Sinonasal Malignancy Following Cranial Irradiation: A Scoping Review and Case Report of Sinonasal Teratocarcinosarcoma.

Background Radiation therapy is a mainstay of treatment for brain tumors, but delayed complications include secondary malignancy which may occur months to years after treatment completion. Methods We reviewed the medical records of a 41-year-old female treated with 60 Gy of radiation for a recurrent astrocytoma, who 6 years later developed a locally advanced sinonasal teratocarcinosarcoma. We searched MEDLINE, Embase, and Web of Science to conduct a scoping review of biopsy-proven sinonasal malignancy in patients who previously received cranial irradiation for a brain tumor. Results To our knowledge, this is the first report of a patient to present with a sinonasal teratocarcinosarcoma after receiving irradiation for a brain tumor. Our scoping review of 1,907 studies produced 14 similar cases of secondary sinonasal malignancy. Median age of primary cancer diagnosis was 39.5 years old (standard deviation [SD]: 21.9), and median radiation dose was 54 Gy (SD: 20.3). Median latency time between the primary cancer and secondary sinonasal cancer was 9.5 years (SD: 5.8). Olfactory neuroblastoma was the most common sinonasal cancer ( n = 4). Fifty percent of patients died from their sinonasal cancer within 1.5 years. Conclusion Patients who receive radiation exposure to the sinonasal region for treatment of a primary brain tumor, including low doses or scatter radiation, may be at risk of a secondary sinonasal malignancy later in life. Physicians who monitor at-risk patients must be vigilant of symptoms which may suggest sinonasal malignancy, and surveillance should include radiographic review with careful monitoring for a secondary malignancy throughout the entire irradiated field.

Cerebritis, optic ischemia, and cavernous sinus thrombosis arising from sinonasal mucormycosis.

Brain and ocular infections can be the worst and fatal consequences of sinonasal infections in immunomodulated or immunocompromised patients. We report a case of a 35-year-old female who received an allogenic hematopoietic stem cell transplantation for acute myeloid leukemia, suffering from maxillo-spheno-ethmoidal rhinosinusitis which was complicated by cavernous sinus thrombosis, orbital cellulitis, optic ischemia and cerebritis.

Interferon alpha-2b treatment for exophytic nasal papillomas and human papillomavirus infection.

OBJECTIVES: Exophytic Sinonasal Papilloma (ESP) is a benign tumor of the sinonasal tract. Complete surgical excision by endoscopic surgery is the treatment of choice. However, a high recurrence rate (36% at 5-year follow-up) is associated with this method, which may indicate the presence of microorganisms such as Human Papillomavirus (HPV). It is important to note that the standard treatment for ESP does not include antiviral drugs. In our study, we are testing the effectiveness of an interferon-containing drug in reducing recurrence and postoperative reactions in patients with ESP. METHODS: We included 78 patients aged 23-83 years with a confirmed diagnosis of ESP by rhinoscopy and nasal endoscopy and a positive PCR test for HPV in nasal scrapings. To compare the results, we divided the patients into main and control groups. The main group received recombinant human interferon after surgery, while the control group did not receive the drug. We performed a statistical analysis to compare the proportion of patients without reactive manifestations at different stages of the postoperative period, as well as to compare the proportion of patients with recurrent ESP at certain stages of observation. RESULTS: The introduction of recombinant human interferon accelerated the resolution of postoperative reactions and promoted the healing of the nasal mucosa after surgical removal of the ESP. We also found a statistically significant association between treatment with recombinant interferon and a reduction in the recurrence rate of ESP. CONCLUSION: According to the results of the study, it was found that in the main group of patients who received rhIFN-α2b (recombinant human Interferon alpha 2b) in the postoperative period, the frequency of relapses of ESP and the time of postoperative recovery were significantly lower than in patients in the control group who did not take the drug. LEVEL OF EVIDENCE: Cohort Study.

Outcomes of SWI/SNF complex-deficient sinonasal carcinomas in a Southeast Asian cohort.

BACKGROUND: SWI/SNF complex-deficient sinonasal carcinomas are rare, genetically distinct, and aggressive entities. METHODS: SMARCB1 and SMARCA4 immunohistochemistry was retrospectively performed on a cohort of undifferentiated, poorly differentiated, and poorly defined sinonasal carcinomas. Survival outcomes were compared between SMARCB1/SMARCA4 (SWI/SNF complex)-deficient and -retained groups. RESULTS: Eight SWI/SNF complex-deficient (six SMARCB1-deficient, two SMARCA4-deficient) cases were identified among 47 patients over 12 years. Triple-modality treatment was more frequently utilized in SWI/SNF complex-deficient carcinomas than in SWI/SNF complex-retained carcinomas (71.4% vs. 11.8%, p = 0.001). After a median follow-up of 21.3 (IQR 9.9-56.0) months, SWI/SNF complex-deficient sinonasal carcinomas showed comparable recurrence rates (57.1% vs. 52.9%, p = 0.839), time-to-recurrence (7.3 [IQR 6.6-8.3] vs. 9.1 [IQR 3.9-17.4] months, p = 0.531), and overall survival (17.7 [IQR 11.8-67.0] vs. 21.6 [IQR 8.9-56.0] months, p = 0.835) compared to SWI/SNF complex-retained sinonasal carcinomas. CONCLUSION: Triple-modality treatment may improve survival in SWI/SNF complex-deficient sinonasal carcinomas.

Long-term outcomes in advanced anterior skull base malignancy: a single quaternary institution experience.

BACKGROUND: Advanced skull base malignancies are a heterogenous subset of head and neck cancers, and management is often complex. In recent times, there has been a paradigm shift in surgical technique and the advent of novel systemic options. Our goal was to analyse the long-term outcomes of a single quaternary head and neck and skull base service. METHODS: A retrospective review of 127 patients with advanced anterior skull base malignancies that were treated at our institution between 1999 and 2015 was performed. Multiple variables were investigated to assess their significance on 5 and 10-year outcomes. RESULTS: The mean age was 60.9 (± 12.6 SD). Sixty-four percent were males and 36% were females. Ninety percent of patients had T4 disease. Median survival time was 133 months. The 5-year overall survival (OS) was 66.2%, disease-specific survival (DSS) was 74.7%, and recurrence-free survival (RFS) was 65.0%. The 10-year OS was 55.1%, DSS was 72.1%, and RFS was 53.4%. Histological type and margin status significantly affected OS & DSS. CONCLUSION: Surgical management of advanced skull base tumours has evolved over the last few decades at our institution with acceptable survival outcomes and complication rates. Histological diagnosis and margin status are the main predictors of survival. The addition of neoadjuvant systemic agents in current trials may improve outcomes.

Surgical therapy in advanced sinonasal carcinomas - retrospective study.

BACKGROUND AND AIM: Sinonasal tumors are a rare and heterogeneous group of malignant tumors with different histopathological characteristics and clinical presentation. These tumors are usually treated through surgery. The aim of this study is to present our results of surgical therapy in patients with an advanced sinonasal tumor. METHODS: This retrospective study included patients with an advanced sinonasal tumor who were surgically treated. The surgical technique combined both a frontal transbasal approach together with an endoscopic endonasal approach. The parameters used for evaluation were the histological type of tumor, the radicality of resection (complete vs. incomplete), the frequency of recurrence, the surgical and postoperative complications, the type of subsequent oncological therapy and the overall survival. RESULTS: The group consisted of ten patients seven were men and three were women. Complete resection (defined as R0) was achieved in 8 (80%) of the cases, subcomplete resection was achieved in 2 (20%) of the cases. The overall survival period was 28.7 months (95% confidence interval 15.9-41.6). CONCLUSION: The combination of the frontal transbasal approach with the endoscopic endonasal approach is a suitable surgical strategy that enables easier achievement of complete tumor resection, reconstruction of the anterior skull base and reduces the need for extensive surgical approaches.

SMARCB1-Retained and SMARCB1-Deficient SNUC are Genetically Distinct: A Pilot Study Using RNA Sequencing.

Background Understanding the genetic basis for the molecular classification of sinonasal undifferentiated carcinoma (SNUC) based on SMARCB1 may improve our understating regarding the nature of the disease. The objective of the study was to compare the genetic profile of SMARCB1-retained (SR-SNUC) and SMARCB1-deficient SNUC (SD-SNUC). Methods Formalin-fixed, paraffin-embedded tissue from treatment-naive patients with SNUC were selected. Three cases of SR-SNUC, four cases of SD-SNUC, and four samples of nontumor tissue (control samples) were selected. Ribonucleic acid (RNA) sequencing was performed. Results SR-SNUC had a higher number of variants (1 variant for every 15,000 bases) compared with SD-SNUC (1 variant every 29,000 bases). The ratio of missense to silent mutation ratio was higher for SR-SNUC (0.8) as compared with SD-SNUC (0.7). Approximately 1,500 genes were differentially expressed between SR-SNUC and SD-SNUC. The genes that had a higher expression in SR-SNUC included TPD52L1, B3GNT3, GFY, TJP3, ELL3, CYP4F3, ALDH3B2, CKMT1B, VIPR1, SLC7A5, PPP2R2C, UPK3B, MUC1, ELF5, STY7, and H2AC14. The gene that had a higher expression in SD-SNUC was ZFHX4. Most of these genes were related to either protein translation or immune regulation. The most common ( n = 3, 75%) mechanisms of loss of SMARCB1 gene in SD-SNUC was loss of heterozygosity. Conclusion RNA sequencing is a viable and informative approach for genomic profiling of archival SNUC samples. Both SR-SNUC and SD-SNUC were noted to have distinct genetic profiles underlying the molecular classification of these diseases.

Clinical Outcome in Patients with Large Sinonasal Tumors with Intracranial Extension.

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

Impact of Treatment Delay in Head and Neck Mucosal Melanoma on Overall Patient Survival.

Objectives Head and neck mucosal melanoma (HNMM) is a rare malignancy with high mortality. This study evaluates the impact of treatment delays on overall survival in HNMM. Design/Setting/Participants A retrospective review of patients with surgically managed HNMM treated with adjuvant radiation was performed from the 2004-2016 National Cancer Database. Main Outcome Measures Durations of diagnosis-to-treatment initiation (DTI), surgery-to-radiotherapy initiation (SRT), duration of radiotherapy (RTD), surgery-to-immunotherapy initiation (SIT), diagnosis-to-treatment end (DTE), and total treatment package (TTP) were calculated. Results A total of 1,011 patients (50.7% female, 90.5% Caucasian) met inclusion criteria. Median DTI, SRT, RTD, SIT, DTE, and TTP were 30, 49, 41, 102, 119, and 87 days, respectively. Only longer DTE was associated with decreased mortality (hazard ratio, 0.720; 95% confidence interval, 0.536-0.965; p = 0.028). Conclusion DTI, SRT, RTD, SIT, and TTP do not significantly affect overall survival in patients with HNMM who undergo surgery and adjuvant radiation. Longer DTE is associated with improved survival in this population. Level of Evidence 4.

Presentation of Rarely Occurring Inverted Squamous Papilloma of Nasal Cavity: A Case Report.

This report presents a case of a rarely occurring inverted squamous papilloma, which shows papillary proliferation in squamous epithelium. Inverted papillomas (IPs) are benign epithelial growths that occur in the underlying stroma of the nasal cavity and paranasal sinuses. While viral infections, allergies, and chronic sinusitis have all been proposed as potential causes, the pathophysiology of this lesion is still unknown. Most of the time, IP reflects residual disease, yet the recurrence rates are extremely high. A 60-year-old male patient has chief complaints of right-sided nasal congestion and excessive sneezing and discharge from the nose, which cause discomfort to the patient and make him unable to sleep at night. Computed tomography reveals both the enlargement of the osteomeatal complex and soft-tissue density opacification of the right side of the nasal cavity. The only way to diagnose this type of squamous papilloma is through histopathological examination. In this work, we evaluated the histological characteristics of sinonasal IP and presented a case report of an uncommon instance of inverted squamous papilloma of the nasal cavity.

Endoscopic-assisted transorbital extended orbital exenteration: A multi-institutional preclinical study.

BACKGROUND: Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called "extended-OE (EOE)," showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic-EOE). METHODS: The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, ("impossible" to "easy," and "high risk" to "low risk," respectively), most likely complication(s) were hypothesized. RESULTS: The step-by-step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported. CONCLUSIONS: Endoscopic-EOE is a challenging but feasible procedure. Clinical validation is required to assess real-life outcomes.

Rare and common manifestation of musculoskeletal and sinonasal sarcoidosis: A case report.

Sarcoidosis is a systemic granulomatous disease that can affect multiple organ systems. Although many sarcoidosis patients are asymptomatic, the variable clinical progression of symptomatic patients and the nonspecific presentation make diagnosis difficult in certain cases. Musculoskeletal and sinonasal involvement of sarcoidosis are uncommon manifestations, and they are often only seen in patients with widespread disease. Diagnosis of osseous sarcoidosis, sarcoid arthropathy, and sarcoid rhinosinusitis are typically based on a combination of clinical history, radiological findings, and pathologic specimens. Although there are classic image findings, such as lacelike honeycomb appearance of small bones of the hands or hilar/mediastinal lymphadenopathy, sole reliance on image findings for the diagnosis of sarcoidosis is unreasonable as many findings are nonspecific. However, failure to include sarcoidosis in the differential diagnosis often leads to a delay in recognition of musculoskeletal or sinonasal involvement and results in ineffective treatment plan. Even in patients with biopsy-proven sarcoidosis, some image findings in isolation that may represent granulomatous infiltrates are disregarded as nonspecific without raising the possibility of sarcoidosis due to its rare occurrence. Here we discuss a case of multisystemic sarcoidosis in a 42-year-old female with a constellation of classic and rare findings of biopsy-proven sarcoidosis.

Surgical and regenerative treatment options for empty nose syndrome: A systematic review.

Objectives: Patients with empty nose syndrome usually suffer from paradoxical nasal congestion, nasal dryness, epistaxis and suffocation. Conservative management is general option for the empty nose syndrome. However, there are several patients who continually complain of symptoms. If symptoms persist, surgical options are considered. Therefore, we reviewed surgical and regenerative treatment options of empty nose syndrome. Methods: PubMed, Embase, Scopus, Cochrane Register of Controlled Trials, and Google Scholar were searched from the earliest date provided in the database until December 2022. In the studies, treatment outcomes were measured by patient symptom scores such as Sino-Nasal Outcome Test (SNOT-20, 22, and 25), and Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) along with various clinical examiniations. Results: Twenty-eight studies were analyzed. Submucosal injectable materials, allografts/xenografts/cadaveric implants, autologous implants, and synthetic implants were used. Among them, polyethylene implant was most commonly used (23.3%), followed by autologous, homologous, or cadaveric costal cartilage (20%). The most common administration site was the anterior-inferior lateral nasal wall. Most of the studies showed that surgical intervention brought significant improvements in clinical findings including endoscopic exam, acoustic rhinometry, and CT, as well as patients reporting nasal symptom-, psychological-, or overall health-related quality of life questionnaires. However, several studies did not confirm improvement effects in some psychological-related questionnaires or saccharin transit time. The average follow-up duration was 12.0 (2.0-27.6) months. Postoperative adverse effects were reported in only two studies. Conclusion: Several surgical options and recent tissue regeneration techniques have shown its positive efficacy in treating empty nose syndrome. However more detailed investigations with a larger number and a randomized control study are needed to establish a standardized protocol in treating empty nose syndrome patients.

Expression of immune checkpoint molecules TIGIT and TIM-3 by tumor-infiltrating lymphocytes predicts poor outcome in sinonasal mucosal melanoma.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a rare but aggressive tumor with a poor prognosis. The co-inhibitory receptors T cell immunoglobulin and mucinodomain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) are promising new targets in anti-cancer immunotherapy. The expression profiles of these immune checkpoint molecules (ICMs) and potential prognostic implications have not been characterized in SNMM yet. METHODS: Immunohistochemical staining for TIGIT, LAG-3 and TIM-3 was performed on tumor tissue samples from 27 patients with primary SNMM. Associations between ICM expression and demographic parameters, AJCC tumor stage, overall survival, and recurrence-free survival were retrospectively analyzed. RESULTS: SNMM patients with low numbers of TIGIT+ and TIM-3+ tumor infiltrating lymphocytes (TILs) in the primary tumor survived significantly longer than patients with a high degree of TIGIT+ and TIM-3+ TILs. High infiltration with TIM-3+ or TIGIT+ lymphocytes was associated with the higher T4 stage and decreased 5-year survival. CONCLUSION: We identified high densities of TIM-3+ and TIGIT+ TILs as strong negative prognostic biomarkers in SNMM. This suggests that TIM-3 and TIGIT contribute to immunosuppression in SNMM and provides a rationale for novel treatment strategies based on this next generation of immune checkpoint inhibitors. Prospective studies with larger case numbers are warranted to confirm our findings and their implications for immunotherapy.

Unveiling the Rarity: A Fascinating Case of Chondro-Osseous Respiratory Epithelial Adenomatoid Hamartoma (COREAH) in the Sinonasal Tract.

Chondro-osseous respiratory adenomatoid hamartoma (COREAH) are extremely rare benign lesions of the sinonasal tract. It is present in 3 to 83-year-olds. It originates from various sites of the sinonasal tract; the most common site is the posterior lateral wall of the nasal cavity. Imaging calcification is an important finding in COREAH. In this case report, we present an exceptionally rare occurrence involving a 55-year-old female patient who exhibited symptoms of nasal obstruction, bleeding from the left side of the nasal cavity and loss of smell. We aim to share our experience in managing this unique condition. Diagnostic nasal endoscopic examination of the patient revealed a reddish, fleshy polypoidal mass in the left nasal cavity arising from the lateral wall of the left nasal cavity posteriorly and extending anteriorly into the left nasal cavity. The patient underwent an excisional biopsy. Upon microscopic examination, we observed a hamartomatous proliferation of respiratory-type glands exhibiting mucinous metaplasia. Additionally, numerous spicules of mature bone were present, a distinctive feature of COREAH. The patient underwent a 6-month follow-up, during which no recurrent growth was detected within the nasal cavity.

A Case Report of Sinonasal Primary Squamous Cell Carcinoma.

This case report presents a 64-year-old male diagnosed with sinonasal primary squamous cell carcinoma (SNSCC), a rare and aggressive upper aerodigestive tract malignancy. Initially, he presented with unilateral recurrent epistaxis. Imaging and histopathology confirmed the diagnosis. The patient's non-compliance with clinic appointments led to significant disease progression, culminating in his unfortunate demise. This case underscores the importance of early detection and continuous monitoring in SNSCC, given its nonspecific early symptoms and poor prognosis. It emphasizes the necessity for heightened suspicion in patients with recurrent or unresolved sinonasal complaints, as timely intervention is crucial for better outcomes.

Sinonasal immunoglobulin G4-related disease: a case report of an atypical and rare entity.

BACKGROUND: Immunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to 1.39 per 105 person-years. Sinonasal immunoglobulin G4-related disease is atypical and exceedingly uncommon in the existing literature, frequently manifesting clinically as chronic rhinosinusitis, epistaxis, and facial pain. CASE PRESENTATION: This report describes a 25-year-old Iraqi female who has been suffering from symptoms of chronic rhinosinusitis for 8 years. Despite undergoing several surgeries, there has been no improvement in her symptoms. A tissue biopsy that revealed dense lymphoplasmocytosis with noticeable plasma cell infiltration, storiform fibrosis, and obliterative angitis, along with positive immunohistochemical staining for Immunoglobulin G4 plasma cells, finally confirmed the diagnosis of sinonasal immunoglobulin G4-related disease. The patient responded well to oral prednisolone and methotrexate treatments. CONCLUSIONS: The main objective of the current report is to raise awareness among physicians about the significance of promptly identifying and diagnosing this rarity, thus preventing the adverse consequences linked to delayed diagnosis and treatment initiation.

A Case of SMARCB1-Deficient Sinonasal Carcinoma With Clear Cell Morphology.

SMARCB1 is a gene known to cause carcinogenesis in many soft tissue tumors, including malignant rhabdoid tumors and epithelioid sarcoma. Since the first report of a subtype of sinonasal carcinoma characterized by a deficiency of the SMARCB1 gene in 2014 to date, fewer than 200 cases have been reported. We report a case of SMARCB1-deficient sinonasal carcinoma with clear cell morphology. In our case, there are no evident basaloid or plasmacytoid/rhabdoid tumor cells, which are typical histopathological features of SMARCB1-deficient sinonasal carcinoma. SMARCB1-deficient sinonasal carcinoma is prone to recurrence and has a very poor prognosis. As the development of molecularly targeted agents progresses, therapeutic efficacy is expected to improve. Simultaneously, the importance of early and accurate diagnosis of SMARCB1-deficient sinonasal carcinoma will increase. With the limited information provided by biopsy specimens, it is necessary to confirm the loss of SMARCB1 expression by immunohistochemistry and investigate the presence of SMARCB1 gene deletion by molecular genetics, considering the possibility of SMARCB1-deficient sinonasal carcinoma even in atypical cases without basaloid or plasmacytoid/rhabdoid cell morphology, as in our case.