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PubMed2005

Allelic loss in parathyroid neoplasia can help characterize malignancy.

Parathyroid carcinoma can be difficult to diagnose, and the final pathologic diagnosis relies on clinicopathologic correlation. Clinical features of malignancy include high preoperative calcium levels and an intraoperative impression that the gland is adherent to local structures. Histologic features of malignancy include increased mitoses, vascular invasion, and broad bands of fibrosis. This study used molecular genotyping to assess parathyroid neoplasia for loss of heterozygosity across a panel of known tumor suppressor genes that have been previously identified as being important in the pathogenesis of parathyroid diseases. Parathyroid adenomas, hyperplasia, and carcinomas were included in the study, and a fractional allelic loss was calculated for each lesion. Losses of 1q25, 7q13.3, 10q23, 13q14.3, and 11p15.5 were particularly prevalent. In addition, almost all adenomas and carcinomas had loss of the markers for 1p. The benign parathyroid diseases (adenomas and hyperplasia) had low mean fractional allelic loss (11% and 15%, respectively). The parathyroid carcinomas, in contrast, showed high mean fractional allelic loss (63%). This difference in the mutational profile suggests that this type of assay may be useful as an adjunctive diagnostic test in cases of parathyroid neoplasia.

Adenoma↗

PubMed2001

The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred.

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disease characterized by the occurrence of parathyroid tumours and fibro-osseous tumours of the jaw bones. Some HPT-JT patients may also develop renal abnormalities, which include Wilms' tumours, hamartomas and polycystic disease. The HPT-JT gene has been mapped to chromosome 1q25-q31, and we report the clinical and genetic findings in a kindred from central Portugal. HPT-JT was observed in six members from three generations; all had primary hyperparathyroidism (five had parathyroid adenomas, one a parathyroid carcinoma). Ossifying jaw fibromas affecting the maxilla and/or mandible were observed in 5/6. Renal cysts (<2.5 cm) were observed in four. Genetic studies using 18 polymorphic loci from chromosome 1q25-q31, together with leukocyte DNA from 11 family members and tumour DNA from three parathyroids (two adenomas and one carcinoma), revealed loss of tumour heterozygosity in the parathyroid carcinoma only, and the retained haplotype was found to cosegregate with the disease in the six affected members. A new Portuguese kindred with the HPT-JT syndrome that maps to chromosome 1q25-q31 has been identified, and these findings will help in the further characterization of this inherited disorder.

Adenoma↗

PubMed1987

Parathyroid adenoma imaged by gallium-67 citrate. A case report.

A parathyroid adenoma imaged by Ga-67 citrate in a 17-year-old man with primary hyperparathyroidism and a palpable solid tumor in the neck is presented. Although preoperative examination and intraoperative findings suggested a parathyroid carcinoma, histologic studies showed a parathyroid adenoma with predominant chief cell type.

Adenoma↗

PubMed2003

Paratracheal cervical mass in a dog.

A 14-year-old female Welsh Terrier was presented for evaluation of multiple skin masses. Two of them were diagnosed as a follicular (epidermal) cyst and a sebaceous epithelioma by cytology and histopathology. The third mass was located in the subcutis adjacent to the cervical trachea. Clinical findings, thoracic radiography, and laboratory results were otherwise unremarkable. Cytologically, the cervical mass was characterized by the presence of round to polygonal cells with distinct cell borders, mild to moderate anisocytosis, round to oval eccentric nuclei with prominent nucleoli, and a variable amount of finely granular, eosinophilic cytoplasm. Differential diagnoses included endocrine/neuroendocrine tumors such as thyroid adenocarcinoma, medullary thyroid carcinoma, carotid body chemodectoma, and parathyroid carcinoma. The mass was removed surgically and submitted for histopathologic and immunohistochemical examination. Histologically, the mass was composed of rows and nests of densely packed cells separated by thin fibrovascular stroma. Neoplastic cells had moderate to large amounts of pale eosinophilic dusty or finely vacuolated cytoplasm and round to oval nuclei with finely dispersed chromatin and 1 or 2 small nucleoli. On immunohistochemistry, neoplastic cells were positive for chromogranin A, calcitonin, and neuronspecific enolase, and were negative for cytokeratin and thyroglobulin. The final diagnosis was medullary thyroid carcinoma, an uncommon endocrine tumor of dogs that has cytologic and histopathologic features similar to other endocrine and neuroendocrine tumors. Immunohistochemistry or immunocytochemistry should be performed to differentiate medullary thyroid carcinoma from other endocrine/neuroendocrine tumors of dogs.

Animals↗

PubMed1987

Primary hyperparathyroidism in dogs: 21 cases (1976-1986).

Case records from 21 dogs with hypercalcemia and hyperparathyroidism were evaluated. The dogs were greater than or equal to 7 years old, and 6 were Keeshonds. The most common clinical signs were polydipsia/polyuria, listlessness, and muscle weakness. The serum calcium concentrations were 12.1 to 19.6 mg/dl. Serum phosphorus concentrations were low in 5 dogs, within the reference range in 13 dogs, and high in 3 dogs that also had high concentrations of BUN. Twenty dogs had a parathyroid adenoma, and 1 had a parathyroid carcinoma. Nineteen dogs had their parathyroid tumor surgically removed. Within 5 days of tumor removal, 11 of the 19 dogs became hypocalcemic and the remaining 8, normocalcemic. Nine of the 11 hypocalcemic dogs developed clinical signs. Iatrogenic hypercalcemia was induced in 7 of 16 dogs treated orally with calcium carbonate plus vitamin D. Only 1 of 19 dogs that had their parathyroid tumor excised died in hypocalcemic tetany. Two additional dogs died within 2 weeks of surgery, one because of pancreatitis, the other due to renal failure. Eight dogs died 9 to 37 months after surgery of unrelated problems. Eight dogs were alive for at least 7 to 28 months after surgery.

Adenoma↗

PubMed1984

Parathyroid hyperplasia and carcinoma within one gland.

A 47-year-old Scottish woman vacationing in the United States presented with a serum calcium level greater than 20 mg/dl and a parathyroid hormone level 16 times greater than normal after a one-week history of severe vomiting and unrelenting abdominal pain. Surgical exploration of the thymus revealed the very rare association of a large (7 by 4 by 0.8 cm) parathyroid carcinoma adjacent to apparently normal parathyroid tissue, separated by a thin fibrous band. Two other hyperplastic and one normal parathyroid glands were also identified. Postoperatively, the patient became hypocalcemic and, for the past nine months, has received maintenance 1-alpha-hydroxycholecalciferol therapy (1 microgram per day) with normal calcium and barely detectable parathyroid hormone levels.

Carcinoma↗

PubMed1985

Co-existent parathyroid adenoma and thyroid carcinoma. Nonspecificity of dual tracer parathyroid imaging for parathyroid lesions.

Dual tracer parathyroid imaging (DTPI) using Tc-99m and TI-201 has a reported sensitivity of 92% for the detection of parathyroid adenomas. A patient with biopsy-proven parathyroid adenoma as well as papillary thyroid carcinoma is presented. To date, this is the first such case ever to be reported and implies that DTPI, although a sensitive diagnostic modality for parathyroid adenoma detection, is not specific. The diagnosis of primary hyperparathyroidism has recently been established more frequently than in the past due to detection of elevated serum calcium levels on routine blood samples, relatively sensitive parathormone (PTH) assays, and noninvasive imaging modalities such as nuclear medicine, CT scanning, and ultrasonography. At our institution, we have successfully detected the location of parathyroid adenomas in many cases, using the dual tracer method with TI-201 and Tc-99m, confirmed at surgery. We present a case of primary hyperparathyroidism in which two distinct lesions were detected by nuclear imaging: one lesion was proven at surgery to be a parathyroid adenoma, while the other represented thyroid carcinoma.

Adenoma↗

PubMed2000

A newly recognized germline mutation of MEN1 gene identified in a patient with parathyroid adenoma and carcinoma.

We report on a patient with primary hyperparathyroidism, owing to the concurrence of parathyroid adenoma with carcinoma, who had a newly recognized germline mutation of the multiple endocrine neoplasia type 1 gene (MEN1 gene). The patient underwent total parathyroidectomy, and histological examination revealed parathyroid carcinoma and multiple adenoma of the other three glands. Genetic analysis revealed a newly recognized heterozygous germline mutation (842delC, exon 4) of the MEN1 gene. Both imaging studies and laboratory data showed no evidence of MEN1 in the patient. Four family members--three sisters and one daughter--had neither clinical features of MEN1 nor genetic evidence of the MEN1 gene. This is the first report of a germline mutation of the MEN1 gene found in a patient who exhibited the concurrence of parathyroid adenoma with carcinoma, suggesting that long-term hyperactivity of the parathyroids may result in the formation of carcinoma.

Adenoma↗

PubMed1990

Parathyroid imaging by Tc/Tl scintigraphy.

Between 1983 and 1988, a total of 224 99mTc/201Tl subtraction parathyroid scintigraphy studies were performed in 214 patients (136 women, 78 men, average age 50, +/- 15 years) with clinical and biochemical signs of hyperparathyroidism. Of the 214 patients, 113 underwent surgical exploration, and 127 benign parathyroid lesions were found, 48 of which were correctly localized by scintigraphy (sensitivity 38%). We detected 30 of 71 adenomas (42%) and 18 of 56 hyperplastic glands (32%). Additionally, the scans localized 2 of 6 parathyroid carcinomas in 5 patients. Overall, 83 parathyroid lesions were missed. There was no significant difference in size between detected and missed lesions. Previous neck surgery (65 of 113 patients) was not a significant detriment to scan sensitivity; but correct detection did depend upon the anatomic site of the lesion: 39% (n = 109) were detected in the typical site, 44% (n = 9) intrathyroidal, and 11% (n = 9) in the anterior and/or superior mediastinum. In conclusion, these results show only limited value for this 99mTc/201Tl subtraction scintigraphy protocol as the initial procedure for localization of abnormal parathyroid tissue prior to surgical exploration.

Female↗

PubMed2003

Parathyroid surgical failures with misleading falls of intraoperative parathyroid hormone levels.

According to earlier reports, a decrease below 50% of baseline of intraoperative PTH levels measured 5 min after resection of the parathyroid adenoma predicts a cure of hyperparathyroidism. To reveal previously unrecognized pitfalls of intraoperative PTH measurements, we reviewed surgical failures in our series of parathyroidectomies combined with intraoperative PTH sampling. PTH measurements were performed in 251 patients with primary hyperparathyroidism (PHPT) between November 1999 and December 2002. PHPT due to parathyroid hyperplasia were found in 8 cases, double parathyroid adenomas in 6 cases, parathyroid carcinoma in 1 case and single parathyroid adenomas in 236 cases, all confirmed by histological examination. Of the 236 cases of single adenomas, initial surgery failed to cure PHPT in 4 patients. In 3 patients a false-positive decrease of intraoperative PTH (from 269 to 40 pg/ml, from 211 to 27 pg/ml, and from 140 to 59 pg/ml) was observed, whereas in the fourth patient a true-negative decrease of intraoperative PTH (from 758 to 401 pg/ml) was mistakenly interpreted as indication for a cure of PHPT. In each of the 4 patients in whom initial surgery failed the intervention included thyroid surgery and reoperative parathyroid surgery resulted in a permanent cure of PHPT. These observations support the possibility that thyroid surgery may compromise the blood supply of parathyroid adenomas resulting in a misleading drop of intraoperative PTH levels. Therefore, a careful evaluation of intraoperative PTH levels and, perhaps, other intraoperative aids such as histological evaluation of frozen sections are recommended when parathyroid surgery is combined with simultaneous thyroid intervention.

Adenoma↗

PubMed1987

Synaptophysin immunoreactivity and small clear vesicles in neuroendocrine cells and related tumours.

Synaptophysin (protein p38) immunoreactivity has been detected immunohistochemically in neuroendocrine cells of the human adrenal medulla, carotid body, skin, pituitary, thyroid, lung, pancreas and gastrointestinal mucosa as well as in 87 out of 93 neuroendocrine tumours investigated, including pheochromocytomas, chromaffin and non-chromaffin paragangliomas, ganglioneuromas, pituitary adenomas, thyroid medullary carcinomas, parathyroid adenomas, lung carcinoids and neuroendocrine carcinomas, pancreatic and gut endocrine tumours and cutaneous merkelomas. Parallel ultrastructural investigation of synaptophysin-reactive cells and tumours revealed the presence, in addition to dense-cored, secretory granules, of a population of pleomorphic, small, clear vesicles resembling synaptic vesicles of nerve terminals as well as the synaptophysin immunoreactive vesicles already described in rat adrenal medullary and pituitary cells. Synaptophysin immunoreactivity showed several differences in its distribution among tumour and non-tumour endocrine cells when compared to chromogranin A immunoreactivity, a well known marker of the core of endocrine granules. Synaptophysin represents a reliable general marker of neuroendocrine cells and tumours, which may be useful in diagnostic histopathology.

Chromogranin A↗

PubMed1992

Surgical potpourri.

Six unusual surgical case are reported and the literature reviewed. The cases are: 1. Adenoid cystic carcinoma of the submaxillary gland 2. Parathyroid carcinoma 3. Squamous cell cancer of the pancreas 4. Leiomyosarcoma of the abdomen (two cases) 5. Myelolipoma of the adrenal gland These are representative cases from a general surgeon's practice, emphasizing the variety of interesting patients that the general surgeon cares for, and the scope of surgical knowledge that must be continually maintained. One of the attractions of having a practice in general surgery is that it provides the opportunity to diagnose and treat patients with a variety of conditions requiring surgical intervention. Reviewed here are six recent operative cases, their presentation, and management.

Abdominal Neoplasms↗

PubMed1987

Abnormal parathyroid glands: high-resolution MR imaging.

High-resolution magnetic resonance (MR) images of the neck were obtained in 23 patients with hyperparathyroidism. Surgical confirmation was available in all cases. MR imaging allowed accurate localization of 14 of 17 parathyroid adenomas, two of two parathyroid carcinomas, and five of eight hyperplastic glands, the latter from three patients. MR depicted nine of 11 (82%) abnormal glands that were 0.5-1.0 cm in size and 12 of 14 (85.7%) glands larger than 1 cm in diameter. In all but one case, abnormal glands had signal intensity greater than or equal to that of fat on spin-echo images with long repetition time and echo time. Parathyroid adenomas, carcinomas, and hyperplasia could not be distinguished from each other. The overall sensitivity and specificity of MR imaging in the detection of parathyroid abnormalities was 77.8% and 95.4% respectively, resulting in an accuracy of 90.2%. This compares favorably with other imaging modalities.

Adenoma↗

PubMed1998

Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues.

An altered control of the mechanisms involved in cell proliferation and programmed cell death (apoptosis) might play an important role in parathyroid tumorigenesis. We evaluated by immunohistochemistry the expression of bcl-2 and p53 proteins, as markers of apoptosis control, and MIB-1, as marker of cell proliferation, in a series of normal and neoplastic parathyroid tissues. The specimens were 33 normal parathyroids, 43 parathyroid adenomas and 3 parathyroid carcinomas. Results were scored as positive when more than 1% of cells were stained for MIB-1 and p53, and more than 10% for bcl-2. All normal parathyroids showed numerous bcl-2 positive cells (> or = 80%), low proliferation rate (MIB-1) and no p53 protein expression. Twenty-four (55%) adenomas were bcl-2 positive; in 16 of these the number of positive cells was high (> 50%) and immunoreactivity was diffusely distributed within the adenoma; 8 cases showed a zonal staining pattern, in which groups of stained cells were surrounded by negative cells. Nineteen adenomas (45%) and all carcinomas were bcl-2 negative. A high proliferative rate (MIB-1) was found in all carcinomas and 4 adenomas (9%); all MIB-1 positive adenomas were bcl-2 negative. p53 was negative in all specimens. No significant differences in serum calcium and intact PTH levels nor in tumor size were found between bcl-2 negative and bcl-2-positive and MIB-1-positive and MIB-1-negative adenomas. An inverse, but not statistically significant (p = 0.06) correlation was observed between the percentage of bcl-2 positive cells and serum calcium level in parathyroid adenomas. In conclusion, parathyroid adenomas are a heterogeneous group of lesions in which the pattern of bcl-2 and MIB-1 protein expression ranges between that of normal parathyroid (bcl-2 positivity and MIB-1 negativity) and that of parathyroid carcinoma (bcl-2 negativity and MIB-1 positivity). The question of whether the finding of the MIB-1 positive-bcl-2 negative phenotype identifies a subgroup of clinically more aggressive adenomas remains to be established.

Adenoma↗

PubMed2001

[Tumor markers for endocrine neoplasms].

Tumor markers for thyroid neoplasms include thyroglobulin, calcitonin, and CEA. Thyroglobulin is particularly useful in discriminating follicular carcinoma from its benign counterparts. The measurement may also be helpful in the postoperative follow-up of patients with either follicular carcinoma or papillary carcinoma. Measuring plasma calcitonin and CEA is essential in the diagnosis and postoperative management of patients with medullary carcinoma. Highly specific genetic tests may become an alternative strategy in cases of familial medullary carcinoma. No specific tumor markers are available for parathyroid carcinoma; however, clinical characteristics provide diagnostic clues.

Biomarkers, Tumor↗

PubMed1976

Transcervical thymectomy: an integral part of neck exploration for hyperparathyroidism.

Thirty-two neck explorations for hyperparathyroidism were done in 18 months. The indication for transcervical thymectomy was a failure to locate either inferior gland. Six of eight patients had adenomatous or hyperplastic glands located within or adjacent to the thymus. One infrathymic lesion was a parathyroid carcinoma and the other was a functioning parathyroid cyst. The abnormal parathyroid gland was not visible in any of these six patients until the thymus had been removed. Had this step been omitted, a sternotomy would probably have been required. Two patients had bilateral normal parathyroid glands within or deep to the thymus. Unless some normal parathyroid tissue has been identified and preserved, the indiscriminate use of transcervical thymectomy could result in the inadvertent excision of both inferior glands and possible iatrogenic hypoparathyroidism.

Humans↗

PubMed2004

Chondrosarcoma in association with primary hyperparathyroidism.

We describe two female patients, 66 and 36 years of age, with both primary hyperparathyroidism and chondrosarcoma. Case 1 had a chondrosarcoma of the right scapula, and case 2 had chondrosarcoma of the left proximal tibia. Both patients underwent surgical resection of their chondrosarcoma and subsequent parathyroid surgery. Histological analysis of the excised parathyroid in case 1 showed a parathyroid carcinoma and in case 2 showed a parathyroid adenoma. Including these two patients, there is now a total of six cases that have been reported in the literature describing the association between hyperparathyroidism and bone malignancy. We believe that this small number makes it unlikely that there is an association between these two conditions, although we speculate that there may be an underlying genetic basis.

Adult↗

PubMed1981

[Characteristic ultrastructural features of parathyroid gland cancer. A report on 9 cases (author's transl)].

Authors have studied 9 parathyroid carcinomas under electron microscope (3% of their parathyroid lesions). Two types of the ultrastructural features were significant: 1) architectural: basal membrane abnormalities, sparse desmosomes, absence of nerve fiber; 2) cytological: nuclei atypism and abnormal mitochondria in tumors cells resembling dark chief cells. Also noticed were signs of cell hyperactivity and/or trouble in parathormon production or regulation.

Adenocarcinoma↗