Tumor PD-L1 IHC positivity in cytology specimens appears to correlate strongly with results obtained from matching surgical specimens. PD-L1 IHC in ICs within cytology specimens does not reflect results in matched surgical specimens and should not be used in clinical decision making. Cancer Cytopathol 2018;126:253-63. © 2018 American Cancer Society.

Resuscitation-promoting factors (Rpfs), apparent peptidoglycan hydrolases, have been implicated in the reactivation of dormant bacteria. We previously demonstrated that deletion of rpfB impaired reactivation of Mycobacterium tuberculosis in a mouse model. Because M. tuberculosis encodes five Rpf paralogues, redundant functions among the family members might obscure rpf single-knockout phenotypes. A series of rpf double knockouts were therefore generated. One double mutant, ⌬rpfAB, exhibited several striking phenotypes. Consistent with the proposed cell wall-modifying function of Rpfs, ⌬rpfAB exhibited an altered colony morphology. Although ⌬rpfAB grew comparably to the parental strain in axenic culture, in vivo it exhibited deficiency in reactivation induced in C57BL/6 mice by the administration of nitric oxide synthase inhibitor (aminoguanidine) or by CD4 ؉ T-cell depletion. Notably, the reactivation deficiency of ⌬rpfAB was more severe than that of ⌬rpfB in aminoguanidine-treated mice. A similar deficiency was observed in ⌬rpfAB reactivation from a drug-induced apparently sterile state in infected NOS2؊/؊ mice upon cessation of antimycobacterial therapy. Secondly, ⌬rpfAB showed a persistence defect not seen with the ⌬rpfB or ⌬rpfA single mutants. Interestingly, ⌬rpfAB exhibited impaired growth in primary mouse macrophages and induced higher levels of the proinflammatory cytokines tumor necrosis factor alpha and interleukin 6. Simultaneous reintroduction of rpfA and rpfB into the double-knockout strain complemented the colony morphology and macrophage cytokine secretion phenotypes. Phenotypes related to cell wall composition and macrophage responses suggest that M. tuberculosis Rpfs may influence the outcome of reactivation, in part, by modulating innate immune responses to the bacterium.Mycobacterium tuberculosis is a globally important human pathogen responsible for an overwhelming burden of disease (10,12,64). The pathogen is well suited for its niche within the human host, as the bacterium is able to enter a persistent and possibly dormant state within infected individuals. This clinically silent persistence can continue for decades, until host immune compromise, as by human immunodeficiency virus infection, steroid administration, or senescence, leads to overt disease. Since a significant proportion of the world's population harbors latent tubercle bacilli, understanding latency and reactivation at a molecular level is critical for devising improved strategies for tuberculosis treatment and control.Our understanding of the latent state remains limited due to both the paucibacillary state associated with tuberculous latency and the inherent difficulties in modeling latent disease. The publication of the complete genome sequence of M. tuberculosis (7) has facilitated the study of mycobacterial genes whose homologues in other organisms possess defined functions. Genome-sequencing studies have revealed that M. tuberculosis encodes five genes with substantial homology to the resuscitation-promoting factor (Rpf)...

Background Porocarcinoma is the malignant counterpart of poroma, a benign tumor derived from the eccrine or apocrine units. In contrast to poroma, porocarcinoma is rare and its diagnosis may be challenging. Recent work has identified YAP1‐associated gene fusions in most poromas, and a subset of porocarcinomas. These included YAP1‐MAML2 and YAP1‐NUTM1, the latter being enriched in porocarcinomas over poromas. Methods We studied YAP1 C‐terminus and NUT immunohistochemistry in a cohort of 12 porocarcinomas, 10 poromas, 10 squamous cell carcinomas, and 6 hidradenocarcinomas. Results Seven of 12 (58%) porocarcinomas showed loss of YAP1 C‐terminus expression, consistent with a YAP1 fusion. Of these seven, five showed NUT positivity, implying the presence of the YAP1‐NUTM1 fusion. One of 12 (8%) cases showed NUT positivity, but retention of YAP1 C‐terminus expression, consistent with a non‐YAP1 NUT‐associated fusion. Eight of 10 (80%) poromas showed loss of YAP1 C‐terminus expression and negative NUT staining, consistent with non‐NUT YAP1 fusions. All squamous cell carcinomas and hidradenocarcinomas retained YAP1 C‐terminus expression and were negative for NUT. Conclusion YAP1 C‐terminus and NUT immunohistochemistry may be helpful in the diagnosis of porocarcinoma, with the combination of YAP1 C‐terminus loss and NUT positivity being particularly informative.