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

Sounak Gupta, Carlos P. Sosa, Farhad Kosari, Andrew Folpe, Kaustubh N. Bhinge, Lin Yang, Alireza Agahi, Sarah H. Johnson, Igor Frank, Stephen A. Boorjian, Donna E. Hansel, Hikmat A. Al-Ahmadie, Victor E. Reuter, George Vasmatzis, Rafael E. Jimenez, Loren Herrera-Hernandez, John C. Cheville

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)48-59
Number of pages12
JournalHuman Pathology
StatePublished - Jun 2019


  • ASCL1
  • Genitourinary
  • High-grade neuroendocrine carcinoma
  • PPP1R12A
  • Rhabdomyosarcoma
  • Sarcomatoid carcinoma
  • Urinary bladder

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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