PMLBCL : Differential Diagnosis

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Differential Diagnosis of Primary Mediastinal Large B-cell Lymphoma (PMLBCL) (continued from previous slide): The list includes - classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma, NOS (DLBCL-NOS), anaplastic large cell lymphoma (ALCL), mediastinal seminoma, thymic carcinoma, and thymic carcinoid.

Features favoring Anaplastic Large Cell Lymphoma: hallmark cells - large anaplastic cells with eccentric horseshoe- or kidney-shaped nuclei and abundant clear, eosinophilic or basophilic cytoplasm, pan B-cell -ve, pan T-cell +/-, ALK+/-, CD30+, EMA+/-, cytotoxic markers +/-

Features favoring PMLBCL: Presence of sclerosis, Pan B-cell+, Pan T-cell-ve, EMA-ve

Features favoring Mediastinal Seminoma: male patient, round nuclei, lymphocytes in fibrous septa separating tumor cells, CD45-, CD117+, PLAP+, OCT3/4+

Features favoring Thymic Carcinoma: cohesive sheets, cytokeratin+, squamoid features, Pan B-cell-, CD45-

Features favoring Thymic Carcinoid: Organoid pattern, rich vasculature, rosettes, cytokeratin+, neuroendocrine markers+, CD45-, Pan B-cell-

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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