Primitive Neuroectodermal Tumor Research Articles

Case report: Metastatic melanoma derived from a somatic-type malignant transformation of a mediastinal teratoma treated with immune checkpoint inhibitors

The treatment of patients affected by a teratoma with somatic-type malignancy (STM) is challenging, since they are characterized by a poor prognosis, due to chemoresistance to standard cisplatin-based regimens. Only five more case reports were described for melanomatous STM and for which there are no data available for efficacy evidences of immune checkpoint inhibitors in this setting. Here we report the case of a patient with an initial diagnosis of mediastinal pure seminoma at the first biopsy. After four cycles of a standard cisplatin-based regimen and a partial response, a radical surgery was performed, revealing a mediastinal teratoma with triple STM component (melanoma, leiomyoarcoma and primitive neuroectodermal tumor). However, during post-surgical follow-up, he developed distant metastases from the melanomatous component and a first-line treatment with immune checkpoint inhibitors (ICI) was started.

EPID-07. MAJOR CONGENITAL ANOMALIES AND RISK OF CHILDHOOD BRAIN TUMORS IN 9 STATES

Abstract Children with congenital anomalies have a higher risk of developing a childhood brain tumor (CBT), but it remains unclear if associations vary by cancer histology, which could inform our understanding of these associations. Thus, we characterized co-occurrences of major congenital anomalies with six CBTs. We leveraged a population-based registry linkage study of live births, congenital anomalies, and cancer from nine states. Dates of birth and last follow-up varied by state, ranging between January 1, 1990 to December 31, 2018, for a total of 22,599,099 live births. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed up to age 18 years. Major congenital anomalies were classified based on the National Birth Defects Prevention Network Surveillance Guidelines. Children with any genetic anomalies were excluded. We used Cox regression to evaluate associations between major congenital anomalies and astrocytoma, medulloblastoma, ependymoma, atypical teratoid/rhabdoid tumor (ATRT), primitive neuroectodermal tumors (PNET), and mixed and unspecified gliomas (“mixed gliomas”), adjusting for sex, state, maternal education, maternal race/ethnicity, and maternal age. Sensitivity analyses were conducted stratifying by number of major anomalies (0, 1, 2+) and age at cancer diagnosis (<1, 1-4, 5-9, 10+ years). There were 5,685 diagnosed with any CBT. Having any major congenital anomaly was significantly associated with astrocytoma, ATRT, medulloblastoma, mixed glioma, and PNET (aHR range: 1.79-5.78) but not ependymoma. When stratified by number of major anomalies, effect estimates were similar. Due to small numbers when stratified by age at cancer diagnosis, unadjusted analyses were conducted. Associations were strongest in children diagnosed with astrocytoma, ATRT, medulloblastoma, mixed glioma, or PNET before age 1 (HR range: 3.03-5.47) compared to other age groups (HR range: 1.25-3.07). Children with any major congenital anomaly have an increased risk of developing astrocytoma, ATRT, medulloblastoma, mixed glioma, or PNET, particularly by 1 year.

CSIG-07. JAK1/STAT1/3 COOPERATES WITH THE CIC-FUSIONS TO DRIVE CIC-REARRANGED SARCOMAS

Abstract CIC-rearranged sarcoma (CRS) is an rare disease driven by a specific fusion protein involving the CIC gene. Occurrence in the brain is 3% in all CRS patients. The native CIC protein is a transcriptional repressor of the (RTK)/Ras/ERK signaling pathway, which is one of the most tumorigenic pathways in cancer. The most common rearrangement is with the double homeobox 4 (DUX4) transcription factor (CIC-DUX4), and others, such as CIC-NUTM1 fusions, have been identified in a subset of pediatric primitive neuroectodermal tumors. However, the molecular mechanisms by which CIC-fusions drive CRS remain unknown. Preliminary data shows that CIC-DUX4/NUTM1 fusions activate JAK and its downstream effector STAT1/3. We hypothesize that the JAK/STAT1/3 signal transduction pathway cooperates with CIC-fusions to induce the expression of oncogenic transcription factors ETV1/4/5 and drive these sarcomas. We show high levels of JAK1/STAT1/3 activation in patient-derived CRS cell lines (NCC-SCC-89/C) as compared to other sarcoma cell lines without the fusion. JAK1 inhibition using Solicitinib and Ruxolitinib reduced phosphorylation of STAT1/3 as well as protein and mRNA expression of ETV1/4/5, promoter activity of ETV5, cell proliferation and tumorgenicity. Interestingly DUX4 is involved in histone acetylation and STAT1 has been shown to activate p300/CBP complex which lead us to evaluating the role of STAT1 in the gene activation CRS. We elucidate mechanistically that the fusion proteins increase binding of STAT1/3 at the promoters of ETV 1/4/5. Importantly, JAK1 inhibition effectively reduces histone acetylation induced by CIC-fusions at the promoters of ETV1/4/5. To evaluate the pre-clinical effect of targeting the JAK1/STAT1/3 pathway, A CRS cell line (NCC-SCC-89/C) were grafted into NSG mice. Ruxolitinib treatment significantly reduced tumor volume, STAT activation, and ETV1/4/5. In conclusion, we show that the JAK1/STAT1/3 pathway plays a critical role in cooperating with CIC-fusions to drive CRS, providing insight into potential therapeutic avenues for these aggressive tumors.

CNSC-33. GROUP3 MEDULLOBLASTOMA WITH BONE MARROW AND ABDOMINAL CAVITY METASTASIS:A CASE REPORT

Abstract Medulloblastoma is an infratentorial primitive neuro-ectodermal tumour, which is commonly occurring in childhood. It often spreads through the cerebrospinal fluid pathways with a very low rate of systemic metastases. Extra-central nervous system metastases have a poor prognosis in medulloblastoma. Here, we reported a case of Group3 medulloblastoma with bone marrow and abdominal cavity metastasis. A 10-year-old girl complained of headache, dizziness, vomiting and nausea. Magnetic resonance imaging(MRI) of the brain showed a large mass in the fourth ventricle and obstructive hydrocephalus. The surgery was performed to remove the mass and ventriculoabdominnal shunt was performed for obstructive hydrocephalus. Histological verification was proven classic medulloblastoma and next-generation sequencing confirmed molecular group of Gruop3 with MYC amplication. Radiotherapy was subsequently performed one month after the surgery. During the radiotherapy, brain MRI showed metastasis on the surface of the brain, which confer a poor prognosis. After the radiotherapy According to the therapeutic schedule, She would accept chemotherapy one month after the radiotherapy. But She suffered severe bone marrow suppression manifested as anaemia and thrombocytopenia, which can not be improved by medication and blood transfusion. A bone marrow aspiration was subsequently performed, and bone marrow smear showed large numbers of tumor cells at high magnification and was lack of normal hematopoietic cells. The girl was deteriorating rapidly with jaundice, ascites, hepatosplenomegaly and pancreatitis after the bone marrow aspiration. We found a lot of tumor cells in the bleeding tendency ascites and finally confirmed bone marrow and abdominal cavity metastasis concurrently. Eventually, She died less than a month after the metastasis and the overall survival was only 6 months. This typical case demonstrated severe bone marrow suppression of unknown origin should caused alarm and be performed bone marrow aspiration as soon as possible. The prognosis of medulloblastoma with extra-central nervous system metastases is poor and people may die in months.

Adult supratentorial peripheral primitive neuroectodermal tumor with multiple metastases: a case report and literature review

BackgroundIntracranial primitive neuroectodermal tumors (PNETs) are characterized by poorly differentiated, highly malignant, aggressive small round tumor cells originating from the central and peripheral nervous systems.Case presentationA 25-year-old Chinese woman experienced sudden onset headache, vomiting, and severe anemia. Imaging examinations revealed a mass in the left parietal occipital lobe. Following microsurgery, histological confirmation revealed the tumor to be pPNET. Postoperative computed tomography (CT) showed multiple metastases in the lung, liver, and retroperitoneal lymph node. Unfortunately, she died of tumor cachexia 1 month after chemotherapy.ConclusionsDue to the rare presentation of pPNET, pPNET would be misdiagnosed without the histological diagnosis. Here, we aimed to provide clinicians with information about the treatment and relevant literature of pPNET.

Risk factors for treatment-related sensorineural hearing loss and hearing aid use in medulloblastoma patients: an observational cohort study.

This study aimed to analyze treatment-related risk factors for sensorineural hearing loss (SNHL) and an indication for hearing aids (IHA) in medulloblastoma patients after craniospinal radiotherapy (CSRT) and platin-based chemotherapy (PCth). Atotal of 58patients (116 ears) with medulloblastoma and clinically non-relevant pre-treatment hearing thresholds were included. Cranial radiotherapy and PCth were applied sequentially according to the HIT 2000 study protocol or post-study recommendations, the NOA-07 protocol, or the PNET (primitive neuroectodermal tumor) 5MB therapy protocol. Audiological outcomes up to amaximum post-therapeutic follow-up of 4years were assessed. The incidence, post-treatment progression, and time-to-onset of SNHL, defined as Muenster classification grade ≥MS2b, were evaluated. Risk factors for IHA were analyzed separately. While 39patients received conventionally fractionated RT (CFRT; group1), 19patients received hyperfractionated RT (HFRT; group2). Over amedian follow-up of 40months, 69.2% of ears in group1 experienced SNHL ≥MS2b compared to 89.5% in group2 (p = 0.017). In multivariable Cox regressions analysis, younger age and increased mean cochlear radiation dose calculated as the equivalent dose in 2‑Gy fractions (EQD2) were associated with time-to-onset of SNHL ≥MS2b (p = 0.019 and p = 0.023, respectively) and IHA (p < 0.001 and p = 0.016, respectively). Tomotherapy and supine positioning were associated with alower risk for IHA in univariable modelling only (p = 0.048 and p = 0.027, respectively). Young age and cochlear EQD2 Dmean ≥40 Gy are significant risk factors for the incidence, degree, and time-to-event of SNHL as well as for IHA in medulloblastoma patients.

Primary primitive neuroectodermal tumour in the orbit of a domestic shorthair cat (Felis catus)

AbstractA 13‐year‐old, domestic shorthair cat presented for evaluation of left‐sided exophthalmos, epiphora and third eyelid elevation of approximately 4‐month duration. Based on ophthalmic exam findings, a retrobulbar mass was suspected. Computed tomography of the head revealed a fluid to soft‐tissue, non‐contrast‐enhancing mass caudoventral to the left globe. Based on these findings, a retrobulbar abscess was considered the most likely differential, while a neoplastic mass could not be completely excluded. The mass and left globe were surgically excised via a modified lateral orbitotomy and exenteration. Histopathology and special staining of the mass was consistent with an orbital primitive neuroectodermal tumour, while the globe was unremarkable.

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.

Symptomatic cerebral vasospasm after posterior fossa surgery in pediatric patients: single-center study and systematic literature review.

The most common cause of cerebral vasospasm is subarachnoid hemorrhage, less frequently it occurs after trauma, infection, and tumor resection. Vasospasm in children is rare and has not been systematically investigated in posterior fossa surgery. The authors undertook a single-center retrospective study of all the pediatric patients who underwent surgery on the posterior fossa and presented with postoperative symptomatic vasospasm in the period from January 2018 to February 2024. Subsequently, a systematic literature review in accordance with the PRISMA guidelines was performed in the PubMed and Scopus databases to identify the published papers on symptomatic vasospasm after posterior fossa surgery in children. Of the 178 patients who underwent surgery on the posterior fossa, only one patient was diagnosed with symptomatic diffuse vasospasm on postoperative day 21. The systematic literature review provided further 9 children. The underlying pathology comprised 8 intra-axial lesions with 4 medulloblastomas, 1 schwannoma in the medulla oblongata, 1 pilocytic astrocytoma, 1 primitive neuroectodermal tumor, and 1 arteriovenous malformation. The extra-axial lesions were 1 hypoglossal schwannoma and 1 oculomotor nerve schwannoma. Iatrogenic symptomatic vasospasm after posterior fossa surgery in children is a rare complication with an outcome ranging from complete recovery to the death of the patient. It is important for all staff involved in the care of patients undergoing surgery on the posterior fossa to be aware of this rare postoperative complication. The small number of patients affected does not allow a substantiated conclusion to be drawn about predictive risk factors.

Concurrent delayed recurrence of peripheral primitive neuroectodermal tumors in orbital and sellar/suprasellar regions in an older adult.

Peripheral primitive neuroectodermal tumors (pPNETs) are rare and aggressive small round cell tumors, tending to occur in the thoracic and paravertebral soft tissues in children and young adults. This report describes an exceptionally rare case of concurrent delayed recurrence of pPNET in the orbital and sellar/suprasellar regions in an older adult, with a discussion supported by a literature review. We report an 82-year-old woman with a history of orbital pPNETs resection at age 62, followed by gamma knife radiosurgery for local recurrence at age 66. She presented left eye pain, left eye protrusion, decreased vision in the right eye, and right homonymous hemianopia. MRI revealed extensive lesions in the left orbital cavity and sellar/suprasellar region, contiguous through the optic canal. The recurrent tumor was treated through a two-stage resection via transcranial and transsphenoidal approaches, which resulted in symptom improvement and a pathologic diagnosis of pPNETs. This case highlights a highly rare instance of late-onset orbital pPNETs recurrence in an elderly patient, with evidence suggesting tumor progression into the sellar/suprasellar regions through the optic canal.

Opaque Hemithorax in a Young Girl: A Rare Case of Askin’s Tumour

Askin’s tumor is a primitive neuroectodermal tumor primarily affecting the thoracopulmonary region. It typically manifests in children and adolescents, with a notable female preponderance. Histologically, it presents as a malignant small blue cell tumor. Clinical presentation often includes respiratory symptoms such as pain, dyspnoea, and weight loss. Prognosis is generally unfavorable with a median survival of around 8 months and an overall survival rate of approximately 60% at 5 years. This report highlights the case of a 13-year-old female diagnosed with Askin’s tumor. This report highlights the case of a 13-year-old female presented with a 2-month history of back pain, right-sided chest pain, exertional breathlessness, and loss of appetite. Examination revealed dyspnoea, pallor, and bilateral cervical lymphadenopathy. Radiological and histopathological investigations confirmed the diagnosis of Askin’s tumor with malignant pleural effusion and distant metastasis. This case underscores the importance of considering Askin’s tumor in the differential diagnosis of thoracic masses in pediatric patients. Early recognition and a multidisciplinary approach are crucial for optimizing patient outcomes.

Utility of OLIG2 immunostaining in pediatric brain tumors with embryonal morphology.

This study evaluates the diagnostic utility of OLIG2 immunohistochemistry for distinguishing between pediatric high-grade gliomas (pHGG) and embryonal tumors (ETs) of the CNS. Utilizing a retrospective pediatric cohort (1990-2021) of 56 CNS tumors, classified initially as primitive neuroectodermal tumors or CNS ET, we reclassified the cases based on WHO CNS5 criteria after comprehensive review and additional molecular testing that included next-generation sequencing and DNA methylation profiling. Our results indicate that OLIG2 immunopositivity was negative or minimal in a significant subset of pHGG cases (6 out of 11). At the same time, it showed diffuse expression in all cases of CNS neuroblastomas with FOXR2 activation (5/5), demonstrating its limited specificity in differentiating between pHGG and ET. Variable OLIG2 expression in other ETs, ATRT, and ETMR suggests the broader diagnostic implications of the marker. Furthermore, incidental findings of OLIG2 positivity in cases traditionally expected to be negative, such as medulloblastoma and ependymoma, introduce an additional layer of complexity. Together, these findings highlight the challenges of relying solely on OLIG2 immunostaining for accurate tumor classification in pediatric CNS neoplasms and underscore the importance of an integrated diagnostic approach.

Primitive Neuroectodermal Tumors. State of Art

PNETs, also known as primitive neuroectodermal tumors, are extremely uncommon sarcomas that originate from the neural crest. It has been observed that the yearly incidence of these instances is 2.9 cases per million people between the ages of birth and 20.

Neurotrophic tyrosine receptor kinase gene fusions in adult and pediatric patients with solid tumors: a clinicogenomic biobank and record linkage study of expression frequency and patient characteristics from Finland.

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers. Using the Auria Biobank in Finland, we aimed to identify and characterize patients with these gene fusions, and describe their clinical and tumor characteristics, treatments received, and outcomes. We evaluated pediatrics with any solid tumor type and adults with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), sarcoma, or salivary gland cancer. We determined tropomyosin receptor kinase (TRK) protein expression by pan-TRK immunohistochemistry (IHC) staining of tumor samples from the Auria Biobank, scored by a certified pathologist. NTRK gene fusion was confirmed by next generation sequencing (NGS). All 2,059 patients were followed-up starting 1 year before their cancer diagnosis. Frequency of NTRK gene fusion tumors was 3.1% (4/127) in pediatrics, 0.7% (8/1,151) for CRC, 0.3% (1/288) for NSCLC, 0.9% (1/114) for salivary gland cancer, and 0% (0/379) for sarcoma. Among pediatrics there was one case each of fibrosarcoma (TPM3::NTRK1), Ewing's sarcoma (LPPR1::NTRK2), primitive neuroectodermal tumor (DAB2IP::NTRK2), and papillary thyroid carcinoma (RAD51B::NTRK3). Among CRC patients, six harbored tumors with NTRK1 fusions (three fused with TPM3), one harbored a NTRK3::GABRG1 fusion, and the other a NTRK2::FXN/LPPR1 fusion. Microsatellite instability was higher in CRC patients with NTRK gene fusion tumors versus wild-type tumors (50.0% vs. 4.4%). Other detected fusions were SGCZ::NTRK3 (NSCLC) and ETV6::NTRK3 (salivary gland cancer). Four patients (three CRC, one NSCLC) received chemotherapy; one patient (with CRC) received radiotherapy. NTRK gene fusions are rare in adult CRC, NSCLC, salivary tumors, sarcoma, and pediatric solid tumors.

Primary Ewing sarcoma/primitive neuroectodermal tumors of the kidney: Case series of eight cases from a single center with follow-up details.

We aim to share the experience of a single center in the management of eight cases of renal primitive neuroectodermal tumor (PNET) which are uncommon, aggressive tumors. The objectives were to study the presentation of the disease, the treatment offered and its outcomes, and the comparison of the treatment with published literature. The single-center renal PNET data of all patients were retrospectively reviewed from 2011 to 2022. Renal PNET was seen in eight patients. Minimum follow-up period of 1 year was required. Male-to-female ratio was 7:1. The mean age was 26.5 years. All were locally advanced tumors on presentation. One patient had an inferior vena cava thrombus, one patient had metastases on presentation, and two patients had tumor extending to paranephric space. The diagnosis was made by histopathology supported by immunohistochemistry showing CD99 positivity. All patients were treated with radical nephrectomy, followed by chemotherapy in all and radiotherapy in three patients. Two patients expired at 3½ and 6 years after surgery, the remaining six are alive at a median follow-up period of 34.5 months. Renal PNET is an uncommon renal tumor which is aggressive and requires multimodal therapy for prolonged survival.

ETMR-27. ANTI-ANGIOGENIC METRONOMIC THERAPY OF RARE TUMOURS OF THE CENTRAL NERVOUS SYSTEM

Abstract BACKGROUND Improvement of molecular diagnostics has led to significant changes in the categorization of paediatric brain tumours, unveiling novel tumour entities in the latest 2021 WHO classification of central nervous system (CNS) tumours (5th edition), particularly within the group of rare tumours of the CNS (encompassing rare embryonal and sarcomatous tumours (REST) and gliomas). However, treatment recommendations are currently based on small patient cohorts lacking standardized protocols, with even more limited options for progressive or relapsed disease. METHODS Patients from specialized European oncologic centres diagnosed or reclassified as REST receiving anti-angiogenic therapy after relapse (Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial - MEMMAT) will be analysed. RESULTS So far, 14 patients from Austria, Czech Republic, Denmark and France were identified, with molecularly reclassified 4 CNS tumours with BCOR/BCORL1 alteration (CNS BCOR/BCORL1), 4 CNS astroblastomas, MN1-altered (ABM_MN1), 3 embryonal tumours with multi-layered rosettes (ETMR) and 1 DICER1-mutated intracranial sarcoma (CNS DICER1) as well as 2 primitive neuroectodermal tumours (PNETs, reclassification ongoing). Initial histological classifications ranged from ependymoma group 3, ETMR, malignant peripheral nerve sheath tumour (MPNST) to EGFR-positive glioblastoma. In 2 cases categorization was unclear with either anaplastic ependymoma, plexus carcinoma or ETMR. 10 patients received standard MEMMAT protocol (biweekly intravenous Bevacizumab with oral drugs: Celebrex, Thalidomide, Fenofibrate, Cyclophosphamide/Etoposide alternating and intrathecal Etoposide and Cytarabine). In 4 cases therapy was modified with an individualized metronomic treatment regimen. CONCLUSION Therapy at initial diagnosis, duration of relapse-treatment, clinical as well as radiological response, overall survival, progression-free survival and molecular hallmarks will be presented.

LMIC-16. PRE-IRRADIATION CHEMOTHERAPY AND DELAYED RADIATION THERAPY IN INFANTS AND YOUNG CHILDREN WITH WITH CENTRAL NERVOUS SYSTEM EMBRYONAL TUMOURS

Abstract BACKGROUND Established strategies for infants and young children(IYC) with embryonal tumours of the central nervous system(CNSET) - autologous stem-cell rescue(ASCT) and intraventricular chemotherapy(IVCT) – are not universally available. We report the outcomes of IYC with CNSET treated using the strategy of surgery, pre-irradiation chemotherapy and delayed radiation. METHODS Children &amp;lt;3years diagnosed with CNSET- medulloblastoma(MB), atypical teratoid/rhabdoid tumour(ATRT), embryonal tumour with multilayered rosettes(ETMR), CNS primitive neuroectodermal tumours(PNET)- and pineoblastoma(PB),underwent standard evaluation and staging, maximal safe excision, pre-irradiation chemotherapy(cyclophosphamide, etoposide and carboplatin;CEJ) upto 36months of age and either ris-adapted craniospinal with boost or focal irradiation. We performed a retrospective intention-to-treat outcome analysis. RESULTS Of 117children &amp;lt;3years with CNSET treated January2011- December2022, 72 were treated with this strategy.The median age was 25months (range6-35), 49males,histology medulloblastoma-42(58%), ATRT-9(12.5%), PNET-8(11.1%), ETMR-8(11.1%) and PB-5(6.8%); 23(32%) metastatic.The median chemotherapy cycles were 6(range 1-15). 36 children went on to receive RT; CSI in 33 (20standard-dose,13reduced-dose) and focal in 3. At last follow-up, 27children are in remission, 43 have relapsed/progressed (9 received salvage treatment) and 2 died due to chemotherapy toxicity. The 3-year and 5-year event-free-survival(EFS) are 35% and 3-year and 5-year overall-survival(OS) are 41.8% and 40.2%. The 3-year EFS/OS for MB are 51.1%/ 62.8%,PNET 25%/25%,ATRT 11.1%/11.1%,ETMR 12.5%/12.5% and PB 0%. Only metastasis was prognostic in medulloblastoma (HR 2;95% CI 0.86-4.6 for EFS and HR 1.7;95% CI 0.67-4.5 for OS); age, molecular group and histology were not prognostic. Long-term follow-up (n=17) documented &amp;gt;grade2 late effects in all (endocrine-16, neurocognitive-8, vision-3, hearing -8 and neurological-10). CONCLUSION The use of moderate-intensity pre-irradiation chemotherapy is feasible and effective in infants and young children with CNSETs. Despite inferior outcomes compared to ASCT or IVCT,this strategy could be used in resource-limited settings.

ETMR-15. RECLASSIFICATION OF CHILDHOOD CENTRAL NERVOUS SYSTEM PRIMITIVE NEUROECTODERMAL TUMOR: CLINICAL FEATURES AND OUTCOME

Abstract BACKGROUND The “central nervous system primitive neuroectodermal tumor” (CNS-PNET) nosology was removed from the World Health Organization (WHO) classification after DNA methylation profiling and new tumor entities characterized by specific recurrent genetic alterations were described. The aim of this study was to re-evaluate the diagnosis of CNS-PNET and to describe their clinical characteristics. METHODS Patients aged &amp;lt; 18 years with CNS-PNET or unclassified tumor, who were treated at Gustave Roussy between 1999 and 2019 or enrolled in the PNET HR trial were retrospectively identified. The study included all patients with sufficient archival material for diagnosis re-evaluation. RESULTS Sixty-two patients were eligible for the current analysis. The central histopathological review proposed a diagnosis according to the WHO classification in 58 cases. Out of these cases, 34 embryonal tumors were identified: 22 Embryonal Tumors with Multilayered Rosettes (ETMR), 4 CNS neuroblastomas with FOXR2 activation (CNS NB-FOXR2), 4 CNS high-grade neuroepithelial tumors with BCOR alteration (CNS HGNET-BCOR), 4 medulloblastomas. Another 24 tumors were classified as non embryonal tumors: 11 high-grade gliomas, 5 ependymomas, 4 pineoblastomas, 2 teratomas, one desmoplastic small round cell tumor, and one pilocytic astrocytoma. Four tumors without suspected diagnosis after first analysis remain unclassified after DNA methylation profiling. The 5-year event-free survival and overall survival for patients with ETMR were 14% (95% CI, 4.7-39%) and 27% (95% CI, 14-54%) respectively. For patients with CNS HGNET-BCOR and CNS NB-FOXR2 the median time to relapse was respectively 11 months (range, 0.5 to 1.3 year) and 3.1 years (range 1.7 to 4.4 years). CONCLUSIONS This study confirmed that the former nosology of CNS PNET does not correspond to a homogenous class but encompasses a diversity of rare histomolecular entities with specific clinical characteristics and outcomes.

Ewing Sarcoma of Kidney: A Rare Entity

AbstractPrimary renal origin of Ewing sarcoma/PNET (primitive neuroectodermal tumor) is a rare entity in the adult population and has an aggressive outcome. The entity was first coined by Arthur Purdy stout in 1918 and recognized under family of small round cell tumor. Radiologically it is difficult to distinguish from primary clear cell carcinoma of kidney from Ewing/PNET. Diagnosis of this requires histopathology, immunohistochemistry (IHC), and cytogenetics studies.A 40-year-old female presented with hematuria and radiology found a mass lower pole of left kidney with extension into renal hilum. Nephrectomy was done for the case and the histopathology diagnosis of small round cell tumor of left kidney was given. Followed by IHC, diagnosis of malignant round cell tumor was suggestive of Ewing sarcoma.Microscopy showed cells with small, round, hyperchromatic nuclei, scant cytoplasm, and inconspicuous nucleoli. Increased mitosis was noted (15/10 high power field). Multiple foci of pseudorosettes, areas of hemorrhage, and necrosis lymphovascular emboli were seen.IHC done outside showed NKX 2-2, synaptophysin positivity, CD99 diffuse membranous positivity, cytokeratin perinuclear dot like positivity, and negative for CD20, CD3, desmin, CD34, S100, and Pax8. Impression of malignant round cell tumor was suggestive of Ewing sarcoma.Ewing sarcoma is one of the rare yet highly aggressive tumors. This should be kept as differential diagnosis in young adults with renal mass, as on radiologically it cannot be differentiated from renal cell carcinoma. Diagnosis of Ewing sarcoma is done using histopathology, IHC, and cytogenetic study. Early diagnosis helps in initiation of surgery, chemotherapy, and radiotherapy and helps in increasing the survival rate.

Posterior fossa primary intracranial extraosseous Ewing’s sarcoma: case report

BackgroundPrimary intracranial Ewing’s sarcoma (ES) is a type of primitive neuroectodermal tumour and is a rare malignant tumour in children and adolescents. The imaging features of ES overlap with other central nervous system embryonal tumours, making it difficult to pinpoint a specific diagnosis. We aim to explore the clinical, neuroimaging and differential diagnoses of this entity.Case presentationWe describe a 6-month-old infant who presented with complaints of enlarging the head size and poor feeding. Imaging revealed a contrast-enhancing large solid-cystic mass lesion with internal calcification, focal bone erosion and haemorrhage in the posterior fossa. Histopathological examinations, immunohistochemistry, and molecular analysis confirmed ES.ConclusionsThe confirmative diagnosis of primary intracranial ES requires histological examination, immunohistochemical analysis, and genetic detection, along with radiological findings. Surgical excision followed by combined radiotherapy and chemotherapy is the treatment of choice.