Histological and molecular analysis of cellular leiomyoma with sclerosis: linked to HMGA2 overexpression.
Histological and molecular analysis of cellular leiomyoma with sclerosis: linked to HMGA2 overexpression.
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在10-15%的平滑肌瘤（LM）中发现HMGA 2过表达。HMGA 2过表达常见于水肿、静脉内和脂LM的变体中。细胞或高度细胞LM（CLM）是一种分子性质不太明确的LM变体。在这项研究中，我们确定并检查了52例细胞增生的LM与硬化胶原，本文定义为细胞平滑肌瘤硬化（CLM-S）。CLM-S显示肿瘤尺寸较大（平均12.2 cm）和肿瘤细胞的特征性组织学，排列为细胞束、片和小梁，带和结节中有丰富的致密粉红色细胞外基质，血管分布增加。肿瘤细胞是均匀的，具有小的、圆形-卵圆形的核和少量的、淡嗜酸性至空泡状的细胞质，使人联想到周细胞。CLM-S的鉴别诊断包括常规CLM、子宫内膜间质肿瘤和血管周围上皮样细胞肿瘤。与匹配的子宫肌层和CLM对照相比，分析了免疫组织化学特征[HMGA 2、富马酸水合酶、平滑肌标志物、Melan A和HMB-45]和分子变化[通过HMGA 2 mRNA逆转录-聚合酶链反应（RT-PCR）、HMGA 2荧光原位杂交和MED 12测序]。值得注意的是，96%（50/52）的CLM-S表现出对HMGA 2的弥漫性阳性免疫反应性，通过RT-PCR测定，HMGA 2 mRNA增加高达80倍。在内含子3和5' UTR处用断裂部分探针进行的FISH分析在47%（18/38）的CLM-S中检测到HMGA 2重排。所有CLM-S保留富马酸水合酶的表达。在任何CLM-S中均未发现MED 12突变。我们的研究结果表明，CLM-S具有独特和特征性的组织形态学，可能是由HMGA 2过表达驱动的。
HMGA2 overexpression is found in 10–15% of leiomyomas (LM). HMGA2 overexpression is common in variants of hydropic, intravenous and lipo-LM. Cellular or highly cellular LM (CLM) is a LM variant with a less well-defined molecular nature. In this study, we identified and examined 52 hypercellular LM with sclerotic collagen, herein defined as cellular leiomyoma with sclerosis (CLM-S). CLM-S shows large tumour size (average 12.2 cm) and characteristic histology of tumour cells, arranged in cellular fascicles, sheets and trabeculae with abundant dense, pink sclerotic extracellular matrix in bands and nodules and increased vascularity. Tumour cells are uniform with small, round–oval nuclei and scant, pale–eosinophilic to vacuolated cytoplasm reminiscent of pericytes. The differential diagnosis of CLM-S includes conventional CLM, endometrial stromal tumours and perivascular epithelioid cell tumour. Immunohistochemical profile [HMGA2, fumarate hydratase, smooth muscle markers, Melan A and HMB-45] and molecular alterations [by HMGA2 mRNA reverse transcription–polymerase chain reaction (RT–PCR), HMGA2 fluorescence in-situ hybridisation and MED12 sequencing] were analysed in comparison to matched myometrium and CLM controls. Remarkably, 96% (50 of 52) of CLM-S demonstrated diffuse positive immunoreactivity for HMGA2 and up to an 80-fold increase in HMGA2 mRNA, determined by RT–PCR. FISH analysis with break-part probes at intron 3 and the 5’ UTR detected HMGA2 rearrangements in 47% (18 of 38) of CLM-S. All CLM-S retained expression of fumarate hydratase. No MED12 mutations were found in any CLM-S. Our findings show that CLM-S has unique and characteristic histomorphology probably driven by HMGA2 overexpression.
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