Manocha U, Kardos J, Selitsky S, et al. - Sixteen cases of lymphoepithelioma-like carcinoma of the bladder (LELC-B) were recognized at Johns Hopkins University and RNAseq was done on 14 cases in order to molecularly identify LELC-B through RNA expression profiling as well as immunohistochemistry to learn its underlying biology. Transcriptomic profiling of LELC-B exhibited that with 12 of 14 LELC-B cases correlating to the basal centroid of the BASE47 PAM classifier, they are enhanced in a basal-like phenotype. The lymphocyte infiltration profile constant with the histomorphology was validated by gene signature analysis. Lack of characteristics to demonstrate the strong lymphocytic infiltrate, like loss of mismatch repair protein expression or expression of Epstein-Barr virus transcripts was noted in LELC-B. Nevertheless, in 93% of LELC cases, PD-L1 immunohistochemistry was positive. Thus, the study shows that in a basal-like molecular subtype, LELC-B tumors are enhanced, share a high level of immune infiltration and PD-L1 expression comparable to basal tumors. Moreover, the basal-like phenotype is constant with the well-known sensitivity of LELC-B to chemotherapy and proposes that in this rare disease, immune checkpoint therapy should be investigated.