Detection of NUT Midline Carcinoma in Retrospective Analysis of Thymic and Mediastinal Neoplasms.
Andrew Evans, Christopher Fletcher, Christopher French, David Jackman, Christopher Lathan, Lynette Sholl. Brigham and Women's Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA
Background: NUT midline carcinomas (NMC) comprise a group of highly aggressive tumors that arise primarily in the head, neck and mediastinum, predominantly in younger individuals. Their defining characteristic is overexpression of the nuclear protein in testis (NUT) due to a chromosomal translocation. Although the earliest cases were described as thymic in origin, an extensive survey for NMC in a series of thymic and unclassified mediastinal carcinomas has not been reported.
Design: We queried our pathology database, including consult files, from 2001-2010 using search terms “thymic”, “mediastinal”, and “carcinoma”; thymomas or tumors for which another primary site was identified were excluded. Diagnosis of NMC was based on strong, diffuse nuclear staining with a clinically validated NUT-specific monoclonal antibody.
Results: Among 119 cases of thymic and unclassified mediastinal carcinomas identified, 38 cases had material currently available for testing. These consisted of 11 unclassified or undifferentiated malignant epithelioid neoplasms, 7 thymic carcinomas, 7 poorly-differentiated carcinomas, 4 squamous cell carcinomas, 4 favor non-small cell carcinomas, 2 poorly-differentiated neuroendocrine carcinomas, 1 favor small cell carcinoma, 1 sarcomatoid carcinoma, and 1 favor malignant germ cell tumor. Patients screened were on average 48.9 years old (ranging from 8 to 89 years) and included 18 females and 20 males. One NMC was identified in a 61 year old female with a mediastinal mass, previously diagnosed as unclassifiable epithelioid malignant neoplasm. This tumor exhibited a nested arrangement of uniform, moderately-sized, epithelioid cells that contained abundant granular eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. The tumor was negative for keratins, p63, neuroendocrine markers, and EMA.
Conclusions: NUT translocations were detected in 2-3% of patients with mediastinal neoplasms in this series. The findings highlight the fact that NMC can arise in patients of advanced age. Although rare, this entity should be considered in the differential diagnosis of any poorly-differentiated mediastinal tumor.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 256, Wednesday Morning