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Aims <p>To describe the morphological features and explore the molecular profiles of pleomorphic adenomas (PA) with abundant lymphoid stroma and <i>HMGA2</i> rearrangements, and to compare them with classic lymphadenomas, in order to identify a potential molecular and morphological overlap.</p> Methods <p>Four cases of PA with abundant lymphoid stroma and <i>HMGA2</i> rearrangements were identified from four different institutions in France and Japan. Their characterisation was performed through a detailed pathological, immunohistochemical, and molecular analysis.</p> Results <p>All tumours were well-circumscribed and encapsulated, predominantly composed of ductal and tubular structures with scattered myoepithelial cells embedded within a dense lymphoid stroma rich in non-atypical lymphocytes. Immunohistochemistry was positive for CK7, p63, p40, SOX10, S100, and HMGA2, and negative for PLAG1. The Ki67 proliferation index was low. Molecular analyses revealed no <i>MDM2</i> amplification and excluded EBV infection. Clonality studies confirmed a polyclonal lymphoid infiltrate. Targeted DNA and RNA sequencing found no mutation; however, three cases harboured <i>HMGA2</i>::<i>WIF1</i> fusions and one harboured <i>HMGA2</i>::<i>RPSAP52</i> fusion. In the transcriptomic analysis, these tumours clustered together with classic lymphadenomas, separated from other salivary gland neoplasms.</p> Conclusions <p>The present study reports four cases of pleomorphic adenoma characterised by abundant lymphoid stroma and <i>HMGA2</i> rearrangements, for which transcriptomic analysis found that the lymphoid stroma shared a profile similar to that observed in lymphadenomas. Given this distinctive morphological and molecular feature, we propose the designation “lymphadenoma-like” for this novel subtype of pleomorphic adenoma.</p>

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Histomolecular Features of a Rare Subtype of Pleomorphic Adenoma Characterised by Abundant Lymphoid Stroma and HMGA2 Rearrangements

  • 期刊论文

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  • 发表日期：

    2025年12月29日

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  • Ziyad Alsugair,
  • Seddig Momenkhan,
  • Marie Donzel,
  • Françoise Descotes,
  • Daniel Pissaloux,
  • Sandrine Paindavoine,
  • Aurelie Houlier,
  • Franck Tirode,
  • Eudeline Alix,
  • Claire Mauduit,
  • Jonathan Lopez,
  • Alexandra Traverse-Glehen,
  • Philippe Céruse,
  • Pierre Philouze,
  • Anne Champagnac,
  • Valérie Costes-Martineau,
  • Yoshinao Kikuchi,
  • Hiroshi Uozaki,
  • Emmanuelle Vaz,
  • Claire Castain,
  • Nazim Benzerdjeb

摘要

Aims

To describe the morphological features and explore the molecular profiles of pleomorphic adenomas (PA) with abundant lymphoid stroma and HMGA2 rearrangements, and to compare them with classic lymphadenomas, in order to identify a potential molecular and morphological overlap.

Methods

Four cases of PA with abundant lymphoid stroma and HMGA2 rearrangements were identified from four different institutions in France and Japan. Their characterisation was performed through a detailed pathological, immunohistochemical, and molecular analysis.

Results

All tumours were well-circumscribed and encapsulated, predominantly composed of ductal and tubular structures with scattered myoepithelial cells embedded within a dense lymphoid stroma rich in non-atypical lymphocytes. Immunohistochemistry was positive for CK7, p63, p40, SOX10, S100, and HMGA2, and negative for PLAG1. The Ki67 proliferation index was low. Molecular analyses revealed no MDM2 amplification and excluded EBV infection. Clonality studies confirmed a polyclonal lymphoid infiltrate. Targeted DNA and RNA sequencing found no mutation; however, three cases harboured HMGA2::WIF1 fusions and one harboured HMGA2::RPSAP52 fusion. In the transcriptomic analysis, these tumours clustered together with classic lymphadenomas, separated from other salivary gland neoplasms.

Conclusions

The present study reports four cases of pleomorphic adenoma characterised by abundant lymphoid stroma and HMGA2 rearrangements, for which transcriptomic analysis found that the lymphoid stroma shared a profile similar to that observed in lymphadenomas. Given this distinctive morphological and molecular feature, we propose the designation “lymphadenoma-like” for this novel subtype of pleomorphic adenoma.