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ALK-Positive Lymphoma: A Single Disease With a Broad
Spectrum of Morphology
Daniel Benharroch,
Zarouhie Meguerian-Bedoyan,
Laurence Lamant,
Chauki Amin,
Laurence Brugières,
Marie-Jose Terrier-Lacombe,
Eugenia Haralambieva,
Karen Pulford,
Stefano Pileri,
Stephan W. Morris,
David Y. Mason, and
Georges Delsol
From the Department of Pathology and CIGH/CNRS, CHU Purpan, Toulouse,
France; the Department of Pediatric Oncology, Institut Gustave Roussy,
Villejuif, France; the LRF Immunodiagnostics Unit, Department of
Cellular Science, John Radcliffe Hospital, Oxford, UK; the Service of
Pathologic Anatomy and Hematopathology Section, Bologna University,
Bologna, Italy; and the Department of Experimental Oncology, St Jude
Children's Research Hospital, Memphis, TN.
The t(2;5)(p23;q35) translocation, associated with anaplastic
large-cell lymphoma (ALCL), results in the expression of a chimeric NPM-ALK protein that can be detected by the ALK1 monoclonal antibody. This report describes the morphologic and phenotypic spectrum of 123 cases of lymphoma that all express ALK protein. The results provide
strong evidence that the morphologic patterns of ALCL described in
previous reports as representing possible subtypes of ALCL, eg, common
type, lymphohistiocytic, or small cell patterns, are morphologic
variants of the same disease entity. All of these morphologic patterns
could be found within this series, and in some patients different
subtypes coexisted in a single biopsy or were found in successive
biopsies from a single patient. The link between these morphologic
subtypes is further reinforced by the presence in all cases of a highly
characteristic large cell, with an eccentric nucleus and an
eosinophilic paranuclear region. We suggest that this cell can be
considered as a major distinguishing feature of ALK-positive lymphomas.
Another characteristic of these tumors was the perivascular pattern of
neoplastic cell infiltration seen in a significant number of cases. In
addition to ALK protein, all tumors expressed epithelial membrane
antigen and lacked CD15, features that may be of value in
differentiating ALCL from Hodgkin's disease. In the majority of cases
(84%), malignant cells showed both a cytoplasmic and nuclear staining
for ALK1 and thus presumably carried the 2;5 translocation, but
staining was restricted to the cytoplasm in a few cases, suggesting
that translocations other than t(2;5) may induce expression of ALK protein. We conclude from this study that ALK-positive neoplasms represent a distinct entity. Because their morphology is often neither
anaplastic nor large cell, we suggest that they should henceforward be
referred to as ALK lymphomas.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 2076-2084
© 1998 by The American Society of Hematology.
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J. L. Cordell, K. A.F. Pulford, B. Bigerna, G. Roncador, A. Banham, E. Colombo, P.-G. Pelicci, D. Y. Mason, and B. Falini
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L. Brugieres, M.C. L. Deley, H. Pacquement, Z. Meguerian-Bedoyan, M.J. Terrier-Lacombe, A. Robert, C. Pondarre, G. Leverger, C. Devalck, C. Rodary, et al.
CD30+ Anaplastic Large-Cell Lymphoma in Children: Analysis of 82 Patients Enrolled in Two Consecutive Studies of the French Society of Pediatric Oncology
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I. Wlodarska, C. De Wolf-Peeters, B. Falini, G. Verhoef, S. W. Morris, A. Hagemeijer, and H. Van denBerghe
The Cryptic inv(2)(p23q35) Defines a New Molecular Genetic Subtype of ALK-Positive Anaplastic Large-Cell Lymphoma
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