Pediatric rhabdoid meningioma: a morphological,immunohistochemical, ultrastructural and molecular case study

Rhabdoid meningioma is an uncommon meningioma variant categorized as WHO grade III. The majority of cases occur in adulthood. Herein, we describe a right fronto‐temporal rhabdoid meningioma affecting a 3‐year‐old boy. The lesion measured approximately 4 cm in diameter and incorporated the ipsilateral middle cerebral artery. Sub‐total surgical excision of the mass was performed. Histologically, the tumor was mainly composed of globoid plump cells with inclusion‐like eosinophilic cytoplasm, peripheral nuclei, prominent nucleoli and occasional intra‐nuclear cytoplasmic pseudo‐inclusion. The cells appeared in many areas loosely arranged and focally disclosed a papillary architecture. At immunohistochemistry, the tumor cells were EMA, vimentin, HHF35, PgR, INI‐1 and p53 positive. The proliferative index (Mib‐1) was 15% in the most positive areas. Ultrastructurally, tumoral cells showed an abundant cytoplasm, which was filled with numerous intermediate filaments. Desmosomal junctions were seen. RT‐PCR revealed the presence of NF2 gene expression. Molecular study did not indicate alterations of the INI‐1 gene, whereas it showed the presence of Pro72Arg in exon 4 at heterozygous state in the TP53 gene. Morphologic features along with immunohistochemical, ultrastructural and molecular results were consistent with the diagnosis of rhabdoid meningioma. The patient was treated with chemotherapy. The lesion remained stable after 33 months of follow‐up. Rhabdoid meningiomas rarely occur in children. Owing to its rarity, each new case should be recorded to produce a better clinical, pathological, molecular, prognostic and therapeutic characterization of this lesion.     

Atypical teratoid rhabdoid tumor involving the nasal cavities and anterior skull base

Rhabdoid tumors are a spectrum of neoplasias composed of cells which show rhabdoid morphology but are devoid of skeletal muscle differentiation. These tumors are characterized by inactivation of the INI1/SMARCB1 gene and they have been described in virtually every anatomical site, including the central nervous system (CNS) and sinonasal tract. Rhabdoid tumor of the CNS was named atypical teratoid rhabdoid tumor (ATRT) and it mainly affects children under the age of 3 years with supra‐ or infra‐tentorial location.Herein we report the first case of ATRT infiltrating the nasal cavities and skull base in an adolescent. Due to its unusual location, differential diagnosis was challenging and included several other entities such as sinonasal carcinoma or meningioma. Awareness that ATRT may infiltrate the nasal tract and knowledge of its clinico‐pathological, immunohistochemical and biomolecular features are essential for its distinction from other rhabdoid tumors which more frequently involve this anatomical site and for appropriate therapeutic management.     

Rhabdoid papillary meningioma: A clinicopathologic case series study

World Health Organization (WHO) grade III meningiomas are subclassified on the basis of their architectural pattern into papillary and rhabdoid subtypes. Some meningiomas even combine papillary architecture with rhabdoid cytology. Additionally, they always show malignant histological features, follow an aggressive clinical course and tend to spread through the CSF after frequent local recurrence. We render the first series of rhabdoid papillary meningioma with review of the literature to further elucidate its biological behavior. From six patients (three male, three female), nine specimens of rhabdoid papillary meningioma were obtained between 1994 and 2010. Correlations of histologic parameters, immunohistochemical study, and clinical features were assessed. The mean age of patients was 44.7 years at their first operation. The mean postoperative follow‐up period was 63.2 months. Five patients experienced tumor recurrence, and one of them died from the disease after diffuse leptomeningeal dissemination. The mean time to first recurrence was 28 months. Only one patient was free of tumoral recurrence after an 8‐year follow‐up. Immunohistochemically, all tumors were positive for vimentin and epithelial membrane antigen. MIB‐1 labeling indices were higher following tumor recurrence. The present study expands the clinicopathologic horizon of rhabdoid papillary meningioma and suggests that it will behave aggressively based on its histology and concomitant features of atypia or malignancy or high MIB‐1 labeling indices. Close follow‐up and aggressive treatments of these tumors are warranted.     

Adult‐onset atypical teratoid/rhabdoid tumor featuring long spindle cells with nuclear palisading and perivascular pseudorosettes

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.     

Rhabdoid glioblastoma: Case report and literature review

Rhabdoid glioblastoma is a recently described entity in which a glioblastoma is associated with a rhabdoid component. Although rhabdoid glioblastoma has not appeared in the new World Health Organization classification of tumors of the CNS, it has a specific morphological feature and highly aggressive clinic process. Up to now, there have been six cases of rhabdoid glioblastoma reported in the literature. We report rhabdoid glioblastoma in the right front temporal lobe from a 31‐year‐old Chinese man. This tumor consisted of rhabdoid tumor cells with an eccentric nucleus and an eosinophilic cytoplasm. The tumor had an area appearing to be glioblastoma with microvascular proliferation and necrosis, and lacked a primitive neuroectodermal tumor component, and a mesenchymal component. Vimentin, epithelial membrane antigen, GFAP and integrase interactor (INI‐1) expression were found in the tumor cells. Genetic abnormalities which include monosomy or a deletion of chromosome 22 were not found in this tumor. After 3 months post‐surgery, the tumor was widespread in leptomeningia and the patient died. In conclusion, rhabdoid glioblastoma is a rare glioblastoma with poor prognosis; the differential diagnosis contained other rhabdoid tumors. This case will contribute to the profile of rhabdoid glioblastoma with typical morphology and immunophenotype, genetic and clinic features.     

Aggressive rhabdoid meningioma with osseous,papillary and chordoma‐like appearance

Meningiomas are the most common primary intracranial tumors. They are usually benign and slowly growing; however, they may show histologically malignant features categorizing them into grade II or III of World Health Organization (WHO) classification. Rhabdoid meningioma (RM) is an uncommon meningioma variant categorized as WHO grade III. The clinical course of RM is determined by local recurrences, invasion of adjacent brain and/or dura, widespread leptomeningeal dissemination, remote metastases and fatal clinical outcome. Herein we report a case with recurrent aggressive left occipital parasagittal region RM in which the patient initially declined radiation treatment. The tumor was resected four times in 5 years. Histopathological examination revealed a rhabdoid meningioma with metaplastic, papillary and chordoid differentiation. Six months after her fourth operation the patient died of progressive disease. RM is a rare subtype of malignant meningioma and the role of different adjuvant therapeutic options are still unknown. Clinical presentation, radiological features and pathologic findings of this uncommon tumor are discussed.     

Epstein‐Barr virus‐associated primary central nervous system cytotoxic T‐cell lymphoma

Primary central nervous system lymphoma (PCNSL) expressing T‐cell markers is rare, among which nasal‐type extranodal NK/T‐cell lymphoma is an extremely rare subtype associated with Epstein‐Barr virus (EBV) infection. Here we report the clinicopathologic features of a case of EBV‐associated PCNSL showing a cytotoxic T‐cell phenotype. The patient, a 73‐year‐old woman, presented with rapidly progressive mental deterioration. Brain MRI revealed multiple lesions with swelling in the bilateral cerebral hemispheres, which were hypointense on T1‐weighted images, hyperintense on T2‐weighted and fluid‐attenuated inversion recovery images, and slightly hyperintense on diffusion‐weighted images. Biopsy specimens from the temporal region showed many medium‐sized anaplastic lymphocytic cells with perivascular and angio‐invasive patterns in the cortex. Immunohistochemically, the cells were positive for CD3, CD8, T‐cell‐restricted intracellular antigen‐1 (TIA‐1), granzyme B and perforin, but negative for CD56 and CD20. In situ hybridization revealed EBV‐encoded RNAs in the tumor cell nuclei. A rearrangement study showed T‐cell receptor γ–chain gene rearrangement with a clonal appearance. The patient died 6 months after surgery, and a general autopsy revealed no lymphoma cells outside the brain. These cellular profiles are inconsistent with those of extranodal NK/T‐cell lymphoma, and have not been previously described. This case appears to represent an unusual CNS manifestation of EBV‐associated T‐cell lymphoma.     

Intracerebral rhabdoid and papillary meningioma with leptomeningeal spread and rapid clinical progression

OBJECTIVE AND IMPORTANCE: Rhabdoid meningioma (RM) is a relatively new, Grade III tumor entity according to the latest WHO classification. We report rhabdoid and partly papillary, highly anaplastic, intracerebral meningioma with diffuse leptomeningeal spread and distant SCF metastasis to the cervical cord. CLINICAL PRESENTATION: This 27-year-old female was admitted to the hospital with radiological findings suggestive of a primary brain tumor or a metastasis. After subtotal resection and during radiotherapy, follow-up MRI revealed recurrence, metastasis to meninges at the high cervical level, and diffuse basal leptomeningeal enhancement indicating infiltrating tumor. She died approximately 3 months after onset of symptoms. RESULTS: Histological examination revealed rhabdoid and papillary meningioma with high proliferation rate (80% of MIB1-positive cells), necrosis and extensive brain invasion. It was positive for vimentin and S-100 protein, showed focal epithelial membrane antigen expression and accumulation of intermediate filaments on ultrastructural examination. The recurrent tumor diffusely infiltrated leptomeninges and subarachnoid space. CONCLUSION: This is a rare example of mixed, rhabdoid and papillary variant of meningioma, located entirely within the brain parenchyma and accompanied by a fulminant clinical course. The combination of the histological anaplasia with the highest reported proliferation rate, and loss of the cohesion of neoplastic cells led to diffused infiltration of the leptomeninges and metastasis to the spinal cord.     

Synchronous meningioma and anaplastic large cell lymphoma

Synchronous primary brain tumors are exceedingly rare. When they occur, most cases are associated with metastatic disease. To the best of our knowledge, we report the first case of an atypical meningioma infiltrated by a T‐cell‐primary central nervous system lymphoma (PCNSL), specifically anaplastic large cell lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin based on theories in the current literature. A 65‐year‐old man with a history of near‐total resection of atypical meningioma presented with a complaint of progressive headaches. Imaging revealed recurrent tumor. Left frontal‐temporal craniotomy with near‐total tumor resection followed by radiation was performed. Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with tumor resection and partial anterior temporal lobectomy. Part of the specimen showed predominantly fibrotic neoplasm composed of nests and whorls of meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining. The remainder of the specimen consisted of densely cellular neoplasm centered in connective tissue, including areas involved by meningioma. This tumor was composed of moderately large lymphoid cells with large nuclei, prominent nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase‐1 (ALK‐1), CD15 or cytotoxic associated antigen TIA‐1. Smaller mature lymphocytes, chiefly T‐cells, were intermixed. The morphologic and immunohistochemical features were considered typical of anaplastic large T‐cell lymphoma. The pathogenesis of this association may have been due to radiation‐mediated breakdown of the blood–brain barrier with subsequent T‐cell infiltration and proliferation. We advocate aggressive resection and long‐term surveillance for individuals with metastasis, especially higher‐grade neoplasms that receive radiotherapy.     

Diffuse craniospinal metastases of intraventricular rhabdoid papillary meningioma with glial fibrillary acidic protein expression: A case report

Rhabdoid papillary meningioma is a recently described clinically aggressive variant of meningiomas with a high recurrence rate. Additionally, only one case of intraventricular rhabdoid meningioma has been reported so far. We present a case of a 50-year-old man who developed an intracranial tumor of the left lateral ventricle at the trigone, for which he underwent total tumor resection followed by gamma knife radiosurgery for recurrence of the tumor. The histological diagnosis was rhabdoid papillary meningioma. Five years after surgery, diffuse craniospinal leptomeningeal metastases developed and subtotal removal of the spinal tumor was performed. The spinal tumor was considered to have metastasized via cerebrospinal fluid (CSF) in view of its histological features that were identical to those of the primary tumor. Immunohistochemistry revealed the unusual cytoplasmic expression of glial fibrillary acidic protein (GFAP) of tumor cells. To our knowledge, this is the first reported case of diffuse craniospinal metastases of intraventricular rhabdoid papillary meningioma with GFAP expression and the second reported case of the rhabdoid subtype amongst intraventricular meningiomas.     

Immunohistochemistry of primary central nervous system malignant rhabdoid tumors: report of five cases and review of the literature

Malignant rhabdoid tumors (MRT) are characterized by a typical light microscopic morphology with uniformly round tumor cells, vacuolated cytoplasm with occasional round, hyaline intracytoplasmic, periodic acid-Schiff-positive inclusions, vesicular nuclei with prominent nucleoli and positive immunoreactivity for vimentin. The histogenesis of MRT is controversial. Five cases of primary central nervous system (CNS) rhabdoid tumors in children are presented. Immunohistochemical, light and electron microscopic features are compared with primary CNS malignant rhabdoid tumors reported in the literature. Expression of various neurofilaments in our cases of primary CNS rhabdoid tumors was prominent and we therefore favor a neural differentiation of extrarenal intracerebral rhabdoid tumors. Received: 13 March 1995 / Revised: 25 September 1995 / Revised, accepted: 21 November 1995     

Pediatric intracerebral histiocytic sarcoma with rhabdoid features: Case report and literature review

A 16‐year‐old boy presented with marked weight loss, weakness of the left extremities and dizziness of 2 months duration and vomiting for 2 days. Brain MRI showed an approximately 6.5 × 5.3 cm‐sized huge heterogeneous enhancing mass located in the corpus callosum, extending into the lateral ventricle. Open biopsy showed that the lesion consisted of lymphoplasmacytes and plump histiocytes with rhabdoid morphology, which were stained with S‐100 protein, CD68 (KP1) and negative for CD1a. Histiocytic tumor was initially diagnosed. Chemotherapy using methotrexate, 6‐mercaptopurine, vinblastine, interferon‐alpha and dexamethasone was performed. After 5 months, partial removal was done. Microscopically, plump and bizarre tumor cells as well as rhabdoid features were found. Occasional spindle cells and necrosis were also found. These cells were positive for CD163, CD68, lysozyme, CD4, INI‐1 and BRG1. BRAF V600E mutation was detected. The lesion was finally diagnosed as histiocytic sarcoma. Radiotherapy (6000 cGy in 30 fractions) was done. Both cerebral and extracerebral histiocytic sarcomas have long been diagnosed by unclarified criteria; its rarity as well as previously unclarified criteria can easily lead to a misinterpretation. Histiocytic sarcoma of the CNS is exceptionally rare in children, associated with an exceptionally poor prognosis. To date, only seven cases of pediatric cerebral histiocytic sarcomas have been reported. The present case is the first pediatric case showing BRAF V600E‐mutated intracerebral histiocytic sarcoma.     

Concurrent spinal nerve root schwannoma and meningioma mimicking single‐component schwannoma

We present a first case of concurrent tumors consisting of schwannoma and meningioma arising at the same spinal level in a patient without neurofibromatosis. A 49‐year‐old man without clinical evidence of neurofibromatosis presented with a 5‐month history of right neck pain. MRI demonstrated an extradural tumor involving the right‐sided C2 nerve root with a small intradural component. T1‐ and T2‐weighted and contrast‐enhanced MRI could not differentiate the intradural tumor as different from the extradural tumor. Total removal of the tumors was performed. No contiguity of the extradural tumor with the intradural tumor was seen. The intradural tumor attached strongly to the dura mater around the C2 nerve root exits. Intraoperative pathological diagnosis confirmed the extradural tumor as schwannoma and the intradural tumor as meningioma. We therefore thoroughly coagulated the dura mater adjacent to the intradural tumor and resected the dura mater around the nerve root exits together with the tumor. Pathological examination revealed that the resection edge of the extradural component consisted of a spinal nerve with thickened epineurium and was free of neoplastic cells. No schwannoma component was evident in the intradural tumor. No obvious transition thus existed between the extra‐ and intradural tumors. Distinguishing these tumors prior to surgery is critical for determining an optimal surgical plan, as schwannoma and meningioma require different surgical procedures. We therefore recommend a careful review of preoperative imaging with the possibility of concurrent tumors in mind.     

Atypical teratoid/ rhabdoid tumor,an immunohistochemical study of potential diagnostic and prognostic markers

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare tumor of the CNS mostly seen in infants and is often associated with a dismal outcome. Despite the heterogeneous morphology and/or immunoprofile, its diagnosis nowadays relies on the negative INI‐1/BAF47 nuclear immunostain in tumor cells. We aim to investigate a number of immunohistochemical antibodies as potential diagnostic and prognostic markers. All AT/RT cases in patients younger than 18 years of age were included. Demographics, clinical features and outcome were collected. Immunostains tested included SALL‐4, OCT3/4, CD99, FLI‐1, cyclin‐D1, β‐catenin, P53, P16, CDX2 and WT‐1. Nineteen cases (10 males) were identified at our center between 2004‐2013 with a median age of 24 months. Ten (52.6%) cases were supratentorial. Six (42.9%) cases showed metastasis at time of presentation. Chemotherapy was administered to 10 (62.5%) and radiotherapy to seven (43.8%). The median overall survival was 11 months. A single long‐term survival of 104 months was identified. Pathologically, most cases showed an admixture of rhabdoid cells and/or small cells and/or pale cells in variable proportions. Of all tested antibodies, only positivity for FLI‐1 was associated with improved survival (P = 0.0012), while positivity for cyclin‐D1 showed a trend toward improved survival (P = 0.0547). CDX2 was positive only in the single long‐term survival. Interestingly, two cases showed co‐expression of CD99 and FLI‐1, and some were positive for SALL‐4. In conclusion, FLI‐1 and cyclin‐D1 are potential prognostic markers associated with better outcome. Occasional AT/RT cases might co‐express CD99 and FLI‐1 as well as SALL‐4, a potential diagnostic pitfall with Ewing sarcoma/ primitive neuroectodermal tumors and germ cell tumors, respectively.     

Dedifferentiated chordoid meningioma with rhabdomyosarcomatous differentiation on the middle cranial fossa

A 46‐year‐old woman presented with headache and right hemiparesis. MRI demonstrated a mass in the left middle fossa. Total resection was performed. A histological examination of the tumor specimen showed several characteristic morphological features. A chordoid meningioma showing an epithelial‐like palisade arrangement was observed. An anaplastic short spindle cell tumor exhibiting a fascicular pattern was considered to be a rhabdomyosarcoma. After conventional radiotherapy, the tumor was well controlled without any neurological deficit for 20 months. When subsequent recurrences were observed, the patient was treated by surgery, stereotactic radiosurgery and chemotherapy. Thirty‐two months after the initial treatment, the patient died due to intracranial dissemination and an autopsy was performed. The histological examination of the recurrent and autopsy specimens showed a prominent sarcoma component. This case appears to be the first reported intracranial tumor diagnosed as a dedifferentiated chordoid meningioma with rhabdomyosarcomatous differentiation.     

Tumor teratoide/rabdoide atípico con diferenciación tipo ganglioglioma: reporte de caso

BackgroundAtypical teratoide/rhabdoid tumor is a very rare and aggressive disease that primarily presents in pediatric patients. To the best of our knowledge, the initial presentation of this type of tumor with ganglioglioma-like differentiation is rare in the literature.Case reportWe present the case of a 9-month-old patient with left facial paralysis. An MRI revealed a lesion at the left cerebellopontine angle. Complete macroscopic surgical resection was performed. Histopathology and immunohistochemistry testing revealed an atypical teratoid/rhabdoid tumor with ganglioglioma-like differentiation.ConclusionsThis case report presents an atypical teratoid/rhabdoid tumor with initial gangligioma-like differentiation. This study adds to the data in the literature and promotes the study of this type of histogenesis. It lays a foundation for encouraging further studies to determine whether changes should be made to existing management protocols and, at the same time, determine whether there would be any variation with regard to disease prognosis.     

A case of congenital supratentorial tumor: Atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor?

Two embryonal CNS tumors, atypical teratoid/rabdoid tumor (AT/RT) and primitive neuroectodermal tumor (PNET), may be confused with each other and misdiagnosed. Here we report an infant with a congenital supratentorial tumor, which was detected by fetal MRI at 37 weeks gestation. On routine histological examination, the tumor was composed mainly of small undifferentiated cells, among which many rhabdoid cells and occasional sickle‐shaped embracing cells were observed. No mesenchymal or epithelial areas were evident. Our impression was that the tumor was an atypical example of AT/RT. Immunohistochemically, almost all the tumor cells were strongly positive for vimentin. However, epithelial membrane antigen was notably negative, and most of the tumor cell nuclei were clearly positive for INI1. In addition, many tumor cells were positive for neurofilament protein. There were also occasional small areas containing many tumor cells positive for glial fibrillary acidic protein. Finally, a diagnosis of PNET, with a rhabdoid phenotype and expression of neuronal and glial markers, was made. In the present case, application of INI1 immunostaining was very helpful for distinguishing PNET from AT/RT.     

Atypical teratoid/rhabdoid tumor of the central nervous system: Clinico‐pathological study

Atypical teratoid/rhabdoid tumor (AT/RT) is a new entity among malignant pediatric brain tumors. This study was performed to investigate the clinicopathologic and cytogenetic features of the tumor. Five cases from a series of the brain tumors were studied. Clinical features of the patients were assessed with age, sex, location of the tumors, treatments and survival periods. Histopathologic features were analyzed by routine HE stain and immunohistochemical stains for epithelial membrane antigen, cytokeratin, vimentin, smooth muscle actin, desmin, GFAP, S‐100 protein, neurofilament protein, synaptophysin and α‐feto protein. Cytogenetic studies for karyotype analysis and fluorescent in situ hybridization were available in three cases. Mean age of patients was 5.6 years, and maximal survival periods were less than 13 months despite surgical and radiation therapy. The tumors were located in infratentorial and supratentorial areas. Histopathologically, the tumors were chiefly composed of rhabdoid cells, modified rhabdoid cells and undifferentiated small cells, mixed with epithelial, mesenchymal, and neural tumor‐like areas. These polyphenotypic features of the tumor cells were supported by diverse immunoreaction. Monosomy of chromosome 22 was demonstrated in two cases of the tumor. These results suggest that AT/RT may be a unique clinicopathologic entity, and histopathologic diagnosis of it should be made judiciously by differentiating other polymorphous tumors of the brain.     

Non-Dura Based Intaspinal Clear Cell Meningioma

A 34-year-old female patient was presented with leg and hip pain for 6 months as well as voiding difficulty for 1 year. Magnetic resonance imaging revealed a well-demarcated mass lesion at L2-3. The mass was hypo-intense on T1- and T2-weighted images with homogeneous gadolinium enhancement. Surgery was performed with the presumptive diagnosis of intradural extramedullary meningioma. Complete tumor removal was possible due to lack of dural adhesion of the tumor. Histologic diagnosis was clear cell meningioma, a rare and newly included World Health Organization classification of meningioma usually affecting younger patients. During postoperative 2 years, the patient has shown no evidence of recurrence. We report a rare case of cauda equina clear cell meningioma without any dural attachment.