Urologic Oncology: Seminars and Original Investigations
Original articleContemporary bladder cancer: Variant histology may be a significant driver of disease1
Introduction
When the World Health Organization (WHO) published its 2004 guidelines for classification of urothelial carcinoma (UC) and chose to recognize distinct variant histology (VH), one of its aims was increasing identification of these variants on pathology specimens [1]. Better understanding of these VH forms of UC leads to greater knowledge of prognosis and treatment strategies specific to individual variants. Despite initial descriptions of variants more than 20 years ago, molecular pathways for the divergent development of specific VH within primary urothelial bladder carcinoma have not been elucidated [2], [3]. Divergent differentiation is poorly understood; although, Cheng et al. [4] have suggested sarcomatoid urothelial cancer developing as the final common pathway in UC differentiation. The true prevalence of VH has likely not increased over the past decade, although this is difficult to prove retrospectively [5]. Rather, increased pathologic awareness of the possible morphologic variants is likely the driver of increased variant diagnosis.
Recognizing the increased identification of less common VH at our institution since 2008, we sought to evaluate clinicopathologic outcomes of patients with VH UC within a contemporary cohort of patients in an attempt to better delineate treatment algorithms.
Section snippets
Methods
Using an institutional database, we conducted a retrospective review of all patients who underwent radical cystectomy for UC of the bladder at our institution between 2008 and June 2013 (n = 698). As the current WHO guidelines recommend that patients with any component of small cell histology be managed as primary small cell carcinoma, we eliminated all patients with small cell variant (n = 22). Patients with locoregional metastatic disease that underwent cystectomy after preoperative
Results
In total, 624 patients were identified as meeting all inclusion criteria. Of these, 462 (74.0%) had NV histology, 68 (10.9%) had SQD, 28 (4.5%) had MPV, 25 (4.0%) had PCV, 15 (2.4%) had SAV, and 26 (4.2%) had other VH. Among the other VH, there were 9 GLD, 6 nested variant, 5 lymphoepitheliomalike, 4 clear cell, and 2 rhabdoid variant. Table 1 shows patient characteristics. The average age of patients was 67.0 years (range: 34–92 y), which varied by variant. Most patients were white men.
Discussion
What is the true prevalence of VH and has it changed over time? We report that 26% of patients had VH, with SQD (10.9%), MPV (4.5%), and PCV (4.0%) being the most common variants. This is in contrast to previous studies that have reported that GLD is the second most common VH and that MPV and PCV constitute less than 3% of cohorts [6], [7], [8]. Our findings likely reflect the use of a contemporary cohort of patients (after 2008), rather than a large cohort spanning from the 1980s until the
Conclusions
MPV and PCV of urothelial cancer are associated with worse survival and account for a disproportionate number of deaths within a contemporary cohort of radical cystectomy patients. Multi-institutional studies examining chemosensitivity and investigational protocols will further elucidate the best management strategies for these patients.
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These authors contributed equally to the manuscript.