Acute-phase electroencephalography for an infantile atypical teratoid/rhabdoid tumor.

BACKGROUND: Primary brain tumor is a leading cause of death in cancer-bearing children. Acutely progressive patterns of electroencephalography (EEG) remain to be investigated for children with rapidly growing brain tumors. CASE REPORT: A 14-month-old boy was transferred to our department for prolonged seizures and unrecovered consciousness on his fifth day of illness. The EEG recording on admission showed highly disorganized background activity with high-voltage rhythmic delta waves. Serial EEG monitoring revealed a rapid transition of the background activity to the suppression-burst pattern, and then to generalized suppression of cortical activity within a few hours after admission. Magnetic resonance imaging detected a midline tumor at the pineal gland extending to the midbrain and pons. The tumor was pathologically confirmed as atypical teratoid/rhabdoid tumor (AT/RT) with absent expression of SMARCB1. He died of tumor progression on the 20th day after admission. CONCLUSION: AT/RT is an additional category of brain tumors that cause the clinically and electro-physiologically critical condition in a few days after the onset.

A 71-year-old man with a rare rhabdoid brain tumour: using a multidisciplinary medical and rehabilitative model of care.

Atypical rhabdoid tumours (AT/RTs) of pineal origin are rare in adults with rapid progression and poor prognosis. We present the case of a 71-year-old man with confusion and memory loss who was diagnosed with a pineal AT/RT after genetic analysis. Due to his limited functional capacity and goal to return home with family, a multidisciplinary care approach was essential for coordination of medical management, radiation treatment and acute inpatient rehabilitation. After diagnosis and rehabilitation, his functional ability improved allowing him to tolerate cranial irradiation, initiate systemic chemotherapy and eventually returned home for a brief period with an improved quality of life. His progress was temporary due to rapid progression of the tumour. He required additional aggressive oncological treatment and was admitted for subsequent inpatient rehabilitation before opting for hospice care. This case underscores the importance of a multidisciplinary approach to cancer treatment in a patient with a rare and aggressive brain tumour, while respecting the individual goals of patients and their families.

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.

Meningioma intramedular tipo rabdoide. Reporte de un caso y revisión de la literatura / Rhabdoid type intramedullary meningioma. A case report and review of the literature

Los meningiomas son los tumores más frecuentes localizados a nivel espinal junto a neurinomas y metástasis. Estos tumores suelen ser intradurales y extramedular. Son pocos los casos descritos en la literatura con una localización puramente intramedular (menos de 10 casos) y frecuentemente se observan en la unión cráneo-cervical. Ante la presencia de un tumor intramedular, realizamos diagnósticos diferenciales con ependimomas, astrocitomas, etc. En este artículo presentamos el primer caso descrito en la literatura de un paciente con un meningioma tipo rabdoide exclusivamente intramedular a nivel del cono medular

Meningiomas are the most frequent tumors located at the spinal level together with neurinomas and metastases. These tumors tend to be intradural and extramedullar. There are few cases described in the literature with a purely intramedullary location (less than 10 cases) and they are frequently observed in the union craneal-cervical. In the presence of an intramedullary tumor we perform differential diagnoses with ependymomas, astrocytomas... In this article we present the first case described in the literature of a patient with a rabdoid-type meningioma exclusively intramedullary at the level of the medullary cone

Extrarenal rhabdoid tumor presented with an immobile arm in a one-year-old boy.

Infants with an immobile arm may be easily overlooked in primary care settings. Differential diagnoses include injuries, infections, neuropathies, ischemia and rarely, neoplasms. We report the case of a one-year-old boy with weakness in his left arm after minor trauma with a diagnosis of brachial plexus palsy initially. After rehabilitation for 2months, his weakness progressed to unsteady gait and quadriparesis. MRI revealed a huge solid tumor in the left supraclavicular fossa, which also involved the left brachial plexus, upper thoracic cavity, and left paravertebral space with invasion into the spinal canal. Microscopically, the medium-large polygonal tumor cells had an eccentric eosinophilic cytoplasm and immunostaining showed a loss of nuclear INI1 expression. Array comparative genomic hybridization of the tumor tissue confirmed a segmental deletion at chromosome region 22q11.23 involving the SMARCB1 gene. The final diagnosis was cervical paravertebral malignant rhabdoid tumor with intraspinal epidural and intradural invasion, a rare case of extrarenal extracranial rhabdoid tumor (ERRT). The intraspinal part of the tumor was resected followed by interval-compressed chemotherapy with vincristine-doxorubicin-cyclophosphamide alternating with ifosfamide-etoposide (VDC/IE). The tumor showed very good partial response to four cycles of chemotherapy with gradual recovery of neurological symptoms. ERRT is a very rare and aggressive tumor that mainly occurs in infants and children and may manifest with vague neurological symptoms when it involves the spinal cord and/or peripheral nerves. A neoplasm such as ERRT originating from or involving the brachial plexus should be considered in the differential diagnosis of an immobile arm in infancy.

Overexpression of TEAD4 in atypical teratoid/rhabdoid tumor: New insight to the pathophysiology of an aggressive brain tumor.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal brain tumor that occurs mainly in early childhood. Although most of the tumors are characterized by inactivating mutations of the tumor suppressor gene, SMARCB1, the biological basis of its tumorigenesis and aggressiveness is still unknown. PROCEDURE: We performed high-throughput copy number variation analysis of primary cell lines generated from primary and relapsed tumors from one of our patients to identify new genes involved in AT/RT biology. The expression of the identified gene was validated in 29 AT/RT samples by gene expression profiling, quantitative real-time polymerase chain reaction, and immunohistochemistry (IHC). Furthermore, we investigated the function of this gene by mutating it in rhabdoid tumor cells. RESULTS: TEAD4 amplification was detected in the primary cell lines and its overexpression was confirmed at mRNA and protein levels in an independent cohort of AT/RT samples. TEAD4's co-activator, YAP1, and the downstream targets, MYC and CCND1, were also found to be upregulated in AT/RT when compared to medulloblastoma. IHC showed TEAD4 and YAP1 overexpression in all samples. Cell proliferation and migration were significantly reduced in TEAD4-mutated cells. CONCLUSIONS: We report the overexpression of TEAD4 in AT/RT, which is a key component of Hippo pathway. Recent reports revealed that dysregulation of the Hippo pathway is implicated in tumorigenesis and poor prognosis of several human cancers. Our results suggest that TEAD4 plays a role in the pathophysiology of AT/RT, which represents a new insight into the biology of this aggressive tumor.

Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors.

BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RT) are among the most malignant pediatric brain tumors. Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs). This study aimed to evaluate the therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs from AT/RT. METHODS: Primary cultured BTICs from AT/RT were stained with Aldefluor and isolated by fluorescence activated cell sorting. The therapeutic effect of DSF against BTICs from AT/RT was confirmed in vitro and in vivo. RESULTS: AT/RT cells displayed a high expression of ALDH. DSF demonstrated a more potent cytotoxic effect on ALDH(+) AT/RT cells compared with standard anticancer agents. Notably, treatment with DSF did not have a considerable effect on normal neural stem cells or fibroblasts. DSF significantly inhibited the ALDH enzyme activity of AT/RT cells. DSF decreased self-renewal ability, cell viability, and proliferation potential and induced apoptosis and cell cycle arrest in ALDH(+) AT/RT cells. Importantly, DSF reduced the metabolism of ALDH(+) AT/RT cells by increasing the nicotinamide adenine dinucleotide ratio of NAD(+)/NADH and regulating Silent mating type Information Regulator 2 homolog 1 (SIRT1), nuclear factor-kappaB, Lin28A/B, and miRNA let-7g. Animals in the DSF-treated group demonstrated a reduction of tumor volume (P < .05) and a significant survival benefit (P = .02). CONCLUSION: Our study demonstrated the therapeutic potential of DSF against BTICs from AT/RT and suggested the possibility of ALDH inhibition for clinical application.

Good response to chemotherapy spares irradiation for extrarenal rhabdoid tumor conferring better activities of daily living.

A 7-year-old girl with stage IIA extrarenal rhabdoid tumor near the left cubital fossa received preoperative chemotherapy and surgical resection with median nerve reconstruction followed by postoperative high-dose chemotherapy. As preoperative chemotherapy resulted in decreased tumor size, disappearance of fluorodeoxyglucose-uptake, and pathologic complete response with total tumor resection, irradiation was successfully spared to avoid injury to the reconstructed nerve and inhibition of normal bone development. Two years after diagnosis, recurrence has not been observed and median nerve palsy is improving. This case suggests that radiation therapy could be spared for clinically and pathologically chemotherapy-good-responders in case total surgical resection is achieved.

Congenital extrarenal malignant rhabdoid tumor in an infant with distal 22q11.2 deletion syndrome: the importance of SMARCB1.

Extrarenal rhabdoid tumor is a rare malignancy of infants and children, typically presenting in the soft tissue of deep, axial locations. We describe a rare dermal presentation of congenital extrarenal rhabdoid tumor in the left paraspinal region of a 6-month-old girl with germline deletion of chromosome 22q11.21q11.23. This case demonstrates that like other rhabdoid tumors, the SMARCB1 gene is also responsible for cutaneous extrarenal rhabdoid tumor oncogenesis.

Rapidly progressive primary leptomeningeal atypical teratoid/rhabdoid tumor: a report of 2 cases.

Atypical teratoid/rhabdoid tumor is a rare, highly malignant central nervous system tumor most commonly occurring in very young children. Atypical teratoid/rhabdoid tumor most often presents as an expanding mass with symptoms consistent with the location of the tumor and may present with metastatic leptomeningeal disease. The authors describe 2 cases of rapidly progressive, diffuse leptomeningeal atypical teratoid/rhabdoid tumor without a solid primary mass. These cases demonstrate a clinical picture that can easily be confused with a basilar meningitis, encephalomyelitis, or vasculitis.

Atypical teratoid/rhabdoid tumor: short clinical description and insight into possible mechanism of the disease.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor typically appearing in childhood. Differentiation of AT/RT from other brain tumors is extremely important because of grim prognosis and necessity of more aggressive treatment. On the other hand, investigation is essential for new therapeutic agents based on continuously developing knowledge of AT/RT development mechanisms. Most AT/RT tumors have been demonstrated to harbor a chromosome 22 mutation in the region of hSNF5/INI1 gene, whose protein product participates in chromatin remodeling. Although the presence of this mutation is rather undisputable, additional molecular pathways underlying AT/RT development are poorly understood. Current paper discusses current views on molecular pathophysiology of the tumor.

Primary malignant rhabdoid tumor of the stomach, a rare case report and review of literature.

Rhabdoid tumor is a distinct entity reported in renal and extrarenal sites. There have been very rare reported cases in the stomach, all of which have shown an aggressive clinical course. Herein, we report a primary gastric neoplasm in an old man who presented with profuse intractable GI bleeding and undergone emergency surgery. Resected specimen showed primary malignant rhabdoid tumor. The patient died 24 h after surgery with no additional therapy. Our case emphasizes on this very rare subtype of gastric tumor, with extremely aggressive behavior.

Intraoperative neurophysiology for surgery in and around the brainstem: role of brainstem mapping and corticobulbar tract motor-evoked potential monitoring.

INTRODUCTION: New advancements of intraoperative neurophysiology for surgery in and around the brainstem have been described. NEUROPHYSIOLOGICAL TECHNIQUES: Brainstem mapping (BSM) is applied to locate cranial nerves and their motor nuclei (CMN) on the floor of the fourth ventricle. Corticobulbar tract (CBT) motor-evoked potential (MEP) monitoring is used to achieve on-line monitoring of the cranial motor nerves' functional integrity. DISCUSSION: Each of these procedures bears a specific role: BSM can help avoid direct damage to CMNs on the fourth ventricular floor; CBT-MEP can provide simultaneous feedback on the functional integrity of the CBT and CMN during surgery, eventually leading to "tailored" modifications of the surgical procedure, based upon neurophysiological responses. CONCLUSIONS: CBT-MEP monitoring has less restriction in terms of clinical indications, but a combination of both procedures is essential for functional preservation of CMNs during surgery in and around the brainstem.

Immunohistochemical study as a tool in differential diagnosis of pediatric malignant rhabdoid tumor.

Malignant rhabdoid tumors (MRTs) are aggressive childhood neoplasms, occurring mainly in the kidney and brain. We describe 2 unusual cases of extrarenal and noncranial location (liver and soft tissue with dissemination) mimicking hepatoblastoma, neuroblastoma or Ewing sarcoma. Both cases revealed a polyphenotypic profile, combined with cytokeratin, vimentin, and CD99 expression. INI1/BAF-47 showed negative protein nuclear expression in both cases, suggesting a diagnosis of MRT. An extensive immunohistochemical panel was performed to exclude pediatric tumors reminiscent of MRT. The genetic studies failed to detected MYCN amplification, 11q23 deletion, and EWS break-apart positivity. No alterations of 22q integrity were demonstrated with the probes used for the study (N25 Di George/22q11.2, 22qter, and EWS/22q12). We discuss the differential diagnosis in pediatric polyphenotypic tumors (Wilms tumor, neuroblastoma, desmoplastic small round cell tumor, and Ewing sarcoma). Analysis of INI1/BAF-47 expression can offer important clues in the diagnosis of pediatric tumors with rhabdoid phenotype. The integration of clinical, morphologic, immunohistochemical, and genetic data is required to approach a correct diagnosis of pediatric tumor in unusual location with atypical or undifferentiated morphology.

Improved survival in patients with breast rhabdoid tumors with multi-agent adjuvant chemotherapy combined with irradiation.

PURPOSE: Malignant rhabdoid tumors (MRT) have poor prognoses. Breast MRT is extremely rare; only three cases have been documented, with a mean prognosis of 7 months. Multi-agent chemotherapy with mastectomy and irradiation, as used in this case, may extend survival in breast MRT. PATIENT AND METHODS: A 68-year-old woman who underwent a standard mastectomy was diagnosed with breast MRT. Postoperatively she received six cycles of cyclophosphamide/methotrexate/5-fluorouracil followed by oral administration of doxifluridine and anastrozole, after which no metastasis was detected. About 8 months postoperative, magnetic resonance imaging revealed cervical bone metastasis, and local irradiation and nine doses of "basic chemotherapy" consisting of biweekly paclitaxel and anastrozole were administered. About 4 months later, multiple lung metastases were revealed, and four doses of "basic chemotherapy" with added pirarubicin hydrochloride were administered. Four months after that, multiple large liver metastases were discovered, and five doses of "basic chemotherapy" with added carboplatin were administered. RESULTS: The 19-month survival period of our case was almost three times that of reported breast MRT patients. CONCLUSION: Multi-agent chemotherapy combined with irradiation may be associated with the relatively long survival of the present case.

Aggressive infantile embryonal tumors.

Embryonal tumors are the most common brain tumors in infants less than 36 months. Histologically characterized as undifferentiated small, round cell tumors with divergent patterns of differentiation, these include medulloblastoma, the most common form of embryonal tumor, as well as supratentorial primitive neuroectodermal tumor, medulloepithelioma, ependymoblastoma, medullomyoblastoma, melanotic medulloblastoma, and atypical teratoid/rhabdoid tumor. All are similarly aggressive and have a tendency to disseminate throughout the central nervous system. Because of efforts to avoid craniospinal irradiation in an attempt to lessen treatment-related neurotoxicity, management of these tumors in infants is unique. Outcomes remain similarly poor among all the tumor types and, therefore, identification of specific molecular targets that have prognostic and therapeutic implications is crucial. The molecular and clinical aspects of the 3 most common aggressive infantile embryonal tumors, medulloblastoma, supratentorial primitive neuroectodermal tumor, and atypical teratoid/rhabdoid tumor, are the focus of this review.

Atypical teratoid/rhabdoid tumor arising from the third cranial nerve.

An otherwise healthy 6-week-old girl who presented with an isolated left third cranial nerve palsy underwent MRI that revealed an enhancing mass intrinsic to the left third cranial nerve. Rapid enlargement of the lesion over 1 month led to subtotal neurosurgical resection of an atypical teratoid/rhabdoid tumor (AT/RT), a rare, highly aggressive malignancy of infancy closely related histologically to medulloblastoma and primitive neuroectodermal tumor. Despite aggressive chemotherapy, the patient died within 6 months of presentation. This is the first report of an AT/RT presenting as an isolated third cranial nerve palsy caused by tumor arising from within the nerve.

Atypical teratoid/rhabdoid tumor mimicking tuberculous meningitis.

Atypical teratoid/rhabdoid tumor of the central nervous system is a highly malignant neoplasm in infants and young children. We report a 6 year-old girl with atypical teratoid/rhabdoid tumor. Based on cerebrospinal fluid examination MRI scan and family history of tuberculosis; we diagnosed tuberculous meningitis. There was inadequate response to the antituberculosis therapy; so we performed stereotactic brain biopsy. Pathologic result revealed high grade atypical teratoid/rhabdoid tumor.

Rhabdoid meningioma: a new subtype of malignant meningioma also apt to occur in children.

CASE REPORT: The case of a 14-year-old girl who presented with a 2-week history of raised intracranial pressure is reported. A left frontal extra-axial tumor was totally removed, whose histopathologic diagnosis was rhabdoid meningioma (RM). DISCUSSION: Rhabdoid meningiomas constitute a special malignant phenotype of meningioma that has been recently included in the WHO classification of tumors of the nervous system. Usually, RMs affect middle-aged and elderly individuals. We report the fourth case of a RM occurring in a child to illustrate that the diagnosis of this tumor subtype, given its prognostic implications, must also be considered in pediatric patients.