A case of high-grade non-intestinal paranasal sinus adenocarcinoma primary in the maxillary sinus: targeted therapy after postoperative immunocombination with chemotherapy.

BACKGROUND: High-grade non-intestinal-type sinonasal adenocarcinoma (non-ITAC) is a rare and aggressive form of adenocarcinoma with poor prognosis. The current standard treatment approach involves surgery combined with radiation therapy. However, there is a need for exploring additional treatment modalities to improve patient outcomes. CASE PRESENTATION: We present a case of a 65-year-old male patient who presented with pain in the right maxillary sinus and was diagnosed with high-grade non-ITAC following surgery. Postoperative pathology revealed tumor invasion into bone tissue and vascular invasion, necessitating further treatment. The patient underwent radiation therapy, followed by immunotherapy with carilizumab combined with chemotherapy. During the maintenance immunotherapy period, tumor progression was observed, and genetic testing identified EGFR and TP53 mutations. Consequently, the patient was treated with gefitinib, a targeted therapy drug. Notably, the patient's lung metastases showed a gradual reduction in size, indicating a favorable treatment response. The patient is currently undergoing oral treatment with gefitinib. CONCLUSIONS: This case report highlights the potential benefit of combining immunotherapy and targeted therapy in the treatment of high-grade non-ITAC. Despite the rarity of this cancer type, this approach may offer an alternative treatment strategy for patients with this aggressive disease. We hope that this case can contribute to a deeper understanding of high-grade non-ITAC and promote the application of immunotherapy and targeted therapy in improving survival rates for patients with this condition.

Role of elective neck dissection in cT2N0 maxillary sinus squamous cell carcinoma.

Our objective was to examine the impact of elective neck dissection (END) on the prognosis of patients with cT2N0 maxillary sinus squamous cell carcinoma (MS-SCC) and to determine factors that predict the occurrence of occult metastasis in this patient population. A retrospective analysis was conducted using data from the SEER database. Patients with cT2N0 MS-SCC were included in the study and divided into two groups: those who received END and those who did not. The impact of END on disease-specific survival (DSS) and overall survival (OS) was assessed using propensity score matching. Multivariate logistic regression analysis was performed to determine predictors for occult metastasis. A total of 180 patients were included in the study, with 40 cases receiving END. Following propensity score matching, patients treated with END and those without showed similar DSS and OS rates. Occult metastasis was observed in 9 patients, corresponding to a rate of 22.5%. High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (hazard ratio 1.52, 95% confidence interval 1.17-2.00). cT2 MS-SCC carries an occult metastasis rate of 22.5%, with histologic grade being the primary determinant of occult metastasis. END does not confer a significant survival benefit in this patient population.

[Comparison of 5-year survival rate and analysis of prognostic factors influencing the prognosis of adenoid cystic carcinoma and squamous cell carcinoma of the maxillary sinus: based on the SEER database].

Objective:To analyze the difference in 5-year survival between maxillary sinus adenoidal cystic carcinoma（maxillary sinus adenoid cystic carcinoma, MSACC） and squamous cell carcinoma（maxillary sinus squamous cell carcinoma, MSSCC） using the National Cancer Institute's Surveillance, Epidemiology, and End. Results:database（SEER） and to explore the factors associated with the prognosis of the two tumors. Methods:The data of 161 patients with MSACC and 929 patients with MSSCC were collected from SEER database, and the 5-year overall survival rate（OS） and tumor specific survival rate（CSS） were compared between the two groups before and after propensity score matching. The forest map of multivariate Cox proportional hazard regression model was established to analyze the prognostic factors affecting the survival rate of patients with MSACC and MSSCC. Results:There were statistical differences in 5-year OS and CSS between MSACC and MSSCC before and after propensity score matching（P<0.001）. Multivariate regression analysis showed that age, side of the disease, lymph node metastasis, operation and radiotherapy were the influencing factors of OS in MSACC, while age and operation were the influencing factors of CSS. Age, race, T grade, lymph node metastasis, systemic metastasis, surgery, radiotherapy and chemotherapy are the influencing factors of OS of MSSCC. Age, T grade, lymph node metastasis, systemic metastasis, surgery, radiotherapy and chemotherapy are the influencing factors of CSS. Conclusion:The 5-year survival rate of MSACC is higher than that of MSSCC. Surgery plays a positive role in the prognosis of the two kinds of tumors. The analysis results can provide some reference for their survival expectations and treatment choices.

Methylation-Based Characterization of a New IDH2 Mutation in Sinonasal Undifferentiated Carcinoma.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172K, R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the Gene Expression Omnibus database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sinonasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, showed the position of our sample to be within 1.02 standard deviation of the other IDH-mutant SNUCs. A molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

Mandibular Osteomyelitis as the Earliest Clinical Manifestation of Maxillary Sinus Lymphoma.

Extranodal natural killer/T-cell lymphoma is a distinct subtype of non-Hodgkin lymphoma that originates from natural killer cells or cytotoxic T cells. Its diagnosis is challenging due to the rarity and lack of awareness, especially in cases where osteomyelitis of the jawbone is the initial symptom. This paper reports a case of extranodal natural killer/T-cell lymphoma presenting primarily with oral ulcers. Through analyzing the clinical and pathological characteristics, differential diagnosis, treatment and prognosis, and reasons for misdiagnosis of the disease, this study aims to provide references for clinical diagnosis and treatment.

Sphenopalatine artery pseudoaneurysm masquerading as a second primary maxillary carcinoma.

PURPOSE: Maxillary sinus carcinomas usually present as a locally advanced disease at the time of diagnosis and it is extremely unusual to have a second primary maxillary carcinoma on the contralateral side after many years of completion of treatment of the first malignancy. We present here a case report of a sphenopalatine artery (SPA) pseudoaneurysm mimicking the second primary maxillary carcinoma. METHODS: We reviewed the literature for SPA pseudoaneurysm. RESULTS/CASE REPORT: This report describes the case of a 90-year-old man with a background of adenoid cystic carcinoma of the right maxillary sinus, diagnosed and treated with surgery and radiotherapy 14 years ago, who presented with a history of multiple episodes of epistaxis. The radiological evaluation showed a heterogeneously enhancing mass with a central hemorrhagic component and surrounding bony erosions in the left maxillary sinus and the patient was planned for biopsy from the suspicious mass along with SPA ligation. However, on opening the maxillary antrum there was excessive bleeding and it was determined unsafe to proceed further. The patient was subsequently taken to interventional radiology for diagnostic angiography which revealed an SPA pseudoaneurysm that was subsequently embolized successfully. CONCLUSIONS: Sphenopalatine artery pseudoaneurysms should be considered as a differential for recurrent epistaxis in patients with a history of sinonasal malignancy. In such cases, endovascular embolization is a viable management option.

Preservation or removal of the lateral nasal wall in endoscopic management of maxillary sinus neoplasia: A comparison of approach related morbidity.

BACKGROUND: The endoscopic modified medial maxillectomy (MMM) and prelacrimal approach (PLA) are two routinely performed endoscopic approaches to the maxillary sinus when access via a middle meatal antrostomy is insufficient. However, there is no data in the literature that has compared outcomes and complication profile between the two procedures to determine which approach is superior. OBJECTIVE: To compare the approach related morbidity of PLA and MMM. METHODS: A retrospective cohort study of all consecutive adult patients undergoing either MMM or PLA from 2009 to 2023 were identified. The primary outcome was development of epistaxis, paraesthesia, lacrimal injury, iatrogenic sinus dysfunction within a minimum of 3 months post-operative follow up. RESULTS: 39 patients (44 sides) underwent PLA and 96 (96 sides) underwent MMM. There were no statistically significant differences between the rates of paraesthesia (9.1 % vs 14.6 %, p = 0.367) or prolonged paraesthesia (2.3 % vs 5.2 %, p = 0.426), iatrogenic maxillary sinus dysfunction (2.3 % vs 5.2 %, p = 0.426) or adhesions requiring removal (4.5 % vs 4.2 %, p = 0.918). No cases of epiphora or nasal cavity stenosis occurred in either arm in our study. CONCLUSIONS: According to our data, the endoscopic modified medial maxillectomy and prelacrimal approach are both equally safe approaches with their own benefits to access.

Post-treatment magnetic resonance imaging predicts outcomes of maxillary sinus cancer treatment using super-selective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT).

OBJECTIVES: This study aimed to evaluate the prognostic value of magnetic resonance imaging (MRI) findings in predicting local recurrence in patients with maxillary sinus cancer treated with super-selective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT). METHODS: This single-center retrospective study included consecutive patients with maxillary sinus squamous cell carcinoma, who underwent RADPLAT between October 2016 and September 2021. MRI was performed before (within 2 weeks) and 1 month after (post-treatment MRI) the start of treatment. Tumor reduction rates and pre-treatment cross-sectional areas were calculated from the maximum cross-sectional areas on pre- and post-treatment MRI T2-weighted axial images. Statistical analyses, including receiver operating characteristic analysis, were performed to assess the predictive value of the tumor reduction rates. RESULTS: Twenty-four patients were included in this study. Recurrence occurred in seven patients with a median time of 213 days. The tumor reduction rates were significantly higher in the benign post-treatment changes group compared to the recurrence group (median, 0.814 vs. 0.174; p < 0.001). The cut-off value for the reduction rate between the groups was 0.3578. No significant difference was observed in the maximum pre-treatment cross-sectional area between the groups (p = 0.664). The inter-observer agreement for the tumor areas was excellent. CONCLUSIONS: The tumor reduction rate calculated from MRI T2-weighted images may be a predictor of local recurrence in patients with maxillary sinus cancer treated with RADPLAT. Patients with lower reduction rates may benefit from early salvage surgeries.

Sinonasal Tumors Masquerading as Invasive Fungal Sinusitis (IFS).

OBJECTIVES: Fungal tissue invasion in the setting of sinonasal malignancy has been rarely described in the literature. Only a handful of studies have discussed cases of suspected chronic and acute IFS (CIFS and AIFS, respectively), having an underlying undifferentiated sinonasal carcinoma, sinonasal teratocarcinosarcoma, and NK/T-cell lymphoma. METHODS: Here, we describe 3 cases of carcinoma mimicking IFS from a single institution. RESULTS: Each of our patients presented with sinonasal complaints as an outpatient in the setting of immunosuppression. Intranasal biopsies consistently were predominated by necrotic debris, with and without fungal elements, ultimately leading to a delay of oncologic care. The final pathologies included NK/T-cell lymphoma and SNEC. All patients were followed by radiation and chemotherapy, with 1 case of mortality. CONCLUSIONS: We aim to emphasize the importance of obtaining viable tissue as pathology specimens as the presence of necrosis with fungal elements may limit the diagnosis and ultimately delay the care of an underlying sinonasal carcinoma.

Analysis of Diagnosis and Treatment Strategies for Primary Juvenile Psammomatoid Ossifying Fibroma Complicated With Primary Aneurysmal Bone Cyst.

BACKGROUND: Juvenile Psammomatoid Ossifying Fibroma (JPOF) is a type of noncancerous bone tumor that usually affects adolescents in the craniomaxillofacial area. Clinical manifestations are usually symptoms caused by the tumor's invasive compression of surrounding tissues. Aneurysmal Bone Cyst (ABC) is also a benign bone tumor, and it typically occurs in long bones and the spine. Only 2% to 3% of cases occur in the head and neck. Due to the rarity of this combination of clinical cases, clinicians face difficulties in comprehensively understanding this complex lesion. Therefore, a comprehensive review of the clinical manifestations and characteristic imaging findings is necessary for surgeons. CASE PRESENTATIONS: On April 6, 2019, a 13-year-old boy presented with left maxillofacial bulge and pain for 1 month. Magnetic resonance imaging of the paranasal sinuses showed an irregular hive-like mass signal in the left maxillary sinus, and cystic changes with fluid levels were seen in the lesion. After the initial diagnosis of JPOF with primary ABC, we decided to perform a facial mid-facial resection of maxillary sinus tumor to remove the tumor tissue. Finally, after 3 recurrences and 4 operations, there was no tumor recurrence for 20 months after the last operation, and the patient was still under continuous follow-up. CONCLUSIONS: This case provided a reference for the diagnosis and treatment of JPOF combined with ABC. In particular, a new understanding of the association between the two diseases and the management of recurrence were proposed, which had the potential to improve clinical understanding of this complicated condition.

Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review.

BACKGROUND: The abscopal effect is a rare phenomenon in which localized radiation therapy triggers tumor reduction in nontargeted areas. Although this phenomenon has been observed in various cancer types, it remains infrequent and not fully understood. CASE: Two patients with maxillary sinus cancer with distant metastases were treated with radiotherapy after immune checkpoint inhibitor (ICI) therapy. The patients demonstrated abscopal effects following ICI therapy and radiotherapy, showing shrinkage in metastatic areas not directly targeted by radiation. CONCLUSION: This report was reviewed to examine the synergistic effects of ICI and radiotherapy and to identify optimal strategies to enhance the abscopal effect in clinical practice. It has also touched on various ongoing debates and clinical trials aimed at understanding and exploiting this effect to improve cancer treatment. The exact mechanisms and optimal treatment protocols remain areas for future research.

Endoscopic management of sinonasal tumours in the Nordic university hospitals: a survey.

PURPOSE: The Nordic countries (27 M) all have comparable, publicly funded healthcare systems, and the management of sinonasal tumours is centralised to the 21 university hospitals. We sought to assess and compare the treatment practice of sinonasal tumours across the Nordic countries. METHODS: A web-based questionnaire was sent to all university hospital departments of otorhinolaryngology-head and neck surgery in the Nordic countries. RESULTS: Answers were obtained from all 21 Nordic university hospitals. The endoscopic approach was widely utilised by all, with most (62%) centres reporting 3-4 surgeons performing endoscopic sinonasal tumour surgery. Finland reported the lowest rates of centralisation among university hospitals despite having the highest number of 0.1-1 M catchment population hospitals. Most centres (88%) opted for the endoscopic approach in a patient case warranting medial maxillectomy. In a case of a Kadish C esthesioneuroblastoma, most (52%) of the centres preferred an endoscopic approach. Most centres (62%) reported favouring the endoscopic approach in a case describing a juvenile angiofibroma. Regarding a case describing a sinonasal undifferentiated carcinoma, consensus was tied (38% vs. 38%) between endoscopic resection followed by postoperative (chemo)radiotherapy (RT/CRT) and induction chemotherapy followed by RT/CRT or surgery followed by RT/CRT. CONCLUSION: Endoscopic approach was widely utilised in the Nordic countries. The case-based replies showed differences in treatment practice, both internationally and nationally. The rate of centralisation among university hospitals remains relatively low, despite the rarity of these tumours.

Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

Durable and dramatic response to checkpoint inhibition combined with COX-2 inhibitor celecoxib in a patient with p16+ metastatic sinonasal undifferentiated carcinoma: A case study.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is an exceedingly rare head and neck malignancy. No consensus exists on treatment for metastatic disease. CASE: A 56-year-old female was diagnosed with SNUC after endorsing sinus congestion, diplopia, and right orbital pain. Initially treated with surgery and radiation, she later developed significant metastatic disease. She demonstrated progression of her hepatic metastases under pembrolizumab therapy. However, the addition of ipilimumab and a COX-2 inhibitor resulted in significant improvement in her lesions as well as an ongoing durable response. Her regimen was complicated by immune-related adverse events successfully treated with steroids. CONCLUSION: Dual checkpoint inhibition deserves consideration when treating metastatic SNUC, especially after single agent therapy has failed. The positive effect of this treatment may be augmented by IDO1 inhibition.

Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0.

PURPOSE: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment, but this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas. We herein report the results of the efficacy confirmation phase in the T4a cohort. METHODS AND MATERIALS: Patients received 100 mg/m2 cisplatin intra-arterially weekly for 7 weeks with concomitant radiation therapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (OS), comparing RADPLAT with the historical control for 3-year OS in surgery (80%). RESULTS: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 men and 11 women with a median age of 64 years (range, 40-78 years) and Eastern Cooperative Oncology Group performance status 0/1 (58/7). After excluding 1 ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3-year OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (grade ≥3), neutropenia (grade ≥3), increased creatinine (grade ≥2), hearing impairment (grade ≥2), and stroke (grade ≥2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported. CONCLUSIONS: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 maxillary sinus squamous cell carcinomas compared with the historical control for 3-year OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.

Minimally Anterior Medial Maxillary Approach (MAMMA): a novel technique for a wide access to the maxillary sinus.

PURPOSE: To describe a novel endoscopic technique to approach the maxillary sinus (MS), the Modified Anterior Medial Maxillary Approach (MAMMA), preserving the inferior turbinate (IT) and the nasolacrimal duct (NLD). To perform radiological measurements and describe a case series to study the feasibility and limits of MAMMA. METHODS: Computed tomography (CT) scans (n = 150 nasal cavities) were used to calculate areas of the MAMMA to define surgical limits and extensions. Measurement of distances to critical anatomy landmarks and total area for the MAMMA were calculated. An instructional case illustrating the surgical technique and outcome was also included. RESULTS: Radiological analysis showed a mean distance from the Piriform Aperture (PA) to the anterior limit of the NLD of 1.03 ± 0.18 cm (range 0.59-1.48) and a mean distance from de PA to the posterior limit of the NLD of 1.57 ± 0.22 cm (range 1.02-2.11). The mean distance from the nasal floor to the Hasner's valve was 1.61 ± 0.27 cm (range 1.06-2.52) and the distance from the nasal floor to the insertion of the IT was 2.20 ± 0.36 cm (range 1.70-3.69). Finally, the mean total area for the MAMMA was 4.04 ± 0.52 cm2 (range 3.17-5.53). No complications or recurrence of the pathology were observed in operated patients. CONCLUSION: The MAMMA provides a wide surgical field of the MS walls comparable to more aggressive techniques, with preservation of the sinonasal and lacrimal function. MAMMA is an effective alternative to treat different MS pathologies including benign recurrent maxillary sinus tumors.