Clinicopathologic study of 60 cases of urothelial neoplasms with inverted growth patterns: Reclassification by international consultation on urologic disease (ICUD) recommendations

Abstract

Background: Most urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking. Methods: Sixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, lumina] necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed. Results: A total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPIJCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (> 1/2), and more frequent apoptosis, lumina] necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2. Conclusions: The 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.