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Head and Neck Pathology Sep 2020Olfactory neuroblastoma (ONB) is a rare malignant neoplasm arising from the superior aspect of the nasal vault. Cases are characterised by insidious clinical...
Olfactory neuroblastoma (ONB) is a rare malignant neoplasm arising from the superior aspect of the nasal vault. Cases are characterised by insidious clinical presentation and high rates of recurrence despite surgical resection and adjuvant radiotherapy. There are a small number of reports showing ONB with divergent epithelial or ganglionic differentiation, and ONB has also been found to coincide with adenocarcinoma. We present a case of mixed ONB with adenocarcinoma. The clinical presentation was unusual, with a tonic-clonic seizure preceded by chronic headache and anosmia. Imaging revealed a mass extending from the olfactory recess of the left nasal cavity through the cribriform plate to the anterior cranial fossa. The pathology demonstrated intraepithelial neuroendocrine cell hyperplasia in the left olfactory groove. This finding provides a unique insight into the cellular origin of this rare tumour, and appears to confirm the theory that ONB arises from neural stem cells in the olfactory neuroepithelium. Despite radical treatment, the patient suffered a distant recurrence within 1 year of treatment, which underlines the aggressive nature of this tumour.
Topics: Adenocarcinoma; Aged; Cranial Fossa, Anterior; Esthesioneuroblastoma, Olfactory; Female; Humans; Hyperplasia; Nasal Cavity; Neoplasms, Complex and Mixed; Neuroendocrine Cells; Nose Neoplasms
PubMed: 31388897
DOI: 10.1007/s12105-019-01062-w -
Oman Medical Journal Sep 2021We sought to determine whether SARS-CoV-2 infections are associated with anosmia and if this virus infects other neuronal cells. We utilized male and female olfactory...
OBJECTIVES
We sought to determine whether SARS-CoV-2 infections are associated with anosmia and if this virus infects other neuronal cells. We utilized male and female olfactory neuronal cell lines and other olfactory cell lines to determine the viral targets.
METHODS
We used four undifferentiated and two partially differentiated human developing neuronal cell lines. Infectivity was confirmed by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), immunofluorescence assay (IFA) probing with anti-SARS-CoV-2 antibody, evaluation of cytopathic effects, and neurite formation. We induced partial differentiation of all cell lines (since both olfactory cell lines were terminally differentiated) with retinoic acid (RA) to determine whether differentiation was a factor in viral permissiveness. The expression of serine protease, transmembrane serine protease 2 (TMPRSS2), and angiotensin-converting enzyme II (ACE2) receptors were examined by RT-qPCR and IFA to determine the mechanism of viral entry.
RESULTS
Four to five days after exposure, both olfactory cell lines exhibited morphological evidence of infection; IFA analyses indicated that ~30% of the neurons were SARS-CoV-2 positive. At two weeks, 70-80% were positive for SARS-CoV-2 antigens. The partially differentiated (CRL-2266 and CRL-2267) and undifferentiated cell lines (CRL-2142, CRL-2149, CRL-127, and CDL-2271) were essentially non-permissive. After RA treatment, only CRL-127 exhibited slight permissiveness (RT-qPCR). The TMPRSS2 receptor showed high expression in olfactory neurons, but low expression in RA treated CRL-127. ACE2 exhibited high expression in olfactory neurons, whereas other cell lines showed low expression, including RA-treated cell lines. ACE2 expression slightly increased in CRL-127 post RA-treatment.
CONCLUSIONS
Our studies confirm neurotropism of SARS-CoV-2 to olfactory neurons with viral entry likely mediated by TMPRSS2/ACE2. Other neuronal cell lines were non-permissive. Our results established that the nerve cells were infected regardless of male or female origin and strengthened the reported association of COVID-19 with loss of smell in infected individuals.
PubMed: 34733553
DOI: 10.5001/omj.2021.128 -
Endocrinology, Diabetes & Metabolism... Oct 2019ACTH-dependent hypercortisolism is caused by an ectopic ACTH syndrome (EAS) in 20% of cases. We report a rare cause of EAS in a 41-year-old woman, presenting with...
SUMMARY
ACTH-dependent hypercortisolism is caused by an ectopic ACTH syndrome (EAS) in 20% of cases. We report a rare cause of EAS in a 41-year-old woman, presenting with clinical features of Cushing's syndrome which developed over several months. Biochemical tests revealed hypokalemic metabolic alkalosis and high morning cortisol and ACTH levels. Further testing, including 24-hour urine analysis, late-night saliva and low-dose dexamethasone suppression test, confirmed hypercortisolism. An MRI of the pituitary gland was normal. Inferior petrosal sinus sampling (IPSS) revealed inconsistent results, with a raised basal gradient but no rise after CRH stimulation. Additional PET-CT showed intense metabolic activity in the left nasal vault. Biopsy of this lesion revealed an unsuspected cause of Cushing's syndrome: an olfactory neuroblastoma (ONB) with positive immunostaining for ACTH. Our patient underwent transnasal resection of the tumour mass, followed by adjuvant radiotherapy. Normalisation of cortisol and ACTH levels was seen immediately after surgery. Hydrocortisone substitution was started to prevent withdrawal symptoms. As the hypothalamic-pituitary-axis slowly recovered, daily hydrocortisone doses were tapered and stopped 4 months after surgery. Clinical Cushing's stigmata improved gradually.
LEARNING POINTS
Ectopic ACTH syndrome can originate from tumours outside the thoracoabdominal region, like the sinonasal cavity. The diagnostic accuracy of IPSS is not 100%: both false positives and false negatives may occur and might be due to a sinonasal tumour with ectopic ACTH secretion. Olfactory neuroblastoma (syn. esthesioneuroblastoma), named because of its sensory (olfactory) and neuroectodermal origin in the upper nasal cavity, is a rare malignant neoplasm. It should not be confused with neuroblastoma, a tumour of the sympathetic nervous system typically occurring in children. If one criticises MRI of the pituitary gland because of ACTH-dependent hypercortisolism, one should take a close look at the sinonasal field as well.
PubMed: 31627184
DOI: 10.1530/EDM-19-0093 -
International Journal of Molecular... Apr 2022The localization and expression of amylin protein in the rodent brain and mouse neuroblastoma Neuro-2a (N2a) are less widely known. Thus, this study investigated the...
The localization and expression of amylin protein in the rodent brain and mouse neuroblastoma Neuro-2a (N2a) are less widely known. Thus, this study investigated the expression distribution of amylin in the rat brain and N2a treated with steroid hormones. Amylin protein was identified in the olfactory bulb, cerebral cortex, dentate gyrus, thalamus, hypothalamus, ventral tegmental area (VTA), cerebellum, and brain stem in the rat brain. Additionally, the amylin protein was localized with the mature neurons of the cerebral cortex and dopaminergic neurons of the VTA. Progesterone (P4) and dexamethasone (Dex) significantly decreased, and 17β-estradiol (E2) increased the amylin protein level in the cerebral cortex. The P4 receptor antagonist RU486 significantly influenced the effects of P4 and Dex, and the E2 receptor antagonist ICI 182,780 slightly changed E2's effect. Amylin protein expression was significantly reduced in the VTA by P4 and Dex, and its expression was changed only following P4 plus RU486 treatment. It was confirmed for the first time that amylin protein is strongly expressed in the cytoplasm in N2a cells using immunofluorescent staining. P4 increased the levels of amylin, and RU486 treatment decreased them. Dex significantly increased the levels of amylin protein. RU486 treatment reversed the effects of Dex. Therefore, amylin protein is expressed in the cerebral cortex neurons and dopaminergic neurons of the VTA of the immature rat brain. P4 and Dex influence the expression of amylin protein in the rat brain and N2a cells.
Topics: Animals; Brain; Estradiol; Islet Amyloid Polypeptide; Mice; Mifepristone; Progesterone; Rats
PubMed: 35457166
DOI: 10.3390/ijms23084348 -
Medicina (Kaunas, Lithuania) Apr 2023Developing in a limited space, rare tumors located at the nose and paranasal sinuses are sometimes difficult to diagnose due to their modest clinical presentation, which...
Developing in a limited space, rare tumors located at the nose and paranasal sinuses are sometimes difficult to diagnose due to their modest clinical presentation, which is uncorrelated with anatomopathological diversity. This limits the preoperative diagnosis without added immune histochemical study; for that reason, we present our experience with these tumors with the intention of raising awareness. The patient included in our study was investigated by our department through clinical and endoscopic examination, imaging investigations, and an anatomic-pathological study. The selected patient gave consent for participation and inclusion in this research study in compliance with the 1964 Declaration of Helsinki.
Topics: Humans; Esthesioneuroblastoma, Olfactory; Nose Neoplasms; Paranasal Sinuses; Nasal Cavity; Hematology
PubMed: 37109689
DOI: 10.3390/medicina59040731 -
Journal of Radiation Research May 2021The purpose of this study was to compare hybrid intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (Hybrid IMRT/VMAT), with non-coplanar (nc)... (Comparative Study)
Comparative Study
Comparison of a Hybrid IMRT/VMAT technique with non-coplanar VMAT and non-coplanar IMRT for unresectable olfactory neuroblastoma using the RayStation treatment planning system-EUD, NTCP and planning study.
The purpose of this study was to compare hybrid intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (Hybrid IMRT/VMAT), with non-coplanar (nc) IMRT and nc-VMAT treatment plans for unresectable olfactory neuroblastoma (ONB). Hybrid IMRT/VMAT, nc-IMRT and nc-VMAT plans were optimized for 12 patients with modified Kadish C stage ONB. Dose prescription was 65 Gy in 26 fractions. Dose-volume histogram parameters, conformation number (CN), homogeneity index (HI), integral dose and monitor units (MUs) delivered per fraction were assessed. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) based on the EUD model (NTCPLogit) and the Lyman-Kutcher-Burman model (NTCPLKB) were also evaluated. We found that the Hybrid IMRT/VMAT plan significantly improved the CN for clinical target volume (CTV) and planning treatment volume (PTV) compared with the nc-VMAT plan. In general, sparing of organs at risk (OARs) is similar with the three techniques, although the Hybrid IMRT/VMAT plan resulted in a significantly reduced Dmax to contralateral (C/L) optic nerve compared with the nc-IMRT plan. The Hybrid IMRT/VMAT plan significantly reduce EUD to the ipsilateral (I/L) and C/L optic nerve in comparison with the nc-IMRT plan and nc-VMAT plan, but the difference in NTCP between the three technique was <1%. We concluded that the Hybrid IMRT/VMAT technique can offer improvement in terms of target conformity and EUD for optic nerves, while achieving equal or better OAR sparing compared with nc-IMRT and nc-VMAT, and can be a viable radiation technique for treating unresectable ONB. However, the clinical benefit of these small differences in dosimetric data, EUD and NTCP of optic nerves may be minimal.
Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Radiation; Esthesioneuroblastoma, Olfactory; Female; Humans; Male; Middle Aged; Nasal Cavity; Nose Neoplasms; Organs at Risk; Probability; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Time Factors; Young Adult
PubMed: 33839761
DOI: 10.1093/jrr/rrab010 -
Journal of Personalized Medicine Oct 2023Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and...
Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence ( = 0.015), especially distant recurrence. The majority of cases showed βIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger βIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression ( = 0.049). Sox2 and βIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility.
PubMed: 37888115
DOI: 10.3390/jpm13101504 -
American Journal of Rhinology & Allergy Jul 2021The short-term adverse events and predictors of morbidity in surgical resection of esthesioneuroblastoma (ENB) are largely unknown, and investigating these variables can...
INTRODUCTION
The short-term adverse events and predictors of morbidity in surgical resection of esthesioneuroblastoma (ENB) are largely unknown, and investigating these variables can help direct planning for at-risk patients.
METHODS
The 2005-2017 National Surgical Quality Improvement Program database was queried to identify patients with a diagnosis of ENB undergoing skull base surgery for tumor resection. Information regarding demographics, patient morbidity score, pre-operative and intra-operative data, and post-operative outcomes were extracted. Cox proportional hazard analysis was utilized to assess complication and readmission/reoperation rates.
RESULTS
A total of 95 patients undergoing skull base surgery for resection of ENB were included. Mean age, BMI, operation time, and post-operative length of stay (LOS) of the cohort were 53.6 ± 16.2 years, 29.1 ± 6.5, 392.0 ± 204.6 minutes, and 5.8 ± 4.6 days, respectively. In total, 31 patients (32.6%) experienced at least one 30-day adverse event, which included blood transfusion intra-operatively or within 72 hours from the operation (22.1%), readmission (10.7%), intubation >48 hours (7.4%), reintubation (4.2%), organ or space infection (4.2%), reoperation (4.0%), superficial or deep surgical site infection (2.1%), sepsis (2.1%), pulmonary embolism (1.1%), and myocardial infarction (1.1%). Patients who experienced at least one adverse event had significantly higher operation time (486.8 ± 230.4 vs. 347.5 ± 176.2 minutes, = 0.002), LOS (9.2 ± 5.6 days vs. 4.2 ± 3.0, < 0.001), and lower hematocrit (37.3 ± 5.9 vs. 41.2 ± 3.8, < 0.001) and albumin levels (3.8 ± 0.6 vs. 4.2 ± 0.3, = 0.009). Patients with a higher American Society of Anesthesiologists (ASA) score (HR = 2.39; = 0.047) or longer operation time (HR = 1.004; = 0.001) had a significantly higher risk for experiencing adverse events. Obesity was not associated with different intra- or post-operative outcomes, but older patients had shorter operations ( = 0.002) and LOS ( = 0.0014).
CONCLUSION
Longer operation time and lower pre-operative hematocrit and albumin levels may all increase complication rates in ENB resection. Patients with high ASA score or more advanced age may have different short-term outcomes.
Topics: Esthesioneuroblastoma, Olfactory; Humans; Length of Stay; Morbidity; Nasal Cavity; Nose Neoplasms; Postoperative Complications; Reoperation; Retrospective Studies; Risk Factors
PubMed: 33121257
DOI: 10.1177/1945892420970468 -
Molecular Neurobiology Jan 2022Human MYCN is an oncogene amplified in neuroblastoma and many other tumors. Both human MYCN and mouse Mycn genes are important in embryonic brain development, but their...
Human MYCN is an oncogene amplified in neuroblastoma and many other tumors. Both human MYCN and mouse Mycn genes are important in embryonic brain development, but their functions in adult healthy nerve system are completely unknown. Here, with Mycn-eGFP mice and quantitative RT-PCR, we found that Mycn was expressed in specific brain regions of young adult mice, including subventricular zone (SVZ), subgranular zone (SGZ), olfactory bulb (OB), subcallosal zone (SCZ), and corpus callosum (CC). With immunohistochemistry (IHC), we found that many Mycn-expressing cells expressed neuroblast marker doublecortin (DCX) and proliferation marker Ki67. With Dcx-creER and Mki67-creER mouse lines, we fate mapped Dcx-expressing neuroblasts and Mki67-expressing proliferation cells, along with deleting Mycn from these cells in adult mice. We found that knocking out Mycn from adult neuroblasts or proliferating cells significantly reduced cells in proliferation in SVZ, SGZ, OB, SCZ, and CC. We also demonstrated that the Mycn-deficient neuroblasts in SGZ matured quicker than wild-type neuroblasts, and that Mycn-deficient proliferating cells were more likely to survive in SVZ, SGZ, OB, SCZ, and CC compared to wild type. Thus, our results demonstrate that, in addition to causing tumors in the nervous system, oncogene Mycn has a crucial function in neurogenesis and oligodendrogenesis in adult healthy brain.
Topics: Animals; Cell Proliferation; Lateral Ventricles; Mice; Mice, Transgenic; N-Myc Proto-Oncogene Protein; Neural Stem Cells; Neurogenesis; Olfactory Bulb; Oligodendroglia
PubMed: 34625907
DOI: 10.1007/s12035-021-02584-7 -
Cancer Radiotherapie : Journal de La... Sep 2022To evaluate the impact of postoperative radiotherapy (PORT) on survival in olfactory neuroblastoma (ONB) patients with different tumor staging.
PUPOSE
To evaluate the impact of postoperative radiotherapy (PORT) on survival in olfactory neuroblastoma (ONB) patients with different tumor staging.
MATERIAL AND METHODS
Patients with ONB were selected in the Surveillance, Epidemiology and End Results (SEER) database from 2004-2016. Survival analyses were performed using Kaplan-Meier (K-M) method, Cox regression analysis, and competing risk model.
RESULTS
A total of 513 patients were included in the study. Univariate and multivariate analysis results demonstrated that PORT was not an independent prognostic factor for overall survival (OS) of modified Kadish stage A and B patients (P=0.699 and P=0.248, respectively). Kadish stage C and D patients who underwent PORT had significantly better OS than those who did not undergo PORT (P=0.03 and P<0.0001). K-M curves revealed that the 5- and 10-year OS rates of patients who underwent PORT vs. non-PORT were 85.3% vs. 70.4% and 68.2% vs. 56.8% in stage C patients, respectively. For stage D patients, the 5-year OS rates were 70.7% and 42.6%, and 10-year OS rates were 53.4% and 29.5% in the PORT and non-PORT groups, respectively. The competitive risk model revealed that the 5-year cancer-specific cumulative mortality incidence decreased by 26.6% while the 10-year mortality incidence decreased by 41.4% in Kadish stage C patients who were treated using PORT; meanwhile, for Kadish stage D patients who were treated with PORT, the 5- and 10-year mortality incidences were reduced by 35.3% and 42.6%, respectively. Furthermore, we found that chemotherapy was not related to the prognosis of ONB patients (all P>0.05).
CONCLUSION
Our results indicate that PORT improved survival outcomes of modified Kadish stage C and D ONB patients. However, PORT may not affect survival for modified Kadish stage A and B individuals. Chemotherapy was not recommended for ONB; therefore, further studies are warranted to determine its therapeutic significance.
Topics: Esthesioneuroblastoma, Olfactory; Humans; Nasal Cavity; Neoplasm Staging; Nose Neoplasms; Prognosis; Retrospective Studies
PubMed: 35249817
DOI: 10.1016/j.canrad.2021.12.006