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PubMed2005

Primary hyperparathyroidism: can parathyroid carcinoma be anticipated on clinical and biochemical grounds? Report of nine cases and review of the literature.

BACKGROUND: Parathyroid carcinoma (PC) mimics benign primary hyperparathyroidism (PHP), but the diagnosis of PC is seldom available at the time of the first operation. Because PC is plagued by recurrences usually beyond cure, one may wonder whether some of these could be prevented by more extensive resections initially, i.e., if the diagnosis of PC were available at that time. METHODS: Over a 25-year period, 311 consecutive patients with PHP underwent operation in our department: 302 had benign disease (adenomas or hyperplasias), and 9 had PC. Several clinical parameters, serum calcium and parathyroid hormone (PTH) levels, and the weight of the parathyroid tumor removed were compared in both groups. Receiver operating characteristic curves and logistical regression analyses were used to distinguish PC from benign PHP. RESULTS: Eight of 9 patients with PC had symptoms, versus 238 (79%) of 302 with benign PHP (not significant). In the PC subgroup, serum calcium and PTH levels and the tumor weights of the parathyroid glands removed were significantly higher than in the benign PHP cohort, even if these three parameters were regularly flawed by low positive predictive values (14%, 20%, and 15%, respectively). CONCLUSIONS: Serum calcium, PTH levels, and tumor weights were significantly greater in the PC subgroup, even if not invariably in a discriminatory way. However, when PTH is <4 times the upper limit of normal and tumor weight is <1.9 g, the probability of PC is nil.

Adult↗
PubMed1988

[An autopsy case of parathyroid carcinoma with primary hyperparathyroidism].

An autopsy case of a 72-year-old woman who was determined as having had a parathyroid carcinoma with primary hyperparathyroidism is reported. On autopsy, a tumor, measuring 6 X 3 X 2 cm, was found beneath the left lobe of the thyroid gland, adherent to the left recurrent nerve and the trachea, though there was no metastasis evident. The tumor was found to be lobulated on cross section inspection. Histologically, the tumor cells were arranged in trabecular and in solid patterns with fibrous bands. A few tumor cells showed mitosis. Invasions to the capsules and the blood vessels were found present. Immunohistochemically, the parathyroid hormone was found positive in the cytoplasm of the tumor cells. Otitis fibrosa generalisata, metastatic calcification, acute pancreatitis, and core pulmonale also were observed.

Aged↗
PubMed1993

Parathyroid carcinoma: the relationship of nuclear DNA content to clinical outcome.

This article reports the use of flow cytometry to determine tumor nuclear DNA content and its correlations with clinical outcome in a series of patients with parathyroid carcinoma. Information concerning nine patients with parathyroid cancer (aged 25 to 88 years) was reviewed. Paraffin-embedded, formalin-fixed archival tissue was used to determine tumor DNA content flow cytometrically. Twenty-five operative procedures were performed in nine patients, including 11 parathyroidectomies, two wide local excisions, six central neck dissections, and four median sternotomies for resection of metastases. With flow cytometry used to determine a tumor DNA index, five patients had evidence of tumor aneuploidy; in two patients two aneuploid peaks were evident. The DNA index ranged from 0.7 (hypodiploid) to 1.92 (mean, 1.31). Follow-up ranged from 1 to 18 years. Four patients died. Five were alive 1 to 13 years after diagnosis of parathyroid disease. Four of the five patients with evidence of tumor aneuploidy had metastatic disease and died, and the fifth has had three local recurrences. The four patients with diploid tumors were alive and free of disease 1, 3, 4, and 8 years after the initial operation. It is concluded that in patients with clinically or pathologically demonstrated parathyroid cancer, flow cytometry may help differentiate those whose cancers are likely to behave indolently (diploid tumors) from those with tumors (aneuploid) more likely to behave aggressively by recurring locally or metastasizing.

Adult↗
PubMedDate not supplied

Parathyroid carcinoma with occult bone metastases diagnosed by fine needle aspiration cytology.

A case with persistent hypercalcemia following complete resection of a primary parathyroid carcinoma is presented. An occult bone metastasis was diagnosed by fine needle aspiration (FNA) cytology of a lytic bone lesion clinically presumed to be a "brown tumor" of hyperparathyroidism. The cytologic features of the metastatic lesion were similar to those of the resected primary lesion and of a previously identified metastasis. The potential usefulness of FNA cytology in this clinical setting is discussed.

Biopsy, Needle↗
PubMed1992

Parathyroid carcinoma. Report of three cases.

Primary or relapsing hyperparathyroidism should not be considered a result only of benign conditions like adenoma or hyperplasia (primary or secondary). Parathyroid carcinoma is often the real cause but, because of its rarity, sometimes it is either overlooked or misdiagnosed. Even histologic classification can be erroneous. Distant metastases or ectopic location of the tumors are another potential cause of misdiagnosis, especially when management is decided without the help of diagnostic imaging modalities, particularly those related to the functional aspect of the tumors or their metastases, such as the Tl-201/Tc-99m subtraction scan and the Tl-201 whole body scan.

Adult↗
PubMed1990

Metastatic calcification in a patient with malignant parathyroid carcinoma. Correlation of clinical, surgical, radiographic, and scintigraphic findings.

A patient whose bone scan showed features typical of a "superscan," having extensive pulmonary, cardiac, and renal calcifications is described. Metastatic parathyroid carcinoma with renal insufficiency and phosphate retention are cited as the cause. Early diagnosis and surgical extirpation offer the best chance for cure or palliation. Pitfalls of plain film radiography in identifying metastases and pathologic soft tissue calcifications in the setting of severe hyperparathyroidism are discussed, and the advantages of functional radionuclide imaging assessments are emphasized.

Bone Neoplasms↗
PubMed2000

Induction of cellular immunity in a parathyroid carcinoma treated with tumor lysate-pulsed dendritic cells.

BACKGROUND: Cytotoxic T-lymphocyte-mediated tumor immunity against major histocompatibility antigen class II-negative tumors requires help from CD4(+) T-cells. The major antigen presenting cells for CD4(+) cell activation are dendritic cells. Studies in mice and humans have demonstrated the potent capacity of these cells to induce specific antitumor immunity. OBJECTIVE: To control the growth of a metastasized parathyroid carcinoma, by immunizing a patient with tumor lysate and parathyroid hormone-pulsed dendritic cells. DESIGN AND METHODS: Mature dendritic cells were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin-4 and tumor necrosis factor alpha. Antigen-loaded dendritic cells were delivered by subcutaneous and intralymphatical injections. After five cycles, we added keyhole limpet hemocyanin (KLH) as a CD4(+) helper antigen. RESULTS: After 10 vaccinations, a specific cellular immune response to tumor lysate was observed. In vitro T-cell proliferation assays revealed a dose-dependent stimulation index of 1.8-5.7 compared with 0.9-1.1 before vaccination. In vivo immune response was demonstrated by positive delayed-type hypersensitivity toward tumor lysate. Intradermal injection of tumor lysate resulted in an erythema and induration, suggesting the efficient generation of tumor lysate-specific memory T-cells. CONCLUSIONS: These data indicate that dendritic cell vaccination can induce in vitro and in vivo responses in a highly malignant endocrine carcinoma. Regardless of the clinical outcome of our patient, this approach might be generally applicable to other advanced, radio- and chemotherapy-resistant endocrine malignancies, such as adrenal carcinomas and metastasized medullary and anaplastic thyroid carcinomas.

CD4-Positive T-Lymphocytes↗
PubMed1985

Parathyroid carcinoma associated with chronic renal failure and previous radiotherapy to the neck.

Carcinoma of the larynx was treated by irradiation followed by laryngectomy in a man who had been receiving regular haemodialysis for two years. At least one, and probably two, parathyroid glands were removed at this time, and the remaining two were removed three years later for tertiary hyperparathyroidism. A portion of one gland was implanted into the forearm. The forearm implant was resected the following year for recurrent hypercalcaemia. Six years later, again with recurrent hypercalcaemia, he died of bronchopneumonia. Metastatic parathyroid carcinoma was found in the apex of the left lung. The source of this parathyroid tissue and the possible role of irradiation in the pathogenesis of parathyroid cancer in this patient were investigated.

Adult↗
PubMed1999

Expression of matrix metalloproteinase gelatinase A messenger ribonucleic acid in parathyroid carcinomas.

BACKGROUND: The incidence of parathyroid cancer in patients with hyperparathyroidism is less than 1%. However, these few cases cause diagnostic problems in the absence of clear-cut invasion of adjacent organs or metastasis. New markers are needed to increase diagnostic accuracy. METHODS: Thirty-one parathyroid tumors from patients with primary hyperparathyroidism were collected worldwide. Eighteen tumors were classified as unequivocal cancers, whereas 13 tumors were considered equivocal because of a lack of infiltrative growth or evidence of recurrence. Paraffin sections were hybridized with a 35S-labeled riboprobe complementary to gelatinase A mRNA, dipped in photographic emulsion, developed, counterstained, and then evaluated by light- and dark-field microscopy. RESULTS: Fourteen of the 18 unequivocal parathyroid cancers expressed gelatinase A, as compared with the equivocal tumors, of which only 4 of 13 showed expression. The strongest hybridization signal was seen in stromal cells at the tumor border, most likely fibroblasts and macrophages. No expression was detected in tumor cells. CONCLUSIONS: Invasive growth of many tumors is facilitated by proteolytic enzymes, such as gelatinase A. The presence of gelatinase A mRNA in parathyroid tumors strengthens the suspicion of malignancy but cannot be used as a definitive marker of malignancy.

Adult↗
PubMed2001

Occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and Hashimoto's thyroiditis.

A 47-year-old female patient with a previous history of right thyroid lobectomy was admitted to the hospital because of a 3 cm nodule in the thyroid gland. Hormonal evaluation showed subclinical hypothyroidism with serum levels of thyroid stimulating hormone slightly elevated to 4.4 microg/dl (normal: 0.4-4 microg/dl). Thyroid ultrasound showed diffuse irregularity of the gland and the presence of a solitary nodule (30x18 mm in diameter) localized in the left lobe. A fine needle aspiration biopsy was performed. Cytological analysis revealed papillary thyroid carcinoma and Hashimoto's thyroiditis. Total thyroidectomy was performed. During the operation, two of the parathyroid glands were detected to be hyperplastic. Histopathological examination of the thyroid and parathyroid glands revealed Hashimoto's thyroiditis with papillary thyroid carcinoma and synchronous carcinoma of the parathyroid gland. To our knowledge, this association of occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and Hashimoto's thyroiditis has not been reported in the literature. Given the high prevalence of autoimmune diseases in elderly women, a random occurrence of this triad represents the most likely explanation.

Biopsy, Needle↗
PubMedDate not supplied

Metastatic nonfunctioning parathyroid carcinoma: ultrastructural evidence of secretory granules and response to chemotherapy.

A 69-year-old woman was admitted to the hospital because of recurrent cervical nodules, a large anterior mediastinal mass, and malignant left pleural effusion. Light and electron microscopy of the resected cervical nodules and cytology of the pleural fluid showed findings consistent with parathyroid carcinoma. There was no evidence of hyperparathyroidism on clinical evaluation, multiple serum calcium and phosphorus determinations, skeletal survey, intravenous pyelogram, or radioimmunoassay of intact and carboxy-terminal parathyroid hormones in the serum. Electron microscopy revealed secretory granules in the cytoplasma of malignant cells. A dramatic and complete resolution of the mediastinal mass and pleural effusion occurred after 18 months of chemotherapy with "MACC" (methotrexate, adriamycin, cyclophosphamide and CCNU).

Aged↗
PubMedDate not supplied

Calcaneal brown tumor with primary hyperparathyroidism caused by parathyroid carcinoma: an atypical localization.

Brown tumors are one of the characteristics of primary hyperparathyroidism, although, in some cases, they are noted with secondary hyperparathyroidism as well. The authors present a case of a 50-year-old woman with primary hyperparathyroidism caused by parathyroid carcinoma with an unusual location of a brown tumor in the calcaneus. She first presented with pain and swelling over the heel and ankle, and the diagnosis was suspected by radiographs. Biopsy of the calcaneal lesion confirmed a brown tumor. After the parathyroid lesion was removed surgically, her symptoms were relieved. The calcaneal lesion was treated with immobilization of the foot.

Bone Neoplasms↗
PubMed2004

Relationship of AgNOR counts and nuclear DNA content to survival in patients with parathyroid carcinoma.

The aim of this study was to evaluate the usefulness of DNA flow cytometry to determine tumor nuclear DNA index (DI), and nucleolar organizer region protein counts visualized by the argyrophil (AgNOR) technique, in confirming diagnosis and predicting clinical outcome of patients with parathyroid carcinoma (PC). We reviewed paraffin-embedded tissue sections, from 15 patients (median age 63 years, range 30-68 years) with PC who died of the disease, which were randomly compared with tissue sections from 15 age- and sex-matched patients with parathyroid adenoma (PA). The proliferative activity in parathyroid tumours as detected by DI and AgNOR counts was evaluated in all specimens. Both DI (1.37 +/- 0.33 vs 1.0 +/- 0.1) and AgNOR (3.01 +/- 0.31 vs 1.54 +/- 0.35) counts were higher (P < 0.001) (Student's t-test) in patients with PC than in those with PA. Diploid (DI = 1), aneuploid (DI > 1) and hypoploid (DI < 1) neoplasms were found in 11 (PC = 4, PA = 7), 14 (PC = 11, PA = 3) and five (PC = 0, PA = 5) patients respectively. The average postoperative survival in patients with PC was 46.9 +/- 37.4 months (range 21-146 months). The survivals of patients with aneuploid (n = 11) and diploid (n = 4) PC were 74.0 +/- 58.1 and 34.1 +/- 18.4 months (P=0.21) respectively. There was a significant relationship between DI and AgNOR counts (R=0.69, P < 0.01), but no correlation was found between survival and both DI (Rho = 0.17, P = 0.55) and AgNOR counts (Rho = 0.26, P = 0.35). Moreover, there was no correlation (P = NS) between the main preoperative biochemical parameters and survival. In conclusion, DI and AgNOR are useful in confirming the diagnosis of PC, but they are of little value in predicting the clinical outcome of patients with PC.

Adenocarcinoma↗
PubMed1984

[Parathyroid carcinoma--a case report and a review of the Japanese literature].

The patient, a 42-year-old female, presented with bone pain and a cervical tumor. The tumor was operated at another hospital under a diagnosis of thyroid adenoma and the bone pain subsequently disappeared. Three years later, a cervical tumor was palpated just under the operative scar; the patient experienced nausea, vomiting. The tumor and the left thyroid lobe were removed and modified radical neck dissection was performed. The histological diagnosis of the resected specimen was parathyroid carcinoma.

Adult↗
PubMed2006

A case of parathyroid carcinoma with hypercalcemia responsive to cinacalcet therapy.

BACKGROUND: A 54-year-old man presented to the emergency department of his local hospital with a 1-year history of fatigue, weight loss, and constipation. He had abused alcohol for many years, and his symptoms were initially attributed to alcoholism. On physical examination, he was confused, his blood pressure was normal, he had no palpable neck masses, and his liver was enlarged. His serum calcium concentration was 4.2 mmol/l and his serum parathyroid hormone concentration was 36 pmol/l. CT-guided biopsy of a liver lesion showed large neoplastic cells, and fine-needle aspiration of the neck showed cells similar to those in the liver. The patient was treated with intravenous saline, pamidronate, and zoledronic acid. He was referred to our hospital on day 35 for treatment of refractory hypercalcemia. INVESTIGATIONS: Sestamibi parathyroid scan, chest and abdominal CT scans, neck ultrasonography, liver biopsy, fine-needle aspiration of neck mass, and measurement of parathyroid hormone in an aspirate of the neck mass. DIAGNOSIS: Primary hyperparathyroidism caused by metastatic parathyroid carcinoma. MANAGEMENT: Intravenous fluids, intravenous doses of pamidronate and zoledronic acid and oral cinacalcet therapy.

Adenocarcinoma↗
PubMed1985

Parathyroid carcinoma: the Lahey Clinic experience.

From 1942 to 1984, 301 operations were performed for hyperparathyroidism; nine patients (3%) had carcinoma. The mean serum calcium level of the patients with carcinoma was 14.0 mg/dl, whereas the mean serum calcium level of patients with benign hyperparathyroidism was 12.0 mg/dl. With follow-up ranging from 2 to 16 years, there has been one death 9 years after the initial operation caused by primary lung cancer. At autopsy the patient also had a recurrence of parathyroid carcinoma in the neck. There were no additional recurrences or deaths. Prognosis was not correlated with any laboratory or pathologic findings. The importance of intraoperative recognition at the time of the initial operation is stressed. En bloc resection is recommended, including ipsilateral thyroid lobectomy and dissection of the tracheoesophageal groove. Radical neck dissection is performed only for extensive cervical node metastases or for reoperations where scarring prevents accurate delineation of the extent of the tumor.

Adult↗