Primary intracranial atypical teratoid/rhabdoid tumor in a child: a case report

Rhabdoid tumors of the central nervous system are rare malignancies. Primary central nervous system atypical teratoid/rhabdoid tumors (ATT/RhTs) mostly occur during early childhood and are almost invariably fatal. These tumors show similar histological and radiological features to primitive neuroectodermal tumormedulloblastoma (PNET-MB) but have different biological behaviors. We report a case of primary intracranial ATT/RhT in the posterior cranial fossa of a child. Preoperative radiological diagnosis was PNET-MB, but pathological diagnosis is ATT/ RhT. The case involved a 16-month-old baby boy who presented with severe headache, vomiting, and gait disturbance. He was treated by surgical resection, chemotherapy, and radiotherapy. Despite aggressive therapy, he died 19 months after diagnosis. Clinical, radiological, and histopathological features of primary intracranial ATT/RhT are discussed with a special emphasis on the differential diagnosis from PNET-MB.     

松果体区不典型畸胎样/横纹肌样肿瘤一例

患儿男,29个月。因精神萎靡半月余,呕吐2 d来吉林大学第一医院就诊。磁共振成像显示松果体区异常信号影,脑积水。患者入院第4天行神经电生理监测显微镜下肿瘤切除术,出院随访4个月,患者死亡。病理检查：镜下见肿瘤细胞弥漫性生长,部分区域可见坏死,细胞核空泡状、核仁明显,个别胞质内可见嗜酸性小体,免疫组织化学肿瘤细胞细胞角蛋...     

Atypical teratoid/rhabdoid tumor: cytology and differential diagnosis in adults

Atypical teratoid/rhabdoid tumors (AT/RTs) are malignant intracranial neoplasms that usually occur in the posterior fossa of children. They are characterized by cells with paranuclear rhabdoid inclusions, a mesenchymal and epithelial immunohistochemical profile, and 22q deletions with inactivation of the INI1/hSNF5 gene. Although they usually occur in young children, AT/RTs are being recognized in adults with increasing frequency. We report the cytologic features of an AT/RT from the cerebellum of a 45-year-old man and discuss the differential diagnosis in adults.     

中枢神经系统非典型畸胎瘤样/横纹肌样瘤临床病理特点

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)的临床病理特征、组织发生及预后。方法应用光镜、特殊染色及免疫组化染色观察1例2岁儿童大脑AT／RT的病理组织学特点，结合国内外文献进行讨论。结果肿瘤含有横纹肌样细胞、原始神经外胚层、上皮及间叶多向分化成分。肿瘤中网状纤维丰．富。免疫组化染色Vim、EMA、CKpan、GFAP、Syn及CgA均呈阳性表达，PLAP、CD117、SMA及：NF?呈阴性反应。结论AT／RT为发生在儿童中枢神经系统罕见的高度恶性肿瘤，多数患者1年内死亡。肿瘤极易误诊为髓母细胞瘤、原始神经外胚叶肿瘤(PNET)、脉络丛乳头状癌及生殖细胞肿瘤。免疫组化染色对确诊AT／RT十分重要。本瘤的组织发生仍不清楚。     

Clinical and molecular features in patients with atypical teratoid rhabdoid tumor or malignant rhabdoid tumor

The SMARCB1 gene status in 50 patients with atypical teratoid rhabdoid tumor and/or malignant rhabdoid tumor recruited to a German registry was prospectively analyzed with FISH and PCR. Altogether we found 40 SMARCB1 mutations in 28 patients. Two patients were positive for SMARCB1 staining at immunochemistry. Germline mutations were identified in 10 of 41 patients with CNS disease, including three large heterozygous deletions, six truncating mutations and one donor splice site mutation. No missense mutation was identified. Analysis of first degree relatives did not detect any carriers. Mutations were distributed over the SMARCB1‐gene without particular clustering. No germline mutation was found in nine patients without CNS disease. Patients with germline mutation had a lower median age at diagnosis in comparison to those without detectable germline mutation (5.5 vs. 13 months, P = 0.001), a higher rate of primary multicentric CNS disease (5/10 vs. 5/36) and synchronous or metachronous mixed CNS and extracranial disease (4/10 vs. 1/36). Two year overall survival was 0% in patients with germline mutation and 48% in those without detectable germline mutation (P < 0.001). Patients with germline mutation of SMARCB1 manifest at an early age and have a very high risk for progression which has to be considered with respect to the outcome of further treatment studies. © 2009 Wiley‐Liss, Inc.     

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.     

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。     

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.     

Atypical teratoid and rhabdoid tumor. Report of a congenital case

The atypical teratoid rhabdoid tumor is a rare brain tumor of childhood. We report a congenital case, revealed by peripheral facial palsy. This polymorphous tumor consisted of rhabdoid cells associated with areas of primitive neuroectodermal tumor. The immunoreactivity for the three proteins vimentin, epithelial membrane antigen and smooth-muscle actin was suggestive of rhabdoid tumor. Genetic study showed a homozygous mutation in the tumoral DNA and a constitutional heterozygous mutation, as it was demonstrated in atypical teratoid rhabdoid tumors and in renal and extra-renal rhabdoid tumors.     

Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system.

The atypical teratoid/rhabdoid tumor, primary to the central nervous system, is a highly malignant and aggressive neoplasm of infancy and childhood. Although having distinct biological features and clinical outcomes, it is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma. To further distinguish the underlying pathogenesis and to identify biological markers for clinical use, an atypical teratoid/rhabdoid tumor-derived cell line was established and its gene expression pattern analyzed in comparison to the human astrocyte SVG12 cell line and the human DAOY medulloblastoma cell line using a complementary DNA microarray method. The osteopontin gene was found specifically upregulated in atypical teratoid/rhabdoid tumor cells. This specificity was confirmed by immunohistochemistry in pathological sections of tissues from atypical teratoid/rhabdoid tumor patients. Even though the role of osteopontin in the cytopathogenesis of atypical teratoid/rhabdoid tumor still needs to be determined, our data support that overexpressed osteopontin is a potential diagnostic marker for atypical teratoid/rhabdoid tumor.     

Atypical teratoid/rhabdoid tumor in a patient with Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome (BWS) is a genetic disorder associated with an increased risk of childhood tumors. Here we describe a patient with BWS who developed a central nervous system atypical teratoid/rhabdoid tumor (AT/RT). To our knowledge, despite the known cancer predisposition, this patient is the first described with BWS to develop an AT/RT. Due to the high propensity of these patients to develop childhood tumors, in addition to routine diagnostic tests, analysis of the tumor DNA using the Illumina Infinium whole-genome genotyping 550K Beadchip was performed to investigate a possible common underlying mechanism for his BWS and AT/RT. The only alteration detected was monosomy 22, which was accompanied by a somatic mutation in the INI1 rhabdoid tumor gene. These results suggest that, despite an underlying cancer predisposition, the occurrence of BWS and AT/RT in this patient may be unrelated.     

Chromosome 22q deletions in atypical teratoid/rhabdoid tumors in adults

Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, malignant brain tumors that usually occur in the posterior fossa. Both AT/RT and the analogous tumor outside the brain, malignant rhabdoid tumor, share a polyphenotypic immunoprofile and frequent 22q deletions with inactivation of the IN11/hSNF5 gene. Reports, so far, indicate that AT/RTs occur almost exclusively in children, most of whom are 5-years-old or less. The rarity of the tumor and the polyphenotypic immunoprofile, characterized by antigen expression that is often patchy, make diagnosis in adults difficult and controversial. We describe three AT/RTs in adults in which the diagnoses were supported by detection of 22q11.2 deletions, INI1 mutation and/or loss of INI1 protein expression. Two patients were female, ages 20 and 31 and one was male, age 45.Two tumors occurred in the sella or sellar region and one in the cerebellum. In all cases, fluorescence in situ hybridization with probes to the BCR (22q11.2) and NF2 (22q12) regions of chromosome 22 revealed single copy deletions of BCR with normal dosages of NF2 and, in all cases, immunohistochemistry demonstrated loss of INI1 protein expression. In one case, a single base pair deletion was detected in the INI1/hSNF5 gene. These molecular findings confirm the occurrence of AT/RTs in adults. Although rare, AT/RT should be considered in the differential diagnosis of poorly differentiated intracranial tumors in adults.     

Atypical teratoid/rhabdoid tumor: analysis of cytomorphologic features in CSF, focused on the differential diagnosis from mimickers

Atypical teratoid and rhabdoid tumor (AT/RT) is a rare tumor with fatal clinical consequences, usually affecting young children. A significant portion of patients present with dissemination to cerebrobspinal fluid (CSF). However, a limited number of studies are available regarding the cytomorphologic findings of AT/RT in CSF. We collected eight cases of CSF cytology of AT/RT and describe the cytomorphologic features of AT/RT in CSF. Typical rhabdoid cells are found in most cases and they are characterized by eccentric nuclei, abundant cytoplasm, and clustering of the tumor cells. The presence of these cells in CSF indicates disseminated diseases and aggressive therapeutic consideration for patient management is required.     

Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor

We describe a four-month-old child who presented with an atypical teratoid/rhabdoid tumor of the brain and subsequently developed a renal rhabdoid tumor. Distinct histologic features, immunophenotypic profiles, and deletions of chromosome 22 were supportive of two primary tumors. An identical mutation in exon 7 of the INI1 rhabdoid tumor suppressor gene was identified in both tumors, as well as in normal kidney tissue. We propose that this germline INI1 mutation predisposed the child to the development of both malignancies. These findings lend support to the hypothesis that rhabdoid tumors in all sites have a common genetic etiology.     

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.     

Paratesticular congenital malignant rhabdoid tumor diagnosed by fine-needle aspiration cytology. a case report

We report the FNA features of a congenital malignant extrarenal rhabdoid tumor (MERT) located in the right paratesticular area of a newborn full-term boy (39 wk gestation), with disseminated metastases in the liver and right parietal region. The diagnosis was suggested two days after birth by fine-needle aspiration biopsy (FNAB) of the parietal mass, which demonstrated an atypical large cell proliferation with vesicular nuclei, prominent nucleoli, and abundant cytoplasm exhibiting paranuclear dense inclusions. The diagnosis was confirmed by histopathologic and immunohistochemical examination of the primary paratesticular tumor. To the best of our knowledge, this is the third MERT reported in the paratesticular region, one of the few congenital extrarenal non-central nervous system cases, and the third congenital case (renal or extrarenal) primarily diagnosed by FNAB. We emphasize the characteristic cytologic features of a congenital rhabdoid tumor, which must be known by pathologists because of the clinical and prognostic implications. Diagn. Cytopathol. 2004;30:46-50.     

Double immunolabeling of central nervous system atypical teratoid/rhabdoid tumors.

The central nervous system atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant tumor with a heterogeneous immunohistochemical profile and with some morphologic similarity to central nervous system primitive neuroectodermal tumors (PNET). Although several studies have investigated double immunolabeling in PNET, we are aware of no studies of double labeling of ATRT. A total of 10 ATRT from surgical and consultation materials at the Children's Hospital of Philadelphia were selected and stained for a variety of antigens using indirect immunofluorescence to detect single and double labeling. Most tumor cells showed only single labeling; rare cells showed double labeling as follows: 70% of tumors coexpressed (VIM) and glial fibrillary acidic protein (GFAP), 30% smooth muscle actin and GFAP, 20% epithelial membrane antigen (EMA) and VIM, 20% EMA/GFAP, and 20% EMA/SMA. These results are discussed in view of current debates over the histogenesis of CNS PNET and ATRT, and in reference to the classification of rhabdoid tumors as an entity or phenotype.