Abstract：
OBJECTIVE: Nuclear receptor subfamily 1 group D member 1 (NR1D1)-rearranged soft tissue tumour is a newly described entity with an epithelioid morphology and a potential for aggressive behaviour. Largely due to under-recognition, this tumour type has not yet been widely acknowledged. Herein, we report four additional cases to further expand its clinicopathological and molecular spectrum.
RESULTS: Four mesenchymal tumours with NR1D1 rearrangement were identified from our consultation files. There were one male and three females with ages ranging from 19 to 47 years (median = 28.5 years). Tumour occurred in the tongue, neck, hip and index finger, respectively. Histologically, two tumours were composed predominantly of epithelioid cells; one tumour had admixed epithelioid-spindle cells and one tumour consisted of monomorphic small round to ovoid cells. By immunohistochemistry, none of the tumours expressed lineage-specific markers. Targeted RNA-sequencing identified NR1D1 fusions in all four tumours, the partner genes being MAML2, MAML3, KMT2A and NCOA2, respectively. The novel MAML3 and NCOA2 rearrangements were confirmed by fluorescence in-situ hybridisation analysis. On follow-up (2-23 months), one patient experienced local recurrence due to incomplete resection and one patient developed lung metastasis. The other two patients were alive without disease.
CONCLUSIONS: This study adds more support for NR1D1-rearranged soft tissue tumour as an emerging entity. The occurrence of two additional tumours in the head and neck region, description of a small round cell variant and identification of novel MAML3, KMT2A and NCOA2 partners further expand its clinicopathological and molecular spectrum. More studies on larger series are necessary to validate the fully malignant potential of NR1D1-rearranged soft tissue tumour.
RESULTS: Four mesenchymal tumours with NR1D1 rearrangement were identified from our consultation files. There were one male and three females with ages ranging from 19 to 47 years (median = 28.5 years). Tumour occurred in the tongue, neck, hip and index finger, respectively. Histologically, two tumours were composed predominantly of epithelioid cells; one tumour had admixed epithelioid-spindle cells and one tumour consisted of monomorphic small round to ovoid cells. By immunohistochemistry, none of the tumours expressed lineage-specific markers. Targeted RNA-sequencing identified NR1D1 fusions in all four tumours, the partner genes being MAML2, MAML3, KMT2A and NCOA2, respectively. The novel MAML3 and NCOA2 rearrangements were confirmed by fluorescence in-situ hybridisation analysis. On follow-up (2-23 months), one patient experienced local recurrence due to incomplete resection and one patient developed lung metastasis. The other two patients were alive without disease.
CONCLUSIONS: This study adds more support for NR1D1-rearranged soft tissue tumour as an emerging entity. The occurrence of two additional tumours in the head and neck region, description of a small round cell variant and identification of novel MAML3, KMT2A and NCOA2 partners further expand its clinicopathological and molecular spectrum. More studies on larger series are necessary to validate the fully malignant potential of NR1D1-rearranged soft tissue tumour.
摘要：
目的：核受体亚家族1组D成员1（NR1D1）重排的软组织肿瘤是一种新描述的实体，具有上皮样形态和潜在的攻击行为。主要是由于认识不足，这种肿瘤类型尚未得到广泛认可。在这里，我们报告了另外4例病例，以进一步扩大其临床病理和分子谱。
结果：从我们的咨询文件中确定了4个具有NR1D1重排的间充质肿瘤。有一名男性和三名女性，年龄在19至47岁之间（中位数=28.5岁）。肿瘤发生在舌头，脖子,臀部和食指,分别。组织学上,两个肿瘤主要由上皮样细胞组成；一个肿瘤混合了上皮样-梭形细胞，一个肿瘤由单形小圆形至卵形细胞组成。通过免疫组织化学，没有一个肿瘤表达谱系特异性标记。靶向RNA测序确定了所有四个肿瘤中的NR1D1融合体，伴侣基因分别为MAML2、MAML3、KMT2A和NCOA2。通过荧光原位杂交分析证实了新的MAML3和NCOA2重排。随访（2-23个月），1例患者因切除不完全而出现局部复发,1例患者出现肺转移.另外两名患者没有疾病就活着。
结论：这项研究为NR1D1重排的软组织肿瘤作为一个新兴实体增加了更多的支持。在头部和颈部区域发生另外两个肿瘤，小圆形细胞变异体的描述和新型MAML3、KMT2A和NCOA2伴侣的鉴定进一步扩展了其临床病理和分子谱。需要对更大系列进行更多研究，以验证NR1D1重排的软组织肿瘤的完全恶性潜力。
结果：从我们的咨询文件中确定了4个具有NR1D1重排的间充质肿瘤。有一名男性和三名女性，年龄在19至47岁之间（中位数=28.5岁）。肿瘤发生在舌头，脖子,臀部和食指,分别。组织学上,两个肿瘤主要由上皮样细胞组成；一个肿瘤混合了上皮样-梭形细胞，一个肿瘤由单形小圆形至卵形细胞组成。通过免疫组织化学，没有一个肿瘤表达谱系特异性标记。靶向RNA测序确定了所有四个肿瘤中的NR1D1融合体，伴侣基因分别为MAML2、MAML3、KMT2A和NCOA2。通过荧光原位杂交分析证实了新的MAML3和NCOA2重排。随访（2-23个月），1例患者因切除不完全而出现局部复发,1例患者出现肺转移.另外两名患者没有疾病就活着。
结论：这项研究为NR1D1重排的软组织肿瘤作为一个新兴实体增加了更多的支持。在头部和颈部区域发生另外两个肿瘤，小圆形细胞变异体的描述和新型MAML3、KMT2A和NCOA2伴侣的鉴定进一步扩展了其临床病理和分子谱。需要对更大系列进行更多研究，以验证NR1D1重排的软组织肿瘤的完全恶性潜力。
