Rearrangements at the 6p25.3 Locus Identify a Subset of Systemic ALK-Negative Anaplastic Large Cell Lymphomas with Favorable Prognosis
Edgardo R Parrilla Castellar, Karen L Grogg, Mark E Law, George Vasmatzis, Stephen M Ansell, Ahmet Dogan, Andrew L Feldman. Mayo Clinic, Rochester, MN
Background: Systemic ALK-negative ALCL typically is an aggressive disease with poorer prognosis than its ALK-positive counterpart. We recently identified recurrent 6p25.3 rearrangements involving the DUSP22-IRF4 locus in ALK-negative ALCLs. Most of these were primary cutaneous cases but occasional systemic cases also were identified. The clinicopathologic features of these systemic cases have not been studied.
Design: We reviewed 139 biopsies from 69 patients (M: 46, F: 23; mean age, 51 yr) with systemic ALCL diagnosed by WHO criteria. Cases were tested for 6p25.3 rearrangements by breakapart fluorescence in situ hybridization and for expression of ALK, T-cell antigens, and cytotoxic markers by immunohistochemistry. Overall survival from date of diagnosis was assessed using the Kaplan-Meier method and the log-rank test.
Results: ALK was positive in 29 and negative in 40 patients. Seven patients (M: 7, F: 0; mean age, 53 yr) had 6p25.3 rearrangements (all ALK-negative). Among ALK-negative ALCLs, secondary cutaneous involvement occurred in 2 patients (29%) with 6p25.3 rearrangement and 11 (33%) without. All tumors expressed at least one T-cell antigen. Cytotoxic markers (granzyme B and/or TIA1) were absent in cases with 6p25.3 rearrangement and present in 11 (65%) without rearrangements (p=0.04). Overall 5-year survival rates were 86% with 6p25.3 rearrangements, 82% for ALK-positive ALCL, and 32% in the remaining ALK-negative cases (p<0.001 for all 3 groups; p=0.06, 6p25.3 present vs. absent among ALK-negative ALCLs).
Conclusions: Systemic ALK-negative ALCLs with 6p25.3 rearrangements had a favorable prognosis similar to that of ALK-positive ALCLs. These tumors tended to occur in men and lacked a cytotoxic phenotype, similar to primary cutaneous ALCLs with 6p25.3 rearrangements. However, most systemic cases never developed cutaneous involvement. These findings suggest 6p25.3 rearrangements identify a distinct subset of systemic ALK-negative ALCLs with some clinicopathologic features overlapping those of primary cutaneous ALCL. Our statistical power was limited by the small number of positive cases and we are assembling a larger, multicenter cohort to determine whether testing for 6p25.3 rearrangements will be prognostically useful in systemic ALK-negative ALCL.
Tuesday, March 20, 2012 8:15 AM
Platform Session: Section C, Tuesday Morning