Exploring the molecular landscape of cutaneous mixed tumors characterized by TRPS1::PLAG1 gene fusion

Ziyad Alsugair ¹, Marie Donzel ^1,2, Nicolas Macagno ³

¹Department of Pathology, Institute de Pathologie Multisite, Groupement Hospitalier Sud, Lyon University Hospital, Pierre-Bénite, France.
²University of Lyon, Université Claude Bernard Lyon 1, Lyon, France.
³Department of Pathology, Aix Marseille University, Marseille, France.
⁴Department of Pathology, AP-HP Hospital Saint-Louis, Paris, France.
⁵Department of Pathology, AP-HP Cochin Hospital, Centre-Université Paris Cité, Paris, France.
⁶Department of Pathology, Université de Tours, Tours University Hospital, Tours, France.
⁷Department of Biopathology, Center Léon Bérard, Lyon, France.
⁸INSERM U1245, Cancer Center Henri Becquerel, Institute of Research and Innovation in Biomedicine (IRIB), University of Normandy, UNIROUEN, Rouen, France.
⁹Department of Pathology, Cancer Center Henri Becquerel, Rouen, France.
¹⁰Biochemistry and Molecular Biology Department, Groupement Hospitalier Sud, Lyon, France.
¹¹Team Genetics, Epigenetics and Biology of Sarcomas, Centre de Recherche en Cancérologie de Lyon, INSERM U1052 - CNRS UMR5286, Centre Léon Bérard,Université Claude Bernard Lyon 1, Lyon, France.
¹²Pathology Department, Montpellier University Hospital, Montpellier, France.

⁰Department of Pathology, Institute de Pathologie Multisite, Groupement Hospitalier Sud, Lyon University Hospital, Pierre-Bénite, France.

The Journal of Pathology +

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October 29, 2024

View abstract on PubMed

Summary

Pleomorphic adenomas (PAs) and cutaneous mixed tumors (CMTs) share histological similarities. The TRPS1::PLAG1 fusion is common in CMTs, aiding in distinguishing tumor origins and improving diagnosis.

Area Of Science

Oncology
Molecular Pathology
Histopathology

Background

Pleomorphic adenomas (PAs) and cutaneous mixed tumors (CMTs) present diagnostic challenges due to histological similarities.
Both tumor types share genetic profiles, notably PLAG1 rearrangements, complicating differential diagnosis.
Limited attention has been given to molecular distinctions, particularly the TRPS1::PLAG1 fusion in CMTs.

Purpose Of The Study

To investigate the diagnostic utility of TRPS1::PLAG1 fusions in differentiating between cutaneous mixed tumors (CMTs) and pleomorphic adenomas (PAs).
To analyze the molecular, histological, and clinical features of CMTs and PAs.
To identify recurrent gene fusions in CMTs and compare them with those found in PAs.

Main Methods

Retrospective analysis of two cohorts: 46 CMTs and 45 salivary gland PAs from French institutions.
RNA sequencing to identify molecular features, specifically focusing on cases with PLAG1 involvement.
Collection and review of clinical, pathological, and molecular data by subspecialty experts.

Main Results

Cutaneous mixed tumors (CMTs) frequently exhibited recurrent gene fusions, with TRPS1::PLAG1 identified in 74% of cases.
CMTs with TRPS1::PLAG1 fusion showed characteristic tubuloductal differentiation (55%) and squamous metaplasia.
Pleomorphic adenomas (PAs) showed diverse PLAG1 gene fusions, with TRPS1::PLAG1 identified in only one case, indicating a significant disparity.

Conclusions

Recurrent TRPS1::PLAG1 fusion is a hallmark of specific cutaneous mixed tumors (CMTs), often associated with tubuloductal differentiation and squamous metaplasia.
The detection of the TRPS1::PLAG1 fusion can serve as a valuable diagnostic marker for determining tumor origin.
TRPS1 immunostaining did not correlate with the presence of the TRPS1::PLAG1 fusion, highlighting the importance of molecular analysis.

Keywords:

TRPS1::PLAG1 apocrine cutaneous mixed tumor chondroid syringoma cutaneous mixed tumor