Malignant Rhabdoid Tumour
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Malignant Rhabdoid Tumour (MRT) is an aggressive sarcomatous neoplasm usually arising in the kidney, with a histology distinct from Wilms' tumour. Occasionally MRT may arise in other parts of the body, including the brain. In a review of 111 cases of MRT of kidney by the National Wilms' Tumor Study (Weeks, 1989) the median age at diagnosis was 11 months (range 0 - 106 months) and the male:female ratio was 1.5:1. Treatment for MRT of kidney is often similar to that for Wilms' tumour (MRT starting in the brain or other non-renal sites have different treatments). A common cytogenetic feature of MRT is deletion of material from chromosome 22q11.2 including the SMARCB1 (SNF5/INI1) gene.

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Wilms' Tumour

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See also: SMARCB1 gene (SNF5 / INI1)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Moreno N, Kerl K
Preclinical Evaluation of Combined Targeted Approaches in Malignant Rhabdoid Tumors.
Anticancer Res. 2016; 36(8):3883-7 [PubMed] Related Publications
BACKGROUND/AIM: Rhabdoid tumors (RT) are aggressive pediatric tumors, which show poor prognosis despite use of multimodal intensive therapy. In these tumors, several different oncogenic pathways and epigenetic regulators (like CDK4/6-cyclinD-Rb-signaling, EZH2, histone deacetylases) are contemporaneously deregulated as a consequence of biallelic SMARCB1/SNF5/INI1 alterations. Since these tumors are highly resistant to current therapies, alternative treatment strategies are urgently required.
MATERIALS AND METHODS: In this study, we evaluated cytotoxic effects (by MTT tests) of small molecular compounds, which specifically target these deregulated pathways, using either single-drug or combined approaches. Half-maximal inhibitory concentration (IC50) and combined index (CI) were calculated.
RESULTS: All target-directed inhibitors blocked cell growth of three different rhabdoid tumor cell lines in vitro. Several combinations of those target-specific drugs synergistically inhibited cell proliferation of rhabdoid tumors.
CONCLUSION: Supporting earlier reports, combined target-directed approaches are a promising tool for the therapy of malignant rhabdoid tumors.

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Agaimy A, Bertz S, Cheng L, et al.
Loss of expression of the SWI/SNF complex is a frequent event in undifferentiated/dedifferentiated urothelial carcinoma of the urinary tract.
Virchows Arch. 2016; 469(3):321-30 [PubMed] Related Publications
Loss of the SWI/SNF chromatin remodeling complex has been recently implicated in the pathogenesis of dedifferentiated carcinomas from different organs, but its possible role in undifferentiated urothelial carcinoma (UC) has not been studied to date. In this study, we analyzed by immunohistochemistry 14 undifferentiated UCs (11 from bladder and 3 from renal pelvis) with a nondescript anaplastic or rhabdoid morphology, using commercially available antibodies against the SWI/SNF components SMARCB1 (INI1), SMARCA2, SMARCA4, SMARCC1, SMARCC2, and ARID1A. Patients were eight females and six males aged 40 to 84 years (median, 65). All tumors were muscle-invasive (9 were T3-4). A conventional UC component was seen in eight cases and varied from in situ to papillary. The undifferentiated component comprised 60-100 % of the tumors. Histologically, most tumors showed diffuse dyscohesive or pseudoalveolar growth of variably sized cells with frequent rhabdoid features. Transition from conventional to undifferentiated UC was abrupt, except in one case. The undifferentiated component almost always expressed pan-cytokeratin AE1/AE3 (13/14) and variably vimentin (8/14) and GATA3 (9/14). Complete loss of at least one SWI/SNF subunit limited to the undifferentiated component was detected in 10/14 cases (71 %). SMARCA2 was most frequently lost (six) followed by ARID1A (four), SMARCB1/INI1 (two), SMARCA4 (one), and SMARCC1 (one). This is the first study exploring SWI/SNF expression in undifferentiated UC of the urinary tract. Our results are in line with recent studies reporting involvement of the SWI/SNF complex in the dedifferentiation process of a variety of epithelial neoplasms in different organs, including the urinary tract, and association with aggressive clinical course.

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Yu F, Chiang F, Bazan C
Atypical teratoid/rhabdoid tumor arising from the trigeminal nerve in an adult.
Neuroradiol J. 2016; 29(6):447-449 [PubMed] Article available free on PMC after 01/12/2017 Related Publications
A 30-year-old male presented with left facial pain and numbness. Initial MRI demonstrated an enhancing mass involving the left trigeminal nerve. Follow-up imaging showed interval growth with erosion of the sphenoid body. Surgical resection was performed and immunohistochemistry staining was consistent with an atypical teratoid/rhabdoid tumor. Awareness of this entity and its imaging features such as diffusion restriction, intratumoral hemorrhage, and bony destruction, can help guide confirmatory diagnostic testing and appropriate therapy.

Wang J, Liu Z, Fang J, et al.
Atypical teratoid/rhabdoid tumors with multilayered rosettes in the pineal region.
Brain Tumor Pathol. 2016; 33(4):261-266 [PubMed] Related Publications
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly malignant tumor of the central nervous system (CNS) that typically occurs during infancy. These tumors exhibit morphologic heterogeneity and differentiate along multiple lineages, thus posing a diagnostic challenge. Here, we present two cases of AT/RT with a primitive neuroectodermal component and histological pattern resembling an embryonal tumor with multilayered rosettes (ETMR), a rare but distinctive embryonal entity with different therapeutic implications. Patient 1, a 23-month-old girl, presented with a history of gait unsteadiness and headache; cranial computed tomography (CT) identified a mass in the pineal and third ventricular regions. Patient 2, a 26-month-old girl, presented with headache and vomiting; CT revealed a mass in the posterior third ventricle. Both patients were treated via gross total tumor resection. Although histologically, AT/RT cases variably comprise primitive neuroectodermal, mesenchymal, and classic rhabdoid cells, the most striking feature of both cases was the presence of multilayered rosettes with a few Homer Wright rosettes and occasional primitive neuroepithelial tubes in focal primitive component areas. Immunohistochemistry revealed considerable heterogeneity within the tumors. We further present our findings in the context of the relevant literature.

Horiguchi H, Nakata S, Nobusawa S, et al.
Adult-onset atypical teratoid/rhabdoid tumor featuring long spindle cells with nuclear palisading and perivascular pseudorosettes.
Neuropathology. 2017; 37(1):52-57 [PubMed] Related Publications
Atypical teratoid/rhabdoid tumors (AT/RTs) are rare malignant neoplasms of the CNS that preferentially affect young children. We herein report an adult case of AT/RT surviving for more than 5 years with the residual tumor. The patient, a 24-year-old man at onset, presented with a contrast-enhancing mass lesion in the left occipital lobe, and underwent partial tumor resection. Histologically, the tumor was predominantly composed of long spindle cells exhibiting nuclear palisading and perivascular pseudorosettes, which appeared to mimic mesenchymal, ependymal and Schwann cell tumors. A small number of isolated rhabdoid cells did not initially attract attention, and a tentative pathological diagnosis of a malignant mesenchymal tumor was made. In a later examination focusing on the small areas of rhabdoid cells, the extensive loss of the nuclear expression of INI1 was detected in all areas. Diffuse staining with vimentin and focal immunoreactivity for epithelial membrane antigen and alpha smooth muscle actin were observed not only in AT/RT foci, but also in spindle cell areas. Thus, polyphenotypic immunoreactivity was evident. Fluorescence in situ hybridization revealed a homozygous deletion of chromosome 22q covering the INI1 locus. Histopathological differences between infant and adult AT/RTs currently remain unclear. In the case of a malignant adult brain tumor showing a hardly classifiable morphology and immunophenotypic diversity, an analysis of the INI1 status may contribute to an accurate diagnosis.

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Matsuo M, Tuneyoshi M, Mine M
Primary mucinous carcinoma with rhabdoid cells of the thyroid gland: a case report.
Diagn Pathol. 2016; 11(1):48 [PubMed] Article available free on PMC after 01/12/2017 Related Publications
BACKGROUND: Primary mucinous carcinoma of the thyroid gland is a rare disease; only 6 cases of primary mucinous carcinoma of the thyroid have been previously reported. Primary mucinous carcinoma of the thyroid gland with incomplete tumor resection tends to be associated with a poor prognosis, resulting in death within a few months. An early and appropriate diagnosis may contribute to improvement in patient prognosis; however, it is extremely difficult to diagnose primary mucinous carcinoma of the thyroid. We present the seventh reported case of primary mucinous carcinoma in the thyroid gland; moreover, rhabdoid cells were detected, which, to our knowledge, is a novel finding.
CASE PRESENTATION: An 81-year-old Japanese woman was initially diagnosed with a poorly differentiated thyroid carcinoma, and she underwent a hemithyroidectomy. Pathological examination revealed the presence of abundant mucus and agglomeration of large atypical cells. Rhabdoid cells were also seen scattered among the tumor cells. Immunostaining was performed for various markers, and on the basis of these results, we diagnosed the lesion as primary mucinous carcinoma with rhabdoid cells in the thyroid gland. Ten months after surgery, recurrence was noted in the paratracheal lymph nodes; therefore, total resection of the residual thyroid gland and paratracheal lymphadenectomy with thyroid-stimulating hormone suppression were performed. The patient is currently alive and disease-free.
CONCLUSIONS: The current case is of interest not only because of the rare histological findings, but also because the patient achieved long-term survival following diagnosis of a mucinous carcinoma. We believe this report will be helpful for diagnosing future cases of mucinous carcinoma of the thyroid.

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Sugimoto M, Kohashi K, Itsumi M, et al.
Epithelial to Mesenchymal Transition in Clear Cell Renal Cell Carcinoma with Rhabdoid Features.
Pathobiology. 2016; 83(6):277-86 [PubMed] Related Publications
AIMS: The aims of this study were to investigate the association of renal cell carcinoma (RCC) displaying rhabdoid features and morphologically mesenchymal characteristics with epithelial to mesenchymal transition (EMT), and to clarify the expression of EMT markers.
METHODS: We investigated the expression of EMT markers (E-cadherin, vimentin, Snail, Slug, ZEB1, ZEB2 and Twist1) using immunohistochemistry, Western blotting and real-time polymerase chain reaction in 18 cases of clear cell RCC (ccRCC) with rhabdoid features and 74 ccRCC cases with Fuhrman grade 1-3 (G1 to G3).
RESULTS: In ccRCCs with rhabdoid features, low E-cadherin and high vimentin expression were found. In G1 to G3 ccRCCs, low E-cadherin expression and high expression of vimentin, ZEB1 and ZEB2 were found. There was no significant difference in the immunoexpression of E-cadherin and vimentin between the two ccRCC groups.
CONCLUSIONS: The rhabdoid features may histologically and biologically be associated with EMT in ccRCC. There is a possibility that in G1 to G3 ccRCCs showing epithelial structures, other cell-cell adhesion mechanisms apart from E-cadherin adhesion may continue to work, and that ccRCC with rhabdoid features may be caused by an inactivation or loss of these mechanisms.

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Yuce I, Eren S, Levent A, et al.
Leptomeningeal Dissemination of Intraventricular Rhabdoid Meningioma: Imaging Findings.
Turk Neurosurg. 2016; 26(3):456-9 [PubMed] Related Publications
A 20-year-old male patient was admitted to our clinic with a 1-year history of headache. The patient's systemic-neurological examination and laboratory findings were normal. Computed tomography and magnetic resonance imaging were performed. Imaging findings showed calcified intraventricular mass and subependymal and gyral nodular lesions. There was a slight increase in ventricular volume. Surgical treatment was performed. Pathological specimens revealed the diagnosis of rhabdoid meningioma. Leptomeningeal dissemination refers to diffuse seeding of the leptomeninges by tumor metastases. To our knowledge, leptomeningeal dissemination of intraventricular rhabdoid meningioma is very rare in the literature. We aimed to discuss imaging findings and differential diagnosis of leptomeningeal dissemination of rhabdoid meningioma.

Lu YT, Huang HI, Yang AH, Tai SK
Thyroid carcinoma with rhabdoid phenotype: Case report with review of the literature.
Auris Nasus Larynx. 2016; 43(6):706-9 [PubMed] Related Publications
OBJECTIVE: This paper aims to comprehensively document a rare case of thyroid carcinoma with rhabdoid phenotype and literature review of this disease.
METHODS: A 59-year-old man presented with a rapidly enlarging, painful left lateral cervical mass. CT scan revealed a tumor over the left the thyroid gland with multiple left cervical lymphadenopathy over left level II-IV and level VI. Fine-needle aspiration cytology reported carcinoma, type undetermined. Total thyroidectomy with central compartment and left neck dissection was performed.
RESULTS: Pathology report showed rhabdoid phenotype of thyroid carcinoma. Final staging was pT4N1M1.
CONCLUSIONS: Although WHO classification of thyroid tumor histology does not define this disease entity, few cases were reported. In the last 20 years, English literature review revealed only 12 cases about thyroid carcinoma with rhabdoid phenotype. Major treatment of thyroid carcinoma with rhabdoid phenotype is surgery, and the benefit of adjuvant therapies as radiotherapy or systemic chemotherapy is not clear. The prognosis of thyroid carcinoma with rhabdoid phenotype is extremely poor, with mean survival of only 6 months.

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Chun HJ, Lim EL, Heravi-Moussavi A, et al.
Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways.
Cancer Cell. 2016; 29(3):394-406 [PubMed] Article available free on PMC after 14/03/2017 Related Publications
Malignant rhabdoid tumors (MRTs) are rare lethal tumors of childhood that most commonly occur in the kidney and brain. MRTs are driven by SMARCB1 loss, but the molecular consequences of SMARCB1 loss in extra-cranial tumors have not been comprehensively described and genomic resources for analyses of extra-cranial MRT are limited. To provide such data, we used whole-genome sequencing, whole-genome bisulfite sequencing, whole transcriptome (RNA-seq) and microRNA sequencing (miRNA-seq), and histone modification profiling to characterize extra-cranial MRTs. Our analyses revealed gene expression and methylation subgroups and focused on dysregulated pathways, including those involved in neural crest development.

Related: MicroRNAs SMARCB1

Johann PD, Erkek S, Zapatka M, et al.
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.
Cancer Cell. 2016; 29(3):379-93 [PubMed] Related Publications
Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.

Related: SMARCB1

Gupta RK, Batra VV, Das MC, et al.
Malignant extra-renal rhabdoid tumor with unusual presentation: A report of two cases.
J Cancer Res Ther. 2015 Oct-Dec; 11(4):963-6 [PubMed] Related Publications
Malignant extra-renal rhabdoid tumor (MERT) is a rare highly aggressive tumor that occurs in young children with the very poor clinical outcome. The tumor is characterized by a diffuse proliferation of "rhabdoid cells," which are round or polygonal with eccentric nuclei, prominent nucleoli, and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies. However, rhabdoid cells are also seen in certain other soft tissue sarcomas such as proximal-type epithelioid sarcoma, rarely synovial sarcoma, and extra-skeletal myxoid chondrosarcoma. Because of its poor prognosis and histomorphological similarities with other soft tissue tumors, an accurate diagnosis is required using a wide immunohistochemical panel. Very few cases of MERT have been reported in the literature and to our knowledge none in the supra-glottis area. Due to the rarity and poor outcome of this tumor, we are reporting two cases of MERT.

Han ZY, Richer W, Fréneaux P, et al.
The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation.
Nat Commun. 2016; 7:10421 [PubMed] Article available free on PMC after 14/03/2017 Related Publications
Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1(flox/flox);Rosa26-Cre(ERT2) mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin.

Related: SMARCB1

Nobusawa S, Hirato J, Sugai T, et al.
Atypical Teratoid/Rhabdoid Tumor (AT/RT) Arising From Ependymoma: A Type of AT/RT Secondarily Developing From Other Primary Central Nervous System Tumors.
J Neuropathol Exp Neurol. 2016; 75(2):167-74 [PubMed] Related Publications
Atypical teratoid/rhabdoid tumors (AT/RT) are rare, aggressive, embryonal brain tumors that occur most frequently in very young children; they are characterized by rhabdoid cells and loss of INI1 protein nuclear expression. Here, we report the case of a 24-year-old man with a left frontal lobe tumor that was composed mainly of rhabdoid cells showing loss of INI1 nuclear reactivity and polyphenotypic immunohistochemical expression, with a small INI1-positive component of ependymoma. Array comparative genomic hybridization separately conducted for each histologically distinct component revealed 22 shared identical copy number alterations, including loss of heterozygosity of chromosome 22q containing the INI1 locus. Furthermore, we found the C11orf95-RELA fusion gene, the genetic hallmark of supratentorial ependymomas, not only in the ependymoma component but also in the AT/RT component by fluorescence in situ hybridization analysis, suggesting that the AT/RT cells secondarily progressed from the preexisting ependymoma cells. A second genetic inactivating event in the INI1 gene was not detected in the AT/RT component. There are several reported cases of AT/RT (or INI1-negative rhabdoid tumors) arising in the setting of other primary brain tumors (gangliogliomas, pleomorphic xanthoastrocytomas, and high-grade gliomas), but the present case

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Arnhold V, Oyen F, Schneppenheim R, et al.
Long-term survival of an infant with an atypical teratoid/rhabdoid tumor following subtotal resection and low-cumulative dose chemotherapy: a case report.
Childs Nerv Syst. 2016; 32(6):1157-61 [PubMed] Related Publications
INTRODUCTION: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive embryonal tumor of the central nervous system with a generally dismal prognosis, especially in patients younger than 12 months.
DISCUSSION: We here describe the unusual case of an infant with AT/RT with long-term survival despite low-cumulative dose chemotherapy after subtotal resection. Due to a poor neurological situation and an unfavorable oncological prognosis, therapy was halted after two partial surgical resections and four of the nine chemotherapy courses recommended by the European Rhabdoid Registry, without the patient receiving either radiotherapy or high-dose chemotherapy. The patient is alive without evidence of disease 52 months after diagnosis.
CONCLUSION: This case report highlights that independent prognostic factors are urgently needed for optimizing treatment stratification and preventing overtreatment.

Vaubel RA, Chen SG, Raleigh DR, et al.
Meningiomas With Rhabdoid Features Lacking Other Histologic Features of Malignancy: A Study of 44 Cases and Review of the Literature.
J Neuropathol Exp Neurol. 2016; 75(1):44-52 [PubMed] Article available free on PMC after 14/03/2017 Related Publications
The behavior of rhabdoid meningiomas otherwise lacking malignant features remains unknown as most of the originally reported aggressive cases showed anaplastic histologic features independently of rhabdoid phenotype. We studied 44 patients with rhabdoid meningiomas lacking anaplastic features. Median age at diagnosis was 48.6 years (range 10-79). Location was supratentorial in 28 (63.6%), skull base in 15 (34.1%), and spinal in 1 (2.3%). Tumor grade was otherwise World Health Organization grade I (n = 22, 50%) or II (n = 22, 50%). Rhabdoid cells represented <20% of the tumor in 12 cases (27.3%), 20% to 50% in 18 (40.9%), and >50% in 14 (31.8%). Median clinical follow-up, available for 38 patients, was 5.0 years (range 0.17-14.2). Recurrence occurred in 9 patients (5-year recurrence-free survival, 73.7%) with a significantly higher risk in subtotally resected tumors (p = 0.043). Rhabdoid cell percentage was not associated with recurrence. Six patients died (4 of disease, 2 of unclear causes); 5-year overall survival was 86.7%, a mortality in excess of that expected in grade I-II meningiomas but much lower than originally reported. Review of 50 similar previously reported cases confirmed our findings. We suggest that rhabdoid meningiomas be graded analogously to nonrhabdoid tumors, with caution that some may still behave aggressively and close follow-up is recommended.

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Sugimoto M, Kohashi K, Kuroiwa K, et al.
Renal cell carcinoma with rhabdoid-like features lack intracytoplasmic inclusion bodies and show aggressive behavior.
Virchows Arch. 2016; 468(3):357-67 [PubMed] Related Publications
In renal cell carcinoma (RCC), tumor cells with rhabdoid features are characterized by eccentric nuclei, prominent nucleoli, and eosinophilic cytoplasm with intracytoplasmic inclusion bodies. In RCC, tumor cells have also been observed resembling rhabdomyoblasts or rhabdoid but without intracytoplasmic inclusion bodies, and here, we defined these rhabdoid-like features of these cells. To this end, we studied a series of clear cell RCC (ccRCC) with rhabdoid features and compared them with a series of ccRCC with rhabdoid-like features to clarify the differences in the immunohistochemical profile and biological behavior. From 695 cases of ccRCC (80.8 % of all RCCs), 18 cases with rhabdoid features (2.1 % of all RCCs) and 25 cases with rhabdoid-like features (2.9 % of all RCCs) were investigated. The 5-year survival rate for ccRCC with rhabdoid features was 44.7 % and for ccRCC with rhabdoid-like features 30.3 %. Although ccRCC with rhabdoid features showed immunohistochemical co-expression of epithelial markers and vimentin as seen in malignant rhabdoid tumors, ccRCC with rhabdoid-like features showed no such co-expression. Multivariate analyses of cancer-specific survival revealed that perinephric tissues invasion was an independent prognostic factor in ccRCC with rhabdoid features (p = 0.0253) but not in ccRCC with rhabdoid-like features. In summary, although their prognosis is similar, the marker profile and pattern of extension of ccRCC with rhabdoid-like is different from that of ccRCC with rhabdoid features. Therefore, ccRCC with rhabdoid-like features should be distinguished from ccRCC with rhabdoid features.

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Fahiminiya S, Witkowski L, Nadaf J, et al.
Molecular analyses reveal close similarities between small cell carcinoma of the ovary, hypercalcemic type and atypical teratoid/rhabdoid tumor.
Oncotarget. 2016; 7(2):1732-40 [PubMed] Article available free on PMC after 14/03/2017 Related Publications
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy diagnosed in women under age 40. We and others recently determined that germline and/or somatic deleterious mutations in SMARCA4 characterize SCCOHT. Alterations in this gene, or the related SWI/SNF chromatin remodeling gene SMARCB1, have been previously reported in atypical teratoid/rhabdoid tumors (ATRTs) and malignant rhabdoid tumors (MRTs). To further describe the somatic landscape of SCCOHT, we performed whole exome sequencing on 14 tumors and their matched normal tissues and compared their genomic alterations with those in ATRT and ovarian high grade serous carcinoma (HGSC). We confirmed that SMARCA4 is the only recurrently mutated gene in SCCOHT, and show that recurrent allelic imbalance is observed exclusively on chromosome 19p, where SMARCA4 resides. By comparing genomic alterations between SCCOHT, ATRT and HGSC, we demonstrate that SCCOHTs, like ATRTs, have a remarkably simple genome and harbor significantly fewer somatic protein-coding mutations and chromosomal alterations than HGSC. Furthermore, a comparison of global DNA methylation profiles of 45 SCCOHTs, 65 ATRTs, and 92 HGSCs demonstrates a strong epigenetic correlation between SCCOHT and ATRT. Our results further confirm that the genomic and epigenomic signatures of SCCOHT are more similar to those of ATRT than HGSC, supporting our previous hypothesis that SCCOHT is a rhabdoid tumor and should be renamed MRT of the ovary. Furthermore, we conclude that SMARCA4 inactivation is the main cause of SCCOHT, and that new distinct therapeutic approaches should be developed to specifically target this devastating tumor.

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Stevic M, Bokun Z, Milojevic I, et al.
Management of Anesthesia in a Child with a Large Neck Rhabdoid Tumor.
Med Princ Pract. 2016; 25(3):290-2 [PubMed] Related Publications
OBJECTIVE: The aim of this paper was to report the management of anesthesia of a child with a large neck rhabdoid tumor.
CLINICAL PRESENTATION AND INTERVENTION: A 9-month- old female patient underwent urgent neck tumor excision due to intratumoral bleeding from a large tumor that compressed and dislocated the trachea; therefore, intubation was expected to be difficult. Sevoflurane inhalation induction was utilized to maintain spontaneous respiration. Oral laryngoscopy revealed Cormack-Lehane grade 3 laryngeal view. The trachea was intubated using a reinforced tube on the third attempt. Fiberoptic bronchoscope-assisted intubation was planned as an alternative in case of conventional intubation failure. Anticipation of massive blood loss necessitated central venous catheterization.
CONCLUSION: Establishing a safe airway, intubation during spontaneous breathing and invasive hemodynamic monitoring are crucial factors in the anesthetic management of pediatric patients with a large neck tumor.

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Geller JI
Current standards of care and future directions for "high-risk" pediatric renal tumors: Anaplastic Wilms tumor and Rhabdoid tumor.
Urol Oncol. 2016; 34(1):50-6 [PubMed] Related Publications
'High risk' renal tumors of childhood generally includes anaplastic Wilms tumor, rhabdoid tumor, and metastatic renal sarcomas and carcinomas. In this review, the epidemiology, biology, treatment and prognosis of anaplastic Wilms tumor and rhabdoid tumor are presented. Future directions related to management of such cancers are discussed, with insights provided into possible clinical trials in development that consider integration of novel targeted therapies.

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Schrey D, Carceller Lechón F, Malietzis G, et al.
Multimodal therapy in children and adolescents with newly diagnosed atypical teratoid rhabdoid tumor: individual pooled data analysis and review of the literature.
J Neurooncol. 2016; 126(1):81-90 [PubMed] Related Publications
Atypical teratoid rhabdoid tumour (ATRT) is a malignant tumour of the central nervous system with a dismal prognosis. There is no consensus on optimal treatment and different multimodal strategies are currently being used in an attempt to improve outcomes. To evaluate the impact of high-dose chemotherapy followed by autologous stem-cell rescue (HD48 SCR), radiotherapy (RT) at first line, intrathecal chemotherapy (IT) and extent of surgical resection upon recurrence-free survival (RFS) and overall survival (OS). An online database search identified prospective and retrospective studies focused on the treatment of children and adolescents with newly diagnosed ATRT. Clinical, therapeutic and outcome data were extracted and an individual pooled data analysis was conducted. Out of 389 publications, 12 manuscripts were included in our review. Data from 332 patients were analysed. Median age at diagnosis was 37 months (range 1-231). HD-SCR, RT and IT had been administered to 28.6% (58/203), 49.6% (118/238) and 21% (65/310) of the patients, respectively. Gross total resection (GTR) had been achieved in 46.5% (152/327) of the cases. In the multivariate analysis, hazard ratios (95% Confidence Interval) for HD-SCR were: RFS-HR = 0.570 (0.357-0.910) p = 0.019, and OS-HR = 0.388 (0.214-0.704) p = 0.002; and for RT: RFS-HR = 0.551 (0.351-0.866) p = 0.01, and OS-HR = 0.393 (0.216-0.712) p = 0.002. IT and GTR were not significantly associated with improved RFS or OS in the multivariate analysis. In our pooled data review, HD-SCR and RT at first line were associated with improved outcomes in children and adolescents with newly diagnosed ATRT.

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Wang L, Han F, Chen M, Chen Y
MRI and FDG PET/CT Uncovered the Cause of a Paraneoplastic Leukemoid Reaction.
Clin Nucl Med. 2016; 41(3):209-10 [PubMed] Related Publications
An 18-year-old man with progressive headache and vomiting for 2 weeks had significantly elevated levels of WBC count, which kept on rising over time during in-hospital evaluation. Exhaustive examinations did not reveal infection or any other explanations of increased WBC count. Instead, brain MRI and FDG PET/CT identified a malignant lesion in the brain without abnormality elsewhere. The pathological examination revealed a rhabdoid meningioma. The level of the WBC counts returned to normal promptly after surgical resection of the tumor, which confirmed the diagnosis of paraneoplastic leukemoid reaction.

Miyahara M, Nobusawa S, Inoue M, et al.
Glioblastoma with Rhabdoid Features: Report of Two Young Adult Cases and Review of the Literature.
World Neurosurg. 2016; 86:515.e1-9 [PubMed] Related Publications
BACKGROUND: There are few previous reports of glioblastoma in young adults, in particular, of the very rare recently proposed rhabdoid or epithelioid types.
CASE DESCRIPTION: We report 2 cases of glioblastoma with rhabdoid features involving a 27-year-old woman and a 41-year-old man. In case 1, the patient presented with generalized seizures, and the initial magnetic resonance imaging showed a very small region of contrast in the left parahippocampal area. After 1 year, the mass suddenly increased in size. Treatment with multiple therapies was administered, but 5 months later, the patient died from multiple systemic metastases. In case 2, the patient presented with a chief complaint of headache for a few weeks. Computed tomography and magnetic resonance imaging showed a left parietal mass with calcification and meningeal dissemination. After undergoing surgical removal, his condition rapidly deteriorated until brain death occurred.
CONCLUSIONS: Glioblastoma with rhabdoid features may represent a specific pattern of clinical progression that emerges from histologic glioblastoma types.

McKillop SJ, Belletrutti MJ, Lee BE, et al.
Adenovirus necrotizing hepatitis complicating atypical teratoid rhabdoid tumor.
Pediatr Int. 2015; 57(5):974-7 [PubMed] Related Publications
Adenovirus-induced fulminant hepatitis is rare. It has been reported in children with primary immunodeficiency, following transplantation or while receiving chemotherapy for hematological malignancy. We present the case of an infant recovering from chemotherapy for atypical teratoid rhabdoid tumor (ATRT) in whom a diagnosis of hepatic necrosis due to adenovirus was made.

Yasui N, Yoshida A, Kobayashi E, et al.
Successful Treatment of Extra-Renal Noncerebral Rhabdoid Tumors with VIDE.
Pediatr Blood Cancer. 2016; 63(2):352-4 [PubMed] Related Publications
Extra-renal noncerebral rhabdoid tumors (ERRTs) are highly aggressive and often lethal. An optimal chemotherapy regimen for ERRT remains undetermined. We report on three pediatric patients successfully treated with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE). Two of our patients who had metastatic or refractory disease have survived more than 2 years, one disease free without myeloablative megatherapy. The treatment with high-dose alkylator therapy is reported to have a beneficial effect on survival. A VIDE regimen containing high-dose ifosfamide is feasible and appears to prolong the survival of patients with ERRT. This regimen may be a promising option for ERRT treatment without myeloablative megatherapy.

Related: Doxorubicin Etoposide Ifosfamide Vincristine

Bahadur S, Pujani M, Jetley S, et al.
Large cell lung carcinoma with rhabdoid phenotype: Report of a rare entity presenting with chest wall involvement.
J Cancer Res Ther. 2015 Jul-Sep; 11(3):657 [PubMed] Related Publications
Large cell lung carcinoma (LCLC), rhabdoid phenotype (RP) is a rare entity, accounting for 0.1-1% of all lung tumors. It is characterized by presence of more than 10% cells with rhabdoid morphology-large cells with abundant cytoplasm, eccentric nuclei, prominent nucleoli and eosinophilic cytoplasmic inclusions. We report a case of rhabdoid variant of large cell carcinoma in a 65-year-old female. Patient presented with a lump in the right axilla. Computed tomography showed a large mass lesion in right lung with involvement of the chest wall. Tru-cut biopsy from the lung lesion was performed and histopathology was compatible with LCLC. A RP was considered due to the presence of tumor cells with eosinophilic cytoplasmic globules and eccentric nuclei. Cytokeratin and vimentin were diffusely positive while thyroid transcription factor was focally positive. INI-1, desmin, calretinin, HMB-45, and neuroendocrine markers were negative. This case highlights that recognition of large cell carcinoma lung, RP is very important because of its aggressive nature and adverse outcome.

Related: Lung Cancer

Darr J, Klochendler A, Isaac S, et al.
Phosphoproteomic analysis reveals Smarcb1 dependent EGFR signaling in Malignant Rhabdoid tumor cells.
Mol Cancer. 2015; 14:167 [PubMed] Article available free on PMC after 14/03/2017 Related Publications
BACKGROUND: The SWI/SNF ATP dependent chromatin remodeling complex is a multi-subunit complex, conserved in eukaryotic evolution that facilitates nucleosomal re-positioning relative to the DNA sequence. In recent years the SWI/SNF complex has emerged to play a role in cancer development as various sub-units of the complex are found to be mutated in a variety of tumors. One core-subunit of the complex, which has been well established as a tumor suppressor gene is SMARCB1 (SNF5/INI1/BAF47). Mutation and inactivation of SMARCB1 have been identified as the underlying mechanism leading to Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms.
METHODS: We present a phosphoproteomic study of Smarcb1 dependent changes in signaling networks. The SILAC (Stable Isotopic Labeling of Amino Acids in Cell Culture) protocol was used to quantify in an unbiased manner any changes in the phosphoproteomic profile of Smarcb1 deficient murine rhabdoid tumor cell lines following Smarcb1 stable re-expression and under different serum conditions.
RESULTS: This study illustrates broad changes in the regulation of multiple biological networks including cell cycle progression, chromatin remodeling, cytoskeletal regulation and focal adhesion. Specifically, we identify Smarcb1 dependent changes in phosphorylation and expression of the EGF receptor, demonstrate downstream signaling and show that inhibition of EGFR signaling specifically hinders the proliferation of Smarcb1 deficient cells.
CONCLUSIONS: These results support recent findings regarding the effectivity of EGFR inhibitors in hindering the proliferation of human MRT cells and demonstrate that activation of EGFR signaling in Rhabdoid tumors is SMARCB1 dependent.

Related: Kidney Cancer Signal Transduction

DiPatri AJ, Sredni ST, Grahovac G, Tomita T
Atypical teratoid rhabdoid tumors of the posterior fossa in children.
Childs Nerv Syst. 2015; 31(10):1717-28 [PubMed] Related Publications
PURPOSE: Atypical teratoid rhabdoid tumors (AT/RT) are rare, aggressive, central nervous system neoplasms that typically affect children under 3 years of age and have a very poor prognosis. Early case series consistently demonstrated rapid recurrence with progression to death, but more recent experience has shown significant improvements in progression free and overall survival.
METHODS: A retrospective analysis of the clinical data of children diagnosed with AT/RT at the Ann & Robert H. Lurie Children's Hospital of Chicago (formerly Children's Memorial Hospital) between 2000 and 2014 was performed. Overall survival (OS) was used to describe outcome. Our small sample size and the utilization of different adjuvant regimens over the study period precluded a detailed statistical analysis.
RESULTS: Eight children with AT/RT of the posterior fossa were included in our report. Gross total resection (GTR) was achieved in five children (63 %), two children underwent subtotal resection (25 %), and there was one who underwent biopsy. Patients were treated with various combinations of chemotherapy with or without conformal radiation therapy (RT). Median overall survival was 5 months (range 1 to 107 months) with two patients achieving sustained responses to 45 and 107 months.
CONCLUSIONS: Our experience is in line with prior reports that show that children diagnosed with AT/RT of the posterior fossa have a poor prognosis, but that long-term survival is possible. These tumors provide many challenges, but contemporary series are beginning to show improvements in survival.

Geller JI, Roth JJ, Biegel JA
Biology and Treatment of Rhabdoid Tumor.
Crit Rev Oncog. 2015; 20(3-4):199-216 [PubMed] Related Publications
Rhabdoid tumor is a rare, highly aggressive malignancy that primarily affects infants and young children. These tumors typically arise in the brain and kidney, although extrarenal, non-central nervous system tumors in almost all soft-tissue sites have been described. SMARCB1 is a member of the SWI/SNF chromatin-remodeling complex and functions as a tumor suppressor in the vast majority of rhabdoid tumors. Patients with germline mutations or deletions affecting SMARCB1 are predisposed to the development of rhabdoid tumors, as well as the genetic disorder schwannomatosis. The current hypothesis is that rhabdoid tumors are driven by epigenetic dysregulation, as opposed to the alteration of a specific biologic pathway. The strategies for novel therapeutic approaches based on what is currently known about rhabdoid tumor biology are presented.

Related: SMARCB1

Wu WW, Bi WL, Kang YJ, et al.
Adult Atypical Teratoid/Rhabdoid Tumors.
World Neurosurg. 2016; 85:197-204 [PubMed] Related Publications
BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant neoplasms that rarely occur in adults. Due to the complex histology of AT/RTs, the differential diagnosis of these tumors is quite challenging and increasingly relies on demonstration of characteristic SMARCB1/INI1 inactivation in tumor cells.
CASE DESCRIPTION: A 51-year-old man presented with diplopia, lethargy, and memory deficit owing to Parinaud syndrome and hydrocephalus. Magnetic resonance imaging revealed a T2-hyperintense and homogeneously enhancing tectal mass that extended to the pineal region. Initial biopsy suggested a World Health Organization grade II myxopapillary astrocytoma. However, subsequent definitive resection revealed an AT/RT, with loss of SMARCB1/INI1 observed through immunohistochemical staining as well as array cytogenetic analysis. Molecular profiling revealed additional mutations in RHPN2(L385I), MDM4(D396G), FLT3(V194M), and NPRL3(D53N).
CONCLUSIONS: Pathologic diagnoses in the modern era increasingly integrate molecular data for confirmation as well as prognostication. We present a rare case of a tectal AT/RT in an adult patient and report several novel mutations previously unrecognized in this tumor subtype, in addition to canonical SMARCB1/INI1 loss. Further investigation of these novel variants may improve understanding of the pathogenesis underlying AT/RTs.

Related: Pituitary Tumors SMARCB1

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