Cytoplasmic expression of Wilms tumor transcription factor-1 (WT1): A useful immunomarker for young-type fibromatoses and infantile fibrosarcoma

There is increasing evidence that Wilms' tumor transcription factor-1 (WT1) isexpressed in the cytoplasm of neoplastic cells from different benign andmalignant tumors. Only a few studies on WT1 cytoplasmic immunolocalization areavailable in pediatric tumors. The aim of the present study was to investigateimmunohistochemically the expression and distribution of WT1 in a large series ofsoft tissue fibroblastic/myofibroblastic lesions occurring in children andadolescents. Notably WT1 was not expressed in nodular fasciitis and desmoid-type (adult) fibromatosis, while it stained diffusely and strongly in severalinfantile-type fibromatoses, such as fibrous hamartoma of infancy,myofibroma/myofibromatosis, and lipofibromatosis. Interestingly, WT1 cytoplasmic expression was also found in all cases (10/10) of infantile fibrosarcomasexamined. The present study shows that a diffuse WT1 cytoplasmic expression is ofcomplementary diagnostic value to conventional myofibroblastic markers (α-smooth muscle actin; desmin) in confirming diagnosis of young-type fibromatoses orinfantile fibrosarcoma and in ruling out both desmoid-type fibromatoses andnodular fasciitis. WT1 cytoplasmic expression in infantile fibrosarcoma is anovel finding which could be exploitable as an immunomarker for this tumor.Although highly sensitive, WT1 cytoplasmic immunostaining is not specific forinfantile fibrosarcoma, and thus it should be evaluated in the context of a wide immunohistochemical panel when pathologists are dealing with spindle cell lesionsof soft tissues in children and adolescents. Accordingly we recommend that acorrect diagnosis of fibroblastic/myofibroblastic soft tissue lesion in pediatricpatients is usually achieved on the basis of a careful correlation ofmorphological and immunohistochemical findings in the appropriate clinicalcontext. The different cellular localization of WT1, namely nuclear, cytoplasmic or nucleo-cytoplasmic, in different benign and malignant tumors supports thehypothesis that this transcription factor plays a complex role in tumorigenesis, likely as a chameleon protein functioning as either a tumor suppressor gene or anoncogene, depending on cellular context.