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Objectives: Sinonasal inverted papilloma (SNIP) is a noncancerous tumor that develops in the mucous membrane of the nasal sinuses. Many malignancies are tightly linked to autophagy, an intracellular self-degradation mechanism. HMGB1 has demonstrated its ability to modulate autophagy in many pathological conditions. This work investigates how HMGB1 and other genes involved in autophagy contribute to SNIP., Material and Methods: The study included 45 patients with SNIP and a control group consisting of 28 individuals. In each group, qPCR was employed to examine the mRNA expression levels of genes correlated with autophagy and HMGB1. HMGB1 and genes associated with autophagy were examined for protein expression levels via Western Blot and immunohistochemical staining assays. At the same time, the association between HMGB1 and genes involved in autophagy was discovered through correlation analysis. Furthermore, Krouse staging was utilized for investigating the expression levels of HMGB1 and other autophagy-related genes at various stages in clinically staged SNIP patients., Results: LC3B, ATG5, and Beclin1 autophagy-related genes and HMGB1 were substantially expressed in SNIP. Additionally, there was a positive correlation between HMGB1 and these genes. During various phases of SNIP, the levels of HMGB1 expression and autophagy-related genes were notably elevated at stage T4 compared with stage T2., Conclusion: Clinical staging in SNIP is correlated with HMGB1 expression in conjunction with autophagy-related genes LC3B, ATG5, and Beclin1, suggesting the possibility of novel prognostic indicators., Level of Evidence: NA Laryngoscope, 134:3941-3946, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: We report a nasal cavity unusual perivascular epithelioid cell tumor (PEComa) mimicking mucosal melanoma., Methods: Immunohistochemistry was performed using BenchMark Ultra and panel of antibodies. The Ion Torrent platform and Ion AmpliSeq cancer hotspot panel were utilized for DNA genotyping. Target-specific RNA libraries for the detection of fusion transcripts were constructed using Archer Universal RNA Reagent Kit v2 and Archer FusionPlex Solid Tumor panel and sequenced on the MiSeqDx instrument., Results: The tumor, diagnosed in 46-year-old female, was composed of spindle cells, and lacked pigmentation. Immunohistochemically, it showed a patchy HMB-45 positivity. Other melanocytic markers (S100 protein, Melan-A, SOX10) were negative. The tumor cells were weakly positive for KIT (CD117) while negative for smooth muscle actin, pancytokeratin cocktail (AE1/AE3), and synaptophysin. Diagnosis of primary sinonasal tract mucosal melanoma was favored. Additional molecular studies detected PRCC :: TFE3 fusion as the sole genetic change, and suggested the diagnosis of unusual PEComa. Previously, TFE3 fusions were reported in a subset of PEComas but not in melanomas, while PRCC involvement has only been documented once in an ocular PEComa. Immunohistochemistry revealed strong nuclear TFE3 expression concordant with the molecular findings., Conclusions: This report emphasis the importance of molecular testing in the differential diagnosis between PEComa and melanoma, especially when the tumor arises in a site typical of melanoma but showing an unusual morphology and immunophenotype. The detection of TFE3 fusion transcripts suggested the diagnosis of SNT PEComa, although it cannot be excluded that this and similar tumors represent a distinct diagnostic category., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sinonasal mucosal melanoma (SNMM) is a rare but aggressive tumor with a poor prognosis. The co-inhibitory receptors T cell immunoglobulin and mucinodomain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) are promising new targets in anti-cancer immunotherapy. The expression profiles of these immune checkpoint molecules (ICMs) and potential prognostic implications have not been characterized in SNMM yet., Methods: Immunohistochemical staining for TIGIT, LAG-3 and TIM-3 was performed on tumor tissue samples from 27 patients with primary SNMM. Associations between ICM expression and demographic parameters, AJCC tumor stage, overall survival, and recurrence-free survival were retrospectively analyzed., Results: SNMM patients with low numbers of TIGIT+ and TIM-3+ tumor infiltrating lymphocytes (TILs) in the primary tumor survived significantly longer than patients with a high degree of TIGIT+ and TIM-3+ TILs. High infiltration with TIM-3+ or TIGIT+ lymphocytes was associated with the higher T4 stage and decreased 5-year survival., Conclusion: We identified high densities of TIM-3+ and TIGIT+ TILs as strong negative prognostic biomarkers in SNMM. This suggests that TIM-3 and TIGIT contribute to immunosuppression in SNMM and provides a rationale for novel treatment strategies based on this next generation of immune checkpoint inhibitors. Prospective studies with larger case numbers are warranted to confirm our findings and their implications for immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The mechanism and predictive biomarkers of sinonasal inverted papilloma (IP) transformation into squamous cell carcinoma (SCC) are still unclear. We investigated the genetic mutations involved and the predictive biomarkers. Fourteen patients with SCC arising from IP and six patients with IPs without malignant transformation (sIP) were included. DNA was extracted separately from areas of normal tissue, IP, dysplasia, and SCC. Whole exome sequencing and immunohistochemistry was performed. Major oncogenic mutations were observed in the progression from IP to SCC. The most frequently mutated genes were TP53 (39%) and CDKN2A (27%). Mutations in TP53 and/or CDKN2A were observed in three of six IPs with malignant transformation (cIP); none were observed in sIPs. Tumor mutational burden (TMB) increased from IP to SCC (0.64/Mb, 1.11/Mb, and 1.25 for IP, dysplasia, and SCC, respectively). TMB was higher in the cIPs than in the sIPs (0.64/Mb vs 0.3/Mb). Three cIPs showed a diffuse strong or null pattern in p53, and one showed a total loss of p16, a distinct pattern from sIPs. Our result suggests that TP53 and CDKN2A status can be predictive markers of malignant transformation of IP. Furthermore, immunohistochemistry of p53 and p16 expression can be surrogate markers for TP53 and CDKN2A status., (© 2024. The Author(s).)

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., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

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.

ALK-positive anaplastic large cell lymphoma is a rare T-cell lymphoma with ALK gene rearrangement that develops in children and young adults. The disease almost always affects the lymph nodes, and extranodal areas are also frequently involved. This article describes two cases of atypical localization of ALK-positive anaplastic large cell lymphoma with involvement of the paranasal sinuses.

To investigate the diagnostic value of casein kinase 1α (CK1α) and phosphatase and tensin homolog (PTEN) in sinonasal inverted papilloma (SNIP), 42 control subjects and 56 SNIP patients were recruited in this study. Demographic and clinical characteristics, computerized tomography scans and endoscopic examinations were analyzed according to the Krouse staging system. Real-time quantitative-polymerase chain reaction and Western blotting were performed to detect CK1α and PTEN expression levels in different subgroups. Receiver operating characteristic and correlation analyses were conducted to assess their clinical significance in SNIP diagnosis. The expression levels of CK1α and PTEN were decreased in SNIP patients. Interestingly, the declined mRNA levels were consistent with the elevated Krouse staging and closely associated with the pathophysiological characteristics. Their expression levels also negatively correlated with neutrophil counts and positively correlated with lymphocyte counts in the blood of SNIP patients. This study suggests that CK1α and PTEN might be useful biomarkers for the occurrence and recurrence diagnosis of SNIP., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The antitumor efficacies of immune checkpoint inhibitors (ICIs) and the usefulness of potential predictive markers such as programmed death-ligand 1 (PD-L1) expression, density of tumor-infiltrating lymphocytes (TILs) and microsatellite instability (MSI) in sinonasal squamous cell carcinoma (SNSCC) have not been fully elucidated. We retrospectively analyzed 131 SNSCCs with immunohistochemistry for PD-L1 expression, TIL subpopulations and loss of mismatch repair (MMR) proteins as a surrogate for MSI-high. We also comprehensively evaluated the mutual relationships among these immuno-markers, high-risk human papillomavirus (HPV) infection, epidermal growth factor receptor (EGFR) gene status, and KRAS mutation. PD-L1 expression (tumor proportion score ≥ 1%) was detected in 60 (45.8%) SNSCC cases and was significantly associated with worse overall survival (OS) (p = 0.0240). High density of cluster of differentiation 8 (CD8)-positive TILs was significantly associated with better progression-free survival (PFS) (p = 0.0368), and high density of forkhead box protein P3-positive TILs was significantly associated with better PFS and OS (p = 0.0007 and 0.0143, respectively). With respect to the combination of CD8 + TIL and PD-L1 expression, the high-CD8/PD-L1-negative group showed the most favorable prognosis, whereas the low-CD8/PD-L1-positive group showed the worst prognosis. MMR loss was detected in 3 (2.3%) of the 131 cases. HPV infection (6.1%), EGFR mutation (14.5%), EGFR copy number gain (26%), and MMR loss were essentially mutually exclusive; patients in these molecular groups showed significant differences in prognosis but not in the degree of PD-L1 expression or TILs. Among the nine ICI-treated patients, three (33.3%) were responders, and the EGFR-wild type cases (n = 7) showed better clinical responses to an ICI compared to the EGFR-mutant cases (n = 2). Among the patients with residual/recurrent EGFR-wild type tumors (n = 43), ICI treatment significantly improved OS (p = 0.0281). The results suggest that the evaluation of immuno-markers and molecular subclassification may be helpful for prognostic prediction and selecting an individualized therapeutic strategy for patients with SNSCC., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Introduction: SMARCB1 encodes for a component of the SWI/SNF complex and is widely implicated in carcinogenesis. In the head and neck, SMARCB1-deficient carcinomas typically arise in the sinonasal tract but can be found at other sites. EZH2 inhibitors have emerged as potential targeted therapy against SWI/SNF-deficient tumors. We sought to characterize the cytomorphology of head and neck carcinomas with SMARCB1 deficiencies to identify potential candidates for targeted therapy., Materials and Methods: Head and neck carcinomas with SMARCB1 mutations were retrospectively identified and confirmed to be SMARCB1-deficient by both molecular (fluorescent in-situ hybridization or next generation sequencing) and immunohistochemical means. Cases with positive cytology were reviewed and their cytologic features cataloged., Results: A total of 19 specimens from 13 patients were reviewed, including 8 specimens from 7 sinonasal carcinomas, 4 specimens from 3 thyroid carcinomas, 3 specimens from 2 skin carcinomas, and 4 specimens from 1 carcinoma of unknown primary origin. High-grade features were common, including mitoses (11 of 19) necrosis (13 of 19) and multinucleation (16 of 19). Tumors showed either dense cytoplasm with distinct cell borders (10 of 19) or delicate cytoplasm with indistinct cell borders (9 of 19). Most tumors showed no distinct epithelial differentiation (12 of 19), while some (7 of 19) showed glandular or signet ring features. A minor cohort demonstrated rhabdoid cells (4 of 19)., Conclusions: Head and neck carcinomas with SMARCB1 deficiencies have a wide array of morphologies and tend to demonstrate high-grade features. Only a minor cohort demonstrate rhabdoid-type cells. Evaluation of SMARCB1 deficiency for potential targeted therapy should not be limited to tumors with rhabdoid morphology., (Copyright © 2020. Published by Elsevier Inc.)

Switch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), also known as integrase interactor 1-deficient sinonasal carcinoma, is a rare entity that was first described in 2014. Since then, there have been 39 cases published in the literature, with basaloid or plasmacytoid/rhabdoid morphology being the most common pathological subtype. We report a patient with switch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (integrase interactor 1)-deficient sinonasal carcinoma who had permanent vision loss after valsalva-induced acute hemorrhage and resultant orbital compartment syndrome., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although there are many studies on the role of PI3K/AKT/mTOR pathway and autophagy genes in the mechanism of head and neck cancer formation and prognostic significance, there is no study investigating the role of the genes in paranasal sinus carcinomas. The aim of the study was to assess the role of the PI3K/AKT/mTOR pathway and autophagy related gene expression changes in squamous cell carcinoma of paranasal sinuses with and without neck metastasis. Eight paranasal squamous cell carcinoma patients (five without and three with neck metastasis) were included. Tissues were obtained during the surgery. Total RNA was isolated from the tissues and cDNA synthesis was performed. Expression levels of the genes were determined using qRT-PCR method. The results were evaluated using the 2 -∆∆Ct method, and fold changes of the gene expression levels in primary tumor and neck metastasis tissues were calculated according to the normal tissue. Expression levels of both PI3K/AKT/mTOR pathway and positive regulators of autophagy were significantly increased in metastasis-related two groups, especially in neck metastasis tissues. The increase in PI3K/AKT/mTOR pathway and autophagy related gene expression levels may support the metastatic character in paranasal squamous cell carcinomas. This is the first study to assess autophagy related genes in paranasal sinus cancer at transcriptome-level. Support of the transcriptome-level findings by the further protein analyses will contribute to the illumination of the rare paranasal sinus cancer molecular biology.

The prevalence and prognostic value of human papillomavirus (HPV) infection and epidermal growth factor receptor (EGFR) alteration in sinonasal squamous cell carcinoma (SNSCC) are not known. The reliability of p16 overexpression as a surrogate for HPV infection in SNSCC is also unclear. We investigated the prognostic and diagnostic significances of HPV infection, EGFR alteration, and p16 expression in SNSCC. We analyzed high-risk HPV infection by HPV-RNA in situ hybridization and EGFR gene copy number gain (CNG) by chromogenic in situ hybridization and by determining the protein expressions of p16, Rb, and EGFR by immunohistochemistry in 101 SNSCC cases. HPV infection (n=9, 8.9%) and p16 overexpression (n=15, 14.9%) were associated with better overall survival (P=0.0042 and 0.005, respectively). The HPV cases were located predominantly at the nasal cavity with nonkeratinizing histology and partial loss of Rb. Notably, 40% (6/15) of p16 SNSCCs were HPV. Two of these cases showed complete loss of Rb expression by immunohistochemistry, suggesting a reason for the above discrepancy. EGFR CNG, detected in 30.5% of the SNSCCs, was correlated with EGFR protein overexpression (P=0.0001). HPV infection and EGFR CNG were mutually exclusive. The HPV/EGFR CNG group had significantly better overall survival than the HPV/EGFR CNG and HPV/EGFR CNG groups (P=0.0471 and 0.0343, respectively). Our results suggest that HPV infection is a favorable prognostic marker in SNSCC, but p16 is not a perfect surrogate marker; the Rb expression pattern may improve the diagnostic accuracy. The molecular subclassification of SNSCCs based on HPV infection and EGFR copy number status might provide important information for therapeutic strategies.

Objective: Neutrophil infiltration in patients with sinonasal inverted papilloma (SNIP) is significantly high. Whether IL-17, which is a potent factor mediating neutrophilic inflammation, is involved in the neutrophilic phenotype of SNIP is investigated in the current study., Study Design: Laboratorial study., Participants: Nasal papilloma and inferior turbinate were collected from patients with SNIP (n = 50) and control subjects with septal deviation (n = 15)., Methods: IL-17 + cells were evaluated in tissues obtained from patients with SNIP and control subjects with septal deviation, by immunohistochemistry and flow cytometry., Main Outcome Measures: The IL-17 + cells were mainly localised in mononuclear cells and neutrophils, and were up-regulated in the SNIP samples compared with those in the controls. The IL-17 + T-cell subsets mainly included CD4+ (Th17, 60.0%) and CD8+ (Tc17, 30.0%), and both subsets were enhanced in the SNIP samples than controls. The total level of IL-17 + cells was significantly correlated with neutrophil infiltration in the SNIP tissues. Furthermore, the SNIP homogenates could significantly promote IL-17 production in peripheral blood mononuclear cells., Conclusions: An increase in IL-17 + cells is evident in SNIP and may be involved in neutrophil infiltration in local tissues. IL-17 could be a potential therapeutic target to relieve the neutrophilic pathological change in SNIP., (© 2019 John Wiley & Sons Ltd.)

We report a case of a 2-year-old female who presented with bilateral progressive proptosis, visual loss, nasal obstruction, and breathing difficulty. Magnetic resonance imaging revealed a large sino-orbital mass that was extending to the orbital apex and skull base. An initial diagnosis of rhabdomyosarcoma was made elsewhere on the basis of the presence of round and spindle cell tumor. Subsequent biopsy with immunohistochemical staining was positive for nuclear staining with β-catenin, shifting the diagnosis to a myofibroblastic tumor, favoring desmoid-type fibromatosis. With image guidance, near complete excision of tumor was performed by a multidisciplinary team, while respecting danger zones such as the skull base and the optic nerve. Following a recurrence over 2 months, additional excision was performed with a 6-month treatment of methotrexate and vinblastine. Desmoid tumor is a rare form of soft tissue tumor uncommonly seen in the orbital area. Although benign, it is known to be recurrent and infiltrative. Few data are known and further information will aid in the management of these tumors.

Background: Currently, the expression patterns of epidermal growth factor receptor (EGFR) family genes in sinonasal inverted papilloma (SNIP) and inverted papilloma with squamous cell carcinoma (IPwSCC) are not clear. Objective: This study aimed to investigate the expression of EGFR family members and their ligands in SNIP and IPwSCC and to analyze their correlations with SNIP histological grade and Krouse stage. Materials and methods: Data from 25 cases of inverted papilloma patients in China were collected and divided into 16 cases in the SNIP group and 9 in the IPwSCC group. In addition, eight cases of normal nasal mucosa (NNM) were collected and used as the control group. The expression levels of EGFR family members and their ligands in the NNM and SNIP groups and EGFR family members in the IPwSCC group were evaluated using immunohistochemistry and qRT-PCR. In addition, their correlations with the SNIP histological grade and Krouse stage were analyzed. The statistical analysis was performed using the GraphPad Prism 7.0 statistical software. Results: The ErbB1 and ErbB2 mRNA and protein expression levels were significantly higher in the SNIP group than in the NNM group ( p  < .01). The ErbB1 and ErbB2 protein expression levels were significantly higher in the IPwSCC group than those in the NNM and SNIP groups ( p  < .01). The ErbB1 and ErbB2 mRNA and protein expression levels in the SNIP group were positively correlated with the SNIP dysplasia grade. Conclusion: Upregulation of ErbB1 and ErbB2 expression may be associated with SNIP pathogenesis and carcinogenesis.

Background: Sinonasal inverted papilloma (IP) is a benign tumor with a high risk of local recurrence and a potential to malignify and Human papillomavirus (HPV) has been suggested an etiological factor. p16INK4a (p16) overexpression is considered a surrogate marker for HPV, but whether p16 and HPV correlate to IP is uncertain. Besides, a prognostic role of tumor infiltrating lymphocytes (TILs) are observed in many tumors, however their role in IP is sparsely studied. Aims/objectives: We hence analyzed IPs for the presence and the prognostic role of HPV and p16 overexpression together with CD8+ and FoxP3+ TILs in a population-based study. Material and methods: 98 IP patients diagnosed 2001-2010 were identified from the Swedish Cancer Registry and analyzed for HPV by PCR and p16, CD8 and FoxP3 was by immunohistochemistry. Results: In total, 12.2% of the IPs were HPV-positive (nine HPV-11, two HPV-6 and one HPV-45). Patients with HPV-positive lesions were younger ( p =  .003) and tended to present with more dysplasia. No correlation was observed between TILs and prognosis. Conclusions and significance: Our data suggests that patients with HPV-positive IPs present with different clinical characteristics, suggesting possibly different disease entities. Moreover, recurrences may occur >5 years, which should be considered in the follow-up.

Objective: SMARCB1-deficient sinonasal tract carcinomas are an emerging subset of rare tumors recently described in the literature, with less than 100 reported cases. Given the aggressive nature of this tumor, timely diagnosis is especially important. We present a case report of a SMARCB1-deficient carcinoma of the sinonasal tract., Methods: Case report with review of the literature., Results: The patient was a 53-year-old male with computed tomography (CT)-proven mass of the right ethmoid and sphenoid sinuses. Rigid nasal endoscopy revealed a purple mass completely obstructing the right nasal cavity that extended inferiorly from the posterior ethmoids and sphenoid sinuses. Initial biopsy in the emergency room was nondiagnostic due to extensive tumor necrosis. Magnetic resonance imaging (MRI) revealed T2 hypointense enhancing mass centered in the right posterior ethmoids with invasion into the right orbital apex, classifying it as a T4b tumor. The patient underwent repeat biopsy with frozen section and tumor debulking. Immunohistochemical analysis of subsequent biopsy revealed complete loss of INI-1 and negative staining for other pertinent markers, alluding to the diagnosis of SMARCB1-deficient sinonasal tract carcinoma., Conclusion: Tumor necrosis may be problematic in obtaining a diagnosis for SMARCB1-deficient sinonasal carcinomas. Thus, sampling various regions of the tumor during initial biopsy can prevent delays in diagnosis and treatment.

In this study we investigated the expression of mucins (MUC1, MUC2, MUC4, MUC5AC and MUC6) in a series of 66 sinonasal adenocarcinomas, in order to establish their distribution and the possible correlation with clinicopathological and prognostic parameters. The series included 51 intestinal type adenocarcinomas, 4 non-intestinal type adenocarcinomas, and 11 salivary gland type carcinomas. The immunohistochemical analysis was conducted on a tissue microarray obtained from formalin fixed-paraffin embedded tumor tissue samples. Thirty-nine adenocarcinomas (59.1%) resulted positive for MUC1, 21 (41.2%) for MUC2, 47 (71.2%) for MUC4, and 16 (24.2%) for MUC5AC, while MUC6 was negative in all cases tested. MUC1 was significantly more expressed in ITACs than in non-ITACs (70% vs 20%, p = 0.0007) while MUC2 was expressed only in ITACs (p = 0.0015) with a clear prevalence in the mucinous subtype (p < 0.0001). Conversely, MUC4 and MUC5AC were similarly expressed in the sinonasal adenocarcinoma subtypes tested. High expression of MUC 1 was related to a significantly shorter overall survival, both in the whole series (p = 0.04), while adenocarcinomas positive for MUC 2 tended to have a worse overall survival (p = 0.07). In addition, MUC2 expression was higher in ITACs with distant metastasis, being expressed in 4 out of 5 cases (p = 0.015). We conclude that sinonasal adenocarcinomas have a characteristic expression of different mucin types, with significant clinicopathologic correlations. In view of the extensive involvement of mucins in different aspects of tumor growth and their emerging role as possible therapeutic targets, our study suggests that these factors could be considered clinically relevant biomarkers and attractive targets for new treatments in sinonasal adenocarcinomas., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Given that the prognosis of patients with sinonasal intestinal-type adenocarcinoma (ITAC) has not significantly changed recently, there is a desire for new therapeutic approaches to improve clinical management. HER2-targeted therapy has remarkably improved the overall survival of patients with HER2 amplified tumors. To date, HER2 assessment has produced contradictory results in ITAC. The aim of this study was to assess HER2 status at both protein and DNA levels in a large series of ITAC. HER2 status was assessed by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in forty-three patients that underwent surgical resection for ITAC at the Otorhinolaryngology Section, Padua University Hospital, between 2007 and 2016. IHC was evaluated using the four-tier score developed for gastroesophageal cancer. As for IHC, 83.7% (36/43) of ITAC were scored 0, 14% (6/43) 1+, and 2.3% (1/43) 2+. No HER2 amplification was detected by CISH. The present is the largest study of sinonasal ITAC tested with both IHC and CISH confirmation for HER2 status. No HER2 overexpression/amplification was detected. Contrary to previous studies, our findings seem to rule out any oncogenetic role of HER2 in ITAC pathogenesis., (Copyright © 2019. Published by Elsevier GmbH.)

Objective: To compare genome-wide DNA methylation between samples of sinonasal inverted papilloma (SNIP) and squamous cell carcinoma (SCC) samples in order to identify aberrantly methylated genes that might be involved in malignant transformation., Methods: Tissue samples were collected from patients. DNA methylation in C-phosphate-G islands and gene promoters was analysed using a DNA methylation microarray kit. The levels of mRNA or protein from aberrantly methylated genes were measured using real-time polymerase chain reaction or Western blot analysis., Results: A total of 27 tissue samples were included in this study; 15 SNIP samples and 12 SCCs arising in SNIPs. A total of 11 201 nominally differentially methylated sites were observed between SNIP and SCC arising in SNIPs. Six sites were significantly different at P < 0.01 and contained three genes ( MIR661, PLEC and OPA3). These three genes were hypermethylated. In addition, the levels of mature miR-661 mRNA and PLEC protein were significantly upregulated in SCC tissues compared with SNIP samples. The levels of OPA3 protein were downregulated in SCC tissues compared with SNIP samples., Conclusions: This study demonstrated hypermethylation and abnormal expression of the MIR661, PLEC and OPA3 genes, suggesting a role for their involvement in the malignant transformation of SNIP.

Background and Objectives: We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma., Material and Methods: The immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC., Results: Loss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (p=0.005). Overexpression of pS6 was associated with a decrease in survival (p=0.008), presence of local recurrences (p=0.055), and worsening of overall prognosis (p=0.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied., Conclusions: Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker., (Copyright © 2018. Publicado por Elsevier España, S.L.U.)

Objective: We aimed to evaluate the contribution of different standardized uptake value (SUV) parameters generated from pretreatment 18 F-FDG PET/CT in the characterization of sinonasal neoplasms with histopathologic correlations., Materials and Methods: This retrospective study included 97 consecutive patients (58 men, 39 women; age range, 20-93 years; mean age, 62 years) with pathologically proven untreated sinonasal neoplasms who underwent FDG PET/CT from February 2010 to August 2017. Semiquantitative analysis of primary tumors were performed to evaluate the maximum standardized uptake value (SUV max ), mean standardized uptake value (SUV mean ), and the ratio of the SUV max of the primary tumor to the SUV mean of mediastinal blood pool, which we refer to here as " SUV ratio ." Various sinonasal tumor histopathologic subgroups (n = 14) were analyzed. The Kruskal-Wallis test was used to compare the SUV max , SUV mean , and SUV ratio with the histopathologic diagnosis., Results: Mean values of SUV max , SUV mean , and SUV ratio for the sinonasal neoplasms were 16.6 ± 9.7 (SD), 8.6 ± 5.1, and 5.9 ± 3.7, respectively, and each parameter was significantly different between histopathologic types (p < 0.05). Mean values of SUV max , SUV mean , and SUV ratio were higher in sinonasal undifferentiated carcinoma (SNUC) than in olfactory neuroblastoma, metastasis, and adenoid cystic carcinoma (p < 0.05). Mean values of SUV max and SUV mean were higher in squamous cell carcinoma (SCC) than in olfactory neuroblastoma and metastasis (p < 0.05). Also, mean SUV max was higher in SCC and SNUC than in poorly differentiated carcinoma (p < 0.05). Mean SUV ratio was higher in SCC than in small cell carcinoma, olfactory neuroblastoma, and adenoid cystic carcinoma (p < 0.05)., Conclusion: We conclude that different SUV parameters from FDG PET/CT can be used as so-called "metabolic biopsy" to categorize sinonasal neoplasms into different histopathologic subgroups because it can help in the characterization of some of the more common subgroups of sinonasal neoplasms. However, we found that there is overlap in FDG uptake values among some of the rare histologic subgroups; hence, surgical biopsy is still needed for differentiation of histologic subtypes of aggressive sinonasal masses.

Introduction: Sinonasal inverted papilloma constitute relevant therapeutic problem due to destructive character of growth, tendency to recur and the possibility of malignant transformation. Therefore, many attempts to identify risk factors for inverted papilloma occurrence have been undertaken, as well as research to find markers that would allow for the earlier detection of tumors and the application of adequate therapy. A widely known risk factor of inverted papilloma is HPV infection. One of the markers of HPV infection and the ongoing effect of this change (although arousing some controversy) is the expression of the p16 protein., Objective: The aim of the study was to analyze the correlation between the expression of p16 as a surrogate of HPV infection in analyzed histopathological material and epidemiological variables, recurrences or malignant transformation., Methods: The retrospective study includes a group of 53 patients (18 women and 35 men) undergoing treatment for sinonasal inverted papilloma in the period of 2002-2012. The intensity of the p16 protein in histopathological material was scored as: 0 - no expression, 1 - diffuse expression (borderline) and 2 - positive expression; or 0 - no expression/diffuse expression (borderline); 1 - positive expression. The Ethics Committee agreement was obtained (1089/12; 245/13)., Results and Conclusion: There was no statistically significant relationship between the expression of p16 and the age of patients, cigarette smoking, tumor location, tumor staging according to the Krouse and Cannady classification, the presence of dysplasia or the occurrence of relapse., (Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Introduction: Biphenotypic sinonasal sarcoma (BSNS) is a recently described mesenchymal tumor exclusive to the sinonasal region. It is a low grade sarcoma, displaying evidence of myogenic and neural differentiation. Role of β-catenin immunohistochemistry in distinguishing it from its morphological mimics is not well-established. We conducted this study to identify cases of BSNS from our archives, and to examine immunopositivity for β-catenin in them as well as in its close differential diagnosis., Methods: All cases of nasal cavity and paranasal sinus mesenchymal neoplasms were identified. Histopathological features were reviewed. Cases showing smooth muscle actin (SMA) and S-100 immunopositivity, and typical morphology were reclassified as BSNS. β-catenin immunoexpression was assessed., Results: Twenty-one mesenchymal tumors, including 12 sinonasal hemangiopericytoma (SNHPC), five solitary fibrous tumors (SFT), three BSNS, and one synovial sarcoma were identified. Three SNHPC cases were reclassified as BSNS. BSNS patients included one male and five females, with mean age of 51years. Five BSNS cases (83.3%) showed nuclear β-catenin immunopositivity. SNHPC cases also were β-catenin positive (60%)., Conclusion: BSNS is a rare sinonasal neoplasm, frequently misdiagnosed as SNHPC and SFT. β-catenin immunopositivity is seen in majority of cases, indicating a role in pathogenesis. However, due to positivity in other tumors like SNHPC, it has limited role in differential diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the correlation between the expression of programmed death-1(PD-1), PD ligand-1(PD-L1), indoleamine 2, 3-dioxygenase 1(IDO-1) and clinical parameters in sinonasal malignant mucosal melanoma (SNM). Methods: Samples from 86 SNM patients who did not receive immune-targeted therapy and radio-chemotherapy were analyzed for PD-1, PD-L1, and IDO-1 expression by immunohistochemistry. Results: High clinical/pathologic staging, brain metastases and advanced age were independent risk factors of poor prognosis. The overall survival rate of SNM without pigment was lower than that with pigment. PD-1, PD-L1 and IDO-1 expression was not correlated with tumor pigmentation, but correlated with different primary site.PD-1, PD-L1 and IDO-1 were expressed in 47.6% (41/86), 53.5% (46/86) and 58.1% (50/86)of SNM samples respectively. PD-1 was associated with brain metastasis. Negative expression of PD-1( P =0.031) and IDO-1( P =0.017 9) correlated with worse disease-free survival. No significant association was found between PD-L1 and prognosis. For stages Ⅲ, ⅣA and ⅣB patients, PD-1 expression was associated with better outcome ( P =0.025), but PD-L1 negative and IDO-1 positive patients hadworse outcome ( P >0.05). PD-1 positive and IDO-1 negative stage ⅣC patients had poorer overall survival. Conclusions: In SNM patients, clinical/pathologic staging, brain metastases, age and pigmentation were prognostic indicator. IDO-1 and PD-1 can also be used as reference to evaluate prognosis. Anti-IDO-1 targeted therapy may be suitable for middle to late stage patients, while advanced stage patients might benefit from anti-PD-1 targeted therapy. PD-1/PD-L1 and IDO-1 may be considered as joint targeted therapy.The predictive value of PD-L1 requires further study.

Background: Sinonasal renal cell-like carcinoma (SRCLC) is an extremely rare low malignant tumor arising in the sinonasal tract, with histological mimicry of renal cell carcinoma., Case Presentation: We present a case of sinonasal renal cell-like carcinoma in a 63-year-old male patient. Computer tomography(CT) scanning revealed a soft tissue mass at the left nasal cavity and choana. Histologically, the predominant tumor architecture was follicular to glandular with intervening fibrous septa. The tumor cells were uniform cuboidal to polyhedral with abundant clear or eosinophilic cytoplasm. Immunohistochemically, the tumor cells were strongly positive for CK7, EMA, vimentin, SOX10, S-100, and focally positive for CA9. During 6 months of follow-up, there was no clinical or radiological evidence of recurrence or metastasis., Conclusion: SRCLC has microscopic features which overlap with tumors that contain clear cells. Thus, several other tumors must be considered in the differential diagnosis of a tumor of the sinonasal region with clear cells, especially metastatic renal clear cell carcinoma. SRCLC is an indolent tumor and none of the reported SRCLC patients had metastatic disease.

Previous studies have confirmed that tropomyosin-related kinase B (TrkB) plays a critical role in the occurrence, development, and metastasis of many kinds of malignant tumour. More recently, TrkB was found to be overexpressed in head and neck squamous cell carcinoma (SCC) and to be involved in multistep tumour progression. In this study, the expression of TrkB was investigated in 27 cases of sinonasal SCC using an immunohistochemical method. The clinical significance and possible role of TrkB as a prognostic marker in these tumours was also explored. The results showed that TrkB was overexpressed in all cases of sinonasal SCC. A high level of expression of TrkB was significantly related with poor-to-moderate differentiation of SCC (P=0.026), high clinical stage (P=0.023), and the presence of local recurrence (P=0.004). Analysis by Kaplan-Meier method indicated that patients with high levels of TrkB expression had shorter overall survival (P=0.006) and disease-free survival (P=0.018). Multivariate analysis revealed that the level of TrkB expression was an independent prognostic factor for both overall and disease-free survival (P=0.019 and P=0.048, respectively). These data suggest that the overexpression of TrkB may play a significant role in sinonasal SCC and that TrkB may be used as a potential prognostic marker for the clinical outcome., (Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Chromosomal translocations at 2p23 cause overexpression of anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase involved in signalling pathways that regulate cell proliferation. This translocation occurs in 5% of lung adenocarcinoma and has been demonstrated to be useful as a therapeutic target for crizotinib. sinonasal adenocarcinomas (SNAC) are histologically similar to lung adenocarcinomas; the aim of this study was to evaluate the presence of ALK alterations in SNAC., Method: Break-apart fluorescent in-situ hybridization was used to analyse the presence of ALK translocations in 96 tumour samples. In addition, ALK protein expression was studied by immunohistochemistry., Results: The samples of SNAC did not show ALK translocation. Moreover, ALK protein expression was absent in all cases., Conclusions: These results suggest that ALK is not involved in SNAC., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.)

Background: Current guidelines have identified 10 to 12 weeks posttreatment as the ideal time-point for improved diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) for deep tissue sites of the head and neck. After treatment, the sinonasal skull base is predisposed to prolonged inflammation that may render this time-point inappropriate for initial posttreatment imaging surveillance for sinonasal malignancies. The purpose of this study is to evaluate temporal trends in 18 F-fluorodeoxyglucose ( 18 FDG) sinonasal uptake after treatment for sinonasal malignancies to better elucidate the optimal time-point for initial PET/CT posttreatment evaluation in this patient population., Methods: A retrospective analysis of all successfully treated and non-locally recurrent sinonasal malignancies over a 15-year study period (2000 to 2015) was performed at our institution. Posttreatment 18 FDG PET/CT standardized uptake value data were collected and compared between various time-points (2 to 4 months, 5 to 12 months, 5 to 24 months, and 13 to 24 months) using an independent-samples t test., Results: A statistically significant difference was noted between the posttreatment time windows 2 to 4 and 5 to 12 months (p = 0.048) as well as 2 to 4 and 5 to 24 months (p = 0.02). A trend toward significance was seen when comparing 2 to 4 and 13 to 24 months (p = 0.083)., Conclusion: Our analysis of PET/CT in patients previously treated for sinonasal malignancy suggests that the posttreatment sinonasal skull base is characterized by a prolonged period of hypermetabolism that endures beyond the period previously described for deep tissue sites of the head and neck. These findings prompt a reevaluation of the previously described 10- to 12-week cutoff point for initial posttreatment PET/CT for head and neck squamous cell carcinoma as applied to sinonasal malignancies., (© 2016 ARS-AAOA, LLC.)

Background: The purpose of this study was to investigate roles of human papillomavirus (HPV) infection and stathmin in sinonasal inverted papilloma (SNIP)., Methods: HPV DNA detection was performed by the fluorescence-based polymerase chain reaction (PCR) method. Stathmin protein expression was investigated by the immunohistochemistry method and mRNA expression of stathmin, Kif2a, and cyclin D1 were assessed by real-time PCR in SNIP and control subjects., Results: The positive rate of HPV DNA detected in SNIP was about 53.6% (15 of 28). Recurrent cases showed a higher rate of HPV infection compared with initial cases and higher Krouse stage (T3 + T4) cases showed higher rate of HPV infection than lower Krouse stage (T1 + T2) cases. Stronger expression of stathmin, Kif2a, and cyclin D1 were observed in SNIP, especially HPV(+) SNIP., Conclusion: HPV infection was closely associated with recurrence and progression of SNIP. Stathmin is a valuable prognostic marker and could be considered as a therapeutic target in patients with SNIP., (© 2015 Wiley Periodicals, Inc.)

The data on the incidence, localization, and histological structure of paranasal sinus osteoma (PSO) are reported along with the authors' experience in the diagnostics and surgical treatment of 42 patients presenting with this condition. The classification of the remote tumours based on their histopathological characteristics is considered. It is shown that 34 (80.9%) patients have osteomas of the compact type, 4 (9.5%) present with the tumours of the spongy type, and another 4 (9.5%) with the mixed type osteomas. It is maintained that the application of boron should be considered to facilitate the surgical removal of paranasal sinus osteomas.

Aims: Sinonasal mucosal malignant melanoma (SNMMM) is a rare disease. The aim of the present study was to describe its clinicopathological features and prognosis in a Chinese population., Methods: Data on 83 SNMMM patients were collected and analyzed. A survival analysis was performed using the Kaplan-Meier method and a log-rank test., Results: The most common presenting symptoms of SNMMM were nasal obstruction, epistaxis, and bloody rhinorrhea. Histopathologically, 38 cases (45.78%) were amelanotic. Five cell types (epithelioid, undifferentiated, plasmacytoid, spindle, and clear) were identified. Positive staining for human melanoma black-45 and Melan-A was diagnostic of SNMMM. Advanced age, multiple tumor sites, and amelanotic-type SNMMM indicated a worse outcome (p = 0.008, p = 0.009, and p = 0.013, respectively). Neither adjuvant therapy nor the tumor stage was associated with overall survival., Conclusions: SNMMM is an uncommon disease with atypical symptoms. Its histopathological appearance is variable, especially in the amelanotic type. Thus, immunohistochemistry is important in the diagnosis, and it should be performed according to the histology., (© 2016 S. Karger AG, Basel.)

Sinonasal malignant melanoma (SNMM) comprises less than 1% of all melanomas and is located in the nasal cavity and the paranasal sinuses. The majority of SNMMs have unknown underlying oncogenic driver mutations. The recent identification of a high frequency of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in cutaneous melanoma led us to investigate whether these mutations also occur in SNMM. Our aim was to determine the TERT promoter mutation frequencies in primary SNMMs. Laser capture microdissection and manual dissection were used to isolate tumour cells from 49 formalin-fixed paraffin-embedded tissues. The tumours were screened for TERT promoter mutations by direct Sanger sequencing. Information on NRAS, BRAF and KIT mutation was available from an earlier study. Overall, 8% (4/49) of SNMMs harboured TERT promoter mutations. One of these mutated tumours had a coexistent NRAS mutation and one had a BRAF mutation. Our findings show that TERT promoter mutations are present in a moderate proportion of SNMM. No conclusion can be drawn on their potential influence on the clinical outcome or tumour progression.

Primary sinonasal tumors with neuroendocrine differentiation (STNDs) are uncommon, with overlapping histology. According to the amount of neuroendocrine component, they can be subcategorized into esthesioneuroblastoma, high-grade sinonasal neuroendocrine carcinoma/small cell carcinoma, and sinonasal undifferentiated carcinoma. Achaete-scute homolog 1 (ASH1) is a master gene for neuroendocrine differentiation and is expressed in fetal and adult neuroendocrine tissues. Expression of ASH1 protein may be a useful marker for cancers with neuroendocrine features. The aim of this study was to compare and assess the value of ASH1 protein expression/levels in STND. We reviewed the morphological features and performed immunohistochemical analyses for ASH1 in 30 samples of surgically resected cancers with neuroendocrine differentiation from our institution. Achaete-scute homolog 1 was found to be expressed in STND, indicating that it is instrumental in the development of a subset of neurons and neuroendocrine cells and plays a key role in regulating neuroendocrine differentiation in tumor cells. Achaete-scute homolog 1 levels were associated with the degree of STND tumor differentiation (high-grade tumors show increased expression of this protein), correlating well with studies indicating that expression of ASH1 appears to be restricted to immature cells., (Published by Elsevier Inc.)

Oncogenic osteomalacia (OOM) is a rare bone disease characterized by inadequate bone mineralization and is caused by a humoral factor mainly produced by benign mesenchymal tumors. We report a case of OOM caused by an occult phosphaturic mesenchymal tumor in the paranasal sinus. The causative tumor was small and localized in the ethmoid sinus, and the patient did not exhibit any nasal symptoms. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) depicted the location of the occult tumor, and systemic venous sampling followed by assessments of the samples' fibroblast growth factor 23 (FGF23) concentrations confirmed that the tumor secreted FGF23. The tumor was resected via an external surgical approach, resulting in the complete relief of the patient's symptoms. The combination of FDG-PET and systemic venous sampling to assess serum FGF23 levels is useful for identifying small asymptomatic OOM-associated tumors. Such tumors are rare, but a significant proportion of them develop in the head and neck region, and complete resection is the most effective treatment. It is important that ENT surgeons are aware of the characteristics of OOM., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To explore the expression and significance of programmed cell death 5 (PDCD5) and Bcelllymphoma/lewkmia-2(Bcl-2) in sinonasal squamous cell carcinoma (SNSCC)., Method: Immunohistochemical method and Western Blot method was used to determine the expression of PDCD5 and Bcl-2 in specimen of SNSCC in thirty cases, sinonasal inverted papillomas (SNIP) in thirty-eight cases, and normal nasal mucosa in twenty cases., Result: (1) The expression of PDCD5 protein in SNSCC significantly decreased compared with SNIP and normal nasal mucosa. (2) The expression of Bcl-2 protein in SNSCC up-regulated obviously compared with SNIP and normal nasal mucosa. (3) Positive rate of PDCD5 protein and Bcl-2 protein in well, moderate and low differentiatied group is respectively 100.00%, 83.33%, 38.89% and 50.00%, 70.83% and 100.00%, the difference was statistically significant (P < 0.05). (4) In the follow-up cases, the survival rate of the patients with higher expression of PDCD5 protein was higher, but that with lower expression of Bcl-2 protein was higher., Conclusion: The inactivation of PDCD5 protein and the activation of Bcl-2 protein may play an important role in the development of SNSCC, and there are a positive correlation between PDCD5 and Bcl-2 protein in SNSCC, which may be identified as a new therapeutic target.

Background: Little is known about the molecular signature of the rare tumor sinonasal squamous cell carcinoma (SNSCC). The purpose of this study was to comprehensively assess various molecular biomarkers in SNSCC., Methods: We chose 13 markers for this study, which have been known as prognostic markers in head and neck squamous cell carcinoma. Expression of these markers was examined by either in situ hybridization or immunohistochemical methods on tissue microarrays made from 70 SNSCC specimens and 28 matched-pair normal tissues from patients who underwent surgical resection at our institution. Expression data were correlated with patient clinicopathologic parameters and survival., Results: Of the 13 markers, only epidermal growth factor receptor (EGFR) protein expression was associated with significantly shorter disease-free survival (DFS; p = .01307). EGFR expression was also associated with shorter overall survival (OS), but the difference was not statistically significant., Conclusion: Targeted inhibition of tumor EGFR expression may be a new approach to treating SNSCC., (Copyright © 2013 Wiley Periodicals, Inc.)

Galectins, a family of endogenous lectins, are multifunctional effectors that act at various sites and can be used in immunohistochemical localization studies of diseased states. Since they form a potentially cooperative and antagonistic network, we tested the hypothesis that histopathological fingerprinting of galectins could refine the molecular understanding of naso-sinusal pathologies. Using non-cross-reactive antibodies against galectin-1, -3, -4, -7, -8 and -9, we characterized the galectin profiles in chronic rhinosinusitis, nasal polyposis, inverted papillomas and squamous cell carcinomas. The expression, signal location and quantitative parameters describing the percentage of positive cells and labeling intensity were assessed for various cases. We discovered that inverted papillomas showed a distinct galectin immunohistochemical profile. Indeed, epithelial overexpression of galectin-3 (p=0.0002), galectin-4 (p<10-6), galectin-7 (p<10-6) and galectin-9 (p<10-6) was observed in inverted papillomas compared to non-malignant diseases. Regarding carcinomas, we observed increased expression of galectin-9 (p<10-6) in epithelial cells compared to non-tumor pathologies. Our results suggest that galectin-3, -4, -7 and -9 could be involved in the biology of inverted papillomas. In addition, we observed that the expression of galectin in naso-sinusal diseases seems to be affected by tumor progression and not inflammatory or allergic phenomena.

Sinonasal squamous cell carcinomas (SCC) are rare tumors, etiologically related to occupational exposure to wood and leather dust. In spite of surgical and radiotherapeutic advances, the 5 year survival is still 30-50%. Therefore, alternative treatment options are needed. We report the establishment and characterization of six unique human sinonasal SCC cell lines, named SCCNC1, 2, 4, 5, 6 and 7. In vitro growth and invasion characteristics were evaluated and genetic profiles were compared to those of the original primary tumors. The population doubling times ranged from 21 to 34 hours. Cell lines SCCNC2 and 7 were highly invasive in matrigel. Five cell lines carried a high number of copy number alterations, including amplifications and homozygous deletions, while one showed only three abnormalities. Sequence analysis revealed three cell lines with TP53 mutation and none with KRAS or BRAF. Overexpression of p53 was observed in five, and of EGFR in four cell lines. None of the cell lines showed strong immunopositivity of p16 or presence of human papilloma virus. In conclusion, we have created six new cell lines that are clinically and genetically representative of sinonasal SCC and that will be a useful tool for the preclinical testing of new therapeutic agents.

Objective: To investigate the expression and clinical significance of phosphatase and tensin homology deleted on chromosome ten (PTEN) and hypoxia-inducible factor 1 alpha (HIF-1α) in sinonasal inverted papilloma (SNIP) of different pathological grades., Methods: Fifty-five paraffin samples from patients with SNIP and a control group of 10 paraffin samples of patients with normal nasal cavity mucosa (NM) who underwent inferior turbinectomy were consisted in this study. Among the 55 cases of SNIP, 30 cases were without dysplasia subtypes, 11 cases were with dysplasia subtypes, and 14 cases with canceration to squamous cell carcinoma (SCC) subtypes. PTEN and HIF-1α expression in SNIP was detected by immunohistochemistry. The differences between NM and SNIP, and among the three subtypes were analyzed, and the relationship between PTEN, HIF-1α expression and SNIP recurrence and the correlation between PTEN expression and HIF-1α expression were also analyzed. SPSS 16.0 software was used to analyze the data., Results: The positive expression rate of PTEN in NM and SNIP was 100% and 65.5%, the difference was significant (U = 147, P = 0.014), while HIF-1α was 0 and 30.9%, the difference was significant (U = 190, P = 0.045). The positive expression rate of PTEN in SNIP without dysplasia, SNIP with dysplasia and NSCC was 83.3%, 63.6%, 28.6%, respectively, the difference was significant (H = 12.644, P = 0.002); while HIF-1α was 16.7%, 45.5%, 50.0%, respectively, the difference was significant (H = 8.292, P = 0.016). A total of 22 SNIP patients recurred. PTEN had lower expression in recurrent SNIP (45.5%) than that in non-recurrent SNIP (82.8%), and the difference was significant(χ² = 7.834, P = 0.005). However, the expression of HIF-1α had no significant difference between recurrent SNIP and the SNIP which had no recurrence (χ² = 0.901, P = 0.343). The expression of PTEN protein was negatively correlated with that of HIF-1α protein (r = -0.503, P = 0.001)., Conclusions: PTEN expression decreased graduately with the severity of malignancy of SNIP, but HIF-1α increased. The expression of HIF-1α was induced by hypoxia, which may negatively effect the expression of PTEN, and both HIF-1α and PTEN may play critical roles in the progress of SNIP. PTEN is one of the factors responsible for the postoperative recurrence of SNIP.

Squamous cell carcinoma (SCC) of the head and neck display high frequencies of DNA copy number gains at chromosomal region 3q26-27. Recently SOX2 has been postulated as a driver oncogene for these amplifications; however, its role as a prognostic marker is still a matter of debate. The aim of this study was to evaluate the involvement of SOX2 protein expression in three different sublocalizations of head and neck SCC and its possible role as prognostic marker. SOX2 expression was analyzed by immunohistochemistry in 102 pharyngeal, 67 laryngeal, and 51 sinonasal SCCs, and the relation to clinicopathological and follow-up data was studied by χ(2) and Kaplan-Meier analysis. SOX2 expression was significantly (P = .002) more frequent in hypopharyngeal and laryngeal SCC (38%, 39/101) and (42%, 28/67), respectively, compared to sinonasal cancer SCC (14%, 7/51). SOX2 expression did not correlate to disease stage, T or N classification, lymph node metastasis, recurrence or clinical outcome in any of the three sublocalizations. These results indicate that SOX2 expression is a common event in hypopharynx and larynx, but not in sinonasal SCC. The absence of correlation to clinical outcome, may suggest a role for SOX2 in tumor initiation, but not in tumor progression., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Primary sinonasal tract and nasopharyngeal adenoid cystic carcinomas (STACC) are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. Eighty-six cases of STACC included 45 females and 41 males, aged 12-91 years (mean 54.4 years). Patients presented most frequently with obstructive symptoms (n = 54), followed by epistaxis (n = 23), auditory symptoms (n = 12), nerve symptoms (n = 11), nasal discharge (n = 11), and/or visual symptoms (n = 10), present for a mean of 18.2 months. The tumors involved the nasal cavity alone (n = 25), nasopharynx alone (n = 13), maxillary sinus alone (n = 4), or a combination of the nasal cavity and paranasal sinuses (n = 44), with a mean size of 3.7 cm. Patients presented equally between low and high stage disease: stage I and II (n = 42) or stage III and IV (n = 44) disease. Histologically, the tumors were invasive (bone: n = 66; neural: n = 47; lymphovascular: n = 33), composed of a variety of growth patterns, including cribriform (n = 33), tubular (n = 16), and solid (n = 9), although frequently a combination of these patterns was seen within a single tumor. Pleomorphism was mild with an intermediate N:C ratio in cells containing hyperchromatic nuclei. Reduplicated basement membrane and glycosaminoglycan material was commonly seen. Necrosis (n = 16) and atypical mitotic figures (n = 11) were infrequently present. Pleomorphic adenoma was present in 9 cases; de-differentiation was seen in two patients. Immunohistochemical studies showed positive reactions for pan-cytokeratin, CK7, CK5/6, CAM5.2, and EMA, with myoepithelial reactivity with SMA, p63, calponin, S100 protein and SMMHC. CD117, CEA, GFAP and p16 were variably present. CK20 and HR HPV were negative. STACC needs to be considered in the differential diagnosis of most sinonasal malignancies, particularly poorly differentiated carcinoma, olfactory neuroblastoma and pleomorphic adenoma. Surgery (n = 82), often accompanied by radiation therapy (n = 36), was generally employed. A majority of patients developed a recurrence (n = 52) 2-144 months after initial presentation. Overall mean follow-up was 19.4 years (range 0.4-37.5 years): 46 patients died with disease (mean 6.4 years); 5 were alive with disease (mean 5.4 years), and 35 patients were either alive or had died of unrelated causes (mean 16.3 years). ACC of the SNT is uncommon. Recurrences are common. The following parameters, when present, suggest an increased incidence of either recurrence or dying with disease: mixed site of involvement, high stage disease (stage IV), skull base involvement, tumor recurrence, a solid histology, perineural invasion, bone invasion, and lymphovascular invasion.

Intestinal-type adenocarcinoma (ITAC) is a rare form of sinonasal cancer characterized by an association with exposure to industrial dusts, aggressive clinical behavior, and histologic/immunophenotypic similarity to tumors of the gastrointestinal tract. ITAC is sometimes very poorly differentiated and difficult to distinguish from other sinonasal neoplasms, particularly in a limited biopsy. CDX-2 and cytokeratin 20 are consistently immunoreactive in ITAC and as a result, these immunostains are often used to support the diagnosis. However, CDX-2 and cytokeratin 20 have not been tested on a broad range of sinonasal tumors, so their specificities remain unknown. Immunohistochemistry for CDX-2 and cytokeratin 20 was performed on 6 sinonasal ITACs as well as 176 non-intestinal-type sinonasal neoplasms. CDX-2 and cytokeratin 20 were positive in all 6 cases of ITAC. CDX-2 immunoexpression was also observed in 17 of 176 (10 %) non-intestinal-type tumors including 6 of 16 (38 %) sinonasal undifferentiated carcinomas, 8 of 81 (10 %) squamous cell carcinomas (including 5 of 39 non-keratinizing variants), 2 of 20 (10 %) salivary-type adenocarcinomas, and 1 of 2 (50 %) small cell carcinomas. In contrast, among non-intestinal types of sinonasal tumors, cytokeratin 20 was only focally observed in 1 of 176 non-intestinal tumors (a non-keratinizing squamous cell carcinoma). All cases of non-intestinal surface-derived adenocarcinoma and esthesioneuroblastoma were negative for both markers. Both CDX-2 and cytokeratin 20 are highly sensitive for the diagnosis of sinonasal ITAC, but cytokeratin 20 is more specific. CDX-2 staining may be observed in other high grade tumor types, especially sinonasal undifferentiated carcinoma and non-keratinizing squamous cell carcinoma. As a result, in the setting of a poorly differentiated sinonasal carcinoma the diagnosis of ITAC should not be based on CDX-2 immunoexpression alone. Clear-cut glandular differentiation and cytokeratin 20 immunoexpression are more reliable features.

Leiomyomas are benign myogenic tumors that seldom occur in the sinonasal cavity. They were commonly found in middle-aged adults with a female predominance. Clinical symptoms include nasal obstruction with discharge, nasal bleeding and pain. We describe the case of a 48 year-old woman with a leiomyoma arising from right inferior nasal turbinate. Transnasal endoscopic excision was performed with satisfied result. The tumor was found to be progesterone receptor positive on immunohistochemical analysis. The clinical findings are addressed with a review of the literature. To the best of our knowledge, this is the third reported case that supports the growth of the tumor may be hormone-dependent.