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Ecancermedicalscience 2023Esthesioneuroblastoma (ENB) or olfactory neuroblastoma is a rare malignant neoplasm arising from the neural crest cells of the olfactory epithelium. The optimum...
Esthesioneuroblastoma (ENB) or olfactory neuroblastoma is a rare malignant neoplasm arising from the neural crest cells of the olfactory epithelium. The optimum treatment for this rare disease is still unclear. Most of the available literature on this rare head and neck tumour is limited to small retrospective series and single institutional reports. We conducted a retrospective study to investigate the clinical profile, treatment outcomes and prognostic factors of patients with ENB treated at a tertiary cancer centre in south India. Patients with a histopathological diagnosis of ENB treated from 2000 to 2019 were included. Patient demographics, tumour characteristics, stage, treatment details and outcome data were identified from medical records. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and the log-rank test was used for comparison. The prognostic factors were identified using Cox regression analysis. Forty-two patients underwent treatment for ENB from 2000 to 2019. Twenty-six patients underwent surgery. Twelve patients received radical radiotherapy (RT) while 24 patients underwent adjuvant radiation. After a median follow-up of 71 months, the estimated OS and DFS at 4 years were 64.4% and 54%, respectively. The estimated 4-year OS for modified Kadish A, B, C and D stages was 75.0%, 90.9%, 56.4% and 0%, respectively. Modified Kadish stage, nodal involvement, orbital invasion, intracranial extension, surgery, RT treatment and use of chemotherapy were significant predictors of OS and DFS in univariate Cox regression analysis. Orbital invasion and RT treatment were significant predictors of DFS in the multivariate analysis as well. However, only RT treatment came out to be a significant predictor for OS in multivariate Cox regression analysis. Surgery is the mainstay of treatment. Adjuvant RT may improve local control and survival in advanced cases. Advanced modified Kadish stage, lymph node involvement and orbital invasion are associated with poor outcomes.
PubMed: 37533955
DOI: 10.3332/ecancer.2023.1584 -
Frontiers in Surgery 2022Olfactory neuroblastoma, or esthesioneuroblastoma, is an uncommon malignant tumor originating from the neural crest that commonly occurs in the upper nasal cavity. Its...
Olfactory neuroblastoma, or esthesioneuroblastoma, is an uncommon malignant tumor originating from the neural crest that commonly occurs in the upper nasal cavity. Its ectopic origin is extremely rare, especially when located in the optical pathways. This paper reports the case of a giant ectopic esthesioneuroblastoma of the optic pathways that were surgically treated through a cranio-orbital-zygomatic (COZ) craniotomy with extensive resection, in addition to a literature review. The patient is a 46-year-old female presenting with a 4-month history of visual loss in the left eye. Since she was previously blind in the right eye from a traumatic injury, it was evolving to loss of bilateral vision. Imaging depicted an expansive infiltrating lesion involving the entire path of the right optic nerve, extending to the optic chiasm, cisternal portion of the left optic nerve, bilateral optic tract, and hypothalamus. Investigation of pituitary function was unremarkable. Esthesioneuroblastoma is a rare tumor with poorly defined standard clinical management. Its ectopic presentation makes the diagnosis even more challenging, making it difficult to manage these cases properly. Surgeons should be aware of this rare possibility, as early aggressive treatment is likely to be associated with better results.
PubMed: 35521435
DOI: 10.3389/fsurg.2022.875881 -
Journal of Neurosurgery. Case Lessons Jun 2022Olfactory neuroblastomas are rare sinonasal tumors that arise from the olfactory epithelium. The authors presented a case of an olfactory neuroblastoma with extensive...
BACKGROUND
Olfactory neuroblastomas are rare sinonasal tumors that arise from the olfactory epithelium. The authors presented a case of an olfactory neuroblastoma with extensive cranial invasion that demonstrated dramatic response to sorafenib, a tyrosine kinase inhibitor.
OBSERVATIONS
A 54-year-old man with history of prostate cancer and melanoma presented with left-sided proptosis and was found to have a 6.5-cm Kadish stage D olfactory neuroblastoma with cranial invasion that was refractory to chemotherapy and everolimus. However, it demonstrated dramatic response to sorafenib, causing extensive skull base defects that prompted operative repair. Genomic analysis of the tumor revealed mutations in and . The patient developed disease progression with liver metastases 35 months after starting sorafenib, prompting a change to lenvatinib. He experienced progression of his olfactory neuroblastoma 10 months following this change and died in hospice 1 month later.
LESSONS
The authors reviewed the clinical presentation and management of a large olfactory neuroblastoma with dramatic response to sorafenib. They highlighted prior uses of targeted therapy in the management of refractory olfactory neuroblastoma within the context of current standard treatment regimens. Targeted therapies may play a vital role in the management of refractory olfactory neuroblastoma.
PubMed: 35733633
DOI: 10.3171/CASE21663 -
The Journal of Laryngology and Otology Jan 2023In presentations of anosmia or dysosmia, magnetic resonance imaging may be required to screen for intracranial pathology such as olfactory neuroblastomas and other...
OBJECTIVE
In presentations of anosmia or dysosmia, magnetic resonance imaging may be required to screen for intracranial pathology such as olfactory neuroblastomas and other intracranial masses impacting on the olfactory pathway. This study aimed to establish positive magnetic resonance imaging findings of anosmia or dysosmia for scans performed before the coronavirus disease 2019 pandemic.
METHODS
The study examined the outcome of patients who presented with isolated olfactory dysfunction and who underwent magnetic resonance imaging between 2015 and 2019.
RESULTS
Of the 131 patients, 41 (31.3 per cent) had normal scan findings, 50 (38.2 per cent) had insignificant paranasal mucosal disease and 6 (4.6 per cent) had mucosal thickening significant enough to require additional intervention. These interventions included repeat nasoendoscopy or commencement of intranasal or oral steroids. No patients had olfactory neuroblastoma.
CONCLUSION
Only 4.6 per cent of the magnetic resonance imaging scans revealed abnormal findings related to anosmia or dysosmia, and none required ENT surgical intervention. None of the magnetic resonance imaging scans identified an olfactory neuroblastoma or intracranial masses impacting on the olfactory pathway.
Topics: Humans; Anosmia; Esthesioneuroblastoma, Olfactory; COVID-19; Smell; Olfaction Disorders; Magnetic Resonance Imaging; Nasal Cavity; Nose Neoplasms
PubMed: 35445651
DOI: 10.1017/S0022215122000913 -
Oncogenesis Jul 2023The tumor suppressor and chromatin modifier cAMP response element-binding protein binding protein (CREBBP) and v-myc avian myelocytomatosis viral oncogene neuroblastoma...
The tumor suppressor and chromatin modifier cAMP response element-binding protein binding protein (CREBBP) and v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), a member of the MYC oncogene family, are critically involved in brain development. Both genes are frequently mutated in the same tumor entities, including high-grade glioma and medulloblastoma. Therefore, we hypothesized that alterations in both genes cooperate to induce brain tumor formation. For further investigation, hGFAP-cre::Crebbp::lsl-MYCN mice were generated, which combine Crebbp deletion with overexpression of MYCN in neural stem cells (NSCs). Within eight months, these animals developed aggressive forebrain tumors. The first tumors were detectable in the olfactory bulbs of seven-day-old mice. This location raises the possibility that presumptive founder cells are derived from the ventricular-subventricular zone (V-SVZ). To examine the cellular biology of these tumors, single-cell RNA sequencing was performed, which revealed high intratumoral heterogeneity. Data comparison with reference CNS cell types indicated the highest similarity of tumor cells with transit-amplifying NSCs or activated NSCs of the V-SVZ. Consequently, we analyzed V-SVZ NSCs of our mouse model aiming to confirm that the tumors originate from this stem cell niche. Mutant V-SVZ NSCs showed significantly increased cell viability and proliferation as well as reduced glial and neural differentiation in vitro compared to control cells. In summary, we demonstrate the oncogenic potential of a combined loss of function of CREBBP and overexpression of MYCN in this cell population. hGFAP-cre::Crebbp::lsl-MYCN mice thus provide a valuable tool to study tumor-driving mechanisms in a key neural stem/ progenitor cell niche.
PubMed: 37407554
DOI: 10.1038/s41389-023-00481-3 -
Health Science Reports Jun 2021In this retrospective surveillance, epidemiology, and end results (SEER) registry analysis, we investigated the role of chemotherapy (CT) in the treatment of olfactory...
BACKGROUND
In this retrospective surveillance, epidemiology, and end results (SEER) registry analysis, we investigated the role of chemotherapy (CT) in the treatment of olfactory neuroblastoma (ON), an exceedingly rare sino-nasal tumor typically treated with surgery and/or radiation therapy (RT).
METHODS
We analyzed all patients in the SEER registry diagnosed with a single primary malignancy of ON, a primary tumor site within the nasal cavity or surrounding sinuses, sufficient staging information to derive Kadish staging, and >0 days of survival, ensuring follow-up data. Receipt of CT in the SEER registry was documented as either Yes or No/Unknown.
RESULTS
Six hundred and thirty-six patients were identified. One hundred and ninety-five patients received CT as part of their treatment for ON. Following propensity score matching and inverse probability of treatment weighting, there was inferior overall survival (OS) (HR 1.7, 95% CI: 1.3-2.2, = .001) and cancer-specific survival (CSS) (HR 1.8, 95% CI: 1.3-2.4, < .001) for patients who received CT compared to those who were not treated with CT or had unknown CT status. On subgroup analysis, the only patient population that derived benefit from CT were patients who did not receive surgery and were treated with CT and/or RT (HR 0.3, 95% CI: 0.14-0.61, < .001).
CONCLUSIONS
Based on this retrospective SEER registry analysis, the use of CT in the management of ON is associated with decreased OS. Our analysis suggests that patients who are considered nonsurgical candidates may benefit from the addition of CT.
PubMed: 33969231
DOI: 10.1002/hsr2.257 -
Frontiers in Neuroscience 2022Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the of the nasal mucosa. They display neurogenic and immunomodulatory properties...
BACKGROUND
Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the of the nasal mucosa. They display neurogenic and immunomodulatory properties and were shown to induce recovery in animal models of spinal cord trauma, hearing loss, Parkinsons's disease, amnesia, and peripheral nerve injury. As a step toward clinical practice, we sought to (i) devise a culture protocol that meets the requirements set by human health agencies and (ii) assess the efficacy of stem cells on neuron differentiation.
METHODS
Nasal olfactory mucosa biopsies from three donors were used to design and validate the good manufacturing process for purifying stem cells. All processes and procedures were performed by expert staff from the cell therapy laboratory of the public hospital of Marseille (AP-HM), according to aseptic handling manipulations. Premises, materials and air were kept clean at all times to avoid cross-contamination, accidents, or even fatalities. Purified stem cells were cultivated for 24 or 48 h and conditioned media were collected before being added to the culture medium of the neuroblastoma cell line Neuro2a.
RESULTS
Compared to the explant culture-based protocol, enzymatic digestion provides higher cell numbers more rapidly and is less prone to contamination. The use of platelet lysate in place of fetal calf serum is effective in promoting higher cell proliferation (the percentage of CFU-F progenitors is 15.5%), with the optimal percentage of platelet lysate being 10%. Cultured OE-MSCs do not show chromosomal rearrangement and, as expected, express the usual phenotypic markers of mesenchymal stem cells. When incorporated in standard culture medium, the conditioned medium of purified OE-MSCs promotes cell differentiation of Neuro2a neuroblastoma cells.
CONCLUSION
We developed a safer and more efficient manufacturing process for clinical grade olfactory stem cells. With this protocol, human OE-MSCs will soon be used in a Phase I clinical based on their autologous transplantation in digital nerves with a neglected injury. However, further studies are required to unveil the underlying mechanisms of action.
PubMed: 36466172
DOI: 10.3389/fnins.2022.1042276 -
Frontiers in Oncology 2020Esthesioneuroblastoma, also known as olfactory neuroblastoma, is a small round blue cell tumor of nasal neuroepithelium first described in 1924. Though this tumor is...
Esthesioneuroblastoma, also known as olfactory neuroblastoma, is a small round blue cell tumor of nasal neuroepithelium first described in 1924. Though this tumor is especially rare in the pediatric population with an incidence of <0.1 per 100,000, it is the most common pediatric nasal cavity neoplasm. The purpose of this systematic review is to examine the treatment modalities utilized for pediatric esthesioneuroblastoma and overall survival. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pubmed, EMBASE, and Ovid MEDLINE databases were queried for studies pertinent to treatment modalities for pediatric esthesioneuroblatoma and survival outcomes. Two hundred and seventy-sixth articles were identified, with seven meeting inclusion criteria. Ninety-four patients with an age range of 0.9-21 years old with esthesioneuroblastoma were included. Nearly 90% of patients were of stage Kadish B or C at time of presentation, while 20% presented with cervical lymphadenopathy. Only about 10% of patients underwent single modality therapy. Overall, 5-year survival ranged from 44 to 91% with a median follow-up of 3-13 years. Children with esthesioneuroblastoma usually present at an advanced stage and undergo multi-modality therapy at a higher rate than adult patients. There is a wide range of documented overall survival though this lack of precision could be due to a paucity of patients.
PubMed: 32793498
DOI: 10.3389/fonc.2020.01247 -
World Journal of Clinical Cases Aug 2021Neuroblastoma (NB) is one of the most common malignancies in children. Metastasis in NB is not uncommon. However, nasal metastases are rare. Here, we reported two...
BACKGROUND
Neuroblastoma (NB) is one of the most common malignancies in children. Metastasis in NB is not uncommon. However, nasal metastases are rare. Here, we reported two pediatric cases of nasal metastases.
CASE SUMMARY
Case 1 was a 3-year-old boy without a history of NB. Case 2 was a 10-year-old girl who had a history of NB for 6 years. Both of them presented with symptoms of nasal and sinus masses such as epistaxis or discharge from the nose. The radiologic imaging results revealed masses in the nasal cavity or nasopharynx in both cases and a mass in the right adrenal gland of case 1. The pathologic examination of biopsy samples of their nasal masses revealed "small round blue-cell tumor" along with abundant vascular fibrous septa. The tumor cells expressed synaptophysin, cluster of differentiation 56, chromogranin A, paired like homeobox protein 2B and a very high Ki67 index in both case but were negative for vimentin, desmin, leucocyte common antigen and cytokeratin. Myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification was detected in both cases. Finally, the two cases were diagnosed as nasal metastases from NB based on the clinical and pathologic findings. The two patients affected by NB were > 18 mo old, the primary tumor location was adrenal gland, and they presented with multiple metastases.
CONCLUSION
It is difficult to differentiate between metastatic NB in the nose and olfactory neuroblastoma in the absence of a history of NB. Paired like homeobox protein 2B can play an important role in the diagnosis and differential diagnosis of this disease.
PubMed: 34447830
DOI: 10.12998/wjcc.v9.i23.6816 -
Cancer Cytopathology Oct 2020Insulinoma-associated protein 1 (INSM1) has recently emerged as a reliable nuclear immunostaining marker for detecting neuroendocrine tumors (NETs) in paraffin-embedded...
BACKGROUND
Insulinoma-associated protein 1 (INSM1) has recently emerged as a reliable nuclear immunostaining marker for detecting neuroendocrine tumors (NETs) in paraffin-embedded surgical samples and cytologic cell blocks, but the reliability of INSM1 staining on cytologic smears is understudied. This study investigated the performance of INSM1 staining on cytologic smears for the detection of various NETs in comparison with chromogranin (CG) and synaptophysin (SYN).
METHODS
INSM1, CG, and SYN were stained on cytologic smears of 70 NETs, including 20 pancreatic NETs, 10 lung carcinoid tumors, 11 small cell lung carcinomas (SCLCs), 10 medullary thyroid carcinomas, 10 Merkel cell carcinomas, 4 thymic atypical carcinoid tumors, and 5 olfactory neuroblastomas. The detection rate, the percentage of positive cells, and the staining intensity were recorded.
RESULTS
The overall detection rate of INSM1 (94%) was higher than the rates of CG (79%) and SYN (89%). The detection rate of INSM1 was higher than the rates of CG and SYN in SCLC, Merkel cell carcinoma, and olfactory neuroblastoma; higher than the rate of CG and equal to the rate of SYN in pancreatic NETs and medullary thyroid carcinoma; equal to the rate of CG and higher than the rate of SYN in thymic atypical carcinoid tumors; and equal to the rate of CG and lower than the rate of SYN in lung carcinoid tumors. INSM1 staining was easier to interpret than CG and SYN staining, especially in high-grade NETs.
CONCLUSIONS
INSM1 can be reliably stained on cytologic smears and outperforms CG and SYN in the verification of clinically or radiologically suspected NETs.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Fine-Needle; Chromogranin A; Female; Follow-Up Studies; Humans; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Prognosis; Repressor Proteins; Retrospective Studies; Small Cell Lung Carcinoma; Synaptophysin
PubMed: 32573984
DOI: 10.1002/cncy.22310