Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a recently described adipocytic tumor predominantly affecting the subcutaneous soft tissues of adults. Previous studies have shown that ASPLT follows a benign clinical course with a 4% to 12% local recurrence rate and no risk of dedifferentiation. Herein, we describe the clinicopathologic and molecular findings of 4 cases of ASPLT showing unequivocal sarcomatous transformation. Three patients were male and one was female, aged 65, 70, 74, and 78 years. Two cases presented as mass-forming lesions, while 1 case was incidentally discovered. The tumors measured 30, 55, 80, and 110 mm and occurred in the chest wall (n = 2) or arm (n = 2); all were subcutaneous. Microscopically, they showed a biphasic appearance comprising a low-grade ASPLT component and a high-grade sarcomatous component. The low-grade components showed features in the spectrum of either atypical pleomorphic lipomatous tumor (n = 2) or atypical spindle cell lipomatous tumor (n = 2). The high-grade components displayed leiomyosarcoma-like (n = 2), pleomorphic liposarcoma-like (n = 1) or undifferentiated sarcoma-like (n = 1) morphology. On immunohistochemistry, tumors were negative for MDM2 and showed loss of RB1 expression. In addition, the leiomyosarcoma-like areas seen in 2 cases were positive for smooth muscle actin and H-caldesmon. Single-nucleotide polymorphism array, performed in 3 cases, showed deletions of , and flanking genes in both components. In contrast, the sarcomatous components showed more complex genomic profiles with rare segmental gains and recurrent loss of (n = 3), (n = 2), and (n = 2) among other genes. Whole exome sequencing identified a variant in one case and an variant in another, each occurring in both tumor components. Limited clinical follow-up showed no recurrence or metastasis after 1 to 13 months (median, 7.5 months) postsurgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offer insights into the molecular mechanisms underlying this event.

中文翻译：

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非典型梭形细胞/多形性脂肪瘤伴肉瘤变：4例临床病理及分子分析

非典型梭形细胞/多形性脂肪瘤（ASPLT）是最近描述的一种主要影响成人皮下软组织的脂肪细胞肿瘤。先前的研究表明，ASPLT 遵循良性临床过程，局部复发率为 4% 至 12%，且无去分化风险。在此，我们描述了 4 例 ASPLT 病例的临床病理学和分子学发现，显示明确的肉瘤转化。 3名患者为男性，1名女性，年龄分别为65岁、70岁、74岁和78岁。 2例表现为肿块性病变，1例是偶然发现的。肿瘤尺寸为 30、55、80 和 110 毫米，发生在胸壁 (n = 2) 或手臂 (n = 2)；全部都是皮下的。显微镜下，它们显示出双相外观，包括低级别 ASPLT 成分和高级别肉瘤成分。低级别成分显示出非典型多形性脂肪瘤性肿瘤 (n = 2) 或非典型梭形细胞脂肪瘤性肿瘤 (n = 2) 谱系的特征。高级别成分显示平滑肌肉瘤样（n = 2）、多形性脂肪肉瘤样（n = 1）或未分化肉瘤样（n = 1）形态。免疫组织化学显示，肿瘤 MDM2 呈阴性，并显示 RB1 表达缺失。此外，2例平滑肌肉瘤样区域平滑肌肌动蛋白和H-caldesmon阳性。在 3 个病例中进行的单核苷酸多态性分析显示，两个组件中的 和 侧翼基因均缺失。相比之下，肉瘤成分显示出更复杂的基因组图谱，其中罕见的片段增益和其他基因中（n = 3）、（n = 2）和（n = 2）的反复丢失。全外显子组测序在一个病例中发现了一个变异，在另一个病例中发现了一个变异，每种变异都出现在两种肿瘤成分中。有限的临床随访显示术后 1 至 13 个月（中位 7.5 个月）切除后未出现复发或转移。总而言之，我们的数据支持 ASPLT 很少会发生肉瘤转化，并为该事件背后的分子机制提供了见解。