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Recurrent postoperative parathyroid carcinoma: FDG-PET and sestamibi-SPECT findings.

Parathyroid carcinoma is a rare cause for primary hyperparathyroidism. A 65-yr-old man presented with postoperative, recurrent hyperparathyroidism after resection of parathyroid carcinoma. Misleading findings were demonstrated by both double-phase 99mTc-sestamibi scintigraphy and MRI. The location and extent of the parathyroid carcinoma were correctly detected by PET using 18F-fluorodeoxyglucose. FDG-PET provided accurate information before reoperation and proved to be valuable for preoperative surgical planning.

Aged↗

[Parathyroid carcinoma: clinical case and review of the literature].

INTRODUCTION: Parathyroid carcinoma is a rare endocrine neoplasm, difficult to define clinically and histopathologically. CASE REPORT: The case concerns of a 20 years old male with situs viscerum inversus (with dextrocardia), and symptoms: asthenia, oliguresis, nausea, emesis, myalgia, lower limb paresthesia and very high levels of calcium and PTH. Laboratory findings (PTH 580 pg/ml; Ca 12.40 mg/dl; P 1.9 mg/dl), echography, TC, and parathyroid scintigraphy, associated with clinical data, have suggested hypothesis of parathyroid carcinoma confirmed by histological examination and immunochemistry. Surgery was efficacious with normalization of Calcium and PTH levels, and disappearance of symptoms. After two years no signs of local recurrence were present, but imaging show pulmonary micronodulations of uncertain pathological meaning. DISCUSSION AND CONCLUSION: No clinical or bio-humoral data allows a preoperative diagnosis of parathyroid carcinoma. Only with definitive pathology and immunohistochemistry it is possible to differentiate an adenoma from a carcinoma. Surgery is the only effective therapy and therefore should be always performed. This neoplasm usually relapses, locally first and later with distant metastases. For this reason after surgery the patients should always undergo a strict follow-up programme including evaluation of PTH and calcemia.

Adult↗

Metastatic parathyroid carcinoma in the MEN2A syndrome.

We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.

Carcinoma↗

Parathyroid carcinoma.

PURPOSE OF REVIEW: This article reviews current knowledge on the etiology, diagnosis and treatment of parathyroid carcinoma. RECENT FINDINGS: Due to its rarity, research on the molecular etiology and treatment of parathyroid carcinoma has been slow. Mutations of the tumor suppressor gene, HRPT2, and resultant loss of expression of its gene product have been found in the majority of parathyroid cancers studied. Recent advances in the field have identified regions on several chromosomes that demonstrate loss of heterozygosity more commonly in parathyroid carcinoma than in benign parathyroid lesions. This has provided clues to the location and identity of additional tumor suppressor genes associated with the development of this cancer. SUMMARY: Parathyroid carcinoma is an extremely rare cause of primary hyperparathyroidism, accounting for fewer than 1% of cases. The etiology of parathyroid cancer is largely unknown. Associations have been made with several inherited syndromes and with specific genetic lesions. Little is known about the most appropriate management of this disease. En bloc resection at the time of initial surgery appears to provide the best chance of cure. Anecdotal experience with adjuvant chemotherapy has shown a modest and short-lived effect. External beam radiation following surgical resection, however, may increase long-term survival compared with surgery alone. Bisphosphonates and a new class of drugs known as calcimimetics have been used effectively in some patients to control the symptoms of severe hypercalcemia in a palliative setting.

Chemotherapy, Adjuvant↗

Mutational analyses of RB and BRCA2 as candidate tumour suppressor genes in parathyroid carcinoma.

OBJECTIVE: Strong evidence indicates that at least one key tumour suppressor gene important for the development of malignant parathyroid tumours is located on chromosome 13, but the critical target gene remains unknown. Importantly, the region of acquired DNA loss includes two established tumour suppressor genes, the retinoblastoma gene, RB (RB1) and BRCA2. Resolution of whether RB or BRCA2 is the critical 13q tumour suppressor gene in parathyroid cancer requires analysis of these genes' sequences for intragenic inactivating mutations. Therefore, RB and BRCA2 were analysed in a group of parathyroid carcinomas in which mutations of these genes should be most readily detectable. PATIENTS AND DESIGN: Six parathyroid carcinomas from four patients which showed loss of heterozygosity (LOH) at the RB locus and/or 13q loss by comparative genomic hybridazation (CGH) were selected from a CGH/LOH-screened panel of 16 carcinoma specimens from 10 patients. These tumours were examined for mutations by direct sequencing of the complete 27-exon coding region, intron-exon boundaries and promoter of RB. The 26 coding exons and intron-exon boundaries of BRCA2 were also directly sequenced in seven parathyroid carcinomas with loss in the BRCA2 region. RESULTS: No microdeletions, insertions, or point mutations were detected in either RB or BRCA2 in any of the carcinomas. CONCLUSION: The absence of tumour-specific somatic mutations in RB and BRCA2 suggests that they are unlikely to act as classic tumour suppressor genes in the pathogenesis of parathyroid carcinomas. While decreased expression of these genes might contribute to parathyroid carcinomatosis in a secondary fashion and 13q loss warrants further study as a diagnostic marker for parathyroid carcinoma, the putative 13q tumour suppressor awaits identification.

Carcinoma↗

Parathyroid carcinoma--the Princess Margaret Hospital experience.

PURPOSE: Carcinoma of the parathyroid gland is a rare disease representing 0.5 to 4% of patients with primary hyperparathyroidism. We reviewed our experience with this disease, with special emphasis on the role of adjuvant postoperative radiotherapy. METHODS: A retrospective review was conducted of all cases of parathyroid carcinoma referred to the Princess Margaret Hospital (PMH) from 1958-1996. Ten patients were identified. Their clinical features, management details, and treatment outcome are described. RESULTS: There were 5 men and 5 women with a mean age of 53 years. Of these, 7 patients underwent en bloc resection; among them, 4 had neck dissection or lymph node sampling. The other 3 patients underwent only limited surgery to remove the tumor. Seven patients were referred for consideration of adjuvant radiation treatment. Six patients were given adjuvant radiation therapy for microscopic residual disease. All patients tolerated the radiation treatment well, with minimal side effects. The 7 patients have been followed regularly with no evidence of recurrence and normal serum calcium. The mean follow-up for the 6 patients who had adjuvant radiotherapy was 62.3 months (range 12 to 156 months). The remaining 3 patients had metastatic disease and were referred for palliative radiotherapy. CONCLUSIONS: Our results in a small number of patients suggest local radiation therapy to the tumor bed may have eliminated the strong predilection for local recurrence of this disease, as reported by other investigators.

Adolescent↗

Technetium-99m MIBI uptake in recurrent parathyroid carcinoma and brown tumors.

Demonstrable parathyroid adenoma in delayed (3-hr) 99mTc-MIBI neck imaging and localization of 201Tl-chloride in brown tumors mimicking skeletal metastases have been reported. Technetium-99m-MIBI scintigraphy is currently the imaging modality of choice for localizing parathyroid tumors in patients with recurrent hyperparathyroidism. This report is a good example of the use of 99mTc-MIBI in the diagnostic work-up of a patient with recurrent hyperparathyroidism, which turned out to be due to parathyroid carcinoma rather than the initial histopathologic diagnosis of parathyroid adenoma. Additionally, the patient's total body 99mTc-MIBI and 99mTc-MDP bone images showed multiple focal lesions in the bone-mimicking metastases.

Adenoma↗

Recurrent hyperparathyroidism due to parathyroid carcinoma.

The case is described of a woman who died with a functioning parathyroid carcinoma 19 years after removal of two parathyroid tumours, considered at the time to be benign. Following operation hyperparathyroidism subsided, with a short period of hypocalcaemia, and severe osteitis fibrosa cystica healed. Five years before death progressive renal failure developed with normal and later raised serum calcium levels. At necropsy a parathyroid carcinoma infiltrated the thyroid at the site of the previous operation and there was a solitary hepatic metastasis. A remaining parathyroid gland was nodularly hyperplastic and the bones showed evidence of active osteitis fibrosa. The relationship between parathyroid hyperplasia and neoplasia is discussed. Acceptable cases of parathyroid carcinoma are rare, but carcinoma is an important cause of recurrent hyperparathyroidism even months or years after removal of an ;adenoma'.

Adenoma↗

Successful resection of hepatic and pulmonary metastases in a patient with parathyroid carcinoma.

We describe the effect of repeated surgical procedures in a patient with metastatic parathyroid carcinoma over a period of seven years. Initially a subtotal parathyroidectomy was performed for adenomatous hyperplasia. After two years of normocalcemia, hypercalcemia recurred. Two subsequent re-explorations, one of the neck and one of the mediastinum, showed no abnormalities. Histopathologic revision of the primary specimen demonstrated parathyroid carcinoma. Attention was then focused on extra-regional disease, and a hepatic metastasis was detected and successfully resected. Within one year, functional pulmonary metastases occurred. These metastases were treated by four thoracotomies, each providing effective palliation. Eventually the patient died of uncontrollable hypercalcemia seven years after the primary procedure. Even at the time of death there were no signs of recurrent disease in the neck. Parathyroid carcinoma is known to produce local and distant metastases causing severe hypercalcemia. Because medical treatment mostly offers only temporary success and surgery facilitates effective palliation with minimal morbidity, an aggressive surgical approach for functional metastases of parathyroid carcinoma is recommended.

Adult↗

Non-functioning parathyroid carcinoma: a case report.

Non-functioning parathyroid carcinoma is a very rare disease. Only 12 cases have been reported in the literature. The clinical behavior is characterized by the appearance and growth of a neck mass or nodule, which often has been present for many years, and is not accompanied by clinical or laboratory evidence of hypercalcemia or elevated levels of parathyroid hormone (PTH) in peripheral blood. Pathologic findings are similar to those of functioning tumors, and the proof of malignancy is established on the basis of an increased mitotic index only. Data on survival from cases reported in the literature are not conclusive; however, the non-functioning type of parathyroid carcinoma seems to be a more aggressive disease. Radiotherapy seems to be effective in the local control of the disease, but most patients become metastatic. Even if no data are available on response to chemotherapy, the course of the disease is relatively indolent.

Adenoma↗

Fatal recurrence of parathyroid carcinoma after seven years.

The case is reported of a woman who died at the age of 36 from parathyroid carcinoma. The removal, seven years earlier, of a large parathyroid tumour, judged at that time to be benign, was followed by a remission of symptoms for about four years after which they recurred. At necropsy, a well-differentiated parathyroid carcinoma showed local invasion and lymph-node metastases in the neck. Review of the original ;adenoma' suggested that this growth might have been a carcinoma. The total number of recorded cases of hyperfunctioning parathyroid carcinoma is still limited but has now reached at least 37. Carcinoma is rarely to be diagnosed except at necropsy; nevertheless, it seems to be the important cause of delayed recurrence of symptoms after parathyroidectomy. The evolution of the growth is often very slow.

Adenoma↗

Huge parathyroid carcinoma: clinical considerations and literature review.

BACKGROUND: Parathyroid carcinoma is a rare malignancy, with an incidence of 0.5 to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative treatment. CASE PRESENTATION: We report the case of a 66-year-old man referred for a large suspicious substernal goitre associated with severe hypercalcemia due to hyperparathyroidism. After normalization of serum calcium levels, patient underwent surgery. The voluminous cervicomediastinal firm mass could not be removed through the cervical incision; therefore a cervicothoracic approach was employed. Histopathology revealed a giant parathyroid cancer of 450 grams. A review of the literature was also undertaken to summarize the current treatment approaches for this rare malignancy. CONCLUSION: Parathyroid cancer is usually not recognized either preoperatively or intra-operatively. En bloc resection of the tumour with the adjacent tissue is the treatment of choice and it is very important to avoid the rupture of the capsule during operation. Neither tumour size, nor the lymph node status appears to play a role in prognosis. The management of parathyroid carcinoma is a challenge even for experienced surgeons.

Journal Article↗

Parathyroid carcinoma: evaluation and interdisciplinary management.

BACKGROUND: A review of recent reports found a distinct clinical behavior pattern in the rare clinical entity of parathyroid carcinoma, although to the authors' knowledge information on oncogenetic changes, prognostic factors, and the potential benefits of adjuvant therapy remain fragmented and scarce. In this report, a composite review of the literature and The University of Texas M. D. Anderson Cancer Center (M. D. Anderson) experience are presented using the presentation of a patient to illustrate critical issues in the evaluation and interdisciplinary management of patients who are afflicted with this disease. METHODS: The current study reflects a retrospective case review of patients who were diagnosed with parathyroid carcinoma, treated, and followed at M. D. Anderson from 1983 to 2002. To assure standardization of pathologic diagnosis as well as evaluations and interdisciplinary management, the investigators reviewed all cases using predetermined criteria within their specialties. RESULTS: It is interesting to note that M. D. Anderson data showed classic pathologic features that were not always present in all parathyroid carcinomas (at most, some features were noted in 37% of patients). Other results of interest indicated local recurrence rates that appeared lower if adjuvant radiation was applied after initial surgery, independent of the type of surgery or disease stage. In the authors' experience, 70% of patient's tumors exhibited local invasion, although their 5-year survival rate of 85% was consistent with that reported previously, and their 10-year survival rate was somewhat higher at 77%. CONCLUSIONS: Parathyroid carcinoma is a rare clinical entity that requires interdisciplinary evaluation and management. Comprehensive surgical excision of parathyroid carcinomas with verification of normalization of intraoperative parathyroid hormone levels should be sought.

Adult↗

Cutaneous spreading of parathyroid carcinoma after fine needle aspiration cytology.

BACKGROUND: Ultrasound-guided fine needle aspiration cytology (FNAC) of suspect parathyroid adenomas is sometimes used for the diagnosis of primary hyperparathyroidism (PHPT). FNAC complications are rare or mild. We describe the first case in literature of cutaneous spread of parathyroid carcinoma after FNAC. CASE: A woman underwent a neck ultrasound which revealed a solid hypoechogenic nodule of 1.5 cm at the level of the inferior pole of the right thyroid. In the same time a FNAC of the nodule was performed. Cytology showed no atypical cells. Successively PHPT was diagnosed and a few weeks later the patient had a subcutaneous lump in the same area of FNAC. The patient underwent surgery and histology of the specimen showed a differentiated parathyroid carcinoma. The postoperative course was regular and calcium and parathormone resulted normal. CONCLUSION: The use of FNAC should be carefully assessed in the presence of suspect parathyroid carcinoma, because this could cause a possible diffusion of a parathyroid carcinoma along the needle tract.

Adult↗

Parathyroid carcinoma; a cause of recurrent primary hyperparathyroidism a few years after removal of a parathyroid adenoma.

This is a case report of recurrent hyperparathyroidism due to parathyroid carcinoma. Primarily a neck exploration revealed an adenoma of the inferior right parathyroid body but at cervical re-exploration 4 years later due to recurrence a parathyroid carcinoma at the opposite side was found. The importance of recognizing the malignancy at operation is emphasized and the author's opinion for the necessity of localizing studies in cases of reoperations at the neck for over-functioning parathyroid glands is expressed.

Adenoma↗

Fatal acute hyperparathyroidism and parathyroid carcinoma.

A 43-year-old man with parathyroid carcinoma died with hypercalcemia before a definitive diagnosis was made. The condition of patients with hypercalcemia may deteriorate rapidly, and delays in treatment may be fatal. Metastatic growth, not mitotic activity, is the best criterion for the pathologic diagnosis of parathyroid carcinoma.

Acute Disease↗

Parathyroid carcinoma in a chronic hemodialysis patient: case report and review of the literature.

Parathyroid carcinoma is a rare disease in normal population as well as in patients with end-stage renal disease. Approximately 700 cases have been reported and, of these, 20 occurred in patients receiving chronic hemodialysis. We describe a case of parathyroid carcinoma in a 59-year-old female patient with end-stage renal disease secondary to membranous glomerulonephritis treated by hemodialysis since 1995. In September 1998, the calcium level was 12.4 mg/dl and intact parathyroid hormone serum levels were 1366 pg/ml (normal range, 25-65). A routine ultrasonographic examination of the neck revealed enlargement of two parathyroid glands, the left inferior gland being the largest and measuring 2x3x2 cm. In October 1998, resection of two parathyroid glands was performed. On the basis of histology, which documented the presence of proliferating cells arranged in sheets or in a trabecular pattern, numerous mitosis and vascular invasion, a diagnosis of parathyroid carcinoma was made.

Calcium↗

Proposal for the histological classification of parathyroid carcinoma.

Although the criteria of Schantz and Castleman are widely used in the diagnosis of parathyroid carcinoma, many tumors diagnosed as carcinoma subsequently do not recur. In addition, although Bondeson's criteria are used to grade parathyroid carcinoma, instances of patient mortality have been documented even in cases where the histological features did not conform to the criteria for high grade. Considering our experience, we believe that the subclassification of parathyroid carcinomas defining tumors limited local infiltration as low-grade and those with widespread infiltration as high-grade may be useful.

Carcinoma↗