Sinonasal undifferentiated carcinoma (SNUC) is an exceedingly rare head and neck malignancy. No consensus exists on treatment for metastatic disease.
A 56-year-old female was diagnosed with SNUC after endorsing sinus congestion, diplopia, and right orbital pain. Initially treated with surgery and radiation, she later developed significant metastatic disease. She demonstrated progression of her hepatic metastases under pembrolizumab therapy. However, the addition of ipilimumab and a COX-2 inhibitor resulted in significant improvement in her lesions as well as an ongoing durable response. Her regimen was complicated by immune-related adverse events successfully treated with steroids.
Dual checkpoint inhibition deserves consideration when treating metastatic SNUC, especially after single agent therapy has failed. The positive effect of this treatment may be augmented by IDO1 inhibition.

Sinonasal undifferentiated carcinoma (SNUC) is a rare tumor highly aggressive most frequently arise in the maxillary sinus and nasal cavity. Oral involvement is extremely rare.
A 62-years-old male presents a large infiltrative mass involving the hard palate and left alveolar ridge. Computed tomography showed bone destruction and invasion of paranasal sinuses and orbits. Histology revealed a malignant neoplasm consisting of small round cells with minimal cytoplasm and hyperchromatic nuclei without any connection with the oral mucosal epithelium. Immunohistochemical analysis showed epithelial origin (CK-7+, CK-20+, AE1/AE3+, EMA+) and lacked strong evidence of squamous and neuroendocrine differentiation (p63-, 34βE12-, NSE-/+, chromogranin-, synaptophysin-). TTF-1 negative ruled out the metastatic origin. A diagnosis of SNUC subtype positive for SMARCB1 (INI1) was reached. The patient was submitted to concurrent radiotherapy and chemotherapy without signs of recurrence after 2 years.
SNUC involving the oral cavity is a rare malignancy that may mimic symptoms of dental infection or sinusitis. A careful correlation of clinical, microscopic, and immunohistochemical characteristics is mandatory for early diagnosis.

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.
A multicenter collaborative study was conducted to assess treatment strategy, oncological outcome, and prognostic factors.
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.
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.