Sinonasal Tumors Research Articles

Modern approaches for management patients with craniofacial tumors (literature review)

Despite a significant amount of information on approaches to managing patients with craniofacial tumors, the increasing number of modern high-tech technologies, there remain a number of controversial issues regarding the choice of treatment strategy that fully satisfies the requirements of objective assessment of effectiveness and the improvement of quality of life for patients suffering from oncological disease. Craniofacial approaches sufficiently adhere to oncological principles and allow for the removal of even extensive tumors which greatly improve immediate and long-term outcomes, reliably enhancing quality of life, which is the most important task in the surgery of malignant skull base tumors. As evident from the aforementioned modifications and classical approaches to reconstruction of defects following craniofacial resections, in order to summarize the vast amount of information on the advantages and disadvantages of corresponding methods, a multicenter independent prospective study is needed, during which data from different clinics would undergo critical analysis using modern evidence-based medicine methods. On the path to methodological comprehension of existing concepts and actions towards creating one’s own algorithms lies a multifactorial analysis of personal experience in management and undoubtedly the care of patients from a group with such an unfavorable prognosis for survival. An immediate observation that follows the realization of the practical significance of a surgical treatment algorithm common to all physicians and mid-level medical staff is that the most effective achievement of the above task lies in learning from one’s own mistakes during patient care. Very encouraging research results, in which attempts are made at mastering new materials, herald a future scientific breakthrough in craniofacial reconstruction. The use of bioprosthetics and synthetic analogs is particularly relevant for those patients for whom reconstruction using their own tissues is contraindicated for various reasons. This article demonstrates the most outstanding achievements in the treatment of patients with sinonasal tumors.Malignant tumors of the sinonasal region are rare and highly diverse in their histological origin neoplasms, accounting for an average of 0.2–1.1 % of all newly diagnosed tumors. Risk factors, to varying degrees pathogenetically linked to disease progression, include a mutation of the TP53 gene in 80 % of cases, prolonged exposure to industrial air pollutants, smoking, male gender, and age over 55 years in 85 % of cases, infection with human papillomavirus and Epstein–Barr virus. Despite a substantial amount of information on approaches to managing this patient population, the increasing number of modern technology-intensive methods has led to ongoing debates regarding the selection of a treatment strategy that fully meets the requirements for objectively assessing efficacy and improving the quality of life of patients suffering from oncological disease.Aim. To investigate modern approaches to treatment of patients with tumors of the craniocephalic location, identify factors of surgical treatment success and favorable long-term prognosis, develop a management algorithm for patients with sinonasal neoplasms, provide rationale for using various reconstruction techniques for postresection defects. Systemic approach to the analysis of effectiveness and expediency of modern approaches to treatment of patients with tumors of the craniocephalic region requires integration of several key concepts. Taking into account individual characteristics of the patient by an experienced surgical team can lead to good treatment results including increased survival rates.Development of algorithms for management of patients of this category and individualization of selection of reconstructive techniques are important problems in practical healthcare. Minimization of complications is one of the main goals of postoperative patient observation. The optimal approach to treatment even in this prospectless in the context of survival and social rehabilitation group of patients assumes greatest possible preservation of facial esthetic features and increased quality of life which can be achieved only with well-coordinated work of highly professional interdisciplinary team.

Demographic and Clinical Characteristics of Sino-Nasal Tumour Patients: A Cross-Sectional Study of 60 Cases

Introduction: Sino-nasal tumors are a rare yet clinically significant group of neoplasms that affect the nasal cavity and paranasal sinuses. Although these tumors represent a small percentage of head and neck cancers, they often present with complex symptoms and can be challenging to diagnose early. This study aimed to evaluate the demographic and clinical characteristics of sino-nasal tumor patients. Methods: This cross-sectional observational study was conducted at the ENT and Head-Neck Surgery department, Rajshahi Medical College Hospital, Rajshahi, from June 2014 to November 2014. A total of 60 patients presenting with sinonasal tumors were selected as study subjects by purposive sampling technique. Data analysis was done by Statistical Package for Social Sciences (SPSS) version 20.0. A descriptive method was adopted. Result: In this study of 60 sino-nasal tumor patients, the age groups 21-30 and 51-60 years had the highest representation (20% each), with the majority being male (76.67%) and primarily woodworkers (40%). Socioeconomically, 75% of patients were classified as "poor." Smoking was the most prevalent habit, affecting 50% of patients. Clinically, nasal obstruction was the most common symptom (93.33%), followed by loss of smell (70%) and epistaxis and headache (50% each). The majority of tumors were benign (93.33%), with only 6.67% being malignant. Among malignancy cases, nasal obstruction was a universal symptom, with facial pain, headache, and hyposmia observed in 75% of these patients. Conclusion: This study concludes that sino-nasal tumors predominantly affect middle-aged men, often with significant occupational exposure to carcinogenic materials like wood dust and industrial chemicals. Socioeconomic and lifestyle factors further compound the risk, highlighting the importance of comprehensive preventive measures and early detection strategies, particularly in high-risk occupations. Awareness of prevalent symptoms such as nasal obstruction, ...

Midface Degloving Approach for Total Maxillectomy Without Orbital Exenteration: A Case Series.

Evaluate the feasibility of the midface degloving approach (MDA) in total maxillectomy without orbital exenteration (TMWOE) and reconstruction for sino-nasal neoplasms. Retrospective case series. Tertiary referral center. This single-center series included 9 consecutive sino-nasal neoplasm patients who had TMWOE using MDA, free tissue reconstruction, and orbital floor implants (April 2018-Dec 2022) assessing tumor characteristics, margins, and complications. There were 3 female and 6 male patients with a median age of 61 years. The median follow-up was 462 days. There were 7 malignant and 2 benign tumors. The median tumor size was 4.6 cm. There were 7 clear margins and 2 positive margins. Most patients underwent some combination of preoperative and or postoperative therapies. After resection, a variety of free tissue reconstruction was performed. Overall, there were no complications clearly attributable to the midface degloving approach. Flap debulking was required in one patient but no long-term complications were encountered. Midface degloving offers an alternative to the Weber-Ferguson for TMWOE and avoids facial incision while providing adequate exposure to the orbital rim. Patient selection is critical, as tumors extending laterally into the zygomatic arch and infratemporal fossa may not be accessible.

Development of paranasal sinus surgery in Austria and Switzerland: past, present, and future

Thanks to our predecessors and technical progress, we can nowadays offer our patients a safe and modern paranasal sinus surgery. This article provides an overview of the historical development of paranasal sinus surgery in Austria and Switzerland and to shed light on the dynamic progress of this discipline in an international context. Paranasal sinus surgery has undergone significant change in recent decades, driven by rapid technological advances that have significantly improved surgical procedures and operative outcomes. While indications were originally limited to treatment of inflammatory diseases, today, endoscopic procedures cover interventions in the area of the anterior skull base, the orbit and sinonasal tumors. The concept of functional endoscopic sinus surgery (FESS) may seem simple, but the anatomic variability, especially in the area of the frontal sinus, as well as the wide spectrum and severity of diseases can be achallenge. Therefore, paranasal sinus surgery should not be acasual operation and should only be performed by well-trained surgeons to prevent disease recurrence as well as medical and economic follow-up costs. Standardized surgical training for aspiring paranasal sinus and skull base surgeons is critical. Preoperative planning through systematic analysis of CT images is an essential factor to achieve optimal results and to avoid intraoperative complications. The pathophysiological understanding of sinonasal disease and the recent developments of new drug therapies such as monoclonal antibodies also enable excellent results in the small subgroup of patients who do not benefit from acombination of surgical rehabilitation and long-term drug therapy. The dynamic development of endoscopic paranasal sinus surgery in recent decades shows the potential of the field for the coming decades.

Morbidity of multimodal treatments including endoscopic surgery for sinonasal malignancies: Results of an international collaborative study on 940 patients (MUSES).

In the management of sinonasal malignancies treatment-induced morbidity and mortality is gaining relevance both for surgical approaches (endoscopic and open resection) and non-surgical therapies. The aim of this multicenter study is to assess complications associated with endoscopic surgery and non-surgical treatments (neoadjuvant and/or adjuvant) for malignant sinonasal tumors. All patients with nasoethmoidal malignancies treated with curative intent with endoscopic or endoscopic-assisted surgery at three referral centers with uniform management policies were included. Neo- and/or adjuvant (chemo)radiotherapy was administered according to histology and pathological report. Demographics, treatment characteristics, and complications related both to the surgical and non-surgical approaches were retrieved. The data were analyzed with univariate and multivariate statistics to assess independent predictors of complications. Nine hundred and forty patients were included, 643 males (68%) and 297 females (32%). A total of 225 complications were identified in 187 patients (19.9%): cerebrospinal fluid (CSF) leak (3.5%), mucocele (2.3%), surgical site bleeding (2.0%), epiphora (2.0%), and radionecrosis (2.0%) were the most common. Treatment-related mortality was 0.4%. Variables independently associated with complications at multivariate analysis were principally dural resection (OR 1.92), cranioendoscopic or multiportal resection (OR 2.93), dural repair with multilayer technique with less than three layers (OR 2.17), and graft different from iliotibial tract (OR 3.29). Our study shows that modern endoscopic treatments and radiotherapy for sinonasal malignancies are associated with limited morbidity and treatment-related mortality. CSF leak and radionecrosis, although rare, remain the most frequent complications and should be further addressed by future research efforts.

Sinonasal extramedullary plasmacytoma: A case report and review of the literature.

Primary solitary extramedullary plasmacytoma is a malignant neoplasm characterized by the monoclonal proliferation of plasma cells outside the bone marrow. The tumor rarely occurs in the sinonasal tract, accounting for about 4% of all non-epithelial sinonasal tumors. Herein, the authors describe a rare case of sinonasal extramedullary plasmacytoma in a 33-year-old man who presented with a 3-month history of progressively increasing nasal mass, causing obstruction. A CT scan showed a soft tissue mass measuring 5*8*3 cm in the right and left nasal cavities, obstructing the nasal airway. The mass extended to the right maxillary sinus. Histopathology and immunohistochemical tests confirmed it to be plasmacytoma. Lymphomas with prominent plasmacytic differentiation and multiple myeloma workups were negative. The patient initially refused treatment. After counseling, the patient consented to undergo surgery and later radiotherapy treatment. At one-year follow-up, the patient is disease-free with no signs of recurrence. Plasmacytomas are either medullary or extramedullary neoplasms. The latter are extremely rare tumors, more commonly presenting in the submucosal tissue of the upper respiratory tract. A mass or swelling causing nasal or pharyngeal symptoms is by far the most common presentation of this entity in the head and neck region. Because these lesions are radiosensitive, radiotherapy is a recommended treatment approach. Further studies are needed to better understand the prognosis and effective treatment regimens.

Differentiating Sinonasal Tumor Entities with Fluorescein-Enhanced Confocal Laser Endomicroscopy: A Step Forward in Precision Diagnostics.

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.

Endoscopic Endonasal Approach to the Inferolateral Intraconal Orbit: An Anatomical Analysis of Exposure and Maneuverability.

Endoscopic endonasal techniques, initially developed for sinonasal tumor resection, have revolutionized the approach to orbital lesions. The emergence of endonasal orbital tumor surgery has prompted anatomical studies focusing on the medial orbit, yet there remains a lack of literature on maneuverability lateral to the optic nerve (ON), with current feasibility assessments relying primarily on the plane of resectability (POR). Bilateral anatomical dissections were conducted on four latex-injected human cadaveric heads using an endoscopic medial and inferior orbitotomy and superomedial displacement of the inferior rectus muscle (IRM) to access the inferolateral intraconal quadrant. Measurements of distances, areas, angles of attack, and volumetric exposure were obtained using stereotactic points from an imaging-based navigation system. Additionally, an illustrative case was presented to demonstrate the endoscopic management of laterally based intraconal lesions. The intraconal space was safely accessed through superomedial displacement of the IRM. The mean intraconal volumetric exposure attained through this maneuver was 2.78cm3 (1.18cm3). The most superolateral point reachable by the ipsilateral endoscopic endonasal approach was consistently lateral and superior to the ON at a mean absolute distance of 1.45cm (0.37cm). Maneuverability at this target point was superior in the sagittal plane, noted by a larger vertical angle of attack compared with the horizontal angle of attack. This study demonstrates that inferolateral intraconal dissection through an ipsilateral endoscopic endonasal approach is feasible via a medial orbitotomy and superomedial retraction of the IRM. Additionally, our findings reaffirm lesions below the POR are suitable for endoscopic endonasal resection.

Psychiatric disorders in patients with benign and malignant sinonasal tumors: a prospective cross-sectional study.

To assess the prevalence of depression, anxiety, insomnia, and somatic symptom disorder (SSD) in patients with benign and malignant sinonasal tumors. Pretreatment patients with sinonasal tumors were prospectively recruited on the rhinology ward of a tertiary hospital from July 2021 to March 2022. The electronic questionnaire which contains the rhinological symptom scale, the 22-item Sinonasal Outcome Test (SNOT-22) Scale, the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), the Insomnia Severity Index (ISI), and the Patient Health Questionnaire-15 (PHQ-15) was filled out by patients at admission. The associations between the scores of symptom/SNOT-22 and psychometric tests were assessed by the Pearson correlation coefficient (r) and simple linear regression. The receiver operating characteristic (ROC) analysis was used to evaluate the performance of the SNOT-22 score in predicting psychiatric disorders. Thirteen patients with benign sinonasal tumors and 15 patients with malignant sinonasal tumors were recruited. The benign and malignant groups did not differ significantly regarding symptomatology and mental wellbeing. Of the total patients, 9 were at risk of depression (PHQ-9 > 4), 10 were at risk of anxiety (GAD-7 > 4), 11 were at risk of insomnia (ISI > 7), and 11 were at risk of SSD (PHQ-15 > 4). The overall symptom, facial pain/pressure, postnasal drip, and SNOT-22 scores were positively associated with scores of psychometric tests. Patients with a high SNOT-22 score (>18) are likely to be affected by comorbid psychiatric disorders. When interpreting the results of this study, it should be noted that screening tools, not diagnostic tools, were used to identify psychiatric risk. Depression, anxiety, insomnia, and SSD are prevalent in patients with sinonasal tumors. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 18.

The added value of narrow band imaging in Sinonasal tumour resection and surveillance: Our experience

Background & purposeNarrow Band Imaging (NBI), developed by Olympus Medical Systems, has played a role in diagnosing digestive tract lesions and cancers, diagnosing and characterizing bladder cancers during cystoscopy and in the diagnosis and management of Head and Neck cancers. We aim to explore the potential use of NBI in the diagnosis, management, and follow-up of sinonasal tumours. MethodsWe present a series of cases treated at our institution, where NBI played a crucial role in the diagnosis, surgical management, intraoperative decision-making, and follow-up. The cases include a patient with sinonasal lymphoma, 2 patients with sinonosal malignant melanoma and a patient with olfactory neuroblastoma. ResultsIn our experience, NBI proved beneficial not only in detecting otherwise unseen nasal lesions but also in targeted biopsies and intraoperative planning, on some occasions altering the course of treatment. NBI may also be a simple, inexpensive surveillance method for detecting sinonasal tumours recurrence after excision. ConclusionWhile there are limitations to its use, there is potential for NBI to be of significant use in rhinology practice, reducing morbidity and tumour recurrence rates and streamlining the diagnostic and surveillance process.

Analyzing The Impact Of Age And Gender On Malignancy Rates In Sino-Nasal Tumors

Introduction: Sino-nasal tumors, a diverse group of neoplasms affecting the nasal cavity and paranasal sinuses, present varying clinical and demographic characteristics. This study aimed to assess the frequency of malignancy in sino-nasal tumors concerning age and gender. Methods: This cross-sectional observational study was conducted at the ENT and Head-Neck Surgery department, Rajshahi Medical College Hospital, Rajshahi, from June 2014 to November 2014. A total of 60 patients presenting with sinonasal tumors were selected as study subjects by purposive sampling technique. Data analysis was done by Statistical Package for Social Sciences (SPSS) version 20.0. A descriptive method was adopted. Result: The highest percentage falls within the 21-30 and 51-60 age groups, each comprising 20%. Males are the majority, with a male-to-female ratio of 3.3:1. The most common symptoms are nasal obstruction (93.33%) and loss of smell (70%). Most cases (93.33%) are benign, with only 6.67% being malignant, predominantly in the older age groups (51-60 and 61-70). Among the malignant cases, 75% are male, giving a male-to-female malignancy ratio of 3:1. Conclusion: This study reveals that sino-nasal tumors are predominantly benign, with malignancies primarily found in patients over 50, particularly males. The strong male predominance in malignant cases aligns with known occupational and lifestyle risk factors. These findings suggest that age and gender are significant factors in malignancy risk for sino-nasal tumors, highlighting the need for focused screening and preventive measures in older male populations who may be at higher risk

Usage of Magnetic Resonance Imaging-Based Texture Analysis Features in Discrimination of Benign and Malignant Sinonasal Tumors

Aim: The objective of this study was to differentiate between benign and malignant sinonasal tumors using magnetic resonance imaging (MRI)-based texture analysis features. Materials and Method: Histopathologically proven benign or malignant sinonasal tumor patients were included in the study from MRI examinations performed between January 2013 and December 2020. Inclusion criteria included a tumor size of at least 1 cm and preoperative magnetic resonance imaging with axial T1W, axial fat-suppressed T2W, and axial T1W postcontrast sequences. After the images were transferred to a dedicated workstation, texture analysis calculations were performed. Differences between benign and malignant groups were compared. Results: The mean age of 37 patients (8 female, 29 male) included in the study was 50.8 ± 21.9 years. In our study, we found no statistically significant difference between malignant and benign sinonasal tumors in nine tissue analysis parameters obtained by MRI. Conclusion: MRI-based texture analysis needs identical MRI protocols for evaluating tumors. MRI-based texture analysis is not a useful diagnostic tool to discriminate between benign and malignant sinonasal tumors when specific pathologic types are not selected and scanning protocols are not identical.

Mucosal Spread of Sinonasal Adenocarcinoma into the Nasolacrimal Duct Without Bony Erosion of the Nasolacrimal Canal: A Case Report.

Sinonasal malignancy is a rare but recognized cause for nasolacrimal obstruction leading to epiphora. While direct mucosal spread through the nasolacrimal duct can occur in benign sinonasal tumors such as inverting papilloma, the same phenomenon has not been described in malignant lesions. The authors present a case of a low-grade nonintestinal type sinonasal adenocarcinoma centered on the inferior meatus of the sinonasal cavity, showing mucosal invasion into the nasolacrimal duct with bony expansion but no erosion of the nasolacrimal canal. The lesion was excised en bloc with a combined endoscopic and external approach with clear margins.

Multimodal management of PD‐L1 positive sinonasal inverted papilloma with malignant transformation

AbstractInverted papillomas (IP) are rare sinonasal tumors (Schneiderian papillomas) characterized by local invasion, with high recurrence rates and potential for malignant transformation into squamous cell carcinoma (SCC ex‐IP). Traditionally, the mainstay of treatment has been surgical resection, often challenging due to invasion of the skull base or vital neurovascular structures. In advanced cases, prognosis is poorer and radiation therapy is the current standard of care with limited role of systemic therapy. We present a case of unresectable SCC ex‐IP treated with sequential chemoradiation and PD‐1 immunotherapy (pembrolizumab) and achieving complete response at 1 year. This case suggests that immunotherapy can effectively treat SCC ex‐IP and we propose that programmed death ligand‐1 (PD‐L1) testing should be performed in all advanced cases. Prospective studies are needed to validate immunotherapy in adjuvant or frontline treatments for advanced SCC ex‐IP, and the role of PD‐L1 as a predictive biomarker.

Medium-term oncological outcome endoscopic surgery malignant tumors of the nasal cavity and paranasal sinuses

Introduction. Transnasal endoscopic resection of sinonasal tumors is currently used in many clinics around the world. Short- and long-term oncological outcomes primarily depend on tumor histology. However, most currently existing studies are based on a small number of observations due to the rarity and heterogeneity of sinonasal malignancy.Aim. To evaluate short- and medium-term oncological outcomes of treatment of malignant sinonasal tumors. Materials and methods. The study is based on retrospective analysis of 95 patients who underwent endoscopic surgery for sinonasal malignancy between 2014 and 2023 at the N.N. Blokhin National medical Research Center of Oncology. Squamous cell carcinoma was diagnosed in 27 (28.4 %) patients, olfactory neuroblastoma in 13 (13.7 %), mucosal melanoma in 30 (31.6 %), adenocarcinoma in (6.3 %), adenoid cystic carcinoma in 7 (7.3 %), sarcomas in 12 (12.7 %). Results. In the study group, 2-years overall survival and recurrence-free survival were 81.3 and 61.4 % respectively, survival without local recurrence was 87.5 %. The outcomes significantly depended on tumor histology.Conclusion. Oncological outcomes of endoscopic resections of sinonasal tumors significantly depend on tumor histology, but in general they allow to achieve good local control. Small number of observations, variety of histological forms, and short follow-up periods do not allow to accurately evaluate the effectiveness of this approach for each tumor type. further research in large populations is needed to establish risk factors.

Applications of vascularized pericranial flaps in endoscopic skull base surgeries

Objective: To study the feasibility and efficacy of pericranial flaps for the repairs of large anterior skull base defects. Methods: The average length of the pericranial flaps needed for skull base repair was determined with computed tomography measurements in 20 adults and anatomical dissections in 5 cadaver specimen. A series of patients who underwent endoscopic skull base surgeries and subsequent reconstructions with pericranial flaps at the Department of Otolaryngology Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital from 2016 to 2022 were retrospectively reviewed. There were 19 males and 6 females, aged from 11 to 59 years, including 13 cases of cerebrospinal fluid (CSF) rhinorrhea (12 traumatic) and 12 cases of sinonasal skull base tumors. Descriptive statistical methods were used. Results: The mean areas of anterior skull base, sellar, and clival defects were 16.13, 14.03 and 13.12 cm2, respectively, and the mean pericranial flap lengths were (18.77±3.44)mm, (133.99±5.08)mm, (181.76±6.31)mm, respectively. Among sinonasal skull base neoplasms, the pathologies included olfactory neuroblastoma (n=6), squamous cell carcinoma (n=3), chondrosarcoma (n=1), osteosarcoma (n=1), and invasive schwannoma (n=1), in whom 8 patients underwent adjuvant radiotherapy after surgery. One patient (7.7%) had acoustic neuroma-related CSF leak before radiotherapy. All 25 patients successfully underwent skull base reconstruction without complications such as CSF leak, intracranial infection, forehead wrinkles disappearance, or scalp necrosis. All flaps survived well with no CSF leaks within the follow-up period of 2-4 years. Conclusion: Pericranial flap is a safe choice for large anterior skull base defects following resection of sinonasal skull base neoplasms and complex traumatic CSF leaks when endonasal flaps are not available.

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

The diagnosis and treatment of sinonasal small round epithelial/neuroepithelial malignancies depends on the expression of conventional neuroendocrine markers (cNEM), such as synaptophysin, chromogranin-A, INSM1, and CD56/NCAM1. However, these tumors remain diagnostically challenging due to overlapping histologic and immunohistochemical features. The transcriptional regulators ASLC1, NEUROD1, POU2F3 and YAP1 are novel NEM (nNEM) used for subtyping of small-cell lung cancer (SCLC). Herein, we assessed the immunoexpression of nNEM in 76 sinonasal malignancies including 27 olfactory neuroblastomas (ONB), 14 small-cell (SCNEC) and 2 large-cell neuroendocrine carcinomas (LCNEC), 12 sinonasal undifferentiated carcinomas (SNUC), 7 olfactory carcinomas (OC), 11 SWI/SNF-deficient carcinomas, and 3 neuroendocrine tumors (NET). We correlated nNEM expression with the extent of neuroendocrine differentiation defined by averaged cNEM expression (NE-high: H-score≥150, NE-low: H-score<150). Dominant NE subtypes were defined by the nNEM with the highest H-score. Co-expression of two nNEM with <100 H-score difference defined a co-dominant NE subtype. NE differentiation positively correlated with NEUROD1 and negatively with YAP1 expression (p<0.0001). ONB were NE-high (96%) and all were NEUROD1-dominant/POU2F3-negative/ASCL1-negative(low)/YAP1-negative(low). In contrast to ONB, all OC were NE-low, mostly (71%) co-dominant subtypes, and NEUROD1-low(negative) (100%, p=0.0001) and YAP1-high (71%, p=0.0001). Most notably, all SNUC were POU2F3-(co)dominant/NEUROD1-negative irrespective of the IDH2 mutations. Sinonasal tumors with high POU2F3 expression showed enrichment for “tuft cell carcinoma” and tuft cell signatures (p=0.009). Similar to SCLC, SCNEC was heterogeneous in terms of nNEM expression comprising several molecular subtypes including ASCL1-(co)dominant (43%) cases. All SWI/SNF-deficient carcinomas were consistently ASLC1/NEUROD1/POU2F3-negative and YAP1-positive. ASLC1/NEUROD1/POU2F3/YAP1 are useful markers in differential diagnosis of ONB, SNUC, OC and SWI/SNF-deficient carcinomas. Subsets of SNUC and LCNEC may represent tuft cell-like carcinomas suggesting that the tuft cell could be explored as the cell of origin for these tumors. The therapeutic vulnerabilities associated with POU2F3 expression in SCLC suggest that a similar approach might be considered for POU2F3-positive carcinomas of the sinonasal tract. Given their diagnostic and possible therapeutic relevance, nNEM have potential to transform the way we approach the diagnosis and management of sinonasal small round epithelial/neuroepithelial malignancies.

Rare Head and Neck Cancers and Pathological Diagnosis Challenges: A Comprehensive Literature Review.

Head and neck cancers (HNCs) arise from anatomically adjacent sites and subsites, with varying etiological factors, diagnostic strategies, prognoses, and treatment approaches. While conventional squamous cell carcinoma (SCC) is the most common histology in the head and neck district, HNCs encompass a variety of rare histopathological entities, categorized into epithelial tumors such as salivary gland cancers, sinonasal tumors, neuroendocrine tumors, malignant odontogenic tumors, and SCC variants versus non-epithelial tumors including soft tissue sarcomas, mucosal melanomas, and hematological malignancies. Rare HNCs (R-HNCs) represent a diagnostic and clinical challenge, requiring histopathological expertise, the availability of peculiar molecular analysis, and the personalization of local and systemic treatments, all guided by a multidisciplinary tumor board. Here, we provide a comprehensive literature review on R-HNCs, emphasizing key histopathological and molecular characteristics that are crucial for guiding treatment decisions. An insight about the latest developments in systemic treatments is also reported.

Advanced tumour-induced osteomalacia secondary to sinonasal phosphaturic mesenchymal tumour.

A rare case of sinonasal PMT is presented, with a focus on the imaging findings and role of the radiologist and nuclear physician.

The role of endoscopic endonasal surgery in the management of sinonasal malignant tumors with skull base involvement

Sinonasal malignant tumors (SNMTs) represent a rare and heterogeneous group of tumors. SNMTs often present late which can lead to complex, patient-specific treatment decisions. Over the last two decades, endoscopic endonasal surgery (EES) has become a more frequently utilized surgical approach to removing these tumors. Increasingly, studies have compared the outcomes of this approach to traditional open approaches for different SNMTs. Differences in histology and extent of invasion impact the utility of EES. Negative margins are critical for improving survival; however, skull base involvement can add anatomical challenges for achieving negative margins during EES. This paper reviews the literature on outcomes of EES for SNMTs with skull base involvement and presents evidence supporting the utility of EES for select patients. EES is a safe and effective treatment in patients with less invasive SNMTs or less aggressive histology and can provide patients with fewer complications and morbidity than traditional open approaches. As such, it plays a key role in surgical management, providing either sole access or a critical avenue for SNMT removal. EES plays a key role in the multimodal oncological approach to the treatment of different SNMT histologies.