Gastroblastoma with a novel EWSR1‐CTBP1 fusion presenting in adolescence

Abstract

Gastroblastomas are rare tumors with a biphasic epithelioid/spindle cell morphology that typically present in early adulthood and have recurrent MALAT1‐GLI1 fusions. We describe an adolescent patient with Wiskott‐Aldrich syndrome who presented with a large submucosal gastric tumor with biphasic morphology. Despite histologic features consistent with gastroblastoma, a MALAT1‐GLI1 fusion was not found in this patient's tumor; instead, comprehensive molecular profiling identified a novel EWSR1‐CTBP1 fusion and no other significant genetic alterations. The tumor also overexpressed NOTCH and FGFR by RNA profiling. The novel fusion and expression profile suggest a role for epithelial‐mesenchymal transition in this tumor, with potential implications for the pathogenesis of biphasic gastric tumors such as gastroblastoma.

Gene fusions in gastrointestinal tract cancers

“…6 In this case, there was transcriptomic evidence of NOTCH and FGFR pathway activation, and the predicted chimeric gene includes the key domains of EWSR1 and CTBP1. 6 From the provided images and description, this case resembles those cases with MALAT1-GLI1 fusion genes and raise the possibility that this another example of a single histologic entity with different underlying fusion genes. Detection of these fusion genes may be used to support a diagnosis of gastroblastoma in the appropriate morphologic context.…”

“…6 This case displayed a EWSR1-CTBP1 fusion instead of MAL-AT1-GLI1 gene. 6 In this case, there was transcriptomic evidence of NOTCH and FGFR pathway activation, and the predicted chimeric gene includes the key domains of EWSR1 and CTBP1. 6 From the provided images and description, this case resembles those cases with MALAT1-GLI1 fusion genes and raise the possibility that this another example of a single histologic entity with different underlying fusion genes.…”

“…Further investigations indicated activation of the hedgehog pathway in these tumors suggesting that this was the pathogenic driver of this tumor. Interestingly, a recent case report described a different fusion gene in a case of gastroblastoma affecting a young patient with an indolent clinical course 6 . This case displayed a EWSR1‐CTBP1 fusion instead of MALAT1‐GLI1 gene 6 .…”

“…Most patients have localized tumors at the time of diagnosis, but metastases have been reported. No deaths due to diseases have been reported 2–6 . Gastroblastoma is histologically distinctive and characterized by biphasic morphology inclusive of bland epithelioid cells in a nested architecture and clusters of monotonous spindle cells (Figure 2).…”

“…No deaths due to diseases have been reported. [2][3][4][5][6] Gastroblastoma is histologically distinctive and characterized by biphasic morphology inclusive of bland epithelioid cells in a nested architecture and clusters of monotonous spindle cells (Figure 2). The immunophenotype is nonspecific with the epithelioid and mesenchymal compartments showing expression of cytokeratins and variable SMA or CD10, respectively.…”