SUO 2017: Aberrant Histology in NMIBC - What Do We Know and Not Know?

Washington, DC ( Dr. Hansel presented a unique viewpoint as a Pathologist in the field of non-muscle-invasive bladder cancer (NMIBC) and variant histology tumors. She started by pointing out that diagnosing specific varieties of disease on TUR specimens can be a very difficult task due to variability in tissues, tissue conditions, and clinical scenarios. It can also difficult for non-pathologists to appropriately understand the precise thoughts of the pathologist, sometimes leading to over-interpretation or misinterpretation of findings. Indeed, although grade and stage classifications may appear distinct by definition, most resected tumors reflect different steps in tumor progression and are not as easily classified. So, what features truly portend poorer outcomes?

Some features that are known to be important include grade, subtype, and possibly sub-staging. Emerging evidence suggests that molecular profiling may be a superior way to classify tumors, but our understanding of molecular markers is still developing. Grade classification must account for a wide spectrum of morphologic features that may be present in any tumor. Grade heterogeneity is defined as an admixture of 2 grades within a papillary lesion, and higher amounts of high-grade morphology portend more aggressive pathology. Perhaps more specific quantification of morphology in reporting could alleviate some confusion, but it could also add to confusion.

Variant histologies are also difficult to pathologically characterize. Unfortunately, many definitions for variant histology have changed, and comparisons over time are nearly impossible for this reason. Dr. Hansel focused discussion on micropapillary and plasmacytoid UCC variants. Although there is no clear answer regarding stage-for-stage differences in outcomes compared to standard UCC, we believe that the amount of variant histology in the tumor does likely impact outcomes. To that end, the WHO now recommends that pathologists include a percentage of each variant in pathological reports.

Micropapillary bladder cancer has a specific definition on paper. Yet, its real-world diagnosis is extremely variable. A remarkable study investigating variability in diagnosis studied academic GU pathologists. Data showed that even in this group of experienced diagnosticians, enormous interobserver variability existed in diagnosis! Diagnoses may even change in the same hands, as studies have shown that pathologic subtypes diagnosed on TUR sometimes differ from final pathology on RC specimens.

Plasmacytoid urothelial carcinoma is another difficult but important histologic subtype. This subtype was previously classified as a number of other entities, including mucinous, adenocarcinoma, and signet-ring cell carcinoma; again, making comparisons over time very difficult. Interobserver variability is a major problem here as well; and although molecular classifiers may alleviate some of this variability, we still lack the appropriate molecular tools for such an analysis.

Dr. Hansel is pursuing work on T1 sub-staging on TUR specimens. This may hold promise in better classifying tumor aggressiveness; and in combination with molecular classification, may be the future of TUR-based prognostication.

This was a very enlightening presentation that offered the Pathologist’s vantage of NMIBC diagnosis and prognostication. We know that variability is a major issue in the field of UCC diagnosis, and we should double-down efforts to generate tools to minimize this variability and improve prognostic clarity for the betterment of patient care.

Presented by: Donna Hansel, MD, PhD, Professor, Director, Anatomic Pathology, UC San Diego School of Medicine, Pathology

Written by: Shreyas Joshi, MD, @ssjoshimd Fox Chase Cancer Center, Philadelphia, PA at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC