A Malignant Neoplasm From the Jejunum With aMALAT1-GLI1Fusion and 26-Year Survival History

Abstract

The transcription factor GLI1 is a critical effector of the sonic hedgehog pathway. Gene fusions that activate GLI1 have recently been reported in several tumor types including gastroblastoma, plexiform fibromyxoma, a subset of pericytomas, and other soft tissue tumors. These tumors arise in a wide variety of anatomical origins and have variable malignant potentials, morphologies, and immunohistochemistry profiles. In this case report, we describe a malignant tumor from the jejunum with a MALAT1-GLI1 gene fusion that expressed a truncated constitutively active GLI1 protein and GLI1 targets that were detectable by immunohistochemistry. The tumor showed high-grade epithelioid and spindle cell morphology, strongly expressed CD56, and focally expressed other neuroendocrine markers and cytokeratins, but not S100 protein or SMA. The tumor recurred multiple times in liver, soft tissue, and lung over the course of 26 years, the longest reported follow-up for a GLI1 fusion-associated tumor. These metastatic tumors were also composed of epithelioid and spindle cells, but showed lower morphological grade than the primary tumor. The metastatic tumors resembled the recently reported “malignant epithelioid neoplasms with GLI1 rearrangements.” The tumor also had a relatively high tumor mutation burden for a sarcoma. This case report expands the sites of origin for GLI1 rearranged neoplasms and shows that despite being associated with high-grade morphology, these malignancies can be associated with very long-term survival.

Plexiform fibromyxoma: Review of rare mesenchymal gastric neoplasm and its differential diagnosis

“…Malignant epithelioid tumor with GLI1 rearrangement is a recently described epithelioid neoplasm of the soft tissue that harbors MALAT1–GLI1 fusion with a metastatic potential[ 65 ]. In the GI tract, only one case in the jejunum has been reported[ 10 ]. Later, Agaram et al [ 66 ] reported GLI1 gene amplifications in a subset of soft tissue tumors with similar morphology, even though these tumors showed broader morphologic spectrum and inconsistent immunohistochemistry.…”

“…While PF behaves in a benign manner, its histologic mimics such as GISTs, smooth muscle tumors and nerve sheath tumors show malignant potential[ 8 , 9 ]. Moreover, its molecular mimics, such as gastroblastoma and malignant epithelioid tumor with glioma-associated oncogene homologue 1 ( GLI1 ) rearrangement, need to be excluded especially when evaluating small samples and when the molecular profiling is included in the work-up[ 10 ]. Herein we provide a concise review of PF focusing on its histologic and molecular differential diagnoses.…”

Recent developments in gastroesophageal mesenchymal tumours

“…Despite this genetic similarity to plexiform fibromyxoma, the differences in clinical behaviour and morphology support maintaining separate classification. There have also been reports of neoplasms with MALAT1 – GLI1 fusions occurring in the jejunum 50 and deep soft tissue 51 . Additionally, a tumour with biphasic morphology and immunohistochemical features similar to those of gastroblastoma was reported in the duodenum, raising the possibility that ‘gastroblastoma’ can involve extragastric sites 52 .…”

Primary cutaneous epithelioid mesenchymal neoplasm with ACTB‐GLI1 fusion: a case report

“…Mesenchymal tumors harboring GLI1 gene fusions are a rare but distinctive group of recently described neoplasms whose clinicopathologic features are currently evolving. Various fusion partners to GLI1 have been described to date, including ACTB , MALAT1 , and PTCH1 , 1‐4 with cases of ACTB‐GLI1 fusion‐positive tumors showing a distinctive monomorphic round‐to‐epithelioid cell morphology and a nested to corded/trabecular pattern of growth, as well as an S100+/CD56+/SOX10−/SMA– immunophenotype 5 . Although few cases of this specific entity (herein termed ACTB‐GLI1 epithelioid mesenchymal neoplasm [EMN]) have been reported in the literature, most cases have occurred in the soft tissues of the limbs, trunk, and head and neck, with none previously reported occurring exclusively in the skin 1 …”