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.

A diagnostic algorithm for sinonasal papillary non-keratinizing squamous cell carcinoma with DEK::AFF2 fusion and mimickers.

Sinonasal carcinomas represent a rare and diverse group of tumors, presenting diagnostic complexities due to their varied histological and molecular features. To ensure accurate differentiation among these malignancies, a systematic and stepwise approach is paramount. Even with the morphological similarities between poorly differentiated (non) keratinizing sinonasal squamous cell carcinoma (SNSCC) and DEK::AFF2 SNSCC, the two lesions are distinguishable using the surrogate immunohistochemical marker AFF2 or molecular testing for DEK::AFF2 mutation. We report a rare case of SMARCB1-retained DEK::AFF2 papillary non-keratinizing SNSCC in a 53-year-old female, who presented with a polypoid mass corresponding to the left middle turbinate. Following the surgical resection of the tumor and locoregional lymph nodes, adjuvant radiotherapy was administered to eradicate any residual cancer cells that may have remained after surgery.

CD34-Positive Spindle Cell Tumor With CTNNB1 Mutation: An Unusual Spindle Cell Variant of Sinonasal Glomangiopericytoma.

Sinonasal glomangiopericytoma is an uncommon mesenchymal tumor with a perivascular myoid phenotype, which is categorized as a borderline/low-grade malignant soft tissue tumor by the current World Health Organization Classification of Head and Neck tumors. Here, we present the case of a 53-year-old woman with an unusual spindle cell morphology of sinonasal glomangiopericytoma arising in the nasal cavity, mimicking solitary fibrous tumor. Microscopically, the tumor showed a cellular proliferation of spindle cells in fascicles including a focal long sweeping arrangement or whorls, or with a storiform growth pattern, associated with hemangiopericytoma-like gaping blood vessels embedded in a fibrous stroma. This arrangement of the spindle cells faintly indicated a solitary fibrous tumor rather than sinonasal glomangiopericytoma. Immunohistochemically, the tumor was positively reactive to not only beta-catenin (in the nuclei) but also CD34, although signal transducers and activators of transcription 6 was negative. Mutational analysis using Sanger sequencing detected a CTNNB1 mutation. We finally diagnosed the tumor as a sinonasal glomangiopericytoma, showing an unusual spindle cell variant. Such unusual spindle cell morphology with CD34-immunoreactivity potentially leads to an incorrect diagnosis of solitary fibrous tumor because such prominent fascicles including long sweeping structures, reminiscent of desmoid-type fibromatosis, have scarcely been described in the literature. Hence, careful morphological scrutiny using appropriate diagnostic adjuncts is necessary for correct diagnosis.

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

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

SMARCB1 (INI1)-deficient sinonasal carcinoma manifesting as oral lesions: A report of two cases.

BACKGROUND: Sinonasal carcinomas represent a rare group of malignancies, accounting for less than 5% of all head and neck cancers and a worldwide incidence of less than 1 case per 100 000 inhabitants annually. Despite the restricted anatomical location, sinonasal carcinomas harbor some of the most histologically and molecularly diverse groups of tumors. SMARCB1 (INI1)-deficient sinonasal carcinomas are locally aggressive tumors commonly detected late, leading to devastating morbidity and mortality. CASE REPORT: We present two cases of SMARCB1-deficient sinonasal carcinoma involving the oral cavity and presenting as progressive radiolucent lesions with local swelling associated with maxillary dentition and alveolar bone. Both cases were initially considered odontogenic in origin and involved the destruction of the left anterior maxilla. CONCLUSION: Given the rarity and the variable presentation of these tumors, they pose a challenge for head and neck surgeons, dentists, and pathologists due to the potential overlapping features with odontogenic and non-odontogenic inflammatory and neoplastic lesions. These cases highlight the importance of a multidisciplinary team and include SMARCB1-deficient sinonasal carcinomas in the differential diagnosis of destructive lesions of the maxilla.

Targeted next-generation sequencing of Japanese patients with sinonasal mucosal melanomas identifies frequent NRAS and CTNNB1 mutations.

OBJECTIVE: Mucosal melanoma is a rare malignancy; however, the reported incidence rate of mucosal melanoma is higher in Asians than in Caucasians. Sinonasal mucosal melanoma (SNMM) is an aggressive malignancy with a poor prognosis due to distant metastasis. Systemic therapy with BRAF inhibitor and MEK inhibitor is one of the standards of care for cutaneous melanoma patients with BRAF V600 mutations. However, no molecular targeted therapy for patients with mucosal melanoma has been established. Relatively few studies have described the genetic mutations associated with mucosal melanoma because of its low frequency. Furthermore, to the best of our knowledge, the genetic mutations among Japanese patients have not been reported. Therefore, in the current study, we evaluated the genetic and clinicopathological characteristics of patients with SNMM. METHODS: A total of 18 tissue samples obtained from patients with SNMM were analyzed for genetic mutations based on targeted next-generation sequencing to investigate the driver of tumorigenesis and/or candidate genes for predicting clinical outcomes in SNMM. We also performed immunohistochemistry for patients identified with CTNNB1 mutations. RESULTS: Eight of the 18 (44 %) patients had genetic mutations. The most frequent mutation was NRAS (6/18, 33 %), followed by CTNNB1 (2/18, 11 %) and BRAF (1/18, 5.6 %). One patient had both NRAS and CTNNB1 mutations. Clinical outcomes did not differ significantly between those with and without genetic mutations. NRAS mutations were associated with relatively higher T classification and worse survival rates, although the differences were not significant. The nuclear translocation of ß-catenin was detected in both tumors with CTNNB1 mutations. The amino acid change in the BRAF mutation was K601R in exon 15. In the current study, no BRAF V600 mutations were detected. CONCLUSION: Genetic mutations were not significantly associated with clinical outcomes. However, NRAS mutations may be a prognostic predictor and CTNNB1 mutation may be a treatment effector for immune check inhibitors. A larger prospective study is required to clarify the clinical importance of genetic mutations in patients with SNMM.

Novel PAX3::INO80D Fusion in Biphenotypic Sinonasal Sarcoma in an Adult.

This case report describes a novel gene fusion of PAX3::INO80D in a biphenotypic sinonasal carcinoma in a woman in her 40s.

Multimodal treatment and immune checkpoint inhibition in sinonasal mucosal melanoma: real-world data of a retrospective, single-center study.

PURPOSE: Local failure and distant metastases occur frequently in sinonasal mucosal melanoma (SNMM). Response rates to chemotherapy are low and targetable mutations are rarely detected. However, there is increasing data indicating efficacy of immune checkpoint inhibition (ICI). The aim of this retrospective monocenter study was to assess the mutational landscape and to evaluate the outcome of surgical treatment and ICI in SNMM in a real-world setting. METHODS: Thirty-eight SNMM patients being treated between 1999 and 2020 at our institution were retrospectively reviewed. Survival curves were generated according to Kaplan-Meier and compared by the log-rank test. RESULTS: Local failure was seen in 60% of patients treated in a curative intent. Overall, 24% of all patients suffered from regional and 66% from distant metastases. Next generation sequencing revealed mutations of BRAF, NRAS and KRAS. One out of three patients treated with a primary ICI showed a complete response (CR) and two showed progressive disease. Eleven patients received ICI as a palliative treatment. CR could be observed in three patients and stable disease in one patient. In the whole study population, the 5-year overall survival rate (OS) was 26%. OS was better for patients who received ICI during the course of disease. CONCLUSIONS: Recurrences and distant metastases are frequent in SNMM. Durable CR could be observed after primary and palliative ICI. Therefore, ICI in a palliative, adjuvant or even neoadjuvant setting might play a promising role in SNMM therapy while targetable mutations are rarely detected.

SMARCB1-Deficient Sinonasal Carcinoma: Case Report and Review of the Literature.

BACKGROUND SMARCB1-deficient sinonasal carcinoma is a rare neoplasm with inactivation of the SWI/SNF complex, with an aggressive clinical course as most of the lesions present as advanced in pT3/T4 stages with frequent recurrence, and many patients succumb to the disease. Reported initially in 2014, the lesion has male predominance, with an age range of 19 to 89 years and predilection for the ethmoid sinus and nasal cavity. Histopathological findings show a proliferation of small- to medium-sized monomorphic basaloid cells with indistinctive cytoplasmic borders and round variably prominent nuclei with scattered cells that show rhabdoid morphology. Cytoplasmic vacuoles are common. It has similar morphological findings to a wide array of neoplasms in the sinonasal area. CASE REPORT We report a case of SMARCB1-deficient sinonasal carcinoma in a 30-year-old man referred to our hospital with a preliminary diagnosis of sinonasal adenocarcinoma, intestinal type. Computed tomography showed a huge destructive soft tissue mass in the left maxillary sinus, extended to involve the left nasal cavity with extension to the skull base and perineural spread along the foramen rotundum. Histological examination revealed a malignant basaloid neoplasm embedded in a myxoid stroma that showed loss of SMARCB1 stain. The patient was treated with induction chemotherapy using etoposide and cisplatin for disease control. CONCLUSIONS SMARCB1-deficient sinonasal carcinoma is a rare neoplasm with an aggressive clinical course and high-grade behavior despite having uniform cytological features. This poses complex diagnoses, especially in small biopsies. Incorporating morphological findings with ancillary tests is required to identify this high-grade malignancy.

SMARCB1 (INI-1) - Deficient sinonasal carcinoma: Report of two cases.

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare, poorly differentiated carcinoma defined by complete loss of tumor suppressor gene SMARCB1 (INI-1) within the neoplastic cell nuclei demonstrated by the immunohistochemical stain. SMARCB1 (INI-1) gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share "rhabdoid" morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma was first reported by Agaimy et al. in 2014. These tumors are often basaloid with focal rhabdoid differentiation, prominent necrosis, increased mitotic activity, and aggressive behavior. Other than being INI-1 and NUT negative, they are positive for pancytokeratin and express variable immunoreactivity for squamous markers like p63 and neuroendocrine markers like synaptophysin. Most patients present with locally advanced disease and hence a combination of chemotherapy, radiotherapy, and surgery is usually recommended.

Impact of Clinical Factors and Treatments on SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma.

The objective of this study was to report outcomes for 19 consecutive patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma. Patients were treated from 2014 to 2021 and followed for a median of 22.3 months. The median overall survival (OS) and disease-free survival (DFS) were 31.8 and 9.9 months, respectively. Patients with nasal cavity or maxillary sinus tumors had 84% better disease-specific survival (DSS) (hazard ratio [HR], 0.136; 95% confidence interval [CI], 0.028-0.66; p = .005) and 71% better DFS (HR, 0.29; 95% CI, 0.097-0.84; p = .041) than patients with other sinonasal sites. Patients who received induction chemotherapy were 76% less likely to die of disease (DSS HR, 0.241; 95% CI, 0.058-1.00; p = .047). In the largest single-institution study of SMARCB1-deficient sinonasal carcinoma to date, OS and DFS approached 3 years and 1 year, respectively, but were better for nasal cavity and maxillary sinus tumors. Patients may benefit from induction chemotherapy.

Sinonasal Adenosquamous Carcinoma - Morphology and Genetic Drivers Including Low- and High-Risk Human Papillomavirus mRNA, DEK::AFF2 Fusion, and MAML2 Rearrangement.

BACKGROUND: Sinonasal adenosquamous carcinoma is rare, and there are almost no studies detailing morphology or characterizing their genetic driver events. Further, many authors have termed sinonasal tumors with combined squamous carcinoma and glands as mucoepidermoid carcinoma but none have analyzed for the presence of MAML2 rearrangement. METHODS: Cases from 2014 to 2020 were collected and diagnosed using World Health Organization criteria. They were tested for p16 expression by immunohistochemistry (70% cut-off), DEK::AFF2 fusion by fluorescence in situ hybridization (FISH) and AFF2 immunohistochemistry, MAML2 rearrangement by FISH, and low- and high-risk HPV by RNA ISH and reverse transcription PCR, respectively. Detailed morphology and clinical features were reviewed. RESULTS: There were 7 male (64%) and 4 female (36%) patients with a median age of 69 years, most Caucasian (10 of 11 or 91%). Most had tobacco exposure (8/11, 73%) and most presented with epistaxis, a visible nasal mass, and/or facial pain. Several had a precursor papillomas (3 of 11, 27%). The squamous component had variable keratinization, 5 of 11 (46%) of which would be described as keratinizing, 3 non-keratinizing, and 2 with mixed features. All had gland formation, by definition, and 2 of 11 (18%) had ciliated tumor cells. None of the 11 cases had MAML2 rearrangement and one had DEK::AFF2 fusion with associated positive nuclear AFF2 protein immunostaining. Most were p16 positive (7 of 11, 64%) and all 7 of these were hrHPV positive either by RNA ISH or RT-PCR. Two of the p16-negative tumors were positive for lrHPV by RNA ISH. Treatment included surgery alone (4 of 11, 36%), surgery with adjuvant radiation (5 of 11, 45%), and surgery with radiation and chemotherapy (2 of 11, 18%). Four of 11 patients (36%) suffered disease recurrence, two requiring re-operation and who were disease free at last follow-up, one receiving additional chemotherapy and who was alive with disease. The other elected to undergo palliative therapy and died of disease. CONCLUSION: Sinonasal adenosquamous carcinoma is a somewhat heterogeneous tumor not infrequently arising ex papilloma and having various drivers including high- and low-risk HPV and rarely DEK::AFF2 fusion. The prognosis appears favorable when proper treatment is possible.

Biphenotypic Sinonasal Sarcoma: A Genetically Confirmed Case Showing Bone Invasion Accompanying a Non-neoplastic Respiratory Epithelium.

Biphenotypic sinonasal sarcoma is a newly established tumor entity that is associated with distinct clinicopathological findings. Biphenotypic sinonasal sarcoma is a rare, low-grade spindle cell sarcoma that arises in middle-aged females, exclusively in the sinonasal tract. A fusion gene involving PAX3 is detected in most biphenotypic sinonasal sarcomas, which aids in its diagnosis. Here, we report a case of biphenotypic sinonasal sarcoma with its cytological findings. The patient was a 73-year-old woman who presented with purulent nasal discharge and dull pain in the left cheek area. Computed tomography showed a mass extending from the left nasal cavity to the left ethmoid sinus, the left frontal sinus, and the frontal skull base. She underwent a combined transcranial and endoscopic approach for en bloc resection with a safety margin. Histologically, spindle-shaped tumor cells have been thought to proliferate mainly in the subepithelial stroma. Here, nasal mucosal epithelial hyperplasia was noted, and the tumor had invaded the bone tissue accompanying the epithelial cells. Fluorescence in situ hybridization (FISH) analysis showed a PAX3 rearrangement, and next-generation sequencing identified a PAX3::MAML3 fusion. Based on FISH, split signals were observed not in respiratory cells but in stromal cells. This indicated that respiratory cells were non-neoplastic. In the diagnosis of biphenotypic sinonasal sarcoma, the inverted growth of the respiratory epithelium can be a diagnostic pitfall. FISH analysis using a PAX3 break-apart probe is helpful not only for an accurate diagnosis but also for detecting the true neoplastic cells.

Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms-A Systematic Review.

Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.

A Low-grade Sinonasal Sarcoma Harboring EWSR1::BEND2: Expanding the Differential Diagnosis of Sinonasal Spindle Cell Neoplasms.

BACKGROUND: Molecular diagnostics has greatly refined sinonasal tumor pathology over the past decade. While much of the attention has focused on carcinomas, it is becoming clear that there are emerging mesenchymal neoplasms which have previously defied classification. METHODS: Here, we present a 33-year-old woman with a multiply recurrent sinonasal spindle cell tumor exhibiting distinctive features, and not easily classifiable into a specific category. RESULTS: The hypercellular tumor was composed of plump spindled cells, with uniform vesicular chromatin arranged as vague fascicles around a prominent hemangiopericytoma-like vasculature. The mitotic rate was brisk at 10 per 10 high power fields. By immunohistochemistry, it was only positive for EMA (focal) and SATB2 (diffuse, weak). Fusion analysis uncovered EWSR1::BEND2, a fusion which is best known for being seen in astroblastoma, but which has not yet been reported in sarcomas. CONCLUSION: This case underscores the utility of fusion analysis when confronted with a sinonasal spindle cell neoplasm which does not neatly fit into any specific category. It remains to be seen if EWSR1::BEND2 sinonasal sarcoma represents a distinct entity.

Targeted next-generation sequencing reveals activating CTNNB1 mutations in SMARCA4/BRG1-deficient sinonasal carcinomas: a report of two new cases and a brief review of the literature with an emphasis on histogenesis.

SMARCA4/BRG1 is a catalytic subunit of the SWItch/sucrose non-fermentable (SWI/SNF) complex and its inactivation is known to drive a variety of cancers across different organs. SMARCA4/BRG1-deficient carcinoma is a relatively new entity in the sinonasal region, and a comprehensive molecular investigation of the underlying genetic abnormalities is largely lacking. In this study, we report two new cases of SMARCA4/BRG1-deficient sinonasal carcinoma with targeted next-generation sequencing analysis, both of which revealed activating mutation of CTNNB1 in addition to somatic loss-of-function mutation of SMARCA4, providing further insights into its tumorigenesis and theoretical basis for the potential future targeted therapy. Activating CTNNB1 mutations in our cases may provide further evidence that SMARCA4-deficient sinonasal carcinoma, sinonasal teratocarcinosarcoma, and olfactory carcinoma are genetically closely related lesions, as recently proposed in the literature.

Comprehensive Molecular Profiling of Sinonasal Teratocarcinosarcoma Highlights Recurrent SMARCA4 Inactivation and CTNNB1 Mutations.

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor defined by intermixed neuroepithelial, mesenchymal, and epithelial elements. While its etiology was historically ambiguous, we recently reported frequent SMARCA4 loss by immunohistochemistry, suggesting that TCS might be related to SMARCA4-deficient sinonasal carcinomas. However, other molecular alterations including CTNNB1 mutation have been reported in TCS, and its full genetic underpinnings are unclear. Here, we performed the first comprehensive molecular analysis of sinonasal TCS to better understand its pathogenesis and classification. We collected 30 TCS including 22 cases from our initial study. Immunohistochemical loss of SMARCA4 was seen in 22 cases (73%), with total loss in 18 cases (60%). ß-catenin showed nuclear localization in 14 cases (64%) of the subset tested. We selected 17 TCS for next-generation sequencing with enrichment for partial or intact SMARCA4 immunoexpression. We identified inactivating SMARCA4 mutations in 11 cases (65%) and activating CTNNB1 mutations in 6 cases (35%), including 5 cases with both. Of 5 cases that lacked SMARCA4 or CTNNB1 mutation, 2 harbored other SWI/SNF complex and Wnt pathway alterations, including 1 with SMARCB1 inactivation and 1 with concomitant APC and ARID1A mutations, and 3 had other findings, including DICER1 hotspot mutation. These findings confirm that SMARCA4 inactivation is the dominant genetic event in sinonasal TCS with frequent simultaneous CTNNB1 mutations. They further underscore a possible relationship between TCS and sinonasal carcinomas with neuroendocrine/neuroectodermal differentiation. However, while SMARCA4 and ß-catenin immunohistochemistry may help confirm a challenging diagnosis, TCS should not be regarded as a molecularly defined entity.

Predictive Value of Magnetic Resonance Imaging Multi-parametric Analysis for Malignant Transformation of Sinonasal Inverted Papilloma: A Comprehensive Prediction Model.

OBJECTIVE: Accurate preoperative prediction of sinonasal inverted papilloma (SNIP) malignant transformation is essential and challenging. In this study, 3.0T magnetic resonance was used for qualitative, quantitative, and multi-parametric analysis to evaluate the predictive value of magnetic resonance imaging (MRI) in malignant transformation. METHODS: The data of patients with SNIP (n=83) or SNIP-transformed squamous cell carcinoma (SNIP-SCC) (n=21) were analysed retrospectively. Univariate analysis and multivariate logistic regression were used to establish models to predict the risk factors for the malignant transformation of SNIP. Receiver operating characteristic (ROC) curves were used to evaluate the ability of independent risk factors and related combination models to predict the malignant transformation of SNIP. RESULTS: Convoluted cerebriform pattern (CCP) mutation, apparent diffusion coefficient ratio (ADCr), and wash-in index (WII) 2 and 3 were independent risk factors for predicting malignant transformation of SNIP, with area under the ROC curve (AUC) values of 0.845, 0.862, 0.727, and 0.704, respectively. The AUC of the quantitative parameter model combined with ADCr and WII 2 and 3 was 0.910 for diagnosing malignant transformation. The AUC of the comprehensive model comprising all independent risk factors was 0.937, with a sensitivity, specificity, and accuracy of 90.48%, 90.36%, and 92.31%, respectively. CONCLUSION: Compared with assessing independent risk factors of CCP mutation, ADCr and WII, and the quantitative parameter model, the comprehensive model could improve the differential diagnosis ability of SNIP and SNIP-SCC, which provides an important imaging basis for the possible accurate preoperative evaluation of the malignant transformation of SNIP.

Treatment for SMARCB1 (INI-1) deficient sinonasal tumor: a single-institution study.

Currently, less than 200 cases of SMARCB1-deficient sinus cancer (SDSC) have been documented. Little information is available about the best treatment options or prognosis for SDSC. From September 2016 to November 2022, the medical records of 22 people with SDSC were evaluated retrospectively. Patient demographics, staging, pathology findings, treatment details, recurrence, metastasis, and survival outcomes were all investigated by the researchers. The 1-, 2-, and 3-year overall survival (OS) rates for the entire cohort were 89.8%, 84.2%, and 45.1%, respectively, as were the 1-, 2-, and 3-year progression-free survival (PFS) rates of 81.8%, 63.8%, and 31.9%. After induction chemotherapy, 66.7% (10/15) of patients exhibited decreased tumor volume. Patients who accepted chemoradiotherapy had a better 2-year OS (100% vs. 72.7%, p=0.048) than those who accepted surgery as a preference. However, there is no difference in 2-year PFS between the two groups (53.0% vs. 75.8%, p=0.59). Patients with progressed or stable disease after induction chemotherapy had a higher risk of developing local recurrence (p=0.007); they also showed poor 2-year PFS (40.0% vs. 82.1%, p=0.019). SDSC had a poor 3-year OS, with a PFS of less than 50%. For locally advanced SDSC, chemoradiotherapy might be managed before surgery, especially in patients who benefit from induction chemotherapy.

HPV Infection is Associated with FoxM1 Overexpression in Dysplastic Changes of Sinonasal Inverted Papilloma.

BACKGROUND: This study aims to describe the factors associated with dysplastic changes in sinonasal inverted papilloma (SIP) including somatic EGFR mutation, FoxM1 expression, HPV status, and their association with dysplastic changes. METHODS: A cross-sectional, analytical study was conducted comprising 34 samples of histologically-confirmed diagnosis of SIP. The samples were further grouped into 2 groups: 20 samples without associated dysplastic changes, and 14 samples with associated dysplastic changes. The numbers of FoxM1 positively-expressed cells, EGFR mutation, and HPV status were compared among two groups using appropriate comparative statistics. RESULTS: There was statistically-significant difference of FoxM1 expression between SIP and SIP with dysplasia (10% vs 100%; p<0.001). EGFR mutation was identified in 6 samples (30.0%) of the SIP and 5 samples (35.7%) of SIP with dysplasia. No difference of EGFR mutant proportion among two groups. HPV DNA was detected in 5 samples (25.0%) of SIP versus 9 samples (64.3%) of SIP with dysplasia. There was significant difference of HPV status among two groups (p=0.022). The high-risk subtypes were found in most HPV positive samples (57.1%), while low-risk subtypes and out panel subtypes were found 14.3% and 21.4%, respectively. CONCLUSIONS: FoxM1 was overexpressed in SIP with malignant transformation. FoxM1 along with HPV status is associated with dysplastic changes in the SIP. FoxM1 immunostaining is potential to be a biomarker of malignant transformation in SIP.