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Muddying the Waters: Syncytial Variant Nodular Sclerosis Classic Hodgkin Lymphomas Exhibit a Primary Mediastinal Large B-cell Lymphoma Like Gene Expression Profile Using the Lymph3Cx Gene Expression Profiling Assay

Cheng, J.; Gibson, S.; Barry, R.; Robetorye, R. S.

2025-05-13 pathology
10.1101/2025.05.12.25327251 medRxiv
Show abstract

Mediastinal B-cell lymphomas are relatively frequent in young patients and include nodular sclerosis classic Hodgkin lymphoma (NSCHL), primary mediastinal large B-cell lymphoma (PMBL), and rarely, mediastinal gray zone lymphoma (MGZL). Occasional NSCHLs contain abundant Hodgkin/Reed Sternberg (HRS) cells that exhibit a syncytial growth pattern, which may create diagnostic challenges. Previous studies have demonstrated that PMBL can be distinguished from subtypes of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures using the Lymph3Cx gene expression profiling assay, which has been validated as a clinical test in our molecular diagnostics laboratory. Here, we demonstrate that syncytial variant NSCHL exhibits a PMBL-like gene expression profile using the Lymph3Cx gene expression profiling assay. It is critical for pathologists and oncologists to be aware of this potential diagnostic pitfall to avoid possible misdiagnosis.

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