Extra Renal Rhabdoid Tumor: A Rare Cause of Congenital Soft Tissue Tumor

Rhabdoid tumors (RTs) are a well-defined entity in the kidney or central nervous system of infants or children. However, soft-tissue involvement is uncommon. It’s an exceptional neonatal tumor of soft tissue. The imaging characteristics of this tumor are not specific. Biopsy allows diagnosis;the histomorphological characteristics of rhabdoid tumors, their immunoreactivity to epithelial markers and vimentin, and the INI-1 loss are important tools for diagnosis. RT tumors are aggressive and have a rapidly fatal clinical course in most cases. Despite multidisciplinary therapy, the survival rate is very low. We report a rare case occurring in a male neonate who presents at birth with a voluminous right axillary mass. A CT scan showed a well-limited tumor mass with lobulated contours. An ultrasound-guided biopsy was performed on day 8, showing the morphology and immunoprofile of RT. The mass showed rapid growth. The child was admitted for respiratory distress at 3 weeks. A thoraco-abdominal CT showed an increase in the size of the mass with the appearance of multiple lymph nodes and pleural, hepatic, and renal metastases. The child died two days later.

The Rhabdoid Tumor of the Kidney in Children—Cases Report

Teratoid rhabdoid tumors are highly malignant, rare and aggressive. The prognosis is very poor, with a pejorative and rapidly lethal evolution. The objective of this study was to show diagnostic and therapeutic approach through the report of four observations of rhabdoid tumor of the kidney in children, treated in the oncology unit at the pediatric department CHU Hassan II Fez Morocco, collected over a period of 10 years. The ages of the patients varied from 8 months and 5 and a half, with 3 girls and a boy. All children have abdominal distention with the discovery of a mass on clinical examination. The patients were treated as nephroblastoma by neoadjuvant chemotherapy followed by enlarged total nephrectomy. The pathological study confirmed the diagnosis of a teratoid rhabdoid tumor. Adjuvant chemotherapy was given in all four children combined with radiotherapy in three cases. The evolution was fatal in three children. Malignant rhabdoid tumors are a particular pathological entity requiring a well codified therapeutic protocol to improve survival which does not exceed 15% to 20%.

Cure of Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System: A Case Report

Atypical teratoid/rhabdoid tumor (AT/RT) is an embryonic central nervous system tumor. It has a low incidence with a high degree of malignancy and a poor prognosis. Five years ago, we successfully treated a child with AT/RT. Treatment comprised total tumor resection, 6 MV X 3D conformal radiotherapy (DT: 36Gy/18FX) and six courses of chemotherapy, including teniposide 25 mg (qd × 5d), ACNU 25 mg (qd × 1d), vincristine 1 mg (qd × 1d). There was no tumor recurrence after 5 years of follow-up. We adjusted the previous AT/RT regimen to make it more suitable for the individual treatment of this patient, and now the patient has achieved a cure. So we think this regimen is effective and it is worthy of recommendation.

Feeder-free differentiation of human iPSCs into natural killer cells with cytotoxic potential against malignant brain rhabdoid tumor cells

Natural killer(NK)cells are cytotoxic immune cells that can eliminate target cells without prior stimulation.Human induced pluripotent stem cells(iPSCs)provide a robust source of NK cells for safe and effective cell-based immunotherapy against aggressive cancers.In this in vitro study,a feeder-free iPSC differentiation was performed to obtain iPSC-NK cells,and distinct maturational stages of iPSC-NK were characterized.Mature cells of CD56^(bright)CD16^(bright)phenotype showed upregulation of CD56,CD16,and NK cell activation markers NKG2D and NKp46 upon IL-15 exposure,while exposure to aggressive atypical teratoid/rhabdoid tumor(ATRT)cell lines enhanced NKG2D and NKp46 expression.Malignant cell exposure also increased CD107a degranulation markers and stimulated IFN-γsecretion in activated NK cells.CD56^(bright)CD16^(bright)iPSC-NK cells showed a ratio-dependent killing of ATRT cells,and the percentage lysis of CHLA-05-ATRT was higher than that of CHLA-02-ATRT.The iPSC-NK cells were also cytotoxic against other brain,kidney,and lung cancer cell lines.Further NK maturation yielded CD56^(-ve) CD16^(bright)cells,which lacked activation markers even after exposure to interleukins or ATRT cells-indicating diminished cytotoxicity.Generation and characterization of different NK phenotypes from iPSCs,coupled with their promising anti-tumor activity against ATRT in vitro,offer valuable insights into potential immunotherapeutic strategies for brain tumors.

Modeling human brain rhabdoid tumor by inactivating tumor suppressor genes in induced pluripotent stem cells

Atypical teratoid/rhabdoid tumor(ATRT)is a rare childhood malignancy that originates in the central nervous system.Over ninety-five percent of ATRT patients have biallelic inactivation of the tumor suppressor gene SMARCB1.ATRT has no standard treatment,and a major limiting factor in therapeutic development is the lack of reliable ATRT models.We employed CRISPR/Cas9 gene-editing technology to knock out SMARCB1 and TP53 genes in human episomal induced pluripotent stem cells(Epi-iPSCs),followed by brief neural induction,to generate an ATRT-like model.The dual knockout Epi-iPSCs retained their stemness with the capacity to differentiate into three germ layers.High expression of OCT4 and NANOG in neurally induced knockout spheroids was comparable to that in two ATRT cell lines.Beta-catenin protein expression was higher in SMARCB1-deficient cells and spheroids than in normal Epi-iPSC-derived spheroids.Nucleophosmin,Osteopontin,and Ki-67 proteins were also expressed by the SMARCB1-deficient spheroids.In summary,the tumor model resembled embryonal features of ATRT and expressed ATRT biomarkers at mRNA and protein levels.Ribociclib,PTC-209,and the combination of clofilium tosylate and pazopanib decreased the viability of the ATRT-like cells.This disease modeling scheme may enable the establishment of individualized tumor models with patient-specific mutations and facilitate high-throughput drug testing.

Molecular targeted therapies for pediatric atypical teratoid/rhabdoid tumors

Atypical teratoid/rhabdoid tumors (AT/RTs) are lethal central nervous system tumors, which are primarily diagnosed in infants. Current treatments for AT/RTs include surgery, radiotherapy, and chemotherapy;these treatments have poor prognoses and challenging side effects. The pivotal genetic event in AT/RT pathogenesis comprises the inactivation ofSMARCB1 orSMARCA4. Recent epigenetic studies have demonstrated mutual and subtype-specific epigenetic derangements that drive tumorigenesis;the exploitation of these potential targets might improve the dismal treatment outcomes of AT/RTs. This review aims to summarize the literature concerning targeted molecular therapies for pediatric AT/RTs.

Clinicopathological study and diagnosis of rhabdoid tumor of kidney combined with metanephric adenoma

Rhabdoid tumor of kidney （RTK） is a highly malignant tumor that occurs in infants and children, and approximately 80% of patients are diagnosed in the first two years of life. It was firstly described in 1978, and was defined as an independent disease in 1981. In the reported literatures, there were less in adolescents and extremely rare in adults.

Desmoplastic small round cell tumor with atypical immunohistochemical profile and rhabdoid-like differentiation

Desmoplastic small round cell tumor(DSRCT) is a rare,aggressive malignant neoplasm of unknown origin, and is comprised of small round cells with a characteristic desmoplastic stroma. DSRCT typically expresses epithelial, mesenchymal and neural markers simultaneously. We describe a case of DSRCT with an atypical immunohistochemical profile and rhabdoid-like tumor cells on electron microscopy. In the present case, the neoplastic cells were positive only for vimentin, desmin(cytoplasmic membranous pattern) and CD56,and negative for smooth muscle actin, synaptophysin,CD117, CD45, myogenin, CAM5.2, pancytokeratin,WT1, EMA, CD99, neurofilament, CD34 and p53. Ki67 showed a low proliferative activity. Electron microscopy showed focal rhabdoid differentiation. However, INI-1(SNF-5/BAF47) demonstrated preservation of nuclear positivity in the neoplastic cells. Cytogenetic studies showed translocation t(11;22)(p13;q12) confirming an EWSR1-WT1 translocation characteristic for DSRCT, and t(1;15)(q11;p11.2) of unknown significance. This case is a diagnostic challenge because of atypical immunohistochemical profile and cytogenetic study is crucial in rendering the correct diagnosis.

儿童侧脑室非典型畸胎瘤样/横纹肌样瘤4例

非典型畸胎瘤样/横纹肌样瘤(atypical teratoid/rhabdoid tumor, AT/RT)临床少见且预后不良,多位于幕下或皮层下方,发生于侧脑室较为罕见且预后极差,目前国内仅有6例侧脑室AT/RT相关报道。本文报道4例儿童侧脑室AT/RT患儿的诊疗经过,并通过文献复习对该病的临床表现、鉴别诊断、治疗及预后进行讨论,以提高临床医生对该病的认识,减少漏诊及误诊发生率。

1例婴儿横纹肌样瘤易感综合征超声表现

患儿男,1个月,监护人发现其左大腿后侧根部肿物1周;否认家族史。查体:左大腿后侧根部隆起,触及4 cm×3 cm×4 cm质硬肿物,活动度欠佳,边界不清;局部皮肤无明显异常。实验室检查:神经元特异性烯醇化酶66.68 ng/ml;糖类抗原CA-153 11.14 ng/ml, 糖类抗原CA-125 5.57 ng/ml, 糖类抗原CA-199 14.32 ng/ml。

儿童颅内非典型畸胎样/横纹肌样瘤的临床分析

目的探讨颅内非典型畸胎样/横纹肌样瘤(AT/RT)的影像学特征、临床表现及病理特点以提高对AT/RT的诊断及治疗认识。方法回顾性分析郑州大学第一附属医院收治的10例AT/RT患儿的临床资料,检索国内外文献进行总结分析。结果10例AT/RT中<2岁的患儿6例(60%),>2岁的患儿4例(40%);镜下全切除4例,次全切除6例。其中2例>3岁的患者接受放化疗处理。所有患者随访2~12个月,所有患者在随访期内复查头颅MRI均不同程度原位复发,其中1例发生脑膜转移及椎管内转移,1例伴发肺部转移,2例因原位复发和脑内转移而再次手术。结论AT/RT临床发病率低,临床多以颅内压增高为主要表现,治疗方法为手术联合放化疗,诊断仍依赖病理诊断,目前仍无标准放化疗方案,该肿瘤恶性程度高,易复发,预后差,病死率高。

纵隔恶性横纹肌样瘤一例

本研究为回顾性研究,遵守《赫尔辛基宣言》,并经兰州大学第二医院伦理委员会审核批准,免除受试者知情同意,批准文号:2023A-356。患者男,16岁,自诉5个月前开始无明显诱因出现间断性颈部疼痛,可自行缓解,2个月前开始出现双上肢麻木,手指麻木明显,自觉影响写字、抓持等精细动作,以“脊髓肿瘤”收入院。专科查体:双上肢浅感觉减弱。

儿童肾恶性横纹肌样瘤的CT、MRI表现

目的探讨儿童肾恶性横纹肌样瘤的CT、MRI表现,以提高该病的影像诊断水平。方法回顾性分析上海市儿童医院2008年5月~2021年3月经病理证实8例肾恶性横纹肌样瘤的患者资料。7例患儿行CT平扫及增强检查,4例患儿行磁共振平扫及增强检查,观察分析肾恶性横纹肌样瘤体的部位、形态、大小、密度/信号特征、强化方式以及转移等。结果6例位于左肾,2例位于右肾,2例病变呈圆形或类圆形,6例为不规则形,6例累及肾窦、肾盂。CT平扫中5例呈稍高密度,2例呈等低密度,肿瘤最大径平均约8.6cm;2例合并出血,3例合并包膜下积液/积血,8例均合并囊变坏死。MRI平扫中4例T1WI呈低信号为主,3例T2WI呈稍高信号,1例T2WI呈混杂信号。2例病变DWI均呈明显高信号、相应ADC为低信号,提示病变弥散受限。增强后呈不均匀轻度强化。5例伴转移。结论儿童肾恶性横纹肌样瘤CT、MRI表现有特征性,儿童肾实质内巨大肿块,合并囊变坏死、出血,集合系统受累,伴有包膜下积液,弥散受限,增强扫描实性成分轻度强化,常合并转移,应高度警惕肾恶性横纹肌样瘤的可能。

Clinicopathologic characteristics of prostatic stromal sarcoma with rhabdoid features: A case report

BACKGROUND Prostatic stromal sarcoma presenting with rhabdoid features is extremely rare,and only four cases have been reported in the English-language literature to date.Accordingly, there is no absolute definition of this group of tumors as yet, and our overall understanding of its morphological features, therapeutic regimen and prognosis is limited.CASE SUMMARY A 34-year-old male patient was referred to our hospital to address a 2-mo history of hematuria and progressive dysuria. Pelvic computed tomography scan revealed a 6.0 cm × 5.2 cm × 7.2 cm mass in the prostate, with bladder invasion.The patient underwent transurethral prostatectomy as upfront therapy. He refused further treatment and died of uncontrollable tumor growth 3 mo after surgery. Pathology analysis revealed the stroma to be pleomorphic, with a huge number of atypical spindle cells. Rhabdomyoblastic cells, with abundant eosinophilic cytoplasm, were detected. The spindle cells were positive for vimentin, INI1 and β-catenin, and the rhabdomyoblastic cells were positive for MyoD1, myogenin and INI1. The spindle cells and epithelial cells were sporadically positive for P53.CONCLUSION The prostatic stromal sarcoma tumor was immunoreactive for β-catenin,suggesting a role for the Wnt/β-catenin pathway in this tumor type.

伴脊索样特征的非典型畸胎样/横纹肌样瘤4例临床病理及分子遗传学分析

目的探讨伴脊索样特征的非典型畸胎样/横纹肌样瘤(atypical teratoid/rhabdoid tumor,AT/RT)的临床病理学及分子遗传学特征。方法回顾性分析4例AT/RT的临床病理学及分子遗传学特征,采用免疫组化、FISH、Sanger测序及NGS进行检测,并复习相关文献。结果4例患者中女性3例,男性1例,年龄3~45岁;病变位于大脑半球1例,小脑2例,颈椎1例。临床表现为视物模糊、夜间枕部疼痛、耳鸣、右上肢疼痛等,病程1~2个月,MRI考虑胶质瘤、室管膜瘤、神经鞘瘤。镜下瘤细胞呈弥漫片巢状、条索状排列,均可见间质黏液样变性呈脊索样形态,瘤细胞主要为原始神经外胚层及横纹肌样细胞。免疫表型:瘤细胞INI-1均表达缺失,vimentin均弥漫表达,3例部分表达SMA,均不表达IDH-1、H3K27M、GFAP、Oligo-2、Brachyury、SOX10,ATRX、H3K27me3均无表达缺失,Ki-67增殖指数50%~80%。FISH及Sanger测序未见阳性。NGS检测:例3检测有SMARCB1缺失突变。随访:例1于术后12个月复发转移,总生存期26个月;例2术后12个月死亡;例3放、化疗结束,术后5个月未复发;例4仍处于治疗中。结论AT/RT临床罕见,好发于儿童,成人亦可发生,易局部复发和沿脑脊髓播散,其显示脊索样特征,需与骨外黏液样软骨肉瘤、脊索样胶质瘤、差分化脊索瘤等鉴别。

儿童中枢神经系统非典型畸胎样/横纹肌样瘤研究进展

非典型畸胎样/横纹肌样瘤(atypical teratoid/rhabdoid tumor,AT/RT)是一种罕见且高度恶性的儿童中枢神经系统胚胎性肿瘤,其组织形态多变、恶性程度高、临床进展迅速,患儿预后不佳。AT/RT的发病机制涉及染色体和基因的突变,特别是SMARCB 1基因功能的丧失。AT/RT的诊断主要依赖于组织学及免疫组化检测。目前关于AT/RT的治疗方案尚无统一标准,主要包括手术、化疗、放疗等多模式治疗以及新兴的靶向治疗和免疫治疗。尽管近年来对AT/RT的研究和临床试验有所进展,但患儿预后仍然不佳,仍需进一步研究以制定更有效的治疗策略,以提高患儿的预后。

临床、CT及MRI诊断横纹肌样瘤研究进展

横纹肌样瘤(RT)为罕见恶性肿瘤,可据其原发部位分为肾RT、中枢神经系统非典型畸胎样RT及肾外非中枢神经系统RT。不同类型RT的临床、CT及MRI表现有其共性亦各具特征,对及时诊断及治疗RT至关重要。本文就临床、CT及MRI诊断RT研究进展进行综述。

儿童颅内非典型畸胎瘤样/横纹肌样瘤的影像表现

目的:探讨儿童颅内非典型畸胎瘤样/横纹肌样瘤(AT/RT)的影像特点。方法:回顾性分析2017年12月-2021年9月在本院经病理证实的15例AT/RT患儿的临床和影像资料。15例均行MRI平扫、DWI及对比增强扫描,10例行3D-ASL及MRS检查,10例行CT平扫。15例中,男9例、女6例;年龄0.17~1.67岁,中位年龄0.83岁。结果:15例中4例肿瘤位于幕上,7例位于幕下,跨幕上和幕下4例;肿瘤最大径2.0~10.0 cm;15例肿瘤合并囊变14例,其中11例囊变位于外周,合并出血8例。所有病灶呈不同程度强化,其中6例呈明显环形不均匀强化;DWI上病灶呈不均匀高信号;ASL上8例呈等灌注,2例呈高灌注;MRS示肿瘤NAA降低,Cho升高。15例肿瘤中侵犯脑膜1例;伴有脑内转移2例,其中1例合并脑脊液播散。结论:颅内AT/RT的影像学表现具有一定的特征性,有助于鉴别诊断。

泛素结合酶2C通过Wnt/β-catenin信号通路促进肾恶性横纹肌样瘤的恶性进展

目的:探讨泛素结合酶2C(ubiquitin-conjugating enzyme 2 C,UBE2C)对肾恶性横纹肌样瘤(malignant rhabdoid tumor of the kidney,MRTK)的影响及作用机制。方法:采用蛋白免疫印迹(Western blot,WB)以及免疫荧光法在收集的MRTK临床标本以及细胞系G401细胞中验证UBE2C的表达情况。从TARGET数据库下载MRTK的基因表达数据进行验证,Kaplan-Meier法(KM法)评估UBE2C与预后的关系。采用小干扰RNA(small interfering RNA,siRNA)抑制UBE2C在G401细胞中的表达。通过CCK-8检测转染后G401细胞增殖情况,流式细胞术检测细胞凋亡能力,划痕实验和Transwell实验分别检测细胞迁移和侵袭能力的改变。采用基因集富集分析(Gene Set Enrichment Analysis,GSEA)探索UBE2C调控的相关通路,并通过WB验证通路蛋白的表达。结果:在MRTK临床标本中,UBE2C表达量是癌旁对照组的(3.189±1.900)倍(P=0.033)。G401细胞系中UBE2C表达量是HEK293细胞的(2.092±0.231)倍(P=0.000),KM生存分析显示,高表达UBE2C的患者预后更差(P=0.019),并且UBE2C在4期患者(680.9±167.7)中高于早期患者(560.5±166.9),差异有统计学意义(P=0.021)。采用siRNA成功将UBE2C的表达敲低至(0.446±0.058)倍(P=0.000),并且发现敲低UBE2C抑制了G401细胞增殖、侵袭、迁移以及促进了细胞凋亡(P=0.000)。GSEA富集分析发现UBE2C与Wnt/β-catenin信号通路相关(P=0.000),敲低UBE2C可以抑制Wnt/β-catenin信号通路及上皮间质转换(epithelial-mesenchymal transition,EMT)(P=0.000)。结论:UBE2C在MRTK中高表达与不良预后相关,参与调控Wnt/β-catenin信号通路,抑制UBE2C可以抑制MRTK的增殖、迁移、侵袭,EMT,促进其凋亡。

20例恶性横纹肌样瘤临床分析

目的 探讨恶性横纹肌样瘤(malignant rhabdoid tumor,MRT)的临床特征、病理特征及诊治疗效。方法 回顾性分析2017年1月至2023年2月华中科技大学同济医学院附属同济医院20例MRT患者的临床资料,对患者随访并分析其生存数据。结果 20例MRT患者,其中男11例,女9例;发病平均年龄7.1岁。患者均经病理确诊,其中肾外非中枢神经系统横纹肌样瘤(extrarenal extracranial rhabdoid tumor,EERT)6例、肾脏横纹肌样瘤(malignant rhabdoid tumor of the kidney,MRTK)4例、中枢神经系统非典型畸胎样横纹肌样瘤(atypical teratoid rhabdoid tumor,ATRT)10例。临床确诊时肿瘤分期Ⅰ期0例,Ⅱ期1例,Ⅲ期6例,Ⅳ期13例。20例患者均接受手术治疗,术后病理免疫组化提示整合酶相互作用因子1 (integrase interactor 1,INI-1)蛋白表达缺失19例,表达不明确1例;肿瘤组织中上皮细胞膜抗原(epithelial membrane antigen,EMA)、波形蛋白(vimentin)及角蛋白(cyto keratin,CK)阳性表达率为90%。术后患者接受放射治疗(简称放疗)、化学治疗(简称化疗)等综合治疗。随访期内16例患者死亡,其中MRTK 4例、EERT 4例、ATRT 8例;4例患者(2例EERT,2例ATRT)截至2023年3月31日存活。结论 MRT好发于低龄儿童,成人罕见,恶性程度高。其诊断主要依据组织病理检查,INI-1是敏感性及特异性免疫组化指标。治疗手段以手术、化疗及放疗为主,但疗效不佳,生存期短。