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.

A re-look at the modified Ryan regression scoring system in esophageal cancer-validation of prognostic significance and comparison with other less commonly used systems.

BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) using CROSS protocol is currently the treatment of choice for esophageal cancer (EC). Tumor response grade (TRG) is a mandatory reporting criterion in most guidelines. One of the most commonly used TRG systems is the modified Ryan system. We aim to assess the TRG using modified Ryan and seven other systems (Mandard, Chireac, Swisher, Japanese esophageal society guidelines, modified rectal cancer regression grading (mRCRG), CROSS, and Becker) to evaluate their reproducibility and role as a prognostic marker. MATERIALS AND METHODS: Two pathologists independently reviewed all cases of post-NACRT (CROSS) EC, to score TRGs and other histological parameters. Inter-rater agreement assessment for different TRG systems and correlation with disease-free survival (DFS) was performed. RESULTS: Our series includes 93 patients with predominantly mid-esophageal squamous cell carcinoma. Complete pathological response (pCR) was noted in 47% (44/93) patients. The kappa inter-rater agreement score for the Ryan system was substantial (0.774), while it was almost perfect agreement for tumor percentage assessment-based systems (Swisher, CROSS, and Becker). Only the mRCRG TRGs correlated significantly with prognosis, while the Ryan system did not. Tumor stage and pCR status did not correlate with DFS, though the nodal stage was clinically significant. CONCLUSION: Though the inter-rater concordance was optimal for all the TRG systems studied, only the mRCRG system showed prognostic significance, while the commonly used modified Ryan system did not. It may be worthwhile to look at further evaluating other systems like mRCRG for inclusion in minimum dataset reporting.

Mullerian adenosarcoma (heterologous) of uterine cervix with sarcomatous overgrowth: A case report with review of the literature.

Mullerian adenosarcoma is a rare biphasic malignant neoplasm of cervix characterized by an admixture of benign epithelial elements and a malignant sarcomatous stromal component, which may be either homologous or heterologous. Mullerian adenosarcoma with stromal overgrowth (MASO) in an aggressive variant of adenosarcoma, which is extremely rare with only two such cases reported till date. In this report, we present a case of MASO of cervix with heterologous elements in a 55/F presenting with postmenopausal bleeding. As it commonly simulates clinically and radiologically as benign cervical polyp, the gynecologists and pathologists should be aware of this extremely rare entity presenting with aggressive clinical course.