Background: Liquid biopsy allows the identification of targetable cancer mutations in a minimally invasive manner. In patients with advanced non-small cell lung cancer (NSCLC), droplet digital PCR (ddPCR) is increasingly used to genotype the epidermal growth factor receptor (EGFR) gene in circulating cell-free DNA (cfDNA). However, the sensitivity of this method is still under debate. The aim of this study was to implement and assess the performance of a ddPCR assay for detecting the EGFR T790M mutation in liquid biopsies.Methods: A ddPCR assay was optimized to detect the EGFR T790M mutation in plasma samples from 77 patients with NSCLC in progression.Results: Our ddPCR assay enabled the detection and quantification of the EGFR T790M mutation at cfDNA allele frequency as low as 0.5%. The mutation was detected in 40 plasma samples, corresponding to a positivity rate of 52%. The number of mutant molecules per mL of plasma ranged from 1 to 6,000. A rebiopsy was analyzed for 12 patients that had a negative plasma test and the mutation was detected in 2 cases.A second liquid biopsy was performed for 6 patients and the mutation was detected in 3 cases.Conclusions: This study highlights the value of ddPCR to detect and quantify the EGFR T790M mutation in liquid biopsies in a real-world clinical setting. Our results suggest that repeated ddPCR tests in cfDNA may obviate tissue re-biopsy in patients unable to provide a tumor tissue sample suitable for molecular analysis.

High altitudes are linked to decreased rates of pulmonary tuberculosis infection, disease and mortality. However, its relevance as a trigger for pulmonary tuberculosis reactivation in immunocompetent patients is not documented. A 28-year-old healthy Nepalese female was admitted in the emergency department with sudden left pleuritic back pain with shortness of breath, two weeks after arriving in Lisbon, having arrived from Kathmandu and undergone a change in altitude of 1400 metres. She also had evening low-grade fever and fatigue since she arrived. Her mother-in-law had died of tuberculosis two years before. Chest radiography and computed tomography scan showed a left upper lobe consolidation. Laboratory analyses were 79 mm/sec. Human immunodeficiency virus serology, blood cultures and urinary antigen testing were negative. Bronchial secretions’ cultures became positive for Mycobacterium tuberculosis complex. The patient was started on anti-tuberculous treatment and made a steady recovery. This case reports a probable reactivation of pulmonary tuberculosis infection that could have been triggered by altitude differences.

Synchronous tumours are defined as two or more independent primary neoplasms of different origins diagnosed at the same time in 1 individual. Although rare, its incidence is increasing and the proper diagnosis and staging of each tumour is crucial in defining the patient prognosis and the best therapeutic choice. We present a case of a 56-year-old woman presenting with a lung adenocarcinoma and pulmonary metastases initially diagnosed as stage IV and who was started on a tyrosine kinase inhibitor (erlotinib). In the meantime, she was also diagnosed with papillary thyroid carcinoma and was submitted to complete thyroidectomy. After 6 cycles of erlotinib, thoracic CT showed a decrease in the dimensions of the primary pulmonary tumour, but an increase in the size and number of pulmonary metastases while blood tests showed elevated thyroglobulin. This therefore raised the possibility that the metastases could have originated from the thyroid carcinoma. Anatomo-pathological examination of the lung metastases confirmed this hypothesis. In conclusion, it is important to confirm the origin of metastases in synchronous tumours given this can lead to a re-staging of tumours and a different prognosis, along with other therapeutic options. A multidisciplinary team meeting is crucial to define management and therapeutic approaches for these patients.

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