Changing epidemiology of sinonasal cancer in the United States.

Sinonasal undifferentiated carcinoma (SNUC), sinonasal neuroendocrine carcinoma (SNEC), and olfactory neuroblastoma (ONB) represent a heterogeneous group of high-grade sinonasal tumors with overlapping morphological and immunophenotypic features, making accurate classification challenging. Our aim was to apply genetic and immunohistochemical analyses to reclassify a cohort of cases and to compare their clinical features. We analyzed 61 tumors originally diagnosed as ONB (n = 15), SNEC (n = 12), and SNUC (n = 34). Immunohistochemistry was performed for cytokeratin (CK), six neuroendocrine (NE) markers (synaptophysin, chromogranin A, CD56, INSM1, NeuroD1, ASCL1), p16, Ki67, SMARCB1, SMARCA4, and NUT. IDH2 R172 mutation status was assessed by Sanger sequencing and immunohistochemistry. Results were correlated with clinical and follow-up data. Reclassification was required in 22/61 cases (36%) and concerned one SMARCA4-deficient carcinoma, one SMARCB1-deficient carcinomas, one NUT carcinoma, 14 IDH2-mutated carcinomas, and five cases consistent with olfactory carcinoma (OC). A NE-high profile was identified in all reclassified tumour subtypes except SMARCB1-, SMARCA4-, and NUT-rearranged carcinomas, occurring in 8/9 (89%) ONB, 4/5 (80%) OC, 3/9 (33%) SNEC, 6/21 (29%) SNUC, and 5/14 (36%) IDH2-mutated carcinomas. IDH2-mutated carcinomas were found across all 3 diagnostic categories and were associated with significantly better 5-year disease-free survival (83% versus 31%, p = 0.027). ONB patients showed the most favorable outcome with 5-year overall survival of 86% versus 46% for combined SNEC and SNUC (p = 0.133). A tendency toward longer overall survival was also observed for CK-negative tumors (81% versus 42%, p = 0.051) and for NE-high tumors (73% versus 40%, p = 0.086).. No associations were found between Ki67 index and outcome. High-grade sinonasal tumors with neuroectodermal differentiation show substantial histological and immunophenotypic overlap, and over one-third required reclassification when applying extended immunohistochemical and genetic profiling. Our findings emphasize the clinical relevance of refining tumor classification, particularly regarding IDH2 mutation status and CK/NE expression patterns, to improve prognostication and therapeutic decision-making.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5-67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8-53.3%) and 39.6% (95% CI: 32.5-46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1-3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p's < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42-5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25-7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

Proceedings of the 2026 North American Society of Head and Neck Pathology Companion Meeting, San Antonio, TX, March 22, 2026: It's a Trap!: Diagnostic Pitfalls in Sinonasal Pathology.

PurposeINI1 (Integrase interactor 1) deficiency (defined as loss of nuclear INI1 expression on immunohistochemistry) identifies an aggressive subtype of sinonasal undifferentiated carcinoma (SNUC) associated with poor prognosis. This study aimed to develop and validate an interpretable clinical-radiomics fusion model for noninvasively prediction of INI1 deficiency and assess its prognostic value.MethodsIn this two-center retrospective study, 183 SNUC patients (training: n = 140; test: n = 43) were enrolled. Clinical variables were analyzed via univariate and multivariate analyses to identify independent predictors. Radiomic features were extracted from T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CEI), and apparent diffusion coefficient (ADC) maps, with feature selection (variance thresholding, mRMR, RFE) applied. Using the AutoGluon-Tabular framework, clinical, radiomics, and fusion models were developed, validated, and evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) and calibration. SHAP analysis assessed interpretability.ResultsTumor location and nasal cavity involvement were two independent clinical predictors. Feature selection identified two key morphological traits: Flatness on CEI and LeastAxisLength on ADC. The fusion model outperformed the clinical model (p = 0.046) with AUC = 0.993 (sensitivity = 96.97%, specificity = 93.46%) in training and AUC = 0.928 (sensitivity = 100%, specificity = 79.41%) in test cohort. SHAP analysis highlighted CE-T1WI Flatness as the top predictor. High- and low-risk groups showed significantly different 2-year disease-free survival (training: 23.1% vs. 79.2%, p = 0.013; test:10.0% vs.73.9%, p = 0.028).ConclusionThe interpretable clinical-radiomics fusion model showed promising performance in noninvasively predicting INI1 deficiency in SNUC and also provided prognostic insights, potentially guiding personalized treatment strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12880-025-02148-4.

Sinonasal tumors are rare and heterogeneous diseases with a low incidence of neck node metastasis. This study aims to analyze the risk of neck nodes recurrences and to assess patterns and predictors of nodal recurrence in sinonasal malignancies. Retrospective observational cohort study on 574 patients affected by sinonasal malignant tumor who were treated via endoscopic-assisted approaches between January 1998 and December 2023 in our tertiary-care referral University hospital. Nodal recurrence-free survival (N-RFS) was analyzed using Kaplan-Meier curves, with univariate and multivariate Cox regression identifying prognostic factors. Nodal involvement at diagnosis was observed in 3.1% (18/574) of patients. During a median follow-up of 62.9 months, nodal recurrence occurred in 6.8% (39/574). Histologies with the highest recurrence included sinonasal neuroendocrine carcinoma (23.5%), sinonasal undifferentiated carcinoma (18.8%), and olfactory neuroblastoma (12.8%). Univariate analysis revealed pT classification (pT > 3), tumor grading (G3/G4), and surgical approach as significant predictors of nodal recurrence. In multivariate analysis, high-grade tumors (HR = 3.109, p= 0.003) and craniofacial/cranio-endoscopic approaches (HR = 2.495, p= 0.023) remained independently associated with worse N-RFS. Histotype is the most important factor in determining the incidence and pattern of regional recurrence. Both high tumor grade and more extensive surgical procedures are independent predictors of regional failure. Therefore, long-term follow-up is essential, especially for specific histologies such as olfactory neuroblastoma and sinonasal neuroendocrine carcinoma. Elective neck treatment should be personalized, taking into account the tumor's histology, grading and overall disease extent to optimize patient outcomes.

INTRODUCTION Over the past decade, the pathology of un differentiated sinonasal malignancies has undergone extensive study, leading to significant advancements in the depiction and histopathological classification of various entities. These entities are now recognized as subsets of "sinonasal undifferentiated carcinomas (SNUC)" and poorly differentiated unclassified carcinomas. Typically, these malignancies are detected at later stages, by which time they have often invaded the facial and cranial regions. Olfactory neuroblastoma, which arises from the olfactory neuroepithelium with neuroblastic immature differentiation, is one such malignancy. CASE REPORT We present a case involving a left-sided nasal mass with blood-tinged discharge that obscured the nasal cavity. Previous biopsies had been inconclusive. Imaging revealed a large heterogeneous mass with bone erosions and extension into the intraorbital and intracranial regions. The patient underwent an endoscopic nasal biopsy. CONCLUSION Olfactory Neuroblastoma is a rare ,highly malignant, often have a long history before diagnosis. Treatment utilises a combination of surgery, external beam radiation, and chemotherapy modalities. Immunohistochemistry plays a crucial role in establishing a definitive diagnosis.

BackgroundThe WHO-fifth edition classified the sinonasal respiratory epithelial malignancies (SREMs) based on their histomorphological, immunohistochemical, and molecular features, due to their diverse manifestations.AimsWe aimed to ambispectively reclassify the SREMs at a North Indian tertiary care center, to understand the clinico-pathological spectrum of the WHO-defined entities and their prognostic implications.Material and MethodsHistopathologically proven, 162 patients with SREMs from 8 years (2016-2023) were retrieved, and re-examined for histomorphology, and relevant immunohistochemistry was performed to reclassify them. The clinical details and the follow-up data were also retrieved.ResultsKeratinizing squamous cell carcinoma (KSCC) was the most common sinonasal carcinoma (n = 76; 46.9%), followed by non-keratinizing squamous cell carcinoma (NKSCC) (n = 29; 17.9%), sinonasal undifferentiated carcinoma (SNUC) (n = 23; 14.2%), sinonasal adenocarcinoma (n = 22; 13.6%), SWI/SNF-deficient carcinoma (n = 6; 3.7%), lymphoepithelial carcinoma (n = 2; 1.2%), NUT carcinoma (n = 2; 1.2%), and teratocarcinosarcoma (n = 2; 1.2%). The median age of presentation of SREMs was 54 (IQR 45-62) years, with a male:female ratio of 2.4:1. Sinonasal adenocarcinoma showed a significantly lower median age of presentation (43.5 years) (P-value = .036). SWI/SNF-deficient carcinoma, NUT carcinoma, and teratocarcinosarcoma showed dismal prognosis irrespective of treatment. The median overall survivals of KSCC, NKSCC, SNUC, and sinonasal adenocarcinoma were 31, 63, 17, and 53 months, respectively, and showed a significant difference (P -value = .047).ConclusionReclassification of the SREMs according to the WHO-fifth edition elucidated their clinico-pathological spectrum and prognosis. This study highlights the relevance of the accurate classification of these entities for accurate treatment options and prognostication.

Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy with poor prognosis, especially with intracranial extension. The authors report a 44-year-old male with T4B SNUC presenting with epistaxis, headache, and diplopia. Initial chemotherapy failed. He underwent combined craniofacial resection (transbasal and endonasal) with pericranial flap reconstruction and titanium mesh cranioplasty, followed by adjuvant chemoradiotherapy (weekly cisplatin). This case highlights the diagnostic challenges, the aggressive nature of SNUC, and the feasibility of radical multimodal treatment, including complex surgery, for extensive disease. Despite aggressive therapy, outcomes remain guarded, emphasizing the need for multidisciplinary management and further research into novel therapeutic strategies for this challenging entity.

A rare diagnostic pitfall: Benign enhancing foramen magnum lesions mimicking perineural tumor spread along the spinal accessory nerves in a patient with sinonasal undifferentiated carcinoma.

Sinonasal cancers (SNC) are heterogeneous diseases with different clinical behavior. We aimed to identify prognostic factors in non-metastatic (M0)-SNC. Electronic health records from M0-SNC patients treated with definitive surgery ± postoperative radiotherapy or chemoradiotherapy at two tertiary institutions were reviewed. p16 staining was performed in the squamous cell carcinoma (SCC) subset. Multivariable analysis (MVA) calculated the adjusted hazard ratio (aHR) for histology type (SCC as the comparator), T/N categories, and primary treatment modality for the risk of locoregional failure (LRF), distant metastasis (DM), and deaths. A total of 376 patients were eligible including 209 (56%) SCC (p16+: 35; p16-/untested: 157), 42 (11%) adenocarcinoma, 35 (9%) sinonasal undifferentiated carcinoma or sinonasal neuroendocrine tumors (SNUC/SNEC), 33 (9%) mucosal melanoma (MM), 30 (8%) esthesioneuroblastoma (ES), and 27 (7%) adenoid cystic carcinoma (ACC). MVA identified MM histology (aHR 2.03, 95% CI 21.23-3.33), older age (aHR 1.02; 95% CI: 1.00-1.03), T3-4 tumor (aHR 5.08, 95% CI 2.77-9.30), and nodal involvement (aHR: 2.15, 95% CI 1.46-3.16) carried higher mortality risk (all p < 0.05); MM (aHR 10.14, 95% CI 4.90-21.01), ACC (aHR 2.97, 95% CI 1.27-6.96), and SNUC/SNEC (aHR 6.80, 95% CI 3.30-14.01) histologies and T3-4 categories (vs. T1-2, HR 4.79, 95% CI 1.53-14.95) had higher DM risk; T3-4 (aHR 2.33, 95% CI 1.37-3.97) and nodal involvement (aHR 1.70, 95% CI 1.11-2.60) conveyed higher LRF risk while SNUC/SNEC histologies had a lower LRF risk (aHR 0.51, 95% CI 0.26-3.33). Different SNC histology types exhibit distinct patterns of relapse and survival, highlighting the need for different management strategies.

Advanced-stage head and neck cancers are associated with high morbidity and mortality, often requiring complex therapeutic interventions. In cases of tumor-associated hemorrhage, intra-arterial (IA) chemotherapy combined with embolization offers a potential treatment strategy. This study assesses the safety and efficacy of this approach in a cohort of patients with bleeding head and neck malignancies. A retrospective case series of five patients with advanced head and neck cancers who underwent IA chemoembolization between November 2023 and August 2024 is presented. Tumors included oropharyngeal squamous cell carcinoma and sinonasal undifferentiated carcinoma. IA chemotherapy (cisplatin or carboplatin) was administered via selective catheterization of tumor-feeding vessels. Tumor response was measured using three-dimensional (3D) volumetric analysis, and clinical outcomes were evaluated for bleeding control, disease progression, and complications. All the patients achieved local tumor control, with tumor volume reductions ranging from 29% to 84% and a mean reduction of 66%. No rebleeding was observed at treated sites over a mean follow-up period of 8 months. All patients had an objective response at the treated site, and one patient showed disease progression on the contralateral side. No neurologic complications occurred. Complications included acute kidney injury in two patients (mitigated by adjusted hydration protocols) and flap necrosis in one patient. IA chemotherapy with embolization appears to be a safe and effective method for managing bleeding in advanced head and neck cancers. The combination offers local tumor control and mitigates the risk of rebleeding, although larger studies are needed to confirm its role in clinical practice.

Background: Sinonasal undifferentiated carcinoma (SNUC) are rare, highly aggressive neoplasms, predominantly affecting middle-aged individuals. We report its occurrence in an adolescent boy who was clinically suspected as juvenile nasopharyngeal angiofibroma (JNA). Clinical Description: A 13-year-old boy presented with headache and nasal blockage for 2 months with intermittent epistaxis. The child was otherwise stable and found to have diffuse swelling and fullness involving the right cheek and temporal region. On anterior rhinoscopy, there was a reddish, lobulated mass, with surface vascularity occupying the entire right nasal cavity, provisionally diagnosed as JNA. Management and Outcome: Imaging studies revealed enhancing mass involving the right nasal cavity, sphenopalatine fossa, and sphenoethmoidal recess with erosion of right lateral pterygoid plate, posterior wall of maxillary sinus as well as skull base erosion; findings not consistent with the benign JNA. A biopsy was done and histopathology along with immunohistochemistry helped in confirming the diagnosis of SNUC, stage IV. The child was started on induction chemotherapy with paclitaxel and carboplatin with radiotherapy at follow-up; symptoms abating by 4 months. Conclusion: The case creates awareness that a highly aggressive neoplasm like SNUC may be the cause of persistent headache, nasal blockage, and epistaxis in an adolescent, and may be misdiagnosed as JNA, if not evaluated thoroughly.

Should Induction Chemotherapy Be Considered First-Line Therapy for Sinonasal Undifferentiated Carcinoma?

6095 Background: ONB, SNEC and SNUC are rare sinonasal epithelial/neuroepithelial tumors, underserved by clinical trials, with few treatments available despite novel therapeutic agents against surface targets approved or in clinical development. Transcriptomic similarities of ONB with small cell lung cancer (SCLC), pheochromocytoma (PH), paraganglioma (PG), glioblastoma (GB) and low-grade glioma (LGG) are reported, but not for SNUC or SNEC. We examined the transcriptome of ONB, SNUC, SNEC, neuroendocrine (NE) and central nervous system tumors from a real-world (RW) patient cohort to identify similarities and uncover therapeutic vulnerabilities. Methods: Tumor specimens (pathology per referring clinician) tested (Caris Life Sciences, Phoenix, AZ) included ONB (n = 26), SNUC (n = 9), SNEC (n = 6), SCLC (n=1751), pancreatic NE tumors (PNET, n=16), PH (n=23), PG (n=50), LGG (n=657), GB (n=4524) and neuroblastoma (NB, n=47). RNA sequencing data were processed to obtain transcripts per million (TPM) values. Clustering was performed with a random subset of 50 samples for tumor types with n&gt;100. ONBs were subtyped to neural and basal (Classe et al . 2018). RW overall survival (rwOS) was calculated from insurance claims (tissue collection to last contact), compared with log-rank test; Cox proportional hazard model was used for hazard ratio (HR). Selected genes encoding surface targets included DLL3 , PMEL , PVRL4 , TACSTD2 , ERBB2 , F3 , CLDN18 , EGFR, ERBB3 , MET , GPC3 , CD276 , VTCN1 and FOSL1 . Median TPM values for genes of interest in ONB, SNUC and SNEC were examined. Results: There were 5 transcriptomic clusters (C1-5) (Table). Across clusters, median rwOS was worse for C1 (11.6 mo) and C3 (16.6 mo) vs. C2, C4, and C5 (all not reached), (p = 0.0) and was numerically better in neural (C4) vs. basal ONB (C0) (HR = 0.388, p=0.199). Highest expression for F3 (34.5), CD276 (15.6), GPC3 (7.2) and CLDN18 (1.1) was in ONB; ERBB2 (16.4), TACSTD2 (13.9), EGFR (9.2), PVRL4 (6.2), PMEL (2.0) and FOLR1 (1.5) in SNUC ; ERBB3 (83.3), MET (32.4), DLL3 (3.5) and VTCN1 (1.7) in SNEC. Conclusions: We show that neural ONBs cluster independently and basal ONBs co-cluster with SCLC and PNET, joined also by SNUC and SNEC. In our dataset, this cluster is associated with worse rwOS. We also show expression of surface target genes in ONB, SNUC and SNEC, indicating the presence of actionable subsets with existing drugs approved in other tumor types. Our findings provide targets for protein expression validation and expansion of therapeutic options for patients with these rare tumors. Cluster Tumor type, samples over N C1 ONB basal, 6/7 SNUC, 9/9 SNEC, 5/6 SCLC, 48/50PNET, 15/16NB, 2/47 C2 ONB neural, 2/18 SNEC, 1/6 PH, 22/23PG, 47/50NB, 4/47 C3 LGG, 50/50GBM, 50/50PG, 1/50 C4 NB, 41/47PG, 1/50PH, 1/23 C5 ONB neural, 16/18 ONB basal, 1/7 PG, 1/16

BackgroundSecondary headaches can signal serious underlying conditions and require early recognition to guide appropriate diagnostic and therapeutic interventions. The SNOOP10 criteria assist clinicians in identifying red flags suggestive of secondary causes. Sinonasal tumors, such as mucoceles and undifferentiated carcinomas, may present with similar symptoms and radiological features, making differentiation challenging without histological confirmation.Case PresentationWe report the case of a 32-year-old woman with a one-year history of right-sided pressing periocular headaches, initially responsive to NSAIDs. Over time, the pain intensified, became less responsive to treatment, and was associated with visual impairment, ptosis, and periorbital paresthesia. Imaging revealed a right maxillary paranasal mass initially suspected to be a mucocele. However, biopsy and immunohistochemistry confirmed a diagnosis of sinonasal undifferentiated carcinoma (SNUC). The patient underwent radiotherapy, with partial recovery of ocular motility and ptosis, though visual loss persisted.ConclusionThis case illustrates the importance of recognizing red flags in headache evaluation and highlights the utility of the SNOOP10 tool in identifying secondary headache disorders. In patients with atypical headache patterns and orbital involvement, early imaging and biopsy are essential for accurate diagnosis and timely management.

Aim of the study The aim of the study is to illustrate MRI characteristics of secondary brain lesions from head and neck tumors. The primary objective is to identify specific features of this subtype of BMs, the secondary objective is to analyze the cohort of patients. Material and methods We selected patients with histopathological confirmation of BMs and with complete MRI acquisitions, diagnosed in our hospital from 2020 to 2023. We performed statistical analysis of numerical and categorical variables through univariate and bivariate analysis, using t-test and Mann-Whitney-U test, for gaussian and respectively non-gaussian distribution of our data. Results In total were included 85 patients, of which 3 (3.5%) had BMs from primary HNC: a female patient of 74 y. old with sinonasal undifferentiated carcinoma and skull base invasion, a male patient of 48 y. old with submandibular duct carcinoma and a male patient of 57 y. old with ectopic thyroid papillary carcinoma. Other three patients had confirmed carcinomas of the pharynx and larynx. Conclusions The patients presented a highly invasive subtype of neoplasia, as both undifferentiated carcinoma and duct carcinoma are aggressive. The BMs were infratentorial, edematous, with heterogeneous signals and solid with central necrosis in the submandibular carcinoma patient. The BMs from the sinonasal carcinoma had multiple small cystic lesions, both supra- and infratentorial. The patient with BMs from an ectopic papillary thyroid carcinoma could be the first confirmed case of its kind, as no other was anteriorly histologically proved with BMs. He had multiple lesions, the largest one, cystic with peripheric enhancement in the left parietal lobe.

Analysis of ASCL1/NEUROD1/POU2F3/YAP1 Yields Novel Insights for the Diagnosis of Olfactory Neuroblastoma and Identifies Sinonasal Tuft Cell-like Carcinoma

Sinonasal undifferentiated carcinoma is a rare and aggressive tumour of the nasal cavity. Treatment involves a multimodal approach: surgical resection, radiotherapy and/or concurrent chemotherapy. A 58-year-old female presented with pain in the medial wall of the left orbital cavity

Background/Objectives: Sinonasal malignancies are rare and highly diverse cancers that pose significant diagnostic challenges due to their variable histological features and complex anatomical locations. Accurate diagnosis is critical for guiding treatment, yet conventional methods often require multiple biopsies. This study aimed to evaluate the potential of confocal laser endomicroscopy (CLE) for real-time imaging of sinonasal tumors to characterize specific features of different entities and improve diagnostic precision. Methods: Ten patients with various sinonasal malignancies, including squamous cell carcinoma, adenocarcinoma, sinonasal undifferentiated carcinoma, olfactory neuroblastoma, sinonasal mucosal melanoma, and endonasal lymphoma, were examined using CLE during diagnostic endoscopy. CLE images were compared descriptively with histopathological cross-sections to identify unique imaging patterns for each tumor type. Results: CLE was feasible across all cases, with high-quality images obtained despite anatomical challenges in some cases. Characteristic features, such as vascular clusters in undifferentiated carcinoma, mucin-filled bubbles in adenocarcinoma, and small round cells in neuroblastoma, were identified and corresponded well with histopathological findings. CLE also helped guide biopsies by revealing areas with diagnostic relevance. Conclusions: CLE demonstrates promise as an adjunct diagnostic tool in sinonasal malignancies, offering real-time imaging that correlates with histopathological findings and aids in targeted biopsies. While this study provides preliminary insights into the utility of CLE, further research with larger cohorts and statistical validation is necessary to establish its diagnostic reliability and broader clinical application.