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PubMed1997

In situ detection of parathyroid hormone-related protein in ovarian clear cell carcinoma.

A case of ovarian clear cell carcinoma associated with hypercalcemia is reported. A 67-year-old woman developed the lung metastasis 8 months after primary surgery. The patient manifested symptoms of humoral hypercalcemia of malignancy (HHM) during the last 3 months of her clinical course. Serum and urinary C-terminus parathyroid hormone-related protein (PTHrP) levels were remarkably high. No increase in interleukin (IL) 1beta, tumor necrosis factor (TNF) alpha, vitamin D3 metabolites or intact PTH was detected. Pamidronate disodium treatment was transiently suppressed her serum calcium level. The patient died despite seven courses of chemotherapy. Autopsy showed multiorgan metastases and accelerated osteoclastic bone resorption; skeletal metastasis was not detected. Immunohistochemical analysis clearly showed the localization of PTHrP at both the primary and metastatic sites. The transcripts of PTHrP at pulmonary metastatic sites were revealed by in situ hybridization and the reverse transcription polymerase chain reaction (RT-PCR) method. PTHrP was the causative factor for HHM in this case. It is therefore suggested that hypercalcemia may have occurred after PTHrP production had overcome the homeostatic level during the terminal stage, although PTHrP production continued irrespective of the patient's serum calcium level.

Adenocarcinoma, Clear Cell↗
PubMed1996

Papillary parathyroid adenoma. A rare occurrence and its importance in differentiation from papillary carcinoma of the thyroid.

The case of a 67-year-old woman with primary hyperparathyroidism manifested by hypercalcemia with anorexia, nausea, and weakness; low serum phosphorus; high circulating parathyroid hormone; and mildly elevated calcitriol and parathyroid hormone-related protein is reported. A cystic lesion was removed from the inferior pole of the right lobe of the thyroid, and serum calcium levels rapidly returned to normal. The lesion was proven histologically to be a parathyroid adenoma with predominate papillary features. The differentiation of such a rare lesion from papillary carcinoma of the thyroid, both histologically and cytologically, is stressed.

Adenoma↗
PubMed1991

[Lectins expression of parathyroid glands with primary hyperparathyroidism].

The binding sites of lectins in parathyroid glands were determined by an immunohistochemical method in normal parathyroid gland, hyperplasia, adenoma and carcinoma, the used lectins were commercially available Glycine max (SBA), Concanavalin enciformis (Con A), Triticum vulgaris (WGA), Richinus communis (RCA), Banderiaea simplicifolia II (BSA II) and Arachis hypogaea (PNA). For normal parathyroid glands (2 cases) and hyperplasia (2 cases), WGA and BSA II were stained in cytoplasma and cell membrane. For carcinoma (1 cases), all lectins but BSA II were positively stained. In particular, SBA revealed more stronger stain than any other hystological types. From the staining patterns of lectins, it was suggested that adenomas (22 cases) be divided into one group similar to carcinoma and the others to normal parathyroid gland and hyperplasia. But there was no difference in clinical data of patients between the two groups.

Adenoma↗
PubMed1988

Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors.

We investigated a variety of endocrine tumors for the presence of chromogranins A and B and secretogranin II. These antigens were identified by one- and two-dimensional immunoblotting and in some cases by immunohistochemistry. An antigen corresponding in electrophoretic behavior to adrenal chromogranin A was present in all types of tumors, including insulinomas, oat cell carcinomas, and Merkel cell tumors of the skin. Chromogranin B had a much more limited distribution. This antigen could not be detected in parathyroid adenomas, oat cell carcinomas, or Merkel cell tumors, either by immunoblotting and immunohistochemistry. The occurrence of secretogranin II was similar to that of chromogranin B, with the exception of a positive reaction in Merkel cell tumors. In benign pheochromocytomas, all three antigens were found consistently; whereas in two of three malignant pheochromocytomas, chromogranin B was absent. Our study establishes that in most cases chromogranins and secretogranin in tumors are identical to the adrenal antigens, but that these antigens are not always stored together. Chromogranin A is the most widely distributed marker for endocrine tumors.

Adrenal Gland Neoplasms↗
PubMed2003

[Hyperplasia and tumors of the parathyroid glands].

Hyperparathyroidism is mainly caused by hyperplasia or adenomas of the parathyroid glands. Formerly, the therapeutic strategy depended on the morphological diagnosis (preferentially already made intraoperatively by examination of frozen sections). Today, however, the extent of parathyroid surgery is in many cases guided both by substantial improvements in the preoperative clinical diagnosis as well as the intraoperatively determined decrease in the serum parathyroid hormone level. Nevertheless, the pathologist should be familiar with the differential diagnostic criteria of parathyroid hyperplasia, adenoma, and carcinoma.

Humans↗
PubMed2005

Genetic aberrance of sporadic MEN 2A component tumours: analysis of RET.

AIM: The molecular pathogenesis of familial multiple endocrine neoplasia (MEN) type 2 (parathyroid adenoma with medullary thyroid carcinoma and adrenal pheochromocytoma) is associated with a germ-line mutation in the RET proto-oncogene. We undertook this study to clarify the relationship between the tumorigenesis of apparently sporadic MEN type 2 component endocrine tumours and RET mutations. METHODS: Direct sequencing for RET exon 10, 11, 12, 13, 14, 15 and 16 and immunohistochemistry for RET monoclonal antibody were performed on the archival tissues of 84 cases of sporadic endocrine tumours, including 22 medullary thyroid carcinomas (MTCs), 35 adrenal pheochromocytomas (APCs), 18 paragangliomas (PGs), and nine parathyroid adenomas (PTAs). RESULTS: PCR-based direct sequencing revealed somatic point missense mutation within 22.7% of exon 13 of the RET proto-oncogene (four cases of E768D, one case of S7781) in MTCs. No RET genotype and morphological association was observed in MTCs or APCs. APCs revealed significantly lower levels of immunoexpression of RET, even versus PGs. CONCLUSIONS: The genetic mutation in RET is relatively low in incidence, and likely to play an insignificant role in the molecular pathogenesis of sporadic MTC. The molecular bases of PG and APC seem to be different despite their embryological and histological similarities.

Adrenal Gland Neoplasms↗
PubMed2006

Parathyroid hormone-related protein as a potential tumor marker: a case report of ovarian clear cell carcinoma.

Hypercalcemia is one of the important paraneoplastic syndromes, mostly occurring in patients with advanced cancer. Clear cell carcinoma is known to be one of the most common histological subtypes of ovarian tumor associated with hypercalcemia. We present a case of ovarian clear cell carcinoma with hypercalcemia caused by elevated serum parathyroid hormone-related protein (PTHrP). PTHrP mRNA and protein were detected by reverse transcription-polymerase chain reaction and immunohistochemical analysis in the primary and metastasis lesions. Serum calcium and PTHrP levels returned to normal after antihypercalcemic treatment and a radical operation, but they elevated along with the recurrence. Because tumor markers such as carcinoembryonic antigen, carbohydrate antigen (CA)125 and CA19-9 were unstable owing to the patient's liver cirrhosis and were not reliable data for management, serum calcium and PTHrP levels are shown to have been a potential indicator of the recurrence in this case.

Adenocarcinoma, Clear Cell↗
PubMed2003

Preoperative parathyroid localization: correlating false-negative technetium 99m sestamibi scans with parathyroid disease.

OBJECTIVE/HYPOTHESIS: The recent trend toward minimally invasive directed parathyroid surgery has increased the surgeon's reliance on preoperative parathyroid localization. Technetium Tc 99m sestamibi scanning is generally viewed as the gold standard for preoperative localization, with reported sensitivities of 75% to 100% and specificities of 75% to 90%. However, in each reported series there exists a group of patients in whom preoperative localization is either equivocal or negative. STUDY DESIGN: We focused on a subset of patients from our parathyroid database with false-negative sestamibi (MIBI) scans, in an attempt to elucidate features that could affect these studies. We identified 20 patients with negative preoperative scans and confirmed parathyroid disease. We compared them with 22 consecutive patients with positive scans, correlating the following variables: patient age, gender, concomitant thyroid disease (Hashimoto's thyroiditis, papillary thyroid carcinoma, thyroid adenoma), preoperative parathyroid hormone values, location and number of enlarged parathyroid glands, parathyroid weight, and the relative proportion of chief cells, clear cells, oxyphil cells, and adipose tissue. METHODS: Retrospective chart review of clinicopathological and radiological findings. RESULTS: We found that patients with false-negative scans were more likely to have an enlarged parathyroid containing a high proportion of clear cells (P =.01). A trend was seen (P =.1) correlating increased parathyroid fat content and false-negative scans. Conversely, positive preoperative scans were more likely to be associated with a higher percentage of oxyphil cells (P =.02). Univariate analysis for other variables, as well as logistic regression analysis, did not achieve statistical significance. CONCLUSIONS: To date, the present study is the largest clinicopathological review of patients with false-negative sestamibi scans. Technetium Tc 99m uptake correlates with parathyroid oxyphil cell content, and false-negative scans can occur with parathyroid glands containing predominantly clear cells.

False Negative Reactions↗
PubMed1998

Immunohistochemical localization of chromogranin A in endocrine tissues and endocrine tumors of dogs.

Chromogranin A is present in the secretory granules of endocrine cells and functions in hormone packaging, secretory granule stabilization, and regulation of hormone secretion. Immunohistochemical identification of chromogranin A can facilitate diagnosis of endocrine neoplasia. Normal and neoplastic canine tissues were stained immunohistochemically for chromogranin A. Staining of normal endocrine tissues demonstrated chromogranin A in chromaffin cells of the adrenal medulla, C cells of the thyroid gland, and pancreatic islets. The parathyroid chief cells and anterior pituitary stained lightly positive for chromogranin A. Pheochromocytomas (7/7), chemodectomas (5/7), islet cell carcinomas (2/6), pituitary adenomas (4/6), parathyroid adenomas (3/7), and a C-cell carcinoma (1/1) stained positive for chromogranin A. The data indicate that chromogranin A is widely distributed in canine endocrine tissues, and immunohistochemical staining of chromogranin A can be used to confirm the presence of secretory granules in endocrine tumors.

Animals↗
PubMed1991

Parathyroid hormone-related protein, chromogranin A, and calcitonin gene products in the neuroendocrine skin carcinoma cell lines MKL1 and MKL2.

We studied the production of parathyroid-hormone-related protein, chromogranin A, calcitonin and calcitonin-gene-related peptide in the neuroendocrine skin cell line, MKL1, and a subsequently derived cell line designated MKL2. Both cell lines had cytological, histological and electron-microscopic features typical of neuroendocrine differentiation. Immunohistology and radioimmunoassay studies demonstrated the presence of parathyroid-hormone-related protein, chromogranin A, calcitonin-gene-related peptide, and calcitonin in the MKL2 cell line and the last three substances in both cell lines. The secretion of each of the first three substances was regulated by phorbol in the MKL2 cells. Additional immunohistochemical studies demonstrated the variable expression of bombesin, substance P, and vasoactive intestinal polypeptide in MKL2 cells, and the expression of synaptophysin in both MKL1 and MKL2 cells. These studies demonstrate the neuroendocrine characteristics of the MKL cell lines and provide a novel model for studies of the production and interactions of several neuroendocrine proteins and peptides by human skin cells.

Bombesin↗
PubMed1975

[Special and functional pathomorphology of parathyroid glands as revealed in non-selected autopsies (589 cases) (author's transl)].

1637 parathyroid gland dissections were performed on 589 unselected autopsy preparations in order to study both pathomorphology and functional aspects in an unselected group of patients. In no case had primary or tertiary hyperparathyroidism been suspected clinically; but in about 10 patients on chronic hemodialysis, a secondary hyperplasia of the glands was known. In about 33% of the cases pathological changes were observed: 3 chief cell adenomas, 3 adenomas combined with hyperplasia, 12 primary nodular hyperplasias including 6 microadenomas and 145 cases with secondary regulative hyperplasia. Cysts, purulent parathyroiditis, lipomatous pseudohyperplasia, metastases of carcinomas, hemorrhagic infarctions and amyloidosis were also detected in serial sections of the parathyroid glands. The remarkably large group of secondary hyperplasias (about 20%) was divided into 3 categories according to weight and cytology. The first category (118 cases) was characterized by a lack of the normal age-related involution of the parenchyma and prevalence of light (active) chief cells. Statistical evaluation of the other autopsy findings, histomorphology of the bone in particular, led to the conclusion that this group represented a slightly activated gland with possibly reversible hyperplasia, mostly connected with pathological alterations in the kidney and with minimal changes in bone morphology consistent with hyperparathyroidism. The microadenomas displayed different levels of endocrine activity as demonstrated by bone histology in accordance with the cytology of the adenomas (dark or resting chief cells versus active chief cells and waterclear cells). No specific alterations with respect to endocrine function could be attributed to diffuse and nodular hyperplasia of oxyphil (oncocytic) cells except their increase with age and arteriosclerosis, especially in women.

Adenoma↗
PubMed2001

Production of parathyroid hormone-related protein in two new cell lines of renal cell carcinoma.

BACKGROUND: Hypercalcemia is the most common of all paraneoplastic syndromes and has been reported to appear in up to 20% of patients with renal cell carcinoma (RCC). Humoral hypercalcemia of malignancy is believed to be induced when parathyroid hormone-related protein (PTHrP) is excessively produced in cancer cells and impairs the homeostasis of serum calcium concentrations. METHODS: Cancer cells were isolated from a surgical specimen and successfully cultured in a monolayer. The present study describes the establishment and characterization of new cell lines of RCC. RESULTS: Two different cell lines, designated SMRC-1 and SMRC-3, were established from human RCC, each of which had been continuously secreting PTHrP in vitro. The patient from whom the SMRC-3 cells were obtained was shown to have elevated levels of PTHrP and resultant hypercalcemia. Cultured SMRC-1 was spindle-shaped in morphology. SMRC-3 had pleomorphic polygonal shapes and formed typical epithelial monolayers. Both cell types secreted intact, C-terminal PTHrP and interleukin-6 in the culture medium. Cellular messenger RNA of PTHrP was analyzed by reverse transcriptase-polymerase chain reaction. The SMRC-1 cells showed chromosome numbers ranging from 42 to 47 with consistent structural abnormalities of add(4)(q23~25) and add(6)(q13). The chromosomal analysis of SMRC-3 revealed a modal number of 95 with consistent structural abnormalities of add(1)(p36) and der(1;3)(q10;p10). CONCLUSIONS: These cell lines could be good models for investigating the mechanism of PTHrP production and the relationship between this hormone and hypercalcemia.

Adult↗
PubMed1978

Magnesium and phosphate in the serum of patients with medullary carcinoma of the thyroid.

Magnesium, phosphate, immunoreactive parathyroid hormone and calcium were measured in the serum of nine patients with medullary carcinoma of the thyroid and high serum calcitonin, and compared with the values in nine patients with normal serum calcitonin. Serum phosphate was significantly higher in the group of patients with high serum calcitonin (P less than 0.025). No correlation was observed between the serum concentrations of magnesium and calcitonin, nor of immunoreactive parathyroid hormone and calcitonin.

Calcitonin↗
PubMed1975

Multiple endocrine adenomatosis type IIb. Diagnosis and treatment.

A 29-year-old man with a marfanoid habitus, peculiar mucosal neuromas of the lips and tongue, high arched palate, hyperplastic corneal nerves, and hypertension was found at operation to have medullary carcinoma of the thyroid, parathyroid hyperplasia, and pheochromocytoma. These symptoms and findings are characteristic of multiple endocrine adenomatosis (MEA IIb) syndromes.

Adrenalectomy↗