PMLBCL : Diagnosis

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Diagnosis of Primary Mediastinal Large B-cell Lymphoma (PMLBCL): The location of tumor in the anterosuperior mediastinum necessitates invasive procedures such as mediastinoscopy or percutaneous CT-guided core needle biopsies to get the diagnostic material. The diagnosis is made on the basis of morphologic features in the biopsy specimen, in conjunction with immunohistochemical profile and appropriate clinical presentation.

After diagnosis has been established, the next step of clinical staging requires physical examination, whole body CT or PET/CT imaging, bone marrow biopsy, whole blood count, and serum biochemistries. Serum lactate dehydrogenase is elevated in 70-80% of cases. β2-microglobulin is normal. Most patients present in clinical stage I or II.

Non-mediastinal PMLBCL: Mediastinal involvement is considered essential for the diagnosis of PMLBCL. However, cases of diffuse large B-cell lymphoma with features of PMLBCL but without detectable mediastinal involvement have been reported. These extra-mediastinal tumors have shown gene expression profile similar to PMLBCL, including alterations in CIITA and PDL1/2 genes.

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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