Context The prevalence of thyroid nodules in the general population is increasingly high, and at least half of those biopsied prove to be benign. Sonographic risk-stratification systems are being proposed as “rule-out” tests that can identify nodules that do not require fine-needle aspiration (FNA) cytology. Objective To comparatively assess the performances of five internationally endorsed sonographic classification systems [those of the American Thyroid Association, the American Association of Clinical Endocrinologists, the American College of Radiology (ACR), the European Thyroid Association, and the Korean Society of Thyroid Radiology] in identifying nodules whose FNAs can be safely deferred and to estimate their negative predictive values (NPVs). Design Prospective study of thyroid nodules referred for FNA. Setting Single academic referral center. Patients Four hundred seventy-seven patients (358 females, 75.2%); mean (SD) age, 55.9 (13.9) years. Main Outcome Measures Number of biopsies classified as unnecessary, false-negative rate (FNR), sensitivity, specificity, predictive values, and diagnostic ORs for each system. Results Application of the systems’ FNA criteria would have reduced the number of biopsies performed by 17.1% to 53.4%. The ACR Thyroid Imaging Reporting and Data System (TIRADS) allowed the largest reduction (268 of 502) with the lowest FNR (NPV, 97.8%; 95% CI, 95.2% to 99.2%). Except for the Korean Society of Thyroid Radiology TIRADS, all other systems exhibited significant discriminatory performance but produced significantly smaller reductions in the number of procedures. Conclusions Internationally endorsed sonographic risk stratification systems vary widely in their ability to reduce the number of unnecessary thyroid nodule FNAs. The ACR TIRADS outperformed the others, classifying more than half the biopsies as unnecessary with a FNR of 2.2%.

To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only.[12] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower.[345] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy.[67] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM.

With stringent negativity cut-offs, American Thyroid Association and Thyroid Imaging Reporting and Data System assessment of cytologically indeterminate thyroid nodules allows high-confidence exclusion of malignancy.

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41BAP1 germline mutations predispose to a cancer predisposition syndrome that includes 42 mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence 43 suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we 44 studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for 45BAP1and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF 46 and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. 47In two out of six families with both mesothelioma and melanoma we identified either a germline 48 nonsense mutation (c.1153C>T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation 49 (c.301G>T, p.Gly101Trp) in CDKN2A. 50Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and 51 mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that 52 these tumors share key steps that drive carcinogenesis and that other genes may be involved in 53 inherited predisposition to malignant mesothelioma and melanoma.