PMLBCL : Immunophenotype

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Image Description

Primary Mediastinal Large B-cell Lymphoma (PMLBCL) - Immunophenotype: PMLBCL expresses pan B-cell antigens CD19, CD20, CD22, and CD79a. Despite functional Ig gene arrangements and the presence of CD79a, most cases lack surface or cytoplasmic immunoglobulin. Surface Ig may be present on flow cytometry in a small subset of cases.

The status of other markers is as follows: PAX5+; CD30+ in 70% of cases with weak and heterogenous staining; CD15+ in minority of cases; EBV absent; IRF4/MUM1+ in 75%; BCL2+ in 55-80%; BCL6+ in 60%; CD10+ in 25%; CD11c+ in 40%; CD21 negative; CD23+ in 70%; PDL1+, PDL2 (CD273)+ in 72%; MYC+ in >30% of cells.

MAL gene on chromosome 2q - a marker associated with thymic medullary B-cells - is expressed in 70% of PMLBCL but only 3% of diffuse large B-cell lymphomas. It can be detected by molecular techniques or immunohistochemistry.

Transcription factors PU.1, OCT2, PAX5, and BOB1 are often positive in a majority of cases.

Image courtesy of: Lorand Kis, MD, Sweden; used with permission.

About the Disease

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare, aggressive, distinct subtype of large B-cell lymphoma localized in anterosuperior mediastinum. It shares clinical, morphologic, and molecular genetic features with nodular sclerosing Hodgkin lymphoma. It makes up 2-3% of non-Hodgkin lymphomas and affects young adults with a female predilection. Patients develop compressive symptoms, such as cough and dyspnea, from the rapidly growing mediastinal mass. About 20-30% have superior vena cava syndrome. Pleural and pericardial effusion develop in 30-50%. Surrounding thoracic structures may be invaded. Bone marrow is rarely involved. Extranodal sites may be invaded in advanced stages. The tumor cells are highly variable, medium-to-large size, with irregular or multilobated nuclei and pale or clear cytoplasm in a sclerotic stroma. Reed-Sternberg-like cells may be present. Immunophenotype: positive for pan B-cell antigens (CD19, CD20, CD22, CD79a), no surface or cytoplasmic immunoglobulins, PDL1+, PDL2+, PAX5%, CD30+ (variable, heterogenous), IRF4/MUM1+, BCL2, BCL6, PU.1, OCT2; variable positivity for CD15, CD10, CD11c, CD23, MYC; negative for EBV. MAL gene (chromosome 2q) is + in 70%. Ig heavy and light chain genes are clonally rearranged. TCR genes are germline. Rearrangements of CCND1, BCL2, BCL6, and MYC are rare/absent. Three molecular pathways are implicated in the pathogenesis - NF-κB signaling pathway, JAK-STAT signaling cascade, and immune privilege. References:Dabrowska-Iwanicka A & Walewski J. Primary Mediastinal Large B-cell Lymphoma. Curr Hematol Malig Rep (2014) 9:273-283. Lees, C. et al. Biology and therapy of primary mediastinal B-cell lymphoma : current status and future directions. British Journal of Haematology, 2019, 185, 25-41. Jaffe, E. S. et al (2017). Hematopathology - Second Edition. Philadelphia, PA. Elsevier. Swerdlow, S. H. et al (2017). WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, Revised 4th Edition; IARC, Lyon, France.

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