| Domain | Best-supported finding | Quantitative data | Evidence type/source year |
|---|---|---|---|
| Definition/classification | Genuine SNUC is now treated as a diagnosis of exclusion among poorly differentiated sinonasal carcinomas and should be separated from SWI/SNF-deficient and NUT carcinomas. | No single numeric metric; classification shift emphasized in modern reviews and pathology overviews. | Review/pathology synthesis, 2022-2023 (pqac-00000008, pqac-00000011) |
| Epidemiology | SNUC is extremely rare and represents a small fraction of sinonasal malignancies. | ~5% of sinonasal malignancies; annual incidence ~0.02/100,000/year; male incidence 0.03/100,000/year vs female 0.01/100,000/year; median age 50-60 years. | Review summarizing SEER and prior series, 2023 (pqac-00000003, pqac-00000006) |
| Presentation at diagnosis | Symptoms are nonspecific and advanced local disease is common. | Nasal obstruction 20.0%; epistaxis 17.1%; diplopia/visual symptoms 15.0%; headache 12.1%; orbital involvement 42.9%; stage IV at diagnosis 72.9%. | Review citing systematic/retrospective SNUC studies, 2023 (pqac-00000003, pqac-00000006) |
| Metastatic behavior | SNUC has substantial regional and distant metastatic risk. | Regional metastasis 5-16%; distant metastasis 20-30%; common sites include bone, cervical lymph nodes, lung, brain, liver. | Review of primary SNUC literature, 2023 (pqac-00000003, pqac-00000006) |
| Pathology/IHC | Typical phenotype supports epithelial differentiation but not specific lineage. | Commonly positive/variable: AE1/AE3, CAM5.2, CK8, CK7/8/19; typically negative: S-100, CK5/6, p40, CD45, desmin, myogenin, MelanA, HMB45. | Review plus multi-institutional pathology study, 2018-2023 (pqac-00000000, pqac-00000008, pqac-00000010) |
| Molecular genetics: IDH | IDH2 hotspot mutation is the strongest recurrent molecular feature of genuine SNUC. | IDH2-mutant frequency reported as 62.5% (10/16), 54.5% (6/11), and 82.4% (14/17) across cited SNUC series; multi-institutional cohort found mutant IDH1/2 IHC positive in 26/53 SNUC (49%), with NGS showing frequent IDH2 R172X and rare IDH1 R132C. | Primary molecular pathology 2018 plus review 2023 (pqac-00000008, pqac-00000010) |
| Molecular co-alterations in IDH2-mutant SNUC | Additional recurrent alterations occur but appear secondary to the IDH-defined subtype. | In one cited SNUC study: TP53 41.7% (5/12), CDKN2A/2B loss 33.3% (4/12), MYC amplification 33.3% (4/12), SETD2 mutation 25% (3/12). Another cohort reported TP53 55%, KIT-activating mutations 45%, PI3K-pathway mutations 36% among IDH-mutant carcinomas. | Primary molecular study 2018 and review 2023 (pqac-00000008, pqac-00000010) |
| Differential diagnosis | SWI/SNF-deficient sinonasal carcinomas are distinct from genuine SNUC and generally lack the characteristic IDH2 mutation. | SMARCB1 deficiency reported in 9/142 cases (6%) in one review summary; <150 SMARCB1-deficient sinonasal carcinoma cases reported overall in pathology overview; all studied SWI/SNF-deficient cases lacked oncogenic IDH2 mutations. | Pathology overview/review, 2022-2023 (pqac-00000008, pqac-00000011) |
| Imaging/staging | Imaging usually shows a large invasive noncalcified mass; staging may use AJCC or modified Kadish. | MRI pattern described qualitatively; no robust SNUC-specific pooled sensitivity/specificity identified here. | Review, 2023 (pqac-00000000, pqac-00000008) |
| Multimodality local control | Combined-modality therapy is favored; trimodality improves locoregional control over less intensive approaches. | Locoregional control: trimodality 63.9% vs bimodality 49.2% vs surgery alone 31.3%. | Meta-analytic summary in review, 2023 (pqac-00000008) |
| Radiotherapy note | IMRT at adequate dose is preferred; some benefit statements derive from broader sinonasal-cancer data rather than SNUC-only cohorts. | RT dose threshold commonly cited as >=60 Gy; where survival/toxicity comparisons are mentioned, they are not always SNUC-exclusive. | Mixed evidence; review, 2021-2023; explicitly not always SNUC-specific (pqac-00000000, pqac-00000008) |
| Induction chemotherapy-guided management | Response to induction chemotherapy is a major prognostic and treatment-selection factor in SNUC. | Amit cohort: 95 treatment-naive patients; regimen cisplatin 60-80 mg/m2 day 1 plus etoposide 100-120 mg/m2 or docetaxel 75 mg/m2 days 1-3 every 21 days for 1-5 cycles (median 3). Review summary reports 5-year survival 66% with IC+CRT and 43% with IC+surgery+RT; progression-free survival 74% vs 55%, respectively. | Primary cohort summarized in 2023 review; outcome table in 2022 critical review (pqac-00000008, pqac-00000004) |
| Survival | Prognosis remains poor overall despite aggressive therapy. | Median survival ~22 months reported in pathology study background; historical review table reports 5-year OS ranging from 19% (XRT only) to 66% in modern IC-guided multimodality cohorts. | Primary pathology background 2018 and review-of-studies 2022 (pqac-00000010, pqac-00000004) |
| Current trial: pembrolizumab | Ongoing phase II study tests adding pembrolizumab to neoadjuvant chemotherapy in locally advanced SNUC. | NCT05925491; recruiting; phase II; planned n=28; pembrolizumab 200 mg + cisplatin 75 mg/m2 (or carboplatin AUC5) + docetaxel 75 mg/m2 every 3 weeks for 3 cycles; primary endpoint ORR. | Interventional trial registry, first posted 2023; active update 2026 (pqac-00000005) |
| Current trial: enasidenib | Ongoing phase II study targets IDH2-mutant recurrent/metastatic or unresectable sinonasal/skull-base tumors including SNUC. | NCT06176989; recruiting; phase II; planned n=40; enasidenib 100 mg orally daily; includes documented somatic IDH2 R140/R172 mutations; SNUC-specific secondary endpoints include CBR, PFS, OS. | Interventional trial registry, first posted 2023; active update 2026 (pqac-00000009) |
| All-sinonasal context (explicitly not SNUC-specific) | Overall sinonasal malignancies are rare as a group; this should not be mistaken for SNUC incidence. | Sinonasal malignancies overall: 0.5-1.0/100,000 incidence. | All-sinonasal review statistic, not SNUC-specific, 2023 (pqac-00000000) |


*Table: This table compiles the most supported, SNUC-specific findings available from the gathered sources, emphasizing quantitative epidemiology, presentation, molecular features, treatment outcomes, and active trials. It also explicitly flags when a statistic applies to all sinonasal malignancies rather than genuine SNUC.*