Clinicopathologic Features and Long-term Outcomes of NUT Midline Carcinoma

Abstract

Purpose NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations. Experimental Design A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of NMC patients studied to date. Outcome data from 54 patients were available for survival analyses. Results The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (p<0.05). Geographic distribution of NMC patients has been concentrated in the United States (n=41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% CI of 1%–17% (1-year PFS 15% (5%–24%)) and 2-year overall survival (OS) was 19% with a 95% CI of 7%–31% (1-year OS: 30% (27%–34%). Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome. Conclusions NMC portends a poor prognosis among all squamous cell neoplasms and appears to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.

Novel MXD4–NUTM1 fusion transcript identified in primary ovarian undifferentiated small round cell sarcoma

“…NUTM1 (NUT midline carcinoma family member 1, also known as C15orf55 or NUT ), which maps to chromosome15q14, is typically expressed in a normal testis but not expressed in many other normal and malignant tissues 35, 3637, 38. Approximately two‐thirds of NMC cases harbor a BRD4–NUTM1 fusion gene, which has been functionally validated as an oncogenic event 39, 40.…”

Small round blue cell tumors of the sinonasal tract: a differential diagnosis approach

“…Sinonasal tract involvement by NUT carcinoma is much less common than mediastinal disease, but most head and neck cases affect the nasal cavity and paranasal sinuses (65%), with a median presentation in the 20 s, showing a slight female predominance. [67][68][69][70][71][72][73] There is no known etiologic association. Patients present with a rapidlygrowing, extensively destructive mass, often with orbital involvement, and lymph node metastases in about 50% of patients.…”

“…Patients present with a rapidlygrowing, extensively destructive mass, often with orbital involvement, and lymph node metastases in about 50% of patients. 70,73,74 Histopathology. The tumors invade as sheets of monotonously undifferentiated cells, frequently showing bone invasion and tumor necrosis ( Figure 7).…”

“…Conventional treatments are ineffective, which yields a poor overall prognosis of about 10 months (median survival). 73 Molecular targeted therapies with pharmacogenomic agents may yield growth arrest and prolonged survival, but blood-brain barrier limitations are a consideration for sinonasal tract tumors. 71,78 Sinonasal Neuroendocrine Carcinoma…”

Overview of Carcinomas in Adolescents: A Descriptive Study Over Twenty Years

“…When the histological diagnosis of carcinoma (in case of poorly differentiated malignant tumors) was doubtful, available slides were reviewed and additional IHC was performed using an anti-Pan Cytokeratin (AE1/ AE3) antibody (Ab) to search for epithelial differentiation, anti-INI1 Ab to rule out a malignant rhabdoid tumor, and a monoclonal NUT Ab to detect NUT midline carcinomas (NMC) [7].…”