Central Primitive Neuroectodermal Tumors Research Articles

Axillary lesion in a young adult ends up to a peculiar diagnosis: primitive neuro-ectodermal tumor (PNET) of ulnar nerve: a rare case report

Introduction and importance: Primitive neuro-ectodermal tumor (PNET) is a highly aggressive tumor composed of small round blue cells, mostly developing in children and young adults. Being a member of Ewing’s Sarcoma Family of Tumors (ESFT); it has been discussed in two subcategories of central and peripheral PNET. PNETs of peripheral nerves are very uncommon pathologic findings, as to the best of our knowledge only 12 well-documented cases have been yet reported. Case presentation: A 30-year-old male presented with progressive paresthesia of his right hand’s little finger and painless swelling of the right axilla. Magnetic resonance (MR) neurography demonstrated a heterogeneous, high-signal, round mass within the right axilla fossa in proximity to the medial aspect of brachial plexus branches. The clinical and radiological study failed to an accurate diagnosis, thus surgical resection of the tumor was done for tissue evaluation. Histopathologic study of the lesion revealed a neoplasm comprising sheets of small, round, blue cells (Hematoxylin and Eosin stain), which immunohistochemically consisted with the diagnosis of PNET. Clinical discussion: The differential diagnosis of axillary fossa masses, focusses on peripheral nerve tumors like Schwannoma and PNET. MR neurography aids in evaluation, but tissue diagnosis remains crucial. Treatment involves surgical resection, chemotherapy, and radiotherapy tailored to individual patients. Conclusion: Although pPNET is not apparently the first differential diagnosis coming to mind when encountering a rapidly growing mass in the axillary fossa with peripheral nerve origin, its highly malignant behavior, makes it crucial to be considered in the differential diagnoses.

18F-FDG PET/CT Imaging for Treatment Response Assessment of Cardiac Primitive Neuroectodermal Tumor.

Primitive neuroectodermal tumors (PNETs) are rare and aggressive members of the small round cell carcinoma family. Generally, PNETs are classified into two main groups: PNETs of the central nervous system and PNETs of the peripheral nervous system. Herein, we report the therapy response assessment of a rare case of isolated cardiac PNET using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging. Given that physiological cardiac FDG uptake is typically observed, assessing FDG avid lesions in the myocardium presents a challenge for FDG PET/CT. This case holds significance because of the rarity of the disease and the challenging nature of the site for FDG PET/CT imaging.

C19MC amplification and expression of Lin28A and Olig2 in the classification of embryonal tumors of the central nervous system: A 14-year retrospective study from a tertiary care center.

CNS embryonal tumors (CET) other than medulloblastomas (MB) and atypical teratoid/rhabdoid tumors (AT/RTs), previously designated as 'central nervous system primitive neuroectodermal tumors' ('CNS PNETs'), are a heterogenous subset of tumors with poorly defined diagnostic criteria. Other than the subset of embryonal tumor with multilayered rosettes (ETMR) defined by C19MC amplification, most CETs are diagnosed by exclusion of other molecularly defined entities and histological mimics including MB, AT/RTs, and high-grade gliomas, and termed as CET, not otherwise specified (NOS) in the 2016 WHO classification. To reclassify 'CNS PNETs' as per WHO 2016, and estimate the true proportion of CET, NOS in a tertiary healthcare setting, and to evaluate the diagnostic utility of C19MC amplification, Lin28A and Olig2 expression in the subclassification of CETs. Previously diagnosed cases of 'CNS PNETs' (2002-2016) were first evaluated by immunohistochemistry (IHC) for MIC2, RelaA, L1CAM, IDH1R132H, H3K27M, H3G34R, H3G34V, INI1, and BRG1 proteins and by fluorescence in-situ hybridization (FISH) for EWSR1 translocation to exclude histological mimics. The selected CETs (case cohort) and 79 histological mimics (comparison cohort) comprising of MB, AT/RT, pineal parenchymal tumors, Ewing sarcoma, esthesioneuroblastoma, intraocular medulloepithelioma, and H3G34R mutant high-grade glioma were subject to IHC for Olig2 and Lin28A, and FISH for C19MC amplification. Twenty-two cases of 'CNS PNETs' were retrieved, all of which were negative for the first panel of markers and showed retained INI-1/BRG1 expression. Three of them (3/22, 13.6%) showed C19MC amplification (ETMR, C19MC-altered) with ETMR histology, Lin28A positivity, and Olig2 negativity. Among the remaining 19 CETs, one showed medulloepithelioma histology (Medulloepithelioma, NOS) and remaining were non-descript small round cell tumors (CET, NOS), all negative for Lin28A. Olig2 was positive in only 3 CETs (13.6%), all being CET, NOS. All tumors in the comparison cohort were negative for C19MC amplification, Lin28A and Olig2 except for 27% of ATRTs that were Lin28A positive. ETMR, C19MC-altered constitute less than 14% of CETs, with majority remaining uncharacterized as CET, NOS. Lin28A is 100% sensitive for the detection of C19MC amplification; however, its specificity is limited by its expression in ATRTs. Olig2 expression is seen only in a small subset of CET, NOS and is of limited diagnostic utility.

Primary sellar neuroblastoma pretending pituitary adenoma: A new case report and review of literature

Introduction Sellar neuroblastoma is hugely rare, only ten cases having been described in the literature. Primary intracranial neuroblastoma mainly occurs in children and arises in the supratentorial parenchyma. These tumors belong to embryonal central nervous system primitive neuroectodermal tumors (PNET). Magnetic resonance imaging (MRI) appearance is non-specific. Management is primary based on surgical resection. Diagnosis relied on histopathological examination. Through this case, it seems relevant to consider neuroblastoma face to MRI atypical aspects of pituitary adenoma. Clinical presentation We report the case of a 58-year-old-man with a 3-year old history of a rapidly growing sellar lesion diagnosed preoperatively as a pituitary non-functioning adenoma. He developed progressive bitemporal hemianopsia and visual field loss. Endocrinal investigations disclosed a functional hyperprolactinemia due to pituitary stalk effect. MRI displayed a sellar and supra-seller mass extension compressing the optic chiasm, with intra-sphenoidal sinus development, skull bone lysis and bilateral cavernous sinus invasion. He underwent near complete surgical removal through an endoscopic transseptal transsphenoidal approach. Histological and immunohistochemical studies yielded a diagnosis of neuroblastoma. Postoperatively his visual deficit improved. Neither endrocinal disturbance nor rhinorrhea occurred. He underwent fractioned radiotherapy a few weeks later. Discussion Primary sellar neuroblastoma could be easily misdiagnosed as pituitary adenoma. Unusual MRI features could lead to consider this diagnosis. The optimal management seems to be surgical resection followed by radiation therapy. Some authors suggested adjuvant chemotherapy in patients with subtotal resection or recurrence however this is no consensual.

Clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor and prognostic analysis

To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis. A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018. The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade. Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.

An unusual biconvex epidural lesion: acutely presenting extraosseous intracranial Ewing\u2019s sarcoma

BackgroundEwing’s sarcoma family of tumors consists of small round cell neoplasms, inclusive of primitive neuroectodermal tumor (PNET), Askin’s tumor, and PNET of the bone. Extraosseous Ewing’s sarcoma occurs commonly at bones of lower extremities and paravertebral region of the spine. It rarely presents as a primary intracranial lesion. When intracranial, it can be misdiagnosed as central PNET (e.g., medulloblastoma, pinealoblastoma, or supratentorial PNET), other intracranial lesions, or even as an epidural hematoma.Case presentationWe report the case of a 20-year-old patient who presented to the emergency department with complaints of drowsiness, headache, and fever for 1 day. On initial computed tomography (CT) scan of the brain, a right temporal biconvex epidural lesion involving squamous-temporal bone with periosteal reaction was noted.The patient underwent urgent craniotomy, and a tumor was found and excised. Biopsy report confirmed Ewing’s sarcoma.ConclusionEwing’s sarcoma is a rare intracranial malignancy with only a few cases reported in literature. In a young patient with a biconvex epidural lesion, in the absence of trauma or ongoing infection, the possibility of Ewing’s sarcoma should be considered as well.

Survival and prognostic factors analysis of primitive neuroectodermal tumor

Objective: To investigate the clinical features and prognosis of primitive neuroectodermal tumor (PNET). Methods: The clinical data of 99 patients with PNET from February 1, 1998 to February 1, 2017 were retrospectively analyzed. Univariate analysis was performed using Kaplan-Meier and Log rank test. Multiviate Cox regression was applied to analyzed independent prognostic factor for patient survival. Results: Among the 99 patients, 81 were peripheral PNET(pPNET) and 18 were central PNET (cPNET) . Biopsy was performed exclusively in 16 cases, with R0 resection in 61 cases, with R1 resection in 4 cases, and with R2 resection in 18 cases. Twelve patients underwent surgery only, nine had chemotherapy only, and one received radiotherapy only. There were 72 patients who had combined treatment including chemotherapy, and 48 patients had combined therapy including radiotherapy. The one-year, three-year and five-year overall survival(OS) rates of the 99 PNET patients were 79.2%, 63.9% and 56.1% respectively, and median OS time was 14.0 months. The one-year, three-year and five-year progression free survival (PFS) rates of these patients were 42.7%, 25.7% and 19.8% respectively, and median PFS time was 8.0 months. The univariate analysis revealed that lymph node metastasis, surgical resection, numbers of cycles of chemotherapy and radiotherapy dose were the main factors affecting the OS (all P<0.05). Gender, age, lymph node metastasis, staging, and chemotherapy cycles were related to PFS in PNET patients (P<0.05). Multivariate analysis showed that the degree of surgical resection, chemotherapy cycle, and radiotherapy dosage were independent influencing factors of OS in PNET patients (risk ratio=1.856, 0.398, and 0.408, respectively, all P<0.05), and gender was an independent factor influencing PFS in PNET patients (risk ratio=0.494, P<0.05). Conclusions: Comprehensive therapy is the main therapy for PNET patients. The surgical resection, cycles of chemotherapy and radiotherapy dosage are independent prognostic factors for patient's OS.

Abstract 2264: RNA sequencing based analysis of transposon-induced tumors reveals novel insights into cancer pathogenesis and progression

Abstract Current challenges in oncology include the discovery of drivers suitable for targeting using small molecules or antibodies and predictive animal models. We're addressing these challenges in several ways. We have developed mouse models using the Sleeping Beauty (SB) transposon system to perform unbiased, forward genetic screens to define strong candidate cancer genes. Further, our studies and others have utilized transposon mutagenesis to derive cancers from all three germ layers including carcinomas, sarcomas, neuroectodermal tumors, and hematopoietic malignancies. We hypothesize that data from these screens will help to identify genetic drivers of human cancer that are altered at the gene copy number or epigenetic levels. Our T2/Onc SB transposons create fusions with endogenous gene transcripts and RNA sequencing (RNA-seq) reveals the genes targeted in the tumor. From these results, correlations can be drawn between the alteration of specific genes and changes in tumor gene expression patterns. Thus, the goals of our recent research have been to discover novel associations between SB-induced tumor phenotypes and specific driver gene alterations (i.e. the tumor genotype). Moreover, RNA-seq has also revealed tumor molecular subtypes, in many cases with correlating transposon insertion mutations. Several examples will be described: mammary tumors, osteosarcoma (OS), medulloblastoma and central nervous system primitive neuro-ectodermal tumors. In each case, RNA-seq has revealed novel genotype-phenotype correlations including drivers of high cell cycle activity, metastasis, white blood cell exclusion from the tumor, SHH pathway activation, and hormone receptor signaling. These models provide a source of genetically heterogenous tumors with the same initiating mutation useful for identifying cooperating pathways and drivers of specific tumor phenotypes. Secondly, we are using SB transposon mutagenesis to understand the genetic basis of chemotherapy resistance in cancer including OS. In our OS model, SB mutagenesis is an ongoing process due to the constitutive expression of SB transposase, which permits the continued mobilization of transposons. We hypothesize that in vivo treatment with chemotherapy agents will allow tumor cells that contain transposon mutations in chemoresistance genes to persist. Preliminary studies with primary tumor cells derived from SB-enhanced OS tumors demonstrate resistance to combination chemotherapy treatment in vivo. Further analysis to identify candidate chemotherapy resistance genes are currently underway. Citation Format: Emily T. Camilleri, Pauli J. Beckmann, Jon D. Larson, Morito Kurata, Jingmin Shu, Emily Pope, Wendy A. Hudson, Nuri A. Temiz, Susan K. Rathe, Rebecca S. LaRue, Anne E. Sarver, Milcah C. Scott, Jyotika Varshney, Jaime F. Modiano, Branden S. Moriarity, Aaron L. Sarver, Somasekar Seshagiri, David A. Largaespada. RNA sequencing based analysis of transposon-induced tumors reveals novel insights into cancer pathogenesis and progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2264.

Two Tumors in 1: What Should be the Therapeutic Target? Pediatric Germ Cell Tumor With Somatic Malignant Transformation.

Germ cell tumors with somatic malignant transformation (GCT with SMT) are rare in children and poorly described. Data are missing to determine if therapies should target the GCT, the SMT compound, or both simultaneously. A retrospective national study was conducted in the Société Française des cancers de l'Enfant (SFCE) Centers. Medical records from patients aged 0 to 18 years diagnosed with GCT with SMT between 2000 and 2015 were analyzed. Any stages and primary sites were considered as well as synchronous and metachronous cases. Fifteen patients were identified. Thirteen patients had synchronous GCT with SMT. In the latter cases, primaries were ovary (5), mediastinum (3), pineal gland (3), sacrococcyx (1), and parametrium (1). SMT histologies were central primitive neuroectodermal tumor (5), embryonal rhabdomyosarcomas (3) or thyroid papillary adenocarcinoma, leukemia, poorly differentiated carcinoma, mixed sarcomas, and miscellaneous histology (1 case each). Chemotherapy was targeted against the GCT (3), the SMT (6), or both components (3). The last patient received surgery exclusively. Partial or complete response to chemotherapy was observed in 5/10 assessable cases: 2/3 patients treated with GCT-dedicated chemotherapy, 3/6 patients treated with SMT-dedicated therapy, and 0/1 treated with combined therapy. In addition, 2 patients with mediastinal GCT primary had metachronous SMT, with acute myeloid leukemia and thyroid papillary adenocarcinoma, 8 months and 8 years, respectively, after the diagnoses of GCT. Two patients (1 synchronous and 1 metachronous) were cured with surgery exclusively. At the end of follow-up, 6 patients died of their disease including all 4 with postsurgical macroscopic residue. GCT with SMT constitutes a very rare entity in children and adolescents. Surgical removal of the tumor is the cornerstone of the treatment and might be sufficient in selected cases. In the remaining cases, the best management is still unknown and should take into account both components and their respective chemosensitivity. Long-term surveillance is advised for patient with unresected teratoma as late transformation can occur.

Fine-Needle Aspiration of Metastatic Central Type Primitive Neuroectodermal Tumors in Patients with a Germ Cell Tumor

Objective: Central type primitive neuroectodermal tumors (PNET) are some of the most frequent somatic type tumors derived from germ cell tumors and can metastasize. We studied the cytomorphological features of metastatic central type PNET by fine-needle aspiration (FNA). Materials and Methods: A computerized search of our laboratory information system was performed for the 9-year period from 2005 through 2014 to identify all cytology cases in which a diagnosis of metastatic central type PNET had been rendered. A total of 5 FNA cases were collected and direct smears were reexamined. Results: All patients had a history of testicular or ovarian germ cell tumors. Direct smears displayed single and clusters of atypical round to oval cells with scant to moderate cytoplasm. Abundant naked nuclei were present in Diff-Quik-stained smears with mild to marked crushed artifacts and nuclear molding. Tumor cells showed fine granular chromatin, nuclear size variation (up to 1:3), and one or more small nucleoli. Pseudorosettes (Homer Wright-like rosette) were noticed in 1 case. Tumor cells were commonly positive for synaptophysin. Conclusion: Metastatic PNET can be reliably diagnosed by FNA. Differential diagnoses include Ewing sarcoma/peripheral PNET, alveolar rhabdomyosarcoma, neuroblastoma, etc. It is important to be familiar with this entity to avoid diagnostic pitfalls.

Primary extraskeletal peripheral primitive neuroectodermal tumor of subcutaneous tissue neck in a young adult: A rare case report

Primitive neuroectodermal tumors (PNETs) are poorly differentiated small round cell neoplasms which primarily affect childhood age and very rarely seen in adults. Peripheral PNET (pPNET) cases are very rare compared to central PNET, and most of them originate from neural crest cells located outside the central nervous system. We report a case of large extraosseous pPNET arising from subcutaneous tissue of left side neck in a young male patient. Despite aggressive inherent nature of histology, structural complexity of neck area and poor predictors like tumor size >6 cm, extraosseous nature, this case advocate that complete resolution is possible with aggressive multimodal treatment including surgery, radiation therapy, and chemotherapy. Other major concerns in such cases of pPNET are difficulty in diagnosis due to low incidence, unpredictable site involvement, histological similarity with other round cell tumors and lack of established treatment guidelines.

Current outcome predictors in childhood primitive neuroectodermal tumors

Central nervous system primitive neuroectodermal tumors (PNET) including cerebellar PNET (medulloblastoma, PNET/MB) are the most common malignant brain tumors in childhood. Because of the high risk of leptomeningeal dissemination, standard postoperative treatment for PNET includes craniospinal radiotherapy and chemotherapy. Such treatment causes long-term morbidity including endocrine and growth disturbances, as well as neurocognitive dysfunction, which is particularly severe in young children. Over the last years, neurotrophin receptor TrkC, neuregulin receptor ErbB2 and oncogene MYC have been identified as biological prognostic factors in PNET/MB. High TrkC mRNA expression, low ErbB2 protein expression and low MYC mRNA expression are powerful independent predictors of favorable clinical outcome in PNET/MB. Upon validation in ongoing prospective biological studies, these biological factors may define risk groups and help direct therapy decisions for children with PNET/MB. In PNET with favorable biological factors and no evidence of leptomeningeal tumor dissemination, therapy with reduced craniospinal radiation might retain the efficacy but reduce the toxicity and therefore improve the quality of life for the survivors. (J Pediatr Neurol 2003; 1(2): 75–82).

Cytomorphologic and clinicoradiologic analysis of primary nonhematologic central nervous system tumors with positive cerebrospinal fluid.

Positive cerebrospinal fluid (CSF) cytology typically indicates leptomeningeal dissemination of metastatic, secondary, or rarely, primary central nervous system (CNS) tumors. To the authors' knowledge, large-scale studies on clinicocytologic features of various primary CNS tumors in CSF are lacking. The authors performed a retrospective cytomorphologic study on 127 positive CSF specimens from 87 patients with a history of primary nonhematologic CNS tumors. Pertinent clinical, radiological, and histologic findings were reviewed. Pediatric tumors accounted for the majority (82.6%) of the primary CNS tumors with positive CSF cytology. The most common radiological finding of neuraxial dissemination was diffuse leptomeningeal enhancement. Greater than 95% of the cases with positive CSF cytology were high-grade or malignant tumors. The most common tumor type was central primitive neuroectodermal tumors (47.2%). Overall, the frequency of initial metastasis was found to be lowest in central primitive neuroectodermal tumors and retinoblastomas (approximately one-third). They also had the longest latency (1.5-2 years) in cases without initial metastasis. The majority of metastatic tumors in CSF demonstrated distinct cytomorphology reminiscent of the histologic features of the primary tumor, such as prominent nucleoli, cell wrapping, and apoptosis in large cell/anaplastic medulloblastomas; rhabdoid morphology and cytoplasmic inclusions in atypical teratoid/rhabdoid tumors; large clusters of cells with scant cytoplasm and nuclear molding in retinoblastomas; nuclear pleomorphism and hyperchromasia in high-grade infiltrating astrocytomas; and small clusters/rosettes of epithelioid cells in ependymomas. The results of the current study provide useful clinicoradiological information and cytomorphologic findings for both common and rare primary CNS tumors that cytopathologists might encounter on CSF examination.

MS-17 * PRIMARY LEPTOMENINGEAL PRIMITIVE NEUROECTODERMAL TUMOR

BACKGROUND: Isolated primary leptomeningeal primitive neuroectodermal tumor (PNET) without intraparenchymal lesion is very rare and to-date few case reports have been published. We report a rare case of leptomeningeal PNET and highlight its neuroimaging features, outcome and literature review. DESIGN AND METHODS: A medline search was conducted for queries including “Children”, “PNET”, leptomeningeal involvement”. Relevant papers were selected for review. CASE REPORT: A 5-year-old female presented with 4-month history of continuous vomiting and repeated headache. CT scan demonstrated communicating hydrocephalus. External ventricular drain was place to relieve the intracranial pressure. An MRI of the brain and the spine showed diffuse leptomeningeal infiltration of the brain and the spinal cord with contrast enhancement. Lumbar cerebrospinal fluid analysis revealed elevated protein but no malignant cells. Pathology of the leptomeningeal biopsywas consistent with neuroepithelial neoplasm. Immunohistochemical stains revealed tumor cells strongly positive for synaptophysin and CD56, retained INI-1, but negative for CD99. Cytogenetical analysis revealed absence of EWS translocation and a diagnosis of primary leptomeningeal PNET was established. Patient received radiation therapy with 36 Gy to the craniospinal axis, concomitantly with vincristine and carboplatin . Follow-up brain and spine MRI showed near complete resolution of the leptomeningeal disease. Family opted not to pursue any therapy and she remains alive with residual disease 8 months since diagnosis. DISCUSSION: Leptomeningeal PNET carries poor prognosis with most patients succumbing to their disease. There are seven case reports in the literature with dismal outcome with survival range from 2 weeks to thirteen months post diagnosis .Rarity of this clinical entity had hindered profiling therapeutic guidelines. Prospective studies are needed to understand if the elusive molecular biology of this rare disease differs from other central PNET. This could help in strategizing optimal therapy and provide a meaningful improvement in the survival of these children.

Antiangiogenic treatment of pediatric CNS tumors in Hungary with the Kieran schedule

In Hungary a new oral antiangiogenic treatment was introduced in cases of primary chemoresistant or recurrent pediatric CNS tumors, called Kieran schedule. The early results of this treatment were analyzed. From 2010 at Semmelweis University on individual decisions a daily combined per oral treatment was introduced in pediatric patients with recurrent or progressive CNS tumor (Kieran schedule: thalidomid, celecoxib, etoposid and cyclophosphamid). Efficacy of therapy was analyzed in terms of demographic data, histology, side effects and tolerability in a retrospective manner. From 2010 through 2013, twenty patients were treated with Kieran schedule (medulloblastoma: 3, ependymoma: 5, anaplastic astrocytoma: 2, GBM: 4, plexus choroideus carcinoma: 1, central primitive neuroectodermal tumor: 1, optic glioma: 2, brainstem tumor: 2). Median treatment time and median progression-free survival were 0.60 and 0.61 years, respectively. Based on the preliminary analysis of a limited cohort of patients, the therapy was efficient in those cases of medulloblastoma, ependymoma, high-grade and optic gliomas, where the expected survival time was more than 3 months at start of treatment. Side effects were slight myelosuppresion in terms of previous therapy, 16% transient ischemic attack (TIA)-like episodes. During therapy patients could live their everyday life. Kieran schedule was well-tolerable and efficient with good quality of life in certain cases of pediatric CNS tumors.

Childhood pheochromocytoma in a survivor of central primitive neuroectodermal tumor

Pheochromocytoma and central nervous system primitive neuroectodermal tumor are both neural crest-derived tumors. The former is usually benign and develops mainly in adulthood and the latter brain tumor mainly occurs in childhood and has a poor prognosis. We report a case of a 15-year-old boy who developed pheochromocytoma after more than 10 years of complete remission of central primitive neuroectodermal tumor. Thus far, there have been no reports of childhood cancer survivors who developed pheochromocytoma. This quite rare occurrence of two tumors in a single patient may imply some unidentified linkage or common genetic background.

Patterns of care study of adult medulloblastoma.

2086 Background: Medulloblastoma (MB) accounts for less than 1% of adult intracranial tumours. While pediatric MB has been investigated in several randomized studies, the evidence in adults is limited to case reports and retrospective series, with no accepted standard of care. The Australian Cooperative Trials Group for Neuro-Oncology (COGNO) sought to determine the range and consistency of clinicians’ approaches to management as a basis for future trials. Methods: We aimed to identify current treatment strategies for adult MB through an international electronic survey launched at the 2012 meeting of the Society of Neuro-Oncology and by email invitation. Clinicians who had treated at least 1 adult patient with MB, central primitive neuroectodermal tumor (cPNET), or pinealoblastoma in the preceding year were asked about their most recent patient and asked to discuss their approach to management of a typical clinical scenario. Results: Between Nov 2012 and Jan 2013, 45 clinicians (11 medical oncologists, 7 radiation oncologists, 5 pediatric oncologists, and 22 others) from Australia (n = 24), USA (n = 3), Europe (n = 4) and other countries (n = 14) completed the survey. Responding clinicians had treated 54 cases in the past 12 months. The commonest histological type was MB (64%), followed by cPNET (20%). Most patients were male (68%), and most had high-risk disease (65%). 56% had complete surgical resection and 32% had molecular testing. Radiotherapy was predominantly craniospinal (92%) and mostly post-resection (80%). Combination chemotherapy was more common than single agent. Vincristine, cisplatin, cyclophosphamide was the most common protocol (43%). Others included carboplatin, etoposide, ifosfamide (29%), vincristine, lomustine, cisplatin (19%), vincristine, lomustine, prednisone (5%). Further details will be presented at the 2013 ASCO Annual Meeting. Conclusions: Our study has shown substantial international variation in the treatment of adult MB, most pronounced in the choice of chemotherapeutic agents, highlighting the need for further collaborative research to guide evidence-based treatment strategies.

Embryonal Tumor With Abundant Neuropil And True Rosettes With Melanotic (Retinal) Differentiation

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare variant of central nervous system primitive neuroectodermal tumor occurring exclusively in the pediatric population. We report a unique case of a 6-month male child presenting with a large intraventricular lesion. Histological examination revealed a tumor composed of primitive neuroectodermal cells in dense aggregates, interspersed by hypocellular areas containing small round cells widely dispersed in neuropil-like material. Few ependymal and occasional ependymoblastic rosettes were appreciated. Focal melanotic neuroepithelium recapitulating retinal differentiation was also seen. Documentation of such cases may expand the neuroectodermal differentiation spectrum of ETANTR.

A supratentorial primitive neuroectodermal tumor presenting with intracranial hemorrhage in a 42-year-old man: a case report and review of the literature

IntroductionWe report on a very rare case of a supratentorial primitive neuroectodermal tumor in an adult, which presented with intracerebral hemorrhage, and review the relevant medical literature.Case presentationA 42-year-old Caucasian man complained of a sudden headache and nausea-vomiting. The patient rapidly deteriorated to coma. An emergency computed tomography scan showed an extensive intraparenchymal hemorrhage that caused significant mass effect and tonsilar herniation. During surgery, an increased intracranial pressure was recorded and extensive bilateral decompressive craniectomies were performed. A cherry-like intraparenchymal lesion was found in his right frontal lobe and resected. The patient died in the intensive care unit after approximately 48 hours. The resected lesion was identified as a central nervous system primitive neuroectodermal tumor.ConclusionSupratentorial primitive neuroectodermal tumors must be considered in the differential diagnosis of space-occupying lesions in adults. Spontaneous supratentorial hemorrhage due to primitive neuroectodermal tumors is an extremely rare but potentially lethal event.

What’s in a name?

Intracranial peripheral primitive neuroectodermal tumors (P-PNET) are extremely rare. They can be easily misdiagnosed as central nervous system primitive neuroectodermal tumors (CNS-PNET) or meningiomas. Little is known about the optimal treatment and prognosis of these tumors. We evaluated the treatment and outcome of 17 patients with intracranial, nonmetastatic, genetically confirmed P-PNET. Three patients were treated at our institutions. Thirteen other cases providing sufficient treatment and follow-up information were extracted from the literature. The median age at diagnosis was 17 years. All patients underwent initial surgery. Complete resection was achieved in 9 of the 17 cases (53 %). Combined adjuvant treatment consisting of radiotherapy (focal, n = 10; craniospinal, n = 1) and chemotherapy was administered to 11 of the 17 patients (59 %). The median follow-up time was 1.4 years. In 8 of the 17 patients (47 %), the disease progressed; 4 of the 17 patients (24 %) died. The 2-year progression-free and overall survival rates were 64 % and 76 %, respectively. The differential diagnosis for intracranial, meningeal-based, small, round-cell tumors should include P-PNET. It is highly probable that complete resection has a positive impact on survival--as previously reported for extracranial P-PNET--but this cannot be shown by our data. Intensive adjuvant treatment consisting of radiotherapy and chemotherapy seems to be essential. A statistically grounded recommendation for the appropriate target volume and radiation dose is not yet possible. However, in most case reports of primary intracranial P-PNET published to date, patients were treated with focal irradiation. The optimal chemotherapy regimen has yet to be established, with both the Ewing tumor and CNS-PNET protocols being promising candidates for effective treatment.