DOTATATE PET Imaging in Olfactory Neuroblastoma and Association with SSTR Expression.

Introduction Olfactory neuroblastoma (ONB), or esthesioneuroblastoma, is a rare neuroectodermal tumor of the nasal cavity and paranasal sinuses. Most of these tumors express somatostatin receptors (SSTRs), providing a potential target for radionuclide imaging with Ga-68 DOTATATE. However, this imaging modality has not been extensively studied in ONB. Methods We conducted a retrospective chart review of 96 endoscopic endonasal skull base surgery cases for ONB performed at our institution between 2000 and 2021. Histo (H) scores were assigned to each tumor and normalized DOTATATE standardized uptake values (nSUVs) were measured as well. Results Nine patients (5 males and 4 females) with ONB were ultimately included in the study. The average age of the patients was 50 years. All ONBs had a positive SSTR2 expression (H-score > 105; mean: 180). All ONBs showed DOTATATE avidity (mean nSUV for ONB: 6.7). However, there was no correlation between H-score and nSUV, with an r 2 of 0.24 ( p = 0.18). Conclusion Our study shows that SSTR2 expression is found in all ONBs with associated DOTATATE avidity, which may serve as a valuable imaging modality to monitor for recurrent and metastatic disease in ONB.

Assessing the Histological Malignancy Grade of Olfactory Neuroblastoma Using the Apparent Diffusion Coefficient Histogram Analysis.

Introduction Olfactory neuroblastoma (ONB) is a rare malignant tumor of the upper nasal cavity. The Hyams classification is an important histological grading system for diagnosing recurrence and predicting survival in ONB. This study aimed to evaluate the utility of apparent diffusion coefficient (ADC) histogram analysis in distinguishing between high-grade and low-grade ONB based on the Hyams classification system. Methods This retrospective study included 17 patients (11 males, six females; mean age 54 years, range 29-84) diagnosed with ONB who underwent pretreatment magnetic resonance imaging (MRI) including diffusion-weighted imaging between December 2017 and September 2022. Two board-certified radiologists outlined the regions of interest on ADC maps of the tumors. Mean, minimum, maximum ADC, standard deviation, skewness, kurtosis, and entropy were calculated from the ADC histograms. Patients were divided into low-grade (Hyams I-II) and high-grade (Hyams III-IV) groups based on histopathological evaluation by a board-certified pathologist. ADC histogram parameters were compared between the two groups using Mann-Whitney U tests. Two-sided p-values of < 0.05 were considered statistically significant. Results The study included 10 low-grade (two grade I, eight grade II) and seven high-grade (five grade III, one grade III/IV, one grade IV) ONB cases. Comparison between the low-grade and high-grade groups showed no statistically significant differences in any of the ADC histogram parameters analyzed: mean ADC (median 1.02 vs 0.95; p = 0.591), minimum ADC (0.84 vs 0.78; p = 0.494), maximum ADC (1.06 vs 1.19; p = 0.625), standard deviation (0.09 vs 0.14; p = 0.433), skewness (-0.48 vs -0.75; p = 0.133), kurtosis (2.79 vs 3.12; p = 0.161), and entropy (4.69 vs 5.06; p = 0.315). Conclusion This study demonstrated that ADC histogram analysis was unable to differentiate between high-grade and low-grade ONB based on the Hyams classification. The findings suggest that preoperative grading of ONB malignancy using ADC histogram parameters is challenging. Thus, grading based on preoperative imaging evaluation is difficult.

Survival Analysis and Prognostic Factors After Endonasal Resection of Advanced Olfactory Neuroblastomas: A Single Institution Experience.

OBJECTIVES: To explore the prognostic factors in patients with advanced olfactory neuroblastoma (ONB) underwent endoscopic surgery. MATERIALS AND METHODS: Retrospective medical records were reviewed of patients with pathologically proven ONB who underwent endoscopic surgical resection. Clinicopathological characteristics including patient demographics, treatment, complications, follow-up, and outcomes were analyzed. Kaplan-Meier overall survival (OS) and disease-free survival (DFS) curves were plotted. Univariate and multivariate Cox regression models were used to determine prognostic factors. RESULTS: Eighty-five patients with Kadish stage C ONB were examined. According to the various staging systems used, most patients harbored modified Kadish stage C (78.8%). Twenty-six patients (30.6%) underwent bony skull base resection, 11 (12.9%) underwent dura resection, and 24 (28.2%) underwent additional intracranial resection that included the olfactory bulb and duct. Median follow-up was 39 months. Five-year OS and DFS rates were 83.7% and 74.9%, respectively. Five-year OS was 100% in patients treated with bony skull base resection and 77.5% in those who were not (P = .052). Dura resection did not improve OS. Multivariate Cox regression analysis identified perioperative complications (P = .009), gross total resection (P = .004), orbital invasion (P = .014), postoperative radiotherapy (P = .030), and bony skull base resection (P = .019) as independent prognostic predictors. CONCLUSION: For patients with advanced ONB, endoscopic surgery in conjunction with radiotherapy and chemotherapy is effective and safe. Dura resection should be performed with caution in selected patients to balance survival and complications. Postoperative radiotherapy is important to improve OS and DFS.

Olfactory neuroblastoma with orbital protrusion arising in the background of maxillary carcinoma.

An uncommon entity in the class of malignant neuroectodermal nasal tumors is the olfactory neuroblastoma, which originates in the roof of the nasal cavity from the olfactory epithelium. It is often mistaken by clinicians for a nasal polyp because it presents with indistinct features such as nasal obstruction and secondary sinus disease. Olfactory neuroblastoma has been observed to cause morbidity by distant metastasis, invasion through the cribriform plate, and secondary meningitis in most instances. It exhibits a range of biologic activities, from slow growth accompanied by long-term patient survival to a very aggressive malignancy with extensive metastases. We report the incidence of a rare case in which a patient, previously operated on and irradiated for squamous cell carcinoma of the maxilla, developed an olfactory neuroblastoma with orbital protrusion.

Olfaction Preservation and Long-Term Outcomes in Patients with Unilateral Endoscopic Resection of Olfactory Neuroblastoma: A Systematic Review and Institutional Experience.

BACKGROUND: Endoscopic endonasal surgical resection is an effective therapeutic approach for olfactory neuroblastoma (ONB). Unilateral excision of ONBs with limited extension has been reported with the purpose of preserving olfactory function. We aimed to review implications of surgical management, olfactory preservation feasibility, and survival outcomes in patients who underwent endoscopic unilateral resection of ONB. METHODS: A systematic literature review was conducted using the search terms [("Olfactory neuroblastoma") OR ("Esthesioneuroblastoma")] AND [("Unilateral resection") OR ("Olfaction preservation")]. Studies reporting cases of unilateral ONB endoscopic resection with postoperative olfaction assessment were included. Concurrently, records of patients who met inclusion criteria at our institution were reviewed retrospectively. The survival and olfactory outcomes were analyzed in both cohorts. RESULTS: Thirty-three patients were identified in the published literature. Twenty-three (69.7%) reported postoperative olfaction preservation. Olfactory function after surgery did not show an association with Kadish stage (P = 0.128). No evidence of disease was observed at the latest follow-up in this group of patients. Nine patients who met inclusion criteria were identified at our institution. The extent of resection influenced the level of olfaction preservation when cribriform plate and nasal septum resection coexisted (P = 0.05). A single patient at our institution developed recurrence after being lost to follow-up for 22 months. CONCLUSIONS: Olfaction preservation can be achieved in patients who undergo endoscopic unilateral resection and adjuvant radiotherapy. The extent of resection should aim for negative margins, particularly in the midline. Larger studies are required to assess the risk of contralateral microscopic disease, and, hence, close follow-up is advised.

Role of induction chemotherapy in advanced-stage olfactory neuroblastoma.

OBJECTIVES: To evaluate the treatment outcomes in patients with advanced-stage olfactory neuroblastoma (ONB) who received induction chemotherapy (IC). MATERIALS AND METHODS: The clinical data of 38 patients with advanced-stage ONB who received initial IC were retrospectively analyzed. The response was defined using the Response Evaluation Criteria in Solid Tumors version 1.1. Patients with complete remission or partial remission were defined as responders. RESULTS: Seventeen (44.7%) patients responded to IC. The response rate was higher in patients with high Hyams grade tumor (III/IV) compared to those with low-grade tumors (I/II) (60% vs. 22.2%, p = 0.038). Overall, the 5-year cancer-specific survival (CSS) rate was 76.0%. Among nonresponders to IC, a significant difference in 5-year CSS rates was observed between surgery with adjuvant radiotherapy (RT) (100%) versus definitive RT or chemoradiotherapy (CRT) (68.6%) (log-rank p = 0.006). However, for responders, there was no significant difference in 5-year CSS rates between surgery with adjuvant therapy (75%) and definitive RT or CRT (51.1%) (log-rank p = 0.536). When only high-grade tumors were considered among responders, the 5-year CSS rate was significantly higher in patients who received RT or CRT (51.4%) compared to those who underwent surgery with adjuvant therapy (0%) (log-rank p = 0.008). CONCLUSION: In advanced-stage ONB, RT or CRT may be preferable for high-grade tumor responding to IC. Higher response rate and a potential role for induction IC in determining the optimal definitive treatment modality suggest a positive role for advanced-stage high-grade ONB.

A case of olfactory ganglioneuroblastoma in a dog: immunohistochemical comparison with olfactory neuroepithelia and olfactory neuroblastomas.

In the present study, histopathological and immunohistochemical findings of olfactory ganglioneuroblastoma in a dog were compared to those of canine olfactory neuroepithelia and neuroblastomas. Olfactory ganglioneuroblastoma consists of ganglion cell-like tumor cells with Schwannian stroma and neuroblast-like tumor cells. Immunohistochemically, ganglion cell-like tumor cells were immunopositive for synaptophysin, ß3-tubulin, and tyrosine hydroxylase, Schwannian stroma was immunopositive for GFAP and SOX2, and neuroblast-like tumor cells were immunopositive for OLIG2, ß3-tubulin, SOX2, cytokeratin AE1/AE3, and p63. The immunohistochemical results of olfactory neuroepithelia and olfactory neuroblastomas were similar to those of neuroblast-like tumor cells. These results suggest that the ganglion cell-like tumor cells in the present case have a sympathetic neuron immunophenotype, whereas neuroblast-like tumor cells have an olfactory neuroepithelial immunophenotype.

Ectopic adrenocorticotropic hormone syndrome in patients with olfactory neuroblastoma.

Olfactory neuroblastomas rarely secrete adrenocorticotropic hormone, leading to ectopic adrenocorticotropic hormone syndrome. However, the prevalence, timing, and triggers of ectopic adrenocorticotropic hormone syndrome in patients with olfactory neuroblastomas remain unclear. This study aimed to investigate these factors and conduct a literature review. Fifteen patients with olfactory neuroblastomas who underwent surgery at our institution were included. The prevalence of ectopic adrenocorticotropic hormone syndrome development was assessed by evaluating adrenocorticotropic hormone expression using immunohistochemistry. Furthermore, 26 patients with olfactory neuroblastomas who developed ectopic adrenocorticotropic hormone syndrome from previous reports were reviewed. Among the 15 patients, three (20%) showed adrenocorticotropic hormone-positive tumor cells at the time of initial surgery, and two (13%) developed ectopic adrenocorticotropic hormone syndrome. The timing of developing ectopic adrenocorticotropic hormone syndrome was 2.5 and 10 years following the initial treatment of olfactory neuroblastoma. Based on the literature review, nine patients with recurrent and metastatic olfactory neuroblastoma developed ectopic adrenocorticotropic hormone syndrome after the initial surgery, of whom, three had confirmed disease after developing ectopic adrenocorticotropic hormone syndrome, three developed during disease progression, two developed after receiving chemotherapy, and one developed after undergoing a biopsy. The timing of ectopic adrenocorticotropic hormone syndrome was 2.5-15 years after initial treatment. Our study revealed that acknowledging olfactory neuroblastomas can manifest as ectopic adrenocorticotropic hormone syndrome with a certain low prevalence is crucial. Moreover, our study speculated that tumor stimulation, such as biopsy or chemotherapy, as well as disease progression, could trigger ectopic adrenocorticotropic hormone syndrome onset. Thus, olfactory neuroblastomas can develop into ectopic adrenocorticotropic hormone syndrome, even long after the initial treatment.

A prospective cohort study on stereotactic radiotherapy in the management of dural recurrence of olfactory neuroblastoma.

BACKGROUND: Treatment for dural recurrence of olfactory neuroblastoma (ONB) is not standardized. We assess the outcomes of stereotactic body radiotherapy (SBRT) in this population. METHODS: ONB patients with dural recurrences treated between 2013 and 2022 on a prospective registry were included. Tumor control, survival, and patient-reported quality of life were analyzed. RESULTS: Fourteen patients with 32 dural lesions were evaluated. Time to dural recurrence was 58.3 months. Thirty lesions (94%) were treated with SBRT to a median dose of 27 Gy in three fractions. Two patients (3 of 32 lesions; 9%) developed in-field radiographic progression, five patients (38%) experienced progression in non-contiguous dura. Two-year local control was 85% (95% CI: 51-96%). There were no >grade 3 acute toxicities and 1 case of late grade 3 brain radionecrosis. CONCLUSION: In this largest study of SBRT reirradiation for ONB dural recurrence to date, high local control rates with minimal toxicity were attainable.

Olfactory neuroblastoma: A rare sinonasal malignancy.

Olfactory neuroblastoma is a rare malignant tumour arising from the olfactory nerve and extending into the nasal cavity. In this case report, the case of a 42-year-old male is presented. The patient had a two-month history of progressive nasal blockage and episodes of epistaxis. No complaint of anosmia or facial pain was reported. All the necessary examinations were performed. Upon investigation, the CT scan and MRI showed a polypoid mass involving the right maxillary sinus, eroding the medial wall and expanding into the osteo-meatal complex. The diagnosis of olfactory neuroblastoma was confirmed through histopathological examination and further validated by immunohistochemistry as it was positive for synaptophysin, chromogranin, gamma enolase, and neurofilament. On staging, the tumour was Kadish B. The mass was excised by lateral rhinotomy. The patient was kept on radiotherapy and was free from recurrence upon follow-up 10 months later. It was concluded that based on the analysis of findings related to olfactory neuroblastomas, clinicians should contemplate the possibility of an ONB when radiographic images depict a dumbbell-shaped mass within the nasal cavity, accompanied by peritumoural cysts. Using a multimodal treatment approach is advisable.

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.

Efficacy of anti-PD-1 monotherapy for recurrent or metastatic olfactory neuroblastoma.

Background: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the head and neck. Due to its rarity, standard systemic therapy for this condition has yet to be established. In particular, the use of immune checkpoint inhibitors (ICIs) for the recurrent or metastatic (R/M) ONB population remains unclear. Methods: We retrospectively evaluated 11 patients with R/M ONB who received any systemic chemotherapy at two Japanese institutions (National Cancer Center Hospital East and Kyushu Medical Center) between January 2002 and March 2022 and analyzed outcomes by use of anti-PD-1 antibody (nivolumab or pembrolizumab) monotherapy. Results: Of the 11 patients, 6 received ICI (ICI-containing treatment group) and the remaining 5 were treated with systemic therapy but not including ICI (ICI-non-containing treatment group). Overall survival (OS) was significantly longer in the ICI-containing group (median OS: not reached vs. 6.4 months, log-rank p-value: 0.035). The fraction of ICI systemic therapy in the entire treatment period of this group reached 85.9%. Four patients (66.7%) in the ICI-containing treatment group experienced immune-related adverse events (irAE), with grades of 1/2. No irAE of grade 3 or more was seen, and no patient required interruption or discontinuation of treatment due to toxicity. Conclusion: ICI monotherapy appears to be effective and to contribute to prolonged survival in R/M ONB.

Endoscopy-assisted medial canthus incision for olfactory neuroblastoma: a case report.

Sinonasal malignant tumors are a group of uncommon malignancies that account for less than 1% of all tumors. These tumors often involve the maxillary sinus and nasal cavity, with less cumulative incidence in the ethmoidal sinus, sphenoidal sinus, and frontal sinus. The lack of consensus on the management of sinonasal malignancies is due to their rarity, diagnostic challenges, and the heterogeneity of treatments. In this paper, we present a case of endoscopic-assisted medial canthus incision combined with radiotherapy in the treatment of sinonasal malignant tumors, with the aim of providing valuable insights to clinicians on the management of these tumors.

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.

A Case of Olfactory Neuroblastoma Developing Bilateral Retropharyngeal Lymph Node Metastasis 14-years After Skull Base Surgery.

Olfactory neuroblastoma (ONB) is an uncommon malignant tumor and is usually treated by a multidisciplinary approach includes surgery, radiotherapy, and chemotherapy. A 62 years-old male had a tumor in the nasal cavity and diagnosed as ONB with Kadish A stage. Anterior skull base surgery was performed as radical treatment. Since the surgical margin was negative, no postoperative radiotherapy was administered. 14 years after the surgery, bilateral otitis media with effusion (OME) was occurred, we found the recurrence tumor at bilateral retropharyngeal lymph node (RPLN) which surrounded the internal carotid arteries. Since these were unresectable, we planned chemoradiotherapy which was 70Gy of intensity modulated radiotherapy combined with two courses of carboplatin and etoposide. The tumor volume was reduced and bilateral OME were improved. He has been alive for 3 years after salvage treatment. Although ONB has a relatively good prognosis, it is known to often cause cervical lymph node metastasis. Grades III and IV of Hyams classification are considered high risk. This case, initial tumor was limited in the nasal cavity and its clinical classification was early stage, but Hyams classification was grade III. In reference to this case, considering that RPLN metastasis are difficult to radically resect at the salvage surgery, including this area in postoperative radiotherapy was considered an option.

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.

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.

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.

Personalized Approach to Olfactory Neuroblastoma Care.

Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine malignancy arising from the olfactory neuroepithelium. ONB frequently presents with nonspecific sinonasal complaints, including nasal obstruction and epistaxis, and diagnosis can be obtained through a combination of physical examination, nasal endoscopy, and computed tomography and magnetic resonance imaging. Endoscopic resection with negative margins, with or without craniotomy, as necessary, is the standard of care for definitive treatment of ONB. Regional metastasis to the neck is often detected at presentation or may occur in a delayed fashion and should be addressed through elective neck dissection or radiation. Adjuvant radiotherapy should be considered, particularly in the case of high grade or tumor stage, as well as positive surgical margins. Systemic therapy is an area of active investigation in both the neoadjuvant and adjuvant setting, with many advocating in favor of induction chemotherapy for significant orbital or intracranial involvement prior to surgical resection. Various targeted immunotherapies are currently being studied for the treatment of recurrent or metastatic ONB. Prolonged locoregional and distant surveillance are indicated following definitive treatment, given the tendency for delayed recurrence and metastasis.