BRAF mutation in cytologically indeterminate thyroid nodules: after reclassification of a variant thyroid carcinoma.

PURPOSE: Fine-needle aspiration biopsy (FNAB) is regarded by the Bethesda system as the gold-standard investigation for stratifying the risk of malignancy of a thyroid nodule. However, some limitations affect the adequacy of the obtained materials, resulting in 30% of the cytological results remaining in the indeterminate category. We aimed to investigate the diagnostic value of the BRAF mutation in cytologically indeterminate thyroid nodules after the reclassification of a variant thyroid carcinoma. PATIENTS AND METHODS: In this prospective diagnostic study, 76 patients with FNAB findings of atypia of undetermined significance (AUS) and suspicious for malignancy (SUS) were included. The BRAF V600 mutation from FNAB was confirmed by a PCR-based method (Sanger sequencing combined with allele-specific real-time PCR techniques) and immunohistochemistry (IHC). Pathological specimens and features, including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), were reviewed and compared to the FNAB results. RESULTS: Using the PCR-based method, the BRAF mutation was positive in 13/76 cases (17.1%), with the diagnostic values of 16.7% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 82.8% negative predictive value (NPV) in the AUS compared to 73.3% sensitivity, 100% specificity, 100% PPV, and 20% NPV in the SUS. For the IHC technique, only 20 of the 76 cytological specimens were qualified for testing. The BRAF mutation was positive in 13/20 cases, with the diagnostic values of 100% sensitivity, 63.6% specificity, 42.9% PPV, and 100% NPV in the AUS compared to 100% sensitivity and PPV in the SUS. The BRAF mutation was not found in the pathological reports for NIFTP. CONCLUSION: The malignancy rate is high in our data, with specific and acceptable accuracy rates for the BRAF mutation from FNAB found by using the PCR-based method. NIFTP has been introduced after the pathological reclassification. Molecular diagnosis might be useful to establish the nature of the disease.

Expression levels of miR-34-family microRNAs are associated with TP53 mutation status in head and neck squamous cell carcinoma.

PURPOSE: The majority of head and neck squamous cell carcinoma (HNSCC) cases in developing countries are associated with cigarette smoking and TP53 mutations. p53 is a transcription factor that activates downstream genes, including the hsa-miR-34a and hsa-miR-34b/c loci, to achieve cell-cycle arrest, senescence, and/or apoptosis. This study examined the differences in expression levels of miR-34 in HNSCC with or without TP53 mutations. METHODS: We examined surgically resected tumor samples and normal adjacent tissues from HNSCC in oral cavity, larynx, and hypopharynx for TP53 mutations (exons 5-8) and miR-34 expression levels. RESULTS: miR-34a, miR-34b, miR-34b*, and miR-34c are significantly up-regulated in tumors with wild-type TP53 genes (n = 23); while such up-regulation is not observed in tumors with mutant TP53 (n = 19). Although expression levels of miR-34-family miRNAs do not correlate with gender, age, or tumor staging, interestingly they are correlated with smoking status and tumor sites. miR-34b/b*/c are up-regulated in tumors from those who ever smoked or recently smoked (quit smoking less than 15 years ago); but such up-regulation was not seen in those who never smoked or quit smoking for at least 15 years. HNSCC of the oral cavity also up-regulated miR-34b/b*/c while no such overexpression was observed in HNSCC of the larynx and hypopharynx. CONCLUSIONS: Surgically resected HNSCC samples with no TP53 mutations have elevated levels of miR-34a and miR-34b/b*/c, while those with TP53 mutations show no such up-regulation. miR-34b/b*/c expression is also correlated with smoking status and tumor sites.

Pathological confirmed diagnosis of asbestosis: the first case report in Thailand.

Asbestosis is an occupational lung disease defined as pulmonary fibrosis caused by asbestos. Asbestosis was previously reported in Thailand based on radiologic findings, which demonstrated interstitial lung with calcified pleural plaques, and the patient worked in a fiber cement factory. However there was some doubt about the diagnosis because clinical and radiological findings are nonspecific; there was no data support of asbestos exposure in the patient and no histologic confirmed diagnosis. Histologic diagnosis is most useful when an equivocal of ahistory of asbestos exposure in patients with interstitial lung diseases take place. The authors report a patient presenting with progressive dyspnea for 2 years. She worked in an electric, wire, mesh fan cover factory to check quality of protective wire mesh for 10 years until the factory was closed 6 years ago. This type of factory had never officially reported asbestos use. Her clinical manifestations and radiologic findings are compatible with interstitial lung disease. She subsequently underwent thoracotomy with wedge lung resection. Pathology revealed interstitial fibrosis with honeycombing. Asbestos bodies were found more than 10 per cm2 in the fibrosis. She was diagnosed asbestosis. The patient is suffering from dyspnea, severe hypoxemia and cor pulmonale. The patient is put on waiting lists for heart lung transplantation. The authors thus confirmed that asbestosis exists in Thailand. A policy to protect workers and people who may have risk of asbestos exposure is necessary, since diseases related to asbestos are incurable, but preventable.