Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Department of Pathology, Charles University, Faculty of Medicine in Pilsen, Pilsen, Czech Republic.
Mod Pathol. 2018 Dec;31(12):1862-1868. doi: 10.1038/s41379-018-0102-y. Epub 2018 Jul 5.
Lipoblastoma-like tumor of the vulva was first described as a benign mesenchymal neoplasm of adipocytic differentiation having features of lipoblastoma, myxoid liposarcoma, and spindle cell lipoma. Prior studies of lipoblastoma-like tumor have evaluated PLAG1, HMGA2, and RB1 immunohistochemistry and DDIT3 rearrangement status, with results supporting its distinction from lipoblastoma and myxoid liposarcoma. However, absent RB1 expression was reported in a majority of tested cases, suggesting that lipoblastoma-like tumor may have underlying 13q alterations and be related to RB1-deleted soft tissue tumors. To further understand the molecular genetics of lipoblastoma-like tumor, we examined 7 cases by RB1 immunohistochemistry, DDIT3 and PLAG1 break apart FISH probes, RB1 enumeration FISH probe, and genomic copy number analysis by microarray. Patient age ranged from 21 to 56 years (median 35 years). Clinical follow up was available for 5 patients (71%) ranging 3-264 months (median 74 months). Microscopically, lipoblastoma-like tumor formed large lobules separated by thin and/or thick bands of fibrous tissue and had a prominent network of thin-walled vessels. Each tumor was predominantly composed of spindle cells and lipoblasts with variable quantities of mature adipocytes. RB1 immunohistochemistry exhibited a heterogeneous or "mosaic" pattern of weak and negative nuclear expression in all seven cases. DDIT3 and PLAG1 FISH were negative in each case. No evidence of RB1 regional gain or loss was identified by FISH. Genomic copy number analysis by chromosomal microarray showed a normal diploid profile in six tumors (86%). One tumor had copy number abnormalities consisting of an 11.9 megabase deletion from 1p13.3 to 1p11.2 and monosomy 14. Although lipoblastoma-like tumor has features of lipoblastoma, myxoid liposarcoma, and spindle cell lipoma, it is genetically different from these tumors. Furthermore, lipoblastoma-like tumor does not appear to have structural abnormalities of 13q resulting in deletion of RB1.
外阴脂肪母细胞瘤样肿瘤最初被描述为一种良性间叶性肿瘤，具有脂肪母细胞瘤、黏液样脂肪肉瘤和梭形细胞脂肪瘤的分化特征。先前对脂肪母细胞瘤样肿瘤的研究评估了 PLAG1、HMGA2 和 RB1 的免疫组织化学和 DDIT3 重排状态，结果支持其与脂肪母细胞瘤和黏液样脂肪肉瘤的区别。然而，大多数测试病例中均未见 RB1 的表达，这表明脂肪母细胞瘤样肿瘤可能存在潜在的 13q 改变，并与 RB1 缺失的软组织肿瘤有关。为了进一步了解脂肪母细胞瘤样肿瘤的分子遗传学，我们通过 RB1 免疫组织化学、DDIT3 和 PLAG1 断裂 FISH 探针、RB1 计数 FISH 探针以及微阵列基因组拷贝数分析检查了 7 例病例。患者年龄为 21 至 56 岁（中位数 35 岁）。5 例患者（71%）有临床随访，随访时间为 3-264 个月（中位数 74 个月）。显微镜下，脂肪母细胞瘤样肿瘤形成大的小叶，由薄的和/或厚的纤维组织带分隔，有明显的薄壁血管网络。每个肿瘤主要由梭形细胞和脂肪母细胞组成，伴有不同数量的成熟脂肪细胞。7 例病例的 RB1 免疫组织化学均表现为弱和阴性核表达的异质性或“镶嵌”模式。每个病例的 DDIT3 和 PLAG1 FISH 均为阴性。FISH 未发现 RB1 区域获得或丢失的证据。通过染色体微阵列的基因组拷贝数分析显示，6 个肿瘤（86%）的染色体组为正常二倍体。一个肿瘤有拷贝数异常，包括从 1p13.3 到 1p11.2 的 11.9 兆碱基缺失和 14 号单体。尽管脂肪母细胞瘤样肿瘤具有脂肪母细胞瘤、黏液样脂肪肉瘤和梭形细胞脂肪瘤的特征，但它在遗传学上与这些肿瘤不同。此外，脂肪母细胞瘤样肿瘤似乎没有导致 RB1 缺失的 13q 结构异常。
