Chronic myeloid neoplasms harboring concomitant mutations in myeloproliferative neoplasm driver genes (JAK2/MPL/CALR) and SF3B1.

JAK2, CALR, and MPL are myeloproliferative neoplasm (MPN)-driver mutations, whereas SF3B1 is strongly associated with ring sideroblasts (RS) in myelodysplastic syndrome (MDS). Concomitant mutations of SF3B1 and MPN-driver mutations out of the context of MDS/MPN with RS and thrombocytosis (MDS/MPN-RS-T) are not well-studied. From the cases (<5% blasts) tested by NGS panels interrogating at least 42 myeloid neoplasm-related genes, we identified 18 MDS/MPN-RS-T, 42 MPN, 10 MDS, and 6 MDS/MPN-U cases with an SF3B1 and an MPN-driver mutation. Using a 10% VAF difference to define "SF3B1-dominant," "MPN-mutation dominant," and "no dominance," the majority of MDS/MPN-RS-T clustered in "SF3B1-dominant" and "no dominance" regions. Aside from parameters as thrombocytosis and ≥15% RS required for RS-T, MDS also differed in frequent neutropenia, multilineage dysplasia, and notably more cases with <10% VAF of MPN-driver mutations (60%, p = 0.0346); MPN differed in more frequent splenomegaly, myelofibrosis, and higher VAF of "MPN-driver mutations." "Gray zone" cases with features overlapping MDS/MPN-RS-T were observed in over one-thirds of non-RS-T cases. This study shows that concomitant SF3B1 and MPN-driver mutations can be observed in MDS, MPN, and MDS/MPN-U, each showing overlapping but also distinctively different clinicopathological features. Clonal hierarchy, cytogenetic abnormalities, and additional somatic mutations may in part contribute to different disease phenotypes, which may help in the classification of "gray zone" cases.

Comparison of Molecular Methods and BRAF Immunohistochemistry (VE1 Clone) for the Detection of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis.

The evaluation of surgically resected papillary thyroid carcinomas (PTC) by immunohistochemistry (IHC) for BRAF mutation has diagnostic, prognostic and therapeutic implications. The goal of this meta-analysis was to perform a systematic review of studies using the VE1 clone (specific for detection of the BRAF V600E mutation) on formalin-fixed paraffin embedded (FFPE) thyroid surgical resection specimens for primary papillary thyroid carcinoma. The authors' molecular techniques, immunohistochemistry protocols, and scoring methods for VE1 immunostaining were also evaluated. This study included 4079 PTCs representing data from 23 studies. The results extracted from each study were split into two different groups, direct sequencing group or PCR group, based on the molecular "gold standard" method used to compare VE1 IHC staining. In the direct sequencing group, the IHC sensitivity was 100% (95% CI 0.97-1.00) and specificity 84% (95% 0.72-0.91). In the PCR group the sensitivity was 98% (95% CI 0.96-0.99) and specificity 89% (95% CI 0.82-0.94). Although immunohistochemical procedures varied by author, the overall performance of the VE1 clone shows that it is highly sensitive and relatively specific for detecting the BRAF V600E mutation in surgical resection specimens. However, standardization of immunohistochemical procedural method and scoring/interpretation criteria may improve the reliability and reproducibility for the use of VE1 clone for future practice.

Comparison of 3 Nucleic Acid Amplification Tests and a Rapid Antigen Test with Culture for the Detection of Group A Streptococci from Throat Swabs.

BACKGROUND: Recently, the US Food and Drug Administration cleared 3 nucleic acid amplification test (NAAT) assays for detection of Streptococcus pyogenes [group A Streptococcus (GAS)] in pharyngeal specimens. However, there are limited studies evaluating the performance of these NAAT assays. METHODS: We compared the results of 3 NAATs (cobas Liat, Luminex Aries, and Cepheid Xpert Xpress) and a rapid antigen assay (Quidel QuickVue in-line strep A) with the accepted gold standard method, bacterial culture. RESULTS: Sixty-eight throat swab specimens collected between August and October 2017 were tested. Compared to bacterial culture, the sensitivities, specificities, positive predictive value, and negative predictive value for detecting GAS were as follows: cobas Liat: 100%, 97.4%, 96.7%, and 100%; Cepheid Xpert: 100%, 97.4%, 96.7%, and 100%; Luminex Aries: 95.2%, 100%, 100%, and 95.5%. The Quidel QuickVue in-line strep A assay showed poor sensitivity, detecting only 5.2% of culture-positive specimens. CONCLUSION: The 3 NAATs have high sensitivity when compared with bacterial culture for detection of GAS. With rapid turnaround time and ease of use, these tests can be considered as reliable point-of-care tests for the diagnosis of GAS, replacing the need for back-up culture.