Abstract A27: INI1 negative hepatoblastoma, a vanishing entity representing malignant rhabdoid tumor

Introduction: Hepatoblastoma (HB) is the most common primary hepatic tumor of childhood. According to the most current Children’s Oncology Group (COG) classification small cell undifferentiated hepatoblastomas (SCU-HB) are a subtype of epithelial hepatoblastomas with adverse outcome. Malignant rhabdoid tumors (MRT) of the liver are a distinct highly aggressive group of tumors with unknown cell of origin diagnosed on the basis of INI1 negative immunoreactivity and rhabdoid morphology. In the absence of rhabdoid morphology, presence of SMARCB1/INI1 deletion on chromosome 22q11.2 is confirmatory. Therefore, MRT lacking classic rhabdoid morphology are often misdiagnosed as SCU-HB, especially on small biopsy samples. We present a case of previously healthy full-term 10 month old female infant with a lobulated heterogeneous right hepatic mass, low serum alpha-fetoprotein (AFP) of 71 ng/ml, and metastatic pulmonary disease. Initial biopsy of mass was consistent with hepatoblastoma, predominantly small cell undifferentiated component. The patient underwent chemotherapy with vincristine, irinotecan, and temsirolimus with less than the 30% response required for partial responder. She subsequently underwent right partial hepatectomy. Results: Histologic evaluation of the biopsy sample revealed solid proliferation of small tumor cells with clear to eosinophilic cytoplasm and prominent nucleoli, compatible with small cell morphology. Immunohistochemistry for INI1 was negative in all tumor cells. In the absence of rhabdoid morphology, the tumor was initially classified as INI1 negative SCU-HB. Subsequently, the resection specimen showed predominantly small cells with only focal areas of rhabdoid morphology. An extensive immunohistochemical panel was performed and the tumor cells were negative for hepatocellular differentiation markers (Hepar-1 and arginase), beta-catenin, desmin, myoD1, cytokeratin 7, cytokeratin 20, and were positive for glypican-3 and cytokeratin in both biopsy and resection specimens. Similar to the biopsy sample, the tumor cells were entirely negative for INI1 on the resection specimen. Cancer Whole-Exome Sequencing (WES) with Transcriptome was performed and showed homozygous deletion of SMARCB1 on chromosome 22q11.23 with evidence of loss of expression of the gene confirming the loss of INI1 expression with IHC. Discussion: MRT of liver are a distinct entity and are in the differential diagnosis of INI-1 negative pediatric liver tumors along with SCU-HB. MRT are also considered in the differential diagnosis of any aggressive liver tumor with low levels of AFP. Current reports indicate that differentiation of MRT from INI1 negative SCU-HB, in the absence of rhabdoid morphology, is mainly based on molecular testing for SMARCB1. In our case, the initial biopsy sample was classified as INI1 negative SCU-HB predominantly based on morphology, and was subsequently reclassified as MRT based on demonstration of SMARCB1 deletion with WES, as well as identification of focal areas of rhabdoid morphology on the resection specimen. Conclusion: Based on this finding, morphology is not a robust method of differentiating MRT from SCU-HB. It is possible that many cases previously classified as SCU-HB mainly based on morphology, if retrospectively analyzed for SMARCB1 would be reclassified as MRT. Citation Format: Ladan Fazlollahi, Susan Hsiao, Mahesh Mansukhani, Julia Glade Bender, Andrew Kung, Darrell Yamashiro, Helen Remotti. INI1 negative hepatoblastoma, a vanishing entity representing malignant rhabdoid tumor. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr A27.