THE T(2-5)-ASSOCIATED P80 NPM ALK FUSION PROTEIN IN NODAL AND CUTANEOUS CD30+ LYMPHOPROLIFERATIVE DISORDERS/

A high percentage of extracutaneous CD30+ anaplastic large cell lympho mas (nodal ALCL) carry a specific chromosomal translocation, t(2;5) (p 23;q35), that results in abnormal expression of p80 NPM/ALK chimeric p rotein (p80). The protein p80 may be detected by immunohistochemistry using polyclonal (anti-p80) or monoclonal (ALK1) antibody directed aga inst the ALK epitope. Although nodal ALCL, primary cutaneous ALCL, and lymphomatoid papulosis type A (lyp A) have similar histologic and imm unohistochemical features, the expression of p80 in these cutaneous le sions has not been extensively studied. We immunostained tissues from 10 nodal ALCL, 8 primary cutaneous ALCL, 24 lyp A, and positive and ne gative controls using polyclonal rabbit anti-p80 and the avidin-biotin -peroxidase labeling method. Reactivity was determined by comparing st aining intensity to positive controls [4 nodal ALCL with t(2;5)] and n egative controls (21 non-ALCL lymphomas). Only cutaneous lesions stain ing positively with anti-p80 were further studied with the monoclonal antibody ALK1 and reverse transcription polymerase chain reaction (RT- PCR) for p80 messenger RNA. All positive controls (4/4), but none of t he negative controls (0/21) nor lyp A (0/24), were immunoreactive for anti-p80. Sixty percent (6/10) of nodal ALCL and a single case (12%) o f primary cutaneous ALCL were immunoreactive for anti-p80. In this exc eptional cutaneous lesion, although we did not find NPM/ALK by RT-PCR, we detected strong expression of ALK using ALK1. We conclude that t(2 ;5) is rarely involved in the pathogenesis of cutaneous CD30+ lymphopr oliferative disorders.