BRST5:Inflammatory myofibroblastic tumour
(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)
Primary Author(s)*
Yajuan Liu, PhD and Katherine Geiersbach, MD
WHO Classification of Disease
(Instructions: This table’s content from the WHO book will be autocompleted.)
| Structure | Disease |
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| Book | |
| Category | |
| Family | |
| Type | |
| Subtype(s) |
WHO Essential and Desirable Genetic Diagnostic Criteria
(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)
| WHO Essential Criteria (Genetics)* | |
| WHO Desirable Criteria (Genetics)* | |
| Other Classification |
*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.
Related Terminology
(Instructions: The table will have the related terminology from the WHO autocompleted.)
| Acceptable | |
| Not Recommended |
Gene Rearrangements
Formerly referred to as inflammatory pseudotumor, inflammatory myofibroblastic tumor of the breast relies upon morphologic, immunohistochemical, and/or molecular features shared in common with other primary tumor sites.[1][2][3][4] Confirmation of rearrangements of ALK or, less commonly other receptor tyrosine kinase genes, supports the diagnosis and can identify therapeutic targets[5]. However, molecular confirmation is not required if ALK immunohistochemistry is definitively positive.[6][7][8] Of note, exceptional situations such as inversions or other cryptic rearrangements of ALK at 2p23 may lead to a false-negative FISH result[9], 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 may be useful.[10][11][12][13][14] (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Driver Gene | Fusion(s) and Common Partner Genes | Molecular Pathogenesis | Typical Chromosomal Alteration(s) | Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|---|
| ALK | TPM3::ALK, TPM4::ALK, EML4::ALK, RANBP2::ALK, CLTC::ALK, and others | Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion breakpoints occur in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. At the DNA level, alternative ALK breakpoints in rare cases occur upstream of exon 19, most commonly in intron 18. | Rearrangements of ALK gene locus at 2p23 | Common | D, T | EXAMPLE: Yes (WHO, NCCN) | |
| ROS1 | TFG::ROS1, YWHAE::ROS1, and others | Fusions result in constitutive activation of the ROS1 tyrosine kinase. Most common ROS1 breakpoints occur in intron 35; at the transcript level, various 5' partner genes are fused to exon 36 of ROS1. | Rearrangements of ROS1 gene locus at 6q22 | Recurrent | D, T | ||
| NTRK3 | ETV6::NTRK3 and others | Fusions result in constitutive activation of the NTRK3 tyrosine kinase. | Rearrangements of NTRK3 gene locus at 15q25. Classically, the reciprocal translocation t(12;15)(p13;q25) is associated with ETV6::NTRK3 rearrangement. | Recurrent | D, T | ||
| PDGFRB | NAB2::PDGFRB and others | Fusions result in constitutive activation of the PDGFRB tyrosine kinase. | Rearrangements of the PDGFRB gene locus at 5q32. | Rare | D, T | ||
| NTRK1 | Fusions result in constitutive activation of the NTRK1 tyrosine kinase. | Rearrangements of the NTRK1 gene locus at 1q23. | Rare | D, T | |||
| RET | Fusions result in constitutive activation of the RET tyrosine kinase. | Rearrangements of the RET gene locus at 10q11. | Rare | D, T | |||
| IGF1R | Fusions result in constitutive activation of the IGF1R tyrosine kinase. | Rearrangements of the IGF1R gene locus at 15q26. | Rare | D, T |
Individual Region Genomic Gain/Loss/LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)
| Chr # | Gain, Loss, Amp, LOH | Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] | Relevant Gene(s) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
Characteristic Chromosomal or Other Global Mutational Patterns
Put your text here and fill in the table (Instructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Chromosomal Pattern | Molecular Pathogenesis | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|
Gene Mutations (SNV/INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Epigenomic Alterations
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Genes and Main Pathways Involved
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| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| ALK, ROS1, NTRK3, NTRK1, RET, PDGFRB, RET, and other tyrosine kinase genes; Activating gene fusions | JAK/STAT3, PI3K, RAS/RAF/MAPK signaling | Increased cell growth and proliferation |
Genetic Diagnostic Testing Methods
Put your text here (Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.)
Familial Forms
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Additional Information
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Links
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References
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Notes
*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 Associate Editor or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
Prior Author(s):
- ↑ Khanafshar, Elham; et al. (2005-06). "Inflammatory myofibroblastic tumor of the breast". Annals of Diagnostic Pathology. 9 (3): 123–129. doi:10.1016/j.anndiagpath.2005.02.001. ISSN 1092-9134. PMID 15944952. Check date values in:
|date=(help) - ↑ Haj, Mahmoud; et al. (2003). "Inflammatory pseudotumor of the breast: case report and literature review". The Breast Journal. 9 (5): 423–425. doi:10.1046/j.1524-4741.2003.09516.x. ISSN 1075-122X. PMID 12968967.
- ↑ Zhao, Hua-Dong; et al. (2013-01). "Primary inflammatory myofibroblastic tumor of the breast with rapid recurrence and metastasis: A case report". Oncology Letters. 5 (1): 97–100. doi:10.3892/ol.2012.948. ISSN 1792-1074. PMC 3525499. PMID 23255901. Check date values in:
|date=(help) - ↑ Kovács, Anikó; et al. (2015). "ALK-Positive Inflammatory Myofibroblastic Tumor of the Nipple During Pregnancy-An Unusual Presentation of a Rare Disease". The Breast Journal. 21 (3): 297–302. doi:10.1111/tbj.12404. ISSN 1524-4741. PMID 25772857.
- ↑ Chmiel, Paulina; et al. (2024). "Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment". Oncology Research. 32 (7): 1141–1162. doi:10.32604/or.2024.050350. ISSN 1555-3906. PMC PMC11209743 Check
|pmc=value (help). PMID 38948020 Check|pmid=value (help).CS1 maint: PMC format (link) - ↑ Coffin, C. M.; et al. (2001-06). "ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 14 (6): 569–576. doi:10.1038/modpathol.3880352. ISSN 0893-3952. PMID 11406658. Check date values in:
|date=(help) - ↑ Cook, J. R.; et al. (2001-11). "Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study". The American Journal of Surgical Pathology. 25 (11): 1364–1371. doi:10.1097/00000478-200111000-00003. ISSN 0147-5185. PMID 11684952. Check date values in:
|date=(help) - ↑ Pickett, Justine L.; et al. (2017-10). "Inflammatory Myofibroblastic Tumors of the Female Genital Tract Are Under-recognized: A Low Threshold for ALK Immunohistochemistry Is Required". The American Journal of Surgical Pathology. 41 (10): 1433–1442. doi:10.1097/PAS.0000000000000909. ISSN 1532-0979. PMC 5598906. PMID 28731868. Check date values in:
|date=(help) - ↑ Haimes, Josh D.; et al. (2017-06). "Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1". The American Journal of Surgical Pathology. 41 (6): 773–780. doi:10.1097/PAS.0000000000000801. ISSN 1532-0979. PMID 28490045. Check date values in:
|date=(help) - ↑ Hornick, Jason L.; et al. (2015-05). "Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 28 (5): 732–739. doi:10.1038/modpathol.2014.165. ISSN 1530-0285. PMC 5874150. PMID 25612511. Check date values in:
|date=(help) - ↑ Yamamoto, Hidetaka; et al. (2016-07). "ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours". Histopathology. 69 (1): 72–83. doi:10.1111/his.12910. ISSN 1365-2559. PMID 26647767. Check date values in:
|date=(help) - ↑ Lovly, Christine M.; et al. (2014-08). "Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions". Cancer Discovery. 4 (8): 889–895. doi:10.1158/2159-8290.CD-14-0377. ISSN 2159-8290. PMC 4125481. PMID 24875859. Check date values in:
|date=(help) - ↑ Alassiri, Ali H.; et al. (2016-08). "ETV6-NTRK3 Is Expressed in a Subset of ALK-Negative Inflammatory Myofibroblastic Tumors". The American Journal of Surgical Pathology. 40 (8): 1051–1061. doi:10.1097/PAS.0000000000000677. ISSN 1532-0979. PMID 27259007. Check date values in:
|date=(help) - ↑ Antonescu, Cristina R.; et al. (2015-07). "Molecular characterization of inflammatory myofibroblastic tumors with frequent ALK and ROS1 gene fusions and rare novel RET rearrangement". The American Journal of Surgical Pathology. 39 (7): 957–967. doi:10.1097/PAS.0000000000000404. ISSN 1532-0979. PMC 4465992. PMID 25723109. Check date values in:
|date=(help)