TLE1 Expression in NUT Carcinoma: A Case Report Highlighting a Potential Diagnostic Pitfall for the Pathologist

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• NUT carcinoma is a rare, aggressive cancer characterized by chromosomal rearrangements involving the nuclear protein in testis (NUTM1) gene.
• Diagnosis can be challenging due to variable morphology and immunohistochemical profiles, sometimes mimicking other small round blue cell tumors.

Observation:

• A mediastinal tumor in a middle-aged male presented with features overlapping Ewing sarcoma and synovial sarcoma, including CD99 and TLE1 positivity.
• Squamous differentiation markers (p40) were negative, and keratinization was absent.
• Next-generation sequencing identified a BRD4::NUTM1 gene fusion.

Findings:

• The identified gene fusion confirmed the diagnosis of NUT carcinoma despite the atypical presentation.
• This is the first reported case of NUT carcinoma exhibiting TLE1 immunoreactivity.

Implications:

• This case underscores the diagnostic challenges posed by NUT carcinoma, especially when classic features are absent.
• Emphasizes the critical role of molecular diagnostics, such as next-generation sequencing, in confirming NUT carcinoma in ambiguous cases.
• Highlights TLE1 as a potential marker to consider in the differential diagnosis, although not definitive for NUT carcinoma.