Challenges in diagnosis: A review of development of NUT Carcinoma within the abdomen and pelvis

Background:

NUT Carcinoma is a subtype of squamous cell carcinoma characterized by a translocation of the nuclear protein in testes (NUTM1) gene to form a fusion with an epigenetic reader, most commonly bromodomain-containing protein 4 (BRD4::NUTM1), bromodomain-containing protein 3 (BRD3::NUTM1), or nuclear receptor binding SET domain protein 3 (NSD3::NUTM1). It is a rare and aggressive tumor with a median survival time of 6-9 months and most commonly affects midline structures of the head and neck, though in recent years reports of primary NUT carcinoma within the abdomen and pelvis have been reported. The purpose of this review is to compare similarities in patient presentations and identify difficulties in diagnosis of NUT carcinoma within the abdomen and pelvis.

Methods:

A systematic search of PubMed, Embase, and Cochrane Central was performed to identify case reports of primary NUT carcinoma within the abdomen and pelvis. After full-text screening, 10 cases were identified and included in this review.

Results:

Most patients presented with vague symptoms related to the organ in which the tumor was growing and all patients had identifiable masses on imaging. Common histological findings included poor cell differentiation, eosinophilic cytoplasm, prominent nucleoli, round-to-oval shaped cells, and keratinization. Six cases reported an initial diagnosis of a poorly differentiated or undifferentiated carcinoma. Two cases reported an initial diagnosis of a small round cell tumor, and one was reported as a moderately differentiated cholangiocarcinoma with squamous differentiation. Two patients did not receive a correct diagnosis until an autopsy was performed. Reported fusion proteins included BRD3::NUTM1, BRD4::NUTM1, and MXI1::NUTM1.

Conclusion:

Definitive diagnosis of NUT carcinoma requires either immunohistochemical staining for NUT protein or molecular analysis for NUT rearrangement by fluorescence in-situ hybridization or next-generation sequencing. Because NUT carcinoma can mimic classic symptoms of typical malignancies of the gastrointestinal and genitourinary tracts and many laboratories are not equipped to assess for NUT carcinoma, diagnosis can be delayed creating a costly time loss for patients. NUT carcinoma within the abdomen and pelvis is an uncommon but likely underdiagnosed malignancy and the presentation of a poorly differentiated carcinoma should prompt testing for the presence of NUT rearrangement.