PMID- 32908253
OWN - NLM
STAT- MEDLINE
DCOM- 20211022
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 34
IP  - 2
DP  - 2021 Feb
TI  - Pseudosarcomatous myofibroblastic proliferations of the urinary bladder are 
      neoplasms characterized by recurrent FN1-ALK fusions.
PG  - 469-477
LID - 10.1038/s41379-020-00670-0 [doi]
AB  - Pseudosarcomatous myofibroblastic proliferation is a descriptive term that 
      designates a group of clinically indolent genitourinary lesions that most 
      commonly arise in the urinary bladder. Given that pseudosarcomatous 
      myofibroblastic proliferation may show morphologic overlap with inflammatory 
      myofibroblastic tumor, the relationship, if any, between the two entities has 
      been unclear. Moreover, pseudosarcomatous myofibroblastic proliferations are 
      known to be positive for ALK immunohistochemistry in a subset of cases, although 
      an inconsistent association with ALK rearrangement (ranging from 0 to 60%) has 
      been reported. The objectives of this study were to determine the frequency of 
      ALK rearrangement and to identify fusion partners using fluorescence in situ 
      hybridization (FISH) and targeted RNA sequencing studies in a contemporary series 
      of 30 pseudosarcomatous myofibroblastic proliferations of the urinary bladder, as 
      well as to investigate ROS1 status by immunohistochemistry. ALK 
      immunohistochemistry was positive in 70% (21/30) of pseudosarcomatous 
      myofibroblastic proliferations; ROS1 immunohistochemistry was consistently 
      negative (0/28). ALK rearrangements were detected by FISH in 86% (18/21) of 
      cases, correlating with ALK immunohistochemical positivity in all but 3 cases. Of 
      eight cases confirmed to be ALK rearranged by FISH, targeted RNA-sequencing 
      detected FN1-ALK fusions in seven (88%) cases, which involved exons 20-26 of FN1 
      (5') and exon 18-19 of ALK (3'). In conclusion, ALK rearrangements are frequent 
      in pseudosarcomatous myofibroblastic proliferations, typically involving exon 19, 
      and FN1 appears to be a consistent fusion partner. Given the significant 
      clinicopathologic differences between inflammatory myofibroblastic tumor and 
      pseudosarcomatous myofibroblastic proliferation, our findings provide further 
      support for classification of pseudosarcomatous myofibroblastic proliferation as 
      a distinct clinicopathologic entity, and propose the alternate terminology 
      "pseudosarcomatous myofibroblastic neoplasm of the genitourinary tract."
FAU - Acosta, Andres M
AU  - Acosta AM
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA, USA.
FAU - Demicco, Elizabeth G
AU  - Demicco EG
AUID- ORCID: 0000-0003-4144-8824
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      ON, Canada.
FAU - Dal Cin, Paola
AU  - Dal Cin P
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA, USA.
FAU - Hirsch, Michelle S
AU  - Hirsch MS
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA, USA.
FAU - Fletcher, Christopher D M
AU  - Fletcher CDM
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA, USA.
FAU - Jo, Vickie Y
AU  - Jo VY
AUID- ORCID: 0000-0003-4808-2714
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA, USA. vjo@bwh.harvard.edu.
LA  - eng
PT  - Journal Article
DEP - 20200909
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (FN1 protein, human)
RN  - 0 (Fibronectins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anaplastic Lymphoma Kinase/genetics
MH  - Child
MH  - Female
MH  - Fibronectins/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms, Muscle Tissue/*genetics/*pathology
MH  - Oncogene Proteins, Fusion/genetics
MH  - Urinary Bladder Neoplasms/*genetics/*pathology
MH  - Young Adult
EDAT- 2020/09/11 06:00
MHDA- 2023/02/11 06:00
CRDT- 2020/09/10 05:33
PHST- 2020/05/14 00:00 [received]
PHST- 2020/08/21 00:00 [accepted]
PHST- 2020/08/21 00:00 [revised]
PHST- 2020/09/11 06:00 [pubmed]
PHST- 2023/02/11 06:00 [medline]
PHST- 2020/09/10 05:33 [entrez]
AID - S0893-3952(22)00687-1 [pii]
AID - 10.1038/s41379-020-00670-0 [doi]
PST - ppublish
SO  - Mod Pathol. 2021 Feb;34(2):469-477. doi: 10.1038/s41379-020-00670-0. Epub 2020 
      Sep 9.