PMLBCL : Treatment & Prognosis

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Image Description

Treatment & Prognosis of Primary Mediastinal Large B-cell Lymphoma (PMLBCL) : The treatment consists of multiagent chemotherapy and rituximab (monoclonal anti-CD20 antibody) with or without radiation. Pembrolizumab - a PD-1 checkpoint inhibitor - has been approved for refractory or relapsed PMLBCL. The overall 5-yr survival rate ranges from 79% to 97% and the cure rate ranges from 50% to 80%. The prognosis is comparable to diffuse large B-cell lymphoma, NOS.

Poor prognostic indicators include: pleural or pericardial effusion, involvement of multiple extranodal sites, high serum LDH level, and low performance scores.

About 10-30% of PMLBCL patients relapse or have refractory disease and require salvage therapy. Recurrent PMLBCL has a tendency to involve unusual sites such as kidney, CNS, adrenal gland, liver, pancreas, GI tract, and ovary.

This image of PMLBCL shows tumor cells with clear or pale cytoplasm and large round, oval, or irregular multilobated nuclei. A few delicate sclerotic bands are seen surrounding the tumor cells.

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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