NEOPLASIA ALK 1 Lymphoma : Clinico - Pathological Findings and Outcome

A distinct pathologic entity (ALK1 lymphoma) that is characterized by expression of the anaplastic lymphoma kinase (ALK) protein has recently emerged within the heterogeneous group of CD301 anaplastic large-cell lymphomas. Information on clinical findings and treatment outcome of ALK1 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 paraffinembedded 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 ALK1 and 25 ALK2). 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, ALK1 lymphoma mostly occurred in children and young adults (mean age, 22.01 6 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 ALK1 lymphoma, ALK2 cases occurred in older individuals (mean age, 43.33 6 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 ALK1 lymphoma was far better than that of ALK2 anaplastic large-cell lymphoma (71% 6 6% v 15% 6 11%, respectively). However, within the good prognostic category of ALK1 lymphoma, survival was 94% 6 5% for the low/low intermediate risk group (age-adjusted International Prognostic Index, 0 to 1) and 41% 6 12% for the high/high intermediate risk group (age-adjusted International Prognostic Index, H2). 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. r 1999 by The American Society of Hematology.