Blood, 15 March 2001, Vol. 97, No. 6, pp. 1901-1902
CORRESPONDENCE
To the editor:
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,1-6
others 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 ALK
expression by tumor cells argues against the former diagnosis.
Sophie Camilleri-Broët and Josée Audouin
Hôtel-Dieu
Paris, France
Christophe Fermé
Hôpital Saint Louis
Paris, France
Josette Brière, and Karen Pulford
Nuffield Department Clinical Laboratory Sciences John
Radcliffe Hospital
Oxford, United Kingdom
Philippe Gaulard, and Marine Diviné
Hôpital Henri Mondor
Créteil, France
Elizabeth Macintyre
Hôpital Necker
Paris, France
Georges Delsol
Hôpital Purpan
Toulouse, France
Françoise Berger
Hôpital Edouard Herriot
Lyon, France
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