ALK重排肾细胞癌:一项关于九个病例的多机构研究,扩大了形态学和分子遗传谱。

IF 7.1 1区 医学 Q1 PATHOLOGY
Ming Zhao , Xiaona Yin , Xiaoqun Yang , Hualei Gan , Ni Chen , Guangjie Duan , Yanfeng Bai , Xiaodong Teng , Jiayun Xu , Rong Fang , Suying Wang , Shan Zhong , Xiaotong Wang , Lisong Teng
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引用次数: 0

摘要

ALK重组肾细胞癌(ALK-RCC)是一种非常罕见的RCC亚型,在最近出版的世界卫生组织第五版肿瘤分类中被分子定义为ALK-RCC。在本研究中,我们从临床病理学、免疫组化和分子遗传学方面描述了9例ALK-RCC,支持并扩展了以往研究对这一罕见RCC亚群的观察。患者中有六名男性和三名女性,年龄在14至59岁之间(平均34.4岁)。所有患者均无镰状细胞特质。八名患者的诊断依据是根治性或部分肾切除术标本,一名患者的诊断依据是活组织检查标本。肿瘤大小从2.5厘米到7.2厘米不等(平均为2.8厘米)。6/9例患者接受了随访(6至36个月),其中5例没有肿瘤复发或转移,1例在24个月时出现肺转移。该患者随后接受了转移性肿瘤切除术和克唑替尼靶向治疗,12个月后无肿瘤存活。组织学上,肿瘤呈多种形态混合生长,包括乳头状、实性、管状、管囊状、楔形和条索状,通常以粘液为背景。肿瘤细胞主要具有嗜酸性细胞质。在肿瘤细胞上还可观察到透明的胞质、两极分化的细胞核和核下空泡(n=1)以及苍白的泡沫状胞质(n=1)。活检的肿瘤显示,拉长的小管与平滑的纺锤形细胞合并,呈实性生长。其他常见和不常见的特征包括:炎性微钙化(5 个)、横纹状细胞(4 个)、突出的胞浆内空泡(4 个)、突出的慢性炎症浸润(3 个)、标志环细胞形态(2 个)和多形性细胞(2 个)。免疫组化结果显示,所有9个肿瘤的ALK(5A4)均呈弥漫阳性,4/8的病例对TFE3蛋白有反应。通过荧光原位杂交分析,9例肿瘤中均发现了ALK重排;没有一例出现TFE3重排(0/4)或7号和17号染色体增益(0/3)。在分析的所有8个病例中,均通过RNA测序发现了ALK融合伙伴,包括EML4(n=2)、STRN(n=1)、TPM3(n=1)、KIF5B(n=1)、HOOK1(n=1)、SLIT1(n=1)和TPM1(3'UTR)(n=1)。我们的研究进一步扩展了ALK-RCC的形态学和分子遗传谱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ALK-Rearranged Renal Cell Carcinoma: A Multi-Institutional Study of 9 Cases With Expanding the Morphologic and Molecular Genetic Spectrum

ALK-rearranged renal cell carcinoma (ALK-RCC) is rare, molecularly defined RCC subtype in the recently published fifth edition of World Health Organization classification of tumors. In this study, we described 9 ALK-RCCs from a clinicopathologic, immunohistochemical, and molecular genetic aspect, supporting and extending upon the observations by previous studies regarding this rare subgroup of RCC. There were 6 male and 3 female patients with ages ranging from 14 to 59 years (mean, 34.4 years). None of the patients had sickle cell trait. The diagnosis was based on radical or partial nephrectomy specimen for 8 patients and on biopsy specimen for 1. Tumor size ranged from 2.5 to 7.2 cm (mean, 2.8 cm). Follow-up was available for 6 of 9 patients (6-36 months); 5 had no tumor recurrence or metastasis and 1 developed lung metastasis at 24 months. The patient was subsequently treated with resection of the metastatic tumor followed by crizotinib-targeted therapy, and he was alive without tumor 12 months later. Histologically, the tumors showed a mixed growth of multiple patterns, including papillary, solid, tubular, tubulocystic, cribriform, and corded, often set in a mucinous background. The neoplastic cells had predominantly eosinophilic cytoplasm. Focally, clear cytoplasm with polarized nuclei and subnuclear vacuoles (n = 1), and pale foamy cytoplasm (n = 1) were observed on the tumor cells. The biopsied tumor showed solid growth of elongated tubules merging with bland spindle cells. Other common and uncommon features included psammomatous microcalcifications (n = 5), rhabdoid cells (n = 4), prominent intracytoplasmic vacuoles (n = 4), prominent chronic inflammatory infiltrate (n = 3), signet ring cell morphology (n = 2), and pleomorphic cells (n = 2). By immunohistochemistry, all 9 tumors were diffusely positive for ALK(5A4) and 4 of 8 tested cases showed reactivity for TFE3 protein. By fluorescence in situ hybridization analysis, ALK rearrangement was identified in all the 9 tumors; none of the tested tumors harbored TFE3 rearrangement (0/4) or gains of chromosomes 7 and 17 (0/3). ALK fusion partners were identified by RNA-sequencing in all 8 cases analyzed, including EML4 (n = 2), STRN (n = 1), TPM3 (n = 1), KIF5B (n = 1), HOOK1 (n = 1), SLIT1 (n = 1), and TPM1(3'UTR) (n = 1). Our study further expands the morphologic and molecular genetic spectrum of ALK-RCC.

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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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