Deficient Sinonasal Carcinoma Research Articles

SMARCA4 (BRG1)-deficient sinonasal carcinoma with yolk sac tumor differentiation: a clinicopathological analysis of two cases

SMARCA4 (BRG1)-deficient sinonasal carcinoma with yolk sac tumor differentiation: a clinicopathological analysis of two cases

Assessment of targeted therapy opportunities in sinonasal cancers using patient-derived functional tumor models

Malignant tumors derived from the epithelium lining the nasal cavity region are termed sinonasal cancers, a highly heterogeneous group of rare tumors accounting for 3 – 5 % of all head and neck cancers. Progress with next-generation molecular profiling has improved our understanding of the complexity of sinonasal cancers and resulted in the identification of an increasing number of distinct tumor entities. Despite these significant developments, the treatment of sinonasal cancers has hardly evolved since the 1980s, and an advanced sinonasal cancer presents a poor prognosis as targeted therapies are usually not available. To gain insights into potential targeted therapeutic opportunities, we performed a multiomics profiling of patient-derived functional tumor models to identify molecular characteristics associated with pharmacological responses in the different subtypes of sinonasal cancer. MethodsPatient-derived ex vivo tumor models representing four distinct sinonasal cancer subtypes: sinonasal intestinal-type adenocarcinoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma and SMARCB1 deficient sinonasal carcinoma were included in the analyses. Results of functional drug screens of 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses of the tumor tissues and the ex vivo cell cultures to establish associations between drug sensitivity and molecular characteristics including driver mutations. ResultsThe different sinonasal cancer subtypes display considerable differential drug sensitivity. Underlying the drug sensitivity profiles, each subtype was associated with unique molecular features. The therapeutic vulnerabilities correlating with specific genomic background were extended and validated with in silico analyses of cancer cell lines representing different human cancers and with reported case studies of sinonasal cancers treated with targeted therapies. ConclusionThe results demonstrate the importance of understanding the differential biology and the molecular features associated with the different subtypes of sinonasal cancers. Patient-derived ex vivo tumor models can be a powerful tool for investigating these rare cancers and prioritizing targeted therapeutic strategies for future clinical development and personalized medicine.

Immunotherapy in SMARCB1 (INI-1)-deficient sinonasal carcinoma: Two case reports

BACKGROUND SMARCB1/INI-1 deficient sinonasal carcinoma (SDSC) is a rare subset of sinonasal undifferentiated carcinoma with a poor prognosis. Here, we present two case reports of SDSC patients. We also review the literature on this tumor. This is the first published report of SDSC treatment with immunotherapy. CASE SUMMARY Here we present two patient cases of SDSC in which initial consultation and diagnosis were complicated but SDSC was ultimately diagnosed. One patient received a traditional treatment of surgery and adjuvant chemoradiotherapy, while the other patient received additional immunotherapy; the prognoses of these two patients differed. We review previous diagnostic literature reports and SDSC treatments and provide a unique perspective on this rare type of tumor. CONCLUSION SDSC is a rare, diagnostically challenging carcinoma with a consistently poor prognosis, early distant metastases, and frequent recurrence. Timely diagnosis and intervention are critical for treatment, for which the standard of care is surgery followed by adjuvant chemoradiotherapy, though immunotherapy may be an effective new treatment for SDSC.

SMARCB1-Deficient Sinonasal Carcinoma–A Case Report and Literature Review

Switch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient sinonasal carcinoma is a rare subtype of sinonasal undifferentiated carcinoma (SNUC). Due to the highly aggressive nature of the disease course, it is important to diagnose early and use multimodal treatments in the course of the disease. Two main morphologic patterns are commonly identified under the microscope: plasmacytoid/rhabdoid and basaloid. Furthermore, it demonstrates a total absence of integrase interactor 1 expression upon immunohistochemical staining. Here, we present two cases of SMARCB1-deficient sinonasal carcinoma with contrasting outcomes.

SINONASAL CARCINOMA: A CASE REPORT

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a newly recognized rare and aggressive subtype of sinonasal undifferentiated carcinoma and defined by the loss of nuclear SMARCB1 (INI-1) expression by immunohistochemistry. This report describes a case of SMARCB1-deficient sinonasal carcinoma in a 62-year-old male. Clinical examination revealed an expansive lesion on the left hemiface that affected the orbital cavity, paranasal region, nose, upper lip, maxilla, buccal mucosa, and oropharynx. Computed tomography confirmed an infiltrative mass of the paranasal sinus, with intraoral and orbital extension. Incisional biopsy from the mass was taken and reported as sinonasal undifferentiated carcinoma. Immunohistochemistry showed that the tumor cells were positive for AE1/AE3 and p63. Accordingly, BRD4-NUT, CD99, Chromogranin, EBV, INSM1, NKX2.2, p16, SMARCA4, S100, and Synaptophysin were all negative. INI-1 stain showed loss of expression. Unfortunately, the patient died before receiving the diagnosis of SMARCB1 (INI-1)-deficient sinonasal carcinoma. SMARCB1 (INI-1)-deficient sinonasal carcinoma is a newly recognized rare and aggressive subtype of sinonasal undifferentiated carcinoma and defined by the loss of nuclear SMARCB1 (INI-1) expression by immunohistochemistry. This report describes a case of SMARCB1-deficient sinonasal carcinoma in a 62-year-old male. Clinical examination revealed an expansive lesion on the left hemiface that affected the orbital cavity, paranasal region, nose, upper lip, maxilla, buccal mucosa, and oropharynx. Computed tomography confirmed an infiltrative mass of the paranasal sinus, with intraoral and orbital extension. Incisional biopsy from the mass was taken and reported as sinonasal undifferentiated carcinoma. Immunohistochemistry showed that the tumor cells were positive for AE1/AE3 and p63. Accordingly, BRD4-NUT, CD99, Chromogranin, EBV, INSM1, NKX2.2, p16, SMARCA4, S100, and Synaptophysin were all negative. INI-1 stain showed loss of expression. Unfortunately, the patient died before receiving the diagnosis of SMARCB1 (INI-1)-deficient sinonasal carcinoma.

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.

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.

Analysis of the diagnosis and treatment of patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma

Objective: To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC). Methods: Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period. Results: Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression (HR=2.87,95%CI:0.92~8.91,P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others (HR=8.61,95%CI:1.38~53.73,P=0.021). Conclusion: SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma: A Systematic Review and Pooled Analysis of Treatment Outcomes.

Simple SummarySMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare but locally aggressive malignancy which usually presents very late with invasion into the orbits and intracranium, and compression of adjacent cranial nerves and their branches at diagnosis, and has a poor survival outcome. So far, less than 200 cases have been reported. The optimal treatment strategy for this rare but intractable malignancy is yet to be determined. We performed a systematic review and included patients treated at our institution for treatment outcome and survival analysis. Multivariable analysis revealed that T4b disease at diagnosis was the only prognostic factor of overall survival. In view of the extreme challenge of managing this malignancy, we are initiating a phase II trial on tazemetostat, an EHZ2 inhibitor, as induction therapy with systemic chemotherapy followed by radical surgery or chemoradiation, and as maintenance therapy for previously untreated stage III to IVA SMARCB1 (INI-1)-deficient sinonasal carcinoma.(1) Background: SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare sinonasal malignancy; since its discovery and description in 2014, less than 200 cases have been identified. It is almost impossible to perform randomized-controlled trials on novel therapy to improve treatment outcomes in view of its rarity. We performed a systematic review of all the published case reports/series and included our patients for survival analysis. (2) Methods: In this systematic review, we searched from PubMed-MEDLINE, EMBASE, Scopus, Cochrane Library, CINAHL, and Google Scholar for individual patient data to identify and retrieve all reported SMARCB1-deficient sinonasal carcinoma. Clarification on treatment details and the most updated survival outcomes from all authors of the published case reports/series were attempted. Survival analysis for overall survival (OS) and identification of OS prognostic factors were performed. This systematic review was registered with PROSPERO (CRD42022306671). (3) Results: A total of 67 publications were identified from the systematic review and literature search. After excluding other ineligible and duplicated publications, 192 patients reported were considered appropriate for further review. After excluding duplicates and patients with incomplete pretreatment details and survival outcomes, 120 patients were identified to have a complete set of data including baseline demographics, treatment details, and survival outcomes. Together with 8 patients treated in our institution, 128 patients were included into survival analysis. After a median follow up of 17.5 months (range 0.3–149.0), 50 (46.3%) patients died. The 1-year, 2-year and 3-year OS rates were 84.3% (95% CI % 77.6–91.0), 62.9% (95% CI 53.1–72.7), and 51.8% (95% CI 40.8–62.8), respectively, and the median OS was 39.0 months (95% CI 28.5–49.5). Males (p = 0.029) and T4b disease (p = 0.013) were significant OS prognostic factors in univariable analysis, while only T4b disease (p = 0.017) remained significant in multivariable analysis. (4) Conclusions: SMARCB1-deficient sinonasal carcinoma is an extremely aggressive sinonasal malignancy with a dismal prognosis. Early diagnosis and a multimodality treatment strategy are essential for a better treatment and survival outcome.

SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma: A Case Report and Literature Review.

Background: SWItch/Sucrose Non-Fermentable related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient sinonasal carcinoma (SDSC) is a malignant tumor classified as sinonasal undifferentiated carcinoma (SNUC). Purpose: Owing to the high aggressiveness and poor prognosis reported in recent literature, patients diagnosed with SNUC should consider further immunohistochemical examination to screen for SDSC. Timely diagnosis is critical and will contribute to follow-up targeted therapy and improved patient prognosis. Research Design: Case report. Study Sample: A case of SDSC with a history of chronic sinusitis with nasal polyps (CRSwNP). Data Collection: We collected all the clinical data of this patient. Results: The patient underwent planned functional endoscopic sinus surgery (FESS) and received chemotherapy combined with immunotherapy postoperatively. There was no evidence of recurrence or metastasis at the 3-month follow-up. Conclusions: The patient in this case presented with right intermittent epistaxis, and surgical histopathological examination confirmed a diagnosis of right SDSC and left CRSwNP. No related research has been reported.

High-grade myoepithelial carcinoma of the palate and maxillary sinus complex: a case report

<h3>Introduction</h3> Myoepithelial tumors typically arise from myoepithelial cells of salivary glands, however myoep- ithelial tumors arising in the skin and soft tissues have been increasingly recognized. Myoepithelial carcinomas (MC) have been described in each of these anatomic locations. Myoepithelial carcinoma of the salivary gland is a rare neoplasm composed exclusively of myoepithelial cells. The diagnosis of myoepithelial carcinoma is based on establishing the immunophenotype of the cellular proliferation, degree of cytologic atypia, presence of mitoses and necrosis, and exclusion of mimics. The morphologic heterogeneity further complicates the diagnosis of MC. <h3>Case Findings</h3> A 54-year-old woman presented with a progressive enlargement of the left palate, with imaging demonstrating involvement of adjacent maxillary sinus with extension to the floor of the orbit. Histologically, the lesion was characterized by malignant appearing epithelioid and clear cells compactly arranged in confluent sheets with no evidence of ductal differentiation. The sheets of tumor cells had a somewhat lobular architecture demar- cated by thin vascular septa. Nuclear pleomorphism, numerous mitoses, and focal necrosis were present. <h3>Results</h3> Positive immunohistochemical staining of tumor cells with CK7, SOX10, S100, P63, P40, and SMA favored a myoepithelial phenotype. <i>SMARCB1</i> (<i>INI1</i>) was expressed, excluding <i>SMARCB1</i>-deficient sinonasal carcinoma. Neg- ative staining of tumor cells for TTF1, CD20, GFAP, calponin, HMB45, PAX8, CD31, CD34 appear to exclude melanoma, renal cell carcinoma, renal cell like sinonasal carcinoma, thyroid carcinoma, lung carcinoma and PEComa. Outside consultation reported positive P16 but the tumor was negative for high risk HPV, thus excluding HPV related mul- tiphenotypic sinonasal carcinoma. Ki-67 revealed a high proliferative index of 70%. <h3>Conclusions</h3> This study demonstrates the clinical and histopathologic findings of a high-grade myoepithelial carci- noma involving the palate and maxillary sinus complex. Exclusive myoepithelial differentiation (morphologic and immunophenotypic) accompanied by established criteria of malignancy allow for definitive diagnosis of this rare salivary gland tumor.

Clinical Diagnosis and Treatment Analyses on SMARCB1 (Integrase Interactor 1)–Deficient Sinonasal Carcinoma: Case Series with Systematic Review of the Literature

This study aims to improve the understanding of SMARCB1 (integrase interactor 1)-deficient sinonasal carcinoma (SDSC) by analyzing its clinical features, treatment strategies, and prognosis. Sixty-nine patients were included in this research: 15 new cases from Beijing Tongren Hospital and 54 previously reported cases. We analyzed and summarized patients' epidemiologic data, clinical features, and treatment regimens. Main outcomes were overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate analyses were performed using a Cox regression model for OS and RFS. SDSC was more common in men than women with a median age of 52 years (range, 21-89 years). Epistaxis (40.0%) and headache (36.7%) were the major symptoms. The most common affected paranasal sinus was the ethmoid sinus (58.0%). For TNM stage, 66.7% cases were first diagnosed as T4N0M0. The tumor cells were complete loss of integrase interactor 1 in all cases by immunohistochemical analysis. However, 72.5% patients were first misdiagnosed initially. The 1-year, 3-year, and 5-year OS and RFS were 85.3%, 51.8%, 47.8%; and 56.8%, 38.2%, and 35.3%, respectively. The RFS of comprehensive treatment based on surgery was better than that of systemic therapy without surgery (P < 0.05). In addition, the OS and RFS of surgery with chemoradiotherapy was better than that of surgery with radiotherapy (P < 0.05). Univariate and multivariate analysis identified treatment modality as an independent prognostic factor for patients with SDSC. Immunohistochemical analysis of SDSC during initial biopsy can prevent delays in diagnosis and treatment. Radical surgery resection combined with chemoradiotherapy may be the preferred treatment modality.

SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma – a Systematic Review and Pooled Analysis of Treatment Outcomes

SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma – a Systematic Review and Pooled Analysis of Treatment Outcomes

Clinicopathological characteristics of SMARCB1(INI1)-deficient sinonasal carcinoma

Objective: To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma (n=10), poorly-differentiated adenocarcinoma (n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma (n=5), neuroendocrine carcinoma (n=10), and other non-epithelial tumors [olfactory neuroblastoma (n=10), rhabdomyosarcoma (n=10), NK/T-cell lymphoma (n=10), malignant melanoma (n=10), Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma (n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results: The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author's unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months. Conclusion: SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

Methylation Drivers and Prognostic Implications in Sinonasal Poorly Differentiated Carcinomas.

Simple SummaryPoorly differentiated sinonasal carcinomas (PDSNCs) are rare neoplasms that include a wide spectrum of malignancies characterized by alteration in different epigenetic mechanisms (SWI/SNF complex, IDH2, NUT). The aim of our study was to verify if the identification of specific genetic and epigenetic alterations can be useful to recognize different clinico-pathological subsets of PDSNCs to guide treatment decisions. In our cohort, 14 cases showed alterations in SWI/SNF complex or IDH2 genes, which were associated with a higher global DNA methylation level and worst prognosis. The integration of genetic and epigenetic features appears to be a good strategy to improve the clinico-pathological classification of these tumors and to recognize distinct prognostic entities that deserve tailored clinical management.Background: Poorly differentiated sinonasal carcinomas (PDSNCs) are rare and aggressive malignancies, which include squamous cell carcinoma (SCC), sinonasal undifferentiated carcinoma (SNUC), and neuroendocrine carcinomas (NEC). Several epigenetic markers have been suggested to support the histopathological classification, predict prognosis, and guide therapeutic decision. Indeed, molecularly distinct subtypes of sinonasal carcinomas, including SMARCB1-INI1 or SMARCA4 deficient sinonasal carcinoma, isocitrate dehydrogenase (IDH)-mutant SNUC, ARID1A mutant PDSNCs, and NUT carcinomas, have recently been proposed as separate entities. Identification of aberrant DNA methylation levels associated with these specific epigenetic driver genes could be useful for prognostic and therapeutic purpose. Methods: Histopathological review and immunohistochemical study was performed on 53 PDSNCs. Molecular analysis included mutational profile by NGS, Sanger sequencing, and MLPA analyses, and global DNA methylation profile using LINE-1 bisulfite-PCR and pyrosequencing analysis. Results: Nine SWI/SNF complex defective cases and five IDH2 p.Arg172x cases were identified. A significant correlation between INI-1 or IDH2 defects and LINE-1 hypermethylation was observed (p = 0.002 and p = 0.032, respectively), which were associated with a worse prognosis (p = 0.007). Conclusions: Genetic and epigenetic characterization of PDSNCs should be performed to identify distinct prognostic entities, which deserved a tailored clinical treatment.

SMARCB1 (INI1)–Deficient Sinonasal Carcinoma With Yolk Sac Tumor Differentiation: Case Report and Review of the Literature

Abstract SMARCB1 (INI1)–deficient sinonasal carcinoma is a recently described primary neoplasm of the sinonasal tract that occurs infrequently and displays aggressive clinical behavior. Classic histopathologic findings of INI1-deficient sinonasal carcinoma include sheets and nests of basaloid tumors cells with a monomorphic appearance. Variable amounts of rhabdoid and glandular differentiation have been reported. Diagnosis of this lesion can be challenging because of significant morphologic and immunohistochemical overlap between other primary lesions of the sinonasal tract, including basaloid and other nonkeratinizing squamous cell carcinomas, sinonasal undifferentiated carcinoma, and the newly described BRG1-deficient sinonasal carcinoma, among others. Recently, yolk sac tumor (YST)–like differentiation has been described in multiple reports of INI1-deficient sinonasal carcinoma, which expands both the histologic spectrum of this lesion and its differential diagnosis. Although there is significant immunophenotypic overlap between primary YST and INI1-deficient sinonasal carcinoma with YST differentiation, loss of INI1 expression by immunohistochemistry is not seen in YST. INI1 immunohistochemistry is a sensitive and specific marker for identifying INI1-deficient sinonasal carcinoma, and pathologists should have a low threshold for performing this test on tumors with a myriad of histologic features.

SMARCB1 (INI1)-deficient sinonasal carcinoma, basaloid subtype: First reported case in Taiwan and literature review

SMARCB1 (INI1)-deficient sinonasal carcinoma is a recently discovered poorly differentiated/undifferentiated sinonasal carcinoma characterized by complete loss of immunoexpression of SMARCB1(INI1) resulting from inactivation of SMARCB1 gene, a known tumor suppressor. Histologically, these tumors have predominant basaloid and rare rhabdoid features. Because other small blue round cell tumors of sinonasal tracts show retained SMARCB1(INI1) expression, this marker should be routinely included in immunohistochemicalpanels together with SMARCA4, p40, p63, p16, NUT, CD99, FLI1, CK7, CD117, and IDH1/2 as well as neuroendocrine markers to make differential diagnoses. If positive for p16, then human papillomavirusin situ hybridization is needed to exclude the possibility of HPV-related tumors. Herein, we describethe first case of SMARCB1 (INI1)-deficient sinonasal carcinoma in Taiwan. The patient, diagnosed as having stage IV disease, was treated with concurrentchemoradiotherapy and remained disease-free at two years, a better outcome than most reported cases. We reviewrelevantliterature to help physicians distinguish this tumor from other ones.

SMARCB1 (INI1)-deficient sinonasal carcinoma: a clinicopathological analysis of six cases

Objective: To study the clinicopathological features, diagnostic features and differential diagnoses of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Six cases of SDSC diagnosed at Eye, Ear, Nose and Throat Hospital, Fudan University from 2016 to 2018 were retrieved; the clinical features, histomorphology, immunophenotype, radiology and outcome were analyzed with review of literature. Results: There were five men and one woman with age range of 37 years to 75 years (mean 56 years). One case was in stage T2, and 5 cases were in stage T4. Computer tomography and magnetic resonance imaging showed a mass occupying the sinonasal cavity with bone destruction in all six patients. Microscopically, the tumors had infiltrative margins. Four tumors were composed mostly of basaloid cells, which possessed high nuclear/cytoplasmic ratio,scant cytoplasm,and minimalnuclear pleomorphism; and the cells were arranged in sheets or nests in a desmoplastic stroma. Two tumors were composed of rhabdoid cells, which possessed abundant, eosinophilic cytoplasm and eccentric nuclei, often growing in a nests or sheets pattern. Immunohistochemical staining showed that 6/6 cases had complete loss of INI1, diffusely and strongly positive for CKpan, and were negative for S-100 and EBER ISH; 4/6 cases were focally positive for p63; 1/5 was focally positive for Syn and p16. The Ki-67 index was 30% to 70%. The follow-up period ranged 1-26 months, with one patient died of extensive metastases, one had local recurrence, and two had lymph node metastases; one was alive without disease, and one was lost to follow-up. Conclusions: SMARCB1 (INI1)-deficient sinonasal carcinoma is mostly aggressive, with rapid progression and poor prognosis. Histomorphological spectrum predominantly consists of basaloid type and rhabdoid type. The complete loss of nuclear expression of INI1 can help to distinguish this tumor from its many mimickers.

SMARCB1 (INI-1)-Deficient Adenocarcinoma of the Sinonasal Tract: A Potentially Under-Recognized form of Sinonasal Adenocarcinoma with Occasional Yolk Sac Tumor-Like Features

The classification of sinonasal adenocarcinoma (SNAC) is complex. The high-grade, non-intestinal SNAC group is particularly heterogeneous, with tumors showing widely variable morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma is a newly described, aggressive tumor that usually resembles sinonasal undifferentiated carcinoma (SNUC) or non-keratinizing squamous cell carcinoma; however, glandular differentiation has been rarely reported and this feature may be under-recognized. We present a dedicated series of 12 SMARCB1-deficient SNACs. All tumors had an oncocytoid/plasmacytoid cytomorphology with variable degrees of glandular differentiation consisting of tubules and cribriform structures with foci of intracellular or intraluminal mucin. Three of 12 tumors exhibited foci of yolk sac tumor-like histologic features. The tumors were uniformly high-grade, with nuclear pleomorphism, elevated mitotic rates and frequent necrosis. By immunohistochemistry, all tumors were entirely SMARCB1-deficient, and 10 of 12 were CK7-positive. Occasional expression of CDX2 (4 of 12), CK20 (3 of 12), and p40 (3 of 10) was seen. Expression of yolk sac markers was variably present in tumors that harbored yolk sac-like areas but also tumors that did not: glypican-3 (10 of 11), SALL4 (6 of 11), HepPar-1 (4 of 11), PLAP (1 of 10), and AFP (1 of 11). SMARCB1-deficient sinonasal carcinoma, particularly the oncocytoid/plasmacytoid form, can demonstrate variable degrees of glandular differentiation. This unexpected morphology combined with variable immunohistochemical results may lead to misdiagnoses of high-grade intestinal or non-intestinal SNAC, myoepithelial carcinoma, or even yolk sac tumor or metastatic hepatocellular carcinoma.

SMARC-B1 deficient sinonasal carcinoma metastasis to the brain with next generation sequencing data: a case report of perineural invasion progressing to leptomeningeal invasion

BackgroundSMARCB1-deficient sinonasal carcinoma (SDSC) is an aggressive subtype of head and neck cancers that has a poor prognosis despite multimodal therapy. We present a unique case with next generation sequencing data of a patient who had SDSC with perineural invasion to the trigeminal nerve that progressed to a brain metastasis and eventually leptomeningeal spread.Case presentationA 42 year old female presented with facial pain and had resection of a tumor along the V2 division of the trigeminal nerve on the right. She underwent adjuvant stereotactic radiation. She developed further neurological symptoms and imaging demonstrated the tumor had infiltrated into the cavernous sinus as well as intradurally. She had surgical resection for removal of her brain metastasis and decompression of the cavernous sinus. Following her second surgery, she had adjuvant radiation and chemotherapy. Several months later she had quadriparesis and imaging was consistent with leptomeningeal spread. She underwent palliative radiation and ultimately transitioned quickly to comfort care and expired. Overall survival from time of diagnosis was 13 months. Next generation sequencing was carried out on her primary tumor and brain metastasis. The brain metastatic tissue had an increased tumor mutational burden in comparison to the primary.ConclusionsThis is the first report of SDSC with perineural invasion progressing to leptomeningeal carcinomatosis. Continued next generation sequencing of the primary and metastatic tissue by clinicians is encouraged toprovide further insights into metastatic progression of rare solid tumors.