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PubMed1997

Mediastinal Parathyroid Tumor: Giant Adenoma or Carcinoma?

A 71-yr-old woman presented with progressive weakness, bone pain, polydipsia, and epigastric pain. Laboratory studies established the diagnosis of primary hyperparathy roidism with excessively elevated levels of parathyrod hormone (PTH) complicated by renal failure and anemia. Preoperative imaging using (99m)technetium hexakis 2-methoxy-isobutylisonitrile (MIBI) demonstrated an area of intense uptake in the mediastinum, which on T(2) -weighted magnetic resonance imaging revealed the presence of a hyperintense mediastinal mass of 25 mm in diameter adjacent to the ascending aorta Surgical exploration and resection of the mass were performed, and histological examination of the tumor revealed solid masses of epithelial cells growing in a trabecular pattern, hyaline bands, and low mitotic activity. Immunohistochemical staining of the tumor specimens using monoclonal mouse antihuman antibodies revealed markedly positive immunoreactivity of tumor cells for p53 protein and absence of nuclear immunoreactivity for the retinoblastoma tumor-suppressor protein, findings consistent with parathyroid carcinoma. Improved imaging techniques and advances in molecular pathology of parathyroid disorders may help to improve clinical management of patients with parathyroid neoplasia.

Journal Article↗
PubMed1999

Esophageal carcinoma with high serum parathyroid hormone-related protein (PTHrP) level.

We report two patients with esophageal carcinoma with high levels of serum parathyroid hormone-related protein (PTHrP). Patient 1 was a 66-year-old man in whom the serum calcium level was also high, and patient 2 was an 81-year-old woman. The serum PTHrP level was 411 pM (normal range, 13.8-55.3pM) in patient 1 and 94.5 pM in patient 2 (in whom the serum granulocyte colony-stimulating factor level was also high). We demonstrated PTHrP immunohistologically in esophageal carcinoma cells in both patients. After admission, patient 1 died of pneumonia on the 17th day of hospitalization (the 48th day after he had had an episode of frequent hiccuping) and patient 2 died of acute circulatory failure on the 12th day of hospitalization (the 25th day after she had vomited after a meal). Neither of these patients died of cancer. Pneumonia in patient 1 was believed to be due to weakened body defenses, while the acute circulatory failure in patient 2 was due to emaciation. Since esophageal carcinoma with humoral hypercalcemia of malignancy and leukocytosis is characterized by rapid progression and metastasis, early diagnosis and treatment are mandatory.

Aged↗
PubMed1977

Incidence of hypoparathyroidism after radical surgery for thyroid carcinoma and autotransplantation of parathyroid glands.

Ninety-seven consecutive patients had radical surgery for thyroid carcinoma. Eighty-six of these had one or more parathyroids implanted into muscle tissue. At follow-up, ninety-one patients were normocalcemic without substitution, fifteen of those with only implanted glands. The results show that radical surgery can be performed with a low incidence of hypoparathyroidism, provided the parathyroids are carefully searched for and liberally implanted.

Adenocarcinoma↗
PubMed1974

Secretion of parathyroid hormone in patients with medullary thyroid carcinoma.

The secretion of parathyroid hormone (PTH) and calcitonin (CT) was studied in 30 patients with medullary thyroid carcinoma. Most patients with elevated levels of CT were normocalcemic and also had normal basal levels of PTH. Five of six patients with associated hyperparathyroidism were hypercalcemic and had elevated basal PTH levels. Hormone secretion was also studied during infusions with standard and low doses of calcium. PTH unexpectedly increased during 12 of 18 calcium infusions. Such a paradoxical increase in PTH was seen in those patients with the greatest increase in CT and the least increase in calcium during the calcium infusion. Accordingly, increases in PTH concentration during the calcium infusions could be correlated directly with increases in CT and correlated inversely with increases in calcium. These observations suggest that, in some patients with medullary thyroid carcinoma, a further increase in the abnormally elevated CT levels may stimulate PTH secretion. Therefore, at least in acute studies, there may be a functional, as well as a genetic, relationship between the secretion of these two hormones in patients with this thyroid tumor.

Calcitonin↗
PubMed1997

Clonal heterogeneity of the growth and invasive response of a human breast carcinoma cell line to parathyroid hormone-related peptide fragments.

It has been previously reported that 8701-BC cells, derived from a primary carcinoma of the breast, constitutively express parathyroid hormone (PTH)-related peptide (PTHrP) and PTH/PTHrP receptor (PTH/PTHrP-R) genes, that N-terminal, mid-regional and C-terminal immunoreactive PTHrP can be found in cell conditioned medium and, furthermore, that exogenously added PTHrP (1-34), (67-86) and, to a minor extent, (107-139) are anti-mitogenic but promote Matrigel invasion by this cell line. It has also been reported that PTHrP gene expression is selectively switched on in those 8701-BC clonal lines endowed with a higher proliferation rate and invasive ability in vitro. Here we have first examined the presence of PTH/PTHrP-R transcript in the different 8701-BC clones by PCR and Southern blot analysis. Second, we have studied the growth and invasive response in vitro to PTHrP fragments by some of these clones, i.e. BC-3A, BC-61 and BC-66, selected on the basis of their lower (BC-3A) or higher (BC-1 and BC-66) Matrigel invasion ability and their expression of PTHrP (positive for BC-61 and BC-66) and PTH/PTHrP-R (positive for BC-61). Our data show the existence of clonal heterogeneity for PTH/PTHrP-R mRNA and for the proliferative and invasive responses elicited by treatment with diverse PTHrP fragments. In particular: (i) the sensitivity to PTHrP (1-34) is restricted due to the uneven expression of PTH/PTHrP-R; (ii) BC-3A cells (the less 'aggressive' clone) are resistant to the anti-mitogenic effect of the PTHrP domains and, most noticeably, exhibit a growth-potentiating response to PTHrP (67-86) opposite to that found for both the parental 8701-BC cells and the two other clones; (iii) all PTHrP fragments tested induced the expression of a growth-restraining and invasion-promoting phenotype by BC-61 cells (one of the more 'aggressive' clones). Present data in vitro support the hypothesis that in vivo PTHrP may be a key element in local control of the invasive process during breast carcinoma development and that its role may be, in turn, dependent upon the biological characteristics and the level of malignancy of the target cells within the multiclonal population of a primary tumour.

Breast Neoplasms↗
PubMed1995

Parathyroid adenoma and gastric carcinoma as manifestations of Cowden's disease.

Cowden's disease is a well-described clinical syndrome, the primary symptoms of which are orocutaneous hamartomas and disseminated gastrointestinal polyposis. In general, the gastrointestinal polyps are benign, and the incidence of malignant transformation is believed to be low. Other associated manifestations of Cowden's disease include breast cancer and thyroid disease (benign and malignant). A patient with previously unrecognized Cowden's disease underwent upper gastrointestinal endoscopy for surveillance of hyperplastic gastric polyps, and a gastric carcinoma in situ was detected. During the course of follow-up the patient was found to have primary hyperparathyroidism resulting from a parathyroid adenoma. Although several benign proliferative and malignant conditions are associated with Cowden's disease, neither parathyroid adenoma nor gastric carcinoma has been reported previously.

Adenoma↗
PubMed1978

[Parathyroid neoplasm associated with hyperparathyroidism].

Over a 25-year period, two carcinomas of the parathyroid were observed in 67 cases of primary hyperparathyroidism. The most important signs and symptoms were bone disease, palpable neck metastases, renal stones, and hypercalceamia with high blood levels of parathyroid hormone. Histology revealed that in principle parathyroid carcinoma can be distinguished from adenoma by a trabecular pattern and thick fibrous bands. The presence of cellular atypia and variation or mitotic figures (regressive polymorphia) was not a useful criteria for carcinoma. Local recurrence occurred in both cases.

Carcinoma↗
PubMed2006

Sex-specific survival advantage with parathyroid hormone-related protein in non-small cell lung carcinoma patients.

PURPOSE: Parathyroid hormone-related protein (PTHrP) is commonly expressed in non-small cell lung carcinomas (NSCLC). Expression of the protein could have implications for progression of the disease because it regulates cancer cell growth, apoptosis, and angiogenesis. However, its relationship with survival has not been evaluated in a large-scale investigation. EXPERIMENTAL DESIGN: PTHrP expression was assessed in paraffin-embedded tumor samples from 407 patients with NSCLC by immunohistochemistry. A pathologist unaware of the clinical history classified specimens as PTHrP positive or PTHrP negative. The log-rank test was used to compare survivals of PTHrP-positive and PTHrP-negative groups, and Cox regression was used to adjust for additional covariates. RESULTS: Median survival was 55 versus 22 months (P < 0.001) in female patients with and without tumor PTHrP, respectively. Male survival was 38 months independent of PTHrP status. Stage, histology, age, and smoking history were also associated with increased longevity. PTHrP remained a significant predictor of survival for female patients after controlling for stage, histology, and age. CONCLUSIONS: In this study, PTHrP expression was associated with a survival advantage in female patients. Additional investigations must be done to ascertain whether the result is reproducible and independent of potential confounding covariates. Sex-dependent effects of PTHrP in lung cancer would open new avenues of research into the role of sex in cancer progression.

Adenocarcinoma↗
PubMed2000

Head and neck squamous cell carcinoma: measurement of plasma parathyroid hormone-related protein and serum and urine calcium concentrations.

OBJECTIVES: Parathyroid hormone-related protein (PTHrP) is expressed by squamous cell carcinomas. Our first objective was to examine the stability of PTHrP in normal human plasma. Our second objective was to determine whether plasma PTHrP could be used in patients with head and neck squamous cell carcinoma (HNSCC) as an indicator of tumor burden or relapse. STUDY DESIGN AND SETTING: Blood and urine samples from 55 HNSCC patients undergoing tumor resection at The Ohio State University were measured for plasma PTHrP (1-86) concentration, serum ionized calcium concentration, and urine calcium/creatinine ratio. RESULTS: Two of 55 HNSCC patients had detectable levels of plasma PTHrP. Serum ionized calcium concentrations and urinary calcium/creatinine ratios were within normal limits in all patients. CONCLUSIONS: Plasma PTHrP was not a valuable indicator of tumor presence or recurrence in our patient population. SIGNIFICANCE: Plasma PTHrP is not a useful marker of tumor presence or recurrence in patients with stage II to IV or recurrent HNSCC.

Adolescent↗
PubMed1986

[Recurrence of hyperparathyroidism following a parathyroid autograft. Hyperplasia or carcinoma?].

The authors report a case in which hyperparathyroidism recurred after total parathyroidectomy and autogenous parathyroid graft into the fore-arm musculature, in a patient with chronic renal failure. Light and electron microscopic studies of the grafted tissue show a severe, nodular hyperplasia. This case report illustrates the rapid "tumour-like" growth of the hyperplastic parathyroid grafted tissue; according to some authors, the hyperplastic parathyroid tissue displays an increased propensity to become malignant.

Adult↗
PubMed1971

Medullary carcinoma of the thyroid with parathyroid adenoma and hypercalcaemia.

A patient with hyperparathyroidism due to a parathyroid adenoma was found to have metastatic medullary carcinoma in lymph nodes close to the thyroid gland. The finding of normal calcitonin and parathormone concentrations after removal of the adenoma suggested that the parathyroid lesion was not the result of the hypocalcaemic action of calcitonin produced by the tumour in the thyroid. Seventeen other examples of the association between medullary carcinoma and parathyroid enlargement are briefly reviewed.The pathogenesis of the parathyroid lesions is discussed, and it is suggested that some may be caused by the hypocalcaemic action of calcitonin, while others may be part of a syndrome of multiple endocrine adenomatosis.

Adenoma↗
PubMed1991

Pre-operative localization of parathyroid tumor by ultrasonography.

From July 1984 to June 1989, 24 cases with hypercalcemia and surgical proof of parathyroid adenoma or carcinoma received preoperative parathyroid sonographic examination in Chang Gung Memorial Hospital. There were 10 male patients with mean age of 51.5 +/- 12.3, and 14 female patients with mean age of 49.4 +/- 12.6. Parathyroid enlargement was detected by sonography examination in 22 of the 24 cases. The maximal diameter of the enlarged parathyroid in this series ranged from 1 cm to 3 cm. The accuracy of case diagnosis with sonography is 83.3%. In 96 parathyroid glands examined by sonography, the sensitivity is 83.3%, the specificity is 95.8% and the positive predictive value is 87%. From the results, it suggests that parathyroid sonography can be used as the first line localization method to detect parathyroid enlargement in hypercalcemia patients.

Adenoma↗
PubMed2006

Immunohistochemical analysis of low-grade and high-grade prostate carcinoma: relative changes of parathyroid hormone-related protein and its parathyroid hormone 1 receptor, osteoprotegerin and receptor activator of nuclear factor-kB ligand.

AIM: To investigate multiple bone cytokines produced by prostate carcinoma (PCa) as a novel strategy to differentiate potential aggressiveness in localised PCa using immunohistochemical analysis. METHODS: A total of 47 cases of PCa undergoing radical prostatectomy or transurethral prostatic resection at our institution (Fundación Jiménez Díaz (Grupo Capio), Madrid, Spain) between January 1991 and June 1998 were identified as low-grade (< or =4; n = 22) or high-grade (> or =7, excluding 7 (3+4) cases; n = 25) PCa according to Gleason grade. PCa specimens were immunostained for: parathyroid hormone (PTH)-related protein (PTHrP), the PTH1 receptor, osteoprotegerin and receptor activator of nuclear factor-kappa B ligand (RANKL), as well as Ki67 (a proliferation marker) and CD34 (an angiogenesis marker). RESULTS: PCa samples showed an increased immunostaining for both osteoprotegerin and RANKL, associated with tumour grade and PTHrP positivity, in the tumoral epithelium. Using a score value of 4-corresponding to moderate staining - as cut-off, the best sensitivity value was for PTHrP (with C-terminal antiserum C6; 100 %); wheras the best specificity value was for RANKL (95 %). CONCLUSIONS: All the evaluated factors are overexpressed mainly in the high-grade tumours. Our findings indicate that, in most patients with PCa (with Ki67 values between 1% and 9%), sequential determination of C-terminal PTHrP and RANKL immunoreactivities is a useful approach to discriminate low-grade and high-grade tumours.

Aged↗
PubMed1990

Modulation of the production of a parathyroid hormone-like protein in human squamous carcinoma cell lines by interaction with fibroblasts.

Normal human keratinocytes as well as human squamous cell carcinomas produce a parathyroid hormone-like protein (PLP). However, PLP production by these cells is not a constant phenomenon. Since nothing is known about factors which regulate the production of PLP, in vitro studies were performed with normal keratinocytes and squamous carcinoma cell lines in order to establish conditions under which PLP production may vary. PLP was measured as cyclic AMP production in parathyroid hormone target cells (osteoblasts) which could be inhibited by a parathyroid hormone antagonist. The presence of PLP was confirmed using a radioimmunoassay specific for PLP. Results from the bioassay correlated very well with the data obtained by radioimmunoassay for PLP. The results confirm that human squamous carcinoma cells and normal keratinocytes produce PLP. PLP production appeared to be very sensitive to modulation of coculture of squamous carcinoma cells with fibroblasts. The effect of fibroblasts was not mediated by an effect on squamous carcinoma cell viability. Murine transformed fibroblasts (3T3 cells) as well as human normal foreskin fibroblasts were equally effective in inducing PLP production in these cells. The fibroblastic factor was apparently present in a soluble form in the coculture system which prevented direct cell-cell contact but allowed communication through the medium. Nevertheless, conditioned medium from 3T3 cells failed to induce PLP production by squamous carcinoma cells. This suggests a more complicated interaction between the two cell types than a one way message from fibroblasts to keratinocytes. Production of PLP by a number of squamous carcinoma cell lines was variable and not evidently correlated with the ability of these carcinoma cells to differentiate. Production of parathyroid hormone-like protein not only is the expression of a disturbed metabolism of a specific cell type but also reflects the cell-cell interaction in tumor tissue.

Animals↗