View source for BRST5:Inflammatory myofibroblastic tumour

==Primary Author(s)*==

Yajuan Liu, PhD, University of Washington

__TOC__

==Cancer Category / Type==

Mesenchymal tumours of the breast

==Cancer Sub-Classification / Subtype==

Fibroblastic and myofibroblastic tumors 

==Definition / Description of Disease==

Inflammatory Myofibroblastic Tumor (IMT) of the breast originate from mesenchymal tissue and is composed of both myofibroblastic and fibroblastic spindle cells and is accompanied by an inflammatory infiltrate, which may include plasma cells, lymphocytes, and/or eosinophils. It has intermediate biological potential (low-grade malignant) and rarely metastasizes.  

Essential and desirable diagnostic criteria include loose fascicles of plump spindle cells without substantial atypia or pleomorphism; inflammatory infiltrate of lymphocytes and plasma cells; consistent SMA expression; frequent ALK expression; ''ALK'' or other gene rearrangements in some cases.

==Synonyms / Terminology==

Related terminology: inflammatory pseudotumour (historical, not recommended), inflammatory fibrosarcoma (historical, not recommended); plasma cell granuloma (historical, not recommended) 

==Epidemiology / Prevalence==

Breast IMTs most often affect young to middle-aged females, although the age range is broad.<ref name=":0">{{Cite journal|last=Coffin|first=C. M.|last2=Watterson|first2=J.|last3=Priest|first3=J. R.|last4=Dehner|first4=L. P.|date=1995-08|title=Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases|url=https://pubmed.ncbi.nlm.nih.gov/7611533|journal=The American Journal of Surgical Pathology|volume=19|issue=8|pages=859–872|doi=10.1097/00000478-199508000-00001|issn=0147-5185|pmid=7611533}}</ref><ref>{{Cite journal|last=Makhlouf|first=Hala R.|last2=Sobin|first2=Leslie H.|date=2002-03|title=Inflammatory myofibroblastic tumors (inflammatory pseudotumors) of the gastrointestinal tract: how closely are they related to inflammatory fibroid polyps?|url=https://pubmed.ncbi.nlm.nih.gov/11979371|journal=Human Pathology|volume=33|issue=3|pages=307–315|doi=10.1053/hupa.2002.32213|issn=0046-8177|pmid=11979371}}</ref>

==Clinical Features==
{| class="wikitable"
|'''Signs and Symptoms'''
|Breast IMT usually presents as a painless, circumscribed mass.
|-
|'''Laboratory Findings'''
|
|}

==Sites of Involvement==

Breast IMT is rare and fewer than 25 reported cases.<ref>{{Cite journal|last=Khanafshar|first=Elham|last2=Phillipson|first2=Julia|last3=Schammel|first3=David P.|last4=Minobe|first4=Lorraine|last5=Cymerman|first5=Judith|last6=Weidner|first6=Noel|date=2005-06|title=Inflammatory myofibroblastic tumor of the breast|url=https://pubmed.ncbi.nlm.nih.gov/15944952|journal=Annals of Diagnostic Pathology|volume=9|issue=3|pages=123–129|doi=10.1016/j.anndiagpath.2005.02.001|issn=1092-9134|pmid=15944952}}</ref><ref>{{Cite journal|last=Haj|first=Mahmoud|last2=Weiss|first2=Michael|last3=Loberant|first3=Norman|last4=Cohen|first4=Isaac|date=2003|title=Inflammatory pseudotumor of the breast: case report and literature review|url=https://pubmed.ncbi.nlm.nih.gov/12968967|journal=The Breast Journal|volume=9|issue=5|pages=423–425|doi=10.1046/j.1524-4741.2003.09516.x|issn=1075-122X|pmid=12968967}}</ref><ref>{{Cite journal|last=Zhao|first=Hua-Dong|last2=Wu|first2=Tao|last3=Wang|first3=Jun-Qing|last4=Zhang|first4=Wen-Dong|last5=He|first5=Xian-Li|last6=Bao|first6=Guo-Qiang|last7=Li|first7=Yi|last8=Gong|first8=Li|last9=Wang|first9=Qing|date=2013-01|title=Primary inflammatory myofibroblastic tumor of the breast with rapid recurrence and metastasis: A case report|url=https://pubmed.ncbi.nlm.nih.gov/23255901|journal=Oncology Letters|volume=5|issue=1|pages=97–100|doi=10.3892/ol.2012.948|issn=1792-1074|pmc=3525499|pmid=23255901}}</ref><ref>{{Cite journal|last=Kovács|first=Anikó|last2=Máthé|first2=Gyöngyvér|last3=Mattsson|first3=Jan|last4=Stenman|first4=Göran|last5=Kindblom|first5=Lars-Gunnar|date=2015|title=ALK-Positive Inflammatory Myofibroblastic Tumor of the Nipple During Pregnancy-An Unusual Presentation of a Rare Disease|url=https://pubmed.ncbi.nlm.nih.gov/25772857|journal=The Breast Journal|volume=21|issue=3|pages=297–302|doi=10.1111/tbj.12404|issn=1524-4741|pmid=25772857}}</ref> IMT shows a wide anatomical distribution, most frequently arising in the respiratory tract, abdominal cavity, and retroperitoneum, followed by the lung, mediastinum, head and neck, gastrointestinal tract, and genitourinary tract (including the bladder and uterus).<ref name=":0" /><ref name=":1">{{Cite journal|last=Gleason|first=B. C.|last2=Hornick|first2=J. L.|date=2008-04|title=Inflammatory myofibroblastic tumours: where are we now?|url=https://pubmed.ncbi.nlm.nih.gov/17938159|journal=Journal of Clinical Pathology|volume=61|issue=4|pages=428–437|doi=10.1136/jcp.2007.049387|issn=1472-4146|pmid=17938159}}</ref><ref>{{Cite journal|last=Karnak|first=I.|last2=Senocak|first2=M. E.|last3=Ciftci|first3=A. O.|last4=Cağlar|first4=M.|last5=Bingöl-Koloğlu|first5=M.|last6=Tanyel|first6=F. C.|last7=Büyükpamukçu|first7=N.|date=2001-06|title=Inflammatory myofibroblastic tumor in children: diagnosis and treatment|url=https://pubmed.ncbi.nlm.nih.gov/11381424|journal=Journal of Pediatric Surgery|volume=36|issue=6|pages=908–912|doi=10.1053/jpsu.2001.23970|issn=0022-3468|pmid=11381424}}</ref><ref>{{Cite journal|last=Tsuzuki|first=Toyonori|last2=Magi-Galluzzi|first2=Cristina|last3=Epstein|first3=Jonathan I.|date=2004-12|title=ALK-1 expression in inflammatory myofibroblastic tumor of the urinary bladder|url=https://pubmed.ncbi.nlm.nih.gov/15577680|journal=The American Journal of Surgical Pathology|volume=28|issue=12|pages=1609–1614|doi=10.1097/00000478-200412000-00009|issn=0147-5185|pmid=15577680}}</ref> Unusual locations include somatic soft tissues, pancreas, liver, and CNS.<ref name=":0" /><ref name=":1" /><ref>{{Cite journal|last=Ramachandra|first=S.|last2=Hollowood|first2=K.|last3=Bisceglia|first3=M.|last4=Fletcher|first4=C. D.|date=1995-10|title=Inflammatory pseudotumour of soft tissues: a clinicopathological and immunohistochemical analysis of 18 cases|url=https://pubmed.ncbi.nlm.nih.gov/8847061|journal=Histopathology|volume=27|issue=4|pages=313–323|doi=10.1111/j.1365-2559.1995.tb01521.x|issn=0309-0167|pmid=8847061}}</ref>

==Morphologic Features==

Most tumors are < 5 cm in size, with white to grey and sometimes yellow cut surfaces.

Loose fascicles of uniform, plump spindle cells with vesicular chromatin, small nucleoli, and pale eosinophilic to amphophilic cytoplasm are typically observed. <ref name=":0" /> The stroma may be myxoid or collagenous, usually containing an inflammatory infiltrate dominated by lymphocytes and plasma cells, with fewer eosinophils and neutrophils. Some tumours exhibit a compact, fascicular architecture with minimal stroma. A subset of tumour cells may resemble ganglion cells. Mitotic activity is low and necrosis is usually absent. 

==Immunophenotype==

Essential and desirable diagnostic criteria include loose fascicles of plump spindle cells without substantial atypia or pleomorphism; inflammatory infiltrate of lymphocytes and plasma cells; consistent SMA expression; frequent ALK expression.

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||SMA
|-
|Positive (subset)||desmin, ALK (~60%),<ref name=":2">{{Cite journal|last=Cook|first=J. R.|last2=Dehner|first2=L. P.|last3=Collins|first3=M. H.|last4=Ma|first4=Z.|last5=Morris|first5=S. W.|last6=Coffin|first6=C. M.|last7=Hill|first7=D. A.|date=2001-11|title=Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study|url=https://pubmed.ncbi.nlm.nih.gov/11684952|journal=The American Journal of Surgical Pathology|volume=25|issue=11|pages=1364–1371|doi=10.1097/00000478-200111000-00003|issn=0147-5185|pmid=11684952}}</ref><ref name=":3">{{Cite journal|last=Pickett|first=Justine L.|last2=Chou|first2=Angela|last3=Andrici|first3=Juliana A.|last4=Clarkson|first4=Adele|last5=Sioson|first5=Loretta|last6=Sheen|first6=Amy|last7=Reagh|first7=Jessica|last8=Najdawi|first8=Fedaa|last9=Kim|first9=Yoomee|date=2017-10|title=Inflammatory Myofibroblastic Tumors of the Female Genital Tract Are Under-recognized: A Low Threshold for ALK Immunohistochemistry Is Required|url=https://pubmed.ncbi.nlm.nih.gov/28731868|journal=The American Journal of Surgical Pathology|volume=41|issue=10|pages=1433–1442|doi=10.1097/PAS.0000000000000909|issn=1532-0979|pmc=5598906|pmid=28731868}}</ref> ROS1 (~5%)<ref name=":4">{{Cite journal|last=Hornick|first=Jason L.|last2=Sholl|first2=Lynette M.|last3=Dal Cin|first3=Paola|last4=Childress|first4=Merrida A.|last5=Lovly|first5=Christine M.|date=2015-05|title=Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors|url=https://pubmed.ncbi.nlm.nih.gov/25612511|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=28|issue=5|pages=732–739|doi=10.1038/modpathol.2014.165|issn=1530-0285|pmc=5874150|pmid=25612511}}</ref> <ref name=":5">{{Cite journal|last=Antonescu|first=Cristina R.|last2=Suurmeijer|first2=Albert J. H.|last3=Zhang|first3=Lei|last4=Sung|first4=Yun-Shao|last5=Jungbluth|first5=Achim A.|last6=Travis|first6=William D.|last7=Al-Ahmadie|first7=Hikmat|last8=Fletcher|first8=Christopher D. M.|last9=Alaggio|first9=Rita|date=2015-07|title=Molecular characterization of inflammatory myofibroblastic tumors with frequent ALK and ROS1 gene fusions and rare novel RET rearrangement|url=https://pubmed.ncbi.nlm.nih.gov/25723109|journal=The American Journal of Surgical Pathology|volume=39|issue=7|pages=957–967|doi=10.1097/PAS.0000000000000404|issn=1532-0979|pmc=4465992|pmid=25723109}}</ref>
|-
|Negative (universal)||keratin
|-
|Negative (subset)||CD34, S100, SOX10, and EMA
|}

==Chromosomal Rearrangements (Gene Fusions)==

Confirmation of ALK or other gene rearrangements supports the diagnosis. However, molecular confirmation is not required if ALK immunohistochemistry is definitively positive.<ref name=":6">{{Cite journal|last=Coffin|first=C. M.|last2=Patel|first2=A.|last3=Perkins|first3=S.|last4=Elenitoba-Johnson|first4=K. S.|last5=Perlman|first5=E.|last6=Griffin|first6=C. A.|date=2001-06|title=ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor|url=https://pubmed.ncbi.nlm.nih.gov/11406658|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=14|issue=6|pages=569–576|doi=10.1038/modpathol.3880352|issn=0893-3952|pmid=11406658}}</ref> Of note, exceptional situations such as inversion of ALK on the same chromosome arm may lead to a false-negative FISH result. <ref>{{Cite journal|last=Haimes|first=Josh D.|last2=Stewart|first2=Colin J. R.|last3=Kudlow|first3=Brian A.|last4=Culver|first4=Brady P.|last5=Meng|first5=Bo|last6=Koay|first6=Eleanor|last7=Whitehouse|first7=Ann|last8=Cope|first8=Nichola|last9=Lee|first9=Jen-Chieh|date=2017-06|title=Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1|url=https://pubmed.ncbi.nlm.nih.gov/28490045|journal=The American Journal of Surgical Pathology|volume=41|issue=6|pages=773–780|doi=10.1097/PAS.0000000000000801|issn=1532-0979|pmid=28490045}}</ref>, and other molecular testing such as RNA-Seq can be used to detect ALK fusions efficiently. In ALK-negative cases, immunohistochemistry for ROS1 and/or molecular tests for non-ALK gene fusions (e.g. NTRK3) may be useful.<ref name=":7">{{Cite journal|last=Yamamoto|first=Hidetaka|last2=Yoshida|first2=Akihiko|last3=Taguchi|first3=Kenichi|last4=Kohashi|first4=Kenichi|last5=Hatanaka|first5=Yui|last6=Yamashita|first6=Atsushi|last7=Mori|first7=Daisuke|last8=Oda|first8=Yoshinao|date=2016-07|title=ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours|url=https://pubmed.ncbi.nlm.nih.gov/26647767|journal=Histopathology|volume=69|issue=1|pages=72–83|doi=10.1111/his.12910|issn=1365-2559|pmid=26647767}}</ref><ref name=":8">{{Cite journal|last=Lovly|first=Christine M.|last2=Gupta|first2=Abha|last3=Lipson|first3=Doron|last4=Otto|first4=Geoff|last5=Brennan|first5=Tina|last6=Chung|first6=Catherine T.|last7=Borinstein|first7=Scott C.|last8=Ross|first8=Jeffrey S.|last9=Stephens|first9=Philip J.|date=2014-08|title=Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions|url=https://pubmed.ncbi.nlm.nih.gov/24875859|journal=Cancer Discovery|volume=4|issue=8|pages=889–895|doi=10.1158/2159-8290.CD-14-0377|issn=2159-8290|pmc=4125481|pmid=24875859}}</ref><ref name=":9">{{Cite journal|last=Alassiri|first=Ali H.|last2=Ali|first2=Rola H.|last3=Shen|first3=Yaoqing|last4=Lum|first4=Amy|last5=Strahlendorf|first5=Caron|last6=Deyell|first6=Rebecca|last7=Rassekh|first7=Rod|last8=Sorensen|first8=Poul H.|last9=Laskin|first9=Janessa|date=2016-08|title=ETV6-NTRK3 Is Expressed in a Subset of ALK-Negative Inflammatory Myofibroblastic Tumors|url=https://pubmed.ncbi.nlm.nih.gov/27259007|journal=The American Journal of Surgical Pathology|volume=40|issue=8|pages=1051–1061|doi=10.1097/PAS.0000000000000677|issn=1532-0979|pmid=27259007}}</ref><ref name=":5" />

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|t(2;var)(p23;var)||5'var::3'''ALK''
(various 5’partner genes include ''TPM3'', ''TPM4'', ''CLTC'', ''CARS'', ''ATIC'', ''SEC31L1'', ''PPFIBP1'', ''DCTN1'', ''EML4'', ''PRKAR1A'', ''LMNA'', ''TFG'', ''FN1'', ''HNRNPA1'', etc)
|der(var)||50-60%<ref name=":10">{{Cite journal|last=Bridge|first=J. A.|last2=Kanamori|first2=M.|last3=Ma|first3=Z.|last4=Pickering|first4=D.|last5=Hill|first5=D. A.|last6=Lydiatt|first6=W.|last7=Lui|first7=M. Y.|last8=Colleoni|first8=G. W.|last9=Antonescu|first9=C. R.|date=2001-08|title=Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor|url=https://pubmed.ncbi.nlm.nih.gov/11485898|journal=The American Journal of Pathology|volume=159|issue=2|pages=411–415|doi=10.1016/S0002-9440(10)61711-7|issn=0002-9440|pmc=1850566|pmid=11485898}}</ref><ref>{{Cite journal|last=Chen|first=Sung-Ting|last2=Lee|first2=Jen-Chieh|date=2008-12|title=An inflammatory myofibroblastic tumor in liver with ALK and RANBP2 gene rearrangement: combination of distinct morphologic, immunohistochemical, and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/18701132|journal=Human Pathology|volume=39|issue=12|pages=1854–1858|doi=10.1016/j.humpath.2008.04.016|issn=1532-8392|pmid=18701132}}</ref><ref>{{Cite journal|last=Debelenko|first=Larisa V.|last2=Arthur|first2=Diane C.|last3=Pack|first3=Svetlana D.|last4=Helman|first4=Lee J.|last5=Schrump|first5=David S.|last6=Tsokos|first6=Maria|date=2003-09|title=Identification of CARS-ALK fusion in primary and metastatic lesions of an inflammatory myofibroblastic tumor|url=https://pubmed.ncbi.nlm.nih.gov/13679433|journal=Laboratory Investigation; a Journal of Technical Methods and Pathology|volume=83|issue=9|pages=1255–1265|doi=10.1097/01.lab.0000088856.49388.ea|issn=0023-6837|pmid=13679433}}</ref><ref>{{Cite journal|last=Griffin|first=C. A.|last2=Hawkins|first2=A. L.|last3=Dvorak|first3=C.|last4=Henkle|first4=C.|last5=Ellingham|first5=T.|last6=Perlman|first6=E. J.|date=1999-06-15|title=Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors|url=https://pubmed.ncbi.nlm.nih.gov/10383129|journal=Cancer Research|volume=59|issue=12|pages=2776–2780|issn=0008-5472|pmid=10383129}}</ref><ref>{{Cite journal|last=Lawrence|first=B.|last2=Perez-Atayde|first2=A.|last3=Hibbard|first3=M. K.|last4=Rubin|first4=B. P.|last5=Dal Cin|first5=P.|last6=Pinkus|first6=J. L.|last7=Pinkus|first7=G. S.|last8=Xiao|first8=S.|last9=Yi|first9=E. S.|date=2000-08|title=TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors|url=https://pubmed.ncbi.nlm.nih.gov/10934142|journal=The American Journal of Pathology|volume=157|issue=2|pages=377–384|doi=10.1016/S0002-9440(10)64550-6|issn=0002-9440|pmc=1850130|pmid=10934142}}</ref><ref>{{Cite journal|last=Takeuchi|first=Kengo|last2=Soda|first2=Manabu|last3=Togashi|first3=Yuki|last4=Sugawara|first4=Emiko|last5=Hatano|first5=Satoko|last6=Asaka|first6=Reimi|last7=Okumura|first7=Sakae|last8=Nakagawa|first8=Ken|last9=Mano|first9=Hiroyuki|date=2011-05-15|title=Pulmonary inflammatory myofibroblastic tumor expressing a novel fusion, PPFIBP1-ALK: reappraisal of anti-ALK immunohistochemistry as a tool for novel ALK fusion identification|url=https://pubmed.ncbi.nlm.nih.gov/21430068|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=17|issue=10|pages=3341–3348|doi=10.1158/1078-0432.CCR-11-0063|issn=1557-3265|pmid=21430068}}</ref><ref>{{Cite journal|last=Yamamoto|first=Hidetaka|last2=Kohashi|first2=Kenichi|last3=Oda|first3=Yoshinao|last4=Tamiya|first4=Sadafumi|last5=Takahashi|first5=Yukiko|last6=Kinoshita|first6=Yoshiaki|last7=Ishizawa|first7=Shin|last8=Kubota|first8=Masayuki|last9=Tsuneyoshi|first9=Masazumi|date=2006-10|title=Absence of human herpesvirus-8 and Epstein-Barr virus in inflammatory myofibroblastic tumor with anaplastic large cell lymphoma kinase fusion gene|url=https://pubmed.ncbi.nlm.nih.gov/16984614|journal=Pathology International|volume=56|issue=10|pages=584–590|doi=10.1111/j.1440-1827.2006.02012.x|issn=1320-5463|pmid=16984614}}</ref><ref>{{Cite journal|last=Inamura|first=Kentaro|last2=Kobayashi|first2=Maki|last3=Nagano|first3=Hiroko|last4=Sugiura|first4=Yoshiya|last5=Ogawa|first5=Masahiro|last6=Masuda|first6=Hitoshi|last7=Yonese|first7=Junji|last8=Ishikawa|first8=Yuichi|date=2017-11|title=A novel fusion of HNRNPA1-ALK in inflammatory myofibroblastic tumor of urinary bladder|url=https://pubmed.ncbi.nlm.nih.gov/28504207|journal=Human Pathology|volume=69|pages=96–100|doi=10.1016/j.humpath.2017.04.022|issn=1532-8392|pmid=28504207}}</ref><ref name=":8" />
|Yes
|Yes (ALK-negative IMTs may have a higher likelihood of metastasis)
|Yes
|IMT with ''ALK'' genomic rearrangement features activation and overexpression of the ALK C-terminal kinase region, which is restricted to the neoplastic myofibroblastic component <ref name=":10" /><ref name=":6" /><ref name=":2" />
|-
|t(3;6)(q12.2;q22.1), t(6;17)(q22.1;p13.3)
|''TFG''::''ROS1'', ''YWHAE''::''ROS1''
|der(var)
|5-10%<ref name=":8" /><ref name=":4" /><ref name=":9" /><ref name=":5" /><ref name=":7" />
|Yes
|No
|Yes
|
|-
|t(12;15)(p13.2;q25.3)
|''ETV6''::''NTRK3''
|der(15)
|>5%<ref name=":8" /><ref name=":5" />
|Yes
|No
|Yes
|Therapy options for ''NTRK'' fusions include larotrectinib and entrectinib (clinically approved)
|-
|t(5;12)(q32;q13.3)
|''NAB2''::''PDGFRB''
|der(5)
|>1%<ref name=":8" />
|Unknown
|No
|Yes
|
|-
|rea(10q11.21)
|rea(''RET'')
|der(10)
|>1%<ref name=":5" />
|Unknown
|No
|Yes
|Detected by FISH break-apart probe
|}		
			
==Individual Region Genomic Gain / Loss / LOH==

NA

{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|NA
|NA
|
|
|
|
|
|
|-
|NA
|NA
|
|
|
|
|
|.
|}
==Characteristic Chromosomal Patterns==

NA

{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|NA
|
|
|
|
|}
==Gene Mutations (SNV / INDEL)==

NA

{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|NA
|
|
|
|
|
|
|
|
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

==Epigenomic Alterations==

NA

==Genes and Main Pathways Involved==

IMTs are genetically heterogeneous. About two thirds of inflammatory myofibroblastic tumours harbour receptor tyrosine kinase gene rearrangements, most often involving the ''ALK'' locus at 2p23, with diverse fusion partners. <ref>{{Cite journal|last=Mariño-Enríquez|first=Adrian|last2=Dal Cin|first2=Paola|date=2013-11|title=ALK as a paradigm of oncogenic promiscuity: different mechanisms of activation and different fusion partners drive tumors of different lineages|url=https://pubmed.ncbi.nlm.nih.gov/24091028|journal=Cancer Genetics|volume=206|issue=11|pages=357–373|doi=10.1016/j.cancergen.2013.07.001|issn=2210-7762|pmid=24091028}}</ref> Approximately 5% of inflammatory myofibroblastic tumours harbour ''ROS1'' gene fusions; other rare gene fusions involve ''NTRK3'', ''PDGFRB'', and ''RET.'' <ref name=":8" /><ref name=":5" /><ref name=":7" /><ref name=":9" /><ref name=":3" />
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|''ALK'' fusion; activating rearrangement
|Kinase fusions, receptor tyrosine kinase/growth factor signaling
|uncontrolled cell proliferation and survival
|-
|''ROS1'' fusion; activating rearrangement
|Kinase fusions, receptor tyrosine kinase/growth factor signaling
|cell growth and differentiation
|-
|''NTRK3'' fusion; activating rearrangement
|Kinase fusions, receptor tyrosine kinase/growth factor signaling
|cell differentiation
|-
|''PDGFRB'' fusion; activating rearrangement
|Kinase fusions, receptor tyrosine kinase/growth factor signaling
|cell growth
|-
|''RET'' fusion; activating rearrangement
|Kinase fusions, receptor tyrosine kinase/growth factor signaling
|cell growth
|}
==Genetic Diagnostic Testing Methods==

FISH, RT-PCR, RNA-seq 

==Familial Forms==

<br />

==Additional Information==

<br />

==Links==

<br />

==References==
<references />

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==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.