High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining

Abstract

Fifty-six cases of anaplastic large cell lymphoma (ALCL), 23 cases of Hodgkin's disease, and 16 cases of diffuse large cell lymphoma were investigated for the t(2;5)(p23;q35) translocation. The translocation was detected by using cytogenetic analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry with P80 antibody directed against the kinase domain of anaplastic lymphoma kinase (ALK) of the chimeric NPM/ALK protein. In all but three cases of ALCL, we found an agreement between cytogenetic analysis, RT-PCR, and P80 staining. However, in one case, the t(2;5) translocation was detected with cytogenetic analysis, but RT-PCR and P80 staining were found to be negative. Conversely, in another case the karyotype was normal, but the hybrid mRNA and P80 staining were found to be positive. In one case, malignant cells showed a translocation involving chromosomes 1q25 and 2p23 and were strongly positive for P80 staining. Such a result could be expected because P80 antibody detects the kinase domaine of the ALK protein encoded by chromosome 2p23. Overall 73.2% (41 of 56) of cases were found to be positive. However, the highest percentage (23 of 26 cases; 88.5%) of P80 positive cases was found in children compared with 60% (18 of 30 cases) in adult ALCL (P < .05). In Hodgkin's disease, Reed-Sternberg cells were found to be clearly negative by RT-PCR and with P80 antibody. The latter results suggest that Hodgkin's disease and t(2;5)-positive ALCL are distinct biological entities and that the demonstration of the t(2;5) translocation is of diagnostic importance in differentiating these two entities. The results of the present study indicate that immunohistochemistry with P80 antibody is a reliable method for detecting NPM/ALK chimeric protein.

A lymphohistiocytic variant of anaplastic large cell lymphoma with demonstration of the t(2;5)(p23;q35) chromosome translocation

“…RT-PCR analysis demonstrated the presence of the NPM/ALK fusion product and p80 NPM/ALK expression was found in the tumour cells. Therefore this case provides evidence that the lymphohistiocytic variant belongs to the spectrum of anaplastic large cell lymphoma and confirms recent data from Lamant et al (1996) describing NPM/ALK fusion products in two of six cases analysed by RT-PCR and from Pileri et al (1997) who found immunohistochemical evidence for the expression of the NPM/ALK fusion protein in three of five cases. However, no cytogenetic data were available in either series.…”

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

“…2 However, there are differences in clinical behaviour and outcome which might be dependent on other factors such as the expression of adhesion molecules or molecular abnormalities. Thus, despite some controversies, NPM/ALK rearrangements resulting in ALK protein expression, are mostly found in a proportion of systemic ALCL, 41 and only rarely detected in cutaneous ALCL. 42 Absence of detectable ALK expression in all cases of CD30þ CTCL and LP in the present series, further supports the concept that distinct genetic events may be implicated in systemic ALCL and cutaneous CD30þ lymphoproliferative disorders.…”

Bone marrow histopathology in peripheral T‐cell lymphomas

“…In contrast, primary nodal ALCL is a systemic disease characterized by large atypical lymphoid cells with abundant cytoplasm and characteristic horseshoe shaped nuclei (hallmark cells) (Stein et al , 2000). Most cases of primary nodal ALCL have translocations involving the ALK‐1 gene, which leads to overexpression of the gene product (Lamant et al , 1996; Benharroch et al , 1998). A subset of the cases with identical histological and immunophenotypic features lack ALK‐1 translocation.…”