Malignant Neuroectodermal Tumor Research Articles

Esthesioneuroblastoma: an institutional based descriptive study of a rare tumor

Background: Esthesioneuroblastoma is a slow-growing rare malignant neuroectodermal tumor arising from the olfactory epithelium. It has a bimodal incidence with peaks in the second and third decades of life and the sixth and seventh decades of life with equal incidence among men and women. Prognostic factors include the Hyams grade and modified Kadish stage. This study analyzed the clinicopathological features of esthesioneuroblastoma. Materials and methods- Retrospective study of patients who were diagnosed with esthesioneuroblastoma at a tertiary care hospital between January 2012 and May 2019 was conducted. The research was performed according to the World Medical Association Declaration of Helsinki. Institutional research committee approval (IEC: 473/2019) was obtained. Results: Clinicopathological profiles of 8 patients who were diagnosed with esthesioneuroblastoma during the period were included. Among the eight patients, five were female and three were male. Common presenting complaints were nasal obstruction, difficulty in breathing, epistaxis, local pain, and anosmia. The average age of presentation was 52 years, ranging from 14 to 73 years. Anterior rhinoscopic examination in these cases showed a polypoid mass located in the nasal cavity. According to the Hyams grading system, three of the eight cases were grade-2 and the remaining five cases were grade-3 Hyams histological grade. Three cases exhibited foci of ganglioneuroblastic transformation. Three patients had metastases to cervical lymph nodes and three patients had recurrence. Conclusions: Esthesioneuroblastoma is a rare aggressive malignant tumor. It can exhibit divergent epithelial or ganglionic differentiation. A proper diagnosis should be made, graded and staged before proceeding to treatment.

Olfactory neuroblastoma: Up-to-date review and our experience

Abstract Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignant neuroectodermal tumor originating primarily from the basal layer of the olfactory epithelium in the roof of the nasal cavity. The most common symptoms are nasal obstruction, anosmia, recurrent epistaxis, rhinorrhea and excessive lacrimation. Imaging studies are helpful for assessing the extent of olfactory neuroblastoma, as well as grading the tumor. The definitive diagnosis is based on histopathological exam and immunohistochemistry profile and it might be quite challenging because the tumor can mimic other sinonasal malignancies. Because of the small number of reported cases and the lack of prospective research, the optimal treatment for olfactory neuroblastoma is still controversial. However, it is generally believed that surgical resection followed by radiotherapy gives the best outcome in terms of recurrence and survival rates. Keeping in mind the rarity of olfactory neuroblastoma and the diagnostic difficulty, the aim of this study is to improve the understanding of the clinical features by reviewing the literature focusing on the recent advances in the diagnosis and treatment of ONB. Moreover, we are reporting an atypical case of an aggressive type of olfactory neuroblastoma treated through a multimodal approach, with no signs of tumor recurrence after a 3-month follow-up.

Olfactory neuroblastoma: A case report

Olfactory neuroblastoma (ON) is a rare malignant neuroectodermal tumor of the nasal cavity. The malignancy accounts for <3% of tumours originating in the nasal cavity. Through the nasal cavity, ON may infiltrate the sinuses, the orbit and the cranium. The tumour is characterized by a pattern of slow growth and local recurrences. Olfactory neuroblastoma is a neoplasm that can histologically mimic many tumours within the sinonasal tract. Treatment options are surgical excision combined with a radiotherapy and/or chemotherapy combination treatment.The present study reports the case of a 45 year-old male patient with a mass in the nasal cavity who was treated by combined surgical excision and radiotherapy. The literature for ON and the treatment of the tumour are also discussed.

Medulloblastoma like Neuroectodermal Tumour Arising from Ovarian Teratoma in a 16 Year Old Patient: A Case Report

Malignant neuroectodermal tumor with differentiation medullo-blastoma-like in an immature ovarian teratoma is a very rare and aggressive tumor. Only few cases are reported and most occur in adolescence. In our experience we performed a conservative surgery for a FIGO stage 1A tumor but bone recurrence followed within 5 months from surgery. Association of CHT (cisplatin-etoposide followed by tandem high-dose Thiotepa and auto transplantation of hematopoietic stem cell) and external beam radiotherapy was effective for the management of the recurrence but no guidelines are still available.

Calvarial melanotic neuroectodermal tumor of infancy: A rare case report

Abstract Background: Melanotic neuroectodermal tumor of infancy (MTNI) is a rare congenital tumor of neural crest origin. It is a locally aggressive tumor affecting infants during the first year of life. It commonly arises in the maxilla, mandible, and in the cranial vault. MTNI is usually a benign lesion. Occasionally, it may turn malignant. Though the tumor can be detected by computed tomography and magnetic resonance imaging, an exact diagnosis can only be made by histopathology and immunostaining. Complete surgical excision of the tumor is the gold standard treatment of choice. Benign cranial vault tumors have a good prognosis in contrast to malignant tumors. Case Description: A 3-year-old male child was brought by his mother to the outpatient department with complaints of a large swelling on the left temporal-parieto-occipital region. Computed tomography and magnetic resonance imaging were done which revealed a large hyperdense and hypointense mass in the left temporal-parieto-occipital region with lytic alterations in the skull. The tumor was excised, and tissue sent for histopathology and immunostaining, which revealed a diagnosis of a malignant neuroectodermal tumor of infancy. The patient recovered well in the follow-up period. Conclusion: We report an exceedingly rare case of giant malignant neuroectodermal tumor of infancy (progonoma).

OLFACTORY NEUROBLASTOMA: A CASE SERIES FROM A SINGLE INSTITUTION

<h3>Introduction</h3> Olfactory neuroblastoma (ONB) is an uncommon malignant neuroectodermal sinonasal tumor, which comprises approximately 2% to 3% of all sinonasal tumors. These tumors originate from specialized sensory neuroepithelial/neuroectodermal olfactory cells and occur most frequently in the upper nasal cavity, in the region of the cribriform plate. All age groups are affected, and patients often present with locally advanced disease resulting from delay in presentation. This is attributed to the slow growth by tumors and nonspecific symptomatology. <h3>Objective</h3> To evaluate the histologic features and management outcomes for patients with ONB at our institution. <h3>Results</h3> Over a 10-year period (2009-2019) 6 patients were identified with ONB. The majority of tumors (n = 4) were locally advanced at the time of presentation with extension beyond the nasal cavity and paranasal sinuses (Kadish stage C). One tumor was stage B, and one was stage A. Three tumors were Hyams grade I, 2 tumors were grade II, and 1 tumor was grade III. One grade I tumor demonstrated ganglioneuromatous differentiation. Glandular differentiation was seen in 1 grade II ONB. All patients had surgical resection, with 3 patients receiving postoperative radiotherapy. One patient was found to have multiple bony and left cervical metastases by cross-sectional staging imaging and therefore received postoperative chemotherapy. All patients are alive with 4 patients free from disease (follow-up period ranging from 1-108 months). <h3>Conclusions</h3> At our center patients typically presented with advanced disease with most patients receiving multimodality treatment comprising surgery and radiotherapy. All patients are alive with only 1 patient with disseminated disease.

Giant congenital nodular melanoma in a newborn: a case report and literature review

BackgroundMalignant melanoma (MM) arises predominantly after adolescence and is uncommon in children. Congenital MM in newborns is even rarer with a dearth of published literature; as a consequence, there is no uniform standard for the pathogenesis and treatment for neonatal malignant melanoma. Herein we report a case of giant congenital nodular MM in a newborn, including its clinical, imaging, pathological and molecular pathological features. This case is the largest giant congenital primary nodular malignant melanoma in utero in neonates currently reported in China.Case presentationA female neonatal patient was found to have a 2.97 cm× 1.82 cm×1.50 cm mass with a clear boundary at the right acromion in color Doppler ultrasound examination at 24 weeks of gestation. The mass increased to 3.0 cm×5.0 cm×9.0 cm at birth, and local ulceration was seen. MRI demonstrated that the mass was located on the right shoulder and underarm in a lobulated appearance, and surrounded the right scapula which was deformed. Clinical stage:IV(AJCC 8th Edition (2017)). α-Fetoprofein (AFP) by hematological examination: 1210ng/ml, NSE: 21.28ng/ml, LDH: 842U/L. The patient underwent surgical resection of the tumor, and was pathologically diagnosed as neonatal congenital malignant melanoma; immunohistochemistry (IHC): S-100 (+), HMB45 (+), Melan A (+), and Tyrosinase (+). Molecular pathological examination for BRAF V600E showed no mutations (Quantitative Real-time PCR, qPCR); And so were NRAS, C-kit (exons 9,11,13,14,17,18), and TERT (promoter locus, C228T and C250T) (Sanger sequencing). Non-surgical therapies were not carried out after the surgical resection of the tumor. After 6 months of follow-up, the child developed normally, and color Doppler ultrasound showed no obvious tumor growth or abnormality in the original tumor site.ConclusionsIt is extremely rare to see giant congenital primary nodular MM in utero in neonates. The pathogenesis, treatment and prognosis of congenital MM need further research. The diagnosis mainly depends on histopathology and immunohistochemistry, and it needs to be differentiated from malignant lymphoma and primitive neuroectodermal tumor. The current treatment strategy for MM relies on the surgical excision of the mass. Research directed at molecular detection for genetic mutations would contribute to targeted therapy and better prognosis.

Review of the cytological features of olfactory neuroblastoma: A retrospective single-center study.

Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor. Due to the rarity, there are scarce reports describing the cytological features of ONB. Thus, we aimed to analyze these cytological features and discuss their differences depending on the histological grading of ONB. Patients with a histopathological diagnosis of ONB who underwent fine-needle aspiration cytology were enrolled in the study. The cytological features, including arrangement and shape of neoplastic cells, nuclear features, and presence of rosettes, were analyzed. Eight patients with ONB were enrolled; cytological specimens of seven patients were obtained from metastatic lesions and that of one patient were obtained from the nasal cavity tumor. The cytological specimens demonstrated variable-sized clusters of neoplastic cells and single cells. Two-cell pattern, composed of large-sized viable neoplastic cells and small-sized apoptotic cells, was noted in 3 of 4 high-grade ONBs but in none of 4 low-grade ONBs. This reflects that the presence of the two-cell pattern may represent higher proliferation in neoplastic cells. The neoplastic cells had scant cytoplasm and round to oval nuclei containing fine to granular chromatin without conspicuous nucleoli. Rosettes and paranuclear blue bodies were observed in one patient. Most cytological specimens of ONB were obtained from metastatic lesions, especially from the cervical lymph node. Thus, ONB should be differentiated from malignant lymphoma and small cell neuroendocrine carcinoma. Recognition of these cytological features of ONB while considering patient history can aid in correctly diagnosing ONBs. Moreover, the presence of two-cell pattern might reflect high-grade histology of ONB.

Olfactory Neuroblastoma of the Sinonasal Tract with Prominent Orbital Protrusion: A Case Report and Literature Review

Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor of the nasal cavity. Olfactory neuroblastoma centered in the posterior right orbit with prominent orbital protrusion is even rare. Grading ONB is extremely important as individualized treatment plans must be formulated according to tumor grade. We report the case of a 67-year-old female who presented with the chief complaints of persistent nasal congestion with intermittent epistaxis and unilateral proptosis over the past five years. Radiological imaging was suggestive of a large heterogeneous mass in the right superior nasal cavity with extensions into the right medial orbit, nasopharynx, the right maxillary sinus, the anterior cranial fossa, right ethmoidal, frontal and bilateral sphenoidal sinuses, as well as into the right frontal lobe. Assessment of the radiologic features revealed the diagnostic possibility of olfactory neuroblastoma. A nasopharyngeal biopsy confirmed an olfactory neuroblastoma. Frontal osteoplastic craniotomy and excision of the intracranial part of the tumor from above and transnasal endoscopic removal of the mass in the nasal cavities, paranasal sinuses and right medial orbit from below was done. Evaluation of histopathological characteristics and immunohistochemical findings revealed a diagnosis of WHO grade IV olfactory neuroblastoma. Because of poor economic condition, the patient did not take adjuvant radiotherapy and chemoradiation and post-operative examination. We report a huge ONB centered in the posterior right orbit with prominent orbital protrusion. Magnetic resonance image and computed tomography are helpful for evaluating the appearance and the extent of ONB, as well as grading this tumor, which may aid therapeutic decisions and improve survival.

PATH-40. INTRAGENIC DMD DELETIONS ARE THE MOST COMMON RECURRENT GENOMIC ALTERATIONS IN ESTHESIONEUROBLASTOMA

Abstract INTRODUCTION Esthesioneuroblastoma (ENB) is a rare, malignant neuroectodermal tumor of the olfactory epithelium. To date, a few recurrent genetic alterations have been identified in ENB. Here, we sought to examine the genomic signature on a series of clinically well-characterized aggressive ENB samples. METHODS We performed whole-exome sequencing in a cohort of 26 ENB samples from 12 patients, containing 11 matched primary-metastatic samples. Additionally, targeted sequencing was carried out in all samples to determine TERT promoter hotspot mutations. Furthermore, we performed immunohistochemistry (IHC) using an antibody that recognizes the dystrophin central rod domain in all available specimens. RESULTS Our cohort consisted of 9 male and 3 female patients with a median age of 66 years at first diagnosis (4- 77 years). One patient was staged Kadish B at the time of diagnosis and eleven were staged Kadish C. The median overall survival was 3.85 years (0.3 – 16 years). Consistent with previous findings, each tumor exhibited a different mutational signature and the mutational landscape appears to be predominantly driven by copy number variations. Interestingly, we detected intragenic deletions in dystrophin (DMD) as the most common and consistent alteration in ENB patients (in 11 of 12 patients, 91.6%). DMD deletions, when identified within the primary ENB, were preserved in all subsequent metastatic lesions. Moreover, DMD deletions where concurrently identified in three cases with multiple metastases. IHC revealed the concurrent loss of dystrophin expression, the protein encoded by DMD, in all cases with DMD deletions. Otherwise, no other recurrent genomic findings were detected, including TERT promoter mutations. CONCLUSIONS Our findings validate previously described DMD deletions as the most common recurrent genomic alteration in primary ENB. Furthermore, our data demonstrate that DMD deletions were perpetuated in subsequent metastatic lesions, and when identified in any metastasis, were present in other metastases from the same patient.

Survival in adult and pediatric patients with medulloblastoma: A 2018 SEER-based analysis.

e14529 Background: Medulloblastoma (MB) is a malignant neuroectodermal tumor accounting for 30% of pediatric and only 1% of adult brain tumors. In previous studies comparing survival in pediatric and adult MB from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database no difference has been found. However, diagnostic subgroup analyses have been limited. Methods: We examined survival in children (age 0-19) and adults (20-79) coded as MB in the 2018 SEER database (2000-2016). We used Kaplan Meier analysis, log-rank test and Cox proportional hazard ratios (HR) with 95% confidence intervals (CI). MB in SEER-18 is defined as ICD-O-3 histology codes 9470–9474 (n = 1,728). ICD 9473, supratentorial PNET (sPNET, n = 97) is biologically distinct and therefore it was analyzed separately. Results: We found that 5-year survival for MB, excluding sPNET, was similar in children (n = 1,091, 75.3%) and adults (n = 488, 79.1%) (HR = 0.97, CI: 0.79 – 1.17, p = 0.50). Furthermore, subtype analyses showed no survival difference comparing adults and children with desmoplastic nodular MB (n = 222, p = 0.09), large cell MB (n = 73, p = 0.46), or MB NOS (n = 1330, p = 0.10). Yet, children with sPNET had improved 5-year survival (n = 65, 72.3%) compared to adults (n = 29, 51.7%) (HR = 2.0, CI: 1.10 – 3.92; p = 0.02,). These findings indicate that while survival in patients with MB is similar across age groups, children with sPNET have improved outcomes. Conclusions: In summary, 2018 SEER data for MB continue to show no survival difference between adults and children, suggesting adult patients could appropriately be entered on pediatric MB treatment protocols. Further analyses of the 2018 data are ongoing adjusting for sex, race, and treatment (chemotherapy or radiation). For sPNET, the apparent improved outcomes for children merit further detailed investigation and will be re-evaluated using the new 2016 World Health Organization classification.

Esthesioneuroblastoma With Probable Paraneoplastic Hypertension: A Case Report

Abstract Objectives Esthesioneuroblastoma or olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor accounting for 2% of all intranasal tumors with a reported incidence of 0.4 per million. We report an interesting case of ONB associated with hypertension, suspicious for paraneoplastic syndrome. Methods A 41-year-old male with clinical symptoms of chronic sinusitis presented with gradually worsening unilateral nasal obstruction. Computerized tomography demonstrated a 2.1-cm expansile mass in left ethmoid sinus. Examination revealed a swollen, erythematous middle turbinate. A left ethmoidectomy was performed. Results Histologic examination of the specimen revealed lobular nests of monomorphic small cells with round nuclei, salt and pepper chromatin, and indistinct cytoplasm embedded in a fibrillary stroma with abundant neuropil. Mitosis, necrosis, and nuclear pleomorphism were absent. Immunohistochemically, the neoplastic cells were positive for synaptophysin, chromogranin, CD56, and neuron-specific enolase and negative for pancytokeratin AE1/AE3, CAM 5.2, and CD45. S-100 focally highlighted the sustentacular cells. A diagnosis of ONB, Hyams grade 1 was made. Of note, the patient had a history of hypertension and the original surgery had been cancelled due to hypertensive urgency. With the suspicion of a paraneoplastic hypertension, his catecholamines were ordered; however, he failed to follow up for his scheduled testing. Five weeks postoperative, he was seen in the emergency department and found to be normotensive without antihypertensive medication. The clinical findings are strongly suggestive of paraneoplastic hypertension associated with ONB. Conclusion ONB is a rare tumor associated with a high recurrence rate due to its anatomical location. Survival rates are best with surgical resection followed by radiotherapy. ONB may rarely be associated with paraneoplastic syndromes. Review of available literature reveals only five reported cases of ONB with paraneoplastic hypertension. The rarity of this tumor and the clinical presentation highly suspicious for paraneoplastic hypertension make this case uniquely interesting.

Cytogenetic characterization of the malignant primitive neuroectodermal SK-PN-DW tumor cell line

BackgroundThe SK-PN-DW cell line was established in 1979 and is commercially available. Despite the use of this cell line as an in vitro model for functional and therapeutic studies of malignant primitive neuroectodermal tumor (PNET), there is a lack of complete information about the genetic alterations that are present at the cytogenetic level. Thus, the current study aimed to characterize the cytogenetic profile of this cell line.MethodsRoutine G-banded chromosome analysis, fluorescence in situ hybridization, and oligonucleotide array comparative genomic hybridization assays were performed to characterize the chromosomal changes in this cell line.ResultsThe G-banded karyotype analysis showed that the number of chromosomes in this cell line ranged between 36 and 41. Importantly, all cells displayed a loss of chromosomes Y, 11, 13, and 18. However, some cells showed an additional loss of chromosome 10. Additionally, the observed structural changes indicated: a) unbalanced translocation between chromosomes 1 and 7; b) translocation between chromosomes 11 and 22 at breakpoints 11q24 and 22q12, which is a classical translocation that is associated with Ewing sarcoma; c) a derivative chromosome due to a whole arm translocation between chromosomes 16 and 17 at likely breakpoints 16p10 and 17q10; and d) possible rearrangement in the short arm of chromosome 18. Moreover, a variable number of double minutes were also observed in each metaphase cell. Furthermore, the microarray assay results not only demonstrated genomic-wide chromosomal imbalance in this cell line and precisely placed chromosomal breakpoints on unbalanced, rearranged chromosomes, but also revealed information about subtle chromosomal changes and the chromosomal origin of double minutes. Finally, the fluorescence in situ hybridization assay confirmed the findings of the routine cytogenetic analysis and microarrays.ConclusionThe accurate determination of the cytogenetic profile of the SK-PN-DW cell line is helpful in enabling the research community to utilize this cell line for future identity and comparability studies, in addition to demonstrating the utility of the complete cytogenetic profile, as a public resource.

Endonasal endoscopic sinus surgery with rhinobasis resection due to esthesioneuroblastoma: case report.

Aim: Esthesionevroblastoma is a rare malignant neuroectodermal tumor that begins development of neuroepithelial cells of the olfactory membrane. Therefore the biology of the tumor, surgery is a method of choice. Endoscopic transnasal method with craniobasal resection is favorable alternative to more invasive surgical methods in a rigorous assessment of patients. Our aim is to describe the first case in the country operated endonasal with typical clinical and histopathological findings of olfactory neuroblastoma, and to discuss opportunities for radical surgery by endoscopic endonasal sinus surgery. Material and methods: We present a patient with nasal obstruction, epistaxis, smell disturbance, headache and eye symptoms. Results: Single step transnasal endoscopic resection with craniektomia, then undergoes postoperative radiotherapy is made on the patient. One year after surgery, no clinical, endoscopic and radiologic evidence of disease recurrence. Conclusion: Esthesionevroblastoma is a rare malignant tumor that untypical because its initial symptoms are often diagnosed at later stages. Early detection and timely performed treatment is important moment for the prognosis.

ISOLATED SPLENIC METASTASIS IN A PATIENT WITH ESTHESIONEUROBLASTOMA

Esthesioneuroblastoma is included in the group of rare malignant neuroectodermal tumors. Since 1924 up to the present, around 1,000 cases of this tumor have been detected worldwide, with only one case of splenic metastasis in a patient with esthesioneuroblastoma described. We present yet another clinical observation of splenic metastasis in a patient with esthesioneuroblastoma (nasal cavity tumor).

Abstract 4913: Engineering dendritic cell-based vaccines as targeted immunotherapy against medulloblastoma, neuroblastoma, and Ewing sarcoma

Abstract Medulloblastoma (MB), Neuroblastoma (NB), and Ewing Sarcoma (ES) are malignant pediatric neuroectodermal solid tumors. Current treatments are highly intensive but toxic and subsets of patients such as metastatic and/or relapsed patients have a dismal outcome (Esiashvili N et al, 2008; Leavey PJ et al, 2008; Bernstein ML et al, 2006). Targeted treatments with reduced side effects are urgently needed. Immunotherapy is a promising approach to inducing tumor control. Among various strategies of immunotherapy, dendritic cell-based vaccines have shown promising preliminary activity in the setting of minimal residual disease (Lasky JL et al, 2013; Westers TM et al, 2011; Shumway NM et al, 2009). To evaluate the feasibility of dendritic cell based vaccine in pediatric solid tumors, we incubated HLA A02+ human peripheral blood mononuclear cells (PBMC) with monocyte-derived autologous dendritic cells (DCs) pulsed with or without whole tumor cell lysates in interferon-ã (INFã) ELISPOT assays. We demonstrated that the number of spots detected in test wells (Daoy: 141.6±3, SKPNDW: 233.3±33.5, EWS502: 157.6±22.3, TC71: 249.6±24.5) is significantly (p&amp;lt;0.05) greater than control wells (PBS: 42±2), suggesting successful tumor antigen presenting of DCs and specific immune response from PBMC. To test T-cell responses, we isolated CD8+ T cells from PBMC and incubated them with tumor cell lysate pulsed mature DCs. Interestingly, we observed a similar trend in activation but fewer number of spots (PBS: 27±9, Daoy: 52.6±14.5, SKPNDW: 76.6±30.1, EWS502: 44.6±8.3, TC71: 68.6±19) in ELISPOT assays. Further analysis using HLA-DR blocking antibody (L243) showed that CD4+ T cell function is required for the responsive activity of PBMC because the number of spots was significantly (p = 0.03) reduced in test wells with the antibody (45.5±4.9) compared to that in control wells (352.5±17.6). These data indicate that both CD4+ and CD8+ T cells are required for the T-cell immune response to tumor antigens in whole tumor cell lysate presented by DCs. We next tested in vitro cytotoxic activity of DC-activated PBMCs to MB, NB, and ES cells by DELFIA cytotoxicity assay. PBMCs incubated with tumor lysate pulsed DCs induced significantly increased cell lysis compared to control PBMCs in Daoy (78±4.8% vs. 46.5±3.5% at E:T = 10:1, p = 0.019), SKPNDW (80±14.1% vs. 15±2.3% at E:T = 10:1, p = 0.016), and TC71 (82.5±3.5% vs. 39.5±13.4% at E:T = 20:1, p = 0.036). Taken together, our proof-of-principle studies demonstrated the efficacy of DC-based vaccines using whole tumor cell lysate as antigens in pediatric neuroectodermal solid tumors. Further investigation in the preclinical setting in a xenograft NSG model is warranted. Citation Format: Stacey Zahler, Wen Luo, Janet Ayello, Mitchell S. Cairo. Engineering dendritic cell-based vaccines as targeted immunotherapy against medulloblastoma, neuroblastoma, and Ewing sarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4913.

CT and clinical findings of peripheral primitive neuroectodermal tumour in children.

To describe the clinical, CT and pathological findings of paediatric peripheral primitive neuroectodermal tumours (pPNETs) to enhance the recognition of these rare tumours. The clinical, CT and pathological findings of 18 paediatric patients with pPNETs confirmed by biopsy or surgical pathology were retrospectively reviewed. The age of these 18 paediatric patients with pPNETs ranged from 4 months to 15 years, with a mean age of 7.7 years. The lesions of these 18 paediatric patients with pPNETs were located in the head and neck (n = 4), chest (n = 2), abdomen and pelvic cavity (n = 6), spine (n = 3), ilium (n = 2) and femur (n = 1). Immunohistochemical examination revealed Homer-Wright rosettes in seven lesions, and 94.4% of lesions showed consistent positive staining for CD99. On plain CT images, the majority of pPNETs showed lesions that were ill-defined (72.2%), irregularly shaped (83.3%), heterogeneous (66.7%) or hypodense masses (94.4%), and together with osteolytic bone destruction when the lesion originated in the bone. Calcifications were found in three lesions. After contrast administration, all soft-tissue masses were persistently enhanced heterogeneously with various cystic or necrotic regions, and 71.4% of them had linear enhancement. 94.4% of soft-tissue masses showed a moderate degree of enhancement. Seven cases had lymph node metastasis at diagnosis. Paediatric pPNET can involve any part of the body, and a large, ill-defined, aggressive soft-tissue mass and moderate heterogeneous enhancement with varying cystic regions and linear enhancement, with or without osteolytic bone destruction, on CT images could suggest the diagnosis. Primitive neuroectodermal tumours constitute a rare type of malignant neuroectodermal tumours that have chromosomal translocations identical to Ewing's sarcoma, and reports about radiological characteristics of this disease in children are insufficient. This study has described the clinical features and CT and pathological findings in 18 paediatric patients diagnosed with pPNETs in different locations, as a way to enhance the recognition of these tumours and help to differentiate from other types of paediatric malignant bone and soft-tissue tumours.

ATNT-09BEVACIZUMAB FOR METASTATIC DURAL AND ORBITAL ESTHESIONEUROBLASTOMA

Esthesioneuroblastoma is a malignant neuroectodermal tumor originating from the olfactory neuroepithelium. Bevacizumab is a specific inhibitor of the vascular endothelial growth factor ligand, preventing its interaction with receptors on endothelial cells. We report two cases of metastatic dural esthesioneuroblastoma that responded to bevacizumab. Patient 1, a 45 year-old man, had been treated initially for local disease with resection and radiation therapy (RT); for submandibular recurrence with radical neck dissection, RT, and cis-platinum plus etoposide; and subsequently for leptomeningeal disease with temozolomide plus sunitinib. He had an enlarging right orbital mass with progressive dural and leptomeningeal involvement. Patient 2, a 66 year-old woman, had been treated initially for local disease with craniotomy, RT, and cis-platinum; then for local recurrence with both regional and stereotactic RT. She developed enlarging orbital, dural and scalp masses. Both patients were treated with bevacizumab, 5 mg/kg every 2 weeks. Patient 1 achieved a partial response, with reduction in dural contrast enhancement, tumor cyst volumes, and perilesional edema, along with improvement in left leg weakness and right ptosis. His tumors progressed on imaging after 260 days of therapy. He died after 602 days of bevacizumab despite the addition of lomustine. Patient 2 achieved stable disease for 457 days but died of respiratory complications after developing a cerebrospinal fluid leak, without tumor progression. These patients with metastatic orbital and dural esthesioneuroblastoma achieved durable responses with bevacizumab therapy. Anti-angiogenic strategies may play a role in salvage therapy for this tumor.

Microvessel density and Ki-67 labeling index in esthesioneuroblastoma: is there a prognostic role?

Esthesioneuroblastoma (ENB) is a malignant neuroectodermal tumor. Hyams grading has an established role in its prognostication. The importance of microvessel density (MVD) and Ki-67 labeling index (Ki-67 LI) is well studied in various tumors, but the same remains understated in ENB. The aims of the study were to estimate proliferation index and MVD in ENB and to correlate them with Hyams grade. Twenty-six ENB cases diagnosed over a period of 5 years were included. Hyams grade, MVD, and Ki-67 LI were evaluated for each of them. The cases were categorized as low (Hyams grades 1 and 2) and high (Hyams grades 3 and 4) grades. Microvessel density and Ki-67 LI were correlated with grade. The treatment response was analyzed in different grades. The commonest histologic grade was 4 (42%). The mean Ki-67 LI was 2%, 8.2%, 30.8%, and 40.5% and mean MVD was 81.67/mm(2), 37/mm(2), 24/mm(2), and 25.2/mm(2) in grades 1, 2, 3, and 4, respectively. A statistically significant correlation of grade with Ki-67 LI (P < .001) and MVD (P < .007) was noted. Hyams grade in ENB correlates well with treatment response. Ki-67 LI is an important prognostic factor in ENB. We propose a cutoff of 25% for Ki-67 LI to differentiate low- vs high-grade ENB, but larger studies are needed for validation. Contrary to epithelial tumors, there is a decrease in MVD with increasing grade in ENB.

Radiologic and clinicopathologic findings of peripheral primitive neuroectodermal tumors.

Primitive neuroectodermal tumors (PNETs) constitute a rare type of malignant neuroectodermal tumors that have chromosomal translocations identical to Ewing's sarcoma (ES), and the characteristics of this disease remain unclear. To describe the clinical, radiological, and pathological features of peripheral PNETs (pPNETs) to enhance their recognition. The clinical, imaging, and pathologic findings of 35 patients with pPNETs were retrospectively reviewed, all being confirmed by biopsy or surgical pathology. All 35 patients had preoperative computed tomography (CT) examinations; 10 patients had preoperative magnetic resonance imaging (MRI) studies. Of 35 pPNET patients, 54.3% had a primary tumor in soft tissue, the others in bone. On plain CT images, 33 lesions demonstrated heterogeneous hypodense masses with multiple lamellar lower density, and with osteolytic destruction if the tumor originated in bone. Calcification was only found in five lesions arising in soft tissue. All lesions enhanced heterogeneously with varying areas of cystic changes, and all lesions in bone and 52.6% of lesions in soft tissue showed ill-defined margins after contrast administration. On MRI, these tumors appeared in conjunction with osteolytic bone destruction and irregular soft tissue masses iso- to hypointense to skeletal muscle on T1-weighted images and showed heterogeneously high intensity on T2-weighted images. All lesions enhanced heterogeneously with cystic changes. Homer-Wright rosettes were observed in 15 lesions, and 97.1% lesions were positive for CD99 in histopathological results. pPNETs can involve any part of the body, and a large, ill-defined, aggressive soft tissue mass and heterogeneous enhancement with or without osteolytic bone destruction on CT or MR images could suggest the diagnosis.