Anaplastic lymphoma kinase expression in inflammatory pseudotumors

Anaplastic lymphoma kinase (ALK), a hallmark of anaplastic large cell lymphoma, has recently been implicated in the genesis of some inflammatory pseudotumors (inflammatory myofibroblastic tumors) in children and young adults. The aim of this study was to determine the frequency of its expression among inflammatory pseudotumors, and to characterize the clinicopathologic features of the positive cases. Sixty-one cases of inflammatory pseudotumors were retrieved from the surgical pathology archives and consultation files. Paraffin sections were immunostained with the antibody ALK1. The patients ranged in age from 0.5 to 79 years (median age, 50 years), with 10 patients (16.4%) younger than 20 years. Five cases (8.2%) were ALK+, including two of six urogenital inflammatory myofibroblastic tumors, none of eight pulmonary inflammatory pseudotumors, three (one adrenal, one small bowel, one liver) of 31 extrapulmonary inflammatory pseudotumors, none of nine hepatic/splenic inflammatory pseudotumors expressing follicular dendritic cell markers and harboring Epstein-Barr virus, and none of seven inflammatory pseudotumors of the lymph node. When only those patients 40 years or younger were considered, the ALK positivity rate became 21.7% (five of 23). All five ALK+ cases occurred in young patients aged 0.5 to 37 years, who were alive and well at 3.5 to 17 years. The tumors exhibited a spectrum of histologic features typical of inflammatory pseudotumors/myofibroblastic tumors, but there was at least focal nuclear atypia. Immunostaining for ALK produced fibrillary or granular cytoplasmic staining in the neoplastic cells, sometimes with cell membrane accentuation. This study confirms that ALK is implicated in a proportion of inflammatory pseudotumors, and is generally associated with a favorable outcome. The results also support the heterogeneity of inflammatory pseudotumors, with the follicular dendritic cell/Epstein-Barr virus-positive cases and those occurring in lymph nodes representing different biologic entities.