Sinonasal Carcinoma Research Articles

Texture analysis of conventional magnetic resonance imaging and diffusion-weighted imaging for distinguishing sinonasal non-Hodgkin's lymphoma from squamous cell carcinoma.

To evaluate the value of texture analysis (TA) of conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the differential diagnosis between sinonasal non-Hodgkin's lymphoma (NHL) and squamous cell carcinoma (SCC). Forty-two patients with sinonasal SCC and 30 patients with NHL were retrospectively enrolled. TAs were performed on T2-weighted image (T2WI), apparent diffusion coefficient (ADC) and contrast-enhanced T1-weighted image (T1WI). Texture parameters, including mean value, skewness, kurtosis, entropy and uniformity were obtained and compared between sinonasal SCC and NHL groups. Receiver-operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic value and identify the independent TA parameters. The mean value and entropy of ADC, and mean value of contrast-enhanced T1WI were significantly lower in the sinonasal NHL group than those in the SCC group (all P < 0.05). ROC analysis indicated that the entropy of ADC had the best diagnostic performance (AUC 0.832; Sensitivity 0.95; Specificity 0.67; Cutoff value 6.522). Logistic regression analysis showed that the entropy of ADC (P = 0.002, OR = 26.990) was the independent parameter for differentiating sinonasal NHL from SCC. TA parameters of conventional MRI and DWI, particularly the entropy value of ADC, might be useful in the differentiating diagnosis between sinonasal NHL and SCC.

Is prophylactic neck irradiation indicated for patients with cN0 adenoid cystic carcinoma of the paranasal sinuses?

PurposeTo study the prevalence of nodal metastases in sinonasal adenoid cystic carcinoma (SNACC) and to evaluate whether prophylactic neck irradiation (PNI) should be performed in patients with clinical N0 (cN0) disease. Patients and methodsBetween April 1992 and November 2020, 166 patients with SNACC who had undergone radiotherapy at our department were retrospectively analyzed. The median follow-up time was 71.3 months. ResultsAmong 166 cases of SNACC, a total of 13 (7.8%) had retropharyngeal or cervical nodal metastasis and 93% (12/13) cases occurred in patients with advanced T stage (T3-T4). Levels VIIa, Ib, and IIa were the most common sites of initial nodal involvement. Only 1.2% (2/166) of patients presented late neck recurrence.Lymph node metastasis independently predicted a poor progression-free survival (PFS) (P = 0.017) but had no impact on overall survival (OS) (P = 0.38).PNI was performed on 36% (55/153) of cN0 patients. The OS (P = 0.42), PFS (P = 0.59), nodal recurrence-free survival (NRFS) (P = 0.46) and distant metastasis-free survival (DMFS) (P = 0.63) rates showed no significant difference between cases with and without PNI. Furthermore, cN0 patients with T4b (P = 0.53; P = 0.61), tumor origin from maxillary sinus (P = 0.55; P = 0.53) or nasopharynx involvement (P = 0.56; P = 0.60) showed no extended OS or PFS associated with PNI. ConclusionsRegardless of the T stage or the site of origin, prophylactic neck irradiation (PNI) for cN0 patients did not provide any benefit on OS and PFS, suggesting that its application on such patients is not warranted unless there is clinical suspicion.

Abstract 4012: EGFR inhibition in combination with PI3K/AKT/mTOR and/or Bcl-2 inhibition is a promising novel therapeutic approach for inverted sinonasal papillomas and associated sinonasal carcinomas

Abstract Introduction: Activating EGFR mutations are characteristic of inverted sinonasal papillomas (ISP) and ISP-associated sinonasal carcinomas (SNC). Using standard 2D culture models, our group has shown that targeting EGFR activity in ISP-associated SNC effectively inhibits cellular proliferation in vitro. Targeting EGFR in pre-clinical models that are more representative of in vivo patient responses is a critical next step. Methods: High-throughput drug screening was conducted using a 3D in vitro culture model for two ISP-associated SNC cell lines (SCCNC4 and UM-SCC-112) using a library of &amp;gt;800 curated small molecule inhibitors including inhibitors of EGFR, PI3K/AKT/mTOR (P/A/M), and Bcl-2. Viability was assessed and drug sensitivity scores were calculated. Dual combinations (inhibition of EGFR and P/A/M or Bcl-2) and triple combinations (inhibition of EGFR, P/A/M, and Bcl-2) for select drugs were tested for synergistic killing using the Chou-Talalay and Bliss methods. Treatment-associated transcriptomic changes were monitored using whole-transcriptome RNAseq. Finally, patient-derived organoids (PDOs) from primary sinonasal papilloma or carcinoma tissue were utilized ex vivo for short-term drug screening with EGFR, P/A/M, and/or Bcl-2 inhibitors at maximum human plasma concentration (Cmax) format. Results: Drug screening demonstrated that ISP-associated SNC cell lines are highly resistant to a diversity of standard and targeted therapeutic agents. Indeed, these cell lines demonstrated poorer responses than other highly resistant tumor types previously analyzed by our group, including triple-negative breast cancer and bladder cancer. Our data demonstrated that EGFR inhibition alone does not effectively kill ISP-associated SNC cells in 3D culture; however, dual and triple combinations of EGFR and P/A/M and/or Bcl-2 inhibitors showed synergistic killing. Finally, sinonasal papilloma and carcinoma PDOs showed partial responses to selected EGFR inhibitors in 3D ex vivo culture. Conclusions: While EGFR inhibitors effectively inhibit cellular proliferation in ISP-associated SNC cell lines in 2D culture, drug screening in 3D culture and using PDO material - more representative models of in vivo patient responses - show that EGFR inhibition alone is insufficient to completely eliminate these tumor cells, suggesting that EGFR inhibitors alone are unlikely to generate significant clinical responses for patients with ISP or associated SNCs. However, combining targeting of the P/A/M and/or Bcl-2 pathways revealed synergistic killing of ISP-associated SNC cell lines. Taken together, these data demonstrate that compensatory oncogenic and/or anti-apoptotic pathways must be targeted to potentiate EGFR inhibition for successful treatment of ISP and associated SNCs. Citation Format: Athena M. Apfel, Zhaoping Qin, Albert Liu, Matthew B. Soellner, Sofia D. Merajver, Aaron M. Udager, Nathan M. Merrill. EGFR inhibition in combination with PI3K/AKT/mTOR and/or Bcl-2 inhibition is a promising novel therapeutic approach for inverted sinonasal papillomas and associated sinonasal carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4012.

Determinants of Patient Refusal of Postoperative Radiation Therapy in Sinonasal Squamous Cell Carcinoma.

Objectives Although adjuvant radiotherapy may be indicated in patients with sinonasal squamous cell carcinoma (SNSCC) following primary surgery, some patients choose to forgo recommended postoperative radiation therapy (PORT). This study aimed to elucidate factors associated with patient refusal of recommended PORT in SNSCC and examine overall survival. Methods Retrospective analysis of patients with SNSCC treated with primary surgery from the National Cancer Database diagnosed between 2004 and 2016. A multivariable logistic regression model was created to determine the association between clinical or demographic covariates and likelihood of PORT refusal. Unadjusted Kaplan-Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival. Results A total of 2,231 patients were included in the final analysis, of which 1,456 (65.3%) were males and 73 (3.3%) refused recommended PORT. Patients older than 74 years old were more likely to refuse PORT than those younger than 54 (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.84-6.62). Median survival among the entire cohort, those who received recommended PORT, and those who refused PORT was 83.0 months (95% CI: 74.6-97.1), 83.0 months (95% CI: 74.9-98.2), and 63.6 months (95% CI: 37.3-101.4), respectively. Refusal of PORT was not associated with overall survival (hazard ratio: 0.99, 95% CI: 0.69-1.42). Conclusions PORT refusal in patients with SNSCC is rare and was found to be associated with several patient factors. The decision to forgo PORT is not independently associated with overall survival in this cohort. Further study is required to determine the clinical implications of these findings as the treatment decisions are complex.

Does Reorganization of Clinicopathological Information Improve Prognostic Stratification and Prediction of Chemoradiosensitivity in Sinonasal Carcinomas? A Retrospective Study on 145 Patients.

BackgroundThe classification of sinonasal carcinomas (SNCs) is a conundrum. Consequently, prognosis and prediction of response to non-surgical treatment are often unreliable. The availability of prognostic and predictive measures is an unmet need, and the first logical source of information to be investigated is represented by the clinicopathological features of the disease. The hypothesis of the study was that clinicopathological information on SNC could be exploited to better predict prognosis and chemoradiosensitivity.MethodsAll patients affected by SNC who received curative treatment, including surgery, at the Unit of Otorhinolaryngology—Head and Neck Surgery of the University of Brescia between October 1998 and February 2019 were included in the analysis. The institutional series was reviewed and a survival analysis was performed. Machine learning and multivariable statistical methods were employed to develop, analyze, and test 3 experimental classifications (classification #1, based on cytomorphological, histomorphological, and differentiation information; classification #2, based on differentiation information; and classification #3, based on locoregional extension) of SNC, based on the inherent clinicopathological information. The association of experimental classifications with prognosis and chemoradiosensitivity was tested.ResultsThe study included 145 patients. From a prognostic standpoint, the machine learning-generated classification of SNC provided better prediction than the current World Health Organization classification. However, the prediction of the chemoradiosensitivity of SNC was not achievable.ConclusionsReorganization of clinicopathological information, with special reference to those related to tumor differentiation, can improve the reliability of prognosis of SNC. Prediction of chemoradiosensitivity remains an unmet need and further research is required.

Apparent Diffusion Coefficient-Based Radiomic Nomogram in Sinonasal Squamous Cell Carcinoma: A Preliminary Study on Histological Grade Evaluation.

The aim of the study was to develop and validate a nomogram model combining radiomic features and clinical characteristics to preoperatively differentiate between low- and high-grade sinonasal squamous cell carcinomas. A total of 174 patients who underwent diffusion-weighted imaging were included in this study. The patients were allocated to the training and testing cohorts randomly at a ratio of 6:4. The least absolute shrinkage and selection operator regression was applied for feature selection and radiomic signature (radscore) construction. Multivariable logistic regression analysis was applied to identify independent predictors. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), the calibration curve, decision curve analysis, and the clinical impact curve. The radscore included 9 selected radiomic features. The radscore and clinical stage were independent predictors. The nomogram showed better performance (training cohort: AUC, 0.92; 95% confidence interval, 0.85-0.96; testing cohort: AUC, 0.91; 95% CI, 0.82-0.97) than either the radscore or the clinical stage in both the training and test cohorts ( P < 0.050). The nomogram demonstrated good calibration and clinical usefulness. The apparent diffusion coefficient-based radiomic nomogram model could be useful in differentiating between low- and high-grade sinonasal squamous cell carcinomas.

Prebiotics for Chemotherapy-Induced Lower Intestinal Mucositis (CIM) With Moderate Protein Energy Malnutrition: A Case Report

ObjectivesChemotherapy-induced mucositis (CIM) is the most common side effect of chemotherapy. In addition, it reduces quality of life and leads to a reduction in chemotherapy doses, and eventually increasing mortality rate. CIM can cause malnutrition. Chemotherapy disrupts the symbiotic relationship between the microbiota and the patient. Various modalities are able to simulate colonization of probiotic bacteria in the intestine that have potential to be a strategy to restore healthy gut microbiota. Such as prebiotic.MethodsA 42-years old male with moderately malnourished (Subjective Global Assessment score B, Unintentional weight loss for 5 months (±7%) and body mass index was about 22.94 kg/m2) with diagnosis of Non-Hodgkin Malignant Lymphoma, Sinonasal Carcinoma and chemotherapy induced acute kidney injury. He had Leukopenia (2800/ul), decrease of kidney function (ureum/creatinine 28/1.5 mg/ul) and lymphopenia (926.8 ul).ResultsThe administration of nutrition therapy was initiated from 1000 kcal and increased gradually with total energy expenditure target of 2500 kcal via oral and parenteral nutrition, protein 1.2–1.5 g/Ideal Body Weight/day (15,3%) using high protein formula and amino acids parenteral nutrition. We administered prebiotics with a dose 5 gr/day for 6 weeks. Multivitamin, minerals and nutrition supplementations were administered; which were vitamin A, B1, B2, B6, B12, C, Folic acid, Zinc, Snakehead fish extract, Curcuma extract. During 13 days of nutritional therapy treatment, he achieved an average of 93,6% and 74% of energy and protein target, respectively. His clinical, functional capacity, laboratory were improved. Gastrointestinal symptoms such as nausea, vomiting, sore throat and constipation were improved and chemotherapy dose continued.ConclusionsClinical improvement such as increased oral intake after the prebiotics had given. Therefore, prebiotics had a potential benefit for CIM.Funding SourcesInstitutions from Department of Nutrition, Faculty of Medicine, Hasanuddin University.

Stimulated Raman Histology for Rapid Intra-Operative Diagnosis of Sinonasal and Skull Base Tumors.

Intra-operative stimulated Raman histology (SRH) is a novel technology that uses laser spectroscopy and color-matching algorithms to create images similar to the formalin-fixed paraffin-embedded (FFPE) section. We aim to assess the accuracy of SRH in a novel range of sinonasal and skull base tumors. Select patients undergoing sinonasal and skull base surgery using the Invenio Imaging™ Nio™ Laser Imaging SRH system between June 2020 and September 2021 were assessed. The SRH images were reviewed for pathologic features similar to frozen section (FS) and FFPE. Time taken for results and diagnostic concordance was assessed. Sixty-seven SRH images from 7 tumor types in 12 patients were assessed. Pathologies included squamous cell carcinoma, rhabdomyosarcoma, inverted papilloma, adenoid cystic carcinoma, SMARCB1-deficient sinonasal carcinoma, mucosal melanoma, metastatic colonic adenocarcinoma, and meningioma. Tumor was identified in 100% of lesional specimens, with characteristic diagnostic features readily appreciable on SRH. Median time for diagnosis was significantly faster for SRH (4.3 min) versus FS (44.5 min; p=<.0001). Where SRH sample site matched precisely to FS (n=32/67, 47.8%), the same diagnosis was confirmed in 93.8%. Sensitivity, specificity, precision, and overall accuracy of SRH were 93.3%, 94.1%, 93.8%, and 93.3%, respectively. Near-perfect concordance was seen between SRH and FS (Cohen's kappa [κ]=0.89). Stimulated Raman histology can rapidly produce images similar to FFPE H&E in sinonasal and skull base tumors. This technology has the potential to act as an adjunct or alternative to standard FS. 4 Laryngoscope, 132:2142-2147, 2022.

The Role of Salvage in the Management of Patients with Sinonasal Squamous Cell Carcinoma.

Objectives: This paper presents and discusses the rate and outcome of salvage according to various factors for patients with sinonasal squamous cell carcinoma (SNSCC). Methods: Data of 79 patients treated radically due to SNSCC between 2000 and 2016 in the National Cancer Research Institute, Gliwice branch, were analyzed. Surgery was the primary treatment in 63 (79%) of patients. The ratio, type, and effectiveness of salvage was assessed and correlated with prognostic factors. Probabilities of overall survival (OS), local control (LC), nodal control (NC), and locoregional control (LRC) were assessed and compared between the groups. Results: The 5-year LC, NC, and LRC survival rates were 62%, 75%, and 53%, respectively. The 5-year OS rate was 51%. In 34 (43%) patients, treatment failure was reported, and salvage was performed in 17 (50%) of them. It was shown that patients after any salvage had significantly longer 2- and 3-year OS rates when compared to patients with no salvage: 52% vs. 7% and 38% vs. 0%, respectively (p = 0.004). Two- and three-year OS rates for patients after effective and ineffective salvage were 83% vs. 33% and 83% vs. 11%, respectively (p = 0.02). For patients with effective salvage, OS did not differ significantly when compared to the OS of primarily cured patients (p = 0.6). Conclusions: For SNSCC patients after treatment failure, salvage is possible in half of the cases and can improve their overall survival even if not finally successful. Moreover, effective salvage can compensate for the failure and give the same ultimate OS as in primarily cured patients.

Effect of Hospital Safety Net Burden on Survival for Patients With Sinonasal Squamous Cell Carcinoma.

To examine factors associated with hospital safety net burden and its impact on survival for patients with sinonasal squamous cell carcinoma (SNSCC). Retrospective database study. National Cancer Database from 2004 to 2016. SNSCC cases were identified in the National Cancer Database. Hospital safety net burden was defined by percentage of uninsured/Medicaid patients treated, namely ≤25% for low-burden hospitals, 26% to 75% for medium-burden hospitals, and >75% for high-burden hospitals (HBHs). Univariate and multivariate analyses were used to investigate patient demographics, clinical characteristics, and overall survival. An overall 6556 SNSCC cases were identified, with 1807 (27.6%) patients treated at low-burden hospitals, 3314 (50.5%) at medium-burden hospitals, and 1435 (21.9%) at HBHs. On multivariate analysis, Black race (odds ratio [OR], 1.39; 95% CI, 1.028-1.868), maxillary sinus primary site (OR, 1.31; 95% CI, 1.036-1.643), treatment at an academic/research program (OR, 20.63; 95% CI, 8.868-47.980), and treatment at a higher-volume facility (P < .001) resulted in increased odds of being treated at HBHs. Patients with grade III/IV tumor (OR, 0.70; 95% CI, 0.513-0.949), higher income (P < .05), or treatment modalities other than surgery alone (P < .05) had lower odds. Survival analysis showed that hospital safety net burden status was not significantly associated with overall survival (log-rank P = .727). In patients with SNSCC, certain clinicopathologic factors, including Black race, lower income, treatment at an academic/research program, and treatment at facilities in the West region, were associated with treatment at HBHs. Hospital safety net burden status was not associated with differences in overall survival.

SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma: A Case Report and Literature Review.

Background: SWItch/Sucrose Non-Fermentable related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient sinonasal carcinoma (SDSC) is a malignant tumor classified as sinonasal undifferentiated carcinoma (SNUC). Purpose: Owing to the high aggressiveness and poor prognosis reported in recent literature, patients diagnosed with SNUC should consider further immunohistochemical examination to screen for SDSC. Timely diagnosis is critical and will contribute to follow-up targeted therapy and improved patient prognosis. Research Design: Case report. Study Sample: A case of SDSC with a history of chronic sinusitis with nasal polyps (CRSwNP). Data Collection: We collected all the clinical data of this patient. Results: The patient underwent planned functional endoscopic sinus surgery (FESS) and received chemotherapy combined with immunotherapy postoperatively. There was no evidence of recurrence or metastasis at the 3-month follow-up. Conclusions: The patient in this case presented with right intermittent epistaxis, and surgical histopathological examination confirmed a diagnosis of right SDSC and left CRSwNP. No related research has been reported.

A Clinical-Radiomics Nomogram Based on the Apparent Diffusion Coefficient (ADC) for Individualized Prediction of the Risk of Early Relapse in Advanced Sinonasal Squamous Cell Carcinoma: A 2-Year Follow-Up Study

PurposeTo develop and validate a nomogram model combining radiomic features and clinical characteristics to preoperatively predict the risk of early relapse (ER) in advanced sinonasal squamous cell carcinomas (SNSCCs).MethodsA total of 152 SNSCC patients (clinical stage III-IV) who underwent diffusion-weighted imaging (DWI) were included in this study. The training cohort included 106 patients assessed at the headquarters of our hospital using MR scanner 1. The testing cohort included 46 patients assessed at the branch of our hospital using MR scanner 2. Least absolute shrinkage and selection operator (LASSO) regression was applied for feature selection and radiomic signature (radscore) construction. Multivariable logistic regression analysis was applied to identify independent predictors. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis (DCA). Furthermore, the patients were classified into high- or low-risk ER subgroups according to the optimal cutoff value of the nomogram using X-tile. The recurrence-free survival probability (RFS) of each subgroup was assessed.ResultsER was noted in 69 patients. The radscore included 8 selected radiomic features. The radscore, T stage and surgical margin were independent predictors. The nomogram showed better performance (AUC = 0.92) than either the radscore or the clinical factors in the training cohort (P < 0.050). In the testing cohort, the nomogram showed better performance (AUC = 0.92) than the clinical factors (P = 0.016) and tended to show better performance than the radscore (P = 0.177). The nomogram demonstrated good calibration and clinical utility. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (P < 0.001).ConclusionsThe ADC-based radiomic nomogram model is potentially useful in predicting the risk of ER in advanced SNSCCs.

Analysis of clinicopathologic features and expression of NR4A3 in sinonasal acinic cell carcinoma

Acinic cell carcinoma (AiCC) in the nasal cavity and paranasal sinuses has rarely been reported in literature. A recent study demonstrated that recurrent genomic rearrangement [t(4;9) (q13;q31)] is a driver event in AiCC of the salivary glands that could promote the upregulation of transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). In the current study, we evaluated the clinicopathological characteristics and expression of NR4A3 in four new cases of sinonasal AiCC. All four patients were men (range, 27–70 years). The tumor involved only the nasal cavity in two patients, while the other two patients showed involvement of both the nasal cavity and ethmoid sinus. Histologically, the tumor displayed a predominantly solid growth pattern and was composed of hematoxyphilic serous-like cells and scattered intercalated duct-like cells. Immunohistochemically, all cases expressed DOG-1. However, staining for mammaglobin, S-100, CA9, and P63 was absent in all patients. All four cases showed positive nuclear staining for NR4A3. In contrast, none of the other 39 sinonasal tumors, including secretory carcinomas, pleomorphic adenomas, mucoepidermoid carcinomas, adenoid cystic carcinomas, renal cell-like adenocarcinomas, intestinal-type adenocarcinomas, non-intestinal-type adenocarcinomas, extraskeletal myxoid chondrosarcoma, and carcinoma ex pleomorphic adenomas, presented with any positive NR4A3 nuclear staining. Additionally, NR4A3 rearrangements were observed in three cases with sinonasal AiCC by fluorescence in situ hybridization, and the expression level of NR4A3 mRNA was significantly increased in sinonasal AiCC compared with that in normal parotid tissue. Our study demonstrated that sinonasal AiCCs are characterized by an indolent nature and histopathological similarity to parotid AiCCs. Moreover, NR4A3 is a reliable biomarker for distinguishing sinonasal AiCCs from other sinonasal carcinomas.

Molecular Detection Methods in HPV-Related Cancers.

Human papillomavirus (HPV) is responsible for most cervical cancers and some head and neck cancers, including oropharyngeal squamous cell carcinoma and sinonasal carcinoma. Cervical cancer is commonly diagnosed by liquid-based cytology, followed by HPV testing using commercially available DNA polymerase chain reaction (PCR), p16 immunohistochemistry (IHC), or DNA/RNA in situ hybridization. HPV in head and neck cancers is commonly diagnosed by p16 IHC or by RT-qPCR of HPV-16 E6 and E7 oncoproteins. Droplet digital PCR has been reported as an ultrasensitive and highly precise method of nucleic acid quantification for biomarker analysis and has been used to detect oncogenic HPV in oropharyngeal and cervical cancers.

Sinonasal Tumors With Neuroepithelial Differentiation (Olfactory Carcinoma): Delineation of Their Pathologic and Clinical Features With Insights into Their Relationship to Olfactory Neuroblastoma and Sinonasal Carcinoma.

Olfactory carcinoma is one of many names applied to sinonasal malignancies with histologic similarity to olfactory neuroblastoma (ONB) but cytokeratin expression or gland formation. It is unclear whether these neuroepithelial tumors represent a unified category and if they are separate from ONB and currently-recognized sinonasal carcinomas. This study aims to explore their clinicopathologic characteristics based on a large collective experience. A total of 53 sinonasal tumors with neuroepithelial differentiation were identified affecting 41 men and 12 women, median age 47 years (range: 12 to 82 y). The vast majority arose in the superior nasal cavity and presented at the high Kadish-Morita stage. Frequent histologic findings included (1) lobulated and solid growth, (2) rosettes and/or neurofibrillary stroma, (3) high-grade cytology, (4) complex, often ciliated glands, (5) nonfocal pancytokeratin expression, (6) neuroendocrine pos+itivity, and (7) variable S100-positive sustentacular cells. Twelve patients with available follow-up (48%) developed progressive disease at a median 8 months (range: 0 to 114 mo to progression), and 7 (28%) died of disease. Despite disparate historical terminology, neuroepithelial differentiation is a recurrent and recognizable histologic pattern that is associated with aggressive behavior in sinonasal tumors. While tumors with this phenotype may originate from olfactory mucosa, well-developed epithelial features warrant separation from conventional ONB and neural elements distinguish them from most sinonasal carcinomas. Although their full histogenesis remains uncertain and some heterogeneity may exist, we propose that this pattern is sufficiently distinctive to merit separate recognition as olfactory carcinoma. Use of consistent nomenclature may facilitate greater recognition of tumors with this phenotype and understanding of their pathogenesis and classification.

High-grade myoepithelial carcinoma of the palate and maxillary sinus complex: a case report

<h3>Introduction</h3> Myoepithelial tumors typically arise from myoepithelial cells of salivary glands, however myoep- ithelial tumors arising in the skin and soft tissues have been increasingly recognized. Myoepithelial carcinomas (MC) have been described in each of these anatomic locations. Myoepithelial carcinoma of the salivary gland is a rare neoplasm composed exclusively of myoepithelial cells. The diagnosis of myoepithelial carcinoma is based on establishing the immunophenotype of the cellular proliferation, degree of cytologic atypia, presence of mitoses and necrosis, and exclusion of mimics. The morphologic heterogeneity further complicates the diagnosis of MC. <h3>Case Findings</h3> A 54-year-old woman presented with a progressive enlargement of the left palate, with imaging demonstrating involvement of adjacent maxillary sinus with extension to the floor of the orbit. Histologically, the lesion was characterized by malignant appearing epithelioid and clear cells compactly arranged in confluent sheets with no evidence of ductal differentiation. The sheets of tumor cells had a somewhat lobular architecture demar- cated by thin vascular septa. Nuclear pleomorphism, numerous mitoses, and focal necrosis were present. <h3>Results</h3> Positive immunohistochemical staining of tumor cells with CK7, SOX10, S100, P63, P40, and SMA favored a myoepithelial phenotype. <i>SMARCB1</i> (<i>INI1</i>) was expressed, excluding <i>SMARCB1</i>-deficient sinonasal carcinoma. Neg- ative staining of tumor cells for TTF1, CD20, GFAP, calponin, HMB45, PAX8, CD31, CD34 appear to exclude melanoma, renal cell carcinoma, renal cell like sinonasal carcinoma, thyroid carcinoma, lung carcinoma and PEComa. Outside consultation reported positive P16 but the tumor was negative for high risk HPV, thus excluding HPV related mul- tiphenotypic sinonasal carcinoma. Ki-67 revealed a high proliferative index of 70%. <h3>Conclusions</h3> This study demonstrates the clinical and histopathologic findings of a high-grade myoepithelial carci- noma involving the palate and maxillary sinus complex. Exclusive myoepithelial differentiation (morphologic and immunophenotypic) accompanied by established criteria of malignancy allow for definitive diagnosis of this rare salivary gland tumor.

HPV-Related Multiphenotypic Sinonasal Carcinoma with Unusual Palisading Spindle Cell Morphology

Human papilloma virus (HPV)-related Multiphenotypic Sinonasal carcinoma (HMSC), formerly known as HPV- related Carcinoma with Adenoid Cystic Carcinoma-Like Features, is a newly described entity occurring exclusively in the sinonasal tract. It is a type of HPV-related sinonasal carcinoma displaying salivary carcinoma-like morphol- ogy (especially adenoid cystic carcinoma). It has strong association with high-risk HPV (particularly HPV type 33). Many histologic patterns have been reported in the literature, including solid, cribriform, and tubular growth pat- terns, myoepithelial and plasmacytoid pattern, spindle and sarcomatoid pattern, and glomeruloid growth pattern. Here, we report a case of HMSC with unusual palisading spindle cell morphology. The patient is a 53-year-old woman with a history of nasal obstruction and drainage. A CT scan showed a soft tissue mass in the right nasal cavity with significant deviation of the septum. The patient subsequently received a right sided anterior ethmoidectomy and maxillary antrostomy. Intraoperatively, a fleshy polypoid mass was noted to occlude the nasal airway and push the right middle turbinate and septum. Histologic sections show multiple architectural patterns within the tumor, including cribriform architecture ad- mixed with hyaline globules, tubular/glandular area with biphasic inner ductal and outer myoepithelial elements, small nests with true keratinization and keratin pearls, and palisading spindle cell morphology. Scattered tumor cells show marked nuclear enlargement and nuclear pleomorphism. Multifocal tumor necrosis and increased mi- totic index are identified. Immunohistochemically, the tumor is positive for p63 (diffuse), p40 (diffuse), CAM5.2 (patchy), cytokeratin AE1/AE3, SMA, calponin, S100 and p16 (strong and diffuse, nuclear and cytoplasmic). RNA <i>in situ</i> hybridization for high risk HPV is positive. We report a HMSC with unusual spindle cell morphology. This case highlights the morphological spectrum that can be seen in this rare tumor and the importance for clinicians to be familiar with this entity.

High-risk HPV Does not Appear to be an Important Risk Factor for Sinonasal Carcinomas in Turkish Population: A Tertiary Center Experience.

Background. The sinonasal tract is the second most common site of human papillomavirus (HPV)-related carcinomas in the head and neck. Published data on the association between sinonasal tumors and HPV are quite inconsistent among different regions. Material and methods. We performed high-risk HPV DNA in situ hybridization (ISH) and p16 immunohistochemistry on sinonasal carcinomas diagnosed between 2006 and 2016. Results. Of 105 sinonasal carcinomas, we found only two (2%) HPV-positive cases; both had non-keratinizing morphology and were diffusely positive for p16. By histologic type, HPV DNA positivity rate was 14% in non-keratinizing squamous cell carcinomas, and we did not detect HPV DNA in any other type of sinonasal carcinomas. Thirteen HPV-negative tumors (7 salivary gland carcinomas, 3 sinonasal undifferentiated carcinomas, 2 keratinizing squamous cell carcinomas, and 1 non-keratinizing squamous cell carcinoma) were positive for p16. In nine carcinomas arising from an underlying sinonasal papilloma, p16 and HPV DNA ISH were evaluated in both carcinoma and papilloma areas and all were negative. Follow-up information was available for 104 patients; 46 (44%) were alive and 58 (55%) died of disease. One of the two HPV-positive patients died of the disease; the other was alive at 100 months of follow-up. Conclusions. We detected a much lower percentage of HPV positivity in sinonasal carcinomas when compared to the literature. We believe that our results support various rates of HPV-related carcinomas depending on the geographic and ethnic characteristics.

Feasibility of lattice radiotherapy using proton and carbon-ion pencil beam for sinonasal malignancy.

BackgroundSinonasal malignancies are a treatment challenge because of their complex anatomy and close proximity to organs at risk (OARs). We aimed to investigate the feasibility of lattice radiotherapy (LRT) using pencil beam scanning (PBS) proton or carbon-ion beams in the treatment of sinonasal malignancies.MethodsA total of 10 patients with nonoperative and bulky sinonasal adenoid cystic carcinomas (ACC) were enrolled. Spherical vertices with a 1 cm diameter and average center-to-center (c-t-c) distance of 3.51 cm were delineated within the gross tumor volumes (GTVs). The prescription doses were 15 Gy[relative biologic effectiveness (RBE)] to the vertices and 3 to 3.5 Gy(RBE) to the periphery, delivered as clinical target volume boosts (CTVboosts) in 1 fraction. Photon, proton, and carbon-ion LRT plans were generated. Peak-to-valley dose ratios (PVDRs) and the doses delivered to the vertices, the CTVboost, and OARs were compared among the 3 plans.ResultsThe mean PVDRmin values for the photon, proton, and carbon-ion LRT plans were 4.78 (range, 4.34 to 5.36), 4.82 (range, 4.15 to 5.37), and 4.69 (range, 4.31 to 5.28), respectively. The mean PVDRmean values for the same plans were 3.42 (range, 3.15 to 3.79), 2.93 (range, 2.19 to 3.74), and 3.58 (range, 3.09 to 4.68), respectively. There were no significant differences between the PVDRmin and PVDRmean values across the 3 LRT plans. Most critical organs were better protected in the proton and carbon-ion LRT plans than in the photon LRT plans. The photon LRT plans showed the highest maximum degree (Dmax) of vertices. Furthermore, these plans did not introduce more doses to the OARs compared to the 1-fraction clinical boost plan.ConclusionsDespite minimal differences in PVDR, proton and carbon-ion LRT plans can better protect OARs than photon LRT plans.

Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities.

Simple SummaryIn recent years, there have been several molecular and immunohistochemical additions to the pathologic diagnosis of sinonasal malignancies that could facilitate the identification of clinically relevant groups of sinonasal malignancies. Molecular profiling is progressively integrated in the histopathologic classification of sinonasal carcinomas, and it is likely to influence the management of these tumors in the near future. In this article we review the recent literature on molecular analysis and/or subtyping of sinonasal carcinomas and we discuss the possible clinical implications of a classification of sinonasal tumors based on their molecular features.Sinonasal carcinomas are a heterogeneous group of rare tumors, often with high-grade and/or undifferentiated morphology and aggressive clinical course. In recent years, with increasing molecular testing, unique sinonasal tumor subsets have been identified based on specific genetic alterations, including protein expression, chromosomal translocations, specific gene mutations, or infection by oncogenic viruses. These include, among others, the identification of a subset of sinonasal carcinomas associated with HPV infection, the identification of a subset of squamous cell carcinomas with EGFR alterations, and of rare variants with chromosomal translocations (DEK::AFF2, ETV6::NTRK and others). The group of sinonasal adenocarcinomas remains very heterogeneous at the molecular level, but some recurrent and potentially targetable genetic alterations have been identified. Finally, poorly differentiated and undifferentiated sinonasal carcinomas have undergone a significant refinement of their subtyping, with the identification of several new novel molecular subgroups, such as NUT carcinoma, IDH mutated sinonasal undifferentiated carcinoma and SWI/SNF deficient sinonasal malignancies. Thus, molecular profiling is progressively integrated in the histopathologic classification of sinonasal carcinomas, and it is likely to influence the management of these tumors in the near future. In this review, we summarize the recent developments in the molecular characterization of sinonasal carcinomas and we discuss how these findings are likely to contribute to the classification of this group of rare tumors, with a focus on the potential new opportunities for treatment.