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PubMed2002

Oxyphil parathyroid carcinomas: a clinicopathologic and immunohistochemical study of 10 cases.

Oxyphil parathyroid carcinomas are uncommon neoplasms, and the clinicopathologic features of these tumors are largely unknown. We evaluated the clinicopathologic features of oxyphil parathyroid carcinomas and the expression of cytokeratin 14 (CK14), the high-affinity glucose transporter-4 (Glut-4), as well as the cell cycle proteins p27 and Ki67 and compared these with oxyphil parathyroid adenomas and chief cell parathyroid adenomas and carcinomas. Formalin-fixed, paraffin-embedded archival tissues from primary (n = 6) and recurrent (n = 4) oxyphil carcinomas were analyzed and compared with chief cell parathyroid carcinomas (n = 12), oxyphil parathyroid adenomas (n = 38), and chief cell parathyroid adenomas (n = 17) by immunohistochemistry for CK14, Glut-4, p27, and Ki67 using the avidin-biotin peroxidase system. Patients with primary oxyphil and chief cell carcinoma presented with high levels of serum calcium (n = 15.5 and 13.7 mg/dL, respectively). Approximately half the patients in each group died of disease. The Ki67 labeling index was higher (4.9 vs 1.9) and the p27 index lower (23 vs 66) in primary oxyphil carcinoma compared with primary oxyphil adenomas. CK14 was expressed in most oxyphil adenomas (35 of 38 cases) but not in oxyphil carcinomas (0 of 10 cases). Glut-4 was more commonly expressed in both groups of adenomas compared with carcinomas. These results show that oxyphil parathyroid carcinomas are functional malignancies similar to chief cell carcinomas and are associated with hypercalcemia, recurrence, and death. Expression of CK14 is very different in oxyphil adenomas compared with carcinomas. Although distinction between parathyroid adenomas and carcinomas can only be made by histopathologic and clinical findings, these results suggest that immunostaining for CK14, p27, and Ki67 may provide additional information to help distinguish between difficult cases of parathyroid adenomas and carcinomas. These findings also indicate that the same histopathologic features should be used to diagnose oxyphil and chief cell parathyroid carcinomas.

Adenoma↗
PubMed1981

Surgical resection of metastatic parathyroid carcinoma.

The incidence of parathyroid carcinoma is no more than 0.5 to 3% of parathyroid neoplasms and can often be cured by an adequate initial surgical excision. If the carcinoma has already spread outside the capsule or is implanted at surgery, the chance of local recurrence is high, but is best managed by surgical resection of any recurrence. Distant metastases occur less frequently, but the associated hypercalcemia is poorly controlled by hormonal, chemotherapy, or radiation therapy. Though the chance for cure is small, a review of previously reported cases and our own experience leads us to encourage an aggressive search for metastases, and if possible, surgical resection. If not curative, this approach will often allow prolonged palliation of the effect of hypercalcemia.

Adenocarcinoma↗
PubMed1996

Recurrent secondary hyperparathyroidism due to parathyroid carcinoma: usefulness of Ki-67 immunostaining in the diagnosis of a malignant parathyroid tumor.

Parathyroid carcinoma is a very rare disease occurring in less than 2-3% of all the cases showing clinical features of primary hyperparathyroidism. Several histological markers have been used for distinguishing between benign and malignant tumors of the parathyroid glands. However, most of these markers are not easily applicable and clinical prognosis cannot be predicted by histopathological criteria alone. A recent study has drawn attention to the role of the cell cycle associated antigen Ki-67 detected by MIB-1 monoclonal immunocytochemistry in parathyroid tumors: in fact, Ki-67 seems to be a valuable marker of malignancy in such tumors since it permits an easy detection of proliferating and dividing cells. Here we report in detail a case of severe recurrent hyperparathyroidism in a 51-year-old female patient undergoing regular hemodialysis treatment. In the surgical specimens of the parathyroid glands, the tumor proliferative fraction of 56, expressed as the number of Ki-67-positive nuclei per thousand cells, and the mean mitosis count of 0.5, expressed as the percentage of the total amount of Ki-67 positive nuclei, support the diagnosis of parathyroid carcinoma despite the scanty amount of microscopical signs considered characteristic of malignancy, i.e. extensive thick fibrous bands or prominent nucleoli. To our knowledge this paper is the first clinical report that supports the diagnostic role of the cell cycle associated antigen Ki-67 in parathyroid carcinoma in a case of secondary hyperparathyroidism in a patient undergoing hemodialysis.

Female↗
PubMed2000

Parathyroid carcinoma in a dialysis patient.

A 75-year-old woman who had been receiving dialysis for 3 years and had a long history of chronic renal failure attributable to reflux nephropathy was investigated for progressive hypercalcemia in the context of very high intact parathormone (iPTH) levels. Imaging showed two functional parathyroid glands in the neck. At parathyroidectomy, four variously enlarged parathyroid glands were found and completely resected, without autotransplantation. The histology of one of the glands showed invasive parathyroid carcinoma. Parathyroid carcinoma is a very rare condition, with only 16 previous cases involving dialysis patients described in the literature. We review the literature to draw together presentational and therapeutic information on the management of this problem in the setting of renal replacement therapy.

Aged↗
PubMed1987

[Hyperfunctioning parathyroid carcinoma].

Two cases of parathyroid carcinoma with hyperparathyroidism, a relatively rare endocrine tumor are reported. It accounts for approximately 1-4% of all cases of primary hyperparathyroidism. Parathyroid crisis occurred for three times in one case. It is difficult to make an early diagnosis, frequently leading to misdiagnosis and wrong treatment. During operation iatrogenic implant or incomplete resection may occur, resulting in recurrence and repeated operations. It is important to differentiate from hypercalcemia caused by parathyroid adenoma. Neck mass, hypercalcemia usually above 14 mg%, severe decalcification and pathological fractures are characteristic. Fibrosis and inflammatory reaction of the tumor and metastases in the neck lymph nodes are commonly seen at operation. Histologically active tumor cell mitosis, capsular and vascular invasions usually exist. Local recurrences often occur after surgical treatment. If the surgeon can recognized the malignant change and give a curative resection in the initial operation, more gratifying results can be obtained.

Adult↗
PubMed1982

Parathyroid carcinoma: a clinical study of seven cases of functioning and two cases of nonfunctioning parathyroid cancer.

Seven cases of functioning and two cases of nonfunctioning parathyroid carcinoma are presented together with a general discussion of this disease. Functioning parathyroid carcinoma may be associated with prolonged survival. The morbidity and mortality from this disease are generally related to the prolonged hypercalcemia that occurs. The hypercalcemia is best treated with excision of local recurrences; however, this surgery is most often palliative and seldom curative. The best operative results were obtained when the disease could be localized preoperatively. Neck and mediastinal exploration in the absence of physical or radiographic evidence of recurrence failed to affect serum calcium levels. Two patients with nonfunctioning parathyroid cancer did poorly compared with those with functioning parathyroid carcinoma. The few cases reported in the literature are also suggestive of a more aggressive disease. The failure of this tumor to produce parathyroid hormone may allow it to escape clinical attention until it has achieved an advanced state.

Adenoma↗
PubMedDate not supplied

Thymic parathyroid carcinoma and postoperative hungry bone syndrome.

OBJECTIVE: To describe a case of parathyroid carcinoma localized to ectopic parathyroid tissue within the thymus and the development of hungry bone syndrome postoperatively. METHODS: We present pertinent clinical, radiologic, pathologic, and laboratory details of the study patient and discuss the relevant literature. RESULTS: A 33-year-old man who presented with only symptoms of fatigue and depression was found to have high serum calcium, parathyroid hormone, and alkaline phosphatase levels. A sestamibi scan revealed evidence of activity adjacent to the sternum. He underwent neck exploration after selective staining of the parathyroid glands with methylene blue dye. A mass was found in the thymic bed, and the pathologic features were consistent with parathyroid carcinoma. Postoperatively, symptoms and signs of hypocalcemia developed despite normal serum calcium levels. CONCLUSION: Physicians should be aware that (1) parathyroid carcinoma may originate wherever ectopic parathyroid tissue is found and patients may have only nonspecific symptoms, (2) wide local excision is imperative if carcinoma is suspected, and (3) symptoms and signs of hypocalcemia may be evident even when the serum calcium concentration is normal, if it has rapidly declined from a high level.

Adult↗
PubMed2003

Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma.

BACKGROUND: We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, in sporadic parathyroid carcinoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism--hyperparathyroidism-jaw tumor (HPT-JT) syndrome--that carries an increased risk of parathyroid cancer. METHODS: We directly sequenced the full coding and flanking splice-junctional regions of the HRPT2 gene in 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also sought to confirm the somatic nature of the identified mutations and tested the carcinomas for tumor-specific loss of heterozygosity at HRPT2. RESULTS: Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of which were predicted to inactivate the encoded parafibromin protein. Two distinct HRPT2 mutations were found in tumors from five patients, and biallelic inactivation as a result of a mutation and loss of heterozygosity was found in one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of three patients were identified as germ-line mutations. CONCLUSIONS: Sporadic parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of pathogenetic importance. Certain patients with apparently sporadic parathyroid carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or a phenotypic variant.

Adult↗
PubMedDate not supplied

Parathyroid carcinoma: 50-year experience at The Cleveland Clinic Foundation.

BACKGROUND: Parathyroid carcinoma is rare, with a reported prevalence of 0.6% to 4.0% in patients presumed to have primary hyperparathyroidism. This study examines the long-term results of surgical therapy and combination chemotherapy. PATIENTS: From 1938 to 1988, 1260 operations for primary hyperparathyroidism were performed; only six patients (0.47%) were subsequently found to have parathyroid carcinoma. A seventh patient was referred to our institution after the diagnosis of parathyroid carcinoma had been made. RESULTS: All patients had excessive hypercalcemia (serum calcium concentration > 12.0 mg/dL) with a range of 12.3 to 18.3 mg/dL. Locally recurrent tumors causing recurrent hypercalcemia were managed by repeated neck exploration and tumor resection. Six of the seven patients (85%) survived 5 years, while four patients (57%) survived 10 years. CONCLUSIONS: Diagnosis of parathyroid carcinoma rests upon postoperative surveillance of patients who have undergone previous neck exploration and resection of apparently benign adenomas. Long-term survival is possible with repeated resection of locally recurrent tumors.

Adult↗
PubMed2005

Results of iterative surgery for persistent and recurrent parathyroid carcinoma.

BACKGROUND AND AIMS: Parathyroid carcinoma (PC) is a rare cause of primary hyperparathyroidism. Surgery is the only effective treatment; re-operations are often required, because recurrences occur in most of the cases. The aim of this retrospective study was to analyse the rate of biochemical cure, clinical relief, sensitivity of localizing studies and morbidity after re-operations. PATIENTS AND METHODS: From January 1980 to December 2000, 19 patients underwent surgery for PC. PC persisted or recurred in all cases. Fourteen re-operations were performed in six patients. RESULTS: Twelve re-operations at loco-regional site and two pulmonary metastasectomies were performed. Iterative surgery achieved a symptomatic relief in 86% of cases and a transient biochemical remission only in one patient, but significantly reduced parathormone and calcemia. The sensitivity of scintigraphy, CT and ultrasonography was 86, 79 and 100%, respectively. CONCLUSION: When recurrences occur, complete cure of PC is unlikely, despite re-operations. Iterative surgery is associated with some morbidity and never achieves a definitive cure, but provides significant clinical and biochemical palliation. Localizing studies are mandatory but do not detect all recurrences.

Adult↗
PubMed1987

[Parathyroid carcinoma: report of a case].

A case of parathyroid carcinoma is presented. A 46-year-old female was admitted to our hospital for fractures of both femurs on July 29, 1983. Laboratory data revealed a serum calcium level of 15.2 mg/dl, serum phosphate level of 1.2 mg/dl, serum immunoreactive parathyroid hormone 9.35 ng/ml (less than 0.5), and % tubular reabsorption of phosphate of 57%. X-ray examination showed marked osteitis fibrosa cystica. The diagnosis of primary hyperparathyroidism was made. A hard tumor was palpable on the left anterior side of her neck. Neck exploration was carried out on August 10. The tumor was found to be localized in contact with the left lower lobe of the thyroid gland. Parathyroid carcinoma was strongly suspected, because the tumor severely adhered to surrounding tissues, thus the tumor was resected en bloc. The histopathological diagnosis was typical parathyroid carcinoma. Postoperative course and the treatment of the fractures were uneventful, and she was discharged able to walk five months after the operation. No evidence of recurrence or metastasis has been seen during the eighteen months since the operation. This is the 80th case in the Japanese literature to our knowledge and the clinical features of these 80 cases revealed an average age of 41.5 years old; male/female ratio of 32/48; average weight of tumor of 8.65 g, palpable neck mass in 72%, bone disease in 64%, and renal disease in 34%.

Carcinoma↗
PubMed1976

Magnesium depletion and hypocalcaemia after removal of parathyroid carcinoma.

A case of parathyroid carcinoma is described which presented with severe bone disease, complicated after parathyroidectomy by symptomatic hypocalcaemia and magnesium deficiency, both of which responded dramatically to the administration of magnesium. Urinary cyclic AMP assays were used to monitor parathyroid activity.

Adult↗
PubMed1990

Parathyroid carcinoma with steroid-suppressible plasma immunoreactive parathyroid hormone and human chorionic gonadotrophin.

A 31-year old male presented with bone pain, polyuria and a palpable nodule in the neck. Radiological examination showed generalised osteopenia, subperiosteal erosion and presence of bilateral renal stones. The essential chemical pathological changes were increased plasma calcium, mid-molecule immuno-reactive parathyroid hormone (iPTH), human chorionic gonadotrophin (hCG) levels. Surgical excision of the nodule revealed a parathyroid carcinoma. The uniqueness of this case is the steroid-suppressible plasma calcium, iPTH, and hCG levels. The diagnostic implications of the findings are discussed.

Adult↗
PubMed1990

Two cases of parathyroid carcinoma in patients on long-term hemodialysis.

Two cases of parathyroid carcinoma, in a 46-year-old male on maintenance hemodialysis for 135 months and a 55-year-old female on maintenance hemodialysis for 64 months were reported. In both cases, the parathyroid carcinoma showed local invasion and the other glands were hyperplasia and/or adenoma, which would support the concept of malignant transformation occurring in parathyroid hyperplasia. The concurrence of parathyroid carcinoma with hyperplasia and/or adenoma is a pertinent feature in patients on maintenance dialysis, although it is rare in primary parathyroid carcinoma.

Female↗
PubMed2006

Parathyroid carcinoma: A rare case with mandibular brown tumor.

Parathyroid carcinoma constitutes less than 1 % of primary hyperparathyroidism. The male to female ratio is approximately equal and the mean age at presentation is 40 years. In about half of the patients there is a palpable cervical mass, and serum calcium level is usually above 14 mg/dl. In a case report we present a 21-year-old man with a non-tender, non-mobile bulging mandibular mass. He suffered from fatigue, recent weight loss, hoarseness, polydipsia, polyuria, hematuria, recurrent renal stones and bouts of constipation and diarrhea. A mandibular biopsy confirmed brown tumor. Serum calcium level was 15.4 mg/dl. Cervical ultrasound revealed a hypoecho area suspicious of parathyroid adenoma. Parathyroid carcinoma was later confirmed and en bloc resection was performed. During a two-year follow up there has been no evidence of recurrence or hypercalcemia. This unique case of parathyroid carcinoma in conjunction with brown tumor is the second reported case worldwide.

Adenoma↗
PubMedDate not supplied

Parathyroid carcinoma: difficult management options.

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism and these tumours are usually hyperfunctional as opposed to other malignant endocrine tumors. Surgery is the only effective treatment while nonsurgical modalities yield poor results. We report a patient, who presented with palpable mass in the neck and severe hypercalcemia. He underwent debulking surgery and received allendronate, calcitonin, dacarbazine followed by in- situ alcohol instillation with some success.

Adult↗
PubMed1984

Parathyroid carcinoma--problems in diagnosis and treatment.

Four patients with parathyroid carcinoma operated on at the Karolinska Hospital were reviewed. In three patients the parathyroid carcinoma was suspected at the primary operation and successfully treated with excision of the tumour and ipsilateral hemithyroidectomy. In one patient the diagnosis was made only after local recurrence of the tumour and the appearance of lung metastasis. Although removal of local recurrence and distant metastasis was not curative, the patient improved for a long period of time. When surgical resection did not successfully control the hypercalcemia, Mithramycin, 12.5 micrograms/kg intravenous daily was given for five days. With two days interruption the treatment was repeated. The hypercalcemia could in this manner be controlled for almost one and a half years. It is concluded that parathyroid carcinoma is a relatively rare endocrine tumour which may be cured by adequate initial operation. When surgery is not feasible to control hypercalcemia, Mithramycin seems to be the drug of choice even for long-term therapy.

Adult↗