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Updated: May 20, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

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MITF Pathway-Activated Cutaneous Neoplasms

Michael Michal1, Steven D Billings2, Thomas Brenn3

  • 1Department of Pathology, Faculty of Medicine in Plzen, University Hospital Plzen, Charles University Plzen, Czech Republic Bioptical Laboratory Ltd, Pilsen, Czech Republic.

Advances in Anatomic Pathology
|May 19, 2025
PubMed

Insights

Several dermal tumors activate the microphthalmia (MITF) pathway via gene fusions, leading to a melanocytic phenotype. Understanding these rare tumors, including clear cell sarcoma, is crucial for diagnosis and treatment.

Area of Science:

  • Oncology
  • Genetics
  • Dermatopathology

Background:

  • Dermal tumors can exhibit a melanocytic phenotype due to specific gene fusions.
  • Microphthalmia (MITF) signaling pathway activation is a common mechanism in these tumors.
  • Clear cell sarcoma, characterized by EWSR1 rearrangements, is a well-known example, though rare in the skin.

Purpose of the Study:

  • To provide a comprehensive overview of rare dermal tumors with MITF pathway activation.
  • To highlight the distinguishing features of various fusion-driven cutaneous tumors.
  • To aid in the differential diagnosis of these uncommon neoplasms.

Main Methods:

  • Review of recent scientific literature on cutaneous tumors with gene fusions.
  • Analysis of characteristic genetic alterations (e.g., EWSR1, CRTC1::TRIM11, ACTIN::MITF).
  • Comparison of clinical, histopathologic, and immunophenotypic features.

Main Results:

  • Multiple gene fusions (e.g., CRTC1::TRIM11, ACTIN::MITF, MITF::CREM, MED15::ATF1) have been identified in cutaneous tumors.
  • These tumors share a melanocytic phenotype and MITF pathway activation.
  • Subtle differences in presentation, histology, immunophenotype, and prognosis exist among these entities.

Conclusions:

  • Fusion genes play a significant role in the pathogenesis of a subset of rare dermal tumors.
  • Accurate differentiation requires careful evaluation of multiple clinicopathologic parameters.
  • Further research is needed to fully elucidate the behavior and optimal management of these tumors.
Keywords:
MITFfusion genesmelanocyticneoplasmskintumor

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