Diagnosis and treatment of nail melanoma: a review of the clinicopathologic, dermoscopic, and genetic characteristics.

Nail melanoma (NM) is an important differential diagnosis in patients with longitudinal melanonychia. However, diagnosis is often challenging as it is difficult to differentiate from other pigmented nail disorders. The main challenge for diagnosis is obtaining adequate nail matrix biopsy specimens for histopathological assessment. Furthermore, the histopathological changes in the early stages of NM are subtle and contribute to a delay in diagnosis and care. Therefore, the integration of clinical and histopathological analyses is essential. Clinical and dermoscopic features, such as a broadened width of asymmetric bands in an irregular pattern, with multicolour pigmentation, periungual pigmentation, and continuous growth, are features that support the diagnosis of NM. The essential histological features that must be assessed are cellular morphology, architectural features, melanocyte density, and inflammatory changes. The reported mutations in NMs were BRAF (0-43%), NRAS (0-31%), KIT (0-50%), NF1 (0-50%), and GNAQ (0-25%). Surgery is the primary treatment for NM. The recommended treatment for in situ or minimally invasive NM is functional surgery, but cases with suspected bone invasion should be treated with amputation. Targeted therapy and immunotherapy are indicated for advanced stages of NM. This review summarizes the updated guidelines for the diagnosis and treatment of NM.

Germline mutations and genotype-phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea.

The aim of our study was to assess the frequency of germline mutations and develop the genetic testing strategy in patients with apparently sporadic pheochromocytoma/paraganglioma (PPGL) in Korea. We included 53 patients diagnosed with non-syndromic PPGL without a family history of PPGLs in three referral centers from 2004 to 2011. Succinate dehydrogenase complex B (SDHB), SDHD, Von Hippel-Lindau (VHL), and rearranged during transfection (RET) genes were examined by direct sequencing and multiple ligation-dependent probe amplification. The study patients were composed of 26 men and 27 women, and mean age was 50.1 ± 13.5 years. The frequency of germline mutations was 13.2% (7/53): RET (n = 2), VHL (n = 1), SDHB (n = 2), and SDHD (n = 2). Six of seven mutation carriers were diagnosed before the age of 50. One of two patients harboring an SDHB mutation had malignant PPGLs. One patient with multifocal head and neck paraganglioma (PGL) and pheochromocytoma (PHEO) carried a SDHD mutation. The carriers of germline mutations in patients with apparently sporadic PPGL were 13.2% in our study. We recommend genetic testing in patients below 50 years and SDHD genetic testing in patients with multifocal PPGLs. In malignant PPGLs, SDHB genetic testing may be performed.

Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.

OBJECTIVE: To determine the diagnostic accuracy of the Xpert® MTB/RIF assay using samples obtained through bronchoscopy in patients with suspected pulmonary tuberculosis (PTB). DESIGN: We retrospectively reviewed the records of patients with suspected PTB for whom the Xpert MTB/RIF assay was performed on bronchoscopy specimens. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of active PTB were calculated for acid-fast bacilli (AFB) smear microscopy and the Xpert assay using culture of Mycobacterium tuberculosis from sputum or bronchoscopy specimens as a reference standard. RESULTS: A total of 132 patients were included in the final analysis. Of these, 38 had culture-confirmed PTB. The sensitivity of the Xpert assay using bronchial washing or bronchoalveolar lavage (BAL) fluid for the diagnosis of PTB was 81.6%, and specificity was 100%. The PPV and NPV were 100% and 92.1%, respectively. The sensitivity and specificity of AFB smear microscopy were respectively 13.2% and 98.8%. CONCLUSION: The Xpert assay on bronchoscopy specimens provided an accurate diagnosis of PTB in patients who had a negative AFB smear or who could not produce sputum.

Effect of active smoking on asthma symptoms, pulmonary function, and BHR in adolescents.

BACKGROUND: Active smoking is known to increase asthma symptoms and bronchial hyper-responsiveness (BHR) while decreasing pulmonary function in adults, but few studies have addressed these issues in adolescents. METHODS: We conducted a cross-sectional survey involving questionnaires and assessment of urinary cotinine levels among 1,492 adolescents from three urban areas of South Korea. Current smoking was defined as having smoked more than 1 day in the prior 30 days or having urine cotinine levels >or=100 ng/ml. Spirometry, skin tests, and methacholine challenge tests were performed on adolescents in Seoul (n = 724). RESULTS: The prevalence of current smoking was 8.2% in boys and 2.4% in girls. Reports of wheeze and exercise-induced wheeze in the previous 12 months were more frequent in smokers than nonsmokers (15.2% vs. 8.5%, P = 0.024, and 20.4% vs. 10.7%, P = 0.004, respectively). In multiple logistic regression analysis, current smoking was found to be a significant risk factor for having wheezed in previous 12 months (OR = 4.5, 95% CI 1.5-13.2) and having exercise-induced wheezing in previous 12 months (OR = 8.7, 95% CI, 3.7-20.9). The subgroup analysis revealed that the FEV(1)/FVC was lower in smokers than nonsmokers (mean +/- SD, 105.1 +/- 8.6% vs. 107.8 +/- 7.8%, P = 0.019). In contrast, there was no significant difference in BHR. The effect of smoking on asthma symptoms were more pronounced in non-atopic compared with atopic adolescents. CONCLUSION: Current smoking was significantly associated with symptoms of asthma, such as having recent wheezing and recent exercise-induced wheezing, especially for non-atopics, in Korean adolescent population. Current smoking was further associated with lower pulmonary function, but not BHR.

Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation.

The BRCA1 and BRCA2 genes are the strongest susceptibility genes identified for breast cancer worldwide. However, BRCA1/BRCA2 have been incompletely investigated due to their large size and the genomic rearrangements that occasionally occur within them. Here we performed a comprehensive mutational analysis for BRCA1/BRCA2 in 206 Korean patients with breast cancer. We analyzed all exons and flanking regions of BRCA1/BRCA2 by direct sequencing and screened deletions or duplications involving BRCA1/BRCA2 by multiplex ligation-dependent probe amplification. We reconstructed haplotypes using intragenic single nucleotide polymorphisms (SNPs) to investigate the possibility of a founder effect among recurrent mutations. In our series, 38 patients (18.4%) had one or more BRCA1/BRCA2 mutations including 10 novel ones. Three additional patients carried novel distinct unclassified variants with potentially harmful effects. No large deletions or duplications involving BRCA1/BRCA2 were identified in our series. Haplotype analyses and allele separation suggested that the most frequent mutation in Koreans, BRCA2:c.7480C>T, might have originated from a common ancestor. BRCA1/BRCA2 mutations were more frequent in a group with family history, bilateral cancer or multiple site cancer than in a group without the risk factors described or an unknown risk group. In contrast, mutation frequencies in the early-onset cancer group were not higher than in the unknown risk group. Our results will be helpful to understand the mutation spectrum in BRCA1/BRCA2 genes and establish a genetic screening strategy. In addition, this study suggests the possibility of the first true founder mutation of BRCA1/BRCA2 identified in the Korean population.