Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Shaomin Hu, MD, PhD, staff pathologist, Cleveland Clinic; S. Emily Bachert, MD, associate pathologist, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.
ISUP consensus conference on issues in bladder cancer: grading of mixed grade, invasive urothelial carcinoma
July 2024—The 2022 International Society of Urological Pathology consensus conference on urinary bladder cancer working group two was tasked with providing evidence-based proposals on applying grading to noninvasive urothelial carcinoma with mixed grades; invasive urothelial carcinoma, including subtypes and divergent differentiations; and pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has an intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. Using 2004 World Health Organization (WHO) grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high grade and the rare invasive low-grade tumors show only limited superficial invasion. Using 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached regarding whether T1 tumors should be graded by the 2004 or 1973 WHO system. Because of concern about underdiagnosis and underreporting and, thereby, potential undertreatment, working group participants unanimously recommended that urothelial carcinoma subtypes and divergent differentiations be reported. They reached a consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiations should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high grade according to the 2004 WHO grading system. However, they acknowledged that subtypes and divergent differentiations should not be considered a homogenous group in terms of behavior. Therefore, future studies should focus on individual subtypes and divergent differentiations rather than lumping these entities into a single clinicopathological group. Likewise, clinical recommendations should take into consideration the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. Participants also reached a consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the ISUP working group two proceedings addresses some of the issues that go beyond the traditional application of grading, including those related to papillary urothelial carcinomas with mixed grades and invasive components. The reporting of subtypes and divergent differentiations are also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors.
Paner GP, Kamat A, Netto GJ, et al. International Society of Urological Pathology (ISUP) consensus conference on current issues in bladder cancer. Working group 2: grading of mixed grade, invasive urothelial carcinoma including histologic subtypes and divergent differentiations, and non-urothelial carcinomas. Am J Surg Pathol. 2024;48(1):e11–e23.
Correspondence: Dr. Gladell Paner at gladell.paner@uchospitals.edu
Crohn’s disease features in biopsies from patients with and without Crohn’s disease
Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn’s disease, and histologic disease activity is evolving as a similarly important end point for patient management. However, classical morphologic features of Crohn’s disease (CD) may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies. A clear unmet need exists to better characterize diagnostic and clinically significant histologic features of CD in surgically altered sites. Therefore, the authors conducted a study in which they evaluated ileocolonic and colocolonic/rectal anastomotic biopsies from patients with and without CD that were performed at three academic institutions. The biopsies were blindly assessed for CD histologic features and correlated with clinical and endoscopic characteristics. In CD patients, the presence of each feature was correlated with subsequent clinical exacerbation or relapse. The authors obtained anastomotic biopsies from 208 patients, of which 109 underwent surgery for CD and 99 for another indication, including neoplasia (80 percent), diverticular disease (11 percent), and other (nine percent). Mean time between the anastomotic biopsy and original surgery was 10 years (range, 0–59 years). It was 14 years for the CD group (range, 1–59 years) and six years for the non-CD group (range, 0–33 years). Endoscopic inflammation was noted in 52 percent of cases (68 percent for CD and 35 percent for non-CD). Microscopic inflammation was present in 74 percent of cases (82 percent for CD and 67 percent for non-CD). Only discontinuous lymphoplasmacytosis (P < .001) and pyloric gland metaplasia (P = .04) occurred significantly more often in CD patients. However, none of the histologic features predicted clinical disease progression. In a subset analysis, the presence of histologic features of CD in nonanastomotic biopsies obtained concurrently in CD patients was significantly associated with relapse (P = .03). The authors concluded that due to extensive morphologic overlap between CD and postoperative changes and a lack of specific histologic features of relapse, biopsies from anastomotic sites are of no value in predicting clinical CD progression. Instead, CD activity in biopsies obtained away from anastomotic sites should be used to guide endoscopic sampling and clinical management.
Evaristo G, Szczepanski J, Farag MS, et al. Crohn’s disease features in anastomotic biopsies from patients with and without Crohn’s disease: Diagnostic and prognostic value. Mod Pathol. 2023;36(11). doi:10.1016/j.modpat.2023.100325
Correspondence: Dr. John Hart at john.hart@bsd.uchicago.edu