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Familial isolated primary hyperparathyroidism with parathyroid carcinomas: clinical and molecular features.

OBJECTIVE: Familial isolated primary hyperparathyroidism (FIHP) is a rare hereditary disorder. We present four patients from a single family with FIHP, and genetic analysis of their parathyroid adenomas and parathyroid carcinoma. DESIGN: DNA was extracted from tumours resected at surgery. Tumours were examined for loss of heterozygosity (LOH) with microsatellite polymorphic markers. PATIENTS: The 27-year-old proband (Patient 1) died of parathyroid carcinoma with metastases to the lungs and chest wall. Sixteen years later, his 34-year-old sister (Patient 2) presented with a neck tumour and primary hyperparathyroidism. Family screening revealed parathyroid tumours in his 36-year-old sister (Patient 3) and 29-year-old cousin (Patient 4). Histological examination of resected tumours showed parathyroid carcinoma and adenoma in Patient 2, a parathyroid adenoma in Patient 3, and an atypical parathyroid adenoma in Patient 4. Autopsy of the proband ruled out multiple endocrine neoplasia (MEN) type 1, and the three patients who underwent parathyroidectomy did not exhibit any abnormalities in the pancreas or the pituitary gland. RESULTS: Analysis of tumour DNA from one parathyroid carcinoma (Patient 2), the atypical parathyroid adenoma (Patient 4), and two parathyroid adenomas (Patients 2 and 3) showed limited LOH on chromosomes 13q12.3-q32 in an adenoma of Patient 2 and 9p21-p22 and 13q12.3-q32 in an adenoma of Patient 3. CONCLUSION: These results suggest the possible contribution of tumour suppressor genes including the retinoblastoma gene and the hereditary breast cancer susceptibility gene (BRCA2) on 13q to parathyroid tumours in this family.

Adenoma↗

Parathyroid carcinoma of the oxyphil cell type. A report of two cases, light and electron microscopic study.

Parathyroid adenomas are subdivided into chief cell and oxyphil cell variants. However, the parathyroid carcinomas described thus far have been only of the chief cell type. Two cases of oxyphil cell carcinoma of the parathyroid gland are reported, with light and electron microscopic study. The patients presented apparent clinical hyperparathyroidism with x-ray finding of generalized fibrous osteitis and palpable parathyroid tumors. Initially, a pathologic diagnosis of parathyroid adenoma was made in both of them. However, in due course, pulmonary metastases developed in one patient and a local recurrence occurred in the other, 5 and 8 years after the primary operation, respectively. Review of the microscopic slides showed that both primary tumors met the criteria of parathyroid carcinoma. A matter of interest in both cases is that the neoplasms were composed principally of oxyphil cells. Electron microscopic study confirmed the existence of typical oxyphil cells packed with numerous mitochondria.

Adenoma↗

Surgical treatment of parathyroid carcinoma (Review).

Cancer of the parathyroid gland is rare and most patients suffer from hyperparathyroidism (HPT). Therefore it is often difficult to distinguish between benign HPT and malignant disorders. Prognosis as well as therapeutic approaches are still limited. Surgical treatment should be considered the therapy of choice for primary and recurrent manifestation of parathyroid carcinoma. The initial operation includes en-bloc resection of the tumor and the ipsilateral thyroid lobe. Surgery may cure some patients, but is often only palliative and aims to control hypercalcemia. In some patients hypercalcemia may be refractory to repeated surgery and medical treatment can provide short- or middle-term effects.

Humans↗

Indian primary hyperparathyroidism patients with parathyroid carcinoma do not differ in clinicoinvestigative characteristics from those with benign parathyroid pathology.

INTRODUCTION: No foolproof preoperative diagnostic indicators of parathyroid carcinoma (PC) exist in absence of nonskeletal metastases. Palpable parathyroid tumor, advanced skeletal and renal manifestations, and very high serum calcium and parathyroid hormone levels are considered strong predictors. Most of these features are common in Indian primary hyperparathyroidism (PHPT) patients although only few have PC. The aim of this study was to identify dependable clinicoinvestigative predictors of PC in Indian PHPT patients. MATERIALS AND METHODS: Clinical, biochemical, radiological, and densitometric attributes of 100 PHPT patients who underwent successful parathyroidectomy (1990-2004) were studied. Various parameters of patient groups with parathyroid adenoma (n = 84), primary hyperplasia (n = 12), and carcinoma (n = 4) were compared using ANOVA, with P value < 0.05 considered significant. RESULTS: Mean age of patients was 37.4 years, with no difference in the 3 groups (P = 0.92). Patients in 3 groups had comparably severe bone disease; 36 had coexistent renal disease. Two patients with PC and 27 (32%) with adenoma had palpable parathyroid tumor. None of the biochemical parameters predicted malignant pathology. Mean tumor weight (milligram) in carcinoma patients (15,080 +/- 5,638.02) was significantly higher than those with adenoma (5,724 +/- 1,257.9) (P = 0.002). Postoperative course and recovery in carcinoma patients were similar to those with adenoma. In follow-up (mean: 33 months), none of the adenoma patients were found to have persistent/recurrent PHPT attributable to missed PC. CONCLUSION: Indian patients with parathyroid adenoma, hyperplasia, and carcinoma were not found to differ in their clinical, biochemical, and pathological characteristics except for significantly higher tumor weight in the carcinoma group.

Adenoma↗

[Secreting parathyroid carcinoma. Apropos of a case].

Parathyroid carcinoma is rare and hits diagnosis often difficult. A case is reported, remarkable by the age of the patient (17 years), and the main peculiarities of the disease are reviewed: frequency of complete bone syndrome, palpable tumour of the neck, calcemia more than 140 mg/l, occurrence of recurrent palsy; relapsing course, death being dependent on hypercalcemia rather than metastasis; median survival time about five years, non influenced by chemotherapy. Ultrastructural study, previously realized in about thirty cases, is specially evaluated: it seems able to concur on anatomopathologic diagnosis, when assertion of malignancy is difficult.

Adenoma↗

[Parathyroid carcinoma: clinical aspects and therapy].

Parathyroid carcinoma is a rare entity with an 0,5-1% of incidence on primary hyperparathyroidism (HPP) in literature. The very high values of calcium and parathormone (PTH) and the clinical aspects of hypercalcemia are the characteristics findings in these patients. We present our experience on 6 pts on 153 cases with HPP treated (3,9%). The clinical and diagnostic suspects are frequently intraoperative findings and the decision making for the surgeon is not always easy (parathyroidectomy with or without hemithyroidectomy, lymphadenectomy, surgical resection of other tissues). The mortality rate is high and we have registered three deaths at 8,14 and 64 months.

Aged↗

Synchronous occurrence of parathyroid carcinoma and adenoma in an elderly woman.

The simultaneous occurrence of parathyroid carcinoma and other pathologic conditions of the parathyroid on a sporadic basis is extremely rare. Parathyroid exploration in an otherwise healthy 78-year-old woman with no underlying risk factors revealed synchronous right upper parathyroid adenoma and left upper parathyroid carcinoma. The patient's modest hypercalcemia (11.5 to 12.3 mg/dl) was seemingly at variance with remarkable parathormone elevations of 30 to 70 times normal.

Adenocarcinoma↗

Surgical and medical management of patients with pulmonary metastasis from parathyroid carcinoma.

BACKGROUND: The aim of this study was to characterize patients with pulmonary metastasis of parathyroid carcinoma and to evaluate the long-term effect of surgical and medical therapy. METHODS: Seven patients with pulmonary metastasis of parathyroid carcinoma were treated between 1980 and 1992. Six patients underwent resection of pulmonary metastases, and one patient has had long-term bisphosphonate therapy alone. Bisphosphonate was also given before or after operation to three patients. RESULTS: Two patients underwent a unilateral thoracotomy for a single pulmonary lesion, and four other patients with multiple lesions underwent staged bilateral thoracotomies. The postoperative serum calcium level returned to normal after each thoracotomy in three patients who were alive and well 3, 8, and 12 years after the first thoracotomy. Hypercalcemia persisted in the other three patients. In two of the patients, bisphosphonate therapy was also unable to control hypercalcemia. In one patient the serum calcium level has been maintained in the 13 mg/dl range by bimonthly bisphosphonate therapy alone for 3 years. CONCLUSIONS: The aggressive surgical approach to pulmonary metastasis of parathyroid carcinoma was shown to be effective for palliation in selected patients. Bisphosphonate therapy is an alternative to resection but has only a temporary calcium-lowering effect.

Adolescent↗

Hyperparathyroidism and parathyroid carcinoma.

A patient with hyperparathyroidism due to a functioning parathyroid carcinoma presented with distinctive clinical and laboratory features, including high serum calcium levels, roentgenographic signs of severe bone disease, a markedly elevated alkaline phosphatase level, a palpable cervical mass, and a high parathyroid hormone level. Treatment of parathyroid carcinoma requires en bloc resection of the ipsilateral thyroid lobe and isthmus for the primary tumor and ispilateral neck dissection for metastatic disease. Because the tumor grows slowly, recurrences should be resected to provide relief of hypercalcemia, the usual cause of death.

Bone Diseases↗

Parathyroid carcinoma: features and difficulties in diagnosis and management.

The objective of this review was to study the clinical course and the applicable diagnostic criteria in 12 patients with functioning parathyroid carcinoma, two patients with nonfunctioning parathyroid carcinoma, and a fifteenth patient who had an atypical intrathyroid tumor. The biologic patterns fell into four groups. The patients with functioning parathyroid carcinoma had either a prolonged tumor existence punctuated by hypercalcemic episodes ameliorated by operation to remove the tumor or an aggressive course with widespread metastases. The nonfunctioning cancers were aggressive cancers. The fourth group had one patient (others could have been considered) in whom a definitive diagnosis could not be made. The initial recognition of this cancer is sometimes difficult because consistent diagnostic features, either clinically or pathologically, are lacking. Enbloc resection at the first operation remains the best chance for cure. Surgical resection of recurrent disease appears to be the most effective palliative approach. Death results from hypercalcemia rather than from organ replacement by tumor.

Adult↗

Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: a paraffin immunohistochemical study.

In this study, we assessed the frequency of cyclin D1 protein expression in normal and neoplastic parathyroid tissue (10 parathyroid carcinomas, 28 adenomas, 18 hyperplasias, and 32 normal parathyroid glands) with use of a monoclonal anticyclin D1 antibody and a heat-induced epitope retrieval method. Overexpression of cyclin D1 was identified in 10 (91%) of 11 biopsy specimens from 10 patients with parathyroid carcinomas and in 11 (39%) of 28 parathyroid adenomas. In addition, 11 (61%) of 18 cases of parathyroid hyperplasia also expressed cyclin D1 protein, an observation not reported previously. These results confirm the high frequency of cyclin D1 expression in parathyroid carcinomas and adenomas. In addition, the results of this study indicate that overexpression of cyclin D1 protein is not limited to neoplastic proliferations of parathyroid tissue but is also seen in non-neoplastic proliferations of parathyroid gland. Cyclin D1 protein expression was rarely (<6%) present in normal parathyroid tissue.

Adenoma↗

Detection of metastatic parathyroid carcinoma with Tc-99m sestamibi imaging.

PURPOSE: To assess the use of Tc-99m sestamibi to localize recurrent and metastatic parathyroid carcinoma. METHODS: A patient with a history of parathyroid carcinoma that was resected 6 months before had high serum calcium and high serum parathyroid hormone levels. Tc-99m sestamibi imaging was performed to localize the recurrence. RESULTS: Tc-99 sestamibi imaging detected the recurrence and the metastatic lymph nodes. These findings were confirmed surgically and pathologically. CONCLUSION: Tc-99m sestamibi can be useful in diagnosing and localizing metastatic parathyroid carcinoma.

Carcinoma↗

Lung metastasis from parathyroid carcinoma causing recurrent renal hyperparathyroidism in a hemodialysis patient: report of a case.

We report herein the case of a 46-year-old woman on hemodialysis (HD) who developed recurrent renal hyperparathyroidism induced by lung metastasis from parathyroid carcinoma. The patient had been commenced on HD for chronic renal failure about 20 years earlier and had undergone a parathyroidectomy for advanced renal hyperparathyroidism 8 years later. After the initial operation, further explorations of the neck were performed due to recurrence, despite which the hyperparathyroidism persisted and she was finally referred to our department. The appearance of multiple coinlike lesions on a chest X-ray and computed tomography led to the diagnosis of recurrent hyperparathyroidism induced by lung metastasis from parathyroid carcinoma. A pulmonary wedge resection was performed and the metastatic parathyroid nodules were removed. Of the several hypotheses about the etiology of parathyroid carcinoma in HD patients, it is most likely that the parathyroid hyperplasia induced by chronic renal failure develops into carcinoma. Even in renal hyperparathyroidism, we should bear in mind the possibility that metastatic parathyroid carcinoma is a possible source of excess parathyroid hormone secretion at recurrence.

Carcinoma↗

Parathyroid carcinoma with metastatic calcification identified by technetium-99m methylene diphosphonate scintigraphy.

We describe herein a case of parathyroid carcinoma accompanied with metastatic calcification identified by technetium-99m methylene diphosphonate (Tc-99m MDP) scintigraphy in the lungs, kidneys and stomach. Parathyroid carcinoma remains a rare disorder despite the increased prevalence of primary hyperparathyroidism. Metastatic calcification is noted infrequently even in primary hyperparathyroidism and it may cause respiratory failure. Tc-99m MDP scintigraphy three months after surgery showed a complete disappearance of Tc-99m uptake in the stomach and an obvious reduction in the kidneys but no significant change in the lungs, indicating metastatic calcification can be reversibly reabsorbed. This case indicates that the adequate excision of parathyroid carcinoma as well as the early detection of metastatic calcification by Tc-99m MDP are obligatory.

Calcinosis↗

Primary hyperparathyroidism due to parathyroid carcinoma.

Most cases of primary hyperparathyroidism are due to either a parathyroid adenoma or to parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause of hyperparathyroidism. Although the diagnosis of parathyroid carcinoma is usually established based on pathological criteria of vascular and capsular invasion, some clinical and biochemical features differentiate it from benign forms of hyperparathyroidism. We report the case of a middle-aged woman with a long standing history of nephrolithiasis, who presented with a palpable neck mass, weight loss, severe hypercalcemia and hypophosphatemia, as well as very high serum levels of intact parathyroid hormone. Surgical neck exploration revealed a large tumor that invaded trachea, esophagus, reccurrent laryngeal nerve, right apical pleura and right carotid artery. Pathological examination confirmed the invasive nature of the tumor. Along with the case report, we review the literature and discuss the diagnostic and therapeutic options of this rare condition.

Carcinoma↗

Case of thymic parathyroid carcinoma in a haemodialysis patient: application of tumour chemosensitivity testing.

Parathyroid carcinoma is a rare tumour, which is often difficult to diagnose. This is especially true in patients with pre-existing tertiary hyperparathyroidism of end-stage renal disease. A case is presented of parathyroid carcinoma in a haemodialysis patient with unusual thymic involvement. After demonstrating the difficulty in pre-operative diagnosis and risk of recurrence, the importance of non-surgical treatment options is discussed and the investigation of individual tumour chemosensitivity is introduced, which is new to this type of cancer.

Adult↗

Parathyroid carcinoma: a case series.

INTRODUCTION: We present 3 patients with parathyroid carcinoma and describe their presentations, clinical profiles, and management. MATERIALS AND METHODS: A case series review of medical records. RESULTS: Two women and 1 man (age range, 32 to 57 years) had parathyroid cancer and primary hyperparathyroidism (PHPT). One patient presented with osteitis fibrosa, 1 with renal stone and a neck mass, and 1 with recurrence of PHPT after excision of supposedly benign parathyroid adenoma 4 years ago. All had severe hypercalcaemia and elevated parathyroid hormone levels that ranged from 4 to 43 times above the normal range. Exploration of the neck clearly identified 1 parathyroid tumour with local invasion; 2 other specimens showed capsular and vascular invasion on frozen section and final histology. All 3 patients underwent parathyroidectomy and ipsilateral hemithyroidectomy. Parathyroid size ranged from 1.3 to 4 cm and no lymph node metastasis was identified. No patient had tumour recurrence after a follow-up period of 1 year. CONCLUSION: Parathyroid carcinoma is a rare endocrine malignancy. Suspicious features include marked hypercalcaemia, neck mass, and local recurrence. Parathyroidectomy with ipsilateral hemithyroidectomy and nodal clearance gives the best chance of reducing local tumour recurrence.

Adult↗