BACKGROUND: In the management of sinonasal malignancies treatment-induced morbidity and mortality is gaining relevance both for surgical approaches (endoscopic and open resection) and non-surgical therapies. The aim of this multicenter study is to assess complications associated with endoscopic surgery and non-surgical treatments (neoadjuvant and/or adjuvant) for malignant sinonasal tumors.
METHODS: All patients with nasoethmoidal malignancies treated with curative intent with endoscopic or endoscopic-assisted surgery at three referral centers with uniform management policies were included. Neo- and/or adjuvant (chemo)radiotherapy was administered according to histology and pathological report. Demographics, treatment characteristics, and complications related both to the surgical and non-surgical approaches were retrieved. The data were analyzed with univariate and multivariate statistics to assess independent predictors of complications.
RESULTS: Nine hundred and forty patients were included, 643 males (68%) and 297 females (32%). A total of 225 complications were identified in 187 patients (19.9%): cerebrospinal fluid (CSF) leak (3.5%), mucocele (2.3%), surgical site bleeding (2.0%), epiphora (2.0%), and radionecrosis (2.0%) were the most common. Treatment-related mortality was 0.4%. Variables independently associated with complications at multivariate analysis were principally dural resection (OR 1.92), cranioendoscopic or multiportal resection (OR 2.93), dural repair with multilayer technique with less than three layers (OR 2.17), and graft different from iliotibial tract (OR 3.29).
CONCLUSIONS: Our study shows that modern endoscopic treatments and radiotherapy for sinonasal malignancies are associated with limited morbidity and treatment-related mortality. CSF leak and radionecrosis, although rare, remain the most frequent complications and should be further addressed by future research efforts.

OBJECTIVE: The purpose of this review is to analyze the diagnosis and treatments of the sinonasal malignant tumors throw systematic reviewed literature. The systematic review of the literature was performed according to PRISMA guidelines.
RESULTS: Total 11,653 cases of five article were analyzed. The cohort of 3824 cases received appropriate treatment. The most frequent histotype of the group of sinonasal malignancies was squamous cell carcinoma. Squamous cell carcinoma was represented by 54%. The other histopathological subtypes were esthesioneuroblastoma with 9,9%, melanoma 9,8%, adenocarcinoma 7,5%, sarcoma 7,3%, adeno cystic carcinoma 7,1%, sinonasal undifferentiated carcinoma 3,9%, sinonasal neuroendocrine carcinoma 2,8% respectively. All 772 cases of total 3824 were treated only surgically. All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT. The other 2990 cases of total 3824 were treated with multimodality treatment. The diagnosis and treatment of sinonasal cancers require a interdisciplinary approach and multimodality treatment.

BACKGROUND: Sinonasal malignancies (SNMs) frequently present with orbital invasion. Orbital exenteration (OE) can lead to significant morbidity. Induction chemotherapy (IC) is a promising treatment alternative that may allow for orbit preserving (OP) treatments without compromising patient survival. This systematic review was conducted to synthesize the published data on SNM patients with orbital invasion who underwent IC, including tumor response, orbital outcomes, and survival.
METHODS: The study protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Databases Embase, Cochrane, Medline, and Scopus, from inception to July 17, 2023, were searched.
RESULTS: Nineteen studies were included, encompassing 305 SNM patients with orbital invasion treated with IC. Fourteen studies reported an overall IC response rate (positive response defined as complete or partial tumor volume reduction) of 77.2%. Among included studies, OE rates after IC ranged from 0 to 40%. Three studies reported a high rate of posttreatment functional orbital preservation (89.8-96.0%). Five studies specifically reported that 62.5% (60 out of 96) of patients were downgraded from planned OE to OP treatment following IC. Three studies reported a significant overall survival (OS) improvement in IC responders versus IC nonresponders. Following IC, 5-year OS ranged from 44.2 to 55.5%. Patients with olfactory neuroblastoma demonstrated the highest IC response rate and lowest OE rate (100 and 0%, respectively) versus those with sinonasal undifferentiated carcinomas (68.4 and 0%) or squamous cell carcinomas (76.7 and 16%).
CONCLUSIONS: For select patients, IC may allow for OP in locally advanced SNMs with orbital involvement.

UNASSIGNED: Our study aims to determine the incidence and potential risk factors for cerebral radiation necrosis (CRN) following treatment of sinonasal malignancies.
UNASSIGNED: One hundred thirty-two patients diagnosed with sinonasal malignancies over an 18-year period were identified at two institutions. Forty-six patients meeting inclusion criteria and treated with radiation therapy were included for analysis. Demographic and clinical-pathologic characteristics were collected and reviewed. Post-treatment magnetic resonance imaging (MRI) at least 1 year following treatment was reviewed to determine presence or absence of CRN.
UNASSIGNED: CRN was identified on MRI in 8 of 46 patients (17.4%) following radiation treatment. Patients with a history of reirradiation were more likely to develop CRN (50% vs. 10.5%, p < .05). The BEDs of radiation were also higher in CRN patients compared to non-CRN patients, but this difference was not significant (p > .05). CRN patients had a higher proportion of tumors with skull base involvement than non-CRN patients (100% vs. 57.9%, p = .037). Demographics, comorbidities, pathology, primary tumor subsite, chemotherapy use, and stage of disease demonstrated no significant increase in risk of CRN.
UNASSIGNED: Reirradiation and tumor skull base involvement were significant risk factors associated with CRN. Higher average total prescribed and BEDs of radiation were seen in the CRN groups, but these differences were not statistically significant. Gender, comorbidities, tumor subsite, tumor location, and treatment type were not significantly different between groups.
UNASSIGNED: Level 3.

Objective  Our objective was to compare the long-term outcomes of endoscopic resection versus open surgery in combination with radiotherapy for locally advanced sinonasal malignancies (SNMs). Methods  Data for continuous patients with sinonasal squamous cell carcinoma and adenocarcinoma who received surgery (endoscopic or open surgery) combined with radiotherapy in our center between January 1999 and December 2016 were retrospectively reviewed. A 1:1 matching with propensity scores was performed. Overall survival (OS), progression-free survival (PFS), and local recurrence rate (LRR) were evaluated. Results  We identified 267 eligible patients, 90 of whom were included after matching: 45 patients in the endoscopy group and 45 in the open group. The median follow-up time was 87 months. In the endoscopic group, 84.4% of patients received intensity-modulated radiotherapy (IMRT), with a mean gross tumor volume (GTV) dose of 68.28 Gy; in the open surgery group, 64.4% of patients received IMRT, with a mean GTV dose of 64 Gy. The 5-year OS, PFS, and LRR were 69.9, 58.6, and 24.5% in the endoscopic group and 64.6, 54.4, and 31.8% in the open surgery group, respectively. Multivariable regression analysis revealed that the surgical approach was not associated with lower OS, PFS, or LRR. The overall postoperative complications were 13% in the endoscopic group, while 21.7% in the open group. Conclusion  For patients with locally advanced SNMs, minimally invasive endoscopic resection, in combination with a higher radiation dose and new radiation techniques such as IMRT, yields survival outcomes similar to those of open surgery in combination with radiotherapy.

UNASSIGNED: Nuclear protein in testis (NUT) carcinoma (NC) is a rare, aggressive tumor with a typical NUTM1 gene rearrangement.
UNASSIGNED: Herein, we report a series of 2 cases of sinonasal NC: one in a 16-year-old woman and one in a 37-year-old man. Immunohistochemistry (IHC) staining for NUT (C52B1), fluorescence in situ hybridization (FISH), and next generation sequencing (NGS) sequencing were performed to investigate the morphological and genetic features of sinonasal NC.
UNASSIGNED: The two cases presented similar pathological features and IHC markers, and typical morphological changes, including undifferentiated cells and abrupt keratinization, were observed, with numerous mitotic figures and widespread tumor necrosis. Diffuse expression of NUT, CK, p63, and p40 was noted, while the tumors were negative for synaptophysin, chromogranin A, S-100, EBV-ISH, and PD-L1. Both tumors harbored a NUTM1 rearrangement. Subsequent sequencing revealed a rare BRD3::NUTM1 fusion and a classic BRD4::NUTM1 fusion. In addition, MCL1 copy number gain (2.1), low tumor mutation burden and stable microsatellites, were also confirmed. Case 1 received surgery and chemoradiotherapy but died 13 months after local recurrence and subsequent lung and bone metastasis. Case 2 underwent chemoradiotherapy and unfortunately died from the disease 6 months later. A review of all previously reported cases of sinonasal NCs (n=55) revealed that these tumors occur more frequently in female pediatric patients (n=11, male: female =3:8), whereas this sex difference is not observed in adult patients (n=44, male: female =23:21). The median survival times of pediatric and adult patients were 17 and 13.8 months, respectively.
UNASSIGNED: Sinonasal NC presents typical undifferentiated or poorly differentiated cells, abrupt keratinization features and heterogeneous genotypes, including BRD4::NUTM1 and BRD3::NUTM1 fusions, with low tumor mutation burden and stable microsatellites.

Introduction  Radiation-induced hypopituitarism (RIH) has long been recognized as one of the deleterious side effects of skull base radiation. This study aims to assess the quality of life (QoL) among patients with RIH compared with radiated patients who did not develop hypopituitarism using the validated Anterior Skull Base Questionnaire (ASBQ). Methods  This was a single-institution retrospective cohort study. Included patients had a history of anterior skull base tumor, underwent at least one round of radiation to the skull base, and had filled out at least one ASBQ survey after their radiation treatment. Three statistical models were used to determine the effect of hypopituitarism and treatment on QoL scores. Results  A total of 145 patients met inclusion criteria, and 330 ASBQ surveys were analyzed. Thirty-five percent (51/145) had evidence of RIH at some point after their radiation treatment. Those with hypopituitarism had significantly lower overall ASBQ scores across all three models even after adjusting for potential confounders and intraperson correlation (average decrease of 0.24-0.45 on a 5-point Likert scale; p -values ranging from 0.0004 to 0.018). The increase in QoL with hormonal replacement was modulated by time out from radiation, with long-term survivors (5+ years out from radiation) gaining the most benefit from treatment (increase of 0.89 on a 5-point Likert scale, p 0.0412), especially in the vitality domain. Conclusion  This data demonstrates that hypopituitarism is an independent predictor of lower QoL. Early detection and appropriate treatment are essential to avoid the negative impact of hypopituitarism on QoL.

OBJECTIVE: To analyze the failure patterns in patients with different histological subtypes of sinonasal malignancies (SNMs).
METHODS: Retrospectively gathered data.
METHODS: Academic university hospital.
METHODS: Patients with SNMs treated at a tertiary referral center between January 1999 and January 2019 were included. We assessed the failure patterns within different histological subtypes.
RESULTS: The study included 897 patients. The median follow-up time was 100 months. Adenoid cystic carcinoma (ACC) had a moderate risk of developing local recurrence (LR) and distant metastasis (DM). Compared with ACC, squamous cell carcinoma (SCC), adenocarcinoma (AC), soft tissue sarcoma (STS), and mucosal melanoma (MM) were classified as a high LR risk group. For DM, neuroendocrine carcinoma (NEC), STS, and MM were in the high-risk group.
CONCLUSIONS: ACC had intermediate local and distant failure risks, while SCC, AC, STS, and MM were at high LR risks. NEC, STS, and MM were at high DM risk.

Purpose: The main purpose of this study is to understand the characteristics and management of sinonasal small round blue cell tumors and also to emphasise the role of immunohistochemistry in their diagnosis and on the outcomes after endoscopic/open excision in these patients. Methods: This is a retrospective study conducted at a tertiary care referral centre in India which included 38 patients with sino nasal for a period of 5 years. All the patients were evaluated clinically and radiologically. All cases were confirmed diagnostically with histopathological examination and immunohistochemistry following surgical excision either by endoscopic or open approach. Some of the cases underwent post operative radiotherapy. Results: In our study, among 176 cases diagnosed with Sino nasal malignancies, 38 (21.6%) cases were diagnosed with sinonasal small round blue cell tumors with male to female ratio 1.4:1. Most common histopathological type among all the sinonasal small round blue cell tumors that presented to us was esthesioneuroblastoma i.e., 8 (21%) patients followed by pituitary macroadenoma in 7(8.4%) patients. Other types are undifferentiated squamous cell carcinoma 10(13.1%), craniopharyngioma 8(10.5%), lymphoma 3(7.9%), synovial/spindle cell sarcoma, malignant melanoma and adenocarcinoma 1(2.6%) each. Schwannoma, rhabdomyosarcoma, neuroendocrine carcinoma and neurofibroma 2 (5.2%) each. Conclusion: Sinonasal small round blue cell tumors are extremely rare tumours. Histopathological diagnosis with immunohistochemistry is characteristic of various tumors and is conclusive for diagnosis. Knowledge of these tumor entity is essential as early diagnosis helps in further management in preventing spread to vital structures and improving outcome. Most of the tumors have a multimodality treatment approach which includes surgical excision, radiotherapy and chemotherapy.

Diffusion of endoscopic techniques for the resection of ethmoid bone malignancies through a transcribriform approach (TA) has raised new challenges regarding reconstruction options to reduce post-operative complications. Although there is consensus on the advantages of vascularized flaps over free grafts for large defects, no standard protocol exists on reconstruction procedures. In addition, although the pedicled nasoseptal flap has been extensively discussed, few studies have been published on extranasal pedicled flaps. The aim of this manuscript is to provide a detailed description of a reconstruction technique for large anterior skull base defects with the pericranial flap as part of a multilayered reconstruction. Moreover, patients treated with this approach were retrospectively assessed for post-operative complications.
A detailed description of the reconstruction procedure as performed in our departments is provided. Pictures depicting the main surgical steps are also included. In addition, preliminary functional results from a retrospective series of patients who underwent a TA and subsequent pericranial flap-based multilayer reconstruction for ethmoid roof malignancies between 2016 and 2022 at two institutional centers are reported.
16 patients were included in the study. Nine patients (56.3%) underwent adjuvant radiotherapy. Two patients had a biochemically-confirmed postoperative CSF leak. Only one of the two patients required surgical revision. During follow-up (mean 13 months), no other early nor delayed complications were observed.
A standardized surgical technique with pericranial flap as part of a multilayered reconstruction for large anterior skull base defects following resection of sinonasal malignancies is proposed, which appears to be a safe choice when endonasal flaps are not available.
Level 4 Laryngoscope, 133:2942-2947, 2023.