Anaplastic large-cell lymphomas of T-cell and null-cell phenotype express cytotoxic molecules

Abstract

To further specify the cellular origin and nature of anaplastic large- cell lymphoma (ALCL) and its relationship to other lymphoid neoplasms, particularly Hodgkin's disease (HD), we investigated the presence of cytotoxic molecules in a large well-characterized series of these tumors. For expression of the cytotoxic molecules perforin and granzyme B, in situ hybridization (ISH) and immunohistology were used, respectively. Overall, 23 of 25 ALCLs of T/null phenotype and five (three mixed cellularity and two nodular sclerosis) of 57 HD cases showed the presence of perforin transcripts and/or granzyme B molecules in neoplastic cells. Polymerase chain reaction (PCR) analysis of ALCLs showed that most (10 of 11) cases of null-cell ALCL (null-ALCL) contained a clonal rearrangement of T-cell receptor beta-chain genes, as did T-cell ALCL (T-ALCL; 9 of 10 cases). However, both cytotoxic molecules and clonally rearranged T-cell receptor beta-chain genes were absent in seven of seven and eight of nine cases of B-cell ALCL (B-ALCL), respectively. These data show that all or nearly all T-ALCLs, irrespective of the clinical subform or the lack of T-cell-associated molecules, are derived from activated cytotoxic T cells. The same appears to be true for the neoplastic cells of rare HD cases. These findings indicate that T-ALCLs are different from B-ALCLs and the majority of HD cases, and suggest that some HD cases, especially those with T-cell antigen-positive tumor cells, may be closely related to T- ALCL, at least in terms of cellular origin.

Primary CD30‐positive cutaneous T‐cell lymphomas and lymphomatoid papulosis frequently express cytotoxic proteins

“…Although recent studies agree on the expression of cytotoxic proteins in systemic ALCL, [18][19][20] the results concerning primary cutaneous ALCL are still controversial. [20][21][22] Indeed, in keeping with our data, Foss et al found perforin transcripts in 3/3 cases of cutaneous CD30þ ALCL 21 and Kummer et al found granzyme B protein expression in 10/14 CD30þ cutaneous ALCL. 22 In contrast, Krenacs et al reported no expression of TIA-1 and perforin proteins in three cases of cutaneous CD30þ ALCL.…”

“…20 It is likely that the discrepancies between these studies might be due, at least partly, to the different criteria used to assess positivity. [20][21][22] Our finding that most cases (75%) of LP express at least one…”

“…18,20,21 Concerning cutaneous CD30þ lymphoproliferations, controversial results have been reported. 20,21 However, there is a recent systematic study on CTCL showing that CD30þ ALCL and LP express a cytotoxic phenotype. 22 In that study, 22 the TIA-1 and granzyme B expression was analysed whereas the perforin expression was not investigated.…”

cDNA arrays: Gene expression profiles of Hodgkin's disease and anaplastic large cell lymphoma cell lines

“…Wellmann and coworkers identified clusterin as a differentially expressed gene in ALCL, 8 and the cytotoxic molecule perforin is generally expressed in ALCL but not in HD. 11 Unfortunately, these genes were not part of the cDNA array used in this study. Neither were the B-cell transcription factors Oct-2 and Bob1, which seem to be helpful in the diagnosis of Hodgkin's disease.…”

Primary ALK‐1‐negative anaplastic large cell lymphoma of the brain: Case report and review of the literature

“…2,3 Most ALCLs express T-cell antigens, and the less common "null cell" tumors often show genetic evidence of T-cell lineage. [2][3][4][5][6][7][8] The majority of ALCLs present as nodal disease, but primary involvement and secondary spread to extranodal sites is frequent. 2,8,9 The majority (60-85%) of ALCLs are associated with a characteristic t(2;5) (p23;q35) chromosome translocation that causes the anaplastic lymphoma kinase (ALK) gene on chromosome 2 to fuse with the nucleoplasmin (NPM) gene on chromosome 5, which results in ALK-1 protein expression.…”