PMLBCL : Epidemiology & Sites

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Image Description

Epidemiology: Primary Mediastinal Large B-cell Lymphoma (PMLBCL) accounts for 2-3% of non-Hodgkin lymphomas and about 6% of diffuse large B-cell lymphomas. It occurs mainly in young adults (median age 35 years) with a predilection for females (F:M=2:1). Some cases occur in children and adolescents.

Sites: Most patients present with a rapidly growing bulky mass (> 10 cm size in 75% of cases) localized in the anterosuperior mediastinum. The tumor frequently invades surrounding thoracic structures such as sternum, chest wall, lungs, pleura, and pericardium. Supraclavicular and cervical lymph nodes may be involved. In advanced stages, the lymphoma spreads to extranodal sites such as CNS, liver, kidneys, and adrenals. Bone marrow involvement or leukemic phase are rare (2%) or absent. Rare cases of PMLBCL are extramediastinal with no mediastinal involvement.

This plain radiograph of chest shows an expanded cardiomediastinal contour due to a large superior mediastinal mass. Diagnosis of PMLBCL was confirmed by a CT-guided needle biopsy of the mass (same case as the previous image). Case courtesy of Assoc Prof Frank Gaillard, Radiopaedia.org. From the case rID: 8655

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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