ALK(+) lymphoma: Clinico-pathological findings and outcome

A distinct pathologic entity (ALK(+) lymphoma) that is characterized by exp ression of the anaplastic lymphoma kinase (ALK) protein has recently emerge d 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 In ternational Prognostic Index when applied to this homogeneous disease entit y. To clarify these issues, a recently developed monoclonal antibody ALKc ( directed against the cytoplasmic portion of ALK) was used to detect express ion of the ALK protein in paraffin-embedded biopsies from 96 primary, syste mic T/null anaplastic large-cell lymphomas, and the ALK staining pattern wa s correlated with morphological features, clinical findings, risk factors ( as defined by the International Prognostic Index), and outcome in 78 patien ts (53 ALK(+) and 25 ALK(-)). Strong cytoplasmic and/or nuclear ALK positiv ity 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%; lymphohist iocytic, 8.6%; and small cell, 5.2%) that reflected the ratio of large anap lastic elements (usually showing cytoplasmic and nuclear ALK positivity) to small neoplastic cells (usually characterized by nucleus-restricted ALK ex pression). Clinically, ALK(+) lymphoma mostly occurred in children and youn g adults (mean age, 22.01 +/- 10.87 years) with a male predominance (male/f emale [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, st age Ill-IV disease, frequently associated with systemic symptoms (75%) and extranodal involvement (60%), especially skin (21%), bone (17%), and soft t issues (17%). As compared with ALK(+) lymphoma, ALK(-) cases occurred in ol der individuals (mean age, 43.33 +/- 16.15 years) and showed a lower M/F ra tio (0.9) as well as lower incidence of stage Ill-IV disease and extranodal involvement at presentation. Overall survival of ALK(+) lymphoma was far b etter 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 gro up (age-adjusted International Prognostic Index, 0 to 1) and 41% +/- 12% fo r the high/high intermediate risk group (age-adjusted International Prognos tic Index, greater than or equal to 2). Multivariate analysis identified AL K expression and the International Prognostic Index as independent variable s that were able to predict survival among T/null primary, systemic anaplas tic large-cell lymphoma. Thus, we suggest that such parameters should be ta ken into consideration for the design of future clinical trials. (C) 1999 b y The American Society of Hematology.