Plasmacytoid urothelial carcinoma: a rapid autopsy case report with unique clinicopathologic and genomic profile

Caroline T Simon,Yuanyuan Qiao,Jeffrey Jentzen,Arul M Chinnaiyan,Rohit Mehra,Hikmat Al-Ahmadie,Saravana M Dhanasekaran,Stephanie L Skala,Xuhong Cao,Sandra I Camelo-Piragua,Javed Siddiqui,Paul D Killen,Zachery R Reichert

doi:10.1186/s13000-019-0896-z

Abstract

BackgroundRapid (“warm”) autopsies of patients with advanced metastatic cancer provide important insight into the natural history, pathobiology and histomorphology of disease in treatment-resistant tumors. Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma characterized by neoplastic cells morphologically resembling plasma cells. PUC is typically aggressive, high-stage at presentation, and associated with poor outcomes. Recurrence is common in PUC, with the majority of recurrences occurring in the peritoneum.Case presentationHere, we report rapid autopsy findings from a patient with recurrent PUC. The patient had persistent pain after cystoprostatectomy, although initial post-operative imaging showed no evidence of disease. Imaging obtained shortly before his death showed only subtle growth along vascular tissue planes; however, extensive disease was seen on autopsy. Plasmacytoid tumor cells formed sheets involving many serosal surfaces. Molecular interrogation confirmed a mutation in CDH1 exon 12 leading to early truncation of the CDH1 protein in the tumor cells.ConclusionsThe sheet-like growth pattern of PUC makes early phases of disease spread much more difficult to capture on cross-sectional imaging. Alternative forms of surveillance may be required for detection of recurrent PUC, and providers may need to treat based on symptoms and clinical suspicion.

Highlights

Rapid (“warm”) autopsies, those performed within approximately 3 h after death, of end-stage cancer patients help us to understand the clinical and pathologic aspects of therapy-resistant disease
The sheet-like growth pattern of Plasmacytoid urothelial carcinoma (PUC) makes early phases of disease spread much more difficult to capture on cross-sectional imaging
Alternative forms of surveillance may be required for detection of recurrent PUC, and providers may need to treat based on symptoms and clinical suspicion

Summary

Introduction

Rapid (“warm”) autopsies, those performed within approximately 3 h after death, of end-stage cancer patients help us to understand the clinical and pathologic aspects of therapy-resistant disease. TCGA studies have demonstrated 5 distinct subtypes of muscleinvasive bladder cancer based on mRNA expression clustering: (1) luminal-papillary subtype (FGFR3 mutation, fusion with TACC3 and/or amplification, active sonic hedgehog signaling), (2) luminal-infiltrated subtype (high expression of epithelial-mesenchymal transition and myofibroblast markers, medium expression of PD-L1 and CTLA4), (3) luminal subtype (high expression of luminal markers, KRT20, and SNX31), (4) basal-squamous subtype (squamous differentiation, basal keratin expression, high expression of PD-L1 and CTLA4), and (5) neuronal subtype (expression of neuroendocrine and neuronal genes, and high cellcycle signature) [15] Most of these molecular subtypes have potential therapeutic implications. Molecular interrogation confirmed a mutation in CDH1 exon 12 leading to early truncation of the CDH1 protein in the tumor cells

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