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.

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.

[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.

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.

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.

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.

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.

Oncology for the rhinologist.

PURPOSE OF REVIEW: The purpose of this review is to summarize current evidence regarding the use of induction chemotherapy for a variety of histopathologies of sinonasal malignancy (SNMs) and to review the potential adverse effects of cytotoxic agents. RECENT FINDINGS: Historically, patients with locally advanced SNMs have had relatively poor prognoses and high morbidity from treatment. The available retrospective data suggests that induction chemotherapy may improve outcomes for patients with sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma, squamous cell carcinoma (SSCC), and esthesioneuroblastoma. For SNUC and SSCC, response or nonresponse to induction chemotherapy may prognosticate outcomes and for SNUC specifically, drive selection of definitive therapy. In chemosensitive pathologies, induction chemotherapy appears to improve organ preservation. SUMMARY: Induction chemotherapy may improve functional and oncologic outcomes for patients with SNMs. Because of the rarity of these pathologies, the available data is primarily retrospective. Future randomized, prospective studies should be performed to further optimize and elucidate the role of induction chemotherapy for SNMs.

Sinonasal NUT carcinoma: A consecutive case series and systematic review.

BACKGROUND: Sinonasal NUT carcinoma is an extremely rare, lethal malignancy with limited literature. METHODS: A case series was conduction of all patients with sinonasal NUT carcinoma at a single institution between 2010 and 2022. Survival and associated were evaluated. A systematic review of the literature was performed. RESULTS: In 12 patients, followed for a median of 1.5 years, the median overall survival (OS) and disease-specific survival (DSS) were both 14.6 months. Patients with maxillary sinus tumors were 91% more likely to survive (hazard ratio [HR]: 0.094, 95% confidence interval [CI]: 0.011-0.78, p = 0.011). Patients with higher-stage disease stage had worse OS (stage IVb-c vs. III-IVa, p = 0.05). All three patients who were alive with no evidence of disease received induction chemotherapy. CONCLUSION: For patients with sinonasal NUT carcinoma, the median survival was 15 months but better with lower-stage and maxillary tumors. Induction chemotherapy may be beneficial.

Diagnostic algorithm for challenging blue cell sinonasal carcinoma.

The newly emerging sinonasal carcinomas have demonstrated diverse morphologies and specific molecular rearrangements along with deviant clinical behavior from conventional counterparts. We aim to propose a diagnostic algorithm that is based on molecular findings of each sinonasal cancer and is considering the new entities has been called upon. Such a diagnostic algorithm should help diagnostic pathologists establish a diagnosis of a challenging sinonasal blue cell carcinomas and researchers performing retrospective analysis of archival cases. Along with consulting our archival cases, literature mining was conducted to retrieve the immunohistochemical and molecular findings regarding the newly emerging entities. Our proposed algorithm distinguishes poorly differentiated (non) keratinizing SNSCC, from anaplastic myoepithelial carcinoma, NUT midline carcinoma, SMARCB1/SMARCA4-deficient teratocarcinosarcoma, SMARCB1/SMARCA4-deficient carcinosarcoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, HPV-related multiphenotypic sinonasal carcinoma and other adenocarcinomas. By incorporating morphologic features, immunohistochemical markers, and molecular investigations, the algorithm enhances the accuracy of diagnosis, particularly in cases where comprehensive molecular testing is not readily available. This algorithm serves as a valuable resource for pathologists, facilitating the proper diagnosis of sinonasal malignancies and guiding appropriate patient management.

Long-term outcomes of modern multidisciplinary management of sinonasal cancers: The M. D. Anderson experience.

PURPOSE: To report long-term outcomes of modern radiotherapy for sinonasal cancers. METHODS AND MATERIALS: A retrospective analysis of patients with sinonasal tumors treated with intensity-modulated radiotherapy or proton therapy. Multivariate analysis was used to determine predictive variables of progression free survival (PFS) and overall survival (OS). RESULTS: Three hundred and eleven patients were included, with median follow-up of 75 months. The most common histologies were squamous cell (42%), adenoid cystic (15%), and sinonasal undifferentiated carcinoma (15%). Induction chemotherapy was administered to 47% of patients; 68% had adjuvant radiotherapy. Ten-year local control, regional control, distant metastasis free survival, PFS, and overall survival rates were 73%, 88%, 47%, 32%, and 51%, respectively. Age, non-nasal cavity tumor site, T3-4 stage, neck dissection, and radiation dose were predictive of PFS, while age, non-nasal cavity tumor site, T3-4 stage, positive margins, neck dissection, and use of neoadjuvant chemotherapy were predictive of OS. There was a 13% rate of late grade ≥3 toxicities. CONCLUSION: This cohort of patients with sinonasal cancer treated with modern radiotherapy demonstrates favorable disease control rate and acceptable toxicity profile.

Proceedings of the 2023 North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Navigating New Developments in High Grade Sinonasal Neuroendocrine and Neuroectodermal Neoplasms.

Although the definitions of sinonasal neuroendocrine and neuroectodermal neoplasms did not change substantially in the 5th edition WHO Classification of Head and Neck Tumours, the diagnosis of olfactory neuroblastoma (ONB), small cell neuroendocrine carcinoma, and large cell neuroendocrine carcinoma remains quite challenging in practice. Ambiguities surrounding the amount of keratin expression allowable in ONB and the amount of neuroendocrine differentiation seen in sinonasal undifferentiated carcinoma (SNUC) lead to significant diagnostic discrepancies at the high grade end of this tumor spectrum. Furthermore, a group of problematic neuroepithelial tumors that show overlapping features of ONB and neuroendocrine carcinoma have never been recognized in formal classification schemes. Since publication of the 5th edition WHO, two new tumor entities have been proposed that help resolve these problems. Olfactory carcinoma is defined by high grade keratin-positive neuroectodermal cells with frequent intermixed glands and shows recurrent Wnt pathway, ARID1A, and RUNX1 alterations. IDH2-mutant sinonasal carcinoma is a molecularly-defined category that encompasses tumors with undifferentiated (SNUC), large cell neuroendocrine, and neuroepithelial phenotypes. This review will provide a practical overview of these emerging entities and their application to diagnostic challenges in the post-WHO sinonasal neuroendocrine and neuroectodermal tumor classification.

Modern treatment of sinonasal undifferentiated carcinoma.

PURPOSE OF REVIEW: Sinonasal undifferentiated carcinomas are rare aggressive tumours with traditionally poor outcomes. Although multimodality treatment has been recommended by most centres, the ideal treatment sequence or regimen has not been established. RECENT FINDINGS: Recent evidence suggests that induction chemotherapy may be used for chemoselection and cytoreduction prior to definitive chemoradiotherapy. Where there is a favourable response, concurrent chemoradiotherapy is favoured, with an improved overall survival and improved rates of organ preservation. SUMMARY: Induction chemotherapy may be a useful guide for selection of patients for chemoradiotherapy or surgery and has shown encouraging results. Further research is required to establish the ideal induction chemotherapy regimen for this rare group of tumours.