Meta-Analysis of Treatment Modalities in Metastatic Atypical Teratoid/Rhabdoid Tumors in Children.

BACKGROUND: Metastatic atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive central nervous system tumors that present during infancy and are associated with dismal outcomes. Patients receive multimodal treatment including surgical resection, systemic chemotherapy, and one or more of intrathecal chemotherapy (IT), marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and radiation therapy (XRT). While data regarding treatment modalities for AT/RT patients exist, no comprehensive data have been published regarding the metastatic patients. METHODS: We performed a meta-analysis of 1578 articles published through September 2018, including 44 studies with a total of 123 subjects. In addition, seven patients were included through chart review of patients treated at Nationwide Children's Hospital. RESULTS: Analysis of 130 patients revealed a 3-year overall survival (OS) of 25%. Age at diagnosis had a significant effect on survival (P = 0.0355); 3-year OS for infants less than 18 months was 21%, 18 to 36 months was 26%, and greater than 36 months was 36%. Location of the primary tumor, metastatic stage, and extent of surgical resection did not have a significant impact on OS. On univariate analysis, XRT (P < 0.0001), IT (P = 0.01), and AuHCR (P < 0.0001) were found to significantly improve survival. The most substantial effect was noted in patients who received AuHCR (3-year OS of 60% vs 9% in those who did not). On multivariable analysis, XRT (P = 0.0006), IT (P = 0.0124), and AuHCR (P < 0.0001) were independently associated with reduced risk of death. CONCLUSIONS: Although more research is warranted to make generalizable conclusions, these results suggest that treatment regimens for patients with metastatic AT/RTs should include AuHCR, XRT, and IT.

Atypical Teratoid Rhabdoid Tumor of the Cauda Equina in a Child: Report of a Very Unusual Case.

Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive malignant primitive neoplasms that commonly occur in children younger than 2 years of age. The prognosis is generally dismal with a median survival time of <1 year. The majority of AT/RT occur in the posterior fossa and less frequently the supratentorium. Primary pediatric spinal AT/RT are exceedingly rare and only 15 cases have been reported to date. Here we report a very unusual case of primary spinal AT/RT extensively involving the spinal cord from T11 down to the cauda equina. In this patient, the tumor was highly aggressive and resulted in extensive dissemination into the nerve roots and paraspinal soft tissue rapidly resulting in the patient's death 1 month after diagnosis. to the best of our knowledge, this degree of involvement of the spine by a primary AT/RT has not been described before.

Pediatric Rhabdoid Meningioma with Extension to the Heart: A First Case Report and Literature Review.

BACKGROUND: Meningiomas are the most common benign intracranial neoplasms in adults, but they have a lower incidence in children. Rhabdoid meningioma is a rare subtype of meningioma and is classified as World Health Organization grade III. CASE DESCRIPTION: We present a very rare case of a 9-year-old boy who presented to our institution with a history of headache, dizziness, and vomiting without neurologic deficit. The investigation showed a posterior fossa tumor with hemorrhage inside and hydrocephalus. He underwent tumor resection, and pathology showed rhabdoid meningioma. The patient had extensive recurrence after only 5 months, including extension to the neck, mediastinal veins, and heart. He was treated surgically and received adjuvant chemotherapy followed by radiation therapy. CONCLUSIONS: Rhabdoid meningioma is a malignant subtype of meningioma that occurs very rarely in pediatric patients. Additionally, rhabdoid meningioma, when it does occur in pediatric patients, has a high tendency to recur. Radical surgical resection with adjuvant radiotherapy is essential to prolonging survival. This is the first case with extracranial extension to the mediastinal veins and heart.

[SCCOHT/ovarian rhabdoid tumor: A case report]. / SCCOHT/tumeur rhabdoïde ovarienne : à propos d'un cas.

We report the case of a 22-year-old patient with acute abdominopelvic pain. The diagnosis of hypercalcemic small cell carcinoma (SCCOHT)/ovarian rhabdoid tumor has been made. Small cell carcinoma of hypercalcemic type is a rare and aggressive tumor that occurs in young women. The diagnosis of this tumor and the management must be rapid in view of its aggressiveness. Through this observation, we specify the epidemiological, diagnostic, molecular aspects and discussions about its name.

Neuroendocrine tumor of the pancreas with rhabdoid feature.

Imaging of a 53-year-old Japanese man revealed two tumors in the liver and a tumor in the head of the pancreas with a swelling lymph node. A needle biopsy for the liver tumors was performed, revealing a neuroendocrine tumor. Enucleation, lymphadenectomy, and partial hepatectomy were performed. The microscopic examination identified many tumor cells with intracytoplasmic inclusions arranged in a nested, cord, or tubular fashion. The intracytoplasmic inclusions displayed densely eosinophilic globules and displaced the nuclei toward the periphery, which constitutes "rhabdoid" features. The tumor cells were positive for synaptophysin and weakly positive for NCAM, but negative for chromogranin A. Epithelial markers (AE1/AE3 and CAM5.2) accentuated intracytoplasmic globules. Pancreatic neuroendocrine tumors with rhabdoid features are very rare. Generally, rhabdoid features are aggressive and dedifferentiated characteristics of various types of tumor. Pancreatic neuroendocrine tumors containing rhabdoid cells tend to display extrapancreatic spread at the time of presentation, although some of these tumors with rhabdoid features are not always associated with aggressive behavior.

Malignant Rhabdoid Tumor of Soft Tissue.

Introduction Malignant rhabdoid tumor (MRT) is defined as a high-grade sarcoma derived from an uncertain cell of origin. Its diagnosis is associated with poor prognosis and patient's life expectancy is greatly reduced. Material and method Here, we describe a unique case of 9-month-old boy who presented with a large MRT arising from the soft tissue of the neck. Following intensive multimodal treatment, the patient benefited from a 25 years' remission until the discovery of multiple liver metastases. Conclusion MRT of soft tissue needs to be distinguished from other soft tissue neoplasms, as MRT is highly aggressive and is usually associated with a poor outcome. In addition, this is the longest remission time reported in a patient with soft tissue MRT and this might be related to the use of early intensive multimodal treatments.

Prognostic factors and survival in non-central nervous system rhabdoid tumors.

INTRODUCTION: Non-central nervous system (non-CNS) rhabdoid tumors tend to present at a young age and have an extremely aggressive course, with dismal overall survival rates. Inactivation of the tumor suppressor gene SMARCB1 has been shown in rhabdoid tumors regardless of anatomic location, suggesting a common genetic basis. We retrospectively analyzed our institutional experience with non-CNS rhabdoid tumors to determine overall survival and prognostic variables. METHODS: We reviewed records of pediatric patients (age<22y) with non-CNS rhabdoid tumor at our institution between 1980 and 2014. Variables evaluated for correlation with survival included: age > or <1.5years (median) at diagnosis, M1 status, and radiation therapy. The log-rank test was used to compare Kaplan-Meier probability distributions with P values adjusted for multiple testing using the false discovery rate approach. RESULTS: Nineteen consecutive patients (10 female) with histologically verified rhabdoid tumor were identified. Mean age at diagnosis was 3.2years (median 1.5y, range 1.3mo-21.8y). Primary tumors were located in the kidney (n=10), head and neck (n=5), and in the liver, thigh, mediastinum and retroperitoneum (n=1 each). SMARCB1 expression was absent in all 10 patients tested. Eight patients had distant metastases at diagnosis. Median overall survival was 1.2years. Age greater than the median and radiation therapy were associated with better outcome, with a median overall survival of 2.7years (P=0.049 and P=0.003, respectively). CONCLUSION: Survival rates for rhabdoid tumor remain poor, but prognosis is better in older children, regardless of primary tumor location. Because of its rarity, clinical trials with present agents are difficult to conduct. Further progress will require a focus on therapies targeted at tumor biology rather than anatomic location for non-CNS rhabdoid tumors.

Malignant extrarenal rhabdoid tumour (MERT) with liver metastases as a rare cause of an esophageal tumor in a 57 years old patient.

Tumors with a rhabdoid phenotype are aggressive neoplasms with a dismal prognosis. Malignant extrarenal rhabdoid tumor (MERT) of the esophagus is an extremely rare disease with so far only 6 cases reported. We report on a 57-year-old male patient with rhabdoid tumor situated in the esophagus with metastases to the liver and local lymph nodes. Assuming an undifferentiated esophageal adenocarcinoma a palliative chemotherapy with 5-FU/folinic acid, oxaliplatin, and docetaxel (FLOT) was initiated which was changed towards a combination of doxorubicin and ifosphamide as immunohistochemistry of the primary and the liver metastases revealed a rhabdoid tumor. This treatment with doxorubicin and ifosphamide resulted in a short clinical and radiological response which lasted only for 2 months. Due to the bad general condition at the time of progression no further chemotherapy was initiated. The patient died due to tumor progression 6 months after initial diagnosis which is consistent with other reports on malignant extrarenal rhabdoid tumors (median survival of metastatic disease less than 6 months). Thus, metastatic MERT represents a disease with a poor prognosis and no established standard therapy.

Rhabdoid differentiation is associated with aggressive behavior in renal cell carcinoma: a clinicopathologic analysis of 76 cases with clinical follow-up.

Rhabdoid differentiation has been associated with aggressive behavior in carcinomas from different organ systems. A recent consensus statement of the International Society of Urological Pathology (ISUP), in addition to proposing a nucleolar grading system (ISUP grade) for renal cell carcinoma (RCC) to replace the Fuhrman system, recommended reporting the presence of rhabdoid differentiation in RCC and considering tumors with rhabdoid differentiation to be ISUP grade 4. Although it has been shown that rhabdoid differentiation is associated with increased grade and stage of RCC, it has not been fully demonstrated whether it has an adverse effect independent of this association with increased grade and stage. We provide the largest clinicopathologic analysis of RCC with rhabdoid differentiation to date (76 cases), including characterization of metastatic disease. In addition, by constructing a multivariable model including tumor grade, stage, necrosis, and distant metastasis to compare a series of 49 clear cell RCC with rhabdoid differentiation with a cohort of 41 clear cell RCCs without rhabdoid differentiation, we demonstrate that the presence of rhabdoid differentiation in clear cell RCC confers an increased risk of death (hazard ratio=5.25; 95% confidence interval, 2.1-14.3) independent of these other adverse prognostic factors. These findings underscore the significance of rhabdoid differentiation in RCC as an adverse prognostic factor and support the recent reporting and grading recommendations of the ISUP.

Squamous cell carcinoma with rhabdoid features of the gingiva: a case report with unusual histology.

Squamous cell carcinoma (SCC) with rhabdoid features (SCCRF) is extremely rare in the oral cavity. We report herein a case of oral SCCRF. The patient was a 69-year-old Japanese woman who had been suffering from a mass in the right lower gingiva. Right hemi-mandibulectomy was performed. The gingival tumor was composed of pleomorphic, non-cohesive ovoid tumor cells with abundant cytoplasm and eccentric nuclei, which were positive for both pan-cytokeratin and vimentin. In another portion, moderately differentiated SCC and carcinoma in situ were also seen. A transition zone existed between the components. Finally, we diagnosed SCCRF. Four months after the operation, multiple bone metastases, lung and skin metastases and marked hypercalcemia were found. SCCRF, therefore, might be more aggressive than the usual type of oral SCC.

Cutaneous location of atypical teratoid/rhabdoid tumour.

Atypical teratoid/rhabdoid tumour is a rare and highly malignant tumour of the posterior fossae nervous system that occurs in children especially in the first few years of life. Cutaneous location is not previously reported. A newborn boy was referred for both aqueductal stenosis detected antenatally and skin tags mimicking hamartoma. The cerebral tumour increased in size during a few months leading to both skin and cerebral biopsies. Integrase Interactor-1 (INI-1) immunostaining and tumoural and leukocytes INI-1 gene sequencing confirmed the atypical teratoid/rhabdoid tumour nature of the cerebral tumour. INI-1 immunostaining in skin biopsy confirmed the dermal location of rhabdoid tumour. Thus, unusual cutaneous lesions may be part of atypical teratoid/rhabdoid tumour. The loss of Integrase INI-1 on immunohistochemical staining is characteristic.

Differential expression of miRNAs in rhabdomyosarcoma and malignant rhabdoid tumor.

Alveolar rhabdomyosarcoma (RMA) and malignant rhabdoid tumor (MRT) have a frequent metastatic spread and a poor prognosis. Aberrant miRNA expression is often found in metastatic tumors. The aim of this study was to identify specific miRNA expression patterns in these tumors. We analyzed the expression of miRNAs in RMA and MRT in tissue samples and in the rhabdomyosarcoma (RMS) cell lines (Rh30 and RD). Selected target miRNAs were modulated with mimic or inhibitor oligonucleotides. Functional analysis was monitored by flow cytometry and migration assays. A set of 107 differentially expressed miRNAs showed tissue-specific clustering of RMA and MRT. Comparison with the Sarcoma microRNA Expression Database revealed RMA- and MRT-specific miRNAs. Metastatic invasion associated miRNA miR-9 was overexpressed in RMA. miR-200c-inhibiting migration-was lower expressed in RMA than in MRT. Transient transfection of RMS cells with a miR-200c mimic and miR-9( inhibitor did neither increase the expression of the known target E-cadherin nor decrease migration. Expression of E-cadherin could be induced in RD cells using decitabine, but demethylation did not influence cell migration. Despite a comparable high rate of metastatic invasion pediatric RMA and MRT show a different pattern of miRNA expression possibly allowing risk stratification.

Primary lung metastases in pediatric malignant non-Wilms renal tumors: data from SIOP 93-01/GPOH and SIOP 2001/GPOH.

Malignant non-Wilms renal tumors (NWRT) are a small but relevant subgroup of renal neoplasms in children. In this study we analyzed corresponding data from the trials SIOP 93-01/GPOH and SIOP 2001/GPOH of the Society of Pediatric Oncology and Hematology.Data of 22 patients with NWRT and primary lung metastases were retrospectively reviewed. Analyses included epidemiology, tumor characteristics, chemotherapy, local treatment, and outcome.The following diagnoses were registered: Malignant Rhabdoid tumor of the kidney (MRTK, n=15), Renal-cell carcinoma (RCC, n=3), Clear-cell sarcoma of the kidney (CCSK, n=3), and primitive neuro ectodermal tumor (PNET, n=1). Median age of patients at diagnosis was 14 months. Overall survival was 36.36% (8/22). Of the 15 children with MRTK 3 survived, 3/3 patients with RCC, 1/3 patients with CCSK, and 1/1 patient with PNET survived. Lung metastases disappeared in 6 patients after initial chemotherapy, 6/8 patients undergoing local treatment of lung metastases (surgery, irradiation, or both) achieved complete remission. Only patients with complete clearance of lung lesions, either through neoadjuvant chemotherapy or subsequent local treatment, survived. Mean Follow up was 31 months (1-137).Survival of patients with stage IV NWRT is dismal. Complete removal of lung metastases seems mandatory for survival. An aggressive diagnostic and therapeutic approach seems justified in affected children.

Sequencing of local therapy affects the pattern of treatment failure and survival in children with atypical teratoid rhabdoid tumors of the central nervous system.

PURPOSE: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). METHODS AND MATERIALS: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. RESULTS: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolled into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% ± 9%; progression-free survival was 33.2% ± 10%; and OS was 53.5% ± 10%. Children receiving delayed RT (≥1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. CONCLUSIONS: Delayed RT is associated with a higher rate of local and metastatic disease progression in children with AT/RT. Current treatment regimens for pediatric patients with AT/RT are distinctly age stratified; novel protocols investigating RT volumes and sequencing are needed.

Drop metastases to the pediatric spine revealed with diffusion-weighted MR imaging.

Identifying drop metastases to the spine from pediatric brain tumors is crucial to treatment and prognosis. MRI is currently the gold standard for identifying drop metastases, more sensitive than CSF cytology, but imaging is not uncommonly inconclusive. Although diffusion-weighted imaging (DWI) of the brain is very useful in the evaluation of hypercellular tumors, DWI of the spine has not been clinically useful in children because of susceptibility artifacts and lack of spatial resolution. A new technique, readout-segmented echo planar imaging (EPI), has improved these images, allowing for identification of hypercellular drop metastases. We report a case that illustrates the utility of spine DWI in the detection of metastatic disease in children with primary central nervous system (CNS) tumors. This case suggests that DWI of the spine with readout-segmented EPI should be included in the evaluation for drop metastases.

Congenital malignant rhabdoid tumor of the scalp.

BACKGROUND: Malignant rhabdoid tumors (MRT) are rare but aggressive tumors presenting in the pediatric population. First thought a variant of Wilms' tumor in the kidney, it is recognized as presenting at renal, central nervous system and other extra-renal primary sites. It is uniformly of very poor prognosis, however. CASE REPORT AND DISCUSSION: We present a case of congenital MRT of the scalp, which we believe to be the first described at this site. The clinical and histopathological features of the tumor are discussed in light of the current literature on MRT at other sites. The bleak prognosis at this site appears to be no different from others - the child succumbed at 10 months old despite surgical resection and initial excellent response to chemotherapy. CONCLUSION: Malignant rhabdoid tumor has a very poor prognosis and needs to be considered in the differential diagnosis of similar lesions by clinicians involved in pediatric head and neck care.

Originally misdiagnosed rhabdoid tumour of the kidney. A case report and differential diagnosis.

Rhabdoid tumour of the kidney (RTK) is considered to be one of the most aggressive neoplasms of early life. The histogenesis of RTK still remains a matter of controversy. Immunohistochemistry usually shows diffuse reactivity for vimentin, focal reactivity to the epithelial marker, variable expression of mesenchymal and neuroectodermal markers, and loss of INI1 protein staining. Expression of the Wilms' tumour protein (WT1) was described in the RTK cases. We would like to present a case of rhabdoid tumour of the kidney in Latvia, which caused diagnostic difficulties of a 27-month-old girl, and a short review of literature.