Primitive Neuroectodermal Tumor Research Articles

Uncommon suspect: A case report of a rare renal neoplasm

Primitive neuroectodermal tumors (PNETs) are a group of rare and aggressive malignancies primarily found in children and young patients. Primary renal PNETs are very much uncommon and share clinical and radiological features with renal cell carcinoma (RCC), thus posing a significant diagnostic and therapeutic challenge. This case report presents the clinical, radiological, and pathological findings of a primary renal PNET in an adult female patient, mimicking the radiological appearance of RCC.

Primitive neuroectodermal tumor of the prostate in a 64 years old man: An unusually late presentation

Primitive neuroectodermal tumor of the prostate in a 64 years old man: An unusually late presentation

Primary intracranial peripheral primitive neuroectodermal tumor: lessons from an exceptionally rare neoplasm. Illustrative case.

The primary intracranial peripheral primitive neuroectodermal tumor (pPNET) is a lesion subtype within the Ewing sarcoma family of tumors. pPNETs are extremely uncommon pathologies, accounting for 0.03% of intracranial tumors and 1% to 2% of Ewing sarcoma cases. Given its histological aspect similar to other highly proliferative malignant neuroectodermal neoplasms, pPNET merits extensive workup for accurate diagnosis and treatment. A 36-year-old male presented to the emergency department with a 1-year history of headaches in the right frontoparietal area, generalized tonic-clonic seizures, and a history of the resection of a tumor labeled as a meningioma 5 years before admission. He was neurologically intact. Brain magnetic resonance imaging revealed a heterogeneous focal lesion of 25 × 35 × 23 mm with a necrotic center and neoformative appearance in the right frontal cortex. The patient underwent multimodal treatment with gross-total resection, radiotherapy, and chemotherapy. Histopathological examination results supported the diagnosis of pPNET. At the 2-year follow-up, the patient had no new-onset symptoms, and brain imaging revealed absent signs of tumor recurrence. The present case describes an extraordinary pPNET case, initially confounded as a clear cell meningioma. Managing pPNET requires thorough investigation, careful differentiation from similar neuroectodermal lesions, and multimodal treatment to improve the patient's prognosis.

A Single-center Experience of Radiotherapy in Pediatric Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Chest Wall.

To evaluate the treatment results, prognostic parameters, and treatment-related toxicity in patients with Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the chest wall who underwent surgery, chemotherapy, and radiotherapy (RT) in a tertiary referral center. The data of 24 patients under 18 years of age with a histologic diagnosis of ES/PNET in the chest wall that received RT in our department between February 2003 and July 2020 were retrospectively evaluated. RT was applied to the primary site±whole involved chest wall and to the whole lung in patients with lung metastasis. The median age was 8.5 years (range: 1.5 to 17y), 15 (63%) patients were female and 9 were male (37%). The tumor localization was extrathoracic in 18 (75%) and intrathoracic in 6 (25%) patients. Mediastinal lymph node and distant metastasis (DM) was present in 5 (21%) and 4 (16%) cases at diagnosis, respectively. The median follow-up after RT was 47 months (range: 11 to 162mo). The 2-year and 5-year overall survival, event-free survival, local recurrence-free survival, and pleural recurrence-free survival were 83% and 48%, 48% and 42%, 74% and 48%, and 61% and 52%, respectively. The overall local control rate was 83% and the pleural control rate was 67%. RT was well tolerated, with 1 case of grade 3 acute dermatitis and 1 case of grade 3 subacute radiation pneumonitis. Late toxicity was observed in 3 (13%) cases. Long-term survival can be achieved with extended-field RT even in patients with ES/PNET of the chest wall with DM. The low toxicity rates allow us to draw the conclusion that RT with modern techniques is an effective and safe treatment modality for these patients.

The pivotal role of irradiation-induced apoptosis in the pathogenesis and therapy of medulloblastoma.

Medulloblastoma (MB) is a rare primitive neuroectodermal tumors originating from the cerebellum. MB is the most common malignant primary brain tumor of childhood. MB originates from neural precursor cells in distinctive regions of the rhombic lip, and their maturation occurs in the cerebellum or the brain stem during embryonal development. Also, apoptosis is a programmed cell death associated with numerous physiological as well as pathological regulations. Irradiation (IR)-induce apoptosis triggers cell death, with or without intervening mitosis within a few hours of IR and these share different morphologic alteration such as, loss of normal nuclear structure as well as degradation of DNA. Moreover, MB is strikingly sensitive to DNA-damaging therapies and the role of apoptosis a key treatment modality. Furthermore, in MB, the apoptotic pathways are made up of several triggers, modulators, as well as effectors. Notably, IR-induced apoptotic mechanisms in MB therapy are very complex and they either induce radiosensitivity or inhibit radioresistance leading to potential effective treatment strategies for MB. This review explicitly explores the pivotal roles of IR-induced apoptosis in the pathogenesis and therapy of MB.

Renal primitive neuroectodermal tumor in an adolescent: a case report and review of literature

Renal primitive neuroectodermal tumor is a highly malignant neoplasm that commonly affects young adults and infrequently presented in children and adolescents. We report a case of a 14-year-old female child who presented with abdominal mass. PET-CT showed an FDG avid cystic lesion in the inter and lower polar regions of the right kidney, extending into the right renal fat and renal vein, with multiple FDG avid lesions in the axial and appendicular skeleton, suggesting renal mass with bony metastases. Biopsy confirmed the diagnosis of primitive neuroectodermal tumor of the kidney. The patient completed six cycles of chemotherapy with partial response and subsequently the patient defaulted and lost to follow-up. To emphasize the critical significance of renal PNET in the differential diagnosis of renal tumors in children.

Abstract 1632: Dissecting AMBRA1-cyclin D axis deregulation in embryonal tumors of the central nervous system

Abstract Dissecting AMBRA1-cyclin D axis deregulation in embryonal tumors of the centralnervous systemEmbryonal tumors of the central nervous system (CNS) are malignant growths originating from embryonic neural stem cells, primarily affecting pediatric patients. These tumors pose a significant threat to children's health, leading to high morbidity and mortality rates. To improve survival rates and reduce morbidity, there is a critical need for advanced molecular diagnostics and innovative therapies. Among these tumors are medulloblastomas (MB) and other embryonal tumors, previously classified as primitive neuroectodermal tumors (CNS-PNET). These malignancies are characterized by uncontrolled cell proliferation, primarily driven by abnormalities in cell cycle proteins. Consequently, targeting cell cycle regulators has emerged as a promising approach for their treatment. Two key signaling pathways, namely the MYC and the cyclin D-CDK-RB pathway, govern the decision-making process related to genome replication. Mutations in both MYC and the CDK4/6/cyclin D pathway, leading to the functional inactivation of RB, have been identified as relevant factors in the development of CNS-PNET and medulloblastomas. Our seminal research has highlighted the crucial role of AMBRA1, an upstream master regulator orchestrating the transition from G1 to S phase (Maiani & Milletti et al., 2021). Specifically, AMBRA1 modulates the abundance of D-type cyclins and MYC by facilitating their proteasomal degradation, thereby ensuring genomic stability during DNA replication.Based on these discoveries, we propose that AMBRA1 functions as a multifaceted tumor suppressor across various cancer types. An unbiased Sleeping Beauty analysis identified AMBRA1 as a genetic driver of CNS-PNET, providing a strong foundation for investigating its role further (Beckmann et al., 2019). We hypothesize that the simultaneous deletion of AMBRA1 and p53 in an inducible knockout mouse model can lead to the spontaneous development of CNS-PNET or medulloblastoma, contingent on the specific targeted cell lineage. Additionally, our research demonstrates that AMBRA1 deficiency confers resistance to CDK4/6 inhibitors while creating a synthetic lethality with CHK1 inhibitors. Consequently, we propose that a comparative analysis of AMBRA1, D-type cyclins, and Myc family expression levels could serve as a diagnostic marker. This marker could facilitate patient-based stratification for CHK1 inhibitor treatment efficacy, enabling the differentiation of non- responsive cases to CDK4/6 chemotherapy. Citation Format: Giacomo Milletti, Giulia Cadeddu, Alba Adelantado Rubio, Caterina Ferraina, Apolinar Maya-Mendoza, Francesco Cecconi. Dissecting AMBRA1-cyclin D axis deregulation in embryonal tumors of the central nervous system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1632.

Operative treatment of pulmonary primitive neuroectodermal tumor: a case report and literature review

BackgroundPulmonary primitive neuroectodermal tumor (PNET), a member of the Ewing sarcoma family of tumors, is a rare malignancy that is associated with a grim prognosis. To date, fewer than 30 cases of pulmonary PNET have been reported. In this case report, we present the clinical details of a 12-year-old girl with pulmonary PNET who underwent surgical treatment. We also conducted an analysis and summary of other relevant studies and the surgical outcomes.Case presentationIn May 2018, a 12-year-old girl was admitted with symptoms of cough and blood-tinged phlegm. A computed tomography scan revealed a large mass, measuring 12.9 cm × 8.1 cm, in the right middle and lower lungs. A percutaneous lung biopsy confirmed poorly differentiated tumor cells with a nested growth pattern. Immunohistochemical staining demonstrated positive expression of CD99, CD56, Vimentin, and Synaptophysin. The patient was diagnosed with pulmonary PNET. Following three cycles of neoadjuvant chemotherapy, a substantial reduction in tumor volume was observed. Subsequently, the patient underwent a surgical procedure involving pneumonectomy and partial resection of the left atrium with the assistance of cardiopulmonary bypass. The patient was discharged 37 days after surgery. During a three-year follow-up period, she exhibited no signs of tumor recurrence and has successfully returned to school.ConclusionsThis case highlights the successful management of an advanced PNET with neoadjuvant chemotherapy, pneumonectomy, and partial resection of the left atrium employing cardiopulmonary bypass. The patient remained disease-free after three years. Our analysis of surgically treated cases indicates that neoadjuvant chemotherapy can contribute to improved prognoses for PNET patients. It is crucial to emphasize that complete surgical excision remains the cornerstone of treatment, underscoring the importance of surgeons considering radical surgical approaches whenever feasible for patients with pulmonary PNETs.

Abstract PR-010: Asc1lb progenitor-specific RB conditional inactivation in zebrafish models rare CNS primitive neuroectodermal tumors

Abstract PR-010: Asc1lb progenitor-specific RB conditional inactivation in zebrafish models rare CNS primitive neuroectodermal tumors

A young boy with a rare tumor presenting as an upper gastrointestinal bleed

Abstract We describe an interesting upper gastrointestinal endoscopy image of a mass seen in the stomach of a 19-year-old boy who presented to us with an upper gastrointestinal bleed without any history of pain or illness in the past and was diagnosed as a primitive neuroectodermal tumor or Ewing's sarcoma of the stomach.

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.

Primitive neuroectodermal tumors of the ovary: a multidecade review of the scientific literature.

Primitive neuroectodermal tumor (PNET) is a general term used in scientific literature for a heterogeneous group of small round-cell malignant tumors primarily arising from neural crest cells. These are extremely aggressive neoplasms which usually occur within soft tissue or bone of young adults. Ovarian tumors composed of primitive neuroectodermal elements are extremely rare, with only few case reports in scientific literature. Due to being so exceedingly rare, PNETs are frequently misdiagnosed and there are no standard therapeutic guidelines. Young patients seem to have better prognoses and individualized strategy is recommended. Limited data suggests that various gene deletions as well as amplifications may be crucial factors for tumorigenesis and the aggressive behavior of PNET. In this paper, we performed a brief review of all cases of primary ovarian PNETs published in the scientific literature to date, in regard to their clinical, histopathological, and therapeutic aspects, with the aim to provide a more comprehensive understanding of this exceedingly rare pathology.

Role of Intra-operative Transesophageal Echocardiographic Examination in Inferior Vena Cava Tumor Thrombus Removal in a Case of Renal Ewing’s Sarcoma

Ewing’s sarcoma belongs to primitive neuroectodermal tumors. Renal Ewing’s sarcoma is an extremely rare tumor that can progress to the inferior vena cava (IVC) or right atrium (RA). Renal tumors with IVC/RA extension entail removal of the tumor, including tumor thrombus in IVC with or without the use of cardiopulmonary bypass, depending on the tumor thrombus extent. Intra-operative transesophageal echocardiography provides the latest staging of tumor thrombus, its characteristics, and mobility, guides IVC clamping for tumor removal, aids in troubleshooting hemodynamic instability, and monitors completeness of tumor removal post-procedure. Transesophageal echocardiographic examination forms an indispensable part of intra-operative management in any case of IVC tumor thrombus removal.

[Tumor neuroectodérmico primitivo na coluna cervical de um cão - Relato de Caso]

ABSTRACT A case of peripheral primitive neuroectodermal tumor in the cervical region of a canine is described. The patient was a canine, male, five years old, large size, with acute neurological clinical signs, severe neck pain and tetraplegia. On computed tomography, an oval-shaped mass located dorsally to cervical vertebrae C4 to C7 was observed, with infiltration over the spinal cord between vertebrae C4 and C5, discreetly widening the dorsal intervertebral foramina of the cervical vertebrae and compressing the dorsal portion of the spinal cord of this segment. Under microscopy, the neoplastic cells were small, irregular in shape and with scarce cytoplasm. Immunoreactivity for vimentin, which can only be expressed in PTNEs tumors, was decisive for diagnostic confirmation. Additionally, the positivity of the S-100 protein, which is expressed in neuroectodermal cells mainly of the neural crest cells, reinforced the classification as PTNE, and the negativity in the expression for glial fibrillary acidic protein (GFAP) ruled out the presence of small cell glioma of the central nervous system. Based on the clinical history, imaging exams, cellular morphology and mainly on immunohistochemical staining, the diagnosis of primitive neuroectodermal tumor (PTNE) with infiltration and compression of the spinal cord in the cervical region of the dog was confirmed, considered uncommon in this species.

Ewing’s Sarcoma of the Adrenal Gland; A Rare Extraosseous Presentation

Ewing sarcoma also known as peripheral primitive neuroectodermal tumors (ES/PPNETs) usually produce in the chest wall, extraosseous soft tissues, and long or flat bones, however only rarely in solid organs. Although they can develop in any part of the body, development in the adrenal glands is very uncommon. We present a case of Ewing sarcoma (PNET) of the adrenal gland and the extraordinary diagnostic and therapeutic challenges faced during its diagnosis. Early detection of extraosseous disease with radiological imaging and the multimodality treatment strategy lowers morbidity and death in Ewing’s sarcoma of the adrenal gland.

Recurrent Medulloblastoma: Complete Response and > than 21 Years and Five Months Overall Survival in a One-Year and SevenMonth-Old Male Treated with Antineoplastons

Medulloblastomas arise in the posterior fossa, primarily in the region of the fourth ventricle. Recurrent medulloblastomas are high-risk and have a bad prognosis. Objectives: the case of a male child with recurrent, disseminated medulloblastoma is presented to detail the efficacy of ANP therapy (Antineoplaston A10 {Atengenal} and Antineoplaston AS2-1 {Astugenal}) in the treatment of high-risk medulloblastoma. This child was treated at the Burzynski Clinic (BC), as a Special Exception, according to Protocol BT-12, “Phase II Study of Antineoplastons A10 and AS2-1 in Children with Primitive Neuroectodermal Tumors”, with intravenous (IV) ANP therapy via a subclavian catheter and infusion pump. Tumor response was measured by sequential magnetic resonance imaging (MRI) of the brain with gadolinium enhancement. Findings: This child initially underwent tumor resection, placement of ventricular shunts, and chemotherapy, all performed elsewhere. Baseline MRI at the BC revealed recurrent, disseminated, and enhancing disease measuring 9.10 cm2 in total. IV ANP therapy began in March 2001 and ended in December 2002 after a complete response (CR) was achieved based on MRI criteria. Subsequently, the child received oral Antineoplastons as maintenance therapy, which were discontinued after eight months. At last follow-up, > 21 years and eight months since diagnosis and > 21 years and five months since the start of IV ANP therapy, the patient was well and showing no evidence of tumor recurrence. Conclusions: The utilization of ANP therapy to cure a patient with recurrent medulloblastoma is presented. We conclude that ANP therapy is an attractive therapeutic option for children with medulloblastoma

Cell-binding IgM in CSF is distinctive of multiple sclerosis and targets the iron transporter SCARA5.

Intrathecal IgM production in multiple sclerosis is associated with a worse disease course. To investigate pathogenic relevance of autoreactive IgM in multiple sclerosis, CSF from two independent cohorts, including multiple sclerosis patients and controls, were screened for antibody binding to induced pluripotent stem cell-derived neurons and astrocytes, and a panel of CNS-related cell lines. IgM binding to a primitive neuro-ectodermal tumour cell line discriminated 10% of multiple sclerosis donors from controls. Transcriptomes of single IgM producing CSF B cells from patients with cell-binding IgM were sequenced and used to produce recombinant monoclonal antibodies for characterization and antigen identification. We produced five cell-binding recombinant IgM antibodies, of which one, cloned from an HLA-DR + plasma-like B cell, mediated antigen-dependent complement activation. Immunoprecipitation and mass spectrometry, and biochemical and transcriptome analysis of the target cells identified the iron transport scavenger protein SCARA5 as the antigen target of this antibody. Intrathecal injection of a SCARA5 antibody led to an increased T cell infiltration in an experimental autoimmune encephalomyelitis (EAE) model. CSF IgM might contribute to CNS inflammation in multiple sclerosis by binding to cell surface antigens like SCARA5 and activating complement, or by facilitating immune cell migration into the brain.

Maternal Prenatal Use of Alcohol, Tobacco, and Illicit Drugs and Associations with Childhood Cancer Subtypes.

The association between childhood cancer risk and maternal prenatal substance use/abuse remains uncertain due to modest sample sizes and heterogeneous study designs. We surveyed parents of children with cancer regarding maternal gestational use of tobacco, alcohol, and illicit drugs, using a Likert-type scale, and demographic, perinatal, and clinical variables. Multivariable log-Poisson regression assessed differences in frequency of prenatal substance use across fifteen childhood cancer subtypes, adjusting for birthweight, gestational age, and demographic factors. Respondents from 3,145 unique families completed the survey (92% biological mothers). A minority reported gestational use of tobacco products (14%), illicit drugs including marijuana or cocaine (4%), or more than a moderate amount of alcohol (2%). Prenatal illicit drug use was associated with increased prevalence of intracranial embryonal tumors [prevalence ratio (PR) = 1.94; confidence interval [CI], 1.05-3.58], including medulloblastoma (PR = 1.82) and supratentorial primitive neuroectodermal tumors (PNET; PR = 2.66), and was also associated with retinoblastoma (PR = 3.11; CI, 1.20-8.08). Moderate to heavy alcohol consumption was strongly associated with elevated prevalence of non-Hodgkin lymphoma (PR = 5.94; CI, 1.84-19.21). Prenatal smoking was not associated with elevated prevalence of any childhood cancer subtype. We identify novel associations between illicit drug use during pregnancy and increased prevalence of nonglioma central nervous system tumors, including medulloblastoma, supratentorial PNETs, and retinoblastoma. Gestational exposure to alcohol was positively associated with non-Hodgkin lymphoma. Although alcohol and tobacco use during pregnancy has declined, gestational cannabis use has risen. Investigating its impact on neurodevelopment and brain tumorigenesis is vital, with important implications for childhood cancer research and public health education.

ASKIN’S TUMOR: A CASE REPORT AND LITERATURE REVIEW

Askin tumour is an uncommon form of malignant neoplasm that develops from the soft tissues of the thoracopulmonary wall and has a neuroectodermal origin and possess aggressive behavior. As it mimics other common pediatric disorders such as empyema, tuberculosis, lymphoma, rhabdomyosarcoma and neuroblastoma, it acts as a great diagnostic and therapeutic challenge to the treating clinicians. Its rarity, however, contributes greatly to the absence of standardized treatment protocols further facilitating detrimental prognosis. So, the major deciding factor of its survival rate is early and precise diagnosis followed by its treatment. The present study reports a case Askin’s tumor in a child which is locally aggressive and quite rare. While making the definitive diagnosis of an Askin’s tumour of the thorcopulmonary region the possibility of the occurrence of other primitive neuroectodermal tumors (PNET) was not ruled out.

Case Report: Cytodiagnosis of primitive neuroectodermal tumor (PNET) of sinonasal tract

Malignant sinonasal tumors are rarely encountered in the practice of oncology as they constitute only 1% of total body tumors. The occurrence of primitive neuroectodermal tumor (PNET) in the sinonasal tract is even more uncommon. The PNET belongs to Ewing sarcoma family and forms the differential diagnosis of a large group of lesions generally described as malignant round cell tumors. The unique pathogenetic chromosomal alteration in this lesion is the EWS FLI1 fusion gene. This case report describes the unusual occurrence of PNET for its cytomorphological diagnosis along with its clinical features, radioimaging findings and immunohistochemistry. Such case reports are scarce in literature and cytodiagnosis of PNET in sinonasal tracts warrants its sharing with medical fraternity as such diagnoses are stumbled along rarely in clinical practice.