Nuclear protein in testis midline carcinoma with unusual elevation of α-fetoprotein and synaptophysin positivity: a case report and review of the literature

Abstract

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare cancer that displays a characteristic chromosomal rearrangement of BRD4-NUT t(15;19)(q14;q13.1). Despite occasional dramatic responses to radiation and chemotherapy, NMC usually behaves aggressively and becomes rapidly progressive. Immunohistochemical staining is usually limited to p63, cytokeratins, and monoclonal NUT antibody. Here, we report a NMC case in a 36-year-old man with elevated serum α-fetoprotein (AFP), synaptophysin positivity, and a 9.0 cm mass involving the right lung and mediastinum. Tumor cells demonstrated BRD4-NUT fusion on fluorescence in situ hybridization. To our knowledge, only one other case with elevated serum AFP and one case with synaptophysin positivity have been described. This diagnosis will undoubtedly grow more common as informed physicians become more aware of the disease and begin testing for NMC. Further study is needed to establish the prevalence of NMC and to elucidate the significance of elevated AFP and synaptophysin positivity in this rare tumor.

Keywords:

• α-fetoprotein
• BRD4-NUT
• NUT midline carcinoma
• synaptophysin

Acknowledgement

The authors wish to thank the division of Hematology/Oncology at Loma Linda University, Loma Linda, CA, USA who supported the writing of the manuscript. We would also like to acknowledge Sandra Valle for her administrative support.

Financial & competing interests disclosure

H Mirshahidi has served as a consultant for Boehringer/Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Nuclear protein in testis (NUT) midline carcinoma (NMC) is a poorly differentiated carcinoma that carries poor prognosis.

• NMC is rare; however, it is underdiagnosed as many physicians are not aware of this disease.

• NMC displays a characteristic chromosomal rearrangement of BRD4-NUT t(15;19)(q14;q13.1), rarely BRD3-NUT and NSD3-NUT.

• Immunohistochemical staining is usually limited to p63, cytokeratins, EMA, variable CD34 and CD99, and monoclonal antibody to NUT. Surgeries with negative margins were significant predictors of improved progression-free survival and overall survival, while initial radiation or chemotherapy, type of chemotherapy regimen, and NUT translocation type were not significantly associated with improved outcome.

• Certain groups have started to develop targeted therapy for NMC with inhibitors of Bromodomain and Extra-Terminal and histone deacetylase, and several Phase I/II clinical trials are currently in effect.

Notes