Identifying the driver histology responsible for the inferior clinicopathologic features associated with plasmacytoid bladder cancer.
Authors: Davaro Elizabeth , Davaro Facundo , Rose Kyle M. , Murthy Prithvi , Naidu Shreyas U. , Camperlengo Lucia P. , Grass G. Daniel , Jain Rohit K. , Zemp Logan , Yu Alice , Poch Michael Adam , Spiess Philippe E. , Gilbert Scott Michael , Sexton Wade J. , Chumbalkar Vaibhav , Vosoughi Aram , Li Roger 
Published: June 2023

e16505 Background: Plasmacytoid urothelial cancer (PUC) is notorious for its spread along fascial planes which reportedly induces worse clinicopathologic. Usually, PUC is present with Conventional UC (CUC); however, the precise assessment of the PUC component in key pathological findings and its effect on clinical behavior has not been delineated. Methods: We performed a retrospective review of patients with PUC who underwent cystectomy at Moffitt Cancer Center between 2012-2022. Repeat histological review of all specimens by specialty trained genitourinary pathologists was performed (AV, ED). Positive margins and lymph nodes were examined and classified by histological subtype. We calculate the proportion of tissue sections with peri-vesical fat invasion in tumor tissue sections submitted from cystectomy specimen in pT3 cases as the microscopic surrogate for macroscopic pT3 sub staging (termed Peri-vesical Fat Invasion Ratio, PFIr). Pearson’s correlation coefficient was used to measure strength and direction of relationship between variables. Kaplan-Meier (KM) analysis was performed for overall survival (OS). Results: Population consists of 44 patients undergoing cystectomy for PUC. Median age was 70 (IQR 63-75) years old with 82% being male. Majority of patients (52.5%) had ≥cT3 disease and 55% received neoadjuvant chemotherapy (NAC). Median percent of plasmacytoid histology was 20% (IQR 5-80%) with 6 (14%), 2 (5%), 5 (11%), 16 (36%), and 15 (34%) being pT0, pT1, pT2, pT3, and pT4, respectively. Of the patients with pT3 disease, 6 were pT3a with a median 78% (IQR 39-82%) PFIr while 10 were pT3b with an associated median PFIr of 56% (42-63%). In total, 14 (32%) patients had positive soft tissue surgical margin, with 11 (79%) being of PUC histology and ten patients with a positive ureteral margin, 80% of which consisted of PUC histology. A total of 97 lymph nodes removed were positive for malignancy with 51.5% demonstrating PUC and 48.5% CUC histology. Univariate analysis confirmed an increasing percentage of PUC histology portended a worse OS (HR 3.27, 95% CI 1.22-8.73, p = 0.018). Additionally, we calculated Pearson’s correlation coefficient for percent of plasmacytoid histology with pathologic tumor stage (r = 0.468, p = < 0.001), soft tissue margin (r = 0.283, p = 0.031), and lymph node density (r = 0.264, p = 0.138). Finally, KM analysis for histologic subtype (PUC vs CUC) at positive margin or positive lymph did not affect OS (p > 0.05), likely a product of our small numbers. Conclusions: The plasmacytoid component of bladder cancer is more likely to spread through direct extension along tissue planes to the surrounding soft tissue and ureters rather than through lymphatics. Also, given the discohesive nature of PUC histology, gross peri-vesical extension may be an inadequate method of sub-stratifying stage pT3 disease.