Pleomorphic hyalinizing angiectatic tumour of soft parts
Soft Tissue and Bone Tumors (Who Classification, 5th ed.)
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(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)*
Mokhtar Abdelhammed, MD; Kathleen (Katie) Schieffer, PhD
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Soft Tissue and Bone Tumors (5th ed.) |
| Category | Soft tissue tumors |
| Family | Tumours of uncertain differentiation |
| Type | Pleomorphic hyalinizing angiectatic tumor of soft parts |
| Subtype(s) | N/A |
Related Terminology
| Acceptable | N/A |
| Not Recommended | N/A |
Gene Rearrangements
Pleomorphic hyalinizing angiectatic tumor (PHAT), which is genetically similar to myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT), is characterized by a recurrent t(1;10)(p22;q24) translocation.[1][2][3] Fluorescence in situ hybridization (FISH) studies have identified a rearrangement of TGFBR3 on chromosome 1p22 and OGA (previously known as and commonly reported in the literature as MGEA5) on chromosome 10q24 in a subset of cases.[1][2][3][4][5] However, a subsequent study using targeted RNA-sequencing in a case of PHAT identified FBXW4, as the fusion partner for TGFBR3. Close proximity of FBXW4 and OGA (MGEA5) at 10q24 may have led to initial misidentification with FISH.[6] (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 |
|---|---|---|---|---|---|---|---|
| TGFBR3 |
|
The unbalanced t(1;10) juxtaposes TGFBR3 with a region within or near OGA (MGEA5) on 10q24.[1][2][3] A single study using RNA-sequencing identified FBXW4, located adjacent to OGA (MGEA5) on 10q24 as a fusion partner.[6] The FBXW4::TGFBR3 fusion had breakpoints in exon 6 of FBXW4 (NM_022039.3) and exon 14 of TGFBR3 (NM_003243.4), resulting in an out-of-frame product.[6]
|
der(10)t(1;10)(p22;q24)[1][2][3] | N/A | D | Yes (WHO) | The t(1;10) with TGFBR3 rearrangement is a recurrent genetic event in PHAT and can be a useful diagnostic marker, particularly in challenging cases.[1][2][4][5] |
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 |
|---|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A | N/A |
Characteristic Chromosomal or Other Global Mutational Patterns
Cytogenetic analysis of cultured lesional tissue identified a mosaic karyotype.[8] The predominant cell line was characterized by an abnormal chromosome count of 45 and contained unbalanced translocations: a derivative chromosome 1 from a t(1;3) and a derivative chromosome 10 from a t(1;10). This was accompanied by the loss of one chromosome 3. (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 |
|---|---|---|---|---|---|
| Complex Karyotype | Associated with the t(1;10) translocation; often includes other abnormalities including deletions or rearrangements involving chromosomes 1 and 3.[1][2][3][8] | N/A | Unknown | No | The karyotype is often complex in addition to the t(1;10). |
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 |
|---|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A | N/A |
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
None
Genes and Main Pathways Involved
(Instructions: Please include references throughout the table. Do not delete the table.)
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| TGFBR3; Rearrangement (with FBXW4 or OGA (MGEA5)) | Growth Factor Signaling | Potential upregulation of pro-proliferative signals contributing to tumorigenesis |
Genetic Diagnostic Testing Methods
1. Fluorescence in situ hybridization (FISH)
- Break apart probes for TGFBR3 on 1p22 is a method to detect the rearrangement in PHAT
- In cases with atypical features, FISH can serve as a diagnostic tool
2. Targeted RNA-sequencing
- Can provide a more precise identification of fusion partners involved in the t(1;10) translocation
(Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.)
Familial Forms
No familial syndromes or hereditary conditions are currently known to be associated with pleomorphic hyalinizing angiectatic tumor. (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)
Additional Information
None
Links
None (Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Antonescu, Cristina R.; et al. (2011-10). "Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor". Genes, Chromosomes & Cancer. 50 (10): 757–764. doi:10.1002/gcc.20897. ISSN 1098-2264. PMC 3361892. PMID 21717526. Check date values in:
|date=(help) - ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Hallor, Karolin H.; et al. (2009-04). "Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions". The Journal of Pathology. 217 (5): 716–727. doi:10.1002/path.2513. ISSN 1096-9896. PMID 19199331. Check date values in:
|date=(help) - ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Liu, Huifei; et al. (2019-02). "The t(1;10)(p22;q24) TGFBR3/MGEA5 Translocation in Pleomorphic Hyalinizing Angiectatic Tumor, Myxoinflammatory Fibroblastic Sarcoma, and Hemosiderotic Fibrolipomatous Tumor". Archives of Pathology & Laboratory Medicine. 143 (2): 212–221. doi:10.5858/arpa.2017-0412-RA. ISSN 1543-2165. PMID 29979612. Check date values in:
|date=(help) - ↑ 4.0 4.1 4.2 Carter, Jodi M.; et al. (2014-09). "TGFBR3 and MGEA5 rearrangements in pleomorphic hyalinizing angiectatic tumors and the spectrum of related neoplasms". The American Journal of Surgical Pathology. 38 (9): 1182–1992. doi:10.1097/PAS.0000000000000212. ISSN 1532-0979. PMID 24705316. Check date values in:
|date=(help) - ↑ 5.0 5.1 5.2 Zreik, Riyam T.; et al. (2016-07). "TGFBR3 and MGEA5 rearrangements are much more common in "hybrid" hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcomas than in classical myxoinflammatory fibroblastic sarcomas: a morphological and fluorescence in situ hybridization study". Human Pathology. 53: 14–24. doi:10.1016/j.humpath.2016.02.005. ISSN 1532-8392. PMID 26980036. Check date values in:
|date=(help) - ↑ 6.0 6.1 6.2 6.3 Rougemont, Anne-Laure; et al. (2019-08). "Targeted RNA-sequencing identifies FBXW4 instead of MGEA5 as fusion partner of TGFBR3 in pleomorphic hyalinizing angiectatic tumor". Virchows Archiv: An International Journal of Pathology. 475 (2): 251–254. doi:10.1007/s00428-019-02556-2. ISSN 1432-2307. PMID 30911815. Check date values in:
|date=(help) - ↑ Boland, Jennifer M.; et al. (2017-09). "Hemosiderotic Fibrolipomatous Tumor, Pleomorphic Hyalinizing Angiectatic Tumor, and Myxoinflammatory Fibroblastic Sarcoma: Related or Not?". Advances in Anatomic Pathology. 24 (5): 268–277. doi:10.1097/PAP.0000000000000151. ISSN 1533-4031. PMID 28375867. Check date values in:
|date=(help) - ↑ 8.0 8.1 Wei, Shi; et al. (2012-01). "Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft parts". Human Pathology. 43 (1): 121–126. doi:10.1016/j.humpath.2011.02.023. ISSN 1532-8392. PMID 21733556. Check date values in:
|date=(help)
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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): *Citation of this Page: “Pleomorphic hyalinizing angiectatic tumour of soft parts”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/27/2025, https://ccga.io/index.php/STBT5:Pleomorphic hyalinizing angiectatic tumour of soft parts.