中枢神经系统非典型畸胎瘤样/横纹肌样瘤10例临床病理分析

目的 探讨中枢神经系统非典型畸胎瘤样/横纹肌样瘤(atypical teratoid/rhabdoid tumor,AT/RT)的临床病理学特征、诊断、鉴别诊断及预后.方法 回顾性分析2016年～2019年中南大学湘雅医院诊治的10例AT/RT的临床、影像学及病理学特征,并对其进行随访及相关文献复习.结果 10例患者发...     

中枢神经系统非典型畸胎瘤样/横纹肌样瘤1例临床病理分析

目的 探讨中枢神经系统非典型畸胎瘤样/横纹肌样瘤的临床病理特征、鉴别诊断.方法 对1例非典型畸胎瘤样/横纹肌样瘤应用HE染色、电子显微镜、免疫组织化学染色观察,并结合文献复习.结果 非典型畸胎瘤样/横纹肌样瘤具有特征性的横纹肌样细胞,伴有不同程度的原始神经外胚叶、上皮和间质分化.超微结构见瘤细胞内呈卷发丝样微丝小体,中间可见线粒体.免疫组织化学标记示:EMA、vimentin、CD99、NF和NSE(+),SMA、GFAP、CD117和PLAP(-).结论 非典型畸胎瘤样/横纹肌样瘤是中枢神经系统一种罕见的高度恶性肿瘤,好发于儿童,其诊断需与脑内其他多形性肿瘤鉴别.     

颅内“横纹肌样细胞”形态肿瘤13例临床病理分析

目的对中枢神经系统非典型畸胎样/横纹肌样瘤(atypical teratoid/rhabdoid tumor,AT/RT)及颅内具有"横纹肌样细胞"形态的肿瘤鉴别诊断,评价INI1抗体的应用价值。方法观察13例有"横纹肌样细胞"特征的肿瘤的临床病理特征、免疫组化标记,并进行INI1的检测。结果不同肿瘤中的"横纹肌样细胞"形态有差异且免疫组织化学标记不同。AT/RT除具有典型的横纹肌样细胞成分外还存在原始间叶成分,免疫组织化学显示两种成分vimentin、CD99均阳性,横纹肌样细胞成分SMA阳性、EMA局灶阳性。本组其他肿瘤缺乏上述特征。INI1抗体在AT/RT肿瘤细胞核中呈阴性,而在横纹肌样脑膜瘤、胶质瘤及转移癌中显示核阳性。结论横纹肌样细胞是AT/RT重要的形态特征,但"横纹肌样细胞"形态也出现在颅内其他组织类型的肿瘤中。年龄、形态学、免疫组化标记对鉴别诊断有一定参考价值。重要的诊断依据是INI-1抗体在AT/RT中细胞核为阴性,其他肿瘤阳性。该抗体对AT/RT及其他有横纹肌样细胞形态的肿瘤,包括横纹肌样脑膜瘤的鉴别诊断有重要价值。     

肾外恶性横纹肌样瘤临床病理分析

目的：探讨恶性横纹肌样瘤的临床病理表现。方法：用光镜、免疫组化及特染等方法观察其病理组织学特点。结果：该例具有典型巢团状浸润生长的多边形横纹肌样瘤细胞,胞浆丰富嗜酸性,胞浆内可见或多或少胞浆空泡及包涵体,泡状核、核仁明显。瘤细胞排列有假腺泡状,放射状,副节瘤样及淋巴瘤样等多形性改变。结论：该肿瘤瘤细胞呈免疫多表型,其神经性、上皮性、肌性混合多项阳性。     

颅内非典型畸胎瘤样／横纹肌样瘤的影像学表现（附4例报道和文献复习）

目的：探讨颅内非典型畸胎瘤样/横纹肌样瘤（ AT/RT）的影像学特征,提高对其认识水平。方法：收集我科1997年1月～2011年12月经病理和免疫组化诊断为AT/RT的4例患者的临床资料,对其影像学表现进行回顾性分析,并进行相关文献复习。结果：4例中,病灶位于额叶2例,颞叶1例,桥脑小脑角区（CPA）1例;最大径3．6～6．5 cm。肿瘤边界清楚,3例轻度瘤周水肿,1例无瘤周水肿;4例轻度占位效应,位于CPA的1例可见同侧内听道扩大。肿瘤实质在CT上呈等密度,MRI T1WI呈低信号、T2 WI呈高低混杂信号。4例肿瘤内均见出血,2例见囊变。增强后肿瘤实质呈斑片状强化,囊壁和分隔亦见强化。结论：AT/RT的影像学表现有一定的特征性,但缺乏特异性;提高对本病的认识是诊断的关键。     

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...     

儿童恶性横纹肌样瘤9例临床病理分析

目的探讨儿童恶性横纹肌样瘤(malignant rhabdoid tumor, MRT)的临床病理学特征。方法回顾性分析9例儿童MRT的临床病理学特征、免疫表型、诊断及鉴别诊断、治疗及预后,并复习相关文献。结果 9例MRT中男性7例,女性2例,患儿年龄1个月～9岁。镜检:肿瘤细胞排列成不相黏附的巢状或实性片状。瘤细胞体积大,呈圆形或卵圆形,胞质丰富,嗜伊红色,内含PAS阳性的球形毛玻璃样包涵体,类似横纹肌细胞。核偏位,染色质呈空泡状,可见明显核仁,核分裂象常见。免疫表型:瘤细胞CK(AE1/AE3)、EMA、vimentin和Syn均阳性,MyoD1、desmin和INI-1均阴性。Ki-67增殖指数30%～70%,平均56.3%。结论 MRT是一种罕见的好发于婴幼儿的高度恶性肉瘤,具有相对独特的病理学形态特点,并伴有INI-1基因表达缺失。病理诊断需与近端型上皮样肉瘤、滑膜肉瘤、肾髓质癌等相鉴别。MRT对放、化疗反应不敏感,尤其是发生于肾内者,预后极差,病死率高。     

上皮样血管内皮瘤的临床病理分析

目的：探讨上皮样（组织细胞样）血管内皮瘤的临床病理学特点及其意义。方法：对9例上皮样血管内皮瘤进行光镜和免疫组织化学SP法检测,1例作电镜观察,结果：年龄16－47岁,平均32岁,男女性别差异无显著性意义。部位：头面部4例,上肢3例,下肢2例,形态特征：瘤细胞具有上皮样或组织细胞样的形态;瘤细胞圆形或多角开,三五成群呈小巢状,索状,不规则状排列,分布于粘液间质中;间质可显著或少量粘液样变或玻璃样变,瘤细胞内含有原始血管腔,核分裂角,多形性及坏死少见,部分病例伴有梭形细胞血管内皮瘤改变,1例见破骨细胞样的多核巨细胞,免疫组织化学检测7例,7例波形蛋白均阳性,5例第八因子相关抗原,CD31,CD34阳性,2例细胞角蛋白弱阳性,1例CD68和a1-抗胰蛋白酶阳性,电镜观察1例见胞质内含丰富的微丝和少许的W－P小体,6例随访－8年,3例在原发部位有1或2次复发,但未见有转移,结论：上皮样血管内皮瘤是一种低度恶性的软组织肉瘤,其病因学尚不清楚,熟悉其形态特征对避免误诊为其他类似病变具具有重要意义。     

恶性横纹肌样瘤

恶性横纹肌样瘤朱梅刚恶性横纹肌样瘤（ｍａｌｉｇｎａｎｔｒｈａｂｄｏｉｄｔｕｍｏｒ，ＭＲＴ）是好发于婴幼儿、少见的恶性肿瘤。本瘤首先由Ｂｅｃｋｗｉｔｈ［１］描述，从原诊断ｗｉｌｍｓ′瘤中分出。当时称之为“预后不良的横纹肌肉瘤样ｗｉｌｍｓ′瘤”。１９８１...     

子宫Müllerian腺肉瘤伴间质横纹肌样瘤分化1例并文献复习

目的探讨子宫Muellerian腺肉瘤伴间质横纹肌样瘤分化的临床病理特征。方法用光镜、组织化学及免疫组化方法观察其病理组织学表现。结果肿瘤由良性上皮成分和肉瘤性间质成分组成，肉瘤成分过度生长。肿瘤细胞弥漫浸润性分布，细胞大，胞质丰富嗜酸性并可见嗜伊红包涵体。免疫表型：vimentin、CK、NF、CD57、CD99、CgA、Syn阳性，SMA散在阳性，而desmin、EMA、CD10、GFAP、MyoD1、Inhibin—α、HMB45和S-100蛋白阴性。组织化学染色PAS阴性，网状纤维染色显示网状纤维包绕单个或小巢肉瘤性间质细胞。结论子宫腺肉瘤伴间质横纹肌样瘤分化是一种罕见的混合性Muellerian肿瘤，应与子宫内膜间质肉瘤、子宫横纹肌肉瘤和低分化癌等鉴别。     

Adult variant of atypical teratoid/rhabdoid tumor: Immunohistochemical and ultrastructural confirmation of a rare tumor in the sella tursica

Atypical teratoid/rhabdoid tumor (AT/RT) is a distinctive neoplasm of young children characterized by diverse histology and fatal course. Adult presentation is rare. We describe the diagnostic problems associated with an AT/RT arising in the sellar region in a 46-year-old female.     

Cytomorphological features of atypical teratoid/rhabdoid tumor: An account of 12 years' experience

Atypical teratoid rhabdoid tumor (AT/RT), an aggressive neoplasm mostly affecting young children, is characterized by rhabdoid cells together with epithelial, mesenchymal and primitive differentiation. Diagnosing AT/RT in intraoperative consultation and cerebrospinal fluid (CSF) samples may therefore pose problems. Fourteen immunohistochemically proven AT/RTs diagnosed between 2000 and 2012 were collected. Material consisted of squash smears prepared during intraoperative consultation (thirteen) and CSF smears (three). MGG‐stained CSF smears and H&E stained squash smears were reviewed by a neuropathologist and a cytopathologist. The intraoperative diagnoses were based on squash preparations and 3 out of 13 were consistent with AT/RT, 4 were considered medulloblastoma/primitive neuroectodermal tumors (PNET), 3 were deferred to paraffin section for tumor typing, and another 3 were misdiagnosed as ependymoma, germinoma and malignant glioma. Morphological assessment of intraoperative squash preparations showed that AT/RTs can have a mixture of pseudopapillary and diffuse smearing patterns. Cytomorphologic features consisted of characteristic rhabdoid cells (8/9); primitive appearing cells with a high nuclear to cytoplasmic ratio (7/9); bi‐/multinucleated cells (3/9); rare necrosis/apoptosis and mitoses. Three CSF smears showed high cellularity and inclusion‐bearing large cells. These cells are characterized by reniform/oval, eccentrically placed nuclei with cytoplasmic perinuclear light stained areas which are not seen in intraoperative squash preparations. Differential diagnosis of AT/RT in cytology involves medulloblastoma/PNET, ependymoma, glioma and germinoma among all others. Overlapping features of AT/RT with entities in differential diagnosis are discussed with a special emphasis of rhabdoid cells being the strongest feature to aid in reaching the diagnosis of AT/RT. Diagn. Cytopathol. 2014;42:856–862. © 2014 Wiley Periodicals, Inc.     

Primary atypical teratoid/rhabdoid tumor of central nervous system in children: a clinicopathological analysis and review of literature in China

Atypical teratoid/rhabdoid tumor (AT/RT) is a very rare and highly malignant embryonal tumor in the central nervous system (CNS). Five patients (4 girls and 1 boy) with AT/RT were treated in our hospital. The clinical histories, symptoms, neuroimaging aspects, therapies, histological and immunohistochemical findings and follow-up information were reviewed. The patients ranged from 8 to 40 months with a mean age of 20.6 months. One tumor was located in the spinal cord, two in cerebellum and two in the pineal region. The imagings of the tumors resemble medulloblastomas. Pathological examinations showed that one patient had medulloblastoma differentiation, one had choroid plexus carcinoma differentiation, and one had mesenchymal components. Immunohistochemical staining showed that all of the tumors lost the nuclear expression of integrase interactor 1 (INI1), and were positive for Vimentin, S-100 protein and epithelial membrane antigen. One case with no recurrence after 24 months may have benefited from radical excision and postoperative radiotherapy. The other 4 patients died 8, 4, 1 and 1-month respectively after operation without radiotherapy. The diagnosis of AT/RT depends on full sampling, careful observation the morphological characteristics and INI1 examination, even when the tumor are presented in uncommon sites, such as the spinal cord and the pineal region.     

A case of an atypical teratoid/rhabdoid tumor with distinctive histology in the pineal region in an adult patient

A 31-year-old man suffered from headaches and presented at a hospital after the symptom worsened. Obstructive hydrocephalus and a pineal tumor were identified, and he was transferred to our hospital for further investigation and treatment. Cranial computed tomography revealed a hypodense mass lesion on the right of the pineal region, and calcifications and enlargement of the lateral and third cerebral ventricles were also evident. Blood tests were negative for all tumor markers. Laparoscopic biopsy and third-ventricle fenestration were performed that day as an emergency surgery to treat the obstructive hydrocephalus. Postoperative cranial magnetic resonance imaging revealed a solid tumor that was hypointense on T1-weighted imaging, hyperintense on T2-weighted imaging, and heterogeneously enhanced by Gd. Subsequently, the tumor increased in size, and craniotomy and tumorectomy were performed. Histologically, the tumor proliferated as round or short spindle-shaped cells in a myxoid matrix, forming arrays that surrounded the blood vessels. As a few cells with eosinophilic cytoplasm were also present and immunostaining for INI-1 was negative, the patient was diagnosed with atypical teratoid/rhabdoid tumor (AT/RT). AT/RT of the pineal region in adults is rare, and herein, we report the morphological characteristics of this case and reviewed the relevant literature.     

Claudin-6 is of limited sensitivity and specificity for the diagnosis of atypical teratoid/rhabdoid tumors

Recent gene expression microarray analyses have indicated that claudin-6 is specifically expressed in atypical teratoid rhabdoid tumors (AT/RTs), suggesting a role as a positive diagnostic marker in addition to SMARCB1 (INI1) loss, which is encountered in the majority of AT/RTs. In order to investigate the potential of claudin-6 as a diagnostic marker, expression was investigated in 59 AT/RTs and 60 other primary central nervous system (CNS) tumors, including primitive neuroectodermal tumors, medulloblastomas, choroid plexus tumors, and both pediatric and adult low- and high-grade gliomas using immunohistochemistry. Claudin-6 was expressed in 17/59 AT/RTs (29%), but also in a variety of other primary CNS tumors, including 60% of medulloblastomas and 21% of malignant gliomas. Even though high staining scores (2+ or 3+) were more often encountered in AT/RTs (Chi-square 4.177; P=0.041), the overall frequency of claudin-6 staining was not significantly higher in AT/RTs as compared with the other tumors (17/59 vs. 16/60; Chi-square=0.328; P=0.567). In a subgroup of 43 AT/RT patients, of which follow-up data were available, claudin-6 expression did not show any correlation with survival. In conclusion, claudin-6 immunohistochemistry is of limited sensitivity and specificity for the diagnosis of AT/RT and does not correlate with clinical behavior.     

中枢神经系统非典型畸胎样/横纹肌样瘤临床病理及免疫表型特征

目的 探讨中枢神经系统非典型畸胎样／横纹肌样瘤的临床病理特征、诊断及鉴别诊断。方法 对2例非典型畸胎样／横纹肌样瘤应用光镜行HE、网状纤维染色及免疫组织化学染色观察,并结合文献复习。结果 非典型畸胎样／横纹肌样瘤具有特征性的横纹肌样细胞,伴有不同程度的原始神经外胚叶、上皮和间质分化。肿瘤组织富于网状纤维,免疫组织化学标记示波形蛋白、CD99、上皮细胞膜抗原、细胞角蛋白、胶质纤维酸性蛋白、S-100蛋白、神经微丝蛋白、结蛋白、平滑肌肌动蛋白阳性,突触素、肌调节蛋白、胎盘碱性磷酸酶和HMB45阴性。结论 非典型畸胎样／横纹肌样瘤是中枢神经系统一种罕见的高度恶性肿瘤,好发于儿童,偶见于成人,呈异源性组织学和免疫组织化学表型。其诊断需与脑内其他多形性肿瘤鉴别。     

Epidermal growth factor receptor abnormalities in atypical teratoid/rhabdoid tumors and an unusual case with gene amplification

Atypical teratoid/rhabdoid tumor (AT/RT) is a rhabdoid tumor of the central nervous system comprising a mixture of small round cells and mesenchymal and/or epithelial elements, showing mutation of the SMARCB1 gene or SMARCA4 gene. The epidermal growth factor receptor (EGFR) is one of the tyrosine kinase receptors whose overexpressed protein plays important roles in the malignant characteristics of various tumors. We analyzed 8 Japanese cases of AT/RT for EGFR protein overexpression and egfr gene amplification using immunohistochemistry and fluorescence in situ hybridization. The patients included 7 boys and 1 girl (age range 13 days to 2 years), and the tumors were localized in the frontal lobe (1 case), lateral ventricle (1 case), third ventricle (1 case), fourth ventricle (3 cases), and cerebellum (2 cases). We found that all (100%) of them partially expressed a high level of EGFR protein, and that one case showed amplification of egfr, the amplified area being localized and limited to a specific area within the tumor. We speculate that AT/RT is a tumor with heterogeneous egfr amplification, and that the frequency of amplification may depend on loss of function of the specific chromatin-remodeling member.