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Background. Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff mm score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss. Methods. We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff mm score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %MEmm (%glomeruli with ME in ≥2 lobules, like Banff mm); (2) %MEany (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss. Results. From 1- to 5-y biopsies, the mean Banff mm score increased from 0.18 to 0.34, whereas %MEmm increased from 2.5% to 13.3%. Banff mm score had modest correlations with morphometric ME measures. Moderate-severe %MEmm was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff mm scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff mm score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %MEany had the highest c-statistic (0.872). Conclusions. Banff mm score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.

Introduction: Gene rearrangements are frequent oncologic drivers in NSCLC, and many are suitable for treatment with Food and Drug Administration–approved or experimental targeted therapies. We evaluated the accuracy, specimen acceptance profile, and limits of detection of a rapid fusion assay (Idylla GeneFusion Assay), a commercially available ultrarapid molecular assay, for its clinical utility. Methods: A collection of 97 specimens which had previously undergone next-generation sequencing testing were analyzed using the rapid fusion assay. Accuracy was evaluated by sensitivity and specificity compared with the next-generation sequencing results. The performance characteristics were tested by using a variety of different clinically relevant specimen types. Limits of detection were assessed by evaluating different input of tumor percentage and material amount. Results: The rapid fusion assay was found to have 100% sensitivity in detecting fusions of ALK, ROS1, RET, NTRK1, and MET exon 14 skipping and 83% sensitivity for NTRK2/3 fusions. There were 100% specificity in detecting fusions of ROS1, RET, NTRK2/3, and MET exon 14 skipping and 98% specificity for ALK. Testing was successful with formalin-fixed paraffin-embedded biopsy and surgical tissues, cell blocks from fine-needle aspiration and pleural fluid (down to 5% tumor content, 18 mm2 tissue scraped), cytology smears (≥300 cells), and previously extracted RNA (minimal 20 ng). Conclusions: The rapid fusion assay is quick, accurate, and versatile, allowing reliable detection of ALK, ROS1, RET fusions, and MET exon 14 skipping in NSCLC, and NTRK fusions. Rapid molecular testing may expedite treatment with appropriate targeted therapies.