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.

Transcription Factor Expression in Sinonasal Neuroendocrine Neoplasms and Olfactory Neuroblastoma (ONB): Hyams' Grades 1-3 ONBs Expand the Spectrum of SATB2 and GATA3-Positive Neoplasms.

Sinonasal neuroendocrine neoplasms (SN-NENs) are rare and mostly include neuroendocrine carcinoma (NEC), whereas neuroendocrine tumor (NET) is exceptional in this site. Olfactory neuroblastoma (ONB) is a malignant neuroectodermal neoplasm arising in the nasal cavity. Albeit crucial for correct patients' management, the distinction of high grade ONB from NEC is challenging and requires additional diagnostic markers. The transcription factor SATB2 has been recently introduced in routine diagnostics as an immunohistochemical marker of distal intestine differentiation. No specific data are available about SATB2 and GATA3 expression in SN-NENs. GATA3, SATB2, and, for comparison, CDX2 expression were investigated in a series of epithelial and non-epithelial SN-NENs. We collected 26 cases of ONB and 7 cases of epithelial SN-NENs diagnosed and treated in our Institution. ONBs were graded according to Hyams' system and epithelial NENs were reclassified into 5 NECs, 1 MiNEN, and 1 amphicrine carcinoma. Immunohistochemistry was performed using standard automated protocols. Hyams' grades 1-3 ONBs stained diffusely and intensely for SATB2, whereas grade 4 ONBs and NECs were globally negative. The non-neuroendocrine component of MiNEN and the amphicrine carcinoma were strongly positive. GATA3 was heterogeneously and unpredictably expressed in Hyams' grades 1-3 ONBs, whereas grade 4 ONBs and NECs were completely negative. CDX2 was negative in all cases. Our study identifies, for the first time, SATB2 and GATA3 expression as features of Hyams' grades 1-3 ONBs, expands the spectrum of SATB2 and GATA3-positive neoplasms, and suggests that Hyams' grade 4 ONBs are not only clinically but also biologically different from low graded ONBs.

Decreased Expressions of CK1α and PTEN in Sinonasal Inverted Papilloma.

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.

SSTR2 Expression in Olfactory Neuroblastoma: Clinical and Therapeutic Implications.

Somatostatin receptor 2 (SSTR2) expression has previously been documented in olfactory neuroblastoma (ONB). Here, we fully characterize SSTR2 expression in ONB and correlate staining results with clinicopathologic parameters including Hyams grade. We also assess SSTR2 immunohistochemistry expression in various histologic mimics of ONB to assess its diagnostic functionality. 78 ONBs (51 primary biopsies/excisions and 27 recurrences/metastases) from 58 patients were stained for SSTR2. H-scores based on intensity (0-3 +) and percentage of tumor cells staining were assigned to all cases. 51 histologic mimics were stained and scored in an identical fashion. 77/78 (99%) ONB cases demonstrated SSTR2 staining (mean H-score: 189, range: 0-290). There were no significant differences in staining between primary tumors and recurrences/metastases (mean H-score: 185 vs 198). Primary low-grade ONB had somewhat stronger staining than high-grade tumors (mean H-score: 200 vs 174). SSTR2 expression had no prognostic value when considering disease-free or disease-specific survival. SSTR2 staining is significantly higher in ONB than its histologic mimics (mean H-score: 189 vs 12.9, p < 0.001) suggesting a potential use of the marker in diagnosis of ONB. In conclusion, SSTR2 is consistently expressed in ONB suggesting a role for somatostatin-analog based imaging and therapy in this disease. More generally, SSTR2 may be another marker of neuroendocrine differentiation in ONB.

m6A methyltransferase Wilms' tumor 1-associated protein facilitates cell proliferation and cisplatin resistance in NK/T cell lymphoma by regulating dual-specificity phosphatases 6 expression via m6A RNA methylation.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor survival outcomes that is relatively resistant to chemotherapy. N6-Methyladenosine (m6A) modification, the most prevalent modification of eukaryotic messenger RNA, is involved in the progression of various tumors. However, it is unclear whether it has a physiological role in NKTCL development. To address this question, we probed its function and molecular mechanisms in NKTCL. Initially, we demonstrated that Wilms' tumor 1-associated protein (WTAP), a major RNA N6-adenosine methyltransferase, was obviously upregulated in human NKTCL cell lines (YTS and SNK-6 cells), compared with normal NK cells. Functionally, depletion of WTAP noticeably repressed proliferation and facilitated apoptosis in YTS and SNK-6 cells. Moreover, intervention of WTAP evidently prohibited NKTCL cell chemotherapy resistance to cisplatin, as reflected by a lower inhibition of cell viability and decreased expression of drug resistance-associated protein expression MRP-1 and P-gp in YTS and SNK-6 cells. With regard to the mechanism, we revealed that WTAP enhanced dual-specificity phosphatases 6 (DUSP6) expression by increasing m6A levels of DUSP6 mRNA transcript, leading to oncogenic functions in NKTCL. Interestingly, WTAP contributed to the progression and chemotherapy sensitivity of NKTCL by stabilizing DUSP6 mRNA in an m6A-dependent manner. Taken together, these findings uncovered a critical function for WTAP-guided m6A methylation and identified DUSP6 as an important target of m6A modification in the regulation of chemotherapy resistance in NKTCL oncogenesis. This study highlights WTAP as a potential therapeutic target of NKTCL treatment.

Down-regulating NEAT1 inhibited the viability and vasculogenic mimicry formation of sinonasal squamous cell carcinoma cells via miR-195-5p/VEGFA axis.

The role of long non-coding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) in sinonasal squamous cell carcinoma (SNSCC) remained obscure. Target genes and potential binding sites of NEAT1, microRNA (miR)-195-5p and VEGFA were predicted using StarBase and TargetScan, and confirmed by dual-luciferase reporter assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of NEAT1, vascular endothelial growth factor A (VEGFA) and miR-195-5p. Pearson's correlation analysis of NEAT1, miR-195-5p and VEGFA was conducted. Cell viability, apoptosis and tube formation capability were assessed by MTT assay, flow cytometry and capillary-like tube formation assay, respectively. Expressions of VEGFA and proteins related to the phosphatidylinositide 3-kinase/Protein Kinase B (PI3K/AKT) pathway were measured by Western blot. In SNSCC tissues and cells, the expressions of NEAT1 and VEGFA were up-regulated while the expression of miR-195-5p was down-regulated, and NEAT1 was negatively correlated with miR-195-5p yet positively correlated with VEGFA. Overexpressed VEGFA promoted the viability and capillary-like tube formation of SNSCC cells yet suppressed their apoptosis, while silencing VEGFA led to the opposite results. MiR-195-5p could bind to NEAT1, and down-regulating miR-195-5p reversed the effects of silencing NEAT1 on the expressions of NEAT1 and miR-195-5p, cell viability, apoptosis and capillary-like tube formation as well as PI3K/AKT pathway activation. VEGFA was the target of miR-195-5p, and overexpressed VEGFA reversed the effects of miR-195-5p. Down-regulating NEAT1 inhibited the viability and vasculogenic mimicry formation of SNSCC cells yet promoted their apoptosis via the miR-195-5p/VEGFA axis, providing a possible therapeutic target for SNSCC treatment.

Aberrant Expression of Prohibitin Is Related to Prognosis of Nasal Extranodal Natural Killer/T Cell Lymphoma, Nasal Type.

INTRODUCTION: Nasal extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTCL) is a high-grade Epstein-Barr virus (EBV)-associated malignancy with poor outcomes. There are few biomarkers for the accurate diagnosis and prognostic prediction of the disease. The aim of this study was to investigate the clinicopathological significance of prohibitin (PHB) expression in nasal ENKTCL. METHODS: The expression level of PHB was detected via immunohistochemical staining in 49 nasal ENKTCL tissues and age- and sex-matched controls of 30 nasal mucosa-reactive lymphoid hyperplasia (NRLH) tissues. The correlations between the PHB expression and clinicopathological features of patients with nasal ENKTCL were evaluated. RESULTS: The results indicated a significantly decreased expression of PHB in nasal ENKTCL tissues compared with in NRLH tissues. Low-level PHB expression was significantly associated with younger age and fever (p = 0.008 and 0.018, respectively). The Kaplan-Meier analysis showed that the cytoplasm expression level of PHB in nasal ENKTCL was inversely related to overall survival (p = 0.046). CONCLUSIONS: PHB may be a potential diagnostic marker and prognostic predictor of nasal ENKTCL.

Follicular Thyroid Cancer With Nose-Tip Metastasis and 131I Uptake.

We present a 56-year-old woman with metastatic follicular thyroid cancer at the nose tip with I uptake that is clinically rare, mimicking physiological uptake in the nose, a common finding seen after routine I therapeutic imaging. The lesion revealed a metastatic follicular thyroid cancer with I uptake and response to I therapy. Surgical removal, however, was not performed due to cosmetic and functional considerations. Active surveillance is warranted owing to its relative aggressiveness in nature.

68Ga-DOTATATE and 18F-FDG PET/CT for the Management of Esthesioneuroblastoma of the Sphenoclival Region.

We present a 48-year-old woman with an olfactory neuroblastoma who was referred for accurate staging using PET/CT. The Ga-DOTATATE PET/CT showed a 51 × 32-mm mass with an SUVmax of 7.59 in the sphenoidal sinuses, whereas radiotracer uptake on F-FDG PET/CT was similar to that of brain tissue. Ga-DOTATATE PET/CT might be especially useful in regions with difficult tumor visualization resulting from high background, such as brain tissue. The results of this case may suggest that somatostatin receptor imaging in patients with esthesioneuroblastoma may facilitate the potential application of radiotheranostic agents for the treatment of this aggressive subtype of tumors.

Prostate-Specific Membrane Antigen Expression in Primary Juvenile Nasal Angiofibroma-A Pilot Study.

PURPOSE: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and is exploited for imaging and treatment of patients with prostate cancer. Prostate-specific membrane antigen expression is also demonstrated in the tumor-associated neovasculature endothelium. Juvenile nasal angiofibroma (JNA), being a similar highly vascular tumor, may also demonstrate significant PSMA expression, which may be utilized for its imaging and treatment. METHODS: In this prospective study, 25 clinicoradiologically diagnosed primary JNA patients underwent PSMA PET/CT scan. The scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi (74-111 MBq) of Ga-PSMA-HBED-CC on a dedicated PET/CT scanner. Low-dose CT scan was acquired from vertex to sternoclavicular joint (100 mA, 20 kVp, 3-mm slice thickness, 0.8 pitch). Images were reconstructed with iterative reconstruction technique (4 iterations, 24 subsets). The objective was to assess the intensity and pattern of PSMA uptake in primary JNA patients. RESULTS: All cases (n = 25) of primary JNA showed PSMA expression in the tumor (100%). The median PSMA SUVmax ratio of tumor to background was 4.57 (range, 2.08-7.27). Intracranial extension in 14 of 25 patients was prominently visualized because of absence of background uptake in the brain. Advanced stage tumors demonstrated greater uptake than early tumors (P = 0.011). A statistically nonsignificant trend was noted for decreasing uptake with increasing age after normalizing for stage (Spearman correlation coefficient r = -0.08). CONCLUSIONS: Assessment of PSMA expression in JNA by PSMA PET/CT opens up a new window of opportunity with respect to its radiological staging, vascularity assessment, and molecular characterization. A potential role in identification of the difficult residual-recurrent disease is anticipated and perhaps also in radioligand therapy for residual/recurrent JNA.Clinical Trials Registry of India (CTRI/2018/08/015479).

[Expression of mTOR and 4E-BP1 in extranodal Nasal-type NK/T-cell Lymphoma and implication for prognosis].

Objective: To study the expression of mTOR and 4E-BP1 in extranodal Nasal-type NK/T-cell Lymphoma(ENKTCL) and the correlation with the clinicopathological factors and prognosis of ENKTCL.Method: Immunohistochemistry was used to detect the expresstion of mTOR and 4E-BP1 in the tissues of ENKTCL and nasal pharyngeal lymphoid hyperplasia. The relationship between the expression of mTOR and 4E-BP1 and clinicopathological features was analyzed using the Chi-square test, which including sorting clinical stage, general condition score and international prognostic index(IPI). Result: The expression rates of mTOR and 4E-BP1 in ENKTCL were 63.9% and 58.3% respectively, and significantly higher than those（15.0% and 10.0%）in patients with nasal pharyngeal lymphoid hyperplasia(χ ²=12.355, P=0.0001; χ ²=12.410, P=0.0001). The positive expression rate of mTOR was linked to clinical staging, and the positive protein expressions in Stage Ⅲ and Ⅳwere higher than those in stageⅠand Ⅱ(χ ²=17.902, P=0.0001). mTOR expression was related to 4E-BP1(r=0.655,P=0.001). The positive expression rates of 4E-BP1were linked to IPI of lymphoma(χ ²=4.051, P=0.044). Conclusion: High-expressions of mTOR and 4E-BP1 in patients with ENKTCL are related to the biological progression and recurrence of ENKTCL and are malignant indicators to identify ENKTCL from nasal pharyngeal lymphoid hyperplasia. mTOR and 4E-BP1 may play important roles to assess ENKTCL prognosis..

Cyclin-dependent kinase 1 and survivin as potential therapeutic targets against nasal natural killer/T-cell lymphoma.

Nasal natural killer/T-cell lymphoma (NNKTL) is closely associated with Epstein-Barr virus (EBV) and is characterized by poor prognosis, resulting from rapid progression of lesions in the affected organs. Recent data have shown that NNKTL is associated with the aberrant expression of cyclin-dependent kinase 1 (CDK1) and its downstream target survivin, but little is known about the functional roles of CDK1 and survivin in NNKTL. In the current study, we show that knockdown of the EBV-encoded oncoprotein latent membrane protein 1 (LMP1) induces downregulation of CDK1 and survivin in NNKTL cells. Immunohistochemistry detected CDK1 and survivin expression in LMP1-positive cells of NNKTL biopsy specimens. Inhibition of CDK1 and survivin in NNKTL cells with several inhibitors led to a dose-dependent decrease in cell proliferation. In addition, the Sp1 inhibitor mithramycin, which can downregulate both CDK1 and survivin, significantly suppressed the growth of established NNKTL in a murine xenograft model. Our results suggest that LMP1 upregulation of CDK1 and survivin may be essential for NNKTL progression. Furthermore, targeting CDK1 and survivin with Sp1 inhibitors such as mithramycin may be an effective approach to treat NNKTL, which is considered to be a treatment-refractory lymphoma.

Predictive value of EGFR-PI3K-pAKT-mTOR-pS6 pathway in sinonasal squamous cell carcinomas. / Valor pronóstico de la ruta de EGFR-PI3K-pAKT-mTOR-pS6 en los carcinomas epidermoides nasosinusales.

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.

Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny.

Esthesioneuroblastoma (ENB) is a rare cancer of the olfactory mucosa, with no established molecular stratification to date. We report similarities of ENB with tumors arising in the neural crest and perform integrative analysis of these tumors. We propose a molecular-based subtype classification of ENB as basal or neural, both of which have distinct pathological, transcriptomic, proteomic, and immune features. Among the basal subtype, we uncovered an IDH2 R172 mutant-enriched subgroup (∼35%) harboring a CpG island methylator phenotype reminiscent of IDH2 mutant gliomas. Compared with the basal ENB methylome, the neural ENB methylome shows genome-wide reprogramming with loss of DNA methylation at the enhancers of axonal guidance genes. Our study reveals insights into the molecular pathogenesis of ENB and provides classification information of potential therapeutic relevance.

Distinctive expression profiles of Caveolin-1 and Notch-1 protein in patients with nasal polyps or sinonasal inverted papillomas.

BACKGROUND: Nasal polyposis (NP) and sinonasal inverted papillomas (SIP) are considered benign lesions capable of recurrence or malignant transformation although not with the same prevalence. Since fluctuations of Caveolin-1 and Notch-1 proteins expression have been reported in many pathologies, the current study aimed to investigate their involvement in the epithelial transformation observed in SIPs compared to NP. METHODS: Immunohistochemical expression of Caveolin-1 and Notch-1 proteins was assessed in 104 patients with sinonasal lesions (45 NP, 45 SIP and 14 NP with SIP), semiquantively (percentage times intensity). Proteins expression profiles were evaluated statistically for their correlation with patients demographic and clinicopathological variables (grade of dysplasia, inflammation, recurrence) as well as with markers of proliferation (Ki67) and apoptosis (7-AAD) as determined by flow cytometry analysis. RESULTS: SIP lesions presented increased Caveolin-1 immunopositivity compared to NP (62.2%, vs 40.9%; p = 0.045). Cytoplasmic staining was observed only in epithelium's basal and suprabasal layers. Caveolin-1 positivity was not related to Ki67 expression, apoptosis, inflammation or dysplasia, eventhough 81.8% of highly immunopositive lesions were dysplastic (p = 0.03). Also, smokers presented significantly increased immunopositivy (p = 0.03). In contrast SIP lesions presented reduced Notch-1 expression compared to NP (68.9% vs 100%; p < 0.001). Dysplastic lesions presented low Notch-1 immunopositivity (p < 0.001). Enhancement of Notch-1 gene expression was also associated with inflammation. CONCLUSIONS: The herein presented data suggest that the expression profiles of Caveolin-1 and Notch-1 proteins in sinonasal pathologies are distinctive and that could be explored as potential targets for the development of alternative therapeutic approaches.

Identification and Functional Evaluation of miR-4633-5p as a Biomarker and Tumor Suppressor in Metastatic Melanoma.

BACKGROUND/AIMS: Sinonasal mucosal melanoma (SMM) is a rare but extremely aggressive disease. Interestingly, however, as lethal as SMM, a few patients could survive for over 5 years without metastasis. However, biomarkers for metastatic SMM are lacking. METHODS: Laser-capture microdissection combined with microRNA microarray and RT-qPCR was performed in formalin-fixed paraffin-embedded tissue samples from SMM patients whose follow-up studies were carried out in parallel. In vitro cell proliferation and invasion assays, gelatin zymography, western blot analysis and RT-qPCR were performed in melanoma cell lines. RESULTS: In the discovery stage, miR-4633-5p expressed differentially in sinonasal mucosal melanoma patients with short and long disease-specific survival. Subsequent large-sample validation revealed that expression of miR-4633-5p was lower in metastatic SMM than in non-metastatic patients (P< 0.001). Moreover, miR-4633-5plow was able to identify metastatic SMM with specificity of 100% (5/5) and sensitivity of 87.5% (21/24). Multivariate analysis further pinpointed miR-4633-5p as an independent marker for metastasis (relative risk: 54.22, P< 0.001). In vitro, overexpression of miR-4633-5p suppressed the growth and invasiveness of melanoma cells through inhibiting activation of Akt pathway and secretion of MMP2, while knockdown of miR-4633-5p reversed the inhibitory effects. CONCLUSION: Our findings underpin miR-4633-5p as a predictive biomarker in metastatic SMM and a pivotal tumor suppressor that negatively regulates the invasive growth of melanoma cells. Quantitative detection of miR-4633-5p can diagnostically predict the risk of metastasis in SMM patients, which, in turn, may lead to more personalized treatment with better prognosis.

Biphenotypic sinonasal sarcoma: A series of six cases with evaluation of role of ß-catenin immunohistochemistry in differential diagnosis.

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 ß-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 ß-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. ß-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 ß-catenin immunopositivity. SNHPC cases also were ß-catenin positive (60%). CONCLUSION: BSNS is a rare sinonasal neoplasm, frequently misdiagnosed as SNHPC and SFT. ß-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.

PD-L1 is a positive prognostic factor in squamous cell carcinoma of the nasal vestibule.

BACKGROUND: Aim was to analyse the role of PD-L1 in squamous cell carcinomas of the nasal vestibule. Advanced squamous cell carcinoma of the nasal vestibule is a highly aggressive tumour. The role of PD-L1 expression is unclear in this tumour type. METHODOLOGY: Forty-six patients diagnosed between 1995 and 2014 were analyzed. Baseline characteristics and outcome were correlated to immunohistochemical staining of PD-L1. PD-L1 positivity of tumour cells and tumour infiltrating immune cells (TIIC) was defined by any staining of more than 1% of the tumour cells. RESULTS: PD-L1 expression was interpretable in 31 of 46 patients (67.4%). PD-L1 positivity was present in 14 (45.2%) patients tumour cells and 17 (54.8%) patients TIIC. PD-L1 positivity of tumour cells was associated with a favourable disease free survival (p=0.019). CONCLUSIONS: Positivity for PD-L1 in tumour cells is a prognostic factor in squamous cell carcinoma of the nasal vestibule and might enable a patient-tailored treatment.