Mediastinal Grey Zone Lymphoma

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Image Description

Mediastinal Grey-zone Lymphoma (MGZL): This is a category of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). They have overlapping clinical, morphologic, immunohistochemical, and molecular genetic features with primary mediastinal large B-cell lymphoma (PMLBCL), DLBCL, and cHL.

They occur in young patients (median age 33 years) but with a male predominance. Clinical presentation is similar to PMLBCL. Microscopic features are variable and the tumor cells range in appearance from centroblasts to lacunar-like, or Hodgkin-like cells. Background stroma is fibrotic with a sparse inflammatory infiltrate. Coagulative necrosis may be seen. Mediastinal grey-zone lymphomas are more aggressive than both PMLBCL and cHL with a worse prognosis.

Image courtesy of: Lucas R. Massoth, MD (@LucasMassoth); 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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