A comparison of adult rhabdomyosarcoma and high-grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma Journal Article

   

Authors:	Gupta, S.; Sosa, C. P.; Kosari, F.; Folpe, A.; Bhinge, K. N.; Yang, L.; Agahi, A.; Johnson, S. H.; Frank, I.; Boorjian, S. A.; Hansel, D. E.; Al-Ahmadie, H. A.; Reuter, V. E.; Vasmatzis, G.; Jimenez, R. E.; Herrera-Hernandez, L.; Cheville, J. C.
Article Title:	A comparison of adult rhabdomyosarcoma and high-grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma
Abstract:	Some rhabdomyosarcomas and sarcomatoid carcinomas with heterologous rhabdomyosarcomatous elements resemble high-grade neuroendocrine carcinoma, creating a diagnostic difficulty. The purpose of this study was to characterize the overlap of adult genitourinary rhabdomyosarcomas, excluding those occurring at paratesticular sites, with high-grade neuroendocrine carcinoma and identify features helpful in their separation. Seventeen cases of rhabdomyosarcoma (11 from the urinary bladder and 3 each from kidney and prostate)were compared to 10 cases of high-grade neuroendocrine carcinoma from the urinary bladder. These tumors were analyzed by immunohistochemistry for desmin, MyoD1, myogenin, chromogranin, synaptophysin, CD56, TTF1, and ASCL1, and RNA sequencing was performed on 4 cases of bladder rhabdomyosarcoma (2 rhabdomyosarcomas and 2 sarcomatoid-rhabdomyosarcoma)and 10 cases of bladder high-grade neuroendocrine carcinoma. This was compared to public data from 414 typical urothelial carcinomas from The Cancer Genome Atlas dataset. Morphologic and immunophenotypic overlap with high-grade neuroendocrine carcinoma was seen in half of the bladder tumors, which included 4 rhabdomyosarcomas and 2 sarcomatoid rhabdomyosarcomas. RNA sequencing confirmed expression of neuroendocrine markers in these cases (2 rhabdomyosarcomas and 2 sarcomatoid rhabdomyosarcomas). Differential neuroendocrine differentiation was highlighted by ASCL1 protein expression only in high-grade neuroendocrine carcinoma. Moreover, both a pure alveolar rhabdomyosarcoma and sarcomatoid rhabdomyosarcoma of the urinary bladder demonstrated a fusion involving PPP1R12A. In summary, adult rhabdomyosarcomas of the urinary bladder are molecularly distinct from high-grade neuroendocrine carcinomas based on specific patterns of expression of myogenic and epithelial to mesenchymal transition–related transcription factors as well as the presence of a novel PPP1R12A fusion which is seen in a subset of cases. © 2019 Elsevier Inc.
Keywords:	urinary bladder; sarcomatoid carcinoma; rhabdomyosarcoma; genitourinary; ascl1; high-grade neuroendocrine carcinoma; ppp1r12a
Journal Title:	Human Pathology
Volume:	88
ISSN:	0046-8177
Publisher:	Elsevier Inc.
Date Published:	2019-06-01
Start Page:	48
End Page:	59
Language:	English
DOI:	10.1016/j.humpath.2019.03.007
PUBMED:	30946934
PROVIDER:	scopus
PMCID:	PMC8078053
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065121410&doi=10.1016%2fj.humpath.2019.03.007&partnerID=40&md5=931d81bfc0958d760bb0bab4826fae40
Notes:	Article -- Export Date: 3 June 2019 -- Source: Scopus

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