## 2 Case Report  
A 68-year-old man with a history of heavy smoking was admitted to the emergency department of Sant' Anna and San Sebastiano Hospital in Caserta, Italy, in April 2021. He presented with dyspnea and cough, which had worsened over the past few months. After being tested for SARS-CoV-2, he was referred for an urgent CT scan of the lungs. The scan revealed bilateral pleural effusions, a solid lesion of about 57 \(\times\) 45 mm with spiculated margins in the left lower lobe with carcinomas lymphangitis, and multiple parenchymal micromodulations in the right lung. In addition, it revealed pathological per-centimetric para-tracheal, pre- and sub-carinal homolateral, aortic-pulmonary, and Barety lymphadenopathies, measuring up to 25 mm in maximum diameter (Figure 1A-C). No lesions were reported in other body regions. He underwent evacative palliative thoracentesis of about 1500 mL bloody pleural fluid and diagnostic bronchoscopy. The cytological picture depicted atypical epithelial cells with severe nuclear abnormalities organized in glandular structures; ICC analysis evidenced positivity for thyroid transcription factor 1 (TTF-1) and negativity for calretinin and Wilms tumor protein (WT1). Based on these clinical, radiological, morphological, and ICC features, he was diagnosed with NSCLC _favor_ adenocarcinoma. The patient was thus referred to our clinical laboratory for molecular assessment of _EGFR_, _ALK_, _ROS1_, _BRAF_, and _KRAS_ and evaluation of PD-L1 expression. The molecular test and the evaluation of PD-L1 expression were performed. No actionable mutations were identified, and PD-L1 was not expressed (tumor proportion score (TPS) \(<\) 1). Hospitalized in the Oncology Unit of Sant' Anna and San Sebastiano Hospital in June 2021, he was begun on a first treatment cycle with carboplatin plus pemetrexed plus pembrolizumab based on the high burden of the disease and breathing difficulties. Moreover, a physical examination detected the presence of ascites, which were later confirmed by ultrasound (Figure 1D). Thus, evacative paracentesis was immediately practiced and about 5 L of yellow citrine liquid was removed. Peritoneal cytological examinations identified TTF-1 positive malignant cells, suggesting peritoneal carcinomatosis (PCM) from lung cancer. Carcinoembryonic antigen (CEA) levels in the ascites were above 500 ng/mL. Cell-block analysis, which was performed in our clinical laboratory, revealed the atypical p.K601E of exon 15 of _BRAF_ mutation and a PD-L1 expression level \(\geq\) 50%. Owing to the limited data on targeted therapy in patients with _BRAF_ exon 15 p.K601E-mutant lung adenocarcinoma, (Figures 2 and 3) we preferred chemo-immunotherapy over targeted therapy to control the symptoms. Figure 1: April 2021. (**A**,**B**) Computer tomography showing bilateral pleural effusions, a solid lesion of about 57 \(\times\) 45 mm\({}^{2}\) with spiculated margins in the left lower lobe with carcinomas lymphangitis. (**C**) Chest X-ray describing bilateral pleural effusion and synchronous carcinomas lymphangitis. (**D**) Abdominal ultrasound highlighting pleural effusion. Remarkably, after the fourth cycle, ascites completely regressed. Concomitantly, breathlessness was significantly reduced. Indeed, home oxygen therapy was gradually reduced to 3 L/min for 15 min a day and used only on exertion. Overall, the patient's performance status and appetite were markedly improved. Clinically, the size of the right lung nodules and of the primary heteroplastic lesion was reduced; carcinomas lympangitis was also decreased (Figure 4A,B). However, when seen at a follow-up outpatient visit in February 2022, his overall performance status seemed to have deteriorated. He complained of abdominal heaviness, swollen legs, and a worsening of dyspnea, thereby needing to increase oxygen therapy to 6 L/min for a couple of hours a day, even when at rest. Disease progression was also seen. Ascites had returned, as confirmed by ultrasound.