---
title: "Malignant MITF‑Rearranged PEComa Harboring a Novel EEF1A1::MITF Fusion"
id: "pubmed-42671146"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42671146"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42671146/"
doi: "10.1002/gcc.70168"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Malignant MITF‑Rearranged PEComa Harboring a Novel EEF1A1::MITF Fusion
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42671146
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42671146/)
- **DOI:** [10.1002/gcc.70168](https://doi.org/10.1002%2Fgcc.70168)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Report of a malignant superficial soft tissue tumor in a 45-year-old woman located in the thigh that harbored a novel **EEF1A1::MITF** fusion. - Tumor morphology: epithelioid to plump spindle cells in sheets, nests, and short fascicles with prominent capillary vasculature, marked cytologic atypia, brisk mitoses, and necrosis. - Immunoprofile: diffuse strong nuclear **MITF** and diffuse GPNMB expression; patchy SMA, scattered desmin, and multifocal cathepsin K positivity. Negative for S100, SOX10, HMB45, Melan A, PRAME, tyrosinase, pancytokeratin, CD34, and TFE3. - Molecular findings: in-frame **EEF1A1::MITF** fusion; ATRX frameshift mutation; homozygous deletion of CDKN2A/CDKN2B; complex copy-number alterations. No canonical alterations in TSC1, TSC2, or FLCN were detected. - Diagnostic implication: immunophenotype differs from classic PEComa but resembles previously described MITF-overexpressing PEComas; supports that a subset of cutaneous PEComas may be driven by **MITF** rearrangements. - Clinical classification: case report expanding the molecular spectrum of PEComa and contributing evidence for diverse genetic drivers beyond TSC1/TSC2 alterations. - Limitations: single-case report; clinical course and therapeutic implications beyond molecular characterization were not detailed in the source.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. * 2 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. * 3 UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA. * 4 Department of Orthopaedic Surgery, University of Pittsburgh, Pennsylvania, USA. * PMID: **42671146** * DOI: [ 10.1002/gcc.70168 ](https://doi.org/10.1002/gcc.70168) Item in Clipboard Case Reports # Malignant MITF-Rearranged PEComa With Novel EEF1A1::MITF Fusion Sierra Raney et al. Genes Chromosomes Cancer. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Genes Chromosomes Cancer Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Genes+Chromosomes+Cancer%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Genes+Chromosomes+Cancer%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671146/) . 2026 Sep;65(9):e70168. doi: 10.1002/gcc.70168. ### Authors [Sierra Raney](https://pubmed.ncbi.nlm.nih.gov/?term=Raney+S&cauthor_id=42671146)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-1 "Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [Arivarasan Karunamurthy](https://pubmed.ncbi.nlm.nih.gov/?term=Karunamurthy+A&cauthor_id=42671146)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-1 "Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [Jonhan Ho](https://pubmed.ncbi.nlm.nih.gov/?term=Ho+J&cauthor_id=42671146)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-1 "Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [Robert Bubar](https://pubmed.ncbi.nlm.nih.gov/?term=Bubar+R&cauthor_id=42671146)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-1 "Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [Maedeh Mohebnasab](https://pubmed.ncbi.nlm.nih.gov/?term=Mohebnasab+M&cauthor_id=42671146)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-1 "Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [John Skaugen](https://pubmed.ncbi.nlm.nih.gov/?term=Skaugen+J&cauthor_id=42671146)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-1 "Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [Mohamed Elmoryah](https://pubmed.ncbi.nlm.nih.gov/?term=Elmoryah+M&cauthor_id=42671146)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-1 "Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [Benjamin Nacev](https://pubmed.ncbi.nlm.nih.gov/?term=Nacev+B&cauthor_id=42671146)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-2 "Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-3 "UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA."), [Richard McGough](https://pubmed.ncbi.nlm.nih.gov/?term=McGough+R&cauthor_id=42671146)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-4 "Department of Orthopaedic Surgery, University of Pittsburgh, Pennsylvania, USA."), [Ivy John](https://pubmed.ncbi.nlm.nih.gov/?term=John+I&cauthor_id=42671146)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671146/#short-view-affiliation-1 "Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.") ### Affiliations * 1 Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. * 2 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. * 3 UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA. * 4 Department of Orthopaedic Surgery, University of Pittsburgh, Pennsylvania, USA. * PMID: **42671146** * DOI: [ 10.1002/gcc.70168 ](https://doi.org/10.1002/gcc.70168) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract MITF-rearranged PEComas are rare, and their relationship to MITF-altered melanocytic tumors remains incompletely characterized. We report a malignant superficial soft tissue neoplasm of the thigh in a 45-year-old woman harboring a novel EEF1A1::MITF fusion. The tumor was composed of epithelioid to plump spindle cells arranged in sheets, nests, and short fascicles with prominent capillary vasculature. Significant cytologic atypia, brisk mitotic activity, and necrosis were present. The tumor cells showed diffuse strong nuclear MITF and diffuse GPNMB expression, with patchy SMA, scattered desmin, and multifocal cathepsin K positivity, while S100, SOX10, HMB45, Melan A, PRAME, tyrosinase, pancytokeratin, CD34, and TFE3 were negative. Although atypical for classic PEComa, this immunophenotype resembles that described in MITF-overexpressing PEComas. Molecular studies identified an ATRX frameshift mutation, homozygous CDKN2A/CDKN2B deletion, complex copy number alterations, and an in-frame EEF1A1::MITF fusion. No canonical TSC1, TSC2, or FLCN alteration was identified. These findings expand the molecular spectrum of PEComa and support the emerging concept that a subset of cutaneous PEComas may be driven by MITF rearrangements. **Keywords:** EEF1A1::MITF; MITF; MITF‐overexpressing PEComa; PEComa. © 2026 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Liquid-Based Cytologic Features of a Thyroid TFE3-Rearranged PEComa-Like Neoplasm: A Case Report. ](https://pubmed.ncbi.nlm.nih.gov/41826240/) Lee WY, Chang ST, Huang LE.Lee WY, et al.Diagn Cytopathol. 2026 Jun;54(6):E160-E164. doi: 10.1002/dc.70108. Epub 2026 Mar 13.Diagn Cytopathol. 2026.PMID: 41826240 * [ Genetic correlates of malignancy in TFE3-rearranged PEComa: a series of 14 cases. ](https://pubmed.ncbi.nlm.nih.gov/40462401/) Papke DJ Jr, Odintsov I, Mahadevan NR, Fletcher CD, Hanna J.Papke DJ Jr, et al.Histopathology. 2025 Sep;87(3):436-445. doi: 10.1111/his.15476. Epub 2025 Jun 3.Histopathology. 2025.PMID: 40462401Free PMC article. * [ PEComa With MITF Overexpression: Clinicopathologic and Molecular Analysis of a Series of 36 Cases. ](https://pubmed.ncbi.nlm.nih.gov/38934541/) Hanna J, Russell-Goldman E, Baranov E, Pissaloux D, Li YY, Tirode F, de la Fouchardiere A, Fletcher CDM.Hanna J, et al.Am J Surg Pathol. 2024 Nov 1;48(11):1381-1388. doi: 10.1097/PAS.0000000000002276. Epub 2024 Jun 27.Am J Surg Pathol. 2024.PMID: 38934541 * [ SFPQ::TFE3-rearranged PEComa: Differences and analogies with renal cell carcinoma carrying the same translocation. ](https://pubmed.ncbi.nlm.nih.gov/40239600/) Marletta S, Caliò A, Pierconti F, Harada S, Netto GJ, Antonini P, Segala D, Pedron S, Marcolini L, Stefanizzi L, Martignoni G.Marletta S, et al.Pathol Res Pract. 2025 Jun;270:155963. doi: 10.1016/j.prp.2025.155963. Epub 2025 Apr 10.Pathol Res Pract. 2025.PMID: 40239600Review. * [ TFE3-Altered Perivascular Epithelioid Cell Tumour (PEComa) of the Nasal Cavity With a Novel TRAF3::TFE3 Fusion-A Report of a Case Expanding the Molecular Genetic Spectrum and a Brief Literature Review on PEComas of the Head and Neck Region. ](https://pubmed.ncbi.nlm.nih.gov/40879261/) Chua ZS, Michal M, Petersson F.Chua ZS, et al.Genes Chromosomes Cancer. 2025 Aug;64(8):e70075. doi: 10.1002/gcc.70075.Genes Chromosomes Cancer. 2025.PMID: 40879261Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42671146) ## References 1. 1. C.‐C. Pan, M.‐Y. Chung, K.‐F. Ng, et al., “Constant Allelic Alteration on Chromosome 16p (TSC2 Gene) in Perivascular Epithelioid Cell Tumour (PEComa): Genetic Evidence for the Relationship of PEComa With Angiomyolipoma,” Journal of Pathology 214, no. 3 (2007): 387–393. 2. 1. P. Argani, S. Aulmann, P. B. Illei, et al., “A Distinctive Subset of PEComas Harbors TFE3 Gene Fusions,” American Journal of Surgical Pathology 34, no. 10 (2010): 1395–1406. 3. 1. J. Hanna, E. Russell‐Goldman, E. Baranov, et al., “PEComa With MITF Overexpression: Clinicopathologic and Molecular Analysis of a Series of 36 Cases,” American Journal of Surgical Pathology 48, no. 11 (2024): 1381–1388. 4. 1. A. de la Fourchardiere, D. Pissaloux, F. Tirode, et al., “Clear Cell Tumor With Melanocytic Differentiation and Actin‐MITF Translocation: Report of 7 Cases of a Novel Entity,” American Journal of Surgical Pathology 45, no. 7 (2021): 962–968. 5. 1. S. Alexandrescu, A. Imamovic‐Tuco, K. Janeway, and J. Hanna, “Clear Cell Tumor With Melanocytic Differentiation and MITF::CREM Translocation,” Journal of Cutaneous Pathology 50, no. 7 (2023): 619–622. 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