SAT-125 A Tough NUT (Midline Carcinoma) to Crack

Introduction NUT midline carcinoma (NMC) is a rare, highly aggressive cancer with poor prognosis. To date, there is no established therapeutic strategy; further studies are necessary to compare treatment modalities as well as investigate novel immunotherapeutic agents. Case presentation A 39-year-old female presented with a rapidly enlarging right neck mass and a recent 40-lb weight loss and was found to have a 5 cm poorly defined infiltrative hypoattenuating mass on CT scan concerning initially for anaplastic thyroid malignancy. Endocrinology and ENT were consulted and the patient underwent thyroid biopsy, which was positive for NMC. PET scan demonstrated hypermetabolic lymphadenopathy in the bilateral neck and mediastinum, but no distant metastases were identified. She then underwent total thyroidectomy with extensive dissection of the bilateral neck; pathology revealed one positive lymph node. On endobronchial biopsy, the mediastinal lymph nodes were benign. Immunohistochemistry revealed PD-L1 expression and gene assay showed an NSD3-NUTM1 fusion of the NUT gene. Oncology advised systemic treatment with carboplatin/taxol and considered Pembrolizimab, an anti-PD-L1 immunotherapy agent. Discussion The prognosis of NMC is less than 1 year and only 20-30 cases are reported per year in the USA. NMC is a poorly differentiated subtype of squamous carcinoma characterized by a chromosomal rearrangement of the NUT gene, involving molecular translocation with the BRD4 gene in 70% of cases. It remains challenging to treat NMC, as metastasis is present on diagnosis in most cases and there is currently no established approach. In a report of 40 patients from the NUT Midline Carcinoma Registry, surgical resection correlated with significantly improved survival in contrast to initial radiation or chemotherapy. Recently, BET domain inhibitors have emerged as a promising class of targeted agents for tumors with BRD4-NUT fusions. Their efficacy is unknown for other NUTM1 fusions. Both BET domain and histone deacetylase inhibitors are in clinical trials, and next-generation BET and CDK9 inhibitors have shown preclinical activity. Our patient likely benefited from early intervention with surgical therapy. Her PET scan findings suggest that re-sampling her mediastinal tissue would be prudent. Given her lack of BDR4-NUTM1 fusion, it is unknown if she would benefit from BET inhibitor. Conclusion NMC is an underrepresented cancer that warrants further investigation into treatment modalities and novel immunotherapies. References Bauer, DE et al (2012). Clinicopathologic features and long-term outcomes of NUT midline carcinoma. Clinical cancer research,18(20),5773–5779. Liu S, et al (2018). NUT carcinoma: a rare and devastating neoplasm. Case Reports. Napolitano, M et al (2019). NUT midline carcinoma of the head and neck: current perspectives. OncoTargets and therapy,12,3235–3244.