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Differential Diagnosis of Primary Mediastinal Large B-cell Lymphoma (PMLBCL): 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.

PMLBCL and cHL have a lot of common clinical and morphologic features, including young patient age, origin from thymic B-cells, location primarily in anterior mediastinum, large tumor cells, and sclerosis. CD30 positive tumor cells (a feature of cHL) may be found in PMLBCL and pan-B-cell marker expression (a feature of PMLBCL) may be seen in cHL.

Features favoring cHL over PMLBCL:
  • polymorphous infiltrate in the background with numerous eosinophils
  • tumor cells positive for CD30 and CD15 but negative for CD45
  • B-cell markers, when present, are heterogenous and not uniformly strongly positive
  • negative for immunoglobulin transactivating factors OCT-2 and BOB-1
  • EBV positive
  • Grb2 positive in only 10% (vs 98% for PMLBCL)
  • cyclin E positive (79% in cHL vs 0% in PMLBCL)
Some cases may consist of both PMLBCL and cHL (Composite lymphoma) and show same clone of tumor cells in both components. Others may be PMLBCL to start with but relapse as cHL (Mediastinal sequential lymphoma).

Differential diagnosis continues in the next slide.

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