Version June 2024
| Entity | Histology | Immunophenotype | Genetic features/other |
| ALK-positive anaplastic large cell lymphoma | Large cells with horseshoe-shaped or embryoid nuclei, prominent nucleoli, and abundant cytoplasm ("hallmark cells"). High proliferative fraction. Often shows a cohesive growth pattern often preferentially in the lymph node sinuses or paracortex. | Homogeneous and strong expression of CD30 in a membrane and Golgi pattern. Usually express one or more T cell antigens (ie, CD2, CD3, CD5, CD7). Do not express B cell antigens. CD15 and PAX5/BSAP are negative. | ALK positivity can be detected by immunostains or molecular genetics and is universally present. The majority demonstrate rearranged TCR genes. |
| ALK-negative anaplastic large cell lymphoma | Disease involves the lymph nodes and/or extracutaneous extranodal tissues. Histology resembles ALK-positive ALCL. | Immunophenotype similar to ALK-positive ALCL | ALK negative. TCR genes rearranged. |
| Primary cutaneous anaplastic large cell lymphoma | Disease is confined to the skin. Histology resembles ALK-positive ALCL. | Immunophenotype similar to ALK-positive ALCL | ALK negative. TCR genes rearranged. |
| Diffuse large B cell lymphoma | Large, transformed B cells with prominent nucleoli and basophilic cytoplasm, a diffuse growth pattern and a high proliferation (Ki-67+) fraction. May morphologically resemble ALCL. | Express pan B cell antigens (CD19, CD20, CD22, CD79a). Small subset of tumors with ALK gene rearrangements may be positive for ALK by immunostaining. | The majority has genetic abnormalities, but there is no single cytogenetic change that is typical or diagnostic. Rare tumors have ALK gene rearrangements. |
| Hodgkin lymphoma | The reticular variant of lymphocyte depleted Hodgkin lymphoma may be difficult to distinguish morphologically from ALCL. The HL tumor contains a minority of neoplastic cells (Reed-Sternberg cells and their variants) in an inflammatory background. | The neoplastic cells typically express CD15 and CD30, variably express CD20, and do not express CD3 or CD45. PAX5/BSAP are expressed. T cell antigens are generally negative (rare exceptions). ALK negative. | There is no single cytogenetic change that is typical or diagnostic. Carry IgH gene rearrangements. ALK negative. |
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