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

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.