Thymic pathological examination of non-thymomatous myasthenia gravis patients: A pilot study for prediction of outcome.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder characterized by weakness and fatigability of skeletal muscles. The aim of this study was to determine if pathological characteristics in non-thymomatous patients of MG would correlate with prognosis in a three year follow up. METHODS: Patients who had had their thymectomy at least three years prior to the study were selected from three hospitals and were followed for 3 years. Prognosis was assessed via a devised prognostic scoring system. A pathological exam of the specimen from the thymus was done using the following immunohistochemical markers: Bcl2, CD 3, CD 4, CD 5, CD 7, CD 10, CD 20cy, CD 23, CD 43, and Ki67. RESULTS: Fifteen patients fulfilled the inclusion criteria and had a complete follow-up. This included 3 males and 12 females with a mean age of 36.6 years at the start of the study. The dominant cell population was T lymphocytes. All T cells expressed CD 3, CD 43, CD 5, and Bcl-2. In 2 patients, CD 10 marker was positive in T cells. B cells were negative for activation marker CD 23, except for germinal center dendritic cells. Due to the limited number of patients in the study, the power of the study would not allow for an analysis to assess correlation between histopathological data and prognosis. CONCLUSION: This pilot study was an attempt to discover any prognostic indices from the histopathological examination of the resected thymic tissue in the patients with myasthenia gravis.

Incidental finding of bilateral papillary thyroid carcinoma in a patient with primary hyperparathyroidism.

Primary hyperparathyroidism (PHP) affects 0.5%-1% of the adult population and presents with classical signs of renal lithiasis, cholecystolithiasis, gastrointestinal ulcerations, depression, and osteoporosis. Parathyroid adenoma, hyperplasia and rarely carcinoma are the underlying pathology. Synchronous thyroid and parathyroid pathologies are described in multiple endocrine neoplasia. We report a case of a 47 years old woman with non-syndromic concomitant occurrence of bilateral non-medullary thyroid carcinoma diagnosed by histopathology, and with PHP confirmed by (99m)Tc-MIBI scintigraphy, hypercalcemia and elevated serum parathyroid hormone. A head and neck surgeon needs to be aware of the possible coexistence of thyroid and parathyroid lesions. To our knowledge, this is the first report of concomitant PHP and bilateral papillary thyroid cancer in the literature. In conclusion, it is optimal to remove both tumors in one operative procedure. Therefore careful thyroid evaluation should be considered for all patients with PHP.

Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status.

AIM: To evaluate joint effects of Methylentetra-hydrofolate reductase (MTHFR) C677T genotypes, and serum folate/vitamin B(12) concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS: We examined the associations between MTHFR C677T genotype, and promoter methylation of P16, hMLH1, and hMSH2 tumor-related genes among 151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B(12) concentrations by a commercial radioimmunoassay kit. RESULTS: We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison, we did not find a significant association between methylation in tumors and any single genotype. However, in comparison to controls with the CC genotype, an increased risk of tumor methylation was associated with the CT genotype (OR = 2.5; 95% CI, 1.1-5.6). In case-case comparisons, folate/vitamin B(12) levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high (above median) versus low (below median) serum folate/vitamin B(12) levels were 4.9 (95% CI, 1.4-17.7), and 3.9 (95% CI, 1.1-13.9), respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group, especially in those with MTHFR CT (P = 0.01), and CT/TT (P = 0.002) genotypes, but not in those with the CC genotype (P = 1.0). CONCLUSION: We conclude that high concentrations of serum folate/vitamin B(12) levels are associated with the risk of promoter methylation in tumor-specific genes, and this relationship is modified by MTHFR C677T genotypes.