Atypical teratoid/ rhabdoid tumor, an immunohistochemical study of potential diagnostic and prognostic markers.

ABSTRACT

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare tumor of the CNS mostly seen in infants and is often associated with a dismal outcome. Despite the heterogeneous morphology and/or immunoprofile, its diagnosis nowadays relies on the negative INI-1/BAF47 nuclear immunostain in tumor cells. We aim to investigate a number of immunohistochemical antibodies as potential diagnostic and prognostic markers. All AT/RT cases in patients younger than 18 years of age were included. Demographics, clinical features and outcome were collected. Immunostains tested included SALL-4, OCT3/4, CD99, FLI-1, cyclin-D1, ß-catenin, P53, P16, CDX2 and WT-1. Nineteen cases (10 males) were identified at our center between 2004-2013 with a median age of 24 months. Ten (52.6%) cases were supratentorial. Six (42.9%) cases showed metastasis at time of presentation. Chemotherapy was administered to 10 (62.5%) and radiotherapy to seven (43.8%). The median overall survival was 11 months. A single long-term survival of 104 months was identified. Pathologically, most cases showed an admixture of rhabdoid cells and/or small cells and/or pale cells in variable proportions. Of all tested antibodies, only positivity for FLI-1 was associated with improved survival (P = 0.0012), while positivity for cyclin-D1 showed a trend toward improved survival (P = 0.0547). CDX2 was positive only in the single long-term survival. Interestingly, two cases showed co-expression of CD99 and FLI-1, and some were positive for SALL-4. In conclusion, FLI-1 and cyclin-D1 are potential prognostic markers associated with better outcome. Occasional AT/RT cases might co-express CD99 and FLI-1 as well as SALL-4, a potential diagnostic pitfall with Ewing sarcoma/ primitive neuroectodermal tumors and germ cell tumors, respectively.