Sinonasal Undifferentiated Carcinoma (SNUC): From an Entity to Morphologic Pattern and Back Again-A Historical Perspective.

Since the first description of sinonasal undifferentiated carcinoma (SNUC) as a distinctive highly aggressive sinonasal neoplasm with probable origin from the sinonasal mucosa (Schneiderian epithelium), SNUC has been the subject of ongoing study and controversy. In particular, the SNUC category gradually became a "wastebasket" for any undifferentiated or unclassifiable sinonasal malignancy of definite or probable epithelial origin. However, with the availability of more specific and sensitive immunohistochemical antibodies and increasing implementation of novel genetic tools, the historical SNUC category became the subject of progressive subdivision leading to recognition of specific genetically defined, reproducible subtypes. These recently recognized entities are characterized by distinctive genetic aberrations including NUTM1-rearranged carcinoma (NUT carcinoma) and carcinomas associated with inactivation of different members of the SWI/SNF chromatin-remodeling gene complex such as SMARCB1-deficient and less frequently SMARCA4-deficient carcinoma. The ring became almost closed, with recent studies highlighting frequent oncogenic IDH2 mutations in the vast majority of histologically defined SNUCs, with a frequency of 82%. A review of these cases suggests the possibility that "true SNUC" probably represents a distinctive neoplastic disease entity, morphologically, phenotypically, and genetically. This review addresses this topic from a historical perspective, with a focus on recently recognized genetically defined subsets within the SNUC spectrum.

Paranasal sinus squamous cell carcinoma incidence and survival based on Surveillance, Epidemiology, and End Results data, 1973 to 2009.

BACKGROUND: Paranasal sinus squamous cell carcinomas (PNSSCC) account for 3% of all head and neck malignancies. There has been little information on the trends in incidence and survival, and no randomized trials have been conducted to guide therapy. METHODS: Patients with PNSSCC reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1973 through 2009 were categorized by sex, age, year of diagnosis, primary site, stage, and treatment. The incidence and survival were then compared across different demographic and disease-related categories by calculating rate ratios (RRs) and mortality hazard ratios along with the corresponding 95% confidence intervals (CIs). RESULTS: In total, 2553 patients with PNSSCC were identified. While incidence of PNSSCC showed a gradual decline, survival remained largely unchanged. The proportion of patients with advanced disease decreased from 14.7% during the period from 1983 to 1992 to 12.4% during 1993-2002 and to 9.5% during 2003-2009. Compared with whites, incidence was higher among African Americans (RR 1.63; 95% CI, 1.39, 1.90) and among all other racial groups (RR, 1.78; 95% CI: 1.53-2.07). After adjusting for age, sex, disease stage, tumor site, and treatment, mortality among African American patients also was increased (hazard ratio, 1.22; 95% CI, 1.04-1.43). Among patients with localized disease, the relation between race and mortality was no longer evident once the results were controlled for tumor classification. CONCLUSIONS: The current findings point to racial disparities in the incidence of PNSSCC and, to a lesser extent, in the outcome of patients with PNSSCC. Although there has been a decline in the proportion of patients presenting with advanced PNSSCC, the overall survival remained stable over time.

Maxillary Sinus Floor Infiltration: Results From a Series of 118 Maxillary Sinus Cancers.

OBJECTIVES/HYPOTHESIS: Maxillary cancers are rare and aggressive tumors, which can spread beyond the sinus bony walls. Preoperative assessment of infiltration of maxillary sinus floor (MSF) is paramount for surgical planning, as palatomaxillary demolition significantly impacts patients' quality of life. This study investigates the challenges involved in the preoperative and intraoperative evaluation of MSF infiltration and analyzes its prognostic relevance. STUDY DESIGN: Retrospective case series. METHODS: A retrospective review of patients treated for sinonasal malignancies at a single Institution was performed. Patients receiving surgical-based treatment with curative intent for primary maxillary sinus cancers, between January 2000 and November 2019, were included. RESULTS: A cohort of 118 patients was analyzed. By comparing intraoperative findings (endoscopic assessment and frozen sections) with preoperative radiological assessment, diagnostic changes with regard to MSF infiltration were found in 27.1% (32/118 cases). MSF infiltration negatively affected the prognosis in both univariate and multivariate analyses in the overall population. In the subgroup of pT1-T3 tumors, MSF infiltration was significantly associated with reduced overall (P = .012), disease-free (P = .011), and distant recurrence-free (P = .002) survival rates. Conversely, pT classification was not able to stratify patients according to prognosis, mainly because early-staged cancers (pT1-T2) with MSF infiltration showed reduced survival rates, similar to those observed in pT3 cancers. CONCLUSIONS: Preoperative imaging should be integrated with intraoperative findings based on endoscopic inspection and frozen sections. Future studies are required to investigate the opportunity to incorporate MSF infiltration in the TNM staging system, considering its crucial role in defining the extent of surgery and its potential as prognosticator. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:26-35, 2022.

Clinical Implication of Diagnostic and Histopathologic Discrepancies in Sinonasal Malignancies.

OBJECTIVES: To evaluate the incidence of histopathologic diagnostic discrepancy for patients referred to our institution, identify pathologies susceptible to diagnostic error, and assess the impact on survival of histopathologic diagnostic discrepancies. METHODS: Three hundred ninety-seven patients with sinonasal cancers were identified, and discordance between the outside pathologic report and MD Anderson Cancer Center pathologic report was assessed. Overall survival and disease-specific survival were analyzed using Kaplan-Meier and log rank methods. RESULTS: Discordance of major histopathologic diagnoses was present in 24% (97 of 397) of reports, with sinonasal undifferentiated carcinoma, sarcoma, neuroendocrine carcinoma, and poorly differentiated carcinoma pathologies having the highest change in diagnosis (P < .01). A further 61% (244 of 397) had minor changes such as histologic grade, subtype, or stage, with sarcoma and neuroendocrine carcinoma pathologies being most susceptible to change (P < .02). Overall, the 5-year overall survival (OS) and disease-specific survival (DSS) was reduced in patients with a major change in histopathologic diagnosis (59.2% vs. 70.2% (P = .02) and 72.9% vs. 81.2% (P = .02), respectively). Furthermore, patients with a major change in diagnosis and prior treatment experienced a significant reduction in 5-year OS (61.9% vs. 70.4%, P = .03 < .01) and DSS (72.4% vs. 81.5%, P = .04). CONCLUSION: Histopathological diagnosis of sinonasal tumors is complex and challenging given the rarity of the disease. Obtaining the correct diagnosis is important for treatment selection and survival. In histologies prone to misdiagnoses, obtaining a second opinion from experienced head and neck pathologists at a high-volume institution may potentially lead to a change in treatment recommendations that could result in improved survival in patients with sinonasal malignancies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1468-E1475, 2021.

[Inverted papilloma: a study of 13 cases in the Oto-Rhino-Laryngology at the National University Hospital of Fann]. / Papillome inversé: à propos de 13 cas au Service d'Oto-Rhino-Laryngologie du Centre Hospitalier National Universitaire de Fann.

INTRODUCTION: Inverted Papilloma (IP) is a rare benign tumour of the nose and paranasal sinuses histologically characterized by invagination of the outer layer of the epithelium in the underlying chorion. Its most distinctive feature is a strong local aggressiveness, a tendency to recur and an unpredictable risk of association with epidermoid carcinoma. The purpose of this study was to report the epidemiological, clinical, paraclinical data as well as to assess the outcomes of endoscopic endonasal surgery. METHODS: We conducted a retrospective study on a series of 13 patients whose data were collected in the Oto-Rhino-Laryngology at the National University Hospital Center of Fann, from 1st January 2012 to 31st December 2017. All patients followed up for inverted papilloma confirmed by anathomopathological examination were included in the study. RESULTS: The average age of patients was 44 years, the sex-ratio was 2.25. All patients had nasal obstruction; 53% of them had rhinorrhea followed by epistaxis in 30% of cases. Right-sided symptoms were reported by 69% of patients, left-sided symptoms by 23% and bilateral symptoms by 7% of patients. Anterior rhinoscopy showed endonasal mass in all patients. All patients underwent CT scan; the MRI was performed in a single patient. Endoscopic resection of IP was performed in 10 patients (76.9%) while external approach was used in 23% of cases. Surgery helped to clarify where the tumor had originated: in 46% of cases in the maxillary sinus, in 15% in the lower nasal turbinate, in 15% in the mid-turbinate, in 7% in the ethmoid bulla and in 7% in the lateral wall of the nasal fossa. One patient had recurrence after an average period of 26 months. Malignant transformation to squamous cell carcinoma occurred in one patient. CONCLUSION: Inverted papilloma is a very aggressive tumor. CT scan is essential to highlight its spread, especially to bone. The advent of endoscopic surgery has revolutionised treatment, providing excellent results. But, there is nevertheless a risk of recurrence after surgery which motivates an indication for long term monitoring.

Clinical characteristics and prognostic factors of sinonasal undifferentiated carcinoma: a multicenter study.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a very rare entity with a poor prognosis. Due to the lack of studies on the subject, evidence is lacking concerning its management. METHODS: A multicenter collaborative study was conducted to assess treatment strategy, oncological outcome, and prognostic factors. RESULTS: Definitive analyses focused on 54 patients with a majority of advanced stage; the 3-year overall survival (OS) and 3-year recurrence-free survival (RFS) rates were, respectively, 62.4% and 47.8%. During the follow-up, 18 patients (33.3%) died, 10 (18.5%) developed metastases, 7 had lymph-node involvement (13%), and 12 (22.2%) showed recurrence or local progression. In univariate analyses, treatment modalities associated with improved RFS were induction chemotherapy (p = 0.02) and intensity-modulated radiotherapy (p = 0.007). In the multivariate analyses, only induction chemotherapy (p = 0.047, hazard ratio [HR] = 0.39) was significantly associated with improved RFS. CONCLUSION: Multimodal therapies including induction chemotherapy and intensity-modulated radiotherapy may improve the prognosis of SNUC; surgery might improve local control. Further multicenter studies are required.

Squamous cell carcinoma of the oral cavity, maxillary antrum and lip in a Zimbabwean population: a descriptive epidemiological study.

Squamous cell carcinoma accounts for approximately 90% of oral malignancies. The objective of this study was to document the gender, age, sub-site distribution and histologic differentiation of squamous cell carcinoma of the oral cavity, maxillary antrum and lip in a Zimbabwean population. Hospital records of patients with a histologic diagnosis of squamous cell carcinoma of the oral cavity, maxillary antrum and lip seen at Harare Central Hospital and Parirenyatwa Hospital in Zimbabwe during the period January 1982-December 1991 were reviewed. 20.8% (n = 358/1723) were squamous cell carcinoma of the oral cavity, maxillary antrum and lip. Age ranged from 3 to 70years with a 2:1 male:female ratio. Peak incidence in both sexes were in the 41-50 and 51-60years age groups. Sub-site distribution was mandibular gingiva 18.4%, tongue 17.9%, floor of the mouth 16.2%, maxillary gingiva 9.2%, buccal mucosa 9.2%, maxillary antrum 12.6%, hard palate 7.8%, soft palate 4.8%, lower lip 2.8% and upper lip 1.1%. 64.8% were well differentiated, 24.8% moderately differentiated and 10.4% poorly differentiated. The mandibular gingiva, floor of the mouth and tongue were most commonly affected. Lip squamous cell carcinoma was uncommon. Well-differentiated squamous cell carcinoma was most common in the 41-60 years age group.

A case-control study of past history of nasal diseases and maxillary sinus cancer in Hokkaido, Japan.

A case-control study of maxillary sinus cancer was performed in Hokkaido with 116 cases and 232 controls matched for sex, age (within 5 years), and residence (same health center region). Preliminary univariate analyses showed that a history of chronic sinusitis [relative risk (RR) = 3.1]; nasal polyps (RR = 5.7); an occupational history of being a carpenter, joiner, furniture maker, or other woodworker (RR = 2.9); and a history of current or past cigarette smoking (RR = 3.3) were statistically significant risk factors for men. No single item was a significant risk factor for women.

Nodal metastasis and elective nodal level treatment in sinonasal small-cell and sinonasal undifferentiated carcinoma: a surveillance, epidemiology and end results analysis.

OBJECTIVE: Risk of nodal involvement in patients with sinonasal small-cell carcinoma and sinonasal undifferentiated carcinoma (SNUC) has not been well defined because of their rarity. We describe a population-based assessment of specific nodal level involvement in this group of rare neuroectodermal tumours. METHODS: The Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2011 identified patients with SNUC and sinonasal small-cell carcinoma. Overall neck involvement and individual nodal level involvement at presentation were assessed, and comparison was made with a contemporaneous cohort of patients with a borderline clinically significant risk of nodal involvement and recurrence. RESULTS: Of 141 patients, 31 (22%) had gross nodal involvement at presentation (range 14-33% by site and histology). Non-nasal, non-ethmoid site with SNUC histology has the highest rates of initial nodal involvement, whereas higher stage and size do not predict for higher nodal involvement rates. Bilateral Levels 2-3 for all sinonasal small cell; Levels 2-3 for nasal or ethmoid SNUC; and bilateral Levels 1-3 in non-nasal/non-ethmoid SNUC have the highest rates of involvement compared with a clinical reference standard. CONCLUSION: We found high rates of initial nodal involvement in all SNUC and sinonasal small-cell carcinoma. We found higher initial involvement of Levels 2 and 3 and in certain cases to the Level 1 nodal levels, hypothesizing benefit for elective treatment to those levels. ADVANCES IN KNOWLEDGE: With small single-institution series reporting conflicting nodal involvement rates, our data support high rates of nodal presentation at diagnosis, hypothesizing benefit for elective nodal treatment in this cohort.

Squamous cell carcinoma of the maxillary sinus: A population-based analysis.

OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma (SCC) accounts for > 90% of head and neck cancers and 60% to 75% of malignancies of the paranasal sinuses. The most commonly affected paranasal sinus is the maxillary. Epidemiologic, incidence, and survival trends have been studied for maxillary sinus SCC (MSSCC), but far less is known about its metastatic potential. STUDY DESIGN: Retrospective database analysis. METHODS: The Surveillance, Epidemiology, and End Results database was used to extract frequency, incidence, and survival data for MSSCC between 2004 and 2012. The resultant cases were stratified according to patient demographics and collaborative stage information, including extent of disease, lymph node involvement, TNM staging, and regional and distant metastasis. RESULTS: A total of 854 cases of MSSCC were identified. The mean age at diagnosis was 66.6 years, with 87.4% presenting at > 50 years. Most patients (65.1%) were male. Whites accounted for 74.6% of cases. A majority (64.3%) of cases presented with stage IV disease. Overall 5-year disease-specific survival was 23.4%. Neck involvement was seen in 7.6% of T1 tumors, 22.2% of T2 tumors, 18.5% of T3 tumors, and 12.2% of T4 tumors. Distant metastasis was not seen in T1-T3 tumors, but was present in 6.8% of T4 tumors. CONCLUSIONS: MSSCC is a rare entity with poor overall prognosis. The majority of patients included in this study were white males aged ≥50 years, with most tumors presenting at advanced stages. Nodal involvement and distant metastasis are poor prognostic indicators. T1-T3 tumors did not metastasize to distant sites. LEVEL OF EVIDENCE: 4.

Factors in the pathogenesis of tumors of the sphenoid and maxillary sinuses: a comparative study.

OBJECTIVES/HYPOTHESIS: To explain the processes that lead to the development of tumors in the maxillary and sphenoid sinuses. STUDY DESIGN: A 32-year review of the world's literature on neoplasms of these two sinuses and a randomized case-controlled study comparing the normal mucosal architecture of the maxillary to the sphenoid sinus. METHODS: Analysis of a 32-year world literature review reporting series of cases of maxillary and sphenoid sinus tumors. Tumors were classified by histological type and separated into subgroups if an individual incidence rate was reported. Histomorphometry of normal maxillary and sphenoid sinus mucosa was performed in 14 randomly selected patients (10 sphenoid and 4 maxillary specimens). Specimens were fixed in 10% formalin, embedded in paraffin, and stained with periodic acid-Schiff (PAS) and hematoxylin. Histomorphometric analysis was performed with a Zeiss Axioscope light microscope (Carl Zeiss Inc., Thornwood, NY) mounted with a Hamamatsu (Hamamatsu Photonics, Tokyo, Japan) color-chilled 3 charge coupled device digital camera. The images were captured on a 17-inch Sony (Sony Corp., Tokyo, Japan) multiscan monitor and analyzed with a Samba 4000 Image Analysis Program (Samba Corp., Los Angeles, CA). Five random areas were selected from strips of epithelium removed from each sinus, and goblet and basal cell measurements were made at magnifications x 100 and x 400. RESULTS: The literature review revealed that the number and variety of tumors in the maxillary sinus are much greater than those in the sphenoid. The incidence of metastatic lesions to each sinus is approximately equal. No recognized pattern of spread from any particular organ system could be determined. On histomorphometric study there were no statistically significant differences between the sinuses in the concentration of goblet cells, basal cells, or seromucinous glands. CONCLUSIONS: Factors involved in the pathogenesis of tumors of the maxillary and sphenoid sinuses include differences in nasal physiology, embryology, morphology, and topography. There are no significant histological differences in the epithelium and submucous glands between the two sinuses to explain the dissimilar formation of neoplasms.

Tumours of the nose and maxillary sinus. Ten year survey from Kenya.

Between 1976-1985, 127 cases of malignant tumours of the nose and maxillary sinus were seen at the Department of Human Pathology, Kenyatta National Hospital, Nairobi, Kenya. Cancer of the nose and maxillary sinus was a common diagnosis accounting for 0.8 per cent of all malignancies. Despite this, the incidence was low probably because the rural Kenyans have difficulty in gaining access to the oncology facilities in Nairobi. Incidence rates standardized to world population per 100,000 persons-years were 0.16 for males and 0.12 for females. Clinical information showed that malignancy should be expected in patients with swelling of the cheek and involvement of the orbit. Compared with Denmark the proportion of undifferentiated carcinomas was significantly higher in Kenya. The well known fact that anaplastic carcinoma of the postnasal space is causally associated with the Epstein Barr virus makes it tempting to suggest that anaplastic carcinoma of the nose and maxillary sinus may also be of viral aetiology.

Predominance of squamous cell carcinoma and rarity of adenocarcinoma of maxillary sinus among Japanese.

The reasons for the prevailing predominance of maxillary sinus squamous cell carcinoma and the rarity of maxillary sinus adenocarcinoma among Japanese were investigated in a cooperative study at two institutions. There was little difference in the histological diagnostic criteria. It is hypothesized that the predominance of squamous cell carcinoma and the rarity of adenocarcinoma of the maxillary sinus can be related to the extensive use of softwood in the Japanese furniture industry, to the high prevalence of chronic sinusitis among Japanese in the past or to the popularity of cigarette smoking among Japanese.

[Experience in staging malignant tumors of the orofacial area]. / Esperienze di stadiazione dei tumori maligni del distretto oro-facciale.

The paper reports the authors experience at the Regina Elena Institute for the Study and Treatment of Tumours in Rome during the period 1987-1989 concerning the setting up of a register for primary malignant tumours of the head and neck. This experience has allowed various parameters to be assessed from the initial diagnosis through the subsequent diagnostic and therapeutic procedures [correction of iter]. The stage of disease was assessed in 134 patients using a TNM system proposed by UICC for tumours located in the oral cavity, oro- and hypo-pharynx and maxillary sinuses. At the end of the period a complete definition was made of some typical aspects of the disease in question: firstly, the high incidence of patients with advanced stages of disease found at the first diagnosis, and secondly, the significant delay in confirming the diagnosis of the tumour in spite of the ease with which the area may be explored. In conclusion, the authors comment on current systems of TNM classification, underlining the need for a more correct interpretation and assessment of findings related to neoplastic orofacial pathologies.

Extranodal non-Hodgkin's lymphoma of the maxillofacial region: analysis of 88 consecutive cases.

Examination of the records of 88 consecutive patients with extranodal maxillofacial non-Hodgkin's lymphoma (ENHL) was undertaken. Each patient's complete record was reviewed. Males outnumbered females by 1.7:1. Age at diagnosis ranged from 22 to 94 years (median 60.0). Affected anatomic sites included: maxillary sinus (22), nasal cavity (8), maxilla (13), mandible (8), salivary glands (14), and other (23). The most common presenting symptom was a non-painful mass. Associated dental symptoms were present in 72 patients and included intraoral swelling, pain, and loose teeth. Treatment included chemotherapy and radiation with a follow-up of 1-25 years. Treatment trends indicate a shift towards multimodal therapy. Non-Hodgkin's lymphoma of the head and neck, if discovered early, has an excellent prognosis.

Squamous cell carcinoma at maxillary sinus: clinicopathologic data in a single Brazilian institution with review of literature.

Squamous cell carcinoma arising at maxillary sinus is a rare neoplasm, characterized by aggressive growth pattern and glooming prognosis. There are no studies describing specifically its epidemiology in the South America. The aim of the current paper is to characterize a Brazilian maxillary sinus squamous cell carcinoma sample and to compare such data with others worldwide relevant series. The records of the Brazilian National Cancer Institute (1997-2006) were gathered and plotted. Additionally, an extensive literature review was carry out using electronic database (PUBMED/MEDLINE and LILACS) over a period of 54 years. A descriptive statistics and univariate survival test (log rank) were employed. Maxillary sinus squamous cell carcinoma was the commonest malignancy of sinonasal epithelium found. It affected mainly mid-age white men and most of them were diagnosed at advanced stage. Surgery combined with radiotherapy was the most therapeutic modalities given. The overall mortality rate in our sample was of 65.5%. Overall 1-, 2- and 5-year survival rate was 57.9%, 44.8%, and 17.7%, respectively. Maxillary sinus squamous cell carcinoma is an aggressive tumor normally diagnosed at the advanced stage and most patients present an unfavorable prognosis and reduced survival rate.

Sinonasal carcinomas: recent advances in molecular and phenotypic characterization and their clinical implications.

Sinonasal carcinomas are rare tumors with an aggressive clinical behaviour which frequently pose a number of problems regarding the interpretation of diagnostic findings and the treatment. In addition, in comparison with other malignancies of the head and neck region, an elevated fraction of sinonasal carcinomas can be attributed to occupational exposure. This review is focused on the recent advances in the molecular and phenotypic characterization of sinonasal carcinomas, and their possible implications for the interpretation of epidemiological data, as well as for the diagnosis and treatment of these rare malignancies. The increasing knowledge on their phenotypic and genotypic features is progressively leading to a refinement in diagnosis, especially for poorly differentiated and undifferentiated lesions, as well as to the identification of markers which can be potentially useful to identify the early phases of carcinogenesis, to detect subclinical disease, to predict the response to therapy, and finally, that may represent potential targets for alternative treatments.