Outcome-oriented clinicopathological reappraisal of sinonasal adenoid cystic carcinoma with broad morphological spectrum and high MYB::NFIB prevalence.

Adenoid cystic carcinoma (AdCC) is a salivary gland neoplasm that infrequently appears in the sinonasal region. The aim of this study was to evaluate the outcome and clinicopathological parameters of sinonasal AdCC. A retrospective analysis was conducted on all cases of AdCC affecting the nasal cavity or paranasal sinuses between 2000 and 2018 at the University Hospital Zurich. Tumor material was examined for morphological features and analyzed for molecular alterations. A total of 14 patients were included. Mean age at presentation was 57.7 years. Sequencing revealed MYB::NFIB gene fusion in 11/12 analyzable cases. Poor prognostic factors were solid variant (p < 0.001), histopathological high-grade transformation (p < 0.001), and tumor involvement of the sphenoid sinus (p = 0.02). The median recurrence-free survival (RFS) and OS were 5.2 years and 11.3 years. The RFS rates at 1-, 5-, and 10-year were 100%, 53.8%, and 23.1%. The OS rates at 1-, 5-, and 10- years were 100%, 91.7%, and 62.9%, respectively. In Conclusion, the solid variant (solid portion > 30%), high-grade transformation, and sphenoid sinus involvement are negative prognostic factors for sinonasal AdCC. A high prevalence of MYB::NFIB gene fusion may help to correctly classify diagnostically challenging (e.g. metatypical) cases.

Sphenoid Sinus Fungal Ball and Reestablishing Sinus Function.

OBJECTIVES: The aim was to assess the developmental attributes of sphenoid sinuses affected by fungal balls and describe a surgical approach which reestablishes gravity-dependent drainage to compensate for any mucociliary dysfunction. METHODS: A within-patient case-control analysis was performed on sphenoid sinus dimensions from patients with sphenoid sinus fungal ball (SSFB). Radiological dimensions were assessed to determine the dominant or larger sinus by volume and width. Pneumatization in the sagittal and lateral extent was assessed. The influence of sinus size and pneumatization variants within a patient was analyzed. Patency and the presence of mucostasis from radical reshaping of the sinus cavity were documented at least 3 months after surgery. Complications (bleeding, cerebrospinal fluid leak, and cranial nerve palsy) were recorded. RESULTS: Twenty-three patients (59 ± 19 years, 86% female, 46 sphenoid sinuses) were assessed. Fungal ball was more common in the smaller (non-dominant) sinus, by width (78% vs. 22%, p < 0.01) and by proportion of total sphenoid volume (0.39 ± 0.16 vs. 0.61 ± 0.16, p < 0.01). Pneumatization variants did not influence the development of SSFB within a patient. All patients had patency and the absence of mucostasis or persistent inflammation at last follow-up. No complications were reported. CONCLUSION: The smaller or nondominant sphenoid sinus is more affected by SSFB. Surgical reshaping of the sphenoid to prevent mucostasis is favorable in managing the smaller affected sinus cavity. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Sinonasal mucosal melanoma treatment response assessment to immune checkpoint inhibitors using hybrid positron emission tomography imaging.

The purpose of this retrospective study was to investigate response of sinonasal mucosal melanoma (SMM) patients to treatment with immune checkpoint inhibitors (ICI), using hybrid PET imaging. Fifteen SMM patients underwent hybrid PET imaging before and three months after initiation of ICI. The disease-specific survival (DSS) was calculated. Quantitative PET parameters of the primary tumor and their association with DSS and therapy response were investigated. Nine of the fifteen (60%) patients responded to ICI therapy. Patients with therapy response depicted on hybrid PET imaging had better DSS than those without (p = 0.0058). Quantitative PET parameters of the initial PET harbored no association with DSS or therapy response. However, these findings lack of sufficient statistical power and must be interpreted with caution. The first restaging PET-imaging after ICI initiation can help stratify patients with regard to DSS.

Rhinologic outcome of endoscopic transnasal-transsphenoidal pituitary surgery: an institutional series, systematic review, and meta-analysis.

PURPOSE: We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery. METHODS: Retrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed. RESULTS: The institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher's exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0-2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1-3.0), a postoperative synechiae rate of 7.5% (IQR 1.8-19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5-5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting. CONCLUSION: Early and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care.

Reappraisal of Grading in Intestinal-Type Sinonasal Adenocarcinoma: Tumor Budding as an Independent Prognostic Parameter.

Since sinonasal intestinal-type adenocarcinomas (ITAC) show resemblance to colorectal adenocarcinomas, we aimed to investigate novel prognostic factors of outcome, with particular focus on the role of tumor budding (TB). Retrospective clinico-pathological single-institution study on consecutive ITAC patients between 1996 and 2020. Histopathological parameters including conventional subtypes and TB features (low, intermediate, high) were evaluated with the aid of pancytokeratin (AE1/AE3) immunohistochemical staining. Parameters were correlated to clinical data and outcome. A total of 31 ITAC patients were included. Overall, 19/31 patients (61.3%) presented with stage III/IV disease. Presence of lymph node or distant metastases was rare (1/31 patient, 3.2%). Treatment protocols consisted of tumor resection in 30/31 patients (96.8%) and primary radiochemotherapy in 1/31 patient (3.2%). Adjuvant radiation therapy was conducted in 20/30 surgically treated patients (66.7%). The 3- and 5-year overall survival (OS) was 83.9% and 78.3% and the 3- and 5-years disease-specific survival (DSS) 83.7% % and 78.5%, respectively. The presence of intermediate/high TB (defined as ≥ 5 buds) was associated with both, worse DSS (log rank p = 0.03) and OS (log rank p = 0.006). No patient with low TB revealed progressive disease or died of the disease. No association between TB and tumor stage or conventional tumor subtype was found. Tumor budding seems to be an independent prognostic factor of worse outcome in ITAC.

The Role of Regional Disease and Patterns of Treatment Failure in Primary Sinonasal Malignancies.

BACKGROUND: The question how to treat the clinically negative neck in sinonasal malignancies is controversial. OBJECTIVES: To investigate patterns of treatment failure and to assess outcome measures in patients with primary sinonasal malignancies. METHODS: Retrospective cohort study of patients treated for primary malignant sinonasal malignancies. RESULTS: Lymph node (LN) metastases at initial presentation were present in 8 of 152 patients (5.3%). Ipsi- and contralateral LN levels 1 and 2 were identified as nodal basins at risk. We found a 5-year overall survival (OS) of 75.2% and disease free survival of 61.1%. Among patients with cN0 neck, nodal recurrence free survival was not different between patients with and without elective neck treatment (P = .23). On logistic regression analysis, we found initial T classification as an independent factor for achievement of complete remission (CR) and OS. CONCLUSIONS: LN metastases at initial presentation are rare and initial T classification was identified as the most important prognostic factor for OS and CR, emphasizing the need for a thorough initial staging of the primary tumor.

Diagnostic pathway and stage migration of sinonasal malignancies in the era of the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic bears the risk of delayed cancer diagnoses. METHODS: Study on the diagnostic pathway of sinonasal malignancies during the COVID-19 pandemic. RESULTS: Median time from first symptom to treatment initiation was not increased during the pandemic: 137 days (interquartile range [IQR] 104-193) vs 139 days (IQR 103-219) (P = .60). Median time from first appointment at our institution to treatment initiation was even reduced in 2020: 18 days (IQR 11-25) vs 11 days (IQR 7-17) (P = .02). A trend toward advanced tumor stages during the pandemic was seen: 11/30 patients (36.7%) ≥ stage 4 in 2018 to 2019 vs 12/19 patients (63.2%) ≥ stage 4 in 2020 (P = .064). CONCLUSION: Both, time to diagnosis and time to treatment initiation were similar during the pandemic. However, a higher proportion of advanced tumors stages was observed. Despite the pandemic, we provided a swift diagnostic workflow, including a virtual tumor board decision and a prompt treatment initiation. Level of Evidence: 4.

Reduction of otorhinolaryngological consultations due to the COVID-19 lockdown and its impact on disease progression.

OBJECTIVES: To compare consultations at the Otorhinolaryngological Department at a tertiary referral centre between the COVID-19 lockdown in 2020 and the same period in 2019, as well as to study the impact of deferring visits on disease progression. METHODS: The emergency consultations during these time periods were analysed retrospectively. The effect of postponing appointments on disease progression was examined for 122 patients with chronic rhinosinusitis, for 50 patients with a benign tumour and for 22 patients with the diagnosis of a malignant tumour. To compare disease progression, patients with the diagnosis of a malignant tumour were matched to patients seen over the same period in 2019. RESULTS: During the lockdown, a reduction of 44.1% in emergency consultations compared with 2019 was observed. The largest significant decrease of consultation numbers was seen for otitis media and for Eustachian tube dysfunction. Fewer patients with tonsillitis sought emergency assistance; however, no difference in frequency of abscesses was observed. Disease progression was seen in 44.4% of patients with chronic rhinosinusitis. In 2020, 18.8% of patients with the diagnosis of a malignant tumour showed disease progression, yet no difference from the previous year was observed. CONCLUSION: Fewer emergency consultations took place during the COVID-19 lockdown; among others, there were fewer visits due to otitis media and tonsillitis. However, no change in the incidence of complications was noted. Almost 50% of patients with chronic rhinosinusitis showed disease progression, leading to prolonged suffering due to the rescheduling of appointments. The treatment of patients with the diagnosis of a malignant tumour was not affected by the postponement of consultations.

Whole-body hybrid positron emission tomography imaging yields clinically relevant information in the staging and restaging of sinonasal tumors.

BACKGROUND: Whole-body hybrid positron emission tomography (PET) imaging is increasingly used for sinonasal tumors. However, only empirical data exist on the additional, clinically relevant information derived from these techniques. METHODS: This study included 96 regionalized magnetic resonance imaging (MRI) of the sinonasal tract/neck and separate hybrid FDG-PET/CT or FDG-PET/MRI in 74 patients. Additional radiological information (ARI) obtained from each hybrid examination was analyzed and its clinically relevance was determined. Clinically relevant information (CRI) was categorized with regard to primary tumor site, regional lymph node metastases, distant metastases, second primary tumors, and non-neoplastic findings. RESULTS: A total of 45/96 (46.9%) hybrid PET examinations revealed ARI. CRI was found in 32/96 (33.3%) examinations and concerned the primary tumor site (6.1%), regional lymph node metastases (4.1%), distant metastases (14.3%), second primary tumors (7.3%), and non-neoplastic findings (5.1%). CONCLUSIONS: Hybrid PET imaging yields additional radiological information translating into clinically relevant information in a substantial proportion of patients with sinonasal tumors.

Need for long-term follow-up in sinonasal inverted papilloma: A Single-institution experience.

BACKGROUND: Most studies on sinonasal inverted papillomas (SNIPs) regarding risk factors for recurrence, recurrence rates (RRs) and malignant transformation are biased by a significant proportion of revision cases. METHODS: Retrospective study on patients with consecutive, treatment-naïve SNIPs at a tertiary referral center between 1999 and 2019. RESULTS: Overall, RR was 9.8% (10 of 102 patients), with 2 of 10 recurrences (20%) occurring after more than 5 years. Histopathological workup revealed synchronous malignancy in 2 of 102 patients (2%). Subgroup analysis revealed a significantly higher RR for SNIPs involving the frontal sinus (26.3% vs 6.0%, P = .02). No SNIPs primarily originating from the frontal sinus were observed. CONCLUSION: Overall, RR of treatment-naïve SNIPs is comparably low; however, long-term follow-up is mandatory due to late recurrences. Secondary involvement of the frontal sinus was identified as risk factor for recurrence. No SNIPs primarily originating from frontal sinus were observed.

Is Ethmoidal Air Cell Count Relevant in Chronic Rhinosinusitis?

OBJECTIVES/HYPOTHESIS: Studies analyzing the association between the total number of ethmoid cells (EC) and chronic rhinosinusitis (CRS) are missing. Our aim was to analyze the total number of EC in patients with and without CRS. STUDY DESIGN: Retrospective case-control study. METHODS: A total of 50 computed tomography (CT) scans of patients with CRS, 14 CT scans of patients with odontogenic CRS, and 50 CT scans of healthy controls were retrospectively analyzed. The number of EC has been determined for each side separately. RESULTS: In total 228 sides have been analyzed. The bilateral total EC count in both planes was more than 2 cells higher, when comparing CRS patients to healthy controls or odontogenic CRS patients (P < .01). No difference was observed, when comparing healthy and odontogenic CRS patients. CONCLUSION: The number of EC on CT of CRS patients is significantly higher than in both, the healthy and the odontogenic CRS control group. Cell count could contribute to the pathogenesis of CRS. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1212-1216, 2021.

Hybrid positron emission tomography imaging for initial staging of sinonasal tumors: Total lesion glycolysis as prognosticator of treatment response.

BACKGROUND: To assess hybrid positron emission tomography (PET) imaging in the initial staging and outcome prediction of sinonasal malignancies. METHODS: Retrospective study on patients with sinonasal malignancies undergoing hybrid PET imaging for initial staging. RESULTS: Complete remission (CR) was achieved in 45 of 65 patients (69.2%). Overall sensitivity for detection of primaries using 18F-fluoro-deoxy-d-glucose PET (FDG-PET) was 95.4%, for lymph node metastases 100% and distant metastases (DM) 100%. On univariate analysis, PET parameter total lesion glycolysis (TLG) was associated with achieving CR after primary treatment (176.8 ± 157.2 vs 83.7 ± 110.8, P = .03). Multivariate logistic regression demonstrated that TLG adjusted for the T classification best predicted achievement of CR. CONCLUSIONS: Hybrid PET imaging yields an excellent sensitivity in detecting primary tumors, lymph node metastases and DM in sinonasal malignancies. TLG of the primary tumor is an independent prognostic factor for achieving CR after initial treatment.

Surgery as Single-Modality Treatment for Early-Stage Olfactory Neuroblastoma: An Institutional Experience, Systematic Review and Meta-analysis.

BACKGROUND: For olfactory neuroblastoma (ONB), the combination of surgical tumor resection and radiation therapy (RT) has been considered the "gold standard" in treatment protocols intended to cure. OBJECTIVE: To summarize evidence on the treatment of ONB using surgery alone. METHODS: A retrospective institutional case series, a systematic review of the literature, and an individual patient data (IPD) meta-analysis on only surgically treated ONB patients. RESULTS: At our institution, a total of 10 patients were treated through surgery alone and remained alive and free of disease at last follow-up. The IPD meta-analysis on 128 patients revealed a disease-free survival (DFS) and overall survival (OS) of 67.7% and 75.4% at 5 years and 57.1% and 71.9% at 10 years, respectively. Univariate analysis showed that Kadish stage C/D and Hyams grading III//IV significantly affected OS (P = 0.000 and P = 0.000) and DFS (P = 0.000 and P = 0.002). For low-risk patients, the DFS was 80.6% at 5 years and 67.8% at 10 years, respectively. CONCLUSIONS: Surgery alone is an equivalent alternative to combined treatment in carefully selected low-risk ONB patients with better outcome measures than previously reported.

Diagnostic accuracy of computed tomography and magnetic resonance imaging compared to surgical exploration for anterior skull base and medial orbital wall infiltration in advanced sinonasal tumors.

BACKGROUND: Knowledge of medial orbital wall (MOW) and anterior skull base (ASB) infiltration is of uttermost importance for staging and therapy planning of advanced sinonasal tumors. METHODS: We assessed the diagnostic performance of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) for MOW and ASB infiltration compared to intraoperative exploration. RESULTS: Both CT and MRI yielded higher diagnostic accuracy for MOW infiltration (Reader 1: 83.6% CT; 89.0% MRI, Reader 2: 91.8% CT, 93.2% MRI) than for ASB infiltration (Reader 1: 82.2% CT, 82.2% MRI, Reader 2: 67.7% CT, 67.7% MRI). Both modalities were equal to the gold standard, except for ASB assessment by Reader 2 with MRI. A postoperative change of T classification is common (Reader 1: 28.8%, Reader 2: 31.5%). CONCLUSIONS: CT and MRI are accurate methods for the assessment of MOW infiltration. ASB assessment is challenging and false-positive and false-negative findings are common with both methods, emphasizing the need for intraoperative exploration.

The Monocle Sign in FDG-PET: A Sign of Contralateral Facial Nerve Palsy.

We report three cases of unilateral F-FDG uptake in the orbicularis oculi muscle in subjects with contralateral peripheral facial nerve palsy. We argue that this asymmetric uptake pattern in fact reflects lack of metabolism on the side affected by facial nerve palsy, owing to denervation. Since the unilateral periorbital uptake resembles a monocle, we chose to call this finding the monocle sign. The monocle sign should not be confused with inflammation or tumor, but should prompt a neurological assessment for facial nerve palsy and a potential underlying disease.

Current concepts in advanced sinonasal mucosal melanoma: a single institution experience.

PURPOSE: To present outcome measures of sinonasal mucosal melanoma (SMM) patients with particular focus on current radiological and therapeutic options, especially in the non-curative setting (immunotherapy). METHODS: Retrospective study on SMM patients treated at our institution between January 1992 and December 2018. RESULTS: FDG-PET/MRI has emerged as the new hybrid imaging modality, addressing the need for high local tissue contrast in the paranasal sinuses and the skull base, while allowing for whole-body staging in search for distant metastases, including the brain. Primary treatment protocols consisted of tumor resection in 30/34 patients (88%), palliative radiation therapy (RT) in 3/34 patients (9%) and best supportive care therapy in 1/34 patient (3%). Of all the initially operated patients, 25/30 patients (83%) received adjuvant RT. A total of 9/34 patients (26%) was treated with immunotherapy after the previous combined therapy. For patients treated in curative intention, we observed a 1-year overall survival (OS) of 60% (18/30 patients) and a 3-year OS of 40% (12/30 patients). For patients treated with immunotherapy, median progression-free survival (PFS) was 5 months (IQR 0-13.75), with a maximum PFS of 16 months (combination of nivolumab and ipilimumab). However, there was no difference in OS in patients treated with immunotherapy vs. no immunotherapy (log rank 0.99). CONCLUSIONS: Sinonasal mucosal melanoma is a highly aggressive tumor, requiring multimodal therapy and developing a substantial incidence of distant metastases. The introduction of FDG-PET/MRI offers new possibilities in the radiological assessment of the tumor and immunotherapy has altered the management in the non-curative setting, resulting in a substantial progression-free survival in selected cases.

Use of MRI and FDG-PET/CT to predict fixation of advanced hypopharyngeal squamous cell carcinoma to prevertebral space.

BACKGROUND: We evaluated the ability of different (18F)fluoro-deoxy-d-glucose (FDG)-positron emission tomography (PET)-based and magnetic resonance (MR)-based parameters to identify prevertebral space (PVS) infiltration by hypopharyngeal carcinoma. METHODS: Retrospective study on 59 patients with advanced hypopharyngeal squamous cell carcinoma undergoing cross-sectional imaging and triple endoscopy for staging. RESULTS: Obliteration of retropharyngeal fat plane on T1-weighted MR images was found more often (P < .001) in tumors fixated to the PVS. Complete fat plane obliteration best predicted tumor fixation to PVS (accuracy 99%; CI: 97%-100%; P < .001). With similar accuracy, PET-based models predicted PVS fixation (combination of standardized uptake value [SUVmax ] of the primary tumor and presence of focal FDG-uptake in prevertebral muscles [accuracy 98%; CI 94%-100%; P < .001]; metabolic tumor volume [MTV] [accuracy 98%; CI 95%-100%; P < .001]). CONCLUSION: Both the MR-based parameter of complete fat plane obliteration and PET-based models (increased SUVmax in combination with presence of focal FDG-uptake of prevertebral muscles; increased MTV) predict PVS involvement independently with high accuracy.