Transformation of the small cell variant ki-1(+) lymphoma to anaplastic large cell lymphoma - Pathologic and clinical features

The disease spectrum of anaplastic large cell lymphoma (ALCL) includes a bi ologically aggressive small cell variant (SCV). The SCV may progress to ALC L, but little is known about the transformation process and its significanc e. The goals of this study were (1) to identify the clinical and pathologic features that characterize ALCL arising in SCV and (2) to determine whethe r some cases with ALCL histologic appearance at the outset arose from an SC V. Seventeen SCV were reviewed, and four cases (24%) transformed to ALCL as shown by subsequent biopsy. The ALCLs were predominantly monomorphic (3 ca ses) rather than pleomorphic (1 case). Residual SCV was detected at transfo rmation in 3 of 4 cases. Twenty-one de novo T-cell ALCLs were reviewed for an SCV component; such a component was identified in two ALCLs with monomor phic features, suggesting a preceding SCV phase. There was no change in the immunophenotype between the SCV and ALCL, all marking as EMA+ T cells. Exp ression of p80 was detected in 3 of 4 (75%) SCV with transformation and 10 of 12 (77%) SCV without transformation. Chromosomal abnormalities involving the sex chromosomes and 6, 7, 9, and 15, in addition to the characteristic t(2;5)(p23;q35), were present in 2 cases at transformation. Times to trans formation ranged from 1 to 146 months (mean: 63 months) after diagnosis. Tr ansformation to ALCL signaled a rapid clinical course, with 75% of patients dying in less than a year; one patient remains alive at 15 months. In summ ary, some ALCLs, particularly those with monomorphic features, arise from a n SCV. Transformation to ALCL signals a rapid course, with death occurring in less than a year in most cases. Necrosis in the SCV may be predictive of transformation. Chromosomal abnormalities in addition to the t(2;5)(p23;q3 5) are present at transformation, suggesting that multiple genetic alterati ons are involved in disease progression.