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.

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SUMMARY The immunophenotypic properties of 25 cutaneous non-Hodgkin lymphomas other than mycosis fungoides or Sezary syndrome were investigated and correlated with clinical and histopathological data. The 11 low grade lymphomas were all of B cell origin, whereas the 14 high grade lymphomas comprised B and T cell tumours, true histiocytic proliferations, and one "null" cell lymphoid neoplasm. For the high grade lymphomas correct prediction of the immunological phenotype based on morphological criteria was only possible in three cases. In contrast, all of the low grade lymphomas showed the non-epidermotropic infiltration pattern considered to be characteristic of cutaneous B cell tumours. For these conditions, however, immunophenotypic investigations provided a convenient means of improving discrimination between benign (polyclonal) and malignant (monoclonal) lesions, and also showed similarities with nodal lymphomas in terms of expression of lymphoid subset markers and composition of the non-neoplastic white cell infiltrate. No differences were identified between primary and secondary or concurrent cutaneous and extracutaneous lymphomas.Cutaneous non-Hodgkin lymphomas other than mycosis fungoides or Sezary syndrome constitute a heterogeneous group of neoplasms and most of these disorders are likely to represent cutaneous equivalents of nodal malignancies. Immunophenotypic investigations form a useful supplement to their histogenetic characterisation and may provide a common conceptual basis for their classification.It is generally accepted that cutaneous non-Hodgkin lymphomas can be divided into two principal distinct categories on clinical, histopathological, and immunophenotypic criteria-that is, mycosis fungoides or Sezary syndrome and other variants of lymphoma.