A Malignant Neoplasm From the Jejunum With a MALAT1-GLI1 Fusion and 26-Year Survival History
A Malignant Neoplasm From the Jejunum With a MALAT1-GLI1 Fusion and 26-Year Survival History
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DOI：
10.1177/1066896919900548
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发表时间：
2020-01-13
影响因子：
1.2
通讯作者：
Xu, Huiling
中科院分区：
文献类型：
--
作者：
Prall, Owen William John;McEvoy, Christopher Robert Edward;Xu, Huiling
转录因子 GLI1 是 sonic hedgehog 通路的关键效应子。最近在多种肿瘤类型中报道了激活 GLI1 的基因融合，包括胃母细胞瘤、丛状纤维粘液瘤、周细胞瘤的子集和其他软组织肿瘤。这些肿瘤的解剖起源多种多样，并且具有不同的恶性潜能、形态和免疫组织化学特征。在本病例报告中，我们描述了一种来自空肠的恶性肿瘤，其具有 MALAT1-GLI1 基因融合体，该融合体表达截短的组成型活性 GLI1 蛋白和可通过免疫组织化学检测到的 GLI1 靶标。肿瘤显示高级上皮样细胞和梭形细胞形态，强表达CD56，并局部表达其他神经内分泌标志物和细胞角蛋白，但不表达S100蛋白或SMA。在 26 年的时间里，该肿瘤在肝脏、软组织和肺部多次复发，这是报道的 GLI1 融合相关肿瘤最长的随访时间。这些转移性肿瘤也由上皮样细胞和梭形细胞组成，但形态学分级低于原发性肿瘤。转移性肿瘤类似于最近报道的“具有 GLI1 重排的恶性上皮样肿瘤”。该肿瘤还具有相对较高的肉瘤突变负担。该病例报告扩大了 GLI1 重排肿瘤的起源位点，并表明尽管与高级别形态学相关，但这些恶性肿瘤可能与非常长期的生存有关。
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.