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5-hmC loss is another useful tool in addition to BAP1 and MTAP immunostains to distinguish diffuse malignant peritoneal mesothelioma from reactive mesothelial hyperplasia in peritoneal cytology cell-blocks and biopsies

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Abstract

The differentiation between reactive mesothelial hyperplasia (RMH) and diffuse malignant peritoneal mesothelioma (DMPM) is challenging especially when applied on peritoneal small samples. The use of BRCA-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) immunostains is familiar to identify malignant mesothelial proliferation. Recently, nuclear 5-hydroxymethylcytosine (5-hmC) was reported to be a new recognition tool of pleural mesothelial malignancy on surgical specimens. However, application of 5-hmC immunostaining has not yet studied in peritoneal specimens from small biopsies or cytology cell-blocks. The aim was to assess the diagnostic accuracy of this new marker combination to distinguish DMPM from RMH in biopsies and cell-blocks. Seventy-five cases were analyzed; among which, 38 were of cytological specimens including 6 RMH and 32 DMPM, and 37 tissue biopsies with 7 RMH and 30 DMPM. BAP1, MTAP, and 5-hmC immunostains were performed on all cases. RMH cases exhibited a retained staining with all immunostains. Among DMPM, BAP1 was lost in 71.8% of cytology cell-blocks and 66.7% of biopsies. MTAP was lost in 40.6% of cytology cell-blocks and 33.3% of biopsies. 5-hmC was lost in 40.6% of cytology cell-blocks and 30% of biopsies. The combination of BAP1, MTAP, and 5-hmC showed the best accuracy in differential diagnosis between RMH and DMPM (sensitivity = 0.84, specificity = 1 in cytology cell-blocks; sensitivity = 0.90, specificity = 1 in biopsy). The best diagnostic combination in peritoneal cytology effusion fluids and biopsies samples provided by BAP1, MTAP, and 5-hmC should be applied on a diagnostic step-wise algorithm by pathologists involved into the management of DMPM, because of their therapeutic implications.

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Acknowledgements

The authors wish to thank Philip Robinson for the English language correction and critical suggestions; and Centre de Ressources Biologique de Lyon Sud for the technical support and especially Mathilde Bardou.

Funding

This work was supported by the Association contre les maladies rares du péritoine (AMARAPE).

Author information

Authors and Affiliations

  1. Department of Pathology, Institut de Pathologie Multisite, Groupement Hospitalier Sud, Hospices Civils de Lyon, 165 chemin du Grand-Revoyet, 69310, Pierre-Bénite, France

    Ziyad Alsugair, Sylvie Isaac, Juliette Hommell-Fontaine & Nazim Benzerdjeb

  2. Department of Digestive Surgery, Lyon University Hospital, Pierre-Bénite, France

    Vahan Kepenekian & Olivier Glehen

  3. EA 3738 CICLY, Lyon 1 University, Lyon, France

    Vahan Kepenekian, Olivier Glehen, Laurent Villeneuve, Sylvie Isaac, Juliette Hommell-Fontaine & Nazim Benzerdjeb

  4. French Network for Rare Peritoneal Tumors (RENAPE), Villeurbanne, France

    Vahan Kepenekian, Olivier Glehen, Laurent Villeneuve, Sylvie Isaac, Juliette Hommell-Fontaine & Nazim Benzerdjeb

  5. Department of Pathology, Institut de Pathologie Multisite, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France

    Tanguy Fenouil

  6. Biostatistics Unit, Hospices Civils de Lyon, Lyon, France

    Laurent Villeneuve

  7. Unité de Recherche Clinique, Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Lyon, France

    Laurent Villeneuve

Authors
  1. Ziyad Alsugair
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  2. Vahan Kepenekian
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  3. Tanguy Fenouil
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  4. Olivier Glehen
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  5. Laurent Villeneuve
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  6. Sylvie Isaac
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  7. Juliette Hommell-Fontaine
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  8. Nazim Benzerdjeb
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Contributions

NB and ZA contributed to the design, analysis, and scripting of this manuscript. VJ, TF, OG, LV, SI, and JHF contributed to the writing and reviewing of this manuscript.

Corresponding author

Correspondence to Nazim Benzerdjeb.

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Ethics approval

Approved by the ethics committee of Hospices Civils de Lyon (approval number, 19–74; approval date, April 2019).

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The authors declare no competing interests.

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Alsugair, Z., Kepenekian, V., Fenouil, T. et al. 5-hmC loss is another useful tool in addition to BAP1 and MTAP immunostains to distinguish diffuse malignant peritoneal mesothelioma from reactive mesothelial hyperplasia in peritoneal cytology cell-blocks and biopsies. Virchows Arch 481, 23–29 (2022). https://doi.org/10.1007/s00428-022-03336-1

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  • DOI: https://doi.org/10.1007/s00428-022-03336-1

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