With the widespread application of next-generation sequencing, the genetic landscape of uterine mesenchymal neoplasms has been evolving rapidly to include several recently identified fusion genes. Although chromosomal rearrangements involving the 10q22 and 17q21.31 loci have been reported in occasional uterine leiomyomas decades ago, the corresponding KAT6B::KANSL1 fusion has been only recently identified in 2 uterine tumors diagnosed as leiomyoma and leiomyosarcoma. We herein describe 13 uterine stromal neoplasms carrying a KAT6B::KANSL1 (n=11) and KAT6A::KANSL1 (n=2) fusion. Patient ages ranged from 33 to 81 years (median, 49 y). Tumor size was 2.6 to 23.5 cm (median, 8.2 cm). Nine tumors were myometrium-centered, and 3 had an intracavitary component. Original diagnoses were mostly low-grade endometrial stromal sarcoma (LG-ESS; 10 cases) with atypical features (limited CD10 expression, sex cord-like features, pericytic vasculature, and frequent myxoid changes). Treatment was hysterectomy±bilateral salpingo-oophorectomy (10), myomectomy (1), and curettage (2). Five patients were disease-free at 6 to 34 months, 3 (27%) died of disease at 2 to 47 months, and 3 were alive with disease at 2, 17, and 17 years. Histologically, most tumors showed variable overlap with LG-ESS, but they were generally well-circumscribed lacking the extensive permeative and angioinvasive growth typical of LG-ESS. They were composed of monotonous medium-sized oval and spindle cells arranged into diffuse sheets with prominent spiral-type arterioles and frequent pericytoma-like vascular pattern. Variable myxoid stromal changes were frequent. Mitotic activity ranged from 1 to >20 in 10 HPFs. Immunohistochemistry showed variable expression of CD10 (12/13), estrogen receptor (8/11), progesterone receptor (8/11), smooth muscle actin (9/11), desmin (4/12), h-caldesmon (2/10), calretinin (3/8), inhibin (1/7), WT1 (4/7), cyclin D1 (5/11; diffuse in only 1 case), and pankeratin (5/10). This series characterizes a KAT6B/A::KANSL1 fusion-positive uterine stromal neoplasm within the morphologic spectrum of LG-ESS but with atypical features. The relationship of these neoplasms to genuine LG-ESS remains unclear. This molecular subtype of uterine endometrial stromal sarcoma has the potential for an unfavorable clinical course despite the absence of widely invasive growth; nevertheless, analysis of more cases is necessary to delineate the phenotypic spectrum and biological potential of this tumor.

随着下一代测序的广泛应用，子宫间质肿瘤的遗传图谱正在迅速发展，包括几个最近发现的融合基因。尽管数十年前在子宫平滑肌瘤中已报道了涉及 10q22 和 17q21.31 位点的染色体重排，但直到最近才在诊断为平滑肌瘤和平滑肌肉瘤的 2 种子宫肿瘤中发现了相应的KAT6B::KANSL1融合。我们在此描述了 13 种携带KAT6B::KANSL1 (n=11) 和KAT6A::KANSL1 (n=2) 融合体的子宫间质肿瘤。患者年龄从 33 岁到 81 岁不等（中位年龄 49 岁）。肿瘤大小为 2.6 至 23.5 cm（中位数，8.2 cm）。9 个肿瘤以子宫肌层为中心，3 个肿瘤具有腔内成分。最初诊断大多为低度恶性子宫内膜间质肉瘤（LG-ESS；10例），具有非典型特征（有限的CD10表达、性索样特征、周细胞脉管系统和频繁的粘液样改变）。治疗包括子宫切除术±双侧输卵管卵巢切除术（10）、子宫肌瘤切除术（1）和刮宫术（2）。5 名患者在 6 至 34 个月时无病，3 名患者 (27%) 在 2 至 47 个月时因病死亡，3 名患者在 2、17 和 17 岁时仍患病。在组织学上，大多数肿瘤与 LG-ESS 表现出不同程度的重叠，但它们通常界限清楚，缺乏 LG-ESS 典型的广泛渗透性和血管侵袭性生长。它们由单调的中等大小的椭圆形和梭形细胞组成，排列成弥漫的片状，具有突出的螺旋型小动脉和频繁的周细胞瘤样血管模式。可变的粘液样基质变化很频繁。10 个 HPF 中的有丝分裂活性范围为 1 至 >20。免疫组织化学显示 CD10 (12/13)、雌激素受体 (8/11)、孕激素受体 (8/11)、平滑肌肌动蛋白 (9/11)、结蛋白 (4/12)、h-caldesmon (2/ 10)、钙视网膜蛋白 (3/8)、抑制素 (1/7)、WT1 (4/7)、细胞周期蛋白 D1 (5/11；仅 1 例弥漫) 和 Pankeratin (5/10)。该系列描述了LG-ESS 形态学范围内的KAT6B/A::KANSL1融合阳性子宫间质肿瘤，但具有非典型特征。这些肿瘤与真正的 LG-ESS 的关系仍不清楚。尽管不存在广泛的侵袭性生长，但这种子宫内膜间质肉瘤的分子亚型仍有可能出现不利的临床病程。然而，需要对更多病例进行分析来描绘这种肿瘤的表型谱和生物学潜力。