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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Sinonasal undifferentiated carcinoma is a rare, fast-growing cancer of the nasal cavity and sinuses made of primitive cells with no clear line of differentiation, most carrying an IDH2 mutation. It presents as a large mass pressing on the eye or brain and is treated with chemotherapy first, then surgery or chemoradiotherapy depending on response; SMARCB1- or SMARCA4-deficient tumours are separate.
Sinonasal undifferentiated carcinoma was defined in 1986 as a high-grade carcinoma of the sinonasal tract without squamous or glandular differentiation, negative for EBV and for the neuroendocrine and NUT markers that define its mimics. Genomic studies from 2017 found IDH2 R172 mutations in most cases, giving the tumour a molecular identity and a possible drug target; the 2022 WHO classification also carved out SMARCB1 (INI1)-deficient and SMARCA4-deficient sinonasal carcinomas, which look similar but are driven by loss of SWI/SNF chromatin remodelling proteins, and NUT carcinoma, which has its own page. All present late with a bulky mass causing nasal obstruction, proptosis, diplopia or headache, invading the orbit, skull base and dura, and about a fifth have neck node metastases at diagnosis.
Historically, surgery followed by radiotherapy cured few patients because of the extent of disease, and the MD Anderson group changed the paradigm by giving chemotherapy first. In their series of 95 patients (Journal of Clinical Oncology 2019), those whose tumour responded to induction platinum-etoposide did better with definitive chemoradiotherapy than with surgery, while those who did not respond did better with surgery followed by radiotherapy or chemoradiotherapy, so the response to induction now decides the local treatment. Intensity-modulated or proton radiotherapy is used to spare the optic pathways and brain, and elective neck treatment is standard because nodal relapse is common. Metastatic disease is treated with platinum-etoposide as for neuroendocrine carcinoma, and PD-1 antibodies have produced responses in case series of SMARCB1-deficient and other sinonasal carcinomas. The IDH2 inhibitor enasidenib, approved for IDH2-mutant leukaemia, is being tested in IDH2-mutant sinonasal carcinoma, and EZH2 inhibitors, active in other SMARCB1-deficient tumours, are being explored for the SWI/SNF-deficient group. Five-year survival remains low overall, and referral to a skull base centre with molecular pathology is recommended for every patient.
| Setting | Approach | Guideline |
|---|---|---|
| Diagnosis | Biopsy with immunohistochemistry (cytokeratins, NUT, INI1, SMARCA4, neuroendocrine markers, EBER) and IDH2 testing; MRI and CT of the sinuses, skull base and neck; PET-CT. | not mapped |
| Locally advanced disease, first step | Induction chemotherapy with cisplatin and etoposide (or docetaxel-platinum) for two to three cycles. | not mapped |
| Responders to induction | Definitive chemoradiotherapy with concurrent cisplatin (intensity-modulated or proton), including elective neck irradiation. | not mapped |
| Non-responders to induction | Surgical resection where feasible followed by radiotherapy or chemoradiotherapy. | not mapped |
| Metastatic or recurrent disease | Platinum-etoposide; PD-1 antibodies (pembrolizumab, nivolumab) on case series evidence; enasidenib for IDH2-mutant tumours in trials; EZH2 inhibitors for SWI/SNF-deficient carcinoma in trials. | not mapped |