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PubMed2002

Painful ophthalmoplegia from metastatic nonproducing parathyroid carcinoma: case study and review of the literature.

Parathyroid carcinoma is an uncommon malignancy. Of the fewer than 400 cases reported, most have been cases of producing parathyroid carcinoma with accompanying hypercalcemia. Only 13 patients with nonproducing parathyroid carcinoma have been described. Nine of these 13 patients had metastatic disease. We report a patient with i.c. metastasis. Distal metastases of producing parathyroid carcinoma are treated surgically to prolong survival and prevent complications of hyperparathyroidism and hypercalcemia. One half of the patients with producing parathyroid carcinoma die within 5 years, mostly because of the complications of hypercalcemia. Nonproducing parathyroid carcinoma compares unfavorably with producing parathyroid carcinoma in terms of tumor progression and prognosis. Few data on choice of therapy in nonproducing parathyroid carcinoma are available. We treated our patient with a combination of radiotherapy and chemotherapy. Treatment was followed by an unexpectedly prolonged survival of 31 months after diagnosis of metastatic disease.

Brain Neoplasms↗
PubMed2006

Clinical suspicion and parathyroid carcinoma management.

CONTEXT AND OBJECTIVE: Adequate management of parathyroid carcinoma apparently relates to the surgeons ability to identify it at the first operation. The objective of this paper was to evaluate the role of clinical suspicion in the management of parathyroid carcinoma. DESIGN AND SETTING: Retrospective analysis of parathyroid carcinoma patients treated in Department of Head and Neck Surgery, Faculdade de Medicina da Universidade de São Paulo. METHODS: Cross-sectional study of 143 patients who underwent surgery from 1995 to 2000, due to hyperparathyroidism. These cases were reviewed to ascertain whether preoperative and intraoperative suspicion of parathyroid carcinoma were helpful during the operation, and which factors demonstrated the suspicion of cancer best. RESULTS: Among 66 patients with primary hyperparathyroidism there were four cases of parathyroid carcinoma (6.1%), and one case was found in secondary hyperparathyroidism (1.3%). Palpable nodules were found in five patients with primary hyperparathyroidism, four of them with parathyroid carcinoma. Preoperative levels of calcium in primary hyperparathyroidism with cancer patients varied from 12.0 mg/dl to 18.2 mg/dl. Two patients had gross macroscopic spread of the tumor to adjacent structures. Except for one patient, with extensive disease, tumors were resected en bloc. In secondary hyperparathyroidism, parathyroid carcinoma was found in a fifth mediastinal gland. One atypical adenoma was observed. CONCLUSIONS: High levels of calcium, palpable tumors and adherence to close structures are more common in parathyroid carcinoma. These clinical signs may be helpful for decision-making during parathyroid surgery.

Adenoma↗
PubMed1999

Parathyroid carcinoma in a child.

Parathyroid carcinoma is a rare cause of hypercalcemia in children but should be considered in a child presenting with an extremely elevated serum calcium level. The authors report the fifth case of parathyroid carcinoma in a child less than 16 years of age.

Adolescent↗
PubMed2001

Parathyroid carcinoma: diagnosis and management.

Parathyroid carcinoma is a rare and difficult diagnosis to make based on the histological features alone. We review five cases of parathyroid carcinoma in the past 30 years and the clinical and biochemical features that facilitate the making of the diagnosis. A favourable outcome can be expected with adequate surgical treatment.

Adult↗
PubMed1994

Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma.

BACKGROUND: The origin and molecular pathogenesis of parathyroid carcinoma are unknown. This life-threatening cause of primary hyperparathyroidism cannot be reliably distinguished from its benign counterpart on the basis of histopathological features alone. Because the PRAD1, or cyclin D1, gene, a cell-cycle regulator, has been implicated in a subgroup of benign parathyroid tumors, we examined the possibility that another cell-cycle regulator with possible functional links to PRAD1, the retinoblastoma tumor-suppressor gene (RB), might be involved in the molecular pathogenesis of parathyroid carcinoma. METHODS: Parathyroid carcinomas from 9 patients and adenomas from 21 were studied for evidence of tumor-specific loss of RB gene DNA (allelic loss) by analysis of four DNA polymorphisms and for evidence of altered expression oF RB protein by immunohistochemical staining. RESULTS: All of 11 specimens from 5 patients with parathyroid carcinoma and informative DNA patterns and 1 of 19 specimens from 19 patients with parathyroid adenoma and informative DNA patterns lacked an RB allele. Fourteen of 16 specimens (88 percent) from the nine patients with carcinoma had abnormal expression of RB protein (a complete or predominant absence of nuclear staining for the protein). None of the 19 adenomas, including the tumor with loss of an RB allele, had unequivocally abnormal staining for RB protein. CONCLUSIONS: Inactivation of the RB gene is common in parathyroid carcinoma and is likely to be an important contributor to its molecular pathogenesis. The presence of such inactivation may help to distinguish benign from malignant parathyroid disease and may have useful diagnostic, prognostic, and therapeutic implications.

Adenoma↗
PubMedDate not supplied

Parathyroid carcinoma: clinical presentation and treatment.

Parathyroid tumors account for only a small percentage of all head and neck neoplasms. The overwhelming majority of these are parathyroid adenomas that result in primary hyperparathyroidism. From 0.5% to 4% of hyperparathyroid patients, however, will be found to have a parathyroid carcinoma. In this paper, the authors relate their recent experience with such a patient and with two other such cases. Parathyroid carcinoma patients usually present with striking hyperparathyroidism and hypercalcemia, with the resultant related symptoms being more severe than those associated with parathyroid adenomas. Parathyroid carcinomas also tend to be large and may be detectable by current imaging techniques. The surgical appearance of these lesions is also distinct; the tumors are frequently multilobulated, gray-tan in color, quite firm, and often invasive. These physical findings are important since frozen section diagnosis may be difficult. The final histologic diagnosis depends on the presence of mitotic figures and capsular and vascular invasions. Preoperative medical problems, surgical approach, and prognostic factors are also discussed.

Aged↗
PubMed2001

Parathyroid carcinoma. A concise review.

Parathyroid carcinoma is a very rare malignancy and the least common among endocrine malignat tumors. Its etiology is still unclear and some hypotheses have been suggested: previous external radiation to the neck, pregression from benign to malignant lesion, familial hyperparathyroidism. An early accurate diagnosis is very important since surgery is the most effective therapeutic approach to parathyroid carcinoma. Prognosis is quite variable and stress is laid on the early diagnosis and radical surgery which seem to be most favorable prognostic factors. An accurate follow-up should include frequent measurements of serum calcium and PTH levels to promptly detect recurrence or metastases which are usually associated with severe hyeprcalcemia.

Carcinoma↗
PubMedDate not supplied

Parathyroid carcinoma. Report of a case.

Parathyroid carcinoma is a rare cause of hyperparathyroidism. Its prognosis is mainly related to an en-bloc resection of the tumor and of the involved structures. However because of the small number of cases reported in the international literature, biological behaviour of the disease is not well known. In this report we describe one case of parathyroid carcinoma seen in our Institution. Preoperative presumption of parathyroid carcinoma thanks to clinical features and ultrasound imaging helped us in deciding an adequate surgical resection.

Humans↗
PubMed1988

[A case of parathyroid carcinoma].

A case of parathyroid carcinoma in a 49-year-old female is described. She is found to have renal stones and high serum calcium levels. On physical examination a fixed walnut-sized mass was detected on her right neck. Laboratory studies disclosed a serum calcium level of 12.7 mg/dl, serum phosphorus level of 2.5 mg/dl, serum Ca++ level of 3.12 mEq/l, and positive Gold-Smith test. Computer-assisted tomography scan and ultrasonogram showed a mass in the posterior region of the right lobe of her thyroid. The tumor was resected and histopathological examination showed parathyroid carcinoma. The patient had no evidence of recurrence 2 years following surgery. Our report is the 70th case among Japanese literature.

Calcium↗
PubMed2003

Metachronous spread of parathyroid carcinoma to a retropharyngeal lymph node.

BACKGROUND: Parathyroid carcinoma is rare and accounts for approximately 1% of patients with hyperparathyroidism. It is a slowly progressive disease with frequent recurrence and high incidence of local metastasis. Because of the rarity of this tumor, little is known about the pattern of lymph node metastasis. METHODS: A case of retropharyngeal lymph node metastasis found 2 years after initial diagnosis of parathyroid carcinoma is presented and discussed. RESULTS: A 67-year-old man initially was seen with asymptomatic hypercalcemia, and a 1.7-cm mass was removed along with the left hemithyroid. The mass was found to be parathyroid carcinoma. Serum calcium was again elevated 1 year later, and left neck lymph node dissection revealed an upper jugular lymph node containing parathyroid carcinoma. The patient continued to have an elevated serum calcium level, and a retropharyngeal lymph node was found by MRI and removed the following year. The patient is now without evidence of hyperparathyroidism or recurrent disease at 2-year follow-up. CONCLUSIONS: Persistent parathyroid carcinoma is often a clinical challenge because of the difficulty in localizing recurrent tumor. Retropharyngeal lymph nodes should be considered as a possible site of metastasis in patients with parathyroid carcinoma.

Aged↗
PubMed1993

Documentation of parathyroid carcinoma fifteen years after resection of a parathyroid 'adenoma'.

This report describes a 40-year-old man in whom the diagnosis of parathyroid carcinoma was made almost 15 years after resection of the primary lesion. The case emphasizes the importance of recognizing pre and intraoperative factors that differentiate between parathyroid adenoma and carcinoma and illustrates that surgical palliation is feasible in selected patients with parathyroid carcinoma.

Adenoma↗
PubMed1990

Successful surgical treatment of parathyroid carcinoma in two haemodialysis patients.

Parathyroid carcinoma is rare, occurring in less than 2-3% of the patients with clinical features of primary hyperparathyroidism. In haemodialysis patients parathyroid carcinoma has only once been described, although secondary hyperparathyroidism in these patients is common. We discuss two female haemodialysis patients with parathyroid carcinoma. Both were treated surgically: in one patient only local excision of the malignancy was performed; the other patient underwent a modified neck dissection on the side of the tumour as well. Physical, biochemical and radiological evaluation for 4-7 years after operation gave no evidence of recurrence of the malignancy.

Adenoma↗
PubMed1988

Deoxyribonucleic acid cytometry helps identify parathyroid carcinomas.

It may be difficult in some patients with parathyroid tumors to distinguish between parathyroid carcinoma and parathyroid adenoma on the basis of clinical and histopathological findings. Patients initially diagnosed as having a parathyroid adenoma have subsequently occasionally developed metastases, and thereby their tumor was proven to be a carcinoma. To determine whether the nuclear DNA content would correlate with the clinical course and pathology of parathyroid tumors DNA cytometry was performed on parathyroid carcinomas (9 patients), histologically atypical adenomas (10 patients), adenomas associated with severe hypercalcemia [serum calcium, greater than or equal to 13.0 mg/dL (greater than or equal to 3.24 mmol/L); 11 patients], typical benign adenomas (11 patients), and incidentally removed normal parathyroid glands (6 patients). Sections were cut from the original paraffin-embedded surgical specimens and stained for nuclear DNA using the azure A Feulgen reaction. Nuclear DNA stain content was measured using an integrating image cytometer, and the results were plotted as histograms. Adjusted optical density (AOD) values were measured (in arbitrary units) to estimate the DNA content of whole nuclei in the specimens. The mean nuclear DNA content in the parathyroid carcinomas [24.6 +/- 2.1 (+/- SE) AOD] was significantly greater than that in the three groups of parathyroid adenomas (P less than 0.005, by unpaired t test) and in the normal parathyroid glands (P less than 0.0005). The mean nuclear DNA content in the atypical adenomas (15.8 +/- 1.6 AOD), profoundly hypercalcemic adenomas (16.8 +/- 1.3 AOD), and typical adenomas (16.0 +/- 1.1. AOD) were similar, and all were significantly greater than that in the normal parathyroid glands (11.5 +/- 0.7 AOD, P less than 0.05). Five distinct DNA histogram patterns were present in the parathyroid specimens from these 47 patients. Four of the 9 parathyroid carcinomas had an aneuploid DNA pattern, an abnormal pattern not found in any of the other groups; 2 of these tumors were originally diagnosed as atypical parathyroid adenomas. Both patients developed recurrent disease, and 1 died from a hepatic metastasis. Therefore, DNA cytometry provides valuable information in differentiating some parathyroid carcinomas from adenomas and diagnosing certain parathyroid carcinomas before the appearance of grossly invasive or metastatic tumor.

Adenoma↗
PubMed2006

[Prophylactic parathyroidectomy for familial parathyroid carcinoma].

In contrast to primary hyperparathyroidism, parathyroid carcinoma is a rare disease. In patients with hyperparathyroidism jaw tumor (HPT-JT) syndrome, caused by germline mutations in HRPT2, the development of parathyroid carcinoma is estimated to be 10-15%. This review summarizes the clinical and molecular genetic data of about 100 patients in the literature and three of our own cases. Unfortunately, osteofibromas, which might enable timely diagnosis of HPT-JT syndrome, occur in only about 30% of patients; about 80% have uniglandular disease. Based on the current data, a general recommendation to perform prophylactic parathyroidectomy cannot be given. However, thorough screening of patients at risk is mandatory. Of note in patients thought to have sporadic parathyroid carcinoma, germline HRPT2 mutations are found in up to 20%. Hence, any patient with parathyroid carcinoma should undergo HRPT2 mutation analysis.

DNA Mutational Analysis↗
PubMed1985

Parathyroid carcinoma. A report of five cases.

Parathyroid carcinoma, although rare, represents 0.5-4.0 per cent of the cases of hyperparathyroidism. The authors have encountered five cases of parathyroid carcinoma in their experience treating 445 patients with primary hyperparathyroidism (1.1%) since 1965. All five patients were women, ranging in age fro 29 to 60 years, and had marked hypercalcemia at the time of presentation, with values up to 26 mg/dl in one case. All the tumors were locally adherent to surrounding structures at the time of parathyroidectomy. Pathologically they were characteristic with a dense sclerotic reaction and fibrous bands criss-crossing islands of parathyroid cells. Three patients with local as well as distant metastases have died as a result of recurrent parathyroid carcinoma (follow-up: 2, 3, and 6 years). The remaining two patients became normocalcemic following resection, and have been asymptomatic for 1 and 7 years, respectively. The overall survival and clinical course, in our limited experience with five parathyroid carcinoma cases demonstrates that the morbidity and mortality in these patients is mainly due to local recurrence with the resultant metabolic disturbances, as has been previously noted in the literature.

Adult↗
PubMedDate not supplied

Functioning parathyroid carcinoma: clinicopathologic features and rational treatment.

Parathyroid carcinoma is a rare, reported to be less than 1% of patients with primary hyperparathyroidism. Recently, cell cycle regulators such as the retinoblastoma gene and p53 have been implicated in the pathogenesis of parathyroid carcinoma. Yet definite diagnosis remains difficult not only clinically but also pathologically. However, the clinical presentation, biochemical and hormonal findings, and appearance at the operation may possibly raise suspicion regarding the diagnosis. A radical en bloc resection at the primary operation is most important. Even after a successful initial operation parathyroid carcinoma carries an increased risk of recurrence. There is wide diversity in the interval between the initial operation and the manifestation of metastasis. Histopathology and DNA ploidy are valuable predictors of the clinical outcome. Because the severe hypercalcemia it engenders has catastrophic consequences, proper management of the recurrent hypercalcemia is also mandatory. The lung is the most common site of distant metastasis. Selected patients with pulmonary metastasis of parathyroid carcinoma can obtain significant benefit from aggressive surgical resection even when they have multiple or recurrent lesions. When hypercalcemia is refractory to surgical resection, medical treatment with bisphosphonate has a beneficial effect.

Carcinoma↗
PubMed1998

Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent.

Parathyroid carcinoma is one cause of primary hyperparathyroidism, a condition in which there is hypercalcemia and dysregulated hypersecretion of PTH. In normal, and in some neoplastic parathyroid cells, PTH secretion is mediated by the cell surface calcium-sensing receptor. We describe the first therapeutic use of a novel molecule, a calcimimetic, that has agonist action at the calcium-sensing receptor. A 78-yr-old man with parathyroid carcinoma was admitted with hypercalcemia, markedly elevated PTH, and a change in mental status. He was treated for 17 days with conventional therapy, which included saline hydration, furosemide, pamidronate, and calcitonin. This was ineffective, and on hospital day 18, calcimimetic at a dose of 50 mg, orally, every 6 h was added. On hospital day 25, the dose was increased to 100 mg, orally, every 6 h, and on hospital day 30, saline and furosemide were discontinued. He was discharged on hospital day 40. With several dose adjustments, he has been treated with monotherapy calcimimetic for over 600 days and has not required any other interventions for his parathyroid carcinoma. Mean daily precalcimimetic treatment values of serum ionized calcium and PTH were 1.83 mmol/L and 872 pg/mL, respectively. During hospitalization, at the lower dose of calcimimetic, calcium and PTH decreased to 1.67 mmol/L and 538 pg/mL; with the higher dose they further decreased to 1.51 mmol/L and 444 pg/mL. Since discharge, and despite increasing levels of PTH, serum calcium has remained high, but lower than the admission level and acutely responsive to changes in calcimimetic doses. This compound, a calcimimetic, the first of a new class of compounds with activity at the calcium-sensing receptor, has been used to treat a patient with parathyroid carcinoma. During 2 yr of treatment, no adverse clinical effects have been observed, and it appears to have been effective at controlling hypercalcemia.

Acute Disease↗