A New Subtype of Large B-Cell Lymphoma Expressing the ALK Kinase and Lacking the 2; 5 Translocation

Abstract

Seven cases of large B-cell lymphoma which define a previously unrecognized subgroup are reported. Morphologically they are comprised of monomorphic large immunoblast-like cells, containing large central nucleoli, which tend to invade lymphatic sinuses. Superficially they resemble anaplastic large cell lymphoma (ALCL) but they lack CD30. These lymphomas express epithelial membrane antigen (as do ALCL), but also contain intracytoplasmic IgA of a single light chain type (five cases) and an endoplasmic reticulum–associated marker detected by antibody VS38. They lack lineage-associated leukocyte antigens with the exception of CD4 (5 of 5 cases) and CD57 (5 of 7 cases). They are labeled by antibodies detecting both the intracytoplasmic and extracellular regions of the ALK receptor kinase, suggesting that they express the full-length form of this molecule. This was confirmed by Western blotting (in the one case tested) which showed a band of 200 kD in tumor cell lysates, and by polymerase chain reaction (PCR) amplification of mRNA encoding intracellular and extracellular ALK sequences (in the two cases tested). There was no evidence by cytogenetics (one case analyzed) or reverse transcriptase-PCR (three cases tested) of the 2; 5 translocation or the resultant NPM-ALK gene, as is commonly found in ALCL. All but one of the patients were male and all but one were adults, and in all but the latter case the disease followed an aggressive course.

ALK+ large B‐cell lymphoma: A rare variant of aggressive large B‐cell lymphoma mimicking carcinoma on cytology specimens

“…The new entities were recognized in view of their unique immunohistochemical, cytogenetic, and clinical findings. One of these new recognized entities, ALK+ LBCL, was first described in the literature by Delsol et al in 1997 6. Since the first series, less than 100 cases have been reported in the literature 7–11.…”

A case of anaplastic lymphoma kinase‐positive large B‐cell lymphoma: Aspiration cytology findings

“…Anaplastic lymphoma kinase‐positive (ALK+) large B‐cell lymphoma (LBCL) is a rare subtype of non‐Hodgkin B‐cell lymphoma that was first described by Delsol et al in 1997 and recognized as a separate entity in the World Health Organization classification in 2008 . ALK+LBCL preferentially involves the lymph nodes in men.…”

PAX‐5 is invariably expressed in B‐cell lymphomas without plasma cell differentiation

“…They consisted of de novo CD20− B‐cell lymphomas, a series of known B‐cell lymphoma status post rituximab treatment and well‐defined variants of DLBCL with plasma cell differentiation. The latter were characterized by strong expression of CD138 and/or cytoplasmic immunoglobulin, such as plasmablastic lymphoma, 17 human herpesvirus (HHV8)+ IgMλ plasmablastic lymphoma, 18 primary effusion lymphoma 19 and ALK1+ DLBCL 20 . It should be emphasized that all cases had a definitive diagnosis based on existing criteria of World Health Organization classification independent of PAX‐5 expression.…”