Sinonasal Malignancies Research Articles

Choice of surgery in intestinal-type adenocarcinoma of the sinonasal tract: a long-term comparative study.

Intestinal-type adenocarcinoma (ITAC) is a rare sinonasal malignancy. Curative treatment requires multidisciplinary approach, with surgical options consist of the endonasal endoscopic approach (EEA) and external surgery (EXTS). Here, we provide the post-operative and survival results from a single-center long-term follow-up. We report long-term follow-up of 92 ITAC cases treated between 1998 and 2018, treated with EEA (n = 40) or EXTS (n = 52). Survival estimates, post-operative complications and duration of hospitalization were compared between surgical modalities. Baseline characteristics were similar. A higher number of T4b tumors (16%), and subsequently more tumoral invasion (39%), was present in patients undergoing EXTS compared to EEA (3% and 18%, respectively). No difference in Barnes histology subtypes was noticed. Patients undergoing EEA had a shorter post-operative hospitalization stay versus EXTS (4 versus 7days). Use of EEA was associated to improved disease-specific survival (DSS; 11.4 versus 4.4years; HREEA = 0.53), especially for patients with T3-4a tumors (11.4 versus 3.0years; HREEA = 0.41). Patients with T3-4 stage, tumoral invasion, positive surgical margins, mucinous or mixed histology, and prolonged post-operative hospital stay showed poor local relapse-free, disease-free, overall, and DSS. Long-term follow-up in locally advanced ITAC demonstrates that resection by EEA is correlated with improved DSS compared to EXTS, especially for T3-4 tumors. No significant differences between both treatment modalities was observed regarding per- and post-operative complications, although hospitalization in patients undergoing EEA was shorter than for patients treated with EXTS. These results confirm that EEA should remain the preferred surgical procedure in operable cases of sinonasal ITAC.

Sinonasal malignant melanoma- Diagnostically hidden Gem

Malignant melanoma is a prevalent form of skin cancer, but its occurrence as a sinonasal tumour is exceptionally uncommon, constituting less than 1% of nasal and sinonasal malignancies. Typically diagnosed in individuals aged 50 to 60, these tumours often manifest with symptoms such as nasal obstruction and recurrent, painless epistaxis. Despite their location, malignant melanoma cases generally have a bleak prognosis. Diagnosis primarily relies on Immunohistochemistry and histopathology.

Skull Base Reconstruction by Subsite after Sinonasal Malignancy Resection.

Reconstruction after the resection of sinonasal malignancies is complex and primarily dependent on the defect size and location. While the reconstructive paradigm for sellar mass resection is well delineated, the challenges associated with reconstruction after sinonasal malignancy resection are less well described. This narrative review will address the goals of reconstruction after both endonasal endoscopic and open sinonasal malignancy resection and reconstructive options specific to these subsites. The goals of reconstruction include repairing cerebrospinal fluid leaks, restoring sinonasal function, providing a nasal airway, and optimizing the patient's quality of life. These goals are often complicated by the anatomic nuances of each involved sinus. In this review, we will discuss the methods of reconstruction specific to each sinonasal subsite and describe the factors that guide choosing the optimal reconstructive technique.

Treatment and related morbidity of nasal cavity and paranasal sinus cancers.

Sinonasal malignancies are rare and histologically heterogeneous cancers of the nasal cavity and sinuses. The treatment of choice is usually surgery and, if necessary, adjuvant radiotherapy. In this study, we aimed to investigate treatment modalities and associated morbidity. A consecutive case series of solid sinonasal cancer treated at our tertiary referral center was analyzed. We performed a retrospective chart review and statistical analysis. A total of 156 patients with sinonasal cancer were enrolled in the present study. Male patients were more frequently affected (62%) and the median age was 64 years. Squamous cell carcinoma, adenocarcinoma and malignant melanoma (MM) were the most common histopathological entities. Surgery was the primary treatment modality for 73% of curatively treated patients. Primary radiotherapy alone or in combination with systemic treatment was less frequent. Median overall (OS) and recurrence-free survival (RFS) was 164 months and 71.3 months, respectively. Multivariate analysis revealed negative associations of histology (MM) and skull base involvement on RFS and age, skull base involvement and the type of primary therapy (radiochemotherapy) on OS. Postoperative 30-day morbidity was low, with most patients (84%) experiencing no reported events. Radiotherapy was generally well-tolerated, despite most of patients experienced acute toxicity such as dermatitis (80.6%) or mucositis (72.1%). However, only one event of acute toxicity > grade 3 was reported. Long term morbidity was most frequently reported as pain (23%), dry mucosa (19%) and anosmia (14%). We observed negative associations of histology (MM) and skull base involvement on RFS and age, skull base involvement and the type of primary therapy (radiochemotherapy) on OS. Acute treatment-related morbidity was generally low for surgical patients and considerable for irradiated patients. Moreover, a consistent part of the cohort displayed long term morbidity.

Dural reconstruction with or without a bone graft of paranasal and anterior skullbase malignancies: Retrospective single-center analysis of 11 cases and review of literature

IntroductionThe reconstruction of frontobasal defects following oncologic resections of paranasal and anterior skull base (ASB) malignancies remains challenging. Ineffective reconstruction could lead to cerebrospinal fluid leak, meningitis, and tension pneumocephalus. Research questionAim of this investigation was to analyse postoperative complication rates with or without bone graft for anterior skull base reconstruction. Material and methodsIn this retrospective study, we included patients following resection of paranasal and/or anterior skull base malignancies between October 2013 and December 2022. Complications were analysed with regards to the type of skull base reconstruction. ResultsEleven patients were identified (2 female, 9 male, age (median, SD) 64 ± 14.1 years (range 38–81). There were nine cases of paranasal sinus and nasal cavity carcinomas and two cases of olfactory neuroblastomas. Overall survival was 22.5 ± 28 months (range: 5–78), progression free survival was 17.0 ± 20.3 months (range: 11–78). Bone skull base reconstruction using a split graft was performed in three cases. Postoperative complications requiring surgical intervention were seen in 33% (one tension pneumocephalus) of cases in the bone reconstruction group and 50% (three patients with cerebrospinal fluid leak, one infection) in the non-bone reconstruction group. Discussion and conclusionThe structural reinforcement of structural bone chip grafting might provide additional support of the ASB and prevent CSF leakage or encephalocele. Especially in large (>10 cm2) bone defects of advanced sinonasal malignancies extending into the middle cranial fossa, the full armamentarium of reconstruction possibilities should be considered.

Diagnosis and therapy of sinonasal mucosal melanoma

Sinonasal mucosal melanoma (SNMM) is a rare and aggressive disease representing only 4% of all sinonasal malignancies and 1.4% of all melanomas. With an incidence of approximately 0.2 to 2 cases per million, the disease represents a very rare cancer type. As a result, there is a lack of data and most of the evidence for this highly aggressive disease is based on retrospective observations and analyses. The standard of care is radical tumor resection followed by an adjuvant radiotherapy. Nevertheless, the rate of local recurrence is high, up to 50%. In addition, the majority of patients (up to 70%) develop distant metastases during the course of their disease. Both contribute to the extremely poor prognosis of the disease. Mucosal melanomas (SM) and cutaneous melanomas (CM) behave differently with respect to biology, clinic presentation and prognosis. Compared to CM, survival rates are significantly lower for SM. The 5-year survival rate is around 25% in SNMM but 39-97% in cutaneous melanoma. Similar to CM, immune checkpoint inhibitors achieve promising results in SM. However, response rates are lower in SM compared to CM. The goal of this CME article is to provide an overview on biology, diagnosis, therapy, and prognosis of SNMM.

Validation of the "Rome" Classification for Squamous Cell Carcinoma of the Nasal Vestibule.

Squamous cell carcinoma of the nasal vestibule is considered a rare malignancy that differs from other sinonasal malignancies in many respects. Four staging systems currently exist for this disease, the most recent addition being the "Rome" classification. This study assesses the use of this new classification and its prognostic value regarding various outcome measures. A retrospective multicenter cohort study of patients with a primary squamous cell carcinoma of the nasal vestibule who were treated in three tertiary head and neck oncology referral centers was conducted. A total of 149 patients were included. The median follow-up duration was 27 months. Five-year locoregional control (LRC), disease-specific survival (DSS), and overall survival (OS) were 81.6%, 90.1, and 62.5% respectively. A statistically significant association was observed between the Rome classification and all survival outcomes in both univariable and multivariable analyses. Moreover, it appeared to perform better than the Union for International Cancer Control TNM classification for tumors of the nasal cavity and paranasal sinuses. The new Rome classification can be used effectively and is associated with LRC, DSS, and OS. However, it requires further validation in a larger (prospective) study population.

SMARCB1-deficient sinonasal adenocarcinoma: a rare variant of SWI/SNF-deficient malignancy often misclassified as high-grade non-intestinal-type sinonasal adenocarcinoma or myoepithelial carcinoma

SMARCB1-deficient sinonasal adenocarcinoma is a rare variant of SWI/SNF-deficient malignancies with SMARCB1 loss and adenocarcinoma features. More than 200 high-grade epithelial sinonasal malignancies were retrieved. A total of 14 cases exhibited complete SMARCB1 (INI1) loss and glandular differentiation. SMARCA2 and SMARCA4 were normal, except for one case with a loss of SMARCA2. Next-generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) revealed an alteration in the SMARCB1 gene in 9/13 cases, while 2/13 were negative. Two tumors harbored SMARCB1 mutations in c.157C > T p.(Arg53Ter) and c.842G > A p.(Trp281Ter). One harbored ARID1B mutations in c.1469G > A p.(Trp490Ter) and MGA c.3724C > T p.(Arg1242Ter). Seven tumors had a SMARCB1 deletion. One carried an ESR1 mutation in c.644-2A > T, and another carried a POLE mutation in c.352_374del p.(Ser118GlyfsTer78). One case had a PAX3 mutation in c.44del p.(Gly15AlafsTer95). Histomorphology of SMARCB1-deficient adenocarcinoma was oncocytoid/rhabdoid and glandular, solid, or trabecular in 9/14 cases. Two had basaloid/blue cytoplasm and one showed focal signet ring cells. Yolk sac tumor-like differentiation with Schiller-Duval-like bodies was seen in 6/14 cases, with 2 cases showing exclusively reticular-microcystic yolk sac pattern. Follow-up of a maximum of 26 months (median 10 months) was available for 8/14 patients. Distant metastasis to the lung, liver, mediastinum, bone, and/or retroperitoneum was seen in 4/8 cases. Locoregional failure was seen in 75% of patients, with 6/8 local recurrences and 3 cervical lymph node metastases. At the last follow-up, 5 of 8 (62%) patients had died of their disease 2 to 20 months after diagnosis (median 8.2 months), and 3 were alive with the disease. The original diagnosis was usually high-grade non-intestinal-type adenocarcinoma or high-grade myoepithelial carcinoma. A correct diagnosis of these aggressive tumors could lead to improved targeted therapies with potentially better overall disease-specific survival.

Utility of hospital frailty risk score in predicting postoperative outcomes of sinonasal malignancies.

Hospital frailty risk score (HFRS) correlates with complications, length of stay, and non-routine discharge. HFRS is a better predictor of postsurgical sequelae than age and Elixhauser comorbidity index.

Comment on “Survival Outcomes in Different Sino-nasal Malignancies: An Institutional Review,” Authored by Umesh Preetha et al.

Comment on “Survival Outcomes in Different Sino-nasal Malignancies: An Institutional Review,” Authored by Umesh Preetha et al.

Association of Complication Rates and Intensive Care Unit Use With Sinonasal and Skull Base Malignancies: A Propensity Score Matching Analysis.

Background: Patients with sinonasal and skull base malignancies experience many types of complications after surgery. The intensive care unit (ICU) provides a high level of care for these patients; however, the effect of ICU care on complication rates remains unclear. Methods: Between November 2014 and November 2022, we retrospectively analyzed 151 patients with sinonasal and skull base malignancies. Fifty-six of these patients were admitted to the ICU and 95 were admitted to the non-ICU after surgery. Propensity score matching (PSM) was performed to balance baseline characteristics. The complication rates of the ICU and non-ICU groups were compared. Results: Before PSM, the complication rate was 28.5%. Patients admitted to the ICU had a higher incidence of medical complications (P = .032). Orbital injury (n = 9) and diplopia or visual changes (n = 9) were the most common surgical complications, whereas respiratory tract infections (n = 7) were the most common medical complications. After PSM, the incidences of surgical, medical, and all complications in the ICU and non-ICU groups were 23.8% and 19.0% (P = .791), 16.7% and 9.5% (P = .520), and 38.1% and 26.2% (P = .350), respectively. Conclusions: This preliminary study revealed that ICU admission did not reduce the complication rate of patients with sinonasal and skull base malignancies. Further studies are required to validate these findings and clarify the potential role of the ICU.

Case Report: Cytodiagnosis of primitive neuroectodermal tumor (PNET) of sinonasal tract

Malignant sinonasal tumors are rarely encountered in the practice of oncology as they constitute only 1% of total body tumors. The occurrence of primitive neuroectodermal tumor (PNET) in the sinonasal tract is even more uncommon. The PNET belongs to Ewing sarcoma family and forms the differential diagnosis of a large group of lesions generally described as malignant round cell tumors. The unique pathogenetic chromosomal alteration in this lesion is the EWS FLI1 fusion gene. This case report describes the unusual occurrence of PNET for its cytomorphological diagnosis along with its clinical features, radioimaging findings and immunohistochemistry. Such case reports are scarce in literature and cytodiagnosis of PNET in sinonasal tracts warrants its sharing with medical fraternity as such diagnoses are stumbled along rarely in clinical practice.

Intracranial Anatomy and Surgical Techniques for Extended Orbital Exenteration for Sinonasal Malignancy with Orbital Apex Extension

Gross total tumor resection for sinonasal malignancy with orbital apex extension requires orbital exenteration and bony skull base resection around the orbital apex with sufficient margins. With a detailed discussion of the anatomy, we describe our surgical procedure for extended orbital exenteration with orbital apex resection for sinonasal malignancy.

Combined Photon and Carbon Ion Radiation Therapy for Sinonasal Malignancies: Results of the HIT–SNT Prospective Phase 2 Trial

Radiation treatment of sinonasal malignancies is a challenging task due to proximity to critical structures of the head and neck and skull base. Local tumor control is highly dose-dependent, but dose application is limited due to accompanying toxicity and dose constraints. To evaluate the toxicity and efficacy of combined radiation treatment with intensity-modulated radiation therapy (IMRT) and carbon ion boost, we conducted a prospective phase 2 IMRT-Heidelberg Ion-Beam Therapy Sinonasal Tumors (HIT-SNT) trial. Between 2011 and 2019, we treated 35 patients with histologically proven, incompletely resected or inoperable adeno- (51%) or squamous cell carcinoma (49%) of the paranasal sinuses with combined IMRT (50 Gy) and carbon ion boost (24 Gy relative biologic effectiveness) to a total dose of 74 Gy. Acute mucositis Common Terminology Criteria for Adverse Events (CTCAE) grade 3 occurred in 12% of patients (n = 4) and was accompanied by odynophagia CTCAE grade 3. Except for 1 case of grade 3 weight loss, no other acute high-grade toxicity (grade 3-4) was observed. In a small patient cohort of 15 patients eligible for long-term follow-up we have seen no high-grade (grade ≥3) long-term side effects 2 years after radiation therapy. None of these patients suffered from therapy-associated vision or hearing loss. Secondary endpoints were 2-year overall survival, 2-year local progression-free survival, 2-year progression-free survival, and 2-year metastases-free survival with 79.4%, 61.8%, 61.8%, and 64.8%, respectively. To our knowledge, this is the first prospective data on toxicity and outcome of bimodal radiation therapy for the rare entity of sinonasal malignancies. Our study shows a low rate of CTCAE-reported acute toxicity with reasonable tumor control and survival rates after bimodal radiation therapy, which therefore remains a therapy approach to be further evaluated.

Virtual Surgical Planning and Three-Dimensional Models for Precision Sinonasal and Skull Base Surgery.

Sinonasal and skull base malignancies represent a rare, heterogenous group of pathologies with an incidence of 0.556 per 100,000 persons in the population. Given the numerous critical anatomic structures located adjacent to the sinonasal cavity and skull base, surgery for tumors in this region requires careful pre-operative planning with the assistance of radiological imaging and intraoperative image guidance technologies to reduce the risk of complications. Virtual surgical planning (VSP) and three-dimensional models (3DMs) are adjunctive technologies which assist clinicians to better visualize patient anatomy using enhanced digital radiological images and physical stereolithographic models based on patients' personal imaging. This review summarizes our institutional experience with VSP and 3DMs in sinonasal and skull base surgical oncology. A clinical case series is used to thematically illustrate the application of VSP and 3DMs in surgical ablation, reconstruction, patient communication, medical education, and interdisciplinary teamwork in sinonasal and skull base surgery.

Syndrome of Inappropriate Antidiuretic Hormone Release Secondary to Ectopic Olfactory Neuroblastoma: Case Report and Review of Literature.

Ectopic olfactory neuroblastoma (ONB) is a rare neuroendocrine sinonasal malignancy which arises from sinonasal regions where olfactory neuroepithelium does not exist. Presentation of syndrome of inappropriate antidiuretic hormone release (SIADH) in patients with ectopic ONB is extremely rare. We report a case of a 22-year-old patient with ectopic ONB and paraneoplastic SIADH that was managed at our center. The ONB was arising from the left lamina papyracea and extending into the maxillary and ethmoid sinuses and filling the nasal cavity. Correction of sodium levels occurred within 24 hours of endoscopic resection via a combined trans-nasal transorbital approach. To avoid negative sequela secondary to rapid sodium correction, the patient was managed by desmopressin to obtain gradual sodium correction, which was achieved on the fourth postoperative day. Ectopic presentation of ONB with paraneoplastic SIADH is extremely rare with only 7 cases reported in the literature to date. Management via surgical resection and/or radiotherapy for these patients requires the managing clinician to be vigilant of serum sodium levels. A multidisciplinary approach is essential for optimal outcomes.

Hippocampal-Sparing Radiotherapy in Primary Sinonasal and Cutaneous Head and Neck Malignancies: A Feasibility Study

Patients with primary sinonasal and cutaneous head and neck (H&N) malignancies often receive meaningful hippocampal doses, but the hippocampus is not a classic avoidance structure in radiation planning of these primary sites. This series characterizes the feasibility and tradeoffs of hippocampal-sparing radiotherapy (HSRT) for patients with primary sinonasal and cutaneous H&N malignancies. We retrospectively identified patients at a single institution treated definitively for primary sinonasal or cutaneous malignancies of the H&N. Each patient received (chemo)radiation and all received clinically-significant radiation dose to one or both hippocampi. We created new HSRT plans for each patient with intensity-modulated radiotherapy using original target and organ-at-risk (OAR) volumes. Hippocampi were contoured based on Radiation Therapy Oncology Group guidelines. Absolute and relative differences in radiation dose to the hippocampi, planning target volumes (PTV), and OARs were recorded. We used paired-samples t-tests to compare hippocampal and PTV dosimetric measures with and without HSRT. Thirty-seven patients were included (22 sinonasal, 11 cutaneous H&N, and 4 parotid primary tumors). Median prescription dose was 6600cGy (range: 5000-7440cGy). The most common fractionation regimens were 200cGy/fraction daily (51%, 19/37 patients) and 120cGy/fraction twice daily (41%, 15/37 patients). There were significant decreases in hippocampal Dmax and D100% using HSRT without compromising PTV coverage (Table 1). HSRT resulted in a relative increase of mean lacrimal gland dose by an average of 3.8%, optic chiasm Dmax by 1.3%, and whole brain Dmax of 1.2%. However, other OAR doses were lower with HSRT, including parotid gland mean dose, lens Dmax, optic nerve Dmax, cochlea mean dose, brainstem Dmax, and whole brain mean dose. HSRT is feasible and results in meaningful radiation dose reduction to the hippocampi without reducing PTV coverage or increasing dose to other OARs. The hippocampi should be regularly included as avoidance structures when treating primary sinonasal and cutaneous H&N tumors with radiation. We suggest target hippocampal constraints of Dmax < 1600cGy and D100% < 500cGy when feasible (without compromising PTV coverage). The clinical significance of HSRT in patients with primary H&N tumors should be investigated prospectively.

Induction Chemotherapy for Sinonasal Tumors in Patients Presenting with Brain Invasion and/or Neurological Deficits.

Objective The aim of this study was to investigate the safety of induction chemotherapy (IC) for patients with sinonasal malignancies with brain invasion or a neurological deficit. Methods We conducted a retrospective analysis of patients who underwent IC for sinonasal malignancies with intracranial invasion or a neurological deficit at a single tertiary cancer center from 1992 to 2020. Results In total, 460 patients with sinonasal malignancies were included in the study. Of the patients reviewed, 341 underwent IC and within this group 40 had brain invasion (BI) and 31 had a neurological deficit (ND) at presentation. The most prevalent malignancy was sinonasal undifferentiated carcinoma (BI 40%, ND 41.9%), followed by esthesioneuroblastoma (BI 27.5%, ND 9.7%). All tumors were stage T4 with the majority lacking nodal metastases (BI N0: 72.5%, ND N0: 77.5%). All patients completed at least two cycles of IC. Partial or complete response to IC was seen in 80% of BI and 71% of ND patients. No patients had cessation of treatment due to neurologic decline and none required urgent surgery. Five patients (12.5%) with BI and 2 (6.5%) with ND had interruption of IC for reasons other than neurological decline. In patients with ND, IC led to improvement of 54.5% NDs. Conclusion In patients with sinonasal malignancies with BI or ND who underwent IC, no patients had cessation of treatment due to neurologic decline. In contrast, most patients had improvement of neurologic symptoms with IC. IC was safely administered without interruption due to neurological decline or symptom progression.

Failure Patterns Within Different Histological Types in Sinonasal Malignancies: Making the Complex Simple.

To analyze the failure patterns in patients with different histological subtypes of sinonasal malignancies (SNMs). Retrospectively gathered data. Academic university hospital. 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. 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. 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.

Sinonasal adenocarcinoma: a case series

Sinonasal malignancies are rare head and neck cancers. We present three patients with sinonasal adenocarcinomas that have different characteristics. The first patient was asymptomatic, and the nasoendoscopy revealed a nasopharyngeal mass. He was diagnosed with stage I papillary type adenocarcinoma and was treated with nasal endoscopic surgery, with no evidence of tumour recurrence for one year. In the second case, the patient had a unilateral nasal blockage with blood-stained nasal discharge. Nasoendoscopy showed a septal mass. The patient was diagnosed with stage II low-grade non-intestinal sinonasal adenocarcinoma (NITAC) and underwent two nasal endoscopic surgeries with no tumour recurrence after six months. In the third case, the patient reported ear fullness, blood-stained nasal discharges, and painless neck swelling. Nasoendoscopy showed a right septal mass, and he was diagnosed with stage IVc high-grade NITAC. He received concurrent chemoradiotherapy and is doing well three months after treatment completion.