Orlo H. Clark

BACKGROUND: It is frequently difficult to establish histologically whether a parathyroid tumor is a parathyroid carcinoma, parathyromatosis, or an atypical adenoma. The authors asked whether these tumors have a distinctive molecular profile, whether benign tumors could be distinguished from malignant tumors, and whether parathyromatosis is a low‐grade parathyroid carcinoma or is benign tissue that can invade other organs.METHODS: Samples of parathyroid carcinoma, atypical adenoma, parathyromatosis, parathyroid adenoma, and hyperplasia were obtained for tissue microarray studies. The molecular expression of genes involved in parathyroid tumor progression (HRPT2 [“parafibromin”], galectin‐3, Ki‐67, Rb, p27, and mdm‐2) was investigated by immunohistochemistry.RESULTS: Complete loss of parafibromin expression was seen in 5 of 16 (31.3%) parathyroid carcinomas; all parathyromatosis, atypical adenomas, adenomas, and hyperplasia stained positive for parafibromin. Loss of Rb expression was seen in 5 (33.3%) of 15 parathyroid carcinomas and 1 (7.1%) of 14 parathyroid hyperplasias; all parathyromatosis, atypical adenomas, and adenomas stained positive. Galectin‐3 stained strongly positive in 14 (93.3%) of 15 parathyroid carcinomas, and positive in 3 (18.7%) of 16 cases of parathyromatosis, 2 (100%) of 2 atypical adenomas, 1 (5.6%) of 18 adenomas, and 2 (14.3%) of 14 hyperplasias. The Ki‐67 proliferative index was high in 9 (60%) of 15 parathyroid carcinomas, 1 (6.7%) of 15 cases of parathyromatosis, 1 (5.6%) of 18 adenomas, and no atypical adenomas or hyperplasia. P27 and mdm‐2 protein expression did not differ appreciably among the tumor types.CONCLUSIONS: No single diagnostic marker currently determines whether a parathyroid tumor is a parathyroid carcinoma, but loss of parafibromin and Rb expression, and overexpression of galectin‐3, generally distinguish parathyroid carcinoma from other parathyroid tumors. Parathyromatosis does not appear to be a low‐grade parathyroid carcinoma. Cancer 2009. © 2009 American Cancer Society.

By Dina M Elaraj, MD; Orlo H Clark, MD Winter 2008 - Volume 12 Number 1 Abstract Primary hyperparathyroidism (HPT) is diagnosed in approximately 100,000 patients in the US each year, with a 2-3:1 female-to-male distribution. In most cases, occurrence

The incidence of thyroid cancer has been increasing over the past 30 years, and it is now the seventh most common cancer in women. Papillary thyroid cancer is the most common subtype of thyroid cancer, occurring in 80% of cases. Its main pattern of spread is to cervical lymph nodes, with distant metastases occurring uncommonly. Initial treatment of papillary thyroid cancer involves resection of the primary tumor, with resection of regional lymph nodes if involved with metastatic disease. Postoperative adjuvant therapy consists of radioactive iodine ablation for most patients, followed by thyroid-stimulating hormone (TSH) suppression with thyroxine. An ongoing controversy in the surgical treatment of papillary thyroid cancer is that of extent of thyroid gland and nodal resection. Consensus guidelines recommend total or near-total thyroidectomy, rather than thyroid lobectomy, as the initial procedure of choice, given its advantages of treating potential multicentric disease, facilitating maximal uptake of adjuvant radioactive iodine, and facilitating the post-treatment follow-up by monitoring serum thyroglobulin (Tg) levels. In the hands of an experienced endocrine surgeon, complication rates are comparable to those for lobectomy. Major changes in the management of patients with papillary thyroid cancer over the last 10 years include the use of preoperative neck ultrasound, which can detect nonpalpable cervical lymph node metastases and potentially change the initial operation. In addition, neck ultrasound and measurement of serum Tg levels have taken the place of routine whole body radioactive iodine scans in the postoperative follow-up of patients with papillary thyroid cancer. Recurrent locoregional cervical lymph node disease should be treated by compartmental lymph node dissection, followed by another treatment dose of radioactive iodine. Chemotherapy is generally ineffective for the treatment of metastatic disease. For those patients whose tumor has become radioactive iodine resistant, emerging therapies include redifferentiation agents, antiangiogenic agents, and multi-tyrosine kinase inhibitors.

BACKGROUND.: Parathyroid carcinoma, atypical parathyroid adenoma, and parathyromatosis can be differentiated relatively easily from typical parathyroid adenomas, but distinguishing them from each other is more difficult.METHODS.: A retrospective study of 28 consecutive patients with parathyroid carcinoma, 7 patients with atypical parathyroid adenoma, and 13 patients with parathyromatosis who were treated at the University of California at San Francisco Medical Center between 1966 and 2005 was performed. Patient demographics and clinical characteristics, indication for surgery, intraoperative findings, histopathologic characteristics, disease recurrence or persistence, site of invasion/metastases, and survival were compared in the 3 groups.RESULTS.: Parathyroid carcinoma (19 of 28 patients) and atypical adenoma (4 of 7 patients) were significantly more common in men, whereas parathyromatosis was more common in women (10 of 13 patients) (P = .02). A palpable neck mass and hoarseness were almost exclusively present in patients with parathyroid carcinoma. Prior to the first parathyroid surgery, patients with parathyroid carcinoma were found to have higher blood calcium levels (≥14 mg/dL in 16 of 26 patients [62%]), whereas only 1 of 6 patients with atypical adenoma (17%) and no patients with parathyromatosis were found to have profound hypercalcemia (P < .01). Intraoperatively, patients with parathyroid carcinoma and atypical adenoma presented with single lesions, whereas patients with parathyromatosis had multiple small lesions. Histopathologic findings were well defined in parathyroid carcinoma, but some findings overlapped in the 3 tumors studied.CONCLUSIONS.: Patients with parathyroid carcinoma often differ from those with atypical parathyroid adenoma or parathyromatosis at the time of presentation because patients with parathyroid carcinoma have more profound hypercalcemia as well as invasive tumors. However, at times it is difficult to distinguish between these conditions both clinically and by final histologic examination. Cancer 2007. © 2007 American Cancer Society.