Malignant Rhabdoid Tumor, an Aggressive Tumor Often Misclassified as Small Cell Variant of Hepatoblastoma

Abstract

The clinical management of pediatric liver tumors involves stratification into risk groups. One previously defined, high-risk group of hepatoblastomas is the small cell undifferentiated variant. In light of molecular studies showing SMARCB1 deletion in these tumors, it is now recognized that most small cell, undifferentiated liver tumors represent an aggressive unrelated tumor-the malignant rhabdoid tumor (MRT). SMARCB1 is a member of the chromatin remodeling SWI/SNF complex and encodes the INI1 protein. The histologic diagnosis of MRT is currently based on INI1 negative immunoreactivity and the presence of rhabdoid morphology. INI1-negative small cell liver tumors lacking classic rhabdoid morphology are often misclassified as small cell undifferentiated hepatoblastomas (SCUD-HB), according to the current classification. Pediatric liver tumors diagnosed between 2003-2017 as SCUD-HB (four cases) or MRT (two cases) were identified from the Columbia University Pathology Department Archives. All tumors were associated with normal or low serum alpha fetoprotein levels, and showed an absence of immunohistochemical staining of hepatocellular markers (Hep-par1, Arginase) and loss of INI1 staining. Two cases were initially diagnosed as MRT, one with prominent rhabdoid morphology, the other with predominant small cell morphology. The remaining four cases with small cell morphology were classified as SCUD-HB. Ancillary molecular studies confirmed the loss of SMARCB1, supporting the diagnosis of MRT in all cases, proving morphology an unreliable criterion. It is critical to eliminate the term INI1-negative hepatoblastoma from the current classification scheme, and classify INI1-negative tumors as MRT, particularly since high-risk HB-chemotherapy regimens are not effective for treating MRT.

Keywords: Hepatoblastoma; INI1; Malignant Rhabdoid Tumor (MRT); SMARCB1; small cell Hepatoblastoma; small cell undifferentiated (SCUD) Hepatoblastoma.

Figure 1

Malignant rhabdoid tumor (MRT) showing small cell morphology (A, case 1) versus typical rhabdoid morphology (B, case 3), original magnification 600×.

Figure 2

MRT cases (1–6), showing the spectrum of morphologic features, with predominant small cell morphology. All cases were INI1 negative by immunohistochemistry, original magnification 600×.

Figure 3

(a) Copy number analysis by CCCP. The log2-fold change for each gene is shown. SMARCB1 (indicated by arrow) on chromosome 22 shows a fold change consistent with biallelic deletion. (b) Cancer whole exome sequencing (CWES) was performed in two cases and confirmed bi-allelic SMARCB1 gene deletion involving chromosome 22q11.2.

Figure 4

MRT (Case 5) with molecular findings of SMARCB1 biallelic deletion and SMARCA4 VUS. Immunostaining showed the absence of INI1 and presence of BRG1, original magnification 600×.