The contemporary management of cancers of the sinonasal tract in adults.

Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.

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.

Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study.

PURPOSE: Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery. METHODS: In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo. RESULTS: In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FImean), with SNIP tissue showing a median FImean of 77.54 (IQR 50.47-112.30) compared to 35.99 (IQR 21.48-57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78. CONCLUSIONS: A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery. TRIAL REGISTRATION: NCT03925285.

[ETV6-rearranged low-grade sinonasal non-intestinal-type adenocarcinoma: a clinicopathological analysis].

Objective: To investigate the clinicopathologic features, immunophenotype, molecular genetic changes of ETV6-rearranged low-grade sinonasal non-intestinal-type adenocarcinoma (ETV6-RLGSNAC). Methods: Primary sinonasal epithelial malignant tumors were collected from January 2015 to January 2020 in the Department of Pathology, Eye, Ear, Nose and Throat Hospital affiliated to Fudan University. Through morphological observation, immunohistochemical detection and fluorescence in situ hybridization (FISH), ETV6-RLGSNAC was screened out for clinicopathological feature analysis, and relevant literatures were reviewed. Results: There were 550 cases of primary sinonasal epithelial malignant tumors, among which 82 cases were adenocarcinoma. There were 29 cases of low-grade non-intestinal adenocarcinoma, only 3 cases of ETV6-RLGSNAC were screened out. Of the 3 patients, 2 cases were male and 1 case was female, with a mean age of 54 years (range 37-64 years). The main clinical manifestations were nasal stenosis, nasal obstruction and epistaxis. A neoplasm with smooth surfaces was observed under nasal endoscopy. Imaging showed an expansive mass in the sinonasal area. Gross examination showed gray-yellow cut surface with firm texture and a maximum diameter of 2-3 cm. Microscopically, tumors were non-encapsulated and well-circumscribed with expansive growth pattern. The tumor cells were small and mild, cylindrical and cuboidal, and arranged in regular glandular and trabecular patterns. The cytoplasm was eosinophilic and the nuclei were basally located with inconspicuous nucleoli. By immunohistochemistry (IHC), CK7, SOX-10, DOG1 and vimentin were positive and S-100 expressed in small clusters of cells in all cases. GCDFP-15, CD56, CK20, mammaglobin, TTF-1, NR4A3 were all negative. The Ki-67 value-added index of all cases was low (<5%). ETV6 gene rearrangement was confirmed in all the cases by FISH, and two cases had NTRK3 gene rearrangement. All three patients underwent radical resection after diagnosis, and one also had adjuvant radiotherapy. All three patients were available with a follow-up time of 12-25 months, and all were recurrence free. Conclusions: ETV6-RLGSNAC is a rare low-grade and newly named non-intestinal adenocarcinoma. The histomorphology is similar to other low-grade nasal sinonasal adenocarcinomas and some salivary gland tumors. IHC and FISH are useful for the diagnosis and differential diagnosis.

Nasal polyps and future risk of head and neck cancer: A nationwide population-based cohort study.

BACKGROUND: Nasal polyps are a common condition with a significant effect on quality of life. The association between nasal polyps and future risk of head and neck cancer is unknown. OBJECTIVE: We sought to investigate the relative risk of nasal cavity and paranasal sinus (NCPS) and nasopharyngeal cancers in a nationwide, population-based, longitudinal retrospective cohort of patients with nasal polyps and matched comparators. METHODS: The 2005-2017 National Health Insurance claims and National Health Screening program databases were used to construct a cohort of patients with nasal polyps and matched comparators in Korea. The relative risk of NCPS and nasopharyngeal cancer in patients with nasal polyps was examined. RESULTS: The study consisted of 453,892 patients with nasal polyps and 4,583,938 matched comparators. The mean duration of follow-up was 6.2 years (range, 2-13 years). The incidence rate ratios of patients with nasal polyps compared with the comparators was 7.00 (95% CI, 5.28-9.25) for NCPS cancer and 1.78 (95% CI, 1.28-2.42) for nasopharyngeal cancer. Increased risks of these cancers were only evident in older subjects (age ≥50 years). There were trends toward weaker associations of nasal polyps with these cancers in younger subjects with comorbid asthma or allergic rhinitis (<50 years). CONCLUSION: Although the absolute cancer incidence is very low, the relative risk of NCPS or nasopharyngeal cancers was significantly greater in older patients with nasal polyps. Given the regional and pathologic heterogeneity of nasal polyps, further studies are needed to explore the underlying mechanisms and validate the relationships.

[Radicality of maxillary sinus surgery and size of the maxillary sinus ostium]. / Radikalität der Kieferhöhlenoperation und Größe des Kieferhöhlenfensters.

Until the 1990s, radical sinus surgery was considered a standard procedure for maxillary sinus diseases, but it is no longer favored due to the high morbidity. Today, functional endoscopic sinus surgery (FESS) is considered the gold standard in sinus surgery. Modifications of surgical approaches also allow access to regions of the maxillary sinus that were previously difficult to reach. Depending on anatomy and pathology, different methods for widening the maxillary ostium can be selected. In type I sinusotomy, the natural ostium is widened dorsally by a maximum of 1 cm. Sinusotomy type II involves widening the natural ostium up to a maximum diameter of 2 cm. In sinusotomy type III, the natural ostium is widened dorsally to the posterior wall of the maxillary sinus and caudally to the base of the inferior turbinate. Beside the prelacrimal approach, more invasive approaches are the medial maxillectomy, in which the dorsal part of the inferior turbinate and the adjacent medial wall of the maxillary sinus is resected, as well as its modifications "mega antrostomy" and "extended maxillary antrostomy." Correct selection of the size of the maxillary sinus window is prerequisite for successful treatment and long-term postoperative success. Isolated purulent maxillary sinusitis can usually be treated by a type I sinusotomy. Sinusotomy type II addresses nasal polyps with involvement of the mucosa of the ostium, recurrent stenosis after previous surgery, chronic maxillary sinusitis due to cystic fibrosis, and purulent maxillary sinusitis with involvement of other adjacent sinuses. Sinusotomy type III is required for choanal polyps with attachment to the floor of the maxillary sinus, for extensive polyposis and fungal sinusitis, and for inverted papilloma. Particularly for (recurrent) disease and extensive interventions in the maxillary sinus, medial maxillectomy or a modification thereof may be required.

[SMARCB1 (INI1)-deficient sinonasal carcinoma: a clinicopathological analysis of six cases].

Objective: To study the clinicopathological features, diagnostic features and differential diagnoses of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Six cases of SDSC diagnosed at Eye, Ear, Nose and Throat Hospital, Fudan University from 2016 to 2018 were retrieved; the clinical features, histomorphology, immunophenotype, radiology and outcome were analyzed with review of literature. Results: There were five men and one woman with age range of 37 years to 75 years (mean 56 years). One case was in stage T2, and 5 cases were in stage T4. Computer tomography and magnetic resonance imaging showed a mass occupying the sinonasal cavity with bone destruction in all six patients. Microscopically, the tumors had infiltrative margins. Four tumors were composed mostly of basaloid cells, which possessed high nuclear/cytoplasmic ratio,scant cytoplasm,and minimalnuclear pleomorphism; and the cells were arranged in sheets or nests in a desmoplastic stroma. Two tumors were composed of rhabdoid cells, which possessed abundant, eosinophilic cytoplasm and eccentric nuclei, often growing in a nests or sheets pattern. Immunohistochemical staining showed that 6/6 cases had complete loss of INI1, diffusely and strongly positive for CKpan, and were negative for S-100 and EBER ISH; 4/6 cases were focally positive for p63; 1/5 was focally positive for Syn and p16. The Ki-67 index was 30% to 70%. The follow-up period ranged 1-26 months, with one patient died of extensive metastases, one had local recurrence, and two had lymph node metastases; one was alive without disease, and one was lost to follow-up. Conclusions: SMARCB1 (INI1)-deficient sinonasal carcinoma is mostly aggressive, with rapid progression and poor prognosis. Histomorphological spectrum predominantly consists of basaloid type and rhabdoid type. The complete loss of nuclear expression of INI1 can help to distinguish this tumor from its many mimickers.

[Clinicopathological and molecular features of biphenotypic sinonasal sarcoma].

Objective: To study the clinicopathologic features, immunophenotype, molecular genetics and differential diagnosis of biphenotypic sinonasal sarcoma (BSNS), and to evaluate the role of PAX3 and PAX8 immunohistochemical (IHC) antibodies in the diagnosis of BSNS. Methods: Nasal sinus spindle cell tumors surgically treated at the Jinling Hospital from 2000 to 2019 were collected, including three cases of BSNS, 10 cases of acinar rhabdomyosarcoma, eight cases of schwannoma, five cases of hemangiopericytoma, three cases of fibrosarcoma, and one case of triton tumor. The cases were evaluated by histology, IHC by EnVision for PAX3 and PAX 8 (including PAX8 murine monoclonal antibody, clone number OTI6H8, hereinafter referred to as PAX8-OTI6H8 antibody; PAX8 rabbit monoclonal antibody, clone number EP298, hereinafter referred to as PAX8-EP298 antibody) molecular genetic tests. Results: All three BSNS patients were elderly women with clinical manifestations of nasal congestion and bleeding. Imaging showed a soft tissue density shadow of the nasal cavity and sinuses with bone destruction. The boundaries of tumors which were covered with ciliated columnar epithelium were unclear, and mucosal invasion and squamous metaplasia could be seen. Tumor cells were spindle-shaped, arranged in a bundle-like, braided arrangement, with little cellular atypia and occasional atypical mitotic figures. The tumoral interstitial vessels were mostly thin-walled, some showing staghorn-like changes. There was focal striated muscle differentiation in two cases, and bone invasion was seen in two cases. IHC staining showed that all three cases of BSNS expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. All eight cases of schwannoma, five cases of hemangiopericytoma, and one case of triton tumor did not express PAX3, PAX8-OTI6H8 or PAX8-EP298. Eight of the ten cases of alveolar rhabdomyosarcoma expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. Three cases of fibrosarcoma showed weak PAX3 and PAX8-OTI6H8 expression, but there was no PAX8-EP298 expression. FISH detection showed that PAX3 break apart in the tumor cells from all three patients (four specimens). Conclusions: BSNS is a distinct sinonasal low grade malignancy with dual differentiation which could be readily confused with a variety of spindle cell tumors encountered in the sinonasal cavity. The molecular genetics of PAX3 gene break is the gold standard for diagnosis of this tumor. IHC marker monoclonal PAX3 is 100% expressed in BSNS, while the specificity is limited. PAX8-OTI6H8 is also expressed in BSNS due to the cross reaction with PAX3 antibody, while PAX8-EP298 is all negative for these tumors.

[Sinonasal renal cell-like adenocarcinoma: a clinicopathological analysis of five cases].

Objective: To investigate the clinicopathological features, immunophenotype, differential diagnosis and prognosis of sinonasal renal cell-like adenocarcinoma. Methods: Retrospective analysis was performed on the cases of sinonasal carcinoma from August 2014 to December 2018 at Eye, Ear, Nose and Throat Hospital, Fudan University. Renal cell-like adenocarcinoma was screened for clinicopathologic feature analysis, and relevant literatures were reviewed. Results: There were 460 cases of sinonasal carcinoma, among which 70 cases (15.2%) were adenocarcinoma, with five (1.1%) being renal cell-like adenocarcinomas. Four patients were male and one was female, with a mean age of 46.5 years (range 29-52 years). The main clinical manifestations were nasal obstruction and epistasis. A red polypoid mass was found under nasal endoscopy. Imaging showed nasal cavity and ethmoid sinus mass with invasion into surrounding structures and bone destruction. Microscopically, the tumor cells were arranged in nests, alveoli and microcapsules with abundant intervening capillaries, accompanied by hemorrhage. The cytoplasm of the cells was clear with low nuclear grade, and the nucleoli were inconspicuous. In some areas, the tumor invaded bone tissue. Immunohistochemical markers CKpan, CK7, CAⅨ, S-100 and vimentin were positive, with low Ki-67 proliferation index. RCC, CD10, PAX8, p63, SMA, HHF35, Calponin, CD117, TTF-1 and neuroendocrine markers Syn and CHG were all negative. EWSR1 and ETV6 gene rearrangements were not detected by FISH. All five patients underwent surgical resection after initial diagnosis. One patient underwent surgical resection after second recurrence and adjuvant radiotherapy, one patient received postoperative radiotherapy, one patient underwent surgical resection after recurrence, one patient had no recurrence and one patient received radiotherapy after recurrence. All five patients had no distant metastasis and survived without tumor up to December 2019. Conclusions: Primary sinonasal renal cell-like adenocarcinoma is a special subtype of low-grade non intestinal adenocarcinoma, with low incidence and inert biologic behavior. At present, most of the literatures are case reports. Before a diagnosis is made, other primary and metastatic clear cell tumors need to be excluded. Immunohistochemistry is helpful for diagnosis and differential diagnosis. Surgical resection is the mainstay of treatment, and may be supplemented by radiotherapy.

[Quantitative dynamic contrast enhancement MR imaging parameters in the prediction and evaluation of the treatment response of malignant sinonasal tumors to chemotherapy:a preliminary result].

Objective: To investigate the value of quantitative dynamic contrast enhancement MR imaging (DCE-MRI) parameters in the prediction and evaluation of the response to neoadjuvant chemotherapy in patients with malignant sinonasal tumors by comparing the parameter values before and after chemotherapy. Methods: DCE-MRI was performed in 14 patients (6 male cases, 8 female cases, 16-83 years) with malignant sinonasal tumors before chemotherapy in Beijing Tongren Hospital from January 2012 to December 2013 in which DCE-MRI was performed in 8 patients on the 7th, 21st and 42nd days after chemotherapy. The values of quantitative parameter including K(trans), K(ep), and V(e) of the tumor were assessed and the change rate of these quantitative parameter values after chemotherapy was calculated. Results: Response to chemotherapy of the tumor was found in 11 patients with malignant sinonasal tumors,whereas no response to chemotherapy of the tumor was confirmed in 3 patients. K(trans) ((0.75±0.28)/min) and K(ep) ((3.23±1.48)/min) values of the tumor before chemotherapy in patients with response to chemotherapy were significantly bigger than those ((0.43±0.41)/min, (1.34±0.42)/min) in patients with no response to chemotherapy (all P<0.01).There was no significant difference in V(e) values between two groups (P=0.165). Compared with K(trans) values of the tumor before chemotherapy,the change rate of K(trans) values decreased more than 40% on the 7th,21st and 42nd days after chemotherapy in the patients with treatment response,whereas the change rate did not decrease significantly in the patients without treatment response. Conclusion: The bigger K(trans) and K(ep) values of the tumor before chemotherapy,the better the treatment response of the tumor to chemotherapy.

[Tumors of the paranasal sinus invading the orbit]. / Tumoren der Nasennebenhöhlen mit Übergreifen auf die Orbita.

Invasion of the orbit by tumors of the paranasal sinus represents an advanced state of disease. Prognosis has hardly improved in recent decades, despite multimodal therapeutic approaches. Complete resection of the tumor still remains the most promising therapy. Orbital exenteration implies a dramatic event for the patient's psyche and quality of life. If the eye that would have to be exenterated is the only one remaining with sufficient vision, exenteration should be abandoned in consensus with the patient. Aesthetic improvements following exenteration can be achieved by surgical and prosthetic techniques. The method of prosthesis fixation needs to be determined with respect to the patients' individual expectations and manual abilities. The main aspects of functional rehabilitation are good local cleanability and sufficient nasal breathing without encrusted mucus, which can be achieved by restoring the natural laminar airflow. Tumors of the paranasal sinus with orbital invasion represent a diagnostic and therapeutic challenge. The information regarding prognosis, therapeutic approaches, post-therapeutic quality of life, and rehabilitation options should be thoroughly discussed by patients and therapists prior to treatment.

[Expression of CD117, MITF and NAT10 and their prognostic values in sinonasal mucosal melanoma].

Objective: To investigate the correlation between the expression of CD117, MITF, NAT10 and clinical parameters in sinonasal mucosal melanoma (SNMM). Methods: Formalin-fixed paraffin-embedded tumor specimens of 80 cases of SNMM at the Eye, Ear, Nose and Throat Hospital, Fudan University, from December 1999 to November 2013 were analyzed for CD117, MITF and NAT10 expression by immunohistochemistry. Results: There were 40 men and 40 women. The median age was 61 years, age 26 to 85 years. There was no correlation of the expression of CD117, MITF and NAT10 with the patients' age, gender, tumor site, stage, therapy method and brain metastases (P>0.05). The expression of MITF and NAT10 was associated with lymph node metastasis and the tumors were more likely to metastasize when MITF and NAT10 were positive. However, expression of CD117 had no correlation with lymph node metastasis. Log-rank test revealed that the expression of CD117 was correlated with both three-year and five survival rate (P=0.012, P=0.023; respectively) and patients with tumor having low expression of CD117 had the worse outcome. COX test revealed that low CD117 expression, advanced age and lymph node metastasis were independent risk factors (P<0.05). No significant association was found between the expression of CD117, MITF and NAT10 with disease free survival (P>0.05). Conclusions: Patients with SNMM expressing low level of CD117 have decreased survival rate. Tumors with high level of MITF and NAT10 expression are more likely to metastasize. The expression level of CD117 can be used as an important indicator for the patient survival, and the expression of MITF and NAT10 can be used as a predictor of tumor metastasis.

Prognostic value of tumoral heterogeneity and volumetric parameters as measured by F18-FDG PET/CT in sinonasal cancer.

The objective of this study was to investigate the value of parameters assessed with F18-FDG PET/CT in predicting recurrence-free survival (RFS) and disease-specific survival (DSS) in patients with cancer of nasal cavity and paranasal sinus. Thirty-eight patients with cancer of nasal cavity (n = 14) and paranasal sinus (n = 24) who underwent PET/CT prior to curative treatment were enrolled. A volume of interest was placed on PET/CT images covering the entire tumor volume, and the maximum SUV (SUVmax), the mean SUV (SUVmean), and volumetric parameters of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured using thresholds of 40 % of SUVmax. The heterogeneity factor (HF) defined as the derivative of volume-threshold function from 40 to 80 % of SUV thresholds. RFS and DSS were defined as the time from the diagnosis to recurrence and death. Median values of SUVmax, SUVmean, MTV, TLG, and HF were 14.81, 9.16, 25.84, 150.74, and -0.496. SUVmax was higher in patients with advanced stage and nodal metastasis. High MTV and low HF group showed shorter RFS. Cox proportional hazards regression analysis revealed low HF was the only significant predictive factor on RFS. Furthermore, high TLG was associated with shorter DSS. High TLG was potent predictor of DSS by Cox proportional hazards regression analysis. In conclusion, the tumoral heterogeneity and volumetric parameters as measured by F18-FDG PET/CT could be significant prognostic surrogate markers in patients with sinonasal cancer.

The clinical behavior of sinonasal inverted papilloma with cellular dysplasia: case series and review of the literature.

The prognosis and recurrence rate of inverted papilloma (IP) with concomitant cellular dysplasia are not well-delineated. Demographic, clinical and imaging data of all patients who were surgically treated for sinonasal inverted papilloma (SNIP) in our center between 1996 and 2013 were reviewed. Data regarding the coexistence of dysplastic changes or malignancy within the resected tissues were also retrieved. After the exclusion of malignant cases and patients who were lost for follow-up, 92 patients were included in the study. Five patients had coexisting cellular dysplasia (4.7%), four of them had severe dysplasia and one had mild-to-moderate dysplasia. All four cases with severe dysplasia recurred, three were primarily treated endoscopically and one by external approach. Only the case with mild to moderate dysplasia which had been treated by subcranial approach did not recur. Patients with dysplasia had significantly higher recurrence rate than patients without dysplasia (80 vs. 14%, p = 0.019). This significant relation between histology and recurrence remained even after adjustment to tumor extent. The adjusted odd ratio of dysplasia (dysplasia vs. no dysplasia) is 9.7, p = 0.043. SNIP with dysplasia should be treated aggressively and followed closely. The histopathologic investigation of SNIP specimens should always note the presence of dysplasia and its severity. Further investigation on the clinical behavior of SNIP with dysplasia is needed. Multicenter studies are warranted due to the rarity of dysplastic SNIP.

[Clinicopathologic and molecular genetic characterizations of biphenotypic sinonasal sarcoma].

Objective: To investigate the clinicopathologic characteristics, immunophenotypes, molecular genetics, and diagnostic and differential diagnostic features of biphenotypic sinonasal sarcoma (BSNS). Methods: Three cases of BSNS were retrieved, the histomorphology, immunophenotype and molecular genetics were analyzed with review of literature. Results: There were 2 male and 1 female patient aged 45, 29 and 40 years, respectively.Computed tomography and magnetic resonance imaging examinations showed a large polypoid mass occupying the sinonasal cavity in all 3 patients. Microscopically, these tumors were un-circumscribed and composed of cellular spindle-shaped cells arranged in long and interlaced fascicles. A hemangiopericytoma-like growth pattern was frequently identified. The overlying hyperplastic respiratory epithelium invaginated down into the tumor forming a cystic (2 cases), glandular (1 case) structures and inverted in a papilloma-like (1 case)pattern, and foci of eosinophilic metaplasia were also noted in 2 of the three cases. The tumor nuclei were bland-appearing, mitoses were scarce and necrosis was absent. Immunohistochemically, the tumor cells showed co-expression of neural and myogenic markers in all the 3 cases, including that 3/3 showed diffuse and strong positivity of S-100 protein, 3/3 positivity of smooth muscle actin (1 diffuse and 2 focal), 1/2 diffuse positivity of calponin, 1/3 focal positivity of desmin, and 1/1 focal positivity of MyoD1.In addition, 1 detected for ß-catenin showed focal nuclear positivity. None of the 3 showed positivity to cytokeratin, CD34 or SOX10 in the tumor cells.Ki-67 showed an index <5%, 10% and <2%, respectively. Fluorescence in situ hybridization analysis showed rearrangements of PAX3 gene in all 3 cases. In case 3, reverse transcription polymerase chain reaction, followed by Sanger sequencing, demonstrated an in-frame fusion between PAX3 and FOXO1.Follow-up information (range 3-15 months)showed no evidence of local recurrence or distant metastasis in three cases. Conclusions: BSNS is a newly described entity which can be readily confused with a variety of benign and malignant spindle cell tumors encountered in the sinonasal cavity; immunohistochemistry co-expression of neural and myogenic markers and PAX3 gene rearrangement can help distinguish this tumor from its many mimickers.

Can Diffusion Weighted Imaging Aid in Differentiating Benign from Malignant Sinonasal Masses?: A Useful Adjunct.

BACKGROUND: To evaluate the role of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values at 3 Tesla in characterizing sinonasal masses. MATERIAL/METHODS: After ethical clearance, 79 treatment naive patients with head and neck masses underwent magnetic resonance imaging (MRI), including DWI at 3 Tesla using the following b values - 0, 500 and 1000 s/mm2. Thirty-one patients were found to have sinonasal tumours and were subsequently analysed. Image analysis consisted of a morphological evaluation of conventional MR images, qualitative evaluation of DW trace images and quantitative assessment of mean ADC values. Receiver operating characteristic (ROC) curve was drawn to determine a cut-off ADC value for the differentiation between benign and malignant masses. RESULTS: Sinonasal masses showed an overlapping growth pattern on conventional imaging, irrespective of their biological nature. The mean ADC value of benign lesions was 1.948±0.459×10-3 mm2/s, while that of malignant lesions was 1.046±0.711×10-3 mm2/s, and the difference was statistically significant (p=0.004). When a cut-off ADC value of 1.791×10-3 mm2/s was used, sensitivity of 80% and specificity of 83.3% were obtained for characterization of malignant lesions, which was statistically significant. Juvenile nasopharyngeal angiofibroma (JNA) showed distinctly high ADC values, while meningioma was the only benign lesion with restricted diffusion. Atypical entities with unexpected diffusion characteristics included: adenocarcinoma, adenoid cystic carcinoma, meningioma, chondrosarcoma and fibromyxoid sarcoma. CONCLUSIONS: DWI in conjunction with conventional imaging can potentially enhance the diagnostic accuracy in characterizing sinonasal masses as benign or malignant. Some specific entities such as JNA and meningioma showed distinctive diffusion characteristics.

Evaluation of Some Prognostic Biomarkers in Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma.

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExTMC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExTMC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProExTMC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExTMC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.

The role of histology on the outcome of sinonasal carcinomas treated with radiotherapy: a single institution experience.

PURPOSE: Sinonasal malignancies are a rare group of head and neck cancers. We aimed to report the oncological outcomes based on histological types in patients who underwent radiotherapy. MATERIALS AND METHODS: In this single-institution study, we retrospectively retrieved and analyzed data of patients with sinonasal carcinomas who underwent radiotherapy during 2011-2016 as part of their treatment. The 3-year rate of local, regional, and distant recurrences, and overall survival were evaluated according to the histological type. RESULTS: A total of 28 patients were evaluated in this study, the majority of whom were male (60%). Squamous cell carcinoma (SCC), adenoid cystic carcinoma (ACC), and adenocarcinoma (ADC) were found in 15 patients (53.5%), 8 (28.5%), and 5 (18%), respectively. The highest rates of local and regional recurrences were observed in ACC and SCC, respectively. Distant recurrences were numerically more common in ADC. The 3-year OS was 48%, 50%, and 73% in SCC, ADC, and ACC, respectively. CONCLUSION: Different histopathologies of sinonasal cancer seem to have different patterns of failure, and this may be considered in the treatment approach.

Clinical outcomes of sinonasal inverted papilloma: a retrospective analysis of 139 cases.

OBJECTIVES: Sinonasal inverted papilloma has a high tendency for recurrence, local bone destruction and risk of malignant transformation. Therefore, complete resection of the tumour is required, and close follow up is essential. This article describes the clinical outcomes, recurrence rate and malignant transformation rate of sinonasal inverted papilloma. METHODS: In this study, 139 patients diagnosed with sinonasal inverted papilloma in our hospital from December 2010 to May 2022 were retrospectively analysed. All patients underwent endoscopic surgery. RESULTS: Sinonasal inverted papilloma occurred more often in males than in females. The mean age of patients with sinonasal inverted papilloma was 67.3 ± 5.7 years at diagnosis. The most prevalent site of origin was the maxillary sinus (50.4 per cent). The recurrence rate was 5.75 per cent, and the malignant transformation rate was 6.5 per cent. CONCLUSION: All patients in this study underwent endoscopic surgery. Meticulous resection and regular long-term follow ups are crucial to reducing sinonasal inverted papilloma recurrence after surgery.

Characteristics of Extranodal NK/T-Cell Lymphoma, Nasal Type, Compared with Nasal Diffuse Large B-cell Lymphoma.

Background: Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an aggressive tumour with poor prognosis. Its early diagnosis may improve the prognosis of patients; however, it is often overlooked in many cases and misdiagnosed as an inflammatory sinus disease during its initial stage. Identifying the clinical characteristics of ENKL may aid otorhinolaryngologists in indicating cases early for a pathologic examination. In this study, we aimed to investigate the clinical characteristics of ENKL compared with that of diffuse large B-cell lymphoma (DLBCL), which is the most common nasal malignant lymphoma. Methods: The backgrounds, clinical symptoms, blood test results, and computed tomography images of patients with nasal/paranasal malignant lymphoma in our hospital between 2012 and 2017 were investigated. The characteristics of ENKL and nasal DLBCL were compared to differentiate them. Results: A total of 27 patients with nasal cavity and/or paranasal sinus lymphoma were included. Extranodal NK/T-cell lymphoma, nasal type, was diagnosed in 10 patients, while DLBCL was diagnosed in 17 patients. The median age of patients with ENKL was significantly lower than that of patients with DLBCL. All patients with ENKL had a unilateral lesion in the nasal cavity, with most located at the inferior turbinate. They also experienced nasal symptoms with significantly higher incidence of nasal obstruction and tendency of bleeding. Conclusion: ENKL was often unilateral and caused nasal obstruction, unlike DLBCL. Those who are younger in age and have sinonasal tumour with unilateral nasal obstruction and bleeding should be considered for early and repeated biopsies at multiple sites, with ENKL taken into consideration.