CYP2D6 Genetic Polymorphisms and Phenotypes in Different Ethnicities of Malaysian Breast Cancer Patients.

The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. In Malaysia, the knowledge on CYP2D6 genetic polymorphisms as well as metabolizer status in Malaysian breast cancer patients remains unknown. Hence, this study aimed to comprehensively identify CYP2D6 genetic polymorphisms among 80 Malaysian breast cancer patients. The genetic polymorphisms of all the 9 exons of CYP2D6 gene were identified using high-resolution melting analysis and confirmed by DNA sequencing. Seven CYP2D6 alleles consisting of CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*10, CYP2D6*39, CYP2D6*49, and CYP2D6*75 were identified in this study. Among these alleles, CYP2D6*10 is the most common allele in both Malaysian Malay (54.8%) and Chinese (71.4%) breast cancer patients, whereas CYP2D6*4 in Malaysian Indian (28.6%) breast cancer patients. In relation to CYP2D6 genotype, CYP2D6*10/*10 is more frequently observed in both Malaysian Malay (28.9%) and Chinese (57.1%) breast cancer patients, whereas CYP2D6*4/*10 is more frequently observed in Malaysian Indian (42.8%) breast cancer patients. In terms of CYP2D6 phenotype, 61.5% of Malaysian Malay breast cancer patients are predicted as extensive metabolizers in which they are most likely to respond well to tamoxifen therapy. However, 57.1% of Chinese as well as Indian breast cancer patients are predicted as intermediate metabolizers and they are less likely to gain optimal benefit from the tamoxifen therapy. This is the first report of CYP2D6 genetic polymorphisms and phenotypes in Malaysian breast cancer patients for different ethnicities. These data may aid clinicians in selecting an optimal drug therapy for Malaysian breast cancer patients, hence improve the clinical outcome of the patients.

Diagnostic challenges in fine needle aspiration cytology of salivary gland lesions.

BACKGROUND: Fine needle aspiration cytology (FNAC) has been widely accepted as a safe method for diagnosis of salivary gland lesions and its accuracy is increased with increasing the experience of the physician. This study was conducted to examine the sensitivity, specificity and accuracy of FNAC of salivary gland lesions by cyto-histological correlation and to identify the discrepancies that contribute to false diagnoses. METHOD: A retrospective study was carried out over a 7-year period from 2003 to 2009 to review the cases of patients with salivary gland lesions who underwent FNAC with histopathological confirmation. RESULTS: A total of 101 cases had cytological correlation of whom 76 (75.3%) were neoplastic (58.4% benign, 16.8% malignant) and 25 (24.7%) were nonneoplastic. Pleomorphic adenoma (PA) was the most frequent benign neoplasm while adenoid cystic carcinoma (ACC) was the most frequent malignant neoplasm. FNAC had a sensitivity of 80% and a specificity of 98.8% for overall benign and malignant diagnoses and positive predictive and negative predictive values of 92.3% and 96.4% respectively. The most common false negative cases were pleomorphic adenoma. CONCLUSIONS: This study demonstrated that FNAC of the salivary gland is a useful technique for diagnosis of salivary gland lesions. Combined with clinical and radiological findings, it can provide a preliminary assessment on which management decision can be based.

Hurthle cells in fine needle aspiration cytology of the thyroid: a potential diagnostic dilemma?

Hurthle cells are not uncommonly encountered in thyroid fine needle aspiration cytology (FNAC) smears. They are easily recognized by their distinct cytomorphology in cytological preparations, i.e. large, polygonal cells displaying uniform, rounded nuclei, often prominent nucleoli and abundant granular cytoplasm. Hurthle cells can be seen in both non-neoplastic and neoplastic thyroid lesions which can pose diagnostic dilemma to cytopathologists, especially when the lesions are focally sampled. We describe a case of solitary thyroid nodule in a 46-year-old male, whose aspirates comprised predominantly of Hurthle cells exhibiting nuclear features suspicious of papillary carcinoma, which turned out to be Hurthle cell carcinoma on subsequent histological sections. The potential diagnostic pitfalls of Hurthle cell lesions and associated conditions in thyroid FNA are discussed. The presence of Hurthle cell change in a wide variety of thyroid lesions can be diagnostically challenging. However, accurate diagnosis can still be made with careful observation of the predominant cell population, nuclear features and whether there is abundant colloid or lymphocytes in the background.