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PubMed1985

Natural history of parathyroid carcinoma. Diagnosis, treatment, and results.

From 1948 to 1983, 28 patients with parathyroid carcinoma underwent treatment and analysis at the Massachusetts General Hospital. This represents about 2 percent of the 1,200 patients with hyperparathyroidism managed during the period. Patient ages ranged from 18 to 72 years (mean 45 years) with equal numbers of both sexes (14 women and 14 men). There are several hallmarks that are clues to an increased index of suspicion preoperatively. Nine of the patients (32 percent) presented with palpable neck masses. Eleven patients (39 percent) had a serum calcium level greater than 14 mg/100 ml. Significant elevations of the parathyroid hormone level were noted with values two to three times normal. The incidence and severity of metabolic complications were prominent. These complications included renal stones in 18 patients (64 percent), bone disease in 14 patients (50 percent), peptic ulcer disease in 5 patients (18 percent), parathyroid crisis in 4 patients (14 percent), and pancreatitis in 2 patients (7 percent). Eleven of the patients underwent previous surgical therapy at other institutions, and 17 patients had their initial operation at our institution. Cervical parathyroid carcinomas that ranged from 1.5 to 27 g and 1.5 to 6 cm were excised. The characteristic appearance was a gray-white, stone hard parathyroid mass with invasion of adjacent tissue. The outcome was favorable for 16 surviving patients, with 14 (50 percent) showing no evidence of recurrence 2 to 17 years postoperatively and 2 alive with persistent disease 3 years after operation. Twelve patients died. Of these, eight had unsuccessful initial operative intervention with capsular rupture and dissemination of cancer, one had advanced disease with mediastinal extension which was unresectable, and three died from unrelated causes. Recurrences became apparent within 6 months to 3 years after operation and unfortunately denoted incurable disease. The mean survival time after operation in patients with recurrent disease was 7.6 years, ranging from 1 to 22 years. Carcinoma of the parathyroid gland is a rare entity. Although it is difficult to diagnose preoperatively, there should be an increased index of suspicion in those hyperparathyroid patients with palpable neck masses, profound hypercalcemia (greater than 14 mg/100 ml), marked increase in the parathyroid hormone level to greater than twice normal, and significant metabolic complications. The initial operation must be aggressive yet meticulous with en bloc resection of the parathyroid tumor and all adjacent invaded tissues, avoiding capsular violation or tumor spillage.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2005

Parathyroidectomy for parathyroid carcinoma in renal transplantation.

INTRODUCTION: Hyperparathyroidism (HPT) is a highly prevalent pathology in the chronic renal disease population, which is associated with considerable morbidity, and mortality. The histopathological findings most often reported are solitary adenoma, diffuse hyperplasia, and autonomous hyperplasia. Carcinoma is an unusual cause of primary parathyroid hyperfunction (0.5% to 4% according to data); in renal transplanted patients it is exceptional. We sought to analyze parathyroid gland histology from renal transplant patients in comparison with nontransplanted patients and to report a parathyroid carcinoma case in a renal transplant patient. METHODS: We retrospectively analyzed parathyroidectomies (PTX) and histopathological reports between March 1989 and December 2003. RESULTS: Among 72 PTXs 41 were performed because of primary HPT; 26, secondary HPT; and five, tertiary HPT. Among the 41 primary HPT cases there were two carcinomas (4.88% primary HPT operated patients), one of whom was in a kidney transplant recipient. Among the total number of surgeries, seven were performed in six renal transplant patients, including five diffuse hyperplasia cases; one, nodular hyperplasia with an adenoma focus; and one, parathyroid carcinoma. CONCLUSIONS: Parathyroidectomy indications in the renal transplant population are usually associated with the clinical picture of tertiary HPT, which does not resolve after a functional renal transplant. In spite of this, diffuse hyperplasia, which is associated with secondary HPT, was the most frequent hystological finding. Two carcinomas were observed: one in a renal transplant patient (16.6% parathyroidectomies) and the other in a patient who did not show renal failure. These data coincide with international records.

Female↗
PubMed2006

Implantation of parathyroid carcinoma along fine needle aspiration track.

INTRODUCTION: Fine needle aspiration cytology is not a commonly employed diagnostic modality in the diagnosis of parathyroid tumors. CASE REPORT: A 28 year old lady being followed-up for 5 years after en bloc resection of a parathyroid carcinoma presented with a nodule in the lower neck, away from the parathyroidectomy scar. The 1 cm isolated nodule was located in the muscular and subcutaneous plane and corresponded to the needle track of FNA performed on a neck nodule before the parathyroidectomy. On evaluation, she had mild hypercalcemia and high normal serum parathyroid hormone levels. FNAC and histology including immunohistochemistry for Chromogranin A after local excision of the nodule confirmed the nodule to be a recurrent parathyroid carcinoma along the needle track. DISCUSSION: To the best of the authors' knowledge, this is only the second case of needle track implantation after FNA in parathyroid carcinoma reported to date. This case highlights the risk of engraftment of parathyroid tissue after FNA and cautions against the use of FNA as a preoperative diagnostic modality for the evaluation of parathyroid lesions.

Adult↗
PubMed1986

Nonsecretory parathyroid carcinoma of the mediastinum. Light microscopic, immunocytochemical, and ultrastructural features of a case, and review of the literature.

Nonsecretory parathyroid carcinoma is rare, particularly in extracervical sites. The authors present a case of a 51-year-old man with a large mediastinal mass that was found on a chest x-ray. Light and electron microscopy and immunohistochemical analysis of the resected tumor disclosed findings consistent with parathyroid carcinoma. Clinical and laboratory evaluations failed to reveal evidence of hyperparathyroidism. The nonsecretory state of the tumor was further supported by immunoreactivity for parathormone in tissue sections and, at the same time, normal levels of this peptide in serum. Partial shrinkage of the mediastinal mass occurred after 11 months of combined chemotherapy, with subjective improvement. A literature review of both secretory and nonsecretory parathyroid carcinomas was undertaken, revealing similar clinical features with regard to mean age, age range, and sex incidence among both groups.

Follow-Up Studies↗
PubMedDate not supplied

Metastatic calcifications and severe hypercalcemia in a patient with parathyroid carcinoma.

Primary hyperparathyroidism is rarely produced by parathyroid carcinoma. We present the case of a 63-yr-old man who was admitted due to recent onset of constipation, weakness and progressive lethargy. At physical examination, a left cervical mass was palpated. Marked hypercalcemia (serum calcium 25 mg/dl) (6.22 mmol/l) complicated by renal insuficiency (serum creatinine 4.4 mg/dl) (388 micromol/l) was found, but both were unresponsive to conventional therapy and hemofiltration. Autopsy examination showed a carcinoma of the upper left parathyroid gland, multiple foci of metastatic calficications in the vessel walls and parenchyma of both lungs and kidneys, and the myocardium, which contributed to multi-organ failure and death. In addition to describing the clinical presentation, we review the mechanism of metastatic calcifications as well as the role of renal function and hyperphosphatemia, and the basis for therapy of hypercalcemic crisis.

Autopsy↗
PubMed1999

Control of hypercalcaemia of parathyroid carcinoma by immunisation.

BACKGROUND: Patients with parathyroid tumours can develop extreme hypercalcaemia and osteitis fibrosa cystica. Clinical features result from the action of parathyroid hormone (PTH) on bone receptors. Because this hormone is produced in microgram quantities, inhibition of its metabolic effects with potent PTH antibodies should be possible. We tested whether an immunisation with synthetic human and bovine PTH peptides could stimulate autoantibodies against PTH. METHODS: A patient with metastatic parathyroid carcinoma in the lungs and pleura developed severe bone disease and extreme hypercalcaemia that proved resistant to conventional therapy. She was immunised with 200 microg human and bovine PTH peptides and 50 microg human PTH. Booster doses were also given at 4 weeks and 11 weeks. The patient was then seen every week. FINDINGS: Antibodies against PTH were produced within 4 weeks of initial immunisation and titres increased with repeated doses of immunogens. Total serum calcium concentrations, which had ranged from 3.5 mmol/L to 4.2 mmol/L over the previous 18 months, fell to between 2.5 mmol/L and 3.0 mmol/L over 6 months of therapy. This fall was accompanied by striking clinical improvement. INTERPRETATION: We believe this is the first use of immunotherapy to control remote, non-metastatic complications of malignant disease. B-cell tolerance to human PTH was broken by immunisation with PTH peptides in adjuvant. This therapeutic approach could be used to control excess hormone production in several types of endocrine tumour and may have applications in other diseases.

Animals↗
PubMed1996

Parathyroid carcinoma with postoperative prolonged hypocalcemia in a patient with chronic renal failure.

Parathyroid carcinoma is a rare disease that usually presents with severe hypercalcemia and marked elevation of parathyroid hormone level. A 64-year-old male patient with repeated episodes of renal stones sustained chronic renal failure. Subsequently, he developed acute uremic symptoms and underwent a left upper parathyroidectomy. Parathyroid carcinoma was diagnosed after surgery. Asymptomatic hypocalcemia was the initial presentation. Protracted symptomatic hypocalcemia developed 8 months postoperatively, accompanied by an extremely high parathyroid hormone level. Delayed "bone hunger" syndrome concomitant with down-regulation of the parathyroid hormone receptors or production of parathyroid hormone with diminished bioactivity may have been the possible causes.

Humans↗
PubMedDate not supplied

Case report: clinical pathological correlations in a case of primary parathyroid carcinoma.

Carcinoma of parathyroid accounts for one to two percent of patients with primary hyperparathyroidism. A patient admitted to our medical center gave us the opportunity to follow the course of the clinical laboratory findings and the effect of treatment modalities on these laboratory measurements. The clinical course included hypercalcemia, hypophosphatemia, pancreatitis, consumptive coagulopathy, pancytopenia, and sepsis. As vitamin D3 plays and important role in calcium homeostasis, 1,25-(OH)2- vitamin D3 was measured at several points during the clinical course. These finding may serve to help understand some of the underlying control mechanisms involved in the hypercalcemic state.

Adenocarcinoma↗
PubMed2003

Parathyroid carcinoma: is there a role for adjuvant radiation therapy?

BACKGROUND: The authors proposed to determine risk factors associated with postoperative progression of parathyroid carcinoma within the neck (locoregional) and to assess the efficacy of postoperative adjuvant radiation therapy in preventing disease progression within the neck. METHODS: A retrospective review of patients with pathologically confirmed parathyroid carcinoma who underwent surgical resection was performed. Risk factors identified on univariate analysis were applied in a proportional hazards analysis to identify significant independent predictors of locoregional disease progression and cause-specific survival after surgical resection. Fifty-seven patients were treated with surgery alone (no adjuvant radiation therapy [RT]) and were determined to have sufficient follow-up and pathologically confirmed features to be included in the current analysis. Four patients were treated with surgery and adjuvant RT. Four patients received RT to the neck and mediastinum for unresectable locoregional disease progression. Patients were followed for a median of 75.6 months (range, 8.4-358 months). RESULTS: Twenty-five patients (44%) developed locoregional disease progression at a median of 27.1 months after surgery (range, 6.2-138.3 months). The univariate analysis revealed that surgical margin status and the institution at which the initial surgery was performed were predictive of locoregional progression-free survival. The institution at which the initial surgery was performed was found to be an independent predictor of cause-specific survival. Of the four patients treated with surgery and adjuvant RT, all were alive and without disease at the time of last follow-up. All four patients who received RT for locoregional disease progression after initial surgery achieved locoregional disease control. CONCLUSIONS: Patients with parathyroid carcinoma are reported to have a significant risk of locoregional disease progression after surgery alone. The results of the current study demonstrated that the risk of postoperative disease progression can be predicted by surgical margin status and the institution at which the initial surgery is performed. Patients treated with surgery and postoperative RT may have a lower risk of locoregional disease progression and improved cause-specific survival. RT can be used to provide locoregional control of recurrent disease.

Aged↗
PubMed1962

Parathyroid carcinoma in parabiont rats.

A nonfunctioning parathyroid carcinoma with metastases developed in an irradiated rat of a parabiont pair. The differentiation of this tumor from one of thyroid origin is discussed.

Animals↗
PubMed2003

Resection of pulmonary metastasis from parathyroid carcinoma.

The management of metastasis from parathyroid carcinoma (PC) is an unusual challenge. Systemic therapy has minimal effect on the course of the disease and its associated hypercalcemia. Resection of isolated pulmonary metastases is an attractive option in the setting of recurrent hypercalcemia. We report a case of a patient who underwent resection of multiple functional PC pulmonary metastases almost 20 years after the original neck resection. The patient originally presented in 1982 with what was thought to be hyperparathyroidism secondary to a parathyroid adenoma. Surgical exploration revealed the presence of a well differentiated PC. The patient was transiently normocalcemic, but underwent surgical exploration in 1993 and 1996 for recurrent PC in the neck. The patient again improved, but presented in 2001 with diffuse arthralgia, fatigue, malaise, weight loss, and decreased appetite. She was found to have a serum calcium of 12.7 mg/dL and an intact parathyroid hormone of 1542 pmol/L. Computed tomography identified the presence of two right-sided and two left-sided pulmonary masses. Sternotomy with bilateral pulmonary metastectomy was performed. Functional PC metastasis was confirmed on pathological examination. One year following metastectomy the patient is hypocalcemic, requiring oral calcium and vitamin D supplementation. Functional pulmonary metastasis from PC is a rare cause of hypercalcemia. Complete resection of isolated pulmonary metastases can provide effective palliation with long-term survival.

Adult↗
PubMedDate not supplied

Functional parathyroid carcinoma. Cytology, histology, and ultrastructure of a case.

A case of a functional parathyroid carcinoma that recurred 1 year after being resected is presented. The clinical and laboratory data and the histologic structure are presented with confirmatory electron microscopy. The preoperative aspiration biopsy showed findings suggestive of parathyroid carcinoma although simultaneous core biopsy results were reported as parathyroid adenoma. The differential cytologic diagnosis with thyroid neoplasms is discussed.

Adenoma↗
PubMed1999

Telomerase repeat amplification protocol (TRAP): A new molecular marker for parathyroid carcinoma.

Telomerase results to be active in human germ, stem cells, several malignant cell tumors and in immortalized cell lines. In order to investigate if molecular mechanisms other than Rb gene inactivation can be helpful to diagnose malignancy of parathyroid tumors, we decided to investigate the presence of active telomerase in homogenates from different pathological parathyroid tissues (hyperplastic, adenomatous, carcinomatous, and normal) and primary cell cultures. The TRAP assay was performed to detect this activity in histologically characterized normal, hyperplastic, adenomatous, and carcinomatous human parathyroid tissues, primary cell lines, and one metastatic tissue from parathyroid carcinoma. Only malignant parathyroid glands and the metastatic tissue were TRAP positive. Our findings suggest that telomerase expression could represent an important molecular mechanism underlying the acquisition and progression of an aggressive phenotype of epithelial parathyroid cells and it may help to predict their malignant potential. The TRAP assay is easy to perform and it could become an additional tool to be included in the harmamentarium for the molecular diagnosis of parathyroid carcinoma.

Biomarkers, Tumor↗
PubMed2000

Patterns of chromosomal imbalances in parathyroid carcinomas.

In this study we have characterized chromosomal imbalances in a panel of 29 parathyroid carcinomas using comparative genomic hybridization (CGH). The most frequently detected imbalances were losses of 1p and 13q that were seen in >40% of the cases. The commonly occurring regions of loss were assigned to 1p21-p22 (41%), 13q14-q31 (41%), 9p21-pter (28%), 6q22-q24 (24%), and 4q24 (21%), whereas gains preferentially involved 19p (45%), Xc-q13 (28%), 9q33-qter (24%), 1q31-q32 (21%) and 16p (21%). The distribution of CGH alterations supports the idea of a progression of genetic events in the development of parathyroid carcinoma, where gains of Xq and 1q would represent relatively early events that are followed by loss of 13q, 9p, and 1p, and by gain of 19p. A sex-dependent distribution was also evident for two of the common alterations with preferential gain of 1q in female cases and of Xq in male cases. When the CGH profiles for the 29 carcinomas were compared with our previously published results for sporadic parathyroid adenomas, highly significant differences were revealed. Loss of 1p, 4q, and 13q as well as gains of 1q, 9q, 16p, 19p and Xq were significantly more common in the carcinomas than in the adenomas. In contrast, loss of the 11q13 region, which is the most common CGH abnormality in sporadic adenomas, was not detected in any of the carcinomas. Taken together, the findings identify several candidate locations for tumor suppressor genes and oncogenes that are potentially involved in parathyroid carcinogenesis.

Adenoma↗
PubMed1987

Gallium nitrate for treatment of refractory hypercalcemia from parathyroid carcinoma.

Intractable hypercalcemia is the major cause of morbidity and mortality in patients with parathyroid carcinoma. Because gallium nitrate previously was shown to inhibit the bone resorptive activity of parathyroid hormone (PTH) in vitro, we used it to treat two patients with parathyroid carcinoma and resistant hypercalcemia. In both patients, total serum calcium levels were reduced from initial values of 3.62 and 3.77 mmol/L to posttreatment values of 2.32 and 1.45 mmol/L, respectively. Urinary excretion of calcium and hydroxyproline also declined significantly. Serum PTH levels were lower in both patients after therapy, although all levels remained markedly elevated. Nephrogenous cyclic adenosine monophosphate and tubular reabsorption of phosphate remained unchanged. These data indicate that treatment with gallium nitrate can control hypercalcemia in patients with high circulating levels of PTH. Gallium nitrate antagonizes the bone resorptive activity of PTH without altering renal effects of the hormone.

Adult↗
PubMedDate not supplied

[Hyperparathyroidism due to parathyroid carcinoma located in the mediastinum].

Parathyroid gland carcinoma is a rare cause of primary hyperparathyroidism. The authors discuss the case of a 56-year-old man who presented with hypercalcemia and multiple bone lesions suggestive of tumor metastases. Laboratory and radiological investigations revealed primary hyperparathyroidism in a patient with evidence of osteitis fibrosa cystica, sustained by carcinoma of a mediastinal parathyroid gland. Early titration of parathyroid hormone (PTH) levels in all patients with hypercalcemia of unclear cause is important for early diagnosis of cases that are tumor-sustained and prevention of the most severe complications. The role of immunostaining with anti-PTH antibodies in demonstrating parathyroid gland tissue in ectopic and/or non-functioning primary tumors, as well as metastases, is also discussed.

Bone Neoplasms↗
PubMed1982

Therapy of hypercalcemia due to parathyroid carcinoma with intravenous dichloromethylene diphosphonate.

Dichloromethylene diphosphonate (Cl2MDP) a potent inhibitor of osteoclast-mediated bone resorption, lowers serum calcium in hypercalcemia associated wit malignancies and with primary hyperparathyroidism, and reduces excess calcium mobilization from bone in multiple myeloma and in Paget's disease. We have evaluated the effectiveness of intravenously administered Cl2MDP in five patients with parathyroid carcinoma, a disorder characterized by severe hypercalcemia, very high parathyroid hormone (PTH) levels, and marked osteoclast-mediated bone resorption. All patients had biopsy-proved metastatic parathyroid carcinoma and hypercalcemia which persisted after multiple surgical procedures and other attempts at management. During a three-day observation period, each patients continued to demonstrate stable or progressive hypercalcemia despite infusion with saline solution and furosemide. Cl2MDP was administered over 2 hours at 2.5 mg/kg on day 1 and 5 mg/kg on days 2 through 7. Response was noted in all five patients; there was a gradual decline in the average serum calcium from 16.0 +/- 1.1 mg/dl (SEM) to 11.1 +/- 0.9 mg/dl by the eighth day (p less than 0.01). There were concomitant reductions in urinary calcium excretion, from 798 +/- 153 mg/g creatinine to 350 +/- 96 mg/g creatinine (p less than 0.05) and in the urinary hydroxyproline excretion, from 155 +/- 38 mg/g creatinine to 94 +/- 29 mg/g creatinine (p less than 0.02). Serum PTH levels remained markedly elevated (460 +/- 141 micrograms eq/ml to 493 +/- 169 micrograms eq/ml). In three patients, all indices returned to pretreatment levels by 10 days after the last infusion. In two of these patients there was a response to retreatment with Cl2MDP with a fall in calcium from 16.9 +/- 0.5 mg/dl to 12.4 +/- 1.5 mg/dl. There was no response in one patient. No adverse reactions to Cl2MDP were observed. The decrease in serum calcium and concomitant declines in urinary calcium and hydroxyproline suggest that Cl2MDP can effectively inhibit the excessive bone resorption associated with parathyroid carcinoma.

Aged↗