具有全外显子组测序结果的软组织成纤维网状细胞肿瘤:Lynch综合征的意外表现

IF 0.2
Liurka V Lopez, Daniel F Marker, N. Bailey, Yen‐Chun Liu, Richard L. Mcgough, A. Singhi, I. John
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引用次数: 3

摘要

纤维母细胞网状细胞瘤(FRCT)是一种非常罕见的肿瘤,在组织学上与滤泡树突状细胞肉瘤或交叉指状树突状细胞肉瘤相似,但缺乏这些肿瘤的免疫表型特征。这种肿瘤通常发生在淋巴结和脾脏,只有4例发生在软组织。我们报告一例FRCT表现为右大腿肿块在一个67岁的妇女以前没有恶性肿瘤。大体检查显示一个10.6厘米的棕褐色、边界清楚的肌肉内肿块。镜检显示细胞群不粘连,胞浆不清晰,胞核不规则,不典型,核仁不同程度地突出,胶原背景被淋巴细胞浸润。肿瘤细胞中平滑肌肌动蛋白、细胞角蛋白(呈树突状)和CD163呈阳性,而CD21、CD35和CD23呈阴性,支持FRCT的诊断。全外显子组测序显示肿瘤中存在631个体细胞突变(>10个突变/Mb序列)。突变特征分析提示DNA错配修复缺陷。种系突变分析显示MLH1 (c.2246)存在杂合致病性错义突变T > C, p. [1];随后的免疫组化分析显示肿瘤细胞中MLH1和PMS2完全缺失。据我们所知,这是第一例以测序研究为特征的FRCT病例,并发现与Lynch综合征(LS)相关,扩大了LS相关肿瘤的范围。该病例显示了与LS中更常见的上皮病变相似的基因高突变,它突出了高通量遗传分析识别非典型组织学错配修复缺陷肿瘤的潜力,这可能在免疫治疗时代具有重要的临床意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Soft Tissue Fibroblastic Reticular Cell Tumor With Whole-Exome Sequencing Findings: An Unexpected Presentation of Lynch Syndrome
Fibroblastic reticular cell tumor (FRCT) is an exceedingly rare tumor that is histologically reminiscent of follicular dendritic cell sarcoma or interdigitating dendritic cell sarcoma but lacks the immunophenotypic features of these tumors. This tumor is classically described in lymph nodes and spleen, with only 4 cases described in soft tissues. We report a case of FRCT presenting as a right thigh mass in a 67-year-old woman with no prior malignancies. Gross examination showed a 10.6-cm tan well-circumscribed intramuscular mass. Microscopic examination revealed a discohesive population of cells with indistinct pale cytoplasm and large irregular, atypical vesicular nuclei with variably prominent nucleoli in a collagenous background infiltrated by lymphocytes. The tumor cells were positive for smooth muscle actin, cytokeratins (in a dendritic pattern), and CD163, while negative for CD21, CD35, and CD23, supporting the diagnosis of FRCT. Whole-exome sequencing revealed 631 putative somatic mutations in the tumor (>10 mutations/Mb of sequence). Mutational signature analysis suggested DNA mismatch repair deficiency. Germline mutational analysis revealed a heterozygous pathogenic missense mutation of MLH1 (c.2246 T > C, p. Leu749Pro). Subsequent immunohistochemical analysis showed complete loss of MLH1 and PMS2 in tumor cells. To our knowledge, this is the first case of FRCT characterized by sequencing studies and found to be associated with Lynch syndrome (LS), expanding the spectrum of LS-associated neoplasms. This case demonstrates genetic hypermutation similar to that seen in the more common epithelial lesions arising in LS, and it highlights the potential for high-throughput genetic analysis to identify mismatch repair–deficient tumors of atypical histologies, which may have significant clinical implications in the era of immunotherapy.
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期刊介绍: Each issue of Pathology Case Reviews examines one vital theme in the field with peer-reviewed, clinically oriented case reports that focus on diagnosis, specimen handling and reports generation. Each theme-oriented issue covers both histopathologic and cytopathologic cases, offering a comprehensive perspective that includes editorials and review articles of the newest developments in the field, differential diagnosis hints, applications of new technologies, reviews of current issues and techniques and an emphasis on new approaches.
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