Simone Bertz1, Robert Stöhr1, Nadine T Gaisa2, Bernd Wullich3, Arndt Hartmann1, Abbas Agaimy1. 1. Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany. 2. Institute of Pathology, RWTH Aachen, Aachen, Germany. 3. Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Abstract
AIMS: Pseudosarcomatous myofibroblastic proliferations (PSMPs) of the urinary bladder are diagnostically challenging. Diagnostic difficulties are mainly due to frequent cytokeratin expression, variable ALK expression, and worrisome morphologic features suggestive of malignancy. On the opposite, sarcomatoid urothelial carcinoma (UC) may show bland inflammatory myofibroblastic tumor (IMT)-like morphology. TERT promoter mutations are characteristic events in urothelial cancers, but have not been studied in PSMPs. METHODS: We compared histomorphological and immunohistochemical features and TERT promoter status in 16 PSMPs and 18 sarcomatoid UC. In a subset of PSMPs RNA sequencing was performed. RESULTS: At least focal IMT-like morphology was seen in 9/17 sarcomatoid UC. Atypical mitoses, differentiated urothelial component and heterologous elements were the most reliable distinguishing histomorphological features of sarcomatoid UC, if present. A panel of immunohistochemistry (IHC) including ALK (clone D5F3), p53 pattern, p63 and GATA3 reliably distinguished PSMP from sarcomatoid UC. GATA3 (p=0.001) and p53 patterns (mutant vs wildtype; p<0.001) were differentially expressed between PSMPs and sarcomatoid UC. Diffuse pancytokeratin staining was significantly associated with PSMPs (10/13) compared to 4/14 sarcomatoid UCs (p=0.012). TERT promoter mutations were found in 17/18 sarcomatoid UC vs 0/16 PSMPs (p<0.001). RNA sequencing revealed ALK genetic rearrangements in 1/2 ALK-positive and in 1/10 ALK-negative PSMPs, which revealed a novel FN1/RET gene fusion. CONCLUSION: Careful histomorphological analysis and differential IHC reliably distinguish the majority of PSMPs and sarcomatoid UC. In equivocal cases, TERT promoter mutation analysis and/or detection of ALK expression/rearrangements are valuable additional diagnostic adjuncts strongly supporting sarcomatoid UC and PSMP, respectively. This article is protected by copyright. All rights reserved.
AIMS: Pseudosarcomatous myofibroblastic proliferations (PSMPs) of the urinary bladder are diagnostically challenging. Diagnostic difficulties are mainly due to frequent cytokeratin expression, variable ALK expression, and worrisome morphologic features suggestive of malignancy. On the opposite, sarcomatoid urothelial carcinoma (UC) may show bland inflammatory myofibroblastic tumor (IMT)-like morphology. TERT promoter mutations are characteristic events in urothelial cancers, but have not been studied in PSMPs. METHODS: We compared histomorphological and immunohistochemical features and TERT promoter status in 16 PSMPs and 18 sarcomatoid UC. In a subset of PSMPs RNA sequencing was performed. RESULTS: At least focal IMT-like morphology was seen in 9/17 sarcomatoid UC. Atypical mitoses, differentiated urothelial component and heterologous elements were the most reliable distinguishing histomorphological features of sarcomatoid UC, if present. A panel of immunohistochemistry (IHC) including ALK (clone D5F3), p53 pattern, p63 and GATA3 reliably distinguished PSMP from sarcomatoid UC. GATA3 (p=0.001) and p53 patterns (mutant vs wildtype; p<0.001) were differentially expressed between PSMPs and sarcomatoid UC. Diffuse pancytokeratin staining was significantly associated with PSMPs (10/13) compared to 4/14 sarcomatoid UCs (p=0.012). TERT promoter mutations were found in 17/18 sarcomatoid UC vs 0/16 PSMPs (p<0.001). RNA sequencing revealed ALK genetic rearrangements in 1/2 ALK-positive and in 1/10 ALK-negative PSMPs, which revealed a novel FN1/RET gene fusion. CONCLUSION: Careful histomorphological analysis and differential IHC reliably distinguish the majority of PSMPs and sarcomatoid UC. In equivocal cases, TERT promoter mutation analysis and/or detection of ALK expression/rearrangements are valuable additional diagnostic adjuncts strongly supporting sarcomatoid UC and PSMP, respectively. This article is protected by copyright. All rights reserved.
Authors: Veronika Weyerer; Markus Eckstein; Pamela L Strissel; Adrian Wullweber; Fabienne Lange; Lars Tögel; Carol I Geppert; Danijel Sikic; Helge Taubert; Sven Wach; Bernd Wullich; Arndt Hartmann; Robert Stoehr; Johannes Giedl Journal: Genes (Basel) Date: 2021-02-05 Impact factor: 4.096
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