ALK+ Lymphoma: Clinico-Pathological Findings and Outcome

• Published in: Blood 1999-04, Vol.93 (8), p.2697-2706
• Main Authors: Falini, Brunangelo, Pileri, Stefano, Zinzani, Pier Luigi, Carbone, Antonino, Zagonel, Vittorina, Wolf-Peeters, Chris, Verhoef, Gregor, Menestrina, Fabio, Todeschini, Giuseppe, Paulli, Marco, Lazzarino, Mario, Giardini, Roberto, Aiello, Antonella, Foss, Hans-Dieter, Araujo, Iguacyra, Fizzotti, Marco, Pelicci, Pier-Giuseppe, Flenghi, Leonardo, Martelli, Massimo F., Santucci, Antonella
• Format: Article
• Language: English
• Subjects: Adult; Anaplastic Lymphoma Kinase; Biological and medical sciences; Biomarkers, Tumor - analysis; Cell Nucleus - enzymology; Cytoplasm - enzymology; Female; Hematologic and hematopoietic diseases; Humans; Ki-1 Antigen - analysis; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large B-Cell, Diffuse - enzymology; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medical sciences; Prognosis; Protein-Tyrosine Kinases - analysis; Receptor Protein-Tyrosine Kinases; Retrospective Studies; Survival Analysis; Time Factors; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V93.8.2697

A distinct pathologic entity (ALK+ lymphoma) that is characterized by expression of the anaplastic lymphoma kinase (ALK) protein has recently emerged within the heterogeneous group of CD30+ anaplastic large-cell lymphomas. Information on clinical findings and treatment outcome of ALK+ lymphoma is still limited, and no data are available concerning the value of the International Prognostic Index when applied to this homogeneous disease entity. To clarify these issues, a recently developed monoclonal antibody ALKc (directed against the cytoplasmic portion of ALK) was used to detect expression of the ALK protein in paraffin-embedded biopsies from 96 primary, systemic T/null anaplastic large-cell lymphomas, and the ALK staining pattern was correlated with morphological features, clinical findings, risk factors (as defined by the International Prognostic Index), and outcome in 78 patients (53 ALK+ and 25 ALK−). Strong cytoplasmic and/or nuclear ALK positivity was detected in 58 of 96 ALCL cases (60.4%), and it was associated with a morphological spectrum (common type, 82.7%; giant cell, 3.5%; lymphohistiocytic, 8.6%; and small cell, 5.2%) that reflected the ratio of large anaplastic elements (usually showing cytoplasmic and nuclear ALK positivity) to small neoplastic cells (usually characterized by nucleus-restricted ALK expression). Clinically, ALK+ lymphoma mostly occurred in children and young adults (mean age, 22.01 ± 10.87 years) with a male predominance (male/female [M/F] ratio, 3.0) that was particularly striking in the second-third decades of life (M/F ratio, 6.5) and usually presented as an aggressive, stage III-IV disease, frequently associated with systemic symptoms (75%) and extranodal involvement (60%), especially skin (21%), bone (17%), and soft tissues (17%). As compared with ALK+ lymphoma, ALK− cases occurred in older individuals (mean age, 43.33 ± 16.15 years) and showed a lower M/F ratio (0.9) as well as lower incidence of stage III-IV disease and extranodal involvement at presentation. Overall survival of ALK+ lymphoma was far better than that of ALK− anaplastic large-cell lymphoma (71% ± 6%v 15% ± 11%, respectively). However, within the good prognostic category of ALK+ lymphoma, survival was 94% ± 5% for the low/low intermediate risk group (age-adjusted International Prognostic Index, 0 to 1) and 41% ± 12% for the high/high intermediate risk group (age-adjusted International Prognostic Index, ≥2). Multivariate analysis identified ALK express