Sinonasal Undifferentiated Carcinoma Research Articles

Targeting sinonasal undifferentiated carcinoma with a combinatory immunotherapy approach

PurposeSinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal cavity with poor prognosis and limited treatment options. To investigate the potential for SNUC sensitivity to combinatory immunotherapy, we performed in vitro studies with SNUC cell lines and used multi-spectral immunofluorescence to characterize the in vivo patient SNUC tumor immune microenvironment (TIME). Experimental designHuman-derived SNUC cell lines were used for in vitro studies of tumor cell susceptibility to natural killer (NK) cell-based immunotherapeutic strategies. Tumor samples from 14 treatment naïve SNUC patients were examined via multi-spectral immunofluorescence and clinical correlations assessed. ResultsAnti-PD-L1 blockade enhanced NK cell lysis of SNUC cell lines ∼5.4 fold (P ≤ 0.0001). This effect was blocked by a CD16 neutralizing antibody demonstrating activity through an antibody-dependent cellular cytotoxicity (ADCC) mediated pathway. ADCC-dependent lysis of SNUC cells was further enhanced by upregulation of PD-L1 on tumor cells by exogenous interferon-gamma (IFN-γ) administration or interleukin-15 (IL-15) stimulated IFN-γ release from NK cells. Combination treatment with anti-PD-L1 blockade and IL-15 superagonism enhanced NK-cell killing of SNUC cells 9.6-fold (P ≤ 0.0001). Untreated SNUC patient tumor samples were found to have an NK cell infiltrate and PD-L1+ tumor cells at a median of 5.4 cells per mm2. A striking 55.7-fold increase in CKlow tumor cell/NK cell interactions was observed in patients without disease recurrence after treatment (P = 0.022). Patients with higher CD3+CD8+ in the stroma had a significantly improved 5-year overall survival (P = 0.0029) and a significant increase in CKlow tumor cell/CD8+ cytotoxic T cell interactions was noted in long-term survivors (P = 0.0225). ConclusionThese data provide the pre-clinical rationale for ongoing investigation into combinatory immunotherapy approaches for SNUC.

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.

Neuroendocrine and undifferentiated sinonasal and skull base tumors: An up-to-date narrative review.

Tumors located in the nasal cavity, paranasal sinuses and the skull base comprise a wide range of histologic subtypes. Among them, neuroendocrine and undifferentiated tumors are rare but noteworthy, because of their distinctive features, aggressive nature, and diagnostic complexities. A literature search was conducted in the PubMed/MEDLINE and the Scopus databases from 2019 until inception. The keywords "neuroendocrine", "undifferentiated", "nose", "sinonasal", "paranasal", "skull base" were used. Thirty-eight articles referring to neuroendocrine and undifferentiated tumors of the nose, paranasal sinuses and the skull base were finally included and analyzed. Neuroendocrine and undifferentiated tumors of the nose, paranasal sinuses and the skull base are infrequent malignancies, most commonly affecting middle-aged men. They usually present with non-specific symptoms, even though ocular or neurologic manifestations may occur. Prognosis is generally poor; however, novel targeted and immunological therapies have shown promising results. Sinonasal Neuroendocrine Carcinomas (SNECs) carry distinct histological and immunohistochemical features. Management consists of surgical resection coupled with systematic therapy. Sinonasal Undifferentiated Carcinomas (SNUCs) lack specific squamous or glandular features. They typically stain positive for pancytokeratin and INI1 antibody. Treatment includes induction chemotherapy, followed by a combination of chemotherapy and radiotherapy. Olfactory neuroblastomas (ONBs) have neuroepithelial or neuroblastic features. They show diffuse positivity for various markers, including synaptophysin, chromogranin, and neuron-specific enolase (NSE). Surgical resection plus radiotherapy is considered the treatment of choice. In conclusion, neuroendocrine and undifferentiated tumors arising from the nose, paranasal sinuses and the skull base represent a unique group of malignancies. A thorough understanding of their clinical features, molecular changes, diagnostic approaches, treatment modalities, and prognostic factors is critical for providing optimal patient care. Still, continued research efforts and multidisciplinary collaboration are warranted, in order to improve outcomes for patients diagnosed with these rare and aggressive tumors.

Sino nasal undifferentiated carcinoma – A diagnostic conundrm

Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly aggressive tumour frequently arising from the maxillary sinus and nasal cavity. Here we report a 34-year-old female patient who presented with a pale polypoidal mass which bleeds on touch involving the left nasal cavity and nasopharynx. Imaging showed a multilobulated lesion involving the left nasal cavity and left paranasal sinuses with extension into the left masticator space, pterygopalatine fossa and retropharyngeal space supplied by a branch of the left maxillary artery. It suggested a possibility of a benign vascular mass lesion. The mass was surgically removed via the maxillary swing approach. Immunohistochemical analysis showed epithelial origin (AE1/AE3+, EMA+) and no reactivity for neuroendocrine, melanocytic, hematolymphoid, or mesenchymal markers. A diagnosis of SNUC was reached and the patient was given concurrent radiotherapy and chemotherapy. The patient is disease free one year post surgery. To conclude, a vigilant correlation of clinical, microscopic, and immunohistochemical characteristics is essential for early diagnosis and optimal management of SNUC.

Clinicopathological Profile of Sinonasal Masses in a Tertiary Care Center in Central India: A Retrospective Study.

Diseases of the nose and paranasal sinuses have a significant impact on the patient's functional and structural aspects. They affect all age groups and both sexes. Due to its proximity to vital structures, diseases of the nose and paranasal sinuses sometimes lead to very grave prognoses. This was a retrospective study done in one of central India's largest tertiary care centers. We studied 227 cases of sinonasal masses in both the non-neoplastic and neoplastic categories. Clinicopathological characteristics of masses were analyzed with the help of clinical and imaging findings and subsequently confirmed by tissue diagnosis. The mean age of presentation was 45.5 years, with a male-to-female ratio of 1.25:1. Most of our patients were from lower-middle socioeconomic groups with educational qualifications below the 10th standard. Nasal obstruction was the most common symptom. A computed tomography scan was the preferred radiological investigation. Sinonasal undifferentiated carcinoma was the most common variant of malignancy, with a total number of six out of 22 (27%). The evaluation of sinonasal masses should be carried out systematically and meticulously. Since the initial presentation of most of the diseases of the nose and paranasal sinuses is the same, a proper clinical, radiological, and tissue diagnosis should be carried out to avoid causing malignant lesions.

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.

Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

Sox2 and βIII-Tubulin as Biomarkers of Drug Resistance in Poorly Differentiated Sinonasal Carcinomas.

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed βIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger βIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and βIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility.

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR)

ObjectivesSinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. MethodsThis study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. ResultsA total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. ConclusionIn the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

Induction Chemotherapy for Sinonasal Tumors in Patients Presenting with Brain Invasion and/or Neurological Deficits

Abstract Objective The aim of this study was to investigate the safety of induction chemotherapy (IC) for patients with sinonasal malignancies with brain invasion or a neurological deficit. Methods We conducted a retrospective analysis of patients who underwent IC for sinonasal malignancies with intracranial invasion or a neurological deficit at a single tertiary cancer center from 1992 to 2020. Results In total, 460 patients with sinonasal malignancies were included in the study. Of the patients reviewed, 341 underwent IC and within this group 40 had brain invasion (BI) and 31 had a neurological deficit (ND) at presentation. The most prevalent malignancy was sinonasal undifferentiated carcinoma (BI 40%, ND 41.9%), followed by esthesioneuroblastoma (BI 27.5%, ND 9.7%). All tumors were stage T4 with the majority lacking nodal metastases (BI N0: 72.5%, ND N0: 77.5%). All patients completed at least two cycles of IC. Partial or complete response to IC was seen in 80% of BI and 71% of ND patients. No patients had cessation of treatment due to neurologic decline and none required urgent surgery. Five patients (12.5%) with BI and 2 (6.5%) with ND had interruption of IC for reasons other than neurological decline. In patients with ND, IC led to improvement of 54.5% NDs. Conclusion In patients with sinonasal malignancies with BI or ND who underwent IC, no patients had cessation of treatment due to neurologic decline. In contrast, most patients had improvement of neurologic symptoms with IC. IC was safely administered without interruption due to neurological decline or symptom progression.

Endoscopic management of sinonasal tumours in the Nordic university hospitals: a survey

PurposeThe Nordic countries (27 M) all have comparable, publicly funded healthcare systems, and the management of sinonasal tumours is centralised to the 21 university hospitals. We sought to assess and compare the treatment practice of sinonasal tumours across the Nordic countries.MethodsA web-based questionnaire was sent to all university hospital departments of otorhinolaryngology—head and neck surgery in the Nordic countries.ResultsAnswers were obtained from all 21 Nordic university hospitals. The endoscopic approach was widely utilised by all, with most (62%) centres reporting 3–4 surgeons performing endoscopic sinonasal tumour surgery. Finland reported the lowest rates of centralisation among university hospitals despite having the highest number of 0.1–1 M catchment population hospitals. Most centres (88%) opted for the endoscopic approach in a patient case warranting medial maxillectomy. In a case of a Kadish C esthesioneuroblastoma, most (52%) of the centres preferred an endoscopic approach. Most centres (62%) reported favouring the endoscopic approach in a case describing a juvenile angiofibroma. Regarding a case describing a sinonasal undifferentiated carcinoma, consensus was tied (38% vs. 38%) between endoscopic resection followed by postoperative (chemo)radiotherapy (RT/CRT) and induction chemotherapy followed by RT/CRT or surgery followed by RT/CRT.ConclusionEndoscopic approach was widely utilised in the Nordic countries. The case-based replies showed differences in treatment practice, both internationally and nationally. The rate of centralisation among university hospitals remains relatively low, despite the rarity of these tumours.

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.

Nasopharyngeal Carcinoma Mimicking Sinonasal Undifferentiated Carcinoma

Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that covers the surface and lining of the nasopharynx. It is divided into keratinizing squamous cell carcinoma, and non-keratinizing carcinoma, which can be further divided into differentiated and undifferentiated subtypes. Symptoms of NPC can be obscure due to its anatomic location. On the other hand, sinonasal undifferentiated carcinoma defined as a highly aggressive and clinicopathologically distinctive carcinoma of uncertain histogenesis that typically presents with locally extensive disease. The present report is a case of 66-year-old malay woman with underlying hypertension, hyperlipidemia and ischemic heart disease presented with swelling over the left upper palate for 5 months associated with the nasal symptoms. Cranial nerves were intact. Nasal endoscopy of the left nose revealed a mass occupying the left nasal cavity with histopathology of sinonasal undifferentiated carcinoma. However, CT scan result showed huge left nasopharyngeal carcinoma with local invasion and intracranial extension.

Isolated Frontal Sinus Undifferentiated Carcinoma: First case Report in the Literature.

Sinonasal undifferentiated carcinoma (SNUC) is a rare tumor which is aggressive in nature, has a different clinical course in contrast to sinonasal carcinoma and poor prognosis. Here, we are reporting first case of isolated frontal SNUC which was managed by upfront surgery followed by adjuvant treatment. We want to emphasize the importance of early presentation and timely intervention in form of conservative surgery in this highly aggressive tumor.

Update from the 5th Edition of the WHO Classification of Nasal, Paranasal, and Skull Base Tumors: Imaging Overview with Histopathologic and Genetic Correlation.

Sinonasal and skull base tumors are a heterogeneous group of neoplasms with considerable histologic variation and overlapping imaging features. In 2022, the World Health Organization updated the head and neck tumor classification, further emphasizing the importance of molecular data and genetic alterations in sinonasal neoplasms. The changes include the addition of new entities and discussion of emerging entities, as well as changes to the taxonomy and characterization of tumors. The new classification focuses on entities that develop in these sites either exclusively (eg, olfactory neuroblastoma) or most frequently. Another change includes reduction in the number of categories by creating separate category-specific chapters for soft-tissue, hematolymphoid, and neuroectodermal lesions. In this review, we briefly discuss the various categories in the new classification with a more detailed description of the 2 new entities (SWItch/Sucrose Non-Fermentable complex-deficient sinonasal carcinomas and human papillomavirus-related multiphenotypic sinonasal carcinoma). We also highlight the emerging entities including IDH-mutant sinonasal malignancies and DEK-AFF2 carcinoma, presently classified as sinonasal undifferentiated carcinoma and nonkeratinizing squamous cell carcinoma, respectively.

Induction Chemotherapy for Locoregionally Advanced Sinonasal Squamous Cell Carcinoma and Sinonasal Undifferentiated Carcinoma: A Comprehensive Review.

Sinonasal squamous cell carcinoma (SNSCC) and sinonasal undifferentiated carcinoma (SNUC) are two of the most common, high-grade malignancies of the sinonasal cavity. The standard of care for resectable lesions per the National Comprehensive Cancer Network (NCCN) guidelines includes surgical resection with negative margins plus adjuvant radiation therapy. However, surgery for locally advanced disease with both orbital and intracranial involvement is associated with significant morbidity and poor overall survival. Over the last decade, induction chemotherapy (IC) has emerged as part of a multimodal treatment strategy to optimize locoregional disease control and minimize substantial surgical morbidity such as orbital exenteration without compromising rates of overall survival. The response to IC both guides additional therapy and helps prognosticate a patient's disease. This narrative review examines the data surrounding the management of patients with SNSCC and SNUC. The pros and cons of upfront surgical management plus adjuvant therapy will be explored, and the case for IC will be presented. The IC-specific regimens and treatment paradigms for SNSCC and SNUC will each be explored in detail. Organ preservation, treatment morbidity, and survival data will be presented, and evidence-based recommendations will be presented for the management of these patients.

Diagnostic algorithm for challenging blue cell sinonasal carcinoma

The newly emerging sinonasal carcinomas have demonstrated diverse morphologies and specific molecular rearrangements along with deviant clinical behavior from conventional counterparts. We aim to propose a diagnostic algorithm that is based on molecular findings of each sinonasal cancer and is considering the new entities has been called upon. Such a diagnostic algorithm should help diagnostic pathologists establish a diagnosis of a challenging sinonasal blue cell carcinomas and researchers performing retrospective analysis of archival cases. Along with consulting our archival cases, literature mining was conducted to retrieve the immunohistochemical and molecular findings regarding the newly emerging entities. Our proposed algorithm distinguishes poorly differentiated (non) keratinizing SNSCC, from anaplastic myoepithelial carcinoma, NUT midline carcinoma, SMARCB1/SMARCA4-deficient teratocarcinosarcoma, SMARCB1/SMARCA4-deficient carcinosarcoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, HPV-related multiphenotypic sinonasal carcinoma and other adenocarcinomas. By incorporating morphologic features, immunohistochemical markers, and molecular investigations, the algorithm enhances the accuracy of diagnosis, particularly in cases where comprehensive molecular testing is not readily available. This algorithm serves as a valuable resource for pathologists, facilitating the proper diagnosis of sinonasal malignancies and guiding appropriate patient management.

Molecular Characterization of Sinonasal Undifferentiated Carcinoma—Past, Present, and Future

Molecular Characterization of Sinonasal Undifferentiated Carcinoma—Past, Present, and Future

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.

SMARCB1-Retained and SMARCB1-Deficient SNUC are Genetically Distinct: A Pilot Study Using RNA Sequencing

AbstractBackground Understanding the genetic basis for the molecular classification of sinonasal undifferentiated carcinoma (SNUC) based on SMARCB1 may improve our understating regarding the nature of the disease. The objective of the study was to compare the genetic profile of SMARCB1-retained (SR-SNUC) and SMARCB1-deficient SNUC (SD-SNUC).Methods Formalin-fixed, paraffin-embedded tissue from treatment-naive patients with SNUC were selected. Three cases of SR-SNUC, four cases of SD-SNUC, and four samples of nontumor tissue (control samples) were selected. Ribonucleic acid (RNA) sequencing was performed.Results SR-SNUC had a higher number of variants (1 variant for every 15,000 bases) compared with SD-SNUC (1 variant every 29,000 bases). The ratio of missense to silent mutation ratio was higher for SR-SNUC (0.8) as compared with SD-SNUC (0.7). Approximately 1,500 genes were differentially expressed between SR-SNUC and SD-SNUC. The genes that had a higher expression in SR-SNUC included TPD52L1, B3GNT3, GFY, TJP3, ELL3, CYP4F3, ALDH3B2, CKMT1B, VIPR1, SLC7A5, PPP2R2C, UPK3B, MUC1, ELF5, STY7, and H2AC14. The gene that had a higher expression in SD-SNUC was ZFHX4. Most of these genes were related to either protein translation or immune regulation. The most common (n = 3, 75%) mechanisms of loss of SMARCB1 gene in SD-SNUC was loss of heterozygosity.Conclusion RNA sequencing is a viable and informative approach for genomic profiling of archival SNUC samples. Both SR-SNUC and SD-SNUC were noted to have distinct genetic profiles underlying the molecular classification of these diseases.