The unusual journey of a young man with pulmonary NUT Carcinoma

29-year-old male, no significant past medical history, presented acutely with palpitations and shortness of breath on exertion. Over a few weeks experienced fevers, right sided chest pain with productive cough. Smokes 15 cigarettes a day and cannabis. Normal electrocardiogram, examination but C- Reactive Protein 56 and White Blood Cells 9.5.

Initial chest x-ray demonstrated a bulky right hilum (Figure 1). CT showed 42mm right hilar mass with pretracheal, right paratracheal and anterior to the superior vena cava (SVC) lymphadenopathy (Figure 2). Small right pleural effusion. No abdominal pathology. Within 17 days the right hilar mass demonstrates progression and there is growth of the lymphadenopathy now causing increasing compression of the SVC (Figure 3). There are also new lymphangitic changes within the right upper and middle lobes. 12 days later the positron emission tomography imaging demonstrates the confluent right lung and hilar mass to be metabolically active ( Standard Uptake Value Max 8.6 ) (Figure 4) and no further metastatic disease  11 days later CT Thorax shows a 6mm left upper lobe nodule (Figure 5). 1 month later CT Thorax, Abdomen and Pelvis shows widespread bony lytic lesions and on MRI Head/Spine there are skull base lesions and evidence of nerve root compression (Figure 6) but no parenchymal brain metastases.

Background

Pulmonary NUT carcinoma is rare and very aggressive squamous cell carcinoma defined by a rearrangement involving the NUTM1 (nuclear protein in testis, family member 1) gene on chromosome 15, typically affecting the head and neck and the mediastinum [1]. Diagnosis can be suspected on morphological appearances and confirmed by immunohistochemistry against NUT or detection of rearrangement of specific NUT variants [5].

Clinical perspective

Typically healthy younger adults, mean age 25 at presentation, with no particular smoking history [4]. Our patient had a clinical history consistent with infection, but the imaging findings were in keeping with aggressive malignancy. The patient was a smoker; this could have been a likely cause for shortness of breath. 

Imaging perspective

Characteristic features include a large unilateral lung mass over 5cm with confluent hilar and mediastinal lymphadenopathy. The contralateral lung is usually clear. Bones were a common site for metastatic disease and a negative bone scan may not exclude metastases. Patients don’t typically develop brain metastases although they have been reported. All sites of the tumour are fluorodeoxyglucose avid and occasionally demonstrated necrosis and central photopenia [1]. Imaging is important in order to assess the extent of disease, progression of disease, response to treatment, complications e.g SVC obstruction or nerve root compression and to guide biopsy.

Outcome

The pathology is typically sent to a specialist centre for histological diagnosis which can delay results and the final prognosis for the patient. Unfortunately, the treatment is very limited as patients present with advanced disease and they are limited to chemotherapy and radiotherapy with a restricted role for surgery. Immunotherapy and new drugs are undergoing trials [2]. The prognosis is poor, presenting late in younger healthy adults with a median overall survival of 6.7 months and estimated 9% two-year progression-free survival [3].

Take-home message

This is a very rare and aggressive disease in younger adults who typically do not smoke. The patient needs to have prompt imaging and biopsy to help guide management and to help counsel the patient and their family. There is a pattern of imaging features, which although not specific, the differential of a pulmonary NUT carcinoma should be raised by the Radiologist early. If a biopsy is inconclusive for the suspected diagnosis then ensure a repeat biopsy is undertaken rapidly to facilitate a diagnosis for the patient; sadly, our patient died 84 days after the first biopsy.