Atypical teratoid/rhabdoid tumor of the CNS: Cytopathology and immunohistochemistry of insulin-like growth factor-II, insulin-like growth factor receptor type 1, cathepsin D, and Ki-67

Insulin-like growth factor (IGF)-II is a potent growth factor, normally con trolled by a number of other factors, including IGF binding proteins and IG F binding protein proteases. In general, the latter increase the bioavailab ility of IGF by cleaving IGF binding proteins. Cathepsin D (an IGF binding protein protease) was also implicated in tumor invasion. Although IGF-II wa s implicated in the pathogeneses of various childhood neoplasms, its signif icance in the pathogenesis of atypical teratoid/rhabdoid tumor of the centr al nervous system (ATRT-CNS) was not studied to date. We present clinicopat hologic features of two cases of ATRT-CNS. Ln addition, formalin-fixed, par affin-embedded tissue sections were stained immunohistochemically for IGF-I I, IGF receptor type 1, cathepsin D, and Ki-67. Both tumors demonstrated di ffuse strong cytoplasmic positivity for IGF-II, diffuse cytoplasmic and foc al membranous positivity for IGF receptor type I, and diffuse cytoplasmic p ositivity for cathepsin D. The Ki-67 labeling indices were 10.0% and 1.4%. We conclude that ATRT-CNS cells express both IGF-II and IGF receptor type 1 , supporting the hypothesis that autocrine/paracrine stimulation of cell gr owth by IGF-II might be one mechanism involved in ATRT-CNS tumorigenesis. C athepsin D expressed by the tumor cells might also be involved in both tumo r cell invasion and growth. The exact pathogenesis of ATRT-CNS remains to b e elucidated.