Objectives  Malignant tumors of the sinonasal cavities with extension to the frontal skull base are rare and challenging pathologies. Combined-approach surgery using a frontobasal craniotomy and endoscopic sinus surgery with reconstruction of the anterior skull base followed by adjuvant radiotherapy is a preferred treatment strategy in selected cases. Morbidity and mortality rates are high in this population. We aim to add our experience to the current literature. Design  We performed a retrospective cross-sectional single center study of the long-term clinical outcome in a tertiary university referral hospital in the Netherlands between 2010 and 2021. Descriptive statistics and frequency distributions were performed Participants  Patient, tumor, treatment, complications and survival characteristics of eighteen consecutive patients were extracted from the electronic health records. Main Outcome Measures  The primary outcome measures are progression free survival, overall survival and complication rate. Results  Eighteen consecutive patients were included with a mean age of 61 (SD ± 10) years (range 38-80); ten males and eight females. Gross total resection was achieved in 14 (77%) patients. Eleven (61%) patients underwent local radiotherapy, one (5%) chemotherapy and three (17%) a combination of both. Mean follow-up duration was 49 months (range 3 - 138). Three (17%) patients died in hospital due to post-operative complications. Six (33%) patients died during follow-up due to disease progression. Mean progression-free survival was 47 months (range 0 - 113). Conclusion  In conclusion, the overall survival was 50% for this group of patients with large sinonasal tumors. Progressive disease affects survival rate severely. Surgical complications were seen in five (28%) patients. Radiotherapy is associated with high complication rates. Radiation necrosis was a serious complication in two patients and could be treated with high dose steroids.

OBJECTIVE: Olfactory neuroblastoma is a rare sinonasal malignancy with comparatively positive prognosis and survival, but with a range of biological behaviors that can be difficult to prognosticate with current means of risk stratification. Neutrophil-to-lymphocyte ratio (NLR) has been found across a diverse range of malignancies to be associated with poorer outcomes. This paper aims to elucidate the relationship of NLR with olfactory neuroblastoma to assess its prognostic value in this setting.
METHODS: Retrospective chart review.
METHODS: A single tertiary care academic hospital.
METHODS: The study cohort included all patients treated for initial presentation of olfactory neuroblastoma from 2004 to 2020. NLR was calculated from preoperative labs, and each patient was evaluated for Kadish staging, Hyams grade, intraoperative positive margin, use of adjuvant therapy, posttreatment recurrence, and death. All statistical analysis was conducted using R and relationship between NLR and variables was assessed via binomial logistic regression.
RESULTS: Forty-four patients were included, 24 were male. Average age 52.8, average length of follow-up was 9.6 years. Patients were grouped by low (Kadish A/B) and advanced (Kadish C/D) stage, n = 23 and n = 21, respectively, and low (Hyams I/II) and high (Hyams III/IV) risk, n = 15 and n = 11, respectively. Advanced Kadish stage was associated with elevated NLR, odds ratio 5.69 [2.30, 20.7], P = .001. No other variables were associated with elevated NLR including Hyams grade, margin status, recurrence, and mortality.
CONCLUSIONS: Higher Kadish grade is associated with elevated NLR which may provide novel prognostic value to current risk-stratifying systems.

Objective:To investigate the clinical characteristics of esthesioneuroblastoma and the efficacy of endonasal endoscopic surgery combined with radiotherapy/chemotherapy. Methods:The clinical and surgical data of 17 patients with esthesioneuroblastoma who underwent endonasal endoscopic surgery in our department from September 2009 to June 2023 were retrospectively analyzed. Results:Among all patients, the modified Kadish stage B was identified in 4 patients, C in 10 patients, and D in 3 patients. Ten of them underwent endonasal endoscopic surgery without neck dissection in one day, whose average operation time is （5.2±2.5） hours and average blood loss is （192±162）mL. Skull base reconstructions were performed in 15 patients, postoperative complications were observed in 3 patients, and negative margins were obtained in 13 patients. All 17 patients were followed up for an average of （49.7±40.2） months. Three patients died and 6 had recurrence and/or metastasis. The 1-year, 2-year and 5-year overall survival rates were 88.2%, 80.2%, and 80.2%, respectively, and the 1-year, 2-year and 5-year disease-free survival rates were 82.4%, 82.4%, and 50.8%, respectively. The 2-year overall survival rates of patients with negative and positive margins were 100% and 25%, respectively, while the 2-year disease-free survival rates were 61.5% and 25.0%, respectively. Conclusion:Endonasal endoscopic surgery combined with radiotherapy/chemotherapy can achieve satisfactory effect in esthesioneuroblastoma, and the prognosis of patients with positive margins is poor.
目的：探讨嗅神经母细胞瘤的临床特点和经鼻内镜手术联合放/化疗的治疗效果。 方法：回顾性分析2009年9月—2023年6月我院收治的接受经鼻内镜手术治疗的17例嗅神经母细胞瘤患者的临床、手术资料及随访结果。 结果：17例患者中改良Kadish B期4例，C期10例，D期3例。10例患者一期行鼻内镜手术切除肿瘤（除外颈清），平均手术时长（5.2±2.5） h，平均出血量为（192.0±162.0） mL。15例患者行颅底重建，3例患者出现术后并发症，13例患者达到阴性切缘。所有患者均得以随访，平均随访（49.7±40.2）个月，死亡3例，复发和（或）转移6例。1、2和5年总体生存率分别为88.2%、80.2%和80.2%，1、2和5年无病生存率分别为82.4%、82.4%和50.8%。切缘阴性和切缘阳性的患者2年总体生存率分别为100.0%和25.0%，2年无病生存率分别为61.5%和25.0%。 结论：经鼻内镜手术联合放/化疗治疗嗅神经母细胞瘤疗效可靠，切缘阳性患者预后较差。.

UNASSIGNED: To evaluate the imaging characteristics of the tumor, emphasizing its location, and to determine the frequency of typical and atypical locations of olfactory neuroblastoma (ONB).
UNASSIGNED: We retrospectively reviewed the computed tomography and magnetic resonance imaging findings of patients with pathologically proven ONB between April 2000 and April 2023. Demographic information, chief complaints, tumor location, and tumor extension were extracted.
UNASSIGNED: Of the 58 patients, 50 (86.2%) had the epicenter of the mass at the superior part of the nasal cavity, while eight patients (13.8%) had the epicenter at other atypical locations: seven patients (12.1%) at the middle part of the nasal cavity and one patient (1.7%) within both sphenoid sinuses.
UNASSIGNED: ONB is not always present in the upper part or the roof of the nasal cavity, and a significant number of ONBs are occasionally found in the rest of the nasal cavity and other atypical locations.

BACKGROUND: Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches.
METHODS: Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed.
RESULTS: A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration.
CONCLUSIONS: These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.

The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1+ immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories. ASCL1 loss in RPM ONB leads to emergence of non-neuronal histopathologies, including a POU2F3+ microvillar-like state. Similar to small-cell lung cancer (SCLC), mouse and human ONBs exhibit mutually exclusive NEUROD1 and POU2F3-like states, an immune-cold tumor microenvironment, intratumoral cell fate heterogeneity comprising neuronal and non-neuronal lineages, and cell fate plasticity-evidenced by barcode-based lineage tracing and single-cell transcriptomics. Collectively, our findings highlight conserved similarities between ONB and neuroendocrine tumors with significant implications for ONB classification and treatment.

Olfactory neuroblastoma is a rare sinonasal malignancy arising from the olfactory epithelium that is characterized by skull base involvement and a modest natural history. Because of its rarity and long course, identification of independent prognostic factors is dependent on multivariate analysis of large, long-term data. In this review, we outline evidence for the evaluation and treatment of olfactory neuroblastoma obtained from recent large-scale population-based studies, meta-analyses and multicenter studies. Hyams grade is currently the only pathological grade system for olfactory neuroblastoma. The modified Kadish staging and Dulguerov classification are available for clinical staging. The results of large-scale studies have confirmed Hyams, the modified Kadish and Dulguerov as independent prognostic factors. Surgery followed by radiotherapy provides the best overall survival and recurrence-free survival for resectable disease. The question of whether postoperative radiotherapy should be administered for all cases or only for those at risk of recurrence remains unanswered. Exclusively endoscopic resection is indicated for modified Kadish A/B cases without any increase in the risk of death or recurrence, and is also indicated for modified Kadish C cases if a negative surgical margin is ensured. For more advanced cases, such as those with extensive brain infiltration, the open approach is indicated. Elective nodal irradiation prevents late nodal recurrence of N0 patients. Chemotherapy has failed to show a benefit in survival or disease control. Current needs for olfactory neuroblastoma include the development and validation of refined staging systems suitable for current practice; expansion of indications for endoscopic surgery; less invasive surgery; definitive radiotherapy and novel systemic therapy.

UNASSIGNED: Olfactory neuroblastoma (ONB) is a rare malignant tumor arising from the olfactory neuroepithelium. The standard of care for ONB is surgical resection; however, detailed treatment protocols vary by institution. Our treatment protocol consists of endoscopic skull base surgery (ESBS) for endoscopically resectable cases and induction chemotherapy followed by craniotomy combined with ESBS for locally advanced cases, with postoperative radiotherapy performed for all cases. Chemoradiotherapy (CRT) is performed in unresectable cases. In this study, we evaluate our treatment protocol and outcomes for ONB.
UNASSIGNED: A retrospective review of patients with ONB was conducted. Outcomes included survival outcomes and perioperative data.
UNASSIGNED: Fifteen patients (53.6%) underwent ESBS, 12 (42.9%) underwent craniotomy combined with ESBS, and 1 (3.6%) received CRT. The 5- and 10-year overall survival rates for all patients were 92.9% and 82.5%, respectively, with a median follow-up period of 81 months. The 5- and 10-year disease-free survival rates were 77.3% and 70.3%, respectively, and the 5- and 10-year local control rates were 88.2% and 80.2%, respectively. Patients undergoing ESBS demonstrated a significantly shorter operating time, period from operation to ambulation, hospitalization period, and less blood loss than those undergoing craniotomy combined with ESBS.
UNASSIGNED: Our treatment protocol was found to afford favorable outcomes. Patients who underwent endoscopic resection showed lower complication rates and better perioperative data than those who underwent craniotomy combined with ESBS. With appropriate case selection, ESBS is considered a useful approach for ONB.

UNASSIGNED: Olfactory neuroblastoma or esthesioneuroblastoma is a rare malignant tumour, that develops in the olfactory neuroepithelium and is one of the rarest tumours of the nasal cavity. Ocular manifestations are uncommon. The diagnosis is based on histology: biopsy, immunohistochemistry and ultrastructural findings.
METHODS: We report a case of olfactory neuroblastoma of the olfactory placode in a 36-year-old woman with orbital involvement. Computed tomography and magnetic resonance imaging of the skull, showed a suspicious lesion with significant orbital and cranial extension. After anatomopathological study of the biopsy, a protocol palliative radiotherapy was established.
UNASSIGNED: We discuss the clinical, radiological, anatomopathological and therapeutic aspects of this condition, emphasising the importance of evoking this diagnosis in the presence of unilateral tumour-like exophthalmos associated with suggestive rhinological signs.
CONCLUSIONS: Ophthalmological involvement usually occurs at an advanced stage of esthesioneuroblastoma. This case highlights the fatal course of olfactory neuroblastoma. As it can present with the comlex symptoms related to ocular and nasal sites. Early diagnosis is the key to better therapeutic choices according to its level of extension, purposing at the best possible prognosis for the patient.

BACKGROUND: With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence.
METHODS: A retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses.
RESULTS: A final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation ±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p < 0.001), overall stage (p < 0.001), and modified Kadish scores (p < 0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio = 5.62; p = 0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence.
CONCLUSIONS: Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning.