Tracking the Evolution of Non-Small-Cell Lung Cancer.

BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. METHODS: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. RESULTS: We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10-4), which remained significant in multivariate analysis. CONCLUSIONS: Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).

Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes.

A young female vaper presented with insidious onset cough, progressive dyspnoea on exertion, fever, night sweats and was in respiratory failure when admitted to hospital. Clinical examination was unremarkable. Haematological tests revealed only thrombocytopenia, which was long standing, and her biochemical and inflammatory markers were normal. Chest radiograph and high-resolution CT showed diffuse ground-glass infiltrates with reticulation. She was initially treated with empirical steroids and there was improvement in her oxygenation, which facilitated further tests. Since the bronchoscopy and high-volume lavage was unyielding, a video-assisted thoracoscopicsurgical biopsy was done later and was suggestive of lipoid pneumonia. The only source of lipid was the vegetable glycerine found in e-cigarette (EC). Despite our advice to quit vaping, she continued to use EC with different flavours and there is not much improvement in her clinical and spirometric parameters.

Mycobacterial spindle cell pseudotumour of the brain in a patient with sarcoidosis.

Mycobacterial spindle cell pseudotumours (MSP) are benign lesions characterised by local proliferation of spindle-shaped histiocytes caused by mycobacterial infections. Cerebral MSP due to Mycobacterium avium intracellulare (MAI) infection is rare, and is often misdiagnosed clinically and radiologically as a brain tumour. We present a case with underlying sarcoidosis and known pulmonary MAI infection presenting with partial seizures and headaches. Imaging of the brain revealed a solitary extra axial tumour within the right temporal area. Biopsy of the tumour showed evidence of MPS due to MAI infection. Prolonged treatment with antituberculous therapy showed complete resolution of the cerebral lesion.

A conjunctival leiomyoma.

PURPOSE: To report a conjunctival leiomyoma. DESIGN: Observational case report. METHODS: A 35-year-old man was referred to us for evaluation of a lesion in his left eye. The lesion had been present for 1 year but had recently caused irritation. Ophthalmologic examination revealed an elevated mass in the episclera. There was no associated conjunctival/episcleral injection. Ocular examination was otherwise entirely normal. An excisional biopsy was performed. RESULTS: The histopathologic and immunohistochemistry examinations established the diagnosis of a conjunctival leiomyoma. CONCLUSION: This case represents the first report, known to date, describing the occurrence of a conjunctival leiomyoma.

A case presentation of a pulmonary complication of ulcerative colitis.

We present the case of a 25-year-old Afro-Caribbean man with a longstanding history of ulcerative colitis and primary sclerosing cholangitis. The patient presented to clinic and reported pleuritic-type chest pain. A routine chest radiograph requested from the clinic revealed an incidental right middle zone opacity in the right lung. A subsequent high-resolution CT showed multiple lung nodules. The patient also had a positive cytoplamic anti-neutrophil cytoplasmic antibody (cANCA) and proteinase 3 antibodies. Bronchoscopy was inconclusive. A video-assisted thoracoscopic surgery biopsy was then taken. The histology revealed changes suggestive of bronchiolitis obliterans organising pneumonia. The pulmonary manifestations of inflammatory bowel disease are poorly characterised. Our literature search has revealed cases hypothesising that immune system dysregulation could display pulmonary complications of ulcerative colitis. The aetiology is thought to be related to the treatment with mesalazine. However, our patient also had a positive vasculitic screen. Previous cases have resolved with supportive management or steroid therapy.

A rare association of pulmonary carcinoid, lymphoma, and sjögren syndrome.

Pulmonary carcinoid and pulmonary lymphoma are both rare cancers and are seldom seen together. Cases have been reported of their coexistence in the gastrointestinal tract, but our literature searches only found a single case of their coexistence in the lung. We discuss our case as well as the literature to try to find a connection and explanation for this occurrence.

Intrathymic primary intrathoracic goiter in a patient with breast malignancy.

We report a rare case of an intrathymic primary intrathoracic goiter. The patient with newly diagnosed breast carcinoma was also known to have a distinct large anterior mediastinal mass. This was removed via a median sternotomy, after a thorascopic biopsy had been performed in the past but a diagnosis had not been reached. A discussion relating to the extremely rare occurrence of intrathymic ectopic thyroid tissue and the surgical treatment of primary intrathoracic goiters is included.