Case Presentation:
A 27-year-old male presented with one year history of nonproductive cough and a 4 week history of expiratory wheezing, dyspnea on exertion, facial swelling and episodic hemoptysis.
Past medical history was significant for fatigue, insomnia and headaches. Social history was significant for minimal tobacco use, occasional alcohol consumption, prior use of marijuana and anabolic steroids.
He was diagnosed with bronchitis at an urgent care clinic and was prescribed a course of doxycycline. Because his symptoms progressed, a chest x-ray was done that raised suspicion for a mediastinal mass. CT Thorax then revealed an 8-cm left hilar mass, narrowing of the superior vena cava (SVC), and a 3-cm adrenal mass. Laboratory assessment was unremarkable. Given the patient’s age and clinical presentation, lymphoma versus germ cell tumor was suspected. He was admitted for management of SVC symptoms and diagnostic assessment of the hilar mass.
While hospitalized, the patient experienced acute pain involving the left temporal/retro-orbital area. MRI of brain revealed bony metastatic disease involving the left greater wing of the sphenoid and lateral wall of the left orbit. Periorbital craniotomy with biopsy revealed an initial diagnosis of metastatic squamous cell carcinoma. A subsequent bronchoscopy revealed a left mainstem endobronchial tumor obstructing both the upper and lower bronchi. These biopsies showed poorly-differentiated malignant neoplasm infiltrating below the epithelium. The cytology featured pankeratin, p40, CK5/6, p63 and uniform positivity of nuclear protein in testis (NUT) immunoperoxidase. Because of the morphology and immune staining results, the patient was diagnosed with NUT midline carcinoma. He was then treated with concurrent chemoradiation therapy using carboplatin/paclitaxel with radiation to the mediastinum due to his rapidly progressive disease.
Discussion:
NUT midline carcinoma (NMC) is an aggressive, highly lethal subtype of squamous cell carcinoma, which is often unrecognized due to its rarity and lack of distinctive histological features. Average age of presentation ranges from newborn to 78 years. Median survival is only 6.7 months. NMC is defined by chromosomal rearrangement of the gene encoding the NUT on chromosome 15 fused with bromodomain-containing protein 4 (BRD4) on chromosome 18. NMCs uniformly present in the midline involving the head, neck or mediastinum most commonly. Diagnosis is confirmed by detection of NUT rearrangement by FISH or reverse transcriptase PCR. Unfortunately, there is no established treatment, but there are two available phase 1 clinical trials utilizing BRD inhibitors.
Conclusions:
This case serves to raise awareness amongst hospitalists of the potential of NUT midline carcinoma in patients presenting with midline masses. Prompt diagnosis is imperative to ensure patients will be appropriately screened for targeted BRD inhibitor clinic trials.