The Prognostic Implications of Neutrophil-to-Lymphocyte Ratio in Olfactory Neuroblastoma.

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. STUDY DESIGN: Retrospective chart review. SETTING: 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. CONCLUSION: Higher Kadish grade is associated with elevated NLR which may provide novel prognostic value to current risk-stratifying systems.

[Clinical analysis of endonasal endoscopic surgery in esthesioneuroblastoma].

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.

Olfactory Neuroblastoma Is Not Always Located at the Roof of the Nasal Cavity.

Objectives: 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). Materials and Methods: 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. Results: 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. Conclusion: 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.

Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer.

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.

Augmentation of tumor expression of HLA-DR, CXCL9, and CXCL10 may improve olfactory neuroblastoma immunotherapeutic responses.

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. CONCLUSION: 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.

Development of an evaluation and treatment strategy for olfactory neuroblastoma: a review of evidence from large-scale studies, including population-based and multicenter studies, and meta-analyses.

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.

Clinical outcomes for olfactory neuroblastoma.

Background: 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. Methods: A retrospective review of patients with ONB was conducted. Outcomes included survival outcomes and perioperative data. Results: 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. Conclusion: 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.

Exophthalmos revealing an olfactory esthesioneuroblastoma: A case report.

INTRODUCTION AND IMPORTANCE: 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. CASE PRESENTATION: 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. CLINICAL DISCUSSION: 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. CONCLUSION: 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.

Recurrence morbidity of olfactory neuroblastoma.

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.

Ectopic Olfactory Neuroblastoma: Systematic Review of a Rare Clinical Entity among Sinonasal Tumors.

Objectives Ectopic olfactory neuroblastoma is an uncommon manifestation of an already rare neoplasm. We aimed to systematically review the literature for cases of ectopic olfactory neuroblastoma to better characterize this rare disease entity and to present two new case reports. Methods A search of the PubMed and Embase databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify English-language articles reporting cases of ectopic olfactory neuroblastoma, published from 1955 through November 2021. Results Sixty-six cases of ectopic olfactory neuroblastoma were identified in 62 articles including the current review. Ectopic olfactory neuroblastoma arose in a wide age range (2-89 years) without significant sex predilection. It occurred most commonly in the ethmoid (25%), maxillary (25%), and sphenoid (16%) sinuses. Seventy-three percent of cases presented with low Hyams grade (I and II). The most common symptoms were nasal obstruction (32%) and epistaxis (32%). Paraneoplastic syndromes were observed in 27% of patients. The most common treatment was surgical resection followed by adjuvant radiotherapy. Overall, 76% of all patients were disease-free at the time of last follow-up. Locoregional recurrences and distant metastases were found in 19 and 5% of cases, respectively. Conclusion This systematic review describes previously reported cases of ectopic olfactory neuroblastoma, a disease entity with poorly understood characteristics. Physicians should consider olfactory neuroblastoma in the differential diagnosis for sinonasal masses, as their ectopic presentation may present considerable diagnostic and therapeutic difficulties. Patients with olfactory neuroblastoma may benefit from long-term follow-up and routine endoscopic examinations for surveillance of ectopic recurrences.

Review of neoplasia in fish at a large display aquarium, 2005-2021.

Fish maintained in managed care may have longer lifespans as a result of advances in veterinary medicine and husbandry and reduced risk of predation. Neoplasia is of increasing interest in managed aquarium populations. However, few studies have systematically evaluated neoplasia in managed fish populations. Our objective in this retrospective study was to review and describe neoplasia diagnosed in fish at a large public display aquarium between 2005 and 2021. Any fish diagnosed with neoplasia on either antemortem or postmortem evaluation during the study period was included, and all medical records, biopsy, and autopsy reports were reviewed. Sixty-two fish met the inclusion criteria; 37 species were included in the study population, most of which were tropical freshwater fish (n = 34 fish). Thirty-two types of neoplasia were identified. Ten fish had benign neoplasms, and 53 fish had malignant neoplasms. The most common neoplasms were of epithelial and neuroectodermal origin. The most common site of tumor origin was the skin. Our data suggest that mesenchymal neoplasms may be more common in cold saltwater fish than in tropical freshwater and saltwater fish. Malignant neoplasms were most commonly diagnosed in the study population and should be a top differential when neoplasms are identified in fish managed under human care. Our study contributes to the overall knowledge of the health of aquarium fish and may aid clinicians in characterizing neoplasia that may be present in fish under human care.

Treatment of unilateral olfactory neuroblastoma: Appropriate extent of surgical resection and potential for olfactory preservation.

Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patient's quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low-grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease-free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes.

Patterns of recurrence and disease progression in patients with positive-margin olfactory neuroblastoma following primary resection.

OBJECTIVE: Olfactory neuroblastoma (ONB) is a rare, malignant tumor of the sinonasal tract that arises from olfactory epithelium. Although surgery is the preferred first-line treatment, tumor involvement of adjacent structures may preclude the ability to achieve negative margins during initial resection. Herein, the authors examine the oncological outcomes of patients with positive margins after primary resection of ONB, with the aim of determining predictors of disease progression and patterns of recurrence. METHODS: The authors performed an institutional review of 25 patients with positive-margin ONB after resection. Cox survival analyses were used to determine any statistically significant predictors of worse progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 93 patients who were diagnosed with ONB were identified, of whom 25 patients had positive margins following their primary resection. Eleven (44%) had a delayed finding of positive margins that were initially negative in the operating room but returned as positive on final pathology. Four patients had subtotal resection (STR), whereas the remaining patients underwent gross-total resection. Twenty-four patients received adjuvant radiotherapy (96%), and 15 additionally received adjuvant chemotherapy (60%). Fourteen patients (56%) experienced recurrence/progression at a median time of 35 months following resection (IQR 19-70 months). Local recurrence occurred in 10 patients (40%), regional in 9 (36%), and distant metastasis in 2 (8%). In Cox survival analyses, the 5-year PFS and OS were 55.1% and 79.2%, respectively. Kadish stage D was predictive of worse PFS in univariate (hazard ratio [HR] 15.67, 95% CI 3.38-72.61, p < 0.001) and multivariate (HR 15.46, 95% CI 1.45-164.91, p = 0.023) analyses. Hyams grade, adjuvant chemotherapy, and primary radiotherapy were not associated with PFS. Furthermore, Kadish stage D and STR were predictive of worse OS in univariate analysis (HR 12.64, 95% CI 2.03-78.86, p = 0.007; HR 7.31, 95% CI 1.45-36.84, p = 0.016; respectively). However, local and regional recurrence was not associated with worse OS. CONCLUSIONS: Approximately half of patients with positive-margin ONB may experience disease recurrence. Patients with an advanced disease stage (Kadish D) may have a higher likelihood of developing recurrence/progression. Furthermore, patients with tumor burden following resection (STR and Kadish D) may have worse OS. However, in positive-margin ONB with no gross disease following initial resection, the presence of disease recurrence does not significantly alter survival when receiving salvage therapy.

Treatment Outcomes of Olfactory Neuroblastoma: A Multicenter Study by the Korean Sinonasal Tumor and Skull Base Surgery Study Group.

OBJECTIVES: Due to the rarity of olfactory neuroblastoma (ONB), there is ongoing debate about optimal treatment strategies, especially for early-stage or locally advanced cases. Therefore, our study aimed to explore experiences from multiple centers to identify factors that influence the oncological outcomes of ONB. METHODS: We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and a Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. RESULTS: In our cohort, the 5-year overall survival (OS) rate was 78.6%, and the 5-year disease-free survival (DFS) rate was 62.4%. The Cox proportional hazards model revealed that the modified Kadish (mKadish) stage and Dulguerov T status were significantly associated with DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though the result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. CONCLUSION: Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Similarly, induction chemotherapy also did not show a survival benefit, even after stage matching.

SNOT-22 subdomain outcomes following treatment for sinonasal malignancy: A prospective, multicenter study.

BACKGROUND: Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22-item Sinonasal Outcomes Test (SNOT-22) has been shown to improve with treatment. This study aims to characterize SNOT-22 subdomain outcomes in SNM. METHODS: Patients diagnosed with SNM were prospectively enrolled in a multi-center patient registry. SNOT-22 scores were collected at the time of diagnosis and through the post-treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT-22 subdomains. RESULTS: Note that 234 patients were reviewed, with a mean follow-up of 22 months (3 months-64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow-up at all timepoints showed statistically significant improvement in rhinologic, extra-nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69-8.66])), extra-nasal (2.21 [0.22-4.17]) and ear/facial (5.53 [2.10-8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54-5.93]) and ear/facial (2.97 [0.32-5.65]) subdomains. Positive margins (5.74 [2.17-9.29]) and surgical approach-combined versus endoscopic (3.41 [0.78-6.05])-were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18-4.40]) was associated with worse sleep outcomes. CONCLUSIONS: Sinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra-nasal, psychological, and sleep subdomains.

Upright proton therapy for esthesioneuroblastoma: a single-institution experience.

Aim: This study presents an analysis (efficacy and toxicity) of outcomes in patients with esthesioneuroblastoma after pencil beam proton therapy with a fixed beamline in the upright position. Background: Esthesioneuroblastoma (ENB) is an extremely rare tumor of sinonasal area located in critical proximity to vital structures. Proton therapy (PT) is often considered the optimal radiation treatment for head-and-neck tumors, although of limited availability. Upright PT delivered using fixed pencil beamline and rotating chair is a fairly promising option. Methods: This is a single-center experience describing the outcomes of PT in 14 patients with ENB treated between January 2016 and October 2022; half of the cases had a history of previous irradiation. The therapy was applied using a fixed pencil beamline with 6D-chair for positioning. The median dose was 63 GyRBE (total range 48-70 GyRBE; based on 1.1 RBE multiplier for protons) with 2.0 GyRBE per fraction. The mean gross tumor volume was 109.5 cm3 (17.1-257.7 cm3). Patient demography, pathology, treatment parameters and toxicity data were analyzed. Radiation-induced reactions were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. Results: The median follow-up time was 28 months. The 1- and 2-year locoregional control rates constituted 100% and 88.9%, respectively; the median duration of local control was 52 months. The 1- and 2-year progression-free survival (PFS) rates constituted 92.9% and 75.0%, respectively; the median PFS duration was 52 months. The 1- and 2-year overall survival (OS) rates constituted 92.9% and 84.4%, respectively. Two patients died of non-cancer-related causes (coronavirus-induced pneumonia) and 1 patient died of tumor progression. All patients tolerated PT well without any treatment gaps. Serious late toxicity reactions included glaucoma in 1 patient and cataract in 2 patients, in over half a year since irradiation. Conclusion: PT with upright design of the unit affords promising outcomes in terms of disease control and toxicity rates in ENB, a sinonasal tumor of complicated localization.

Characterizing Immune Infiltration in Esthesioneuroblastoma Subtypes Through Gene Expression Deconvolution.

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear. We used an established machine learning algorithm on ENB transcriptomic profiles. METHODS: The authors characterized 22 immune cell populations using the CIBERSORTx deconvolutional machine learning pipeline on RNA sequencing data from 18 ENB cases. The characterization aimed to elucidate differences in relative proportions and populations of TIICs between basal and neural ENB. RESULTS: No differences in age, Hyams, Dulguerov, IDH2 mutation, or PD-L1 expression were seen between basal and neural subtypes of ENB (P > 0.05). Also, no difference in median overall survival was appreciated (52.0 ± 13.1 months vs. 50.0 ± 43.2 months, P = 0.5). As a cohort, M2 macrophages were the most abundant subpopulation (14%) followed by naïve B cells (13%) and CD4 memory resting T cells (12%). No gross differences in CD20, CD4, or CD8 cells/mm2 were apparent on gross histology (P > 0.05). However, further analysis showed that activated CD4 memory T cells were significantly increased in the basal ENBs, whereas resting dendritic cells were increased in the neural ENB subtype. The TIIC profiles alone could not differentiate between basal and neural ENB, but did suggest immunoprofile differences. CONCLUSIONS: Basal and neural subtypes display distinct TIIC involvement, which may impact their difference in outcome. These findings provide the framework for further investigation in novel immunomodulation strategies for ENB.

Simple and safe resection of the crista galli.

A critical procedure in the transcribriform approach is the resection of the crista galli. However, the standard technique for crista galli resection has several disadvantages. We reviewed the cases of patients with olfactory neuroblastomas who underwent an endoscopic endonasal transcribriform approach using a newly developed technique for crista galli resection. We performed a cadaveric study to measure the superior accessibility limits using the proposed method. We included 38 patients with olfactory neuroblastomas in this study. The tumor invaded the posterior crista galli in four patients. The anterior end of the crista galli was not invaded by the tumor. Our cadaveric study showed that the dura was approachable to the point that was 7.4 ± 1.3 mm superior and 23.2 ± 7.2 mm lateral to the foramen cecum following crista galli removal. By resecting the crista galli in advance, manipulation of the superior dura became feasible.

Outcomes following proton therapy for pediatric esthesioneuroblastoma.

BACKGROUND: Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT). PROCEDURE: Using an IRB-approved prospective outcomes registry, we evaluated patient, tumor, and treatment-related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT. RESULTS: Fifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow-up was 4.8 years. No patients were lost to follow-up. Five-year disease-free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in-field basal cell skin cancer. CONCLUSIONS: A multimodality approach for pediatric EN results in excellent local control. Despite the moderate-dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow-up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage.

International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors.

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.