ALK is not expressed in Hodgkin disease

Hodgkin disease (HD) is defined by a variable number of Hodgkin and Reed-Sternberg cells associated with a mixture of histiocytes, epithelioid cells, neutrophils, eosinophils, lymphocytes, and plasma cells. Some cases, characterized by a large number of tumor cells, are difficult to differentiate from anaplastic large-cell lymphomas (ALCLs) because both entities demonstrate the presence of large CD30⁺ cells. Although some authors have suggested a potential common pathogenesis, several major conceptual differences distinguish the 2 entities. HD seems to be derived from B cells, whereas ALCL is often of T-cell or null-cell phenotype. A subset of the latter is characterized by a specific translocation t(2;5)(p23;q35). This translocation results in a fusion product of the nuclear phosphoprotein nucleophosmin (NPM) and the anaplastic lymphoma kinase (ALK).

Detection of NPM-ALK as a means of distinguishing ALCL from HD is largely based on molecular analysis. Although some studies concluded there is not such an abnormality in HD,1-6others have found the NPM-ALK fusion mRNA in variable numbers of cases.7-9 The fusion product can be detected also by immunohistochemistry with the ALK1 monoclonal antibody. This antibody recognizes the native ALK protein, as well as the fusion product, and represents a reliable method for detecting the chimeric protein in lymphomas because normal ALK expression is restricted to the central nervous system.1 This technique also has the advantage of being easily performed on paraffin-embedded tissue in a routine setting.

The aim of our study was to test a large series of Hodgkin disease cases for ALK expression, in order to evaluate its diagnostic value in the differential diagnosis between ALCL and HD. Two hundred seventy-eight patients with newly diagnosed advanced Hodgkin disease were selected.11 For each case, histological slides were reviewed by a panel of 3 pathologists.

Standard Avidin-Biotin-Peroxidase method was performed on paraffin sections, using a 1/50 dilution of the monoclonal antibody ALK-1 (kindly provided by D. Mason, Oxford, United Kingdom) after microwave pretreatment. Technical quality was checked with a highly positive ALCL.

Eight patients were classified as having “nodular lymphocyte predominance Hodgkin disease” and 69 as having “classic HD with lymphocyte depletion, rich in tumor cells.” None of the 278 patients with Hodgkin disease tested were found to express ALK. Our series has the advantage of representing a large number of cases having undergone panel review.

This result, in accordance with most published results, does not support the hypothesis of HD and ALCL as histogenically related entities. Moreover, when the differential diagnosis is between HD rich in tumor cells and ALCL, our experience suggests that ALKexpression by tumor cells argues against the former diagnosis.