Intestinal-Type Adenocarcinoma in Head and Neck: Dissecting Oncogenic Gene Alterations Through Whole Transcriptome and Exome Analysis.

Adenocarcinomas of the nasal/paranasal sinuses are uncommon, but intestinal-type adenocarcinomas (ITACs) are important. Due to the rarity of these tumors, their molecular profile is not well known. To further investigate the molecular profile and find potential oncogenic drivers, we compared the whole transcriptome and exome of ITACs at different anatomic locations in the head and neck. Twenty-one head and neck adenocarcinomas were used in this study, divided into 10 sinonasal adenocarcinomas (SNT) and 11 extrasinonasal (T) head and neck adenocarcinomas according to anatomic location and histology. Tumor samples along with normal mucosa were microdissected from formalin-fixed, paraffin-embedded samples, and RNA and DNA were subjected to whole-transcriptome and -exome shotgun sequencing. Analysis of ITACs at sinonasal locations showed 410 subtype-specific differentially expressed (DE) genes and noncoding transcripts compared with the group of other anatomic locations, with 2909 subtype-specific DE genes. The groups shared 872 genes, with 17 highly different or opposing DE genes. Whole-exome mutation analysis revealed the gene MLL3 (KMT2C) to be exhibiting the most frequent loss-of-function mutations in all adenocarcinomas investigated. The results suggest that the head and neck ITACs investigated were mainly caused by loss-of-function mutations in MLL3 that disabled chromatin methylation and remodeling of all MLL3-targeted enhancers in the tumors. This changed the activity of multiple genes/gene clusters, supporting oncogenicity mostly via pathways of signaling, dedifferentiation, proliferation, migration, and immune and inflammatory deregulation, indicating a truly epigenetic event as the root cause for the heterogenous diversity of these enteric types of cancer. The data of this study form the basis for understanding cell fate determination and cellular homeostasis in the normal respiratory mucosa at different anatomic sites and show the contribution of different mucosal components to the etiology/molecular pathology of ITAC.

Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma.

Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as keratin expression or gland formation, are a diagnostically challenging group that has never been formally included in sinonasal tumor classifications. Recently, we documented that most of these neuroepithelial neoplasms have distinctive histologic and immunohistochemical findings and proposed the term "olfactory carcinoma" to describe these tumors. However, the molecular characteristics of olfactory carcinoma have not yet been evaluated. In this study, we performed targeted molecular profiling of 23 sinonasal olfactory carcinomas to further clarify their pathogenesis and classification. All tumors included in this study were composed of high-grade neuroectodermal cells that were positive for pankeratin and at least 1 specific neuroendocrine marker. A significant subset of cases also displayed rosettes and neurofibrillary matrix, intermixed glands with variable cilia, peripheral p63/p40 expression, and S100 protein-positive sustentacular cells. Recurrent oncogenic molecular alterations were identified in 20 tumors, including Wnt pathway alterations affecting CTNNB1 (n = 8) and PPP2R1A (n = 2), ARID1A inactivation (n = 5), RUNX1 mutations (n = 3), and IDH2 hotspot mutations (n = 2). Overall, these findings do demonstrate the presence of recurrent molecular alterations in olfactory carcinoma, although this group of tumors does not appear to be defined by any single mutation. Minimal overlap with alterations previously reported in ONB also adds to histologic and immunohistochemical separation between ONB and olfactory carcinoma. Conversely, these molecular findings enhance the overlap between olfactory carcinoma and sinonasal neuroendocrine carcinomas. A small subset of neuroepithelial tumors might better fit into the superseding molecular category of IDH2-mutant sinonasal carcinoma. At this point, sinonasal neuroendocrine and neuroepithelial tumors may best be regarded as a histologic and molecular spectrum that includes core groups of ONB, olfactory carcinoma, neuroendocrine carcinoma, and IDH2-mutant sinonasal carcinoma.

FGFR1/2/3-rearranged carcinoma of the head and neck: expanded histological spectrum crossing path with high-risk HPV in the sinonasal tract.

AIMS: Oncogenic FGFR1/2/3 rearrangements are found in various cancers. Reported cases in head and neck (HN) are mainly squamous cell carcinomas (SCCs) with FGFR3::TACC3 fusions, a subset of which also harbour high-risk human papillomavirus (HPV). However, the knowledge of the clinicopathological spectrum of FGFR-rearranged head and neck carcinomas (FHNC) is limited. METHODS AND RESULTS: A retrospective MSK-fusion clinical sequencing cohort 2016-23 was searched to identify malignant tumours in the HN region harbouring FGFR1/2/3 fusion. FHNC were characterised by histological examination, immunohistochemistry and molecular analysis. Electronic medical records were reviewed. Three FHNC were identified. Two cases (cases 1 and 2) involved sinonasal tract and were high-grade carcinomas with squamous, basaloid, glandular and/or ductal-myoepithelial features. Case 1 arose in a 79-year-old man and harboured FGFR2::KIF1A fusion. Case 2 arose in a 58-year-old man, appeared as HPV-related multiphenotypic sinonasal carcinoma (HMSC), and was positive for FGFR2::TACC2 fusion and concurrent high-risk HPV, non-type 16/18. Case 3 was FGFR3::TACC3 fusion-positive keratinising SCCs arising in the parotid of a 60-year-old man. All three cases presented at stage T4. Clinical follow-up was available in two cases; case 1 remained disease-free for 41 months post-treatment and case 3 died of disease 2 months after the diagnosis. CONCLUSIONS: FHNC include a morphological spectrum of carcinomas with squamous features and may occur in different HN locations, such as parotid gland and the sinonasal tract. Sinonasal cases can harbour FGFR2 rearrangement with or without associated high-risk HPV. Timely recognition of FHNC could help select patients potentially amenable to targeted therapy with FGFR inhibitors. Further studies are needed (1) to determine if FGFR2 rearranged/HPV-positive sinonasal carcinomas are biologically distinct from HMSC, and (2) to elucidate the biological and clinical significance of FGFR2 rearrangement in the context of high-risk HPV.

Development and validation of a nomogram for predicting overall survival in patients with sinonasal mucosal melanoma.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a relatively rare malignant tumour with a poor prognosis. This study was designed to identify prognostic factors and establish a nomogram model to predict the overall survival (OS) of patients with SNMM. METHODS: A total of 459 patients with SNMM were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort. Univariate and multivariate Cox regression analyses were used to screen for independent factors associated with patient prognosis and develop the nomogram model. In addition, external validation was performed to evaluate the effectiveness of the nomogram with a cohort of 34 patients with SNMM from Peking Union Medical College Hospital. RESULTS: The median OS in the cohort from the SEER database was 28 months. The 1-year, 3-year and 5-year OS rates were 69.8%, 40.4%, and 30.0%, respectively. Multivariate Cox regression analysis indicated that age, T stage, N stage, surgery and radiotherapy were independent variables associated with OS. The areas under the receiver operating characteristic curves (AUCs) of the nomograms for predicting 1-, 3- and 5-year OS were 0.78, 0.71 and 0.71, respectively, in the training cohort. In the validation cohort, the area under the curve (AUC) of the nomogram for predicting 1-, 3- and 5-year OS were 0.90, 0.75 and 0.78, respectively. Patients were classified into low- and high-risk groups based on the total score of the nomogram. Patients in the low-risk group had a significantly better survival prognosis than patients in the high-risk group in both the training cohort (P < 0.0001) and the validation cohort (P = 0.0016). CONCLUSION: We established and validated a novel nomogram model to predict the OS of SNMM patients stratified by age, T stage, N stage, surgery and radiotherapy. This predictive tool is of potential importance in the realms of patient counselling and clinical decision-making.

Integrated Molecular and Histological Insights for Targeted Therapies in Mesenchymal Sinonasal Tract Tumors.

PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of mesenchymal sinonasal tract tumors (STTs), a distinct subset of STTs. Despite their rarity, mesenchymal STTs represent a unique clinical challenge, characterized by their rarity, often slow progression, and frequently subtle or overlooked symptoms. The complex anatomy of the sinonasal area, which includes critical structures such as the orbit, brain, and cranial nerves, further complicates surgical treatment options. This underscores an urgent need for more advanced and specialized therapeutic approaches. RECENT FINDINGS: Advancements in molecular diagnostics, particularly in next-generation sequencing, have significantly enhanced our understanding of STTs. Consequently, the World Health Organization has updated its tumor classification to better reflect the distinct histological and molecular profiles of these tumors, as well as to categorize mesenchymal STTs with greater accuracy. The growing understanding of the molecular characteristics of mesenchymal STTs opens new possibilities for targeted therapeutic interventions, marking a significant shift in treatment paradigms. This review article concentrates on mesenchymal STTs, specifically addressing sinonasal tract angiofibroma, sinonasal glomangiopericytoma, biphenotypic sinonasal sarcoma, and skull base chordoma. These entities are marked by unique histopathological and molecular features, which challenge conventional treatment approaches and simultaneously open avenues for novel targeted therapies. Our discussion is geared towards delineating the molecular underpinnings of mesenchymal STTs, with the objective of enhancing therapeutic strategies and addressing the existing shortcomings in the management of these intricate tumors.

Endoscopy-assisted medial canthus incision for olfactory neuroblastoma: a case report.

Sinonasal malignant tumors are a group of uncommon malignancies that account for less than 1% of all tumors. These tumors often involve the maxillary sinus and nasal cavity, with less cumulative incidence in the ethmoidal sinus, sphenoidal sinus, and frontal sinus. The lack of consensus on the management of sinonasal malignancies is due to their rarity, diagnostic challenges, and the heterogeneity of treatments. In this paper, we present a case of endoscopic-assisted medial canthus incision combined with radiotherapy in the treatment of sinonasal malignant tumors, with the aim of providing valuable insights to clinicians on the management of these tumors.

Surgical treatment of 186 sinonasal inverted papillomas and analysis of the immunohistochemical and molecular features associated with recurrences.

INTRODUCTION: Inverted papillomas (IP) are benign epithelial tumors with a tendency to be locally invasive and with disposition to recur. The aim of our study is to present the results of IP treatment, considering pathological, immunohistochemical and molecular features of recurrence. MATERIAL AND METHODS: From 1978 to 2020, 186 sinonasal IPs surgeries corresponding to 152 patients were treated in our center. We performed a pathology evaluation of all the recurrent cases reviewing the histological diagnosis, the presence of mixed component other than IP, the koilocytic changes, the p16 over expression and HPV-DNA detection. RESULTS: Overall recurrence rate was 19 % (35/186). The 35 IP recurrences correspond to 22 patients, 9 of whom presented a single recurrence (single recurrence group) while 13 of them presented more than one recurrence (multi-recurrent group). Immunohistochemical analysis showed a higher percentage of p16 overexpression (54 % vs 33 % p = 0.415) and HPV-DNA presence (23 % vs 0 % p = 0.240) in the multi-recurrent group compared with single recurrence group. In addition, the revision showed more IP with exophytic papilloma focus (38 vs 22 % p = 0.648) and a higher proportion of IP with koilocytotic changes (61 % vs 22 % p = 0.099) in the multirecurrent group. There is no significant difference between groups in our results. CONCLUSION: The analysis of our patients may differentiate between two groups with recurrent papillomas. A single recurrence group where the cause of recurrence is probably an anatomical problem related to an incomplete resection, and a second pattern, the multi-recurrence group, where HPV infection may be the main cause of recurrence.

Impact of facility volume on survival in primary endoscopic surgery for sinonasal squamous cell carcinoma.

OBJECTIVES: To evaluate the impact of facility volume on outcomes following primary endoscopic surgical management of sinonasal squamous cell carcinoma (SNSCC). METHODS: The 2010-2016 National Cancer DataBase (NCDB) was queried for patients diagnosed with T1-T4a SNSCC surgically treated endoscopically as the primary treatment modality. Factors associated with overall survival (OS) were evaluated, including facility volume. RESULTS: A total of 330 patients who underwent endoscopic surgical management of SNSCC were treated at 356 unique facilities designated as either low-volume (LVC; treating 1-2 cases; 0-75th percentile), intermediate-volume centers (IVC; 3-4 cases total; 75th-90th percentile), or 144 high-volume (HVC; treating 5+ cases total; >90th percentile) centers. HVC treated patients with higher T staging (42.1 % vs. 29.8 %) and tumors in the maxillary sinus (26.9 % vs. 13.2 %) and ethmoid sinus (10.3 % vs. ≤8.3 %), while LVCs treated lower T stage tumors (70.2 % vs. 57.9 %) and tumors that were located in the nasal cavity (70.2-78.5 % vs. 62.8 %). On multivariable analysis, factors associated with decreased OS included higher T stage (T3/T4a vs. T1/T2; OR 1.92, 95 % CI 1.06-3.47) and older age (>65 vs. <65; OR 2.69, 95 % CI 1.62-4.49). Cases treated at high-volume centers were not associated with a higher likelihood of OS when compared to low-volume centers (OR 0.70, 95 % CI 0.36-1.35). CONCLUSIONS: HVC are treating more primary tumors of the maxillary and ethmoid sinuses and tumors with higher T stages with endoscopic approaches, although this does not appear to be associated with increased OS. SHORT SUMMARY: Sinonasal squamous cell carcinoma (SNSCC) presents late in disease process with poor prognosis. We investigated the impact of facility volume on outcomes following endoscopic treatment of SNSCC. High-volume centers treat more advanced and complex disease with comparable OS.

Electrochemotherapy as adjuvant treatment in a sinonasal mucosal melanoma in elderly patient: a case report.

BACKGROUND: Sinonasal Mucosal Melanoma (SNMM) is a rare but aggressive disease. Surgery with free margins, when feasible, is the treatment of choice. In the last three decades, electrochemotherapy (ECT) has emerged as a local ablative procedure, performed with the Cliniporator, for cutaneous and mucosal tumours of different histology. We present a case report of an ECT treatment performed by means of a new endoscopic electrode, on an elderly patient affected by primary SNMM. METHODS: An 88-year-old man with a diagnosis of SNMM (cT4aN0M0)-Stage IV, of the left nasal fossa presented at our institution. Symptoms were epistaxis and complete left nasal obstruction. He refused sinonasal extended surgery and radiotherapy. He underwent a tumor debulking followed by ECT exclusively for symptom control, with palliative intent. RESULTS: The patient underwent SNMM debulking under general anaesthesia, followed by ECT on tumour margins. After the procedure, he had been free from symptoms for 5 months, with a good quality of life. Local recurrence was controlled with a new local debulking and ECT procedure on margins. The patient remained symptom free for the next 4 months. Seventeen months after diagnosis, the patient is mild symptomatic for sinonasal disease. Therefore, he developed a systemic disease progression. CONCLUSIONS: In our experience, ECT can be used as an adjuvant tool for symptom and local control in SNMM when extended surgery is out of curative intent or unfeasible. As expected, ECT does not appear to have any effect on systemic disease progression.

What is the rate of occult nodal metastasis in squamous cell carcinomas of the sinonasal tract? A systematic review.

OBJECTIVE: The role of elective neck dissection (END) in the management of clinical N0 (cN0) squamous cell carcinomas (SCC) of the sinonasal tract is unclear. In this systematic review, we evaluate the risk of occult nodal metastasis in sinonasal SCCs with cN0M0 tumors to support clinical decision making. METHODS: A literature search was conducted in the following three electronic databases: Medline/PubMed, ScienceDirect, and Google Scholar. Articles were assessed for eligibility in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two independent authors extracted the data. The Methodological Items for Non-Randomized Studies (MINORS) tool was used for the assessment of biases of each included study. RESULTS: Our systematic review included six studies that met the inclusion criteria, all retrospective in design. The rate of histologically proven metastasis of sinonasal SCC to the clinically negative neck is 12.5%. Almost half of the positive cases are pathologically staged as N2 (6.5%). CONCLUSION: Our systematic review provides the rate of sinonasal SCC occult metastasis to the neck so that the surgeons can discuss with patients the risks and possible merits of adding an elective neck management in the surgical plan.

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.

Therapeutic approaches to sinonasal NUT carcinoma: a systematic review.

PURPOSE: Sinonasal nuclear protein in testis carcinoma (SNUTC) is a rare, aggressive malignancy caused by genetic rearrangements in the NUTM1 gene. The prognosis of SNUTC ranks among the most unfavorable within the naso-sinusal district, with an overall survival of 9.7 months. This systematic review aimed to determine the best therapeutic strategy for SNUTC. METHODS: We reviewed eligible articles for patient demographics, TNM and stage at presentation, best response after primary treatment, disease-free survival and overall survival (OS) times, other following therapy lines, and final outcomes. RESULTS: Among 472 unique citations, 17 studies were considered eligible, with reported treatment data for 25 patients. Most studies (n = 12) were case reports. The most frequently administered treatment regimen was surgery as primary treatment and combined radiochemotherapy as second-line or adjuvant treatment. Four patients were alive at follow-up. CONCLUSION: Basing on the existing literature, a standardized line in the treatment of SNUTC is not yet well delineated. A self-personalized strategy of therapy should be drawn on each patient affected by SNUTC.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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 7 days). Use of EEA was associated to improved disease-specific survival (DSS; 11.4 versus 4.4 years; HREEA = 0.53), especially for patients with T3-4a tumors (11.4 versus 3.0 years; 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. CONCLUSIONS: 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.

Neoadjuvant chemotherapy for organ preservation in sinonasal squamous cell carcinoma.

PURPOSE: In this study, we aimed to evaluate the role of induction chemotherapy (IC) in the treatment of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). METHODS: 130 patients who accepted IC between 2010 and 2022 were retrospectively reviewed. After IC, all the patients underwent chemoradiotherapy (CRT)/ radiotherapy (RT) or CRT/RT followed by surgery. We investigated the objective response to IC, the optimal treatment strategy, organ preservation, and long-term survival. RESULTS:  Eighty-seven patients (66.9%) achieved a partial response after IC. 86% (27/43) of the patients who did not respond to the IC still presented a sensitive response to radiotherapy (χ2 = 9.26, p = 0.005). Patients who respond to IC could benefit from CRT/RT followed by surgery over other treatment modalities. The 3-year overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of 61.2%, 51.3%, 52.1%, 58.1% for the IC response group were significantly superior to those of 37.3% (HR = 0.58, 95% CI 0.34-1.01, p = 0.030), 33.5% (HR = 0.49, 95% CI 0.30-0.82, p = 0.002), 35.9% (HR = 0.54, 95% CI 0.32-0.91, p = 0.009), 36.1% (HR = 0.60, 95% CI 0.35-1.03, p = 0.040) for the IC non-response group. Patients who responded to IC had a high rate of organ preservation compared with patients who did not respond to IC (90.8% vs. 74.4%, χ2 = 6.19, p = 0.013). CONCLUSIONS: The results demonstrated a response rate to IC in patients with advanced SNSCC; furthermore, the response to IC indicated better survival. Patients who responded to IC had a high rate of organ preservation.

Sinonasal cancer incidence in Lombardy, Italy, 2008-20.

BACKGROUND: Epithelial sinonasal cancers (SNC) are rare tumours with recognized associations with known/suspected occupational carcinogens (wood/leather dust, nickel/chromium compounds and formaldehyde). In Italy, a national SNC registry organized as a network of regional registries was established by law in 2008. AIMS: To describe SNC time trends, occupational exposures and geographical distribution in Lombardy, North-West Italy, based on population registry data (2008-20). METHODS: The Lombardy SNC Registry records epithelial SNCs using various sources. Interviews to collect occupational history are performed using a standardized questionnaire. Using several standard populations, we calculated yearly crude and age-standardized rates (ASRs per 100,000 person-years). Standardized incidence ratios (SIR) at municipality level were calculated, and Bayesian models were fitted to produce smoothed SIR maps. RESULTS: We recorded 827 cases (553 men, 274 women). Crude (world standardized) ASRs were 0.9 (0.4) in men and 0.4 (0.2) in women, with no time trends. Interviews were obtained for 485 (88%) men and 223 (81%) women. Among men, 217 (45%) had been exposed to occupational carcinogens (wood/leather dust: 150/65 cases, 31%/13%), while only 36 women (16%) were exposed. Among 201 men with adenocarcinoma, exposure to wood/leather dust occurred in 103/50 cases (75%/50%). Areas with elevated SIRs associated with leather dust were found in the Western areas. Exposure to wood dust was more widespread. CONCLUSIONS: This study found a high frequency of occupational exposures (wood and leather dust), particularly in men with SNC. Employment in shoe industries clustered in the Western part, while work in furniture industries was less spatially structured.

Diagnostic value of serum squamous cell carcinoma antigen and cytokeratin fragment antigen 21-1 for sinonasal inverted papilloma: an exploratory study.

BACKGROUND: Serum tumor markers have not yet been developed for the clinical diagnosis and treatment of sinonasal inverted papilloma (SNIP), one of the most significant sinonasal tumors. Therefore, this study aimed to determine the diagnostic value of serum squamous cell carcinoma antigen (SCCA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) for SNIP. METHODS: Clinical data were obtained from 101, 56, and 116 patients with SNIP, sinonasal squamous cell carcinoma (SNSCC), and unilateral chronic rhinosinusitis (CRS), respectively. Preoperative serum SCCA and CYFRA 21-1 levels were compared, and logistic regression analyses were performed to screen serum tumor markers, which may be used to diagnose SNIP. Diagnostic cut-off values were determined using receiver operating characteristic (ROC) curves, and their diagnostic power was verified. RESULTS: Serum SCCA and CYFRA 21-1 differentiated SNIP from CRS with the cut-off values of 1.97 ng/mL and 2.64 ng/mL and the areas under the ROC curves (AUC) of 0.895 and 0.766, respectively, and the AUC of the combination of the two markers was 0.909. CYFRA 21-1 differentiated SNIP with malignant transformation from that without malignant transformation with a cut-off value of 3.51 ng/mL and an AUC of 0.938. CYFRA 21-1 distinguished SNIP with malignant transformation from SNSCC with a cut-off value of 3.55 ng/mL and an AUC of 0.767. CONCLUSIONS: This study provides novel potential diagnostic tools for SNIP by demonstrating the use of serum SCCA and CYFRA 21-1 in the diagnosis of SNIP.

BiZact-Assisted Endoscopic Resection of a Sinonasal Tumor.

The BiZact device, a bipolar electrosurgical scissor designed for tonsillectomy, minimizes thermal tissue damage and seals blood vessels <3 mm in diameter while dividing the soft tissue. This study describes the authors' experience with sinonasal tumor surgery using a BiZact and discusses its clinical utility and advantages. The authors analyzed BiZact-assisted endoscopic sinonasal tumor surgery cases between January 2021 and May 2023. Data were collected on patients' demographics, histopathology, extent of tumor involvement, surgical records, and postoperative medical records. Clinical utility was assessed using the success rate of complete tumor excision, estimated blood loss during surgery, device-related complications, and operation time. A survey of the surgeons' BiZact experience was also conducted. The diagnoses of the 20 patients in this study included squamous cell carcinoma (n = 2), malignant melanoma (n = 1), sarcoma (n = 1), natural killer cell lymphoma (n = 1), inverted papilloma (n = 12), angiofibroma (n = 2), and schwannoma (n = 1). This pilot study demonstrated a shortened operative time, with a median of 0.8 hours and <100 mL of intraoperative blood loss. In addition, no BiZact-related complications were observed. The BiZact device allows efficient sinonasal surgery because it has the unique advantage of one-step sealing and cutting. BiZact-assisted endoscopic sinonasal tumor surgery is a beneficial and safe procedure that reduces blood loss during surgery, shortens the operative time, and minimizes postoperative complications.

A Pilot Immunohistochemical Study Identifies Hedgehog Pathway Expression in Sinonasal Adenocarcinoma.

Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have analyzed immunohistochemical staining of six Hedgehog pathway proteins, sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched1 (PTCH1), Gli family zinc finger 1 (GLI1), Gli family zinc finger 2 (GLI2), and Gli family zinc finger 3 (GLI3), on 21 samples of sinonasal adenocarcinoma and compared them with six colon adenocarcinoma and three salivary gland tumors, as well as with matching healthy tissue, where available. We have detected GLI2 and PTCH1 in the majority of samples and also GLI1 in a subset of samples, while GLI3 and the ligands SHH and IHH were generally not detected. PTCH1 pattern of staining shows an interesting pattern, where healthy samples are mostly positive in the stromal compartment, while the signal shifts to the tumor compartment in tumors. This, taken together with a stronger signal of GLI2 in tumors compared to non-tumor tissues, suggests that the Hedgehog pathway is indeed activated in sinonasal adenocarcinoma. As Hedgehog pathway inhibitors are being tested in combination with other therapies for head and neck squamous cell carcinoma, this could provide a therapeutic option for patients with sinonasal adenocarcinoma as well.

Sinonasal inverted papilloma and predictors of health-related quality of life after endonasal endoscopic surgery: A prospective cohort study.

OBJECTIVES: Existing knowledge on health-related quality of life (HRQoL) after surgical removal of sinonasal inverted papilloma (IP) is limited. Moreover, predictors for a better or worse post-operative HRQoL outcome are not known. Our aim was to assess HRQoL in all three health domains (physical, psychological, and social), track its post-operative trajectory, investigate if pre-operative observations could predict distinct post-operative HRQoL outcomes, and evaluate whether physicians' interventions could contribute to improved post-operative HRQoL. DESIGN: Prospective cohort study. SETTING: Tertiary referral hospital. PARTICIPANTS: Seventy-four patients who underwent surgery for an IP were included. They were asked to fill in the Endonasal Endoscopic Sinus and Skull-Base Surgery Questionnaire (EES-Q) pre-operatively, and then 2 weeks, 3 months, and 1 year post-operatively. MAIN OUTCOME MEASURES: Linear mixed models analyses were performed to evaluate the overall post-operative HRQoL and the separate health domains, as well as the impact of specific variables (sex, age, American Society of Anaesthesiologists [ASA] classification, smoker, Krouse staging, pre-operative EES-Q score, type of surgery, and post-operative antibiotics) on HRQoL improvement. RESULTS: The total EES-Q score (p < .001) as well as the physical (p < .001), psychological (p = .049), and the social (p = .002) domains significantly improved post-operatively. ASA classification (p = .049), pre-operative EES-Q score (p < .001) and post-operative antibiotics (p = .036) were significant variables. CONCLUSIONS: Overall HRQoL, as well as each of the three health domains, improved significantly. A higher ASA score, a higher pre-operative EES-Q score, and the administration of post-operative antibiotics were significant predictors for better HRQoL recovery post-operatively. Further research is necessary to confirm these results.

[Inverted papilloma of the nose and paranasal sinuses : Diagnosis, treatment, and malignant transformation]. / Invertiertes Papillom der Nase und Nasennebenhöhlen : Diagnostik, Therapie und maligne Transformation.

Inverted papilloma (IP) are benign tumors that show a locally aggressive behavior, a high rate of recurrence, and a potential for malignant transformation. Specific radiological signs such as hyperostosis at the origin of the IP and convoluted cerebriform patterns, as well as the typical endoscopic aspect, can lead to diagnosis and enable preoperative planning of surgical access and the extent of surgery. Endonasal endoscopic techniques are considered the gold standard and the introduction of extended surgical techniques such as the prelacrimal approach, frontal drillout, or orbital transposition facilitate complete subperiosteal resection with preservation of important physiological structures. There is a risk of synchronous and metachronous squamous cell carcinomas (IP-SCC). Research focuses on radiological criteria to differentiate benign IP from IP-SCC, genetic and epigenetic factors in the process of malignant transformation, and estimation of the risk of IP progressing to IP-SCC.