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Molecular analysis of apocrine mixed tumors and cutaneous myoepitheliomas: a comparative study confirming a continuous spectrum of one entity with near-ubiquitous PLAG1 and rare mutually exclusive HMGA2 gene rearrangements

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Abstract

Myoepithelial neoplasms of the skin and soft tissue still represent a confusing and somewhat controversial field in pathology as it appears that this category includes several different entities. However, recent studies have suggested that both apocrine mixed tumors (AMT) and cutaneous myoepitheliomas (CM) harbor identical chromosomal rearrangements involving the PLAG1 gene and hence may represent a morphological spectrum. The aim of the present study was to share our institutional experience with these tumors and specifically focus on studying their immunohistochemical and molecular features to further assess their relatedness. Eleven cases of AMT and 7 cases of CM were collected and analyzed using immunohistochemistry (IHC), PLAG1 FISH, and Archer FusionPlex assay. There were 14 male and 4 female patients with ages ranging from 26 to 85 years (median 55.8 years, mean 58.5 years). AMTs were mainly located in the head and neck (n = 10), while CMs were mainly located in the acral sites (n = 5). PLAG1 IHC was diffusely strongly positive in 14/17 (82%) cases, whereas a single case of AMT diffusely expressed HMGA2. Both tumor groups showed PLAG1 gene fusions which were detected in 6/13 analyzable samples (AMT, n = 4 and CM, n = 2), and included TRPS1::PLAG1 (n = 3), NDRG1::PLAG1 (n = 1), CTNNB1::PLAG1 (n = 1) and a novel PXDNL::PLAG1 fusion (n = 1). The remaining 5 cases were negative, 5 were not analyzable and the single case positive for HMGA2 by IHC revealed a potential HMGA2 gene rearrangement. The cases were further studied by FISH, with 12/17 cases showing PLAG1 gene rearrangement (AMT, n = 8 and CM, n = 4). Altogether, 14/18 cases showed PLAG1 gene rearrangement by at least one of the methods. PLAG1 immunohistochemistry had a 92% specificity and sensitivity. Our study provided additional data to suggest that AMT and CM share overlapping morphological and immunohistochemical features as well as molecular background characterized by PLAG1 gene fusions and thus represent a morphological spectrum. In addition, we identified a novel PXDNL::PLAG1 fusion and suggested that rare cases may harbor HMGA2 gene alterations which seem to be mutually exclusive with PLAG1 gene fusions. The relatedness of these tumors to salivary gland myoepithelial neoplasms and distinctness from eccrine mixed tumors and other skin and soft tissue myoepithelial neoplasms with EWSR1/FUS fusions is discussed.

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Acknowledgments

This project was presented at the 2023 USCAP Annual Meeting.

Availability of data and materials

The complete datasets generated during the current study are available from the corresponding author upon reasonable request.

Funding

This study was supported by study grant SVV 260652 from the Ministry of Education, Czech Republic (BM) and by the Cooperatio program, research area SURG.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic

    Boulos Mansour, Tamás Pancsa, Petr Grossman, Petr Šteiner, Tomáš Vaněček, Kateřina Comová, Michal Michal & Michael Michal

  2. Department of Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200-00128, Roma, Italy

    Michele Donati

  3. Bioptical Laboratory, Ltd., Pilsen, Czech Republic

    Tamás Pancsa, Petr Grossman, Petr Šteiner, Tomáš Vaněček, Kateřina Comová, Michal Michal & Michael Michal

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Contributions

BM and Michael M designed the study, analyzed the data, and drafted the manuscript. TP analyzed some of the data. All authors edited the manuscript and approved the final version of the manuscript.

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Correspondence to Boulos Mansour.

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The study was conducted following the rules set by the Faculty Hospital in Pilsen Ethics Committee. Informed consent was not required for the study.

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Mansour, B., Donati, M., Pancsa, T. et al. Molecular analysis of apocrine mixed tumors and cutaneous myoepitheliomas: a comparative study confirming a continuous spectrum of one entity with near-ubiquitous PLAG1 and rare mutually exclusive HMGA2 gene rearrangements. Virchows Arch (2024). https://doi.org/10.1007/s00428-024-03811-x

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