata, was studied. The parenchyma of the parathyroid gland was consisted of chief cells arranged in cords. Oxyphil cells and water-clear cells were not recognized. The chief cells contained irregular shaped nucleus, moderately-developed mitochondria, granular endoplasmic reticulum and Golgi complexes. A few secretory granules of 100-300 nm in diameter distributed in the cytoplasm. Small aggregations of glycogen particles and lipid droplets were dispersed widely in the cytoplasm. The ultimobranchial glands consisted of follicles and interfollicular aggregates of C-cells. Follicles were invaginated and composed of C-cells, goblet cells and ciliated cells. C-cells were located in the basal position of the follicle and possessed variety of secretory granules of 100-300 nm in diameter in the basal region of the cell. C-cells presented various secretory cycles. Goblet cells projected microvilli into follicular lumen. At the apical region the goblet cells had large granules of 300-1,200 nm in diameter. Ciliated cells projected cilia intermixed with micovilli from the apical surface of the cell into the follicular lumen.

Parathyroid morphology of the brush-tail possum, Trichosurus vulpecula.

Reviews of the comparative anatomy of the parathyroid glands contain very little or no information on this endocrine gland in marsupials. This paper is the initial report of a broader investigation of the parathyroid glands in marsupials and monotremes. Nineteen possums (Trichosurus vulpecula) were used in the study of the anatomy, histology, and ultrastructure of the parathyroid glands. Tissue sections were examined using routine light and electron microscopic techniques. Parathyroid III is larger than parathyroid IV. The former occurs in the vicinity of the carotid bifurcation; the latter is found in the mediastinum, and in 67% of samples it was observed to be associated with thymic tissue. In parathyroid III specimens, 12.5% had follicles, 25% had cysts, and 16% contained thymic tissue. Ultrastructurally, the majority of specimens consisted of principal cells; no oxyphil cells were seen. Light and dark cells were only seen in glands that had been fixed by perfusion. Junctions between thymic and parathyroid tissues showed intervening epithelial reticular cells, but a basal lamina was not always apparent. In three specimens, cells that resembled water-clear cells were present. It is proposed that these unusual cells may reflect a state of impaired health in these possums. Except for the presence of vacuolated cells labelled water-clear cells, the histology of the parathyroid gland in the possum shows many similarities to that in many eutherians.

A study of parathyroid hyperplasia in chronic renal failure

Specimens removed at parathyroidectomy from 41 patients with chronic renal failure, 12 patients with parathyroid adenomas and parathyroid glands from 24 autopsies were studied by light microscopy, immunohistochemistry and electron microscopy. The morphological abnormalities were correlated with clinical data obtained from patients' medical records. Glandular enlargement in chronic renal failure, primarily due to parenchymal cell hyperplasia, was as much as 20 times the normal in contrast to 40 times the normal cases of adenomas. Glandular hyperplasia was mostly due to an increase in the number of chief cells and to a lesser extent increase in the number of oxyphil cells, transitional oxyphil cells and water-clear cells. There was a corresponding reduction in fat and intracellular lipid content. There were differences in the overall morphology of normal, hyperplastic and adenomatous glands. The clear histological distinction between hyperplastic and adenomatous glands was at times difficult. There was no correlation between the extent of hyperplasia, the cause of renal failure, duration of chronic renal failure, levels of serum calcium, phosphate or parathyroid hormone. Immunohistochemical studies showed that all 3 types of cells contained parathyroid hormone but in hyperplastic and adenomatous glands there was a reduction in parathyroid hormone and chromogranin A staining. There were no specific ultrastructural abnormalities which would distinguish between hyperplastic and adenomatous glands.

SURGICAL TREATMENT FOR SECONDARY HYPERPARATHYROIDISM IN PATIENTS ON CHRONIC HEMODIALYSIS

Since 1987 thirteen patients on long-term hemodialysis underwent total parathyroidectomy and autotran-splantation for secondary hyperparathyroidism. There were nine men and four women, with a mean age of 48 years (23-65 years old). The duration of dialysis treatment before parathyroidectomy was a mean of 13.9 years (6.9-11.7 years). As many as 9 patients had a 13.8-17.7 year history of dialysis. Most of them complained of a bone pain at the neck in one case, shoulder in 2, elbow joint in one, lumber region in 3, hip joint in one, and lower extremities in 2. Four patients complained of itching, and all showed elevated serum PTH levels and serum ALP levels. These patients did not respond to medical treatments including calcium supplement through dialysis liquid, oral and intravenous supplement of calcium preparation, and administration of activated vitamin D. Surgical therapy was carried out. Histological examination of excised parathyroid glands revealed chief cells more predominant than water clear cells and oxyphilic cells. Itching improved in a few days and bone pain improved in a few months. Postoperative hypocalcemia was controlled by administrations of Ca-gulconate, 1, 25(OH)2D3 and supplemental calcium. In all cases, remarkable improvement of symptoms by surgical treatment was noticed and the function of grafts seemed to be good.

Ultrastructure of the water-clear cell in the rabbit parathyroid gland.

The ultrastructure of water-clear cells has been described in human hyperplastic parathyroid glands. However, previous studies have failed to demonstrate this type of cell in normal human or other vertebrate parathyroid glands. Upon recently recognizing water-clear cells in the parathyroid glands of the golden hamster, we intended to examine the occurrence of these cells in other animals. In the present study the parathyroid glands of about one-year-old rabbits were observed by electron microscopy. Water-clear cells containing numerous vacuoles were demonstrated dispersed among the chief cells. The cells were generally situated close to the basal lamina of perivascular space which lay against the capillary vessel and were attached by desmosomes to the chief cells. Irregularly shaped vacuoles in the water-clear cells resembled dilated cisternae of the granular endoplasmic reticulum in the chief cells. Several ribosomes could be seen attached to the membrane of some of the irregularly shaped vacuoles. It is conceivable that the water-clear cells are transformed from the chief cells.

Effects of starvation on the water-clear cell in the golden hamster parathyroid gland.

Changes of the water-clear cells of the parathyroid glands in adult and senile golden hamsters 2 and 5 days after starvation were investigated. The ultrastructure of the water-clear cells of the parathyroid glands in the starved adult and senile animals almost resembled that of the control adult and senile animals. However, lipid droplets were very numerous in the water-clear cells in the adult and senile animals after starvation. It is considered that starvation affects functional activity in the water-clear cells of the parathyroid gland.

Origin of the Water-Clear Cell in the Parathyroid Gland of the Golden Hamster

Water-clear cells and transitional forms between the chief cells and water-clear cells were observed in the parathyroid gland of the golden hamster. Their ultrastructure is described, and the origin of the water-clear cell is discussed.

Alteration in density, morphology and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism.

Dispersed parathyroid cells from normal human and bovine glands and from 10 patients with primary (7 adenomas, 3 hyperplasias) and 4 patients with uraemic hyperparathyroidism (HPT) have been investigated with respect to density, morphology and parathyroid hormone (PTH) release. Percoll density gradients enabled an efficient isolation of viable parathyroid cells which generally banded between 1.035-1.090 g/ml. The average density was significantly higher in cells from the normal than the abnormal glands. The pathological glands contained large chief cells, oxyphil and transitional oxyphil cells and, in one case, water-clear cells which were enriched in fractions with densities below 1.055 g/ml. Measurements of cell diameters revealed an increased proportion of enlarged cells in the preparation of abnormal glands. Nuclear diameters were similar in the normal human glands, adenomas and hyperplasias, but the variability was greater among the adenomas. In comparison to normal bovine parathyroid cells, PTH release of cells from the pathological human glands was reduced and abnormally insensitive to extracellular calcium. The oxyphil and water-clear cells secreted similar amounts of PTH as the chief cells of the abnormal glands. The disturbed PTH release in secondary HPT seemed to be confined mainly to cells within nodules of the hyperplastic glands. The results show that the disturbed hormone regulation in HPT is related to morphological changes of the cells and that buoyant density gradients can be used to accumulate the abnormal cells.

Primary hyperparathyroidism in children

We present here a series of seven children with primary hyperparathyroidism caused by parathyroid adenoma. Chief cells were the primary element in six patients and water-clear cells in one patient. A brief review of the literature on primary hyperparathyroidism in children is included. Emphasis is placed on the clinical characteristics of this rare disease in children.