ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor

Background: Inflammatory myofibroblastic tumor (IMT) is an uncommon tumor o f extrapulmonary and pulmonary tissues with an unpredictable clinical cours e, occasional recurrences, and rare malignant transformation. Clonal abnorm alities with rearrangements of chromosome of 2p23 and the ALK gene have bee n reported in a few cases. The purpose of this study is to investigate whet her these are consistent abnormalities among IMTs or represent a distinct s ubset. Design: Formalin-fixed, paraffin-embedded archival tissue sections f rom 47 IMTs in 40 patients were immunostained with monoclonal antibodies ag ainst ALK and p80. Fluorescence in situ hybridization for ALK rearrangement s was done on 22 IMTs from 19 patients. Findings were correlated with clini cal features and outcome. Results: AI;K positivity was observed in 17 of 47 IMTs (36%) and p80 positivity in 16 of 47 IMTs (34%). Fluorescence in situ hybridization showed ALK rearrangements in nine cases (47%), aneuploidy in three cases (16%), and no rearrangement in seven cases (37%). IMTs with AL K abnormalities by immunohistochemistry and/or fluorescence in situ hybridi zation originated in the abdomen/pelvis/retroperitoneum, chest, and extremi ties. The mean age was 6.6 years, with a male/female ratio of 1.3, 64% of p atients had no evidence of disease at last follow-up, 45% had one or more r ecurrences, and 18% displayed histologic evidence of malignant transformati on. The IMTs without ALK abnormalities occurred in older children, were mor e frequent in females, and had fewer recurrences. However, in this group of 40 patients, the differences between the groups with and without ALK abnor malities did not have statistical significance. Aneuploidy without ALK abno rmalities was associated with malignant transformation in three of five cas es. Conclusions: Abnormalities of ALK and p80 and evidence of chromosomal r earrangements of 2p23 occur in a significant proportion of IMTs. These chan ges are most frequent in abdominal and pulmonary IMTs in the first decade o f life and are associated with a higher frequency of recurrence. These find ings confirm the neoplastic nature of a subset IMT with ALK abnormalities a nd suggest that aneuploid IMT is a subset with more aggressive clinical beh avior.