已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

“Renal Cell Carcinoma With Leiomyomatous Stroma” Harbor Somatic Mutations of TSC1, TSC2, MTOR, and/or ELOC (TCEB1): Clinicopathologic and Molecular Characterization of 18 Sporadic Tumors Supports a Distinct Entity

结节性硬化 病理 肾细胞癌 基质 生物 TSC1 清除单元格 免疫组织化学 癌症研究 透明细胞癌 PI3K/AKT/mTOR通路 医学 遗传学 细胞凋亡
作者
Rajal B. Shah,Bradley A. Stohr,Zheng Jin Tu,Yuan Gao,Christopher G. Przybycin,Jane Nguyen,Roni M. Cox,Fariborz Rashid-Kolvear,Michael Weindel,Daniel H. Farkas,Kiril Trpkov,Jesse K. McKenney
出处
期刊:The American Journal of Surgical Pathology [Lippincott Williams & Wilkins]
卷期号:44 (5): 571-581 被引量:84
标识
DOI:10.1097/pas.0000000000001422
摘要

Renal cell carcinoma with (angio) leiomyomatous stroma (RCCLMS) is included as a provisional entity in the 2016 World Health Organization (WHO) classification of renal epithelial neoplasia; however, debate remains whether it represents a distinct entity or a heterogenous group of renal cell carcinomas (RCCs) with overlapping morphology. Also, its relationship to similar tumors occurring in the setting of tuberous sclerosis complex (TSC) is not fully addressed. We analyzed the clinicopathologic, immunohistochemical, and molecular characteristics of 23 sporadic RCCs associated with smooth muscle stroma and classified them into 2 groups, independent of molecular results: (1) RCCLMS (n=18) and (2) clear cell renal cell carcinoma (CCRCC) (n=5). The classification of a case as “RCCLMS” was based on morphologic comparison with 5 “index” RCCs from 3 patients with TSC showing similar features and the presence of diffuse CK7 expression. To investigate mutational and copy number alterations, a 170-gene solid tumor panel was utilized to sequence 14 RCCLMSs and control of 5 CCRCCs. Also, 4 RCCLMSs, suspicious for chromosome 8 monosomy, were further evaluated by a broader 479 gene sequencing panel that included ELOC (also referred to as TCEB1 ). Clinical information and follow-up data were obtained from electronic medical records. The mean age of patients with RCCLMS was 52 years (range, 33 to 69) with male:female ratio of 1:2. Macroscopically, all tumors were solitary and predominantly (82%) tan/red, circumscribed, and solid. The average tumor size was 2.3 cm (range, 1.1 to 4.5). Microscopically, the distinctive feature included tumor nodules of elongated and frequently branching tubules lined by cells with voluminous clear to mildly eosinophilic cytoplasm (100%), separated by focal to prominent smooth muscle stroma. Additional frequently identified features included: biphasic pattern of collapsed acini surrounding tubules with voluminous cytoplasm (50%), focal papillary architecture (39%), peritumoral lymphoid aggregates (39%), and hemosiderin-laden macrophages (33%). All 11 (100%) RCCLMSs with available staging information were pT1; 78% were WHO/International Society of Urologic Pathology (ISUP) grade 2 and 22% grade 3. Immunophenotypically, RCCLMSs were characterized by diffuse CK7, CAM5.2 and CD10 reactivity (100%). All patients with available follow-up (n=10) were alive and without disease progression after a mean and median follow-up of 25.2 (range: 1 to 58) and 25 months, respectively. The molecular results showed recurrent mutations in all RCCLMS: TSC1 (4), TSC2 (4), MTOR (6), and/or ELOC (2). Five control CCRCCs demonstrated primary alterations in VHL gene, while all 14 RCCLMS cases tested had intact VHL gene. Of 2 RCCLMSs with confirmed monosomy 8, 1 showed a hotspot ELOC mutation without TSC/MTOR mutations, and 1 showed a previously undescribed 3-bp in-frame ELOC deletion, along with a truncating TSC1 mutation. In conclusion, RCCLMS, as defined herein, harbors recurrent mutations of TSC1 / TSC2 , MTOR , and/or ELOC , consistent with hyperactive MTOR complex. Our findings argue that these tumors represent the sporadic counterpart to morphologically identical tumors occurring in TSC patients. Finally, the data support that RCCLMS is a novel subtype of RCC with unique morphologic, immunohistochemical, and molecular characteristics that is distinct from CCRCC and clear cell-papillary RCC.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
聪慧的乌完成签到,获得积分10
1秒前
wfrg完成签到 ,获得积分10
5秒前
打打应助FXY采纳,获得10
9秒前
沉静安荷发布了新的文献求助20
10秒前
刻苦的小土豆完成签到 ,获得积分10
14秒前
jackone发布了新的文献求助10
15秒前
Liufgui应助科研达人采纳,获得10
18秒前
21秒前
小熊发布了新的文献求助10
26秒前
29秒前
鲤鱼安青完成签到 ,获得积分10
32秒前
FXY发布了新的文献求助10
35秒前
36秒前
39秒前
42秒前
开霁完成签到 ,获得积分10
43秒前
Christian完成签到,获得积分10
44秒前
霜鸣发布了新的文献求助10
48秒前
江氏巨颏虎完成签到,获得积分10
48秒前
jackone完成签到,获得积分10
49秒前
罗实完成签到 ,获得积分10
54秒前
沉静安荷完成签到,获得积分10
54秒前
汉堡包应助WZ采纳,获得10
56秒前
59秒前
大白完成签到 ,获得积分10
59秒前
小潘完成签到 ,获得积分10
1分钟前
1分钟前
仓鼠球发布了新的文献求助30
1分钟前
赵雨霏完成签到 ,获得积分10
1分钟前
生动丑应助科研通管家采纳,获得10
1分钟前
1分钟前
1分钟前
1分钟前
1分钟前
悄悄完成签到 ,获得积分10
1分钟前
程子完成签到,获得积分10
1分钟前
John完成签到 ,获得积分10
1分钟前
1分钟前
mmyhn驳回了田様应助
1分钟前
1分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990008
求助须知:如何正确求助?哪些是违规求助? 3532034
关于积分的说明 11256121
捐赠科研通 3270913
什么是DOI,文献DOI怎么找? 1805105
邀请新用户注册赠送积分活动 882270
科研通“疑难数据库(出版商)”最低求助积分说明 809216