is a rare epithelial cancer that usually arises in the midline of the body and is characterized by a mutation in the nuclear protein in testis (NUT) gene. There are only 62 known cases with the tumor being refractory to conventional treatments, with a median survival of 6.7 months and an overall survival of 19% at 2 years.
- shortness of breath
- weight loss
Common sites include head, neck, and mediastinum. The median age at diagnosis is 17 years.
Prognosis is very poor with mean survival being approximately 9 months.
NMC is often widely metastatic and unresectable when diagnosed. All known cases of NMC have had a poor clinical course with a mean survival of approximately nine months. The histological diagnosis is usually that of poorly differentiated or squamous cell carvinoma, but occasionally has been classified as other tumors.
However, growing understanding about the function of the key molecular alteration does show promising approaches to overcome the differentiation arrest. The normal function of NUT is hypothesized to aid chromatin compaction during spermatogenesis and interfering with the balance of histone acetylation/decetylation. One means to bring the chromatin into a more relaxed state, which is associated with increased gene transcription and differentiation, is to block the endogenous action of histone deacytelases.
Recent research that utilizes therapeutic histone deacetylase inhibitors (HDACi) to derepress differentiation of the NMC cells appears promising. Cell lines of NUT carcinoma cells and murine models have responded to various HDACi. Vorinostat, a HDACi, was used in the case of a 10 year old boy with NUT midline carcinoma. He was treated for five weeks and had an objective clinical response before toxicities limited its continued use. After stopping the drug, the disease recurred and he died 11 months after diagnosis. Despite the inability to achieve cure in this case, HDACi use remains a focus of ongoing clinical research in treating this disease.
A rare case of NUT midline carcinoma
Allison Ball et al. (2013) Gynecologic Oncology Case Reports, vol. 3:1-3.