SMARCA4/BRG1-Deficient Sinonasal Carcinoma: Morphologic Spectrum of an Evolving Entity

Context.— Molecular analysis of poorly differentiated/undifferentiated sinonasal neoplasms has resulted in identification of a growing number of genetically defined tumors. SMARCA4-deficient sinonasal carcinoma is one such recently described entity that emerged from within sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and teratocarcinosarcoma (TCS). Objective.— To identify SMARCA4-deficient sinonasal carcinomas from a large institutional cohort of poorly differentiated/undifferentiated carcinomas and evaluate their clinicopathologic features. Design.— SMARCA4/BRG1 immunohistochemistry was performed on all tumors diagnosed as SNUC, poorly differentiated carcinoma, NEC, and TCS during a 12-year period. SMARCA2/BRM and INSM1 immunostaining was performed in SMARCA4-deficient cases. Results.— Twelve SMARCA4-deficient sinonasal carcinomas were identified among 299 cases. Morphologically, 5 cases were large cell NEC, 2 cases were small cell NEC, and 5 were TCS. SMARCA4 loss was diffuse and complete in 10 cases, while 2 cases showed focal retention. Most cases showed diffuse cytokeratin staining accompanied by weak, usually focal staining for chromogranin and synaptophysin. INSM-1 showed negativity in most cases. All cases showed retained SMARCA2 expression. IDH1/2 mutation was absent in all cases analyzed. Four of 7 patients died of disease, and aggressive multimodality treatment had better outcome. Conclusions.— SMARCA4-deficient sinonasal carcinomas are morphologically akin to sinonasal poorly differentiated NECs and TCS, display cytokeratin positivity and only focal staining for neuroendocrine markers, and have aggressive biological behavior. Inclusion of SMARCA4 in the immunohistochemical panel for diagnostic workup of all sinonasal NEC and TCS phenotypes will facilitate their early recognition. Comprehensive germline and somatic mutational analyses of these tumors are necessary for further insights into their molecular pathogenesis.

HPV-Related Multi-Phenotypic Sinonasal Carcinoma with Aggressive Clinical Behavior; A Rare Case

Introduction/Objective Human Papilloma Virus (HPV)-related multiphenotypic sinonasal carcinoma, previously known as HPV-related sinonasal carcinoma with adenoid cystic carcinoma-like features, is a rare type of sinonasal carcinoma with both epithelial-derived and salivary gland-type morphologic features. It is associated with high-risk HPV, but lacks MYB gene rearrangements. Methods/Case Report We report a case of a 59-year-old male who presented with a rapidly growing sinonasal mass. On MRI, a left nasal cavity lesion was identified growing laterally along the frontal process of the maxilla, extending into the middle meatus and into the maxillary sinus. Patient underwent a complex left medial maxillectomy, spheno- ethmoidectomy, and sinusotomy. On gross evaluation, the left inferior turbinate and sidewall demonstrated a 4 cm unremarkable turbinate with attached friable soft tissue. Microscopic examination revealed sections of carcinoma with various architectural patterns comprised of foci with adenoid cystic carcinoma-like morphology, basaloid squamous cell carcinoma and adenocarcinoma. The tumor showed positive immunostaining for P40, but focal reactivity to S100 and rare scattered reactivity with CD117. INI-1 immunostain was retained in tumor cells. P16 immunostain was strong and diffuse and high-risk cocktail HPV RNA ISH was positive. However, MYB FISH testing was equivocal. Morphologic and immunophenotypic findings were consistent with HPV-related multiphenotypic sinonasal carcinoma. The tumor involved the olfactory nerve fibers requiring a skull base resection and showed extension into the dura mater. Results (if a Case Study enter NA) NA Conclusion HPV related multiphenotypic sinonasal carcinoma is a recently described entity that can pose significant diagnostic challenge. It typically has an indolent clinical course with potential for late recurrences. This case study highlights the potential aggressive nature of this type of sinonasal carcinoma, despite association with high-risk HPV, and use of ancillary testing in aiding diagnosis.

Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma—An Even Broader Tumor Entity?

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a recently defined tumor subtype with apparent favorable clinical outcome despite aggressive histomorphology. However, in recent years, additional numbers of cases, with more variable features and at locations outside the sinonasal region, have complicated the definition of HMSC. Here, we have performed a systematic review of all cases described so far in order to accumulate more knowledge. We identified 127 articles published between 2013 and 2021, of which 21 presented unique cases. In total, 79 unique patient cases were identified and their clinical and micromorphological nature are herein summarized. In our opinion, better clinical follow-up data and a more detailed tumor characterization are preferably needed before HMSC can finally be justified as its own tumor entity.

A New Risk Score Assessment for Neck Management in T1-T2N0 Sinonasal Squamous Cell Carcinoma Patients: A European Head and Neck Cancer Center Survey Study and Evaluation of 58 Patients with Early Stage Sinonasal Carcinoma

Purpose The purpose of the present study was to assess whether European head and neck cancer centers perform elective neck dissection (END) in early stage sinonasal squamous cell carcinomas (SCCs) and whether END affects oncological outcome. Methods A questionnaire regarding performance of END in T1 - T2 sinonasal SCCs was sent to 38 head and neck cancer centers in Europe. The results were further correlated and compared with clinical data of 58 patients with T1 (n = 37) and T2 (n = 21) sinonasal SCCs, a risk score and a nomogram were generated. Results Only 5–10 % of respondents are performing END in T1 and 26–32% in T2 sinonasal SCCs. In our cohort regional recurrence was evident in 10 (17.2%) patients, representing a significant worse prognostic factor for cancer specific survival (HR 8.13; p = 0.016). Particularly, regional recurrence was more frequent in T2 tumors and in patients where the primary tumor originated from nasal septum and vestibule. Based on our clinical and questionnaire data a new risk-score was determined to predict necessity for END. The risk-score, including T-classification and tumor site, assigned T1-classification with 0 points, followed by 1 point for T2; tumor site: nasal septum or vestibule with 1 point and tumors from other subsites with 0 points. Based on these factors we further created a nomogram for predicting the risk of regional recurrence. Patients with a high-risk score showed 9.52-fold higher risk for regional and or distant recurrence (HR 9.52; p = 0.002;) and their 5-year CSS was 44.4% compared to 92.8% in patients with moderate or low risk (p = 0.017). Conclusions Our proposed risk-score system in T1-2N0 sinonasal carcinoma is helpful to identify patients who may benefit from END. Although to date END has no value in European head and neck cancer centers for T1-T2 sinonasal SCCs, our study indicates that the neck management in these patients should be reconsidered.