Atypical Teratoid Rhabdoid Tumor: 28-years institutional experience

Abstract

Abstract Introduction/Objective Atypical teratoid/rhabdoid tumor (ATRT) is a malignant central nervous system tumor affecting young children, characterized by biallelic mutations of SMARCB1 (hSNF5/INI1), consisting of a varying mixture of rhabdoid cells, small round blue cell (SRBC) and epithelial/mesenchymal components. Combination of surgical resection, chemoradiotherapy and autologous stem cell transplantation (SCT) has led to significant improvement in survival. Methods/Case Report Cases of ATRT in the past 28 years have been re-examined, including H&E stains, immunohistochemistry, available molecular studies and clinical charts. Results (if a Case Study enter NA) A total of 23 cases of ATRT were recruited to include 20 pediatric (age 3-36 months, median 13.5 months) and 3 adult cases (27, 38 and 46 years). 73.9% were male. Two pediatric cases presented in patients with Pierre-Robin sequence and Phelan-McDermid syndrome and one adult had history of Choriocarcinoma. 72.7% of cases initially presented in the posterior fossa, with 3 cases presenting in temporal lobe, 1 in frontal lobe, 1 in 3rd ventricle and 1 in pituitary gland. Mean size at presentation was 4.7 cm (range 2-10 cm). Median survival was 12.5 weeks with 8 patients surviving 5-13 years. 10/22 cases developed recurrences and/or spinal drop metastasis. Median time to first recurrence/ drop metastasis was 3.5 months (range 0-66 months). Cases showed varying proportions of rhabdoid, SRBC, epithelioid and mesenchymal components. By immunohistochemistry, INI1 was lost in 19/19 cases. Keratins, GFAP and Synaptophysin were positive in 13/17, 14/20 and 17/21 cases, respectively. Interestingly, GAB-1 and YAP1 were positive in 5/6 and 4/4 cases, respectively. Five cases had SMARCB1 mutation on NGS, one had NF2 truncation and another showed variation of unknown significance involving mainly NOTCH1 gene. 21/22 patients underwent surgical resection, of which 17 additionally received a combination of chemoradiotherapy and SCT and 1/22 underwent palliation. Conclusion Our data highlights the spectrum of presentation and survival of cases of ATRT and the importance of INI1 immunohistochemistry in the diagnosis, especially for the occasional cases co-expressing GAB1 and YAP, a potential diagnostic pitfall with medulloblastoma.