ALK+ lymphoma: clinico-pathological findings and outcome

• DOI: 10.1182/blood.v93.8.2697
• Publication Date: 1999-01-01
• Authors: B. Falini; S. Pileri; P.I. Zinzani; A. Carbone; V. Zagonel; C. Wolf Peeters; G. Verhoef; MENESTRINA, Fabio; TODESCHINI, Giuseppe; M. Paulli; M. Lazzarino; R. Giardini; A. Aiello; H.D. Foss; I. Araujo; M. Fizzotti; P.G. Pelicci; L. Flenghi; M.F. Martelli; A. Santucci
• Keywords: Adult; Cell Nucleus; Male; Cytoplasm; Time Factors; CD30+ ALK+ ANAPLASTIC LYMPHOMAS; 610; Ki-1 Antigen; Receptor Protein-Tyrosine Kinases; Protein-Tyrosine Kinases; Prognosis; Survival Analysis; Treatment Outcome; 616; Biomarkers, Tumor; Humans; Anaplastic Lymphoma Kinase; Female; Lymphoma, Large B-Cell, Diffuse; Antigens, CD30; Lymphoma, Large B-Cell, Diffuse; Humans; Prognosis; Retrospective Studies; Protein-Tyrosine Kinases; Cell Nucleus; Receptor Protein-Tyrosine Kinases; Cytoplasm; Adult; Treatment Outcome; Tumor Markers, Biological; Time Factors; Female; Male; Survival Analysis; Retrospective Studies

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 expression and the International Prognostic Index as independent variables that were able to predict survival among T/null primary, systemic anaplastic large-cell lymphoma. Thus, we suggest that such parameters should be taken into consideration for the design of future clinical trials.