bluuebunny/crossref_metadata_2025_split huggingface dataset:
RARE-19. PEDIATRIC HIGH GRADE GLIOMA WITH DNA REPAIR PATHWAY ABERRATIONS, CLINICAL CHARACTERISTICS AND OUTCOME
Authors: Baig Muhammad , McCall David , Moss Tyler , Sandberg David , Fuller Gregory , McGovern Susan , Paulino Arnold , Najjar Amer , Chandra Joya , Khatua Soumen , Zaky Wafik 
Published: December 2020

Abstract
DNA mismatch repair machinery is an integral part of the human genome and its defect has been involved in tumorigenesis and treatment resistance. Heterozygous monoallelic germline loss of function in MLH-1, MSH-2, MSH-6 or PMS-2 is involved in Lynch syndrome, whereas biallelic mutations cause constitutional mismatch repair deficiency (CMMRD) which is associated with hematologic malignancies and glioblastoma. We report here the clinical characterization and molecular analyses of 7 patients who presented with gliomas and MMR machinery aberrations. Two patients had a clinical diagnosis of NF-1 with dermatologic stigmata, of whom one patient has CMMRD and the other has Lynch syndrome. Two patients had a known family history of Lynch syndrome upon their diagnosis of glioma. Three patients with high-grade glioma and negative family history, 2 had germline mutations in MMR genes, and one had numerous mutations including MMR genes with microsatellite instability. Patients were initially treated with chemotherapy and radiation for high-grade gliomas (HGG); 5/7 had progression. Median time to progression was 12 months (range: 5–52), and median time from progression to death was 7 months (range: 2–25). One patient had low-grade glioma initially but progressed to HGG and is currently on therapy. Another patient treated with temozolomide and radiation is currently receiving maintenance therapy without any disease recurrence. Although the literature data on brain tumors with MMR deficiency is limited, these consistently show that MMRD-associated gliomas are treatment-resistant and have a dismal outcome. Collaborative efforts are needed to better understand this subgroup of pediatric HGG and to define optimal treatment strategy.
RARE-26. RETROSPECTIVE ANALYSIS OF PEDIATRIC CHOROID PLEXUS TUMORS
Authors: Nakano Yoshiko , Kawamura Atsufumi , Watanabe Yuko , Saito Ryuta , Kanemori Masayuki , Kiyotani Chikako , Yamasaki Fumiyuki , Nakagawa Naoki , Gomi Akira , Nakamura Taishi , Kunihiro Noritsugu , Okada Keiko , Sakamoto Hiroaki , Kitahara Mai , Hibiya Yuko , Nobusawa Sumihito , Ichimura Koichi 
Published: December 2020

Abstract

BACKGROUND
Choroid plexus tumors (CPT) include choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Because of their rarity, limited data are available on the current status of treatment and outcomes for pediatric CPTs.

METHOD
We retrospectively reviewed clinical information on patients with CPT patients aged between 0 and 30 years at diagnosis and were treated in 8 institutions in Japan.

RESULTS
Of forty-two cases initially diagnosed as CPT, 18 cases were reviewed by central pathologists. As a result, the diagnosis of CPC or aCPP in five cases were changed to other tumors including AT/RT and astroblastoma. The remaining 37 cases were subjected to analysis. Median age at diagnosis was two years (0 to 25) and the mean follow-up period was seven years. All 26 patients with CPP (n=20) or aCPP (n=6) underwent gross-total resection without adjuvant therapy. Of them 24 patients are alive without recurrence. Four patients of patients with CPC (n=11) died of cancer. Five patients including three patients experienced local relapse, achieved complete remission after resection of tumor plus chemoradiotherapy. All three patients with dissemination of CPC at diagnosis or relapse died of the disease. At least three patients were diagnosed with Li-Fraumeni syndrome: one died of medulloblastoma and one patient developed osteosarcoma.

CONCLUSION
Compared with the excellent prognosis of CPP, the survival rates for CPC, especially disseminated CPC are unsatisfactory. Our results also underline the importance of considering genetic testing of TP53 for patients with CPC.
RARE-27. DOUBLE MUTATIONS: DIFFERENT GERMLINE AND TUMOR MUTATIONS LEAD TO POOR OUTCOMES
Authors: Hemenway Molly , Nellan Anan , Foreman Nicholas , Suttman Alexandra , Schneider Kami 
Published: December 2020

Abstract

BACKGROUND
As genetic testing for both germline and tumor mutations has increased in completeness, complexity, and availability, more mutations and their impact on patient outcomes have been identified.

METHODS
A retrospective review of pediatric patients who have identified germline mutations and a different tumor mutation was conducted. Data collected included demographics, tumor type, germline mutation status, tumor mutation status, relapse status, and patient outcome.

RESULTS
Six patients aged 8–13 years old (median age 10 years) were identified for analysis. Four patients had pilocytic astrocytoma and two had pilomyxoid astrocytoma. One of the patients with pilocytic astrocytoma also had MPNST diagnosed very early at age 9. The combination of germline/tumor mutations is as follows: Neurofibromatosis Type I (NF1)/BRAF v600e, NF1, CHEK2/MYB-QKI, NF1, Klinefelter, ATM, MUTYH, GPC3/BRAF-KIAA fusion, NF1/BRAF-KIAA (2 patients), and Marfan’s/BRAF-KIAA. The number of relapses per patient following initial diagnosis range from 3–7 with an average of 3.3. Four of the patients are alive and on therapy, which two are deceased. The two deceased patients both had NF1/BRAF-KIAA fusions and pilocytic astrocytomas.

CONCLUSIONS
Patients with differing and compounded germline and tumor molecular genetic mutations have worse outcomes. These patients have more relapses and death when compared to those patients with one mutation, either germline or tumor. Broad molecular testing and germline testing for mutations is crucial in determining patient risk for poor outcomes.
RARE-30. A RARE CASE OF PRIMARY EWING’S SARCOMA OF THE CERVICAL SPINE
Authors: Kalra Amandeep , Neil Jayson , Mann Sarah , Giglio Pierre 
Published: December 2020

Abstract
Ewing sarcoma family of tumors predominantly affect the pediatric population in the long bones of the extremities or the pelvis, and only 8% of cases arise within the spine. Primary Ewing’s sarcoma of the cervical spine is extremely rare and less than 30 cases have been reported in the literature thus far. Here we present a case of primary Ewing’s sarcoma of the cervical spine in a 28-year-old female who presented with a three-month history of neck pain and right arm radiculopathy. MRI revealed a homogeneously contrast enhancing, eccentric mass with dural tail at C2-C7. After undergoing a hemilaminectomy, histopathology confirmed extraosseous Ewing’s sarcoma with CD99 positivity. A comprehensive systemic and neuraxis work-up ruled out overt metastasis. We extrapolated data from children’s cooperative group studies and IESS-II clinical trial to formulate a three phase treatment protocol as described below. To date, patient is in remission with no evidence of any residual disease in the cervical spine. In conclusion, although Primary Ewing’s sarcoma of the cervical spine is extremely rare it should be considered a differential diagnosis in patients with neck pain and a spinal mass under the age of thirty. Less than 25% of EFT’s present with overt metastasis and almost all have subclinical metastatic disease at the time of diagnosis, therefore, a comprehensive evaluation and systemic chemotherapy is recommended. We recommend a multidisciplinary approach of surgical decompression to preserve neurological functions, followed by compressed chemotherapy regimens, reevaluation for local treatment, and adjuvant chemotherapy.
RARE-32. PEDIATRIC METASTATIC SKULL BASE CHORDOMA WITH TP53 MUTATION – A CASE REPORT AND REVIEW OF THE LITERATURE
Authors: Shimada Akira , Kurozumi Kazuhiko , Kanamitsu Kiichiro , Ishida Hisashi Ishida , Fujiwara Kaori , Washio Kana Washio , Kumamoto Tadashi , Ogawa Chitose , Shin Masahiro 
Published: December 2020

Abstract
Chordoma is an uncommon bone tumor arising from notochordal remnant, which accounts for 1–4% of all bone malignancies. It commonly occurs along the cranial-spinal axis, and skull base is one of most frequent sites, representing 35–49% of all chordoma cases. Surgical resection is widely accepted as the first choice of treatment. There are only limited number of reports about pediatric chordoma cases, and its biological behavior including genetic backgrounds were largely unknown. Here, we present a 5 year-old girl with a large aggressive skull base chordoma of 6 cm in maximum diameter, which eventually had multiple systemic metastasis. We initially tried chemotherapy based on the protocol for the osteosarcoma, but in vain. Because the tumor was highly vascularized on angiography, after embolization of the feeding arteries and bilateral internal maxillary arteries, endoscopic endonasal surgery was performed. The tumor was sufficiently removed, achieving effective mass reduction, and the residual tumors involving the lower cranial nerves and craniocervial junction were additionally treated with Gamma Knife radiosurgery. However, one month later, it showed systemic metastasis to bilateral cervical lymph nodes and lung. We tried chemotherapy with nivolmab and imatinib for this patient, whereas they showed the partial effect. The genetic analysis revealed somatic TP53 c.569C&gt;T, (p.P190L) mutation in chordoma specimen. In the past literature, we found only one study of the adult chordoma cases, in which majority of the patients had somatic TP53 mutation (p.P72R). Further investigation with large number of the cases is essential to clarify the molecular biology of pediatric chordomas.
RARE-34. UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG): GUIDELINES FOR THE MANAGEMENT OF MENINGIOMA IN CHILDREN, TEENAGERS AND YOUNG ADULTS
Authors: Szychot Elwira , Goodden John , Gillian Whitfield , Curry Sarah 
Published: December 2020

Abstract
Primary tumours of the meninges are rare accounting for only 0.4–4.6% of all paediatric tumours of the central nervous system. Due to the rarity of these tumours in children, and the consequent absence of collaborative prospective trials, there is no clear consensus on how the unique characteristics of paediatric meningiomas impact clinical status, management approach, and survival. Much of the evidence and treatment recommendations for paediatric meningiomas are extrapolated from adult data. Translating and adapting adult treatment recommendations into paediatric practice can be challenging and might inadvertently lead to inappropriate management. In 2009 Traunecker et al. published guidelines for the management of intracranial meningioma in children and young people on behalf of UK Children’s Cancer and Leukaemia Group (CCLG). Ten years later we have developed the updated guidelines following a comprehensive appraisal of the literature. Complete surgical resection is the treatment of choice for symptomatic meningiomas, while radiotherapy remains the only available adjuvant therapy and may be necessary for those tumours that cannot be completely removed. However, significant advances have been made in the identification of the genetic and molecular alterations of meningioma, which has not only a potential value in development of therapeutic agents but in surveillance of childhood meningioma survivors. This guideline builds upon the CCLG 2009 guideline. We summarise recommendations for the diagnosis, treatment, surveillance and long-term follow up of children and adolescents with meningioma.
RARE-38. CLINICAL PRESENTATION OF MGA-NUTM1 FUSION TRANSCRIPT SARCOMA
Authors: Pongphitcha Pongpak , Sirachainan Nongnuch , Jinawat Artit , Boonkird Atthaporn , Puataweepong Putipun , KhongKhatithum Chaiyos , Pakakasama Samart , Anurathapan Usanarat , Songdej Duantida , Bouffet Eric , Hongeng Suradej 
Published: December 2020

Abstract

BACKGROUND
MGA-NUTM1 fusion gene tumor are recently described as new subtype of NUTM1-rearranged tumors. Regarding its rarity, standard treatment has not been reported. Here we described clinical presentation, radiologic finding, immunohistological profile, and treatment of a boy with MGA-NUTM1 fusion gene tumor. CASE REPORT: A 13-year-old boy with 2-month history of progressive right hemiparesis and headache. Magnetic resonance imaging (MRI) revealed 7.8 x10.6 x 8.0 cm well defined heterogeneous enhancing mass at left fronto-parietal lobe. CT chest and abdomen, bone scan, MRI spine, and CSF studies were unremarkable. He underwent craniotomy with total tumor removal. Pathology demonstrated high grade spindle cell sarcoma. The immunohistological profile was positive for BCOR, NUT1, and TEL1, but negative for CD34, STAT6, desmin, SMA, actin sarcomeric, EMA, PR, S100, SOX10, BCL 6, and SABT2. The INI-1 showed nuclear expression and Ki-67 was positive in 50% of tumor nuclei. Molecular test for MGA-NUTM1 fusion transcript was positive, while SYT-SSX1, SYT-SSX2, and SYT-SSX4 fusion transcripts were negative. Four months after operation, MRI showed newly-seen two small enhancing foci at lateral and inferior aspects of the surgical cavity. He underwent re-surgery. Then focal radiation (54Gy and boost up to 60Gy at recurrent area) to the resection cavity was decided. Post-radiation chemotherapy including ifosfamide 3 g/m2 and etoposide 150 mg/m2 on Day 1–2, and carboplatin 500 mg/m2 on Day 3, every 21–28 days was started. He has completed the first course of chemotherapy without any complication.

CONCLUSION
MGA-NUTM1 fusion CNS sarcoma is rare. Treatment may require surgery, radiation and chemotherapy.
RARE-40. CASE REPORT: LONG-TERM SURVIVOR OF A RARE, PEDIATRIC PRIMARY HISTIOCYTIC SARCOMA (HS) OF THE CENTRAL NERVOUS SYSTEM (CNS) FOLLOWING COMPLETE RESECTION, CHEMOTHERAPY AND ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (ALLO-HCT)
Authors: Osorio Diana S , Abu-Arja Rolla , Abdel-Baki Mohamed S , Leonard Jeffrey R , Sribnick Eric A , Finlay Jonathan L , Ellison David W , Picarsic Jennifer , Kahwash Samir , Boue’ Daniel R 
Published: December 2020

Abstract
We report an unusual case of a patient with primary CNS-HS a very rare neoplasm of histiocytic lineage with usually poor prognosis. An 8 year old boy presented with a one month history of headaches, nausea and vomiting. Physical examination revealed nystagmus and dysmetria. Brain MRI revealed a localized 2.4 cm posterior fossa (cerebellar) mass with restricted diffusion. The patient underwent a gross total resection of the mass. Initial post-operative lumbar puncture was positive for rare malignant cells. Pathology showed a focally necrotic neoplasm, composed of nests and cords of large relatively uniform cells with abundant eosinophilic cytoplasm, moderately pleomorphic nuclei and numerous mitotic figures, consistent with CNS-HS with juvenile xanthogranuloma phenotype, as supported by positive IHC expression of CD163, CD68, CD14, fascin, and Factor XIIIa, while negative for CD1a, Lymphoid and Myeloid markers, and BRAFv600e mutation. He was treated with two cycles of clofarabine and cytarabine and triple intrathecal (IT) chemotherapy. He developed generalized seizures and MRI showed demyelination consistent with IT methotrexate toxicity; MTX was then discontinued. He was then given two additional cycles of cladribine and weekly intrathecal therapy prior to consolidation with an Allo-HCT using a 10/10 HLA allelic-matched unrelated donor. His conditioning regimen included total body irradiation and cyclophosphamide. He did well post-transplant with peripheral blood chimerism at 1 year showing &gt; 95% donor cells. He remains disease-free with an excellent quality of life since August 2016. We report one of the few known survivors of this unusual and highly malignant entity.
RARE-48. CHARACTERISTICS AND OUTCOME OF DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT): A SINGLE INSTITUTION EXPERIENCE
Authors: Pickle Emily Owens , Aguilar-Bonilla Ana , Smith Amy 
Published: December 2020

Abstract
Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare with an unknown etiology and unestablished incidence. Most frequently reported genetic alteration is KIAA1549-BRAF fusion. We present four DLGNT cases diagnosed between 2005–2018. Patient 1 is a female who presented with a 2-year history of back pain subsequently diagnosed with pilocytic astrocytoma. Re-imaging 3 months post-resection revealed a low grade glioneuronal tumor with BRAF duplication. Patient 2 is a female who presented with recurrent vomiting, dizziness, and hydrocephalus. The patient underwent biopsy which was consistent with oligodendrogliomatosis; no genetic analysis was done. Patient 3 is a male who presented with worsening headaches and intermittent vomiting. Approximately 5 months after resection, imaging showed leptomeningeal disease and further testing revealed KIAA1549-BRAF fusion and 1p deletion. Patient 4 is a male who presented with hydrocephalus. Imaging showed disseminated leptomeningeal enhancement without a dominant mass lesion; biopsy and clinical history confirmed the diagnosis. All four patients received chemotherapy, Patients 1 and 3 underwent radiation therapy, and Patient 3 received a MEK-inhibitor to which he had a great response. However, the patient was non-compliant and had PD which continued despite re-starting therapy. Patients 1, 2, and 3 have died of progressive disease; survival was Patient 1, 276 days, Patient 2, approximately 7 years and 8 months, and Patient 3, 2 years and 11 months. Patient 4 remains alive with disease 4.5 years from diagnosis. There is much to be learned about this rare, poorly understood disease but hope for improvement through therapeutic targeting of the MAPK pathway.
RARE-50. TREATMENT RESPONSE OF CNS HIGH-GRADE NEUROEPITHELIAL TUMORS WITH MN1 ALTERATION
Authors: Baroni Lorena V , Rugilo Carlos , Lubieniecki Fabiana , Sampor Claudia , Freytes Candela , Nobre Liana , Hansford Jordan R , Malalasekera Vajiranee S , Zapotocky Michal , Dodgshun Andrew , Ramaswamy Vijay , Alderete Daniel 
Published: December 2020

Abstract

BACKGROUND
CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) are a rare entity recently described as a high-grade tumor containing a mixture of solid and pseudopapillary patterns with MN1 rearrangement.

METHODS
CNS HGNET-MN1 patients were identified using genome wide methylation arrays across 5 institutions (the Hospital JP Garrahan, Hospital for Sick Children, the University Hospital Motol, Royal Children`s Hospital and Christchurch Hospital) and was correlated with treatment and outcome. Central imaging review with radiological features analysis was performed.

RESULTS
We identified 9 patients harboring CNS HGNET-MN1 tumors through application of the Heidelberg brain tumor classifier. Seven tumors were T supratentorial and two in the spinal cord. Median age was 5 (range 3.6–14.6). All patients had surgery (6 GTR and 3 STR) as initial management followed by radiotherapy (focal 5/CSI 1) and systemic chemotherapy in 2 patients. Four of the 9 patients relapsed by 3 years post diagnosis, with 2 local and 2 metastatic failures despite complete surgical resections and radiotherapy. Three patients died due to tumor relapse after 24 months despite upfront radiotherapy. Seven of 9 patients had an initial diagnosis of ependymoma.

CONCLUSION
Treatment of CNS HGNET-MN1 remains a major challenge with multiple failures, despite aggressive surgical resections and upfront involved field radiotherapy. Further multicenter, international prospective studies are required to determine the optimal treatment strategy for this group of tumors.
RARE-55. CHALLENGES AND SPECIFIC STRATEGIES FOR CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY SYNDROME IN LOW RESOURCE SETTINGS. ON BEHALF OF THE INTERNATIONAL RRD CONSORTIUM IN LOW RESOURCE SETTINGS PANEL
Authors: Kebudi Rejin , N Nisreen Amayiri , Abedalthagafi Malak , Rana Asim Noor , Kirmani Slman , Musthaq Naureen , Lamki Zakiya Al , El Houdzi Jamilla , Yazıcı Hulya , El-Naggar S , Edwards Melissa , Bianchi Vanessa , Durno Carol , Tabori Uri , Bouffet Eric 
Published: December 2020

Abstract
Germline biallelic mutations in one of the mismatch repair genes (MSH2/MSH6/MLH1/PMS2 results in constitutional mismatch repair deficiency (CMMRD), a condition associated with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood. The paucity of information with respect to these conditions leads to mismanagement and may be a factor in the high mortality of patients with CMMRD. Two international consortia, the European CARE4CMMRD, and the international replication repair deficiency (RRD) consortium, are addressing the many challenges associated with this condition. To address specific issues surrounding the management of CMMRD in low and middle income countries (LMIC), a multidisciplinary taskforce of 11 specialists from nine countries was formed. Preliminary conclusions are: 1) Immunohistochemistry for CMMRD should be considered for all patients with suggestive clinical features. In countries where CMMRD is common, malignant gliomas, colon cancers and T cell lymphomas should be stained routinely as the prevalence of CMMRD in these tumors can exceed 40%. 2) Temozolomide should not be used in the management of malignant glioma. By contrast, preclinical studies have suggested increased sensitivity to nitrosoureas. For the management of CMMRD related lymphoma and leukemia, mercaptopurines should not be avoided or discontinued as a part of the standard of care before more data are collected. 3) Management with checkpoint inhibitors should be limited to centers with intensive care units and expertise in complex supportive care to manage side effects of immune therapy. 4) Surveillance protocols have demonstrated long term survival benefits and should be implemented in LMIC.
RARE-57. PEDIATRIC CHORDOMA: WHOLE EXOME SEQUENCING OF 11 PEDIATRIC CHORDOMA SAMPLES
Authors: O’Halloran Katrina , Bootwalla Moiz , Merkurjev Daria , Kaneva Kristiyana , Ryutov Alex , Cotter Jennifer , Ji Jianling , Ostrow Dejerianne , Biegel Jaclyn A , Gai Xiaowu 
Published: December 2020

Abstract
Chordoma is a rare tumor and while SMARCB1 alterations have been observed in poorly differentiated chordomas, conventional chordomas are not well understood. We interrogated nuclear and mitochondrial genomes of 11 chordoma samples from 7 children. Frozen tumor tissue DNA was extracted and whole exome libraries generated using Agilent SureSelect Human All Exon V6 kit plus mtDNA genome capture kit. Libraries were sequenced using Illumina Nextseq 500. MuTect2, VarDict and LUBA variant callers were used with allele frequency cutoff 2%. Potential germline variants were filtered bioinformatically. In total, 656±74 high-confidence somatic variants, including 368±43 nonsynonymous variants per sample were detected. Of 2,607 combined unique nonsynonymous variants, 95% were missense. Remaining high impact variants were frameshift (37%), stop gain (39%), splice acceptor/donor (22%), start and stop loss (2%). Of the unique nonsynonymous variants, 137 fall within Cosmic Cancer Census Genes, including high impact variants in SETD2, MLLT4. No previously reported TBXT, CDKN2A, PI3K, LYST mutations identified. Tumor Mutation Burden/Megabase was 10±1. The mitochondrial analysis revealed heteroplasmic m.11727C&gt;T MT-ND4 missense variants in three tumors resected at different time points from the same patient, and another heteroplasmic m.1023C&gt;T rRNA mutation from the primary and recurrent tumors of another patient. Intriguingly, two Children’s Brain Tumor Tissue Consortium patients with chordoma had identical heteroplasmic m.10971G&gt;A MT-ND4 nonsense mutations. Pediatric chordomas appear to lack somatic nuclear mutations. Observing recurrent mitochondrial mutations across multiple tumors from the same and/or different patients is striking, suggesting they may be implicated in tumorigenesis and be potential diagnostic markers.