SWI/SNF-deficient head and neck neoplasms: An overview

Agaimy, Abbas; Bishop, Justin A.

doi:10.1053/j.semdp.2021.02.002

Cited by 34 publications

(41 citation statements)

References 48 publications

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“…The gene products of SMARCB1 are abundantly expressed in the nuclei of all normal human cell types [3], similar to most of the other components of the SWI/SNF complex. Biallelic inactivation of the gene leads to complete loss of SMARCB1 expression, which can be routinely detectable by immunohistochemical staining as the standard diagnostic criteria of SMARCB1-deficient malignancy [43]. Most of the cases are sporadic, while germline mutations have also been reported.…”

Section: Discussionmentioning

confidence: 99%

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

Lee

Tsang

et al. 2022

Cancers

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(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.

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Section: Discussionmentioning

confidence: 99%

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

Lee

Tsang

et al. 2022

Cancers

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“…Rarely, metastatic SMARCA4deficient undifferentiated thoracopulmonary malignancies (indistinguishable from SMARCA4-deficient sinonasal carcinoma) might present in the head and neck sites, although very rare in the sinonasal areas, and should be thought of. Exploring the recent clinical history and review of current chest imaging are diagnostic [42].…”

Section: Differential Diagnosis and Conceptual Reappraisal Of Tcsmentioning

confidence: 99%

Proceedings of the North American Society of Head and Neck Pathology, Los Angeles, CA, March 20, 2022: SWI/SNF-deficient Sinonasal Neoplasms: An Overview

Agaimy

2022

Head and Neck Pathol

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The pathology of poorly differentiated sinonasal malignancies has been the subject of extensive studies during the last decade, which resulted into significant developments in the definitions and histo-/pathogenetic classification of several entities included in the historical spectrum of “sinonasal undifferentiated carcinomas (SNUC)” and poorly differentiated unclassified carcinomas. In particular, genetic defects leading to inactivation of different protein subunits in the SWI/SNF chromatin remodeling complex have continuously emerged as the major (frequently the only) genetic player driving different types of sinonasal carcinomas. The latter display distinctive demographic, phenotypic and genotypic characteristics. To date, four different SWI/SNF-driven sinonasal tumor types have been recognized: SMARCB1(INI1)-deficient carcinoma (showing frequently non-descript basaloid, and less frequently eosinophilic, oncocytoid or rhabdoid undifferentiated morphology), SMARCB1-deficient adenocarcinomas (showing variable gland formation or yolk sac-like morphology), SMARCA4-deficient carcinoma (lacking any differentiation markers and variably overlapping with large cell neuroendocrine carcinoma and SNUC), and lastly, SMARCA4-deficient sinonasal teratocarcinosarcoma. These different tumor types display highly variable immunophenotypes with SMARCB1-deficient carcinomas showing variable squamous immunophenotype, while their SMARCA4-related counterparts lack such features altogether. While sharing same genetic defect, convincing evidence is still lacking that SMARCA4-deficient carcinoma and SMARCA4-deficient teratocracinosarcoma might belong to the spectrum of same entity. Available molecular studies revealed no additional drivers in these entities, confirming the central role of SWI/SNF deficiency as the sole driver genetic event in these aggressive malignancies. Notably, all studied cases lacked oncogenic IDH2 mutations characteristic of genuine SNUC. Identification and precise classification of these entities and separating them from SNUC, NUT carcinoma and other poorly differentiated neoplasms of epithelial melanocytic, hematolymphoid or mesenchymal origin is mandatory for appropriate prognostication and tailored therapies. Moreover, drugs targeting the SWI/SNF vulnerabilities are emerging in clinical trials.

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“…In this regard, patients affected by IDH-mutated poorly differentiated and undifferentiated sinonasal carcinomas could benefit from specific treatments with mutant IDH inhibitors [114], while SWI/SNF-deficient carcinomas could be targeted by inhibitors of EZH2 [115,116]. Bromodomain inhibitors have been tested for treatment of NUT carcinomas but have shown limited efficacy in vivo [117,118].…”

Section: Undifferentiated Carcinomasmentioning

confidence: 99%

Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities

Taverna

Agaimy

Franchi

2022

Cancers

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Sinonasal carcinomas are a heterogeneous group of rare tumors, often with high-grade and/or undifferentiated morphology and aggressive clinical course. In recent years, with increasing molecular testing, unique sinonasal tumor subsets have been identified based on specific genetic alterations, including protein expression, chromosomal translocations, specific gene mutations, or infection by oncogenic viruses. These include, among others, the identification of a subset of sinonasal carcinomas associated with HPV infection, the identification of a subset of squamous cell carcinomas with EGFR alterations, and of rare variants with chromosomal translocations (DEK::AFF2, ETV6::NTRK and others). The group of sinonasal adenocarcinomas remains very heterogeneous at the molecular level, but some recurrent and potentially targetable genetic alterations have been identified. Finally, poorly differentiated and undifferentiated sinonasal carcinomas have undergone a significant refinement of their subtyping, with the identification of several new novel molecular subgroups, such as NUT carcinoma, IDH mutated sinonasal undifferentiated carcinoma and SWI/SNF deficient sinonasal malignancies. Thus, molecular profiling is progressively integrated in the histopathologic classification of sinonasal carcinomas, and it is likely to influence the management of these tumors in the near future. In this review, we summarize the recent developments in the molecular characterization of sinonasal carcinomas and we discuss how these findings are likely to contribute to the classification of this group of rare tumors, with a focus on the potential new opportunities for treatment.

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SWI/SNF-deficient head and neck neoplasms: An overview

Cited by 34 publications

References 48 publications

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

Proceedings of the North American Society of Head and Neck Pathology, Los Angeles, CA, March 20, 2022: SWI/SNF-deficient Sinonasal Neoplasms: An Overview

Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities

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