Anatomic pathology selected abstracts

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A longitudinal comparison of urine cytological classification systems

Urine cytology is used to screen for urothelial carcinoma in patients with hematuria or risk factors, such as smoking or industrial dye exposure, and is an essential clinical-triage and longitudinal-monitoring tool for patients with known bladder cancer. However, urine cytology is semi-subjective and, therefore, susceptible to such issues as inadequate specimen quality, interobserver variability, and hedging towards equivocal, or atypical, diagnoses. These factors limit the predictive value of urine cytology and increase reliance on invasive procedures, such as cysto­scopy. The Paris System for Reporting Urinary Cytology (TPS) was created to provide more quantitative, reproducible endpoints with well-defined criteria for urothelial atypia. TPS is often compared to other assessment techniques to justify its adoption. It results in decreased use of the atypical category and better reproducibility. Previous reports comparing diagnoses pre- and post-TPS did not consider temporal differences between diagnoses made under earlier systems and TPS. By failing to adjust for modifications across time, these previous studies may have underestimated the magnitude of differences between assessment methods. The authors conducted a large-scale longitudinal reassessment of urine cytology using TPS criteria and specimens collected from 2008 to 2018, prior to the mid-2018 adoption of TPS at an academic medical center. Their findings indicated that differences in atypical assignment were greatest at the start of the collection period and progressively decreased towards insignificance right before implementing TPS. The authors concluded that cytopathologists had begun to use the quantitative TPS criteria prior to it being officially adopted, and this approach could more broadly inform adoption, communication, and understanding of evolving classification systems in cytology.

Levy JJ, Liu X, Marotti JD, et al. Large-scale longitudinal comparison of urine cytological classification systems reveals potential early adoption of The Paris System criteria. J Am Soc Cytopath. 2022;11:394–402.

Correspondence: Dr. Joshua J. Levy at joshua.j.levy@dartmouth.edu

A proposed risk-stratification model for uterine inflammatory myofibroblastic tumors

Inflammatory myofibroblastic tumor of the uterus is a rare mesenchymal tumor with largely benign behavior. However, a small subset demonstrate aggressive behavior. Clinicopathologic features have been associated with aggressive behavior, but these reports are based on small series and these features are imperfect predictors of clinical behavior. Inflammatory myofibroblastic tumors (IMTs) are most commonly driven by ALK fusions, with additional pathogenic molecular alterations being reported only in rare examples of extrauterine IMTs. The authors conducted a study in which a series of 11 uterine IMTs, five of which demonstrated aggressive behavior, were evaluated for clinicopathologic variables and subjected to capture-based next-generation sequencing with or without whole transcriptome RNA sequencing. ALK fusions were the sole pathogenic alteration in the six IMTs without aggressive behavior. In contrast, all five aggressive IMTs harbored pathogenic molecular alterations and numerous copy number changes, in addition to ALK fusions, with the majority of the additional alterations present in the primary tumors. The authors combined their series with cases previously reported in the literature and performed statistical analyses to propose a novel clinicopathologic risk-stratification score. The score assigned one point each for age above 45 years, size of 5 cm or larger, four or more mitotic figures per 10 high-power fields, and infiltrative borders. No tumors with zero points had an aggressive outcome, while 21 percent of tumors with one or two points and 100 percent of tumors with three or more points had aggressive outcomes. The authors proposed a two-step classification model that uses a clinicopathologic risk-stratification score combined with molecular data to predict clinical behavior in uterine IMTs.

Ladwig NR, Bean GR, Pekmezci M, et al. Uterine inflammatory myofibroblastic tumors: Proposed risk stratification model using integrated clinicopathologic and molecular analysis. Am J Surg Pathol. 2023;47(2):157–171.

Correspondence: Dr. S. E. Umetsu at sarah.umetsu@ucsf.edu