ALK Expression in Angiomatoid Fibrous Histiocytoma (AFH): A Potential Diagnostic Pitfall
Alison L Cheah, Christopher Lanigan, Galina Batiouchko, Brian P Rubin, Steven D Billings, Jason L Hornick, Raymond R Tubbs, John R Goldblum. Cleveland Clinic, Cleveland, OH; Brigham and Women's Hospital, Boston, MA
Background: We recently identified a case of primary pulmonary AFH (EWSR1- rearranged) that was misdiagnosed as inflammatory myofibroblastic tumor (IMT) based in part on ALK expression by immunohistochemistry. Prompted by this experience, we evaluated ALK expression in AFH as compared to select spindle cell neoplasms with accompanying lymphoplasmacytic infiltrate.
Design: We studied FFPE sections from 10 AFH (9 of 10 confirmed EWSR1-rearranged by FISH) and included 15 IMT and 11 follicular dendritic cell sarcomas (FDC) for comparison. ALK expression was evaluated with 3 different antibody clones: D5F3 (1:100, Cell Signaling Technology), 5A4 (1:40, Novocastra) and ALK-1 (1:200, Dako). ALK IHC positive cases were analyzed with FISH using dual color ALK break apart probe kit (Abbott Molecular Vysis) for rearrangement of the ALK gene (2p23).
Results: The majority of AFH cases studied were positive for ALK IHC with at least one antibody (8/10 DF53, 6/9 5A4, 1/9 ALK-1), most demonstrating moderate to strong cytoplasmic staining. AFH with positive ALK IHC showed no ALK gene rearrangement by FISH (0/8). In select AFH cases, the mean ALK gene copy number was 1.6-2.1. 67% of IMT were ALK positive by IHC (10/15 DF53, 8/15 5A4, 7/15 ALK-1). Of these, ALK gene rearrangement was demonstrated by FISH in 9/10 IMT. All FDC sarcomas were negative for D5F3 and 5A4.
Conclusions: Our results indicate that ALK expression in AFH is common, particularly with the D5F3 and 5A4 antibodies and enhanced detection systems, and is a potential source of diagnostic confusion with IMT. The genetic mechanism behind ALK expression in AFH is not apparent, although it does not appear to be from ALK gene rearrangement or amplification as detected by FISH.
Category: Bone & Soft Tissue
Monday, March 4, 2013 1:00 PM
Poster Session II # 7, Monday Afternoon