NUT midline carcinoma of the larynx: an international series and review of the literature

Abstract

Aims NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive carcinoma that characteristically locates to the midline of the head and neck, and mediastinum. NMC is characterised by chromosomal rearrangements of the gene encoding nuclear protein in testis, NUT, at 15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly rare and we report a case series of seven cases. Material and Methods We searched for cases in files of different hospitals as well as a thorough search of the English literature. The diagnosis of NMC is made by demonstration of NUT rearrangement either by immunohistochemistry, FISH or RT-PCR. We found three previously published cases and add in this series four cases of our own. Conclusions NMC consists of monomorphic, often discohesive, cells with an epithelioid appearance and distinct nucleoli. The tumours typically show abrupt squamous differentiation. The mean age of the patients was 34 years, hence significantly lower than that for conventional laryngeal carcinoma. All tumours were located in the supraglottis and five patients died of the disease after 3, 7, 8, 9 and 11 months. Laryngeal NMC may be underdiagnosed and an increased awareness amongst pathologists is warranted. NMC has characteristic morphological features and positive immunostaining with the NUT antibody is diagnostic. Its aggressive behaviour demands a very intense treatment strategy and the need for its recognition is further emphasised by new promising treatment strategies.

NUT carcinoma in children and adults: A multicenter retrospective study

“…Negative transcripts of other cancers are often necessary to eliminate differential diagnoses . The main differential diagnosis is Ewing's sarcoma/primary neuroectodermal tumor . NUT carcinoma can also be confused with rhabdomyosarcoma, biphasic forms of synovial sarcoma, undifferentiated carcinomas of the nasopharynx, carcinoma of the salivary glands, small cell desmoplastic tumors, or rhabdoid tumors.…”

Successful treatment of a case with NUT midline carcinoma in the larynx and review of the literature

“…Since the first two cases of NMC reported in 1991, the clinic‐pathologic features, treatment characteristics, and prognosis have been widely discussed. NMC is now regarded as a genetically defined neoplasm, considered to be a subtype of squamous cell carcinoma due to presence of histological evidence of abrupt squamous differentiation . Typically, NMC is characterized by chromosomal rearrangements of NUT, at 15q14 and the BRD4 (Bromodomain containing 4) gene, at 19q13, resulting in the t (15; 19) (q14; p13) karyotype .…”

“…However, the laryngeal NMC is still extremely rare with only seven cases reported till now, and we added one new case of our own. There were four males and four females and the mean age of diagnosis is 26.6 years (Table ), which is in accordance with the young age (avg.…”

“…NUT midline carcinoma that arises in the larynx is extremely rare, with only seven cases reported thus far. All the seven cases presented at an extensive clinical stage and showed a poor prognosis with the survival time ranged from 3 to 11 months …”

Pediatric NUT Carcinoma Is a Rare and Challenging Tumor: Single Center Experience of Five Children

“…First described in 1999, NUT carcinoma is probably underdiagnosed, with most literature being single case reports and small case series. However, larger case series, including those from the International NUT Midline Carcinoma Registry, have contributed to our understanding of the biology of this entity . Prognosis of NUT carcinoma is generally poor in spite of aggressive multimodality management, which incorporates surgery and adjuvant chemotherapy and/or radiation .…”