Repercussions of eosinophils in a renal allograft - Predictor of early graft loss!

We present 5-year experience of renal transplantation (RT) with tissue eosinophilia (TE) in renal allograft biopsy (RAB) and its repercussions on the outcome. In total, 1217 recipients underwent RT from 2011 to 2015, and they were evaluated for the presence of ≥4% TE. Group 1 consisted of RT with RAB showing TE, Group 2 consisted of RT with RAB with rejections without TE, and Group 3 consisted of RT without rejections. Group 1 had 27 recipients, Group 2 had 395, and Group 3 had 795 recipients. The outcome in terms of graft function, patient and graft survival were evaluated and compared between three groups. All recipients received standard triple immunosuppression. One-year patient and death-censored graft survival were 80.7% and 82.7% in Group 1, 87.2% and 95.1% in Group 2, and 92.6% and 99.6%, respectively in Group 3 and corresponding mean serum creatinine (SCr, mg/dL) was 1.60 ± 0.45 in Group 1, 1.63 ± 0.58 in Group 2, and 1.19 ± 0.39 Group three, respectively. Five-year patient and death-censored graft survival were 72.9 % and 71.1% for Group 2 and 87% and 98.2% for Group 3 with SCr of 1.63 ± 0.38 and 1.25 ± 0.4, respectively. Group 1 recipients did not appear at five years. At four years posttransplant, patient and death-censored graft survival were 71.7% and 59.5% in Group 1 with SCr of 1.55 ± 0.65 mg/dL. In conclusion, the presence of eosino-phils in a renal allograft is an impending sign of graft damage and eventual graft loss

Advances, recognition, and interpretation of molecular heterogeneity among conventional and subtype histology of urothelial carcinoma (UC): a survey among urologic pathologists and comprehensive review of the literature

Aims Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe. Methods and Results A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety‐six percent of participants agreed that a small‐cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty‐six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy. Conclusion In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to “personalize” therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility