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PubMed1993

Recurrent hyperparathyroidism due to parathyroid autografts: incidence, presentation, and management.

Recurrent hyperparathyroidism (HPT) occurs in a small percentage of patients undergoing parathyroidectomy for primary HPT and is usually due to inadequate excision of hyperfunctioning parathyroid tissue in the neck, a missed ectopic and hyperplastic parathyroid, or, less commonly, parathyroid carcinoma and parathyroid autografts. In order to determine the incidence, clinical characteristics, and outcome of patients with recurrent HPT due to parathyroid autografts, we reviewed our experience with 604 consecutive patients operated on for primary HPT between 1965 and 1989. One hundred of these patients received parathyroid autografts consisting of portions of one or more parathyroid glands. Three patients with autografts, placed in the sternocleidomastoid muscle, developed recurrent HPT due to their autografts for an incidence of 3 per cent. Recurrent disease was diagnosed between 62 and 113 months with an average of 89 months. The autotransplants in all three of these patients were from hyperplastic or adenomatous parathyroid tissue. Two patients had a history of neck irradiation. Preoperative thallium scans accurately localized the hyperfunctioning parathyroid tissue in all three patients. At operation, the hyperfunctioning autografts had grown into a discrete mass with a single vascular pedicle and were resected. Histologic examination disclosed either hyperplastic or adenomatous tissue, and corresponded to the histology and location of the original tissue transplanted in each case. Follow-up ranges from 12 to 67 months, with an average of 48 months. All patients remain cured and none require oral calcium supplementation. We conclude that graft-dependent recurrent HPT is due to the autotransplantation of hyperplastic or adenomatous parathyroid tissue and that thallium scanning is instrumental for diagnosis and localization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2000

Update on the management of parathyroid tumors.

Parathyroid tumors are virtually always benign with an estimated incidence of parathyroid carcinoma causing hyperparathyroidism in only .017% of cases. Virtually all parathyroid neoplasms, including the rare parathyroid carcinoma, are functional and discussion of the management of parathyroid tumors is tantamount to the discussion of primary hyperparathyroidism. The biochemical diagnostic criteria with rare exception is definitive, and the key issue with this functional benign endocrine neoplasm is when to recommend operation and how to ensure optimal results in this curable disease. Patients symptomatic with nephrolithiasis, significant osteoporosis, bone pain, and in some cases constitutional symptoms should undergo a surgical therapy. Also, patients with markedly abnormal laboratory values including a calcium 12.0 mg/dL, or 24-hr urinary calcium >400 mg/day should be treated surgically. The sestamibi nuclear medicine scan has become the best tool available for imaging of abnormal parathyroid glands. This study is positive between 60% and 90% of initial operations and in between 40% and 70% of reoperations. For multi-gland parathyroid disease or hyperplasia, the sensitivity of this test is decreased. Understanding of the ectopic locations of parathyroid adenoma is of utmost importance in the conduct of the parathyroidectomy. For the rare patients with parathyroid carcinoma, aggressive surgical resection with en bloc removal of any adjacent invading structures is the best chance for cure leading to 10-year survival rates of 49%.

Adult↗
PubMed1984

[Surgical management of primary hyperparathyroidism].

We have experienced 186 patients with proven primary hyperparathyroidism operated on during past 16 years. In this series, 147 patients (79%) had adenoma, 24 patients (12.9%) had carcinoma and only 15 (8.1%) had hyperplasia. Because of a 92% of single gland involvement, the removal of an enlarged gland is adequate, if the remaining gland are grossly normal. Besides, interestingly enough, an incidence of parathyroid carcinoma is rather high in Japan, so that surgeons should be alert to recognize the parathyroid carcinoma on the basis of clinical and operative findings. In an effort to minimize recurrence, en bloc resection of the parathyroid carcinoma is important. When a patient with parathyroid carcinoma has a local recurrence or distant metastases, an aggressive surgical approach is recommended to alleviate hypercalcemic symptoms. The majority of patients with hyperplasia belong to multiple endocrine neoplasia, type 1. Recent development of the non-invasive diagnostic methods is remarkable. The last consecutive 31 patients underwent preoperative localization study by 201Thallium (201TI-CI) scanning and ultrasonography. 201TI-CI scanning gave the most accurate results and 100% correct localization was obtained when the parathyroid tumor was more than 1 g. However, it is noteworthy that the parathyroid tumor was less than 1 g in 64% of patients who had no evidence of generalized fibrous osteitis.

Adult↗
PubMed2003

Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis.

We studied 45 patients with typical and 8 with atypical parathyroid adenomas as well as 20 with parathyroid carcinomas. Clinical, pathological, and molecular analyses were conducted on all adenomas. Clinical data were analyzed for 20, histopathologic slides for 16, and tissue specimens for 8 patients with carcinoma. Molecular expression profiles were investigated by immunohistochemistry (IHC) for Ki-67, p53, mdm2, p21, Bcl-2, cyclin D1, and p27 on paraffin-embedded tissues arrayed on tissue microarrays. Trabecular growth and vascular, capsular, and soft-tissue invasion were characteristic of parathyroid carcinomas but not of typical adenomas. No adenomas recurred. Seventy-four percent of carcinomas recurred, most in the neck. Seventy-nine percent of patients with such illness died of disease after an indolent, multiply recurrent course responsive to repeated resections; the 5-year survival rate was 50%. High Ki-67 proliferative index was seen in 2% of adenomas and 25% of carcinomas, whereas p27 expression was present in 80% of adenomas and 18% of carcinomas. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), was observed in 76%, 29%, and 0% of typical and atypical adenomas and carcinomas, respectively. The complexity of molecular phenotypes increased with tumor aggressiveness. Parathyroid carcinoma is an aggressive disease with a propensity for multiple recurrences. It is characterized by capsular, vascular, and soft-tissue invasion. Recurrence portends poor outcome. Molecular markers, Ki-67 and p27, may distinguish parathyroid carcinoma from adenoma. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), appears to be unique to nonmalignant parathyroid tumors, and multimarker phenotypes are more complex in carcinomas.

Adenoma↗
PubMed1978

Occurrence of previous neck radiotherapy among patients with associated non-medullary thyroid carcinoma and parathyroid adenoma or hyperplasia.

Sixteen consecutive patients with co-existent non-medullary thyroid carcinoma and parathyroid adenoma or hyperplasia are reported. Ten of these patients had earlier been treated with external radiation in the neck region. The estimated absorbed dose varied between 5 and 23 gray. The diagnosis of thyroid carcinoma and hyperparathyroidism (HPT) was established 36 years (average) after exposure to radiation. The findings are in accordance with the hypothesis that radiation can serve as an etiological factor in the development of associated thyroid carcinoma and HPT.

Adenocarcinoma↗
PubMed2003

Parathyroid gland carcinoma in a Wistar rat.

An anaplastic carcinoma was found in one of the two parathyroids of a 2-year-old male Wistar rat, which was sacrificed at the end of a carcinogenicity study. Morphologically, it was characterized by the presence of nodular areas of pleomorphic and dense cells with numerous atypical mitoses and large regions of smaller and dark monomorphic cells devoid of mitoses and forming small cystic spaces. Local invasion of the capsule and pronounced compression of the parenchyma of the thyroid gland were observed. Immunohistochemically, the tumor was markedly positive for the parathyroid hormone and negative for the thyroid transcription factor. The proliferative activity was assessed by immunostaining the endogenous cell proliferation associated-antigen Ki-67, and the proliferating cell nuclear antigen. The diagnosis of carcinoma of the parathyroid was made on the basis of microscopic and immunohistochemical findings.

Animals↗
PubMed1993

[Parathyroid gland cancer. Problems in diagnosis and therapy].

Parathyroid carcinoma occurs in 0.1 to 5% as the cause of primary hyperparathyroidism (HPT). It is difficult to determine the true incidence, because parathyroid carcinoma is diagnosed too often due to unreliable histologic criteria. It is only justified to make the diagnosis, when a local recurrence or metastases with the clinical picture of a recurrent or persistent HPT occurred. Treatment of choice is the initial en-bloc resection, which may result in long disease-free intervals. Pharmacological treatment, chemotherapy, and radiation are mostly ineffective in the treatment of parathyroid carcinoma. A satisfactory long-term palliation can only be achieved with repeated resections of the local recurrences and metastases. Diagnostic efforts should be made to localize the recurrent tumor before every reoperation, whereby ultrasonography of the neck is the most sensitive procedure. Occasionally the parathyroid tissue cannot be identified in spite of preoperative diagnostic studies or hypercalcemia persists after surgery. In these cases forced diuresis and medical treatment with calcitonin, diphosphonates or mithramycine can briefly control hypercalcemia. The clinical courses of 3 patients with metastasizing parathyroid carcinoma are presented and discussed. In these patients 3 to 11 surgical interventions were performed in combination with an intermittent medical treatment. By this regimen we achieved long-term palliations up to 13 years.

Adenoma↗
PubMedDate not supplied

Nonequivalent results of tetrofosmin and sestamibi imaging of parathyroid tumors.

OBJECTIVE: To report the case of a patient with a large parathyroid carcinoma missed by dual-phase technetium Tc 99m tetrofosmin (TETRO) parathyroid scanning. METHODS: We present the clinical findings, laboratory results, imaging studies, and surgical pathology report in a man with parathyroid carcinoma and review the literature regarding the use of TETRO scintigraphy in patients with hyperparathyroidism. RESULTS: In an 83-year-old man with hyperparathyroidism, severe hypercalcemia developed in the context of nephrolithiasis. An in-office ultrasonographic evaluation of the neck revealed a partially calcified mass (2.3 by 1.3 by 1.6 cm) at the inferoposterior border of the left thyroid lobe. Technetium Tc 99m sestamibi (MIBI) scanning was requested and reported as "negative." In fact, TETRO scanning had been substituted for MIBI scanning by the management of the nuclear medicine facility. Before neck exploration, performance of dual-phase MIBI parathyroid scintigraphy revealed radionuclide retention in the left lower neck area at 120 minutes, in the same site as the ultrasonographically visualized mass. A limited left inferior parathyroidectomy was performed, and intraoperative parathyroid hormone levels declined from 254 pg/mL to 28 pg/mL 10 minutes after near-complete resection of the mass. Pathology evaluation of the surgical specimen revealed a 2,000-mg parathyroid carcinoma. CONCLUSION: Although both agents incorporate the same technetium Tc 99m radionuclide, TETRO and MIBI parathyroid scanning are not equivalent in the detection of parathyroid tumors with use of the dual-phase technique. We do not recommend substitution of TETRO for MIBI as a cost-control measure in the evaluation of hyperparathyroidism.

Aged, 80 and over↗
PubMed2002

Parathyroid carcinosarcoma: a previously unreported entity.

Parathyroid carcinoma is a rare disease. The first report of parathyroid carcinoma with sarcomatous differentiation is presented. A parathyroid mass measuring 6 x 8 x 9 cm was surgically excised from the left side of the neck in a 54-year-old man who had mild hypercalcemia. Light microscopic examination of the mass showed carcinoma with areas of rhabdomyosarcoma and chondrosarcoma. Immunohistochemical studies confirmed the light microscopic impression. Resolution of hypercalcemia followed excision of the mass, but multiple pulmonary and adrenal masses subsequently developed and led to the patient's death despite aggressive trials of chemotherapy with doxorubicin, ifosfamide, and cisplatin. The sarcomatous elements of the mass excised from this patient are presumed to represent aberrant cellular differentiation previously described in uterine and other tissue but not in parathyroid glands. Sarcomatous differentiation itself appears to be a poor prognostic factor in parathyroid carcinoma.

Carcinosarcoma↗
PubMed1975

Carcinoma of the parathyroid.

The histologic diagnosis of carcinoma of the parathyroid is difficult to make, and invasion of contiguous structures or metastasis must be present before the diagnosis can be established. The serum calcium level is usually high, and the tumor is palpable in approximately one half of the patients. A case of parathyroid carcinoma is presented in which the patient had a high serum calcium level, a palpable tumor with invasion of the thyroid gland and metastasis to a local lymph node. Treatment consists of en bloc resection of the tumor and, if possiblethe metastasis. Usually an ipsilateral neck dissection is indicated.

Carcinoma↗
PubMed2003

Hypercalcemia upon recurrence of renal cell carcinoma producing parathyroid hormone-related protein.

We established a new renal carcinoma cell line that produces parathyroid hormone-related protein (PTHrP) and interleukin-6 in culture. The cellular production of PTHrP was confirmed by Northern blot analysis and immunofluorescence examination. Bone and lung metastases occurred simultaneously 3.5 years after surgery. The patient did not show hypercalcemia at this time, despite the presence of multiple osteolytic metastases. About 7 months after bone metastasis was first shown, serum PTHrP was detected by means of an immunoradiometric assay and the calcium level was found to be elevated to 3.29 mmol/l. The hypercalcemia was successfully controlled by i.v. administration of bisphosphonates.

Adult↗
PubMed2005

[Diagnostic problems with recognition of primary hyperparathyroidism].

The aim of our study was to compare the results of biochemical and imaging investigations with histopathological diagnosis in operated patients with primary hyperparathyroidism. 46 subjects were included into the study, pathologically demonstrated as parathyroid adenoma--23 subjects, parathyroid hypertrophy--16, parathyroid carcinoma--2 and in 5 patients parathyroid gland was not found in resected tissue. The most frequent complications of primary hyperparathyroidism in our group were osteoporosis (87%) and nephrolithiasis (64.1%). 99mTc-MIBI imaging described as a parathyroid adenoma or parathyroid hypertrophy were confirmed pathologically in 52 and 57.1%, respectively. Three typical symptoms of primary hyperparathyroidism assessed in our study (hypercalcemia, hypercalciuria and increased concentration of parathormone) were observed only in about 50% patients with histopathological diagnosis of adenoma and hypertrophy. The lowest average calcium serum level (2.87 mmol/l), urinary calcium level (7.8 mmol/24h) and parathyroid hormone concentration (209.4 pg/ml) were observed in patients with parathyroid adenoma, the highest levels of these parameters were noticed in patients with parathyroid carcinoma (3.41 mmol/l; 14.6 mmol/24h; 687.8 pg/ml, respectively), patients with parathyroid adenoma were characterized by intermediate values (2.98 mmol/l; 9.7 mmol/24h; 285.5 pg/ml, respectively). After parathyroidectomy lowering in average calcium serum level (2.94 vs. 2.16 mmol/l), parathyroid hormone concentration (244.45 vs. 54.15 pg/ml) and increasing in average phosphate serum level (0.81 vs. 1.04 mmol/24h) were observed in our group. Finally, using different biochemical and imaging investigations is necessary for proper recognition of primary hyperparathyroidism due to occurring of oligosymptomatic cases.

Diagnosis, Differential↗
PubMedDate not supplied

High-resolution parathyroid sonography.

The purpose of this study was to assess the diagnostic utility of parathyroid ultrasonography to differentiate causes of hypercalcemia in dogs. We analyzed qualitative and quantitative ultrasound imaging findings and clinical pathology data from 33 dogs that underwent parathyroid ultrasound examination as part of the diagnostic evaluation for hypercalcemia. Diagnoses of the diseases causing hypercalcemia included parathyroid carcinoma (n = 5), parathyroid adenoma (n = 15), parathyroid adenomatous hyperplasia (n = 6), chronic renal insufficiency (n = 3), and hypercalcemia of malignancy (n = 4). All parathyroid lesions were round or oval and hypoechoic compared with surrounding thyroid parenchyma. Adenomatous and adenocarcinomatous glands were 4 mm or larger in longest linear measurement on US examination and were statistically significantly larger than hyperplastic glands. (p < 0.001) Linear measurements of parathyroid glands acquired at the time of ultrasound examination correlated well with direct size determination after surgical excision. (r2 = 0.9, p < 0.0001) Parathyroid lesions > or = 4 mm are highly suspicious for parathyroid adenoma or carcinoma, while US lesions < 4 mm most likely represent primary adenomatous hyperplasia or secondary parathyroid hyperplasia. Parathyroid size estimation from ultrasound examination is an accurate predictor of true size.

Animals↗
PubMed1991

[Parathyroid adenoma and carcinoma. A comparative morphologic study].

A variety of gross, histological and cytological features were analyzed in a comparative study between adenomas and carcinomas of the parathyroid gland. The histological findings more valuable in the differential diagnosis of parathyroid carcinoma were the presence of a thick and irregular capsule infiltrated by the tumor (Fig. 1), broad and irregular intratumoral fibrous septa, and capsular or intratumoral vascular invasion (Table 1). Cytologically, the carcinomas were composed only by chief cells, with a mitotic activity higher than in adenomas, showing the presence of abnormal mitosis (Table 2, Fig 4). Characteristically all carcinomas were composed by a cellular population significantly of greater size than the one observed in adenomas.

Adenoma↗
PubMed2005

HRPT2 mutational analysis of typical sporadic parathyroid adenomas.

CONTEXT: Mutations of HRPT2 are frequent in sporadic parathyroid carcinomas and central to their pathogenesis. However, the potential diagnostic utility of HRPT2 mutation status to distinguish between parathyroid carcinoma and adenoma hinges on the frequency of HRPT2 mutations in benign adenomas. Even a low rate of HRPT2 mutation in adenomas would greatly alter diagnostic specificity, because adenomas are far more prevalent than carcinomas. The issue remains open because of the limited number of typical adenomas, not subjected to additional selection criteria, examined in previous studies. OBJECTIVE/DESIGN/PATIENTS: To determine the frequency of HRPT2 somatic mutations in a substantial series of typical, sporadic parathyroid adenomas, we directly sequenced coding and flanking splice junctional regions of all HRPT2 exons in solitary adenomas from 60 patients. RESULTS/CONCLUSIONS: No intragenic HRPT2 mutations were detected, strengthening the degree of specificity of HRPT2 mutation as a feature of sporadic parathyroid carcinoma as opposed to sporadic adenomas. Our observations encourage additional study of the diagnostic potential of HRPT2 in parathyroid neoplasia and support the view that HRPT2 inactivation is not an important participant in the pathogenesis of typical parathyroid adenomas.

Adenoma↗
PubMed2000

Intranuclear holes (cytoplasmic pseudoinclusions) in parathyroid neoplasms, or "holes happen".

BACKGROUND: A parathyroid adenoma demonstrating intranuclear holes on aspiration cytology prompted a review of parathyroid neoplasms to determine the frequency of this phenomenon. METHODS: Aspiration cytology slides from 30 parathyroid adenomas and 1 parathyroid carcinoma were reviewed. In addition, histologic slides from 136 parathyroid adenomas and 7 parathyroid carcinomas were reviewed. Twenty-two cases had both cytologic and histologic slides available for review. The presence and approximate frequency of intranuclear holes were recorded. RESULTS: On cytologic smears, intranuclear holes were found in 3 of the 31 cases reviewed (2 adenomas and 1 carcinoma). The holes were frequent in only one adenoma (the index case) and moderate-rare in the other two cases. Review of tissue slides showed holes in 9 of 136 adenomas and 3 of 7 carcinomas; 2 adenomas and 2 carcinomas had frequent holes, whereas the remainder had holes infrequently. CONCLUSIONS: Intranuclear holes do occur in parathyroid neoplasia, in rare cases with considerable frequency. When intranuclear holes are observed in aspiration cytology specimens from the thyroid region, various thyroid and parathyroid conditions must be considered.

Adenoma↗