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An extremely rare case of synchronous parathyroid and papillary thyroid carcinoma is reported for a patient presenting with hyperparathyroidism. This case is the first reported in the English literature of hyperfunctioning parathyroid carcinoma and concomitant thyroid carcinoma without a previous history of neck irradiation.
BACKGROUND: The incidence of endocrine carcinomas is about 5.3 persons per 100,000 population. Most frequent are malignancies of the thyroid gland (about 89%). THERAPY: Because of low incidences and missing prospective studies as well as radiotherapy and chemotherapy resistance, general accepted therapy guidelines for endocrine carcinomas are still missing. Surgery and radionucleotide treatment is generally the first-line therapy. Hormonal active carcinomas can be additionally treated with special substances such as octreotide and mitotane. Chemotherapy is frequently not effective. Widely used substances are cyclophosphamide, cisplatin, doxorubicine, dacarbazine, vincristine and etoposide. This first part of the review will present medical therapies of thyroid carcinomas, adrenal carcinomas and parathyroid carcinomas. The second part in one of the next issues will focus on less frequent endocrine carcinomas of the gastrointestinal tract.
Three cases of parathyroid neoplasms in familial hyperparathyroidism are reported. There were not associated with other endocrine glands or parathyroid glands lesions. Parathyroid gland carcinoma was diagnosed in 2 cases. Review of 7 cases of familial parathyroid carcinoma, diagnosed in 5 different families and issued from the literature, indicates that it can be associated to multiple endocrine neoplasia or other parathyroid lesions. The familial parathyroid carcinoma entity needs further studies before to be fully recognised.
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OBJECTIVE: The nm23 gene was initially cloned as a metastasis suppressor gene, but the clinical relevance of nm23 as a metastasis suppressor or prognostic indicator for human cancers remain controversial. To evaluate the role of nm23 protein as a prognostic factor and its role in parathyroid neoplasia, we studied nm23 protein expression by immunohistochemical staining in parathyroid lesions. METHODS: Immunohistochemistry using the avidin-biotin peroxidase complex technique with a polyclonal antibody against the nm23 protein was applied to formalin-fixed, paraffin-embedded tissue specimens obtained from 48 patients. The specimens were collected from 38 patients at the University Health Network, Toronto, Canada and from 10 Saudi patients at the King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. They included parathyroid carcinomas (5 cases), adenomas (22 cases), hyperplasia (21 cases), and normal parathyroid tissue (10 cases). The immunohistochemistry was completed in 2003 at King Abdul-Aziz University Hospital, Jeddah, KSA and University Health Network, Toronto, Canada. RESULTS: Expression of nm23 protein was noted in adenomas and carcinomas as well as in hyperplastic parathyroid glands and there was no significant statistical difference between these groups. Normal parathyroid glands did not show any intense immunoreactivity. CONCLUSION: The results suggest that expression of nm23 in parathyroid lesions is correlated with tumor proliferation rather than suppression of invasion and metastasis. While our data suggest that nm23 may help in the distinction of normal from proliferative parathyroids, these results do not point to nm23 as a reliable prognostic marker in parathyroid lesions.
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BACKGROUND: Parathyroid hormone-related protein (PTHrP) has been shown to be the principal cause of humoral hypercalcemia associated with renal cell carcinoma (RCC). Recent studies have demonstrated that the amino-terminal region of PTHrP has growth factor-like activities, suggesting it may play a role in the development of RCC. In this study, expression of the carboxy-terminal region of PTHrP was assessed immunohistochemically and its significance in predicting the prognosis of RCC was studied. METHODS: Forty radical nephrectomy specimens were immunostained with a murine monoclonal antibody (9H7) against the carboxy-terminal region (amino acids 109-141) of PTHrP using the streptavidin-peroxidase enzyme conjugate method. Staining intensity was evaluated semiquantitatively and compared with clinicopathologic features of the corresponding RCC. RESULTS: Immunoreactivity to 9H7 was observed to be localized to the cytosol of tumor cells at various staining intensities. There were 30 cases (75.0%) with strong staining and 10 cases (25.0%) in which staining was weak or nonexistent. Staining intensity showed no significant correlation with gender, tumor greatest dimension, stage, or grade. Tumors of the clear cell type expressed PTHrP to a significantly greater extent than tumors of the granular cell type. Tumor recurrence was significantly greater in the weakly stained or unstained group compared with the strongly stained group (P = 0.035). Multivariate analysis indicated that PTHrP expression and tumor stage were equally significant prognostic indicators in RCCs measuring <10 cm in greatest dimension. CONCLUSIONS: Evident PTHrP(109-141) expression is present in the majority of RCCs. The results of the current study indicate PTHrP(109-141) may be a possible marker of cellular differentiation and may be useful for predicting recurrence free survival in RCC patients after radical nephrectomy.
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An autopsy case of a 61 year old male with primary squamous cell carcinoma of the lung with associated marked leukocytosis and hypercalcemia is reported. High levels of serum parathyroid hormone-related peptide (PTHrP) and granulocyte colony stimulating factor (GCSF) were detected. The tumor cells distinctly showed positive cytoplasmic immunoreactions with anti-PTHrP and anti-GCSF antibodies. Marked granulocytosis and thin bony trabeculae lacking osteoblasts were observed in the vertebral bone. Calcium deposits were found in the proximal tubules of the kidneys. Infarcts were seen as a result of fibrin thrombosis of the splenic artery. The tumor was successfully transplanted into nude mice in which the high levels of serum PTHrP and GCSF were reproduced. These results indicate that the tumor simultaneously produced both PTHrP and GCSF causing the paraneoplastic syndromes of hypercalcemia and leukocytosis.
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BACKGROUND: Parathyroid hormone-related protein (PTHrP) is the predominant cause of humoral hypercalcemia of malignancy (HHM). METHODS: Using a PTHrP-specific monoclonal antibody (MoAb), 4B3, the authors investigated the immunohistochemical localization of PTHrP in formalin-fixed and paraffin-embedded sections of normal human kidney tissues and tissues from 42 human renal cell carcinomas obtained at operation or autopsy. RESULTS: In normal renal tissues, the distal tubules and collecting ducts showed positive immunostaining. PTHrP was detected in 40 of 42 renal cell carcinoma tissues (95%). Histopathologically, the granular cell subtypes of renal cell carcinomas tended to be more strongly positive than the clear cell subtypes. There was no significant correlation between the level of immunostaining and each patient's serum calcium level. CONCLUSION: PTHrP was commonly observed in renal cell carcinomas, and no significant correlation was seen between the intensity of PTHrP staining and the serum calcium level.