Kerley A-lines represent thickened septal plates between lung segments in patients with lymphangitic carcinomatosis: confirmation using 3D-CT lung segmentation analysis

Purpose Kerley A-lines are generally apparent in patients with pulmonary edema or lymphangitic carcinomatosis. There are two main thoughts regarding the etiology of Kerley A-lines, but no general agreement. Specifically, the lines are caused by thickened interlobular septa or dilated anastomotic lymphatics. Our purpose was to determine the anatomic structure represented as Kerley A-lines using 3D-CT lung segmentation analysis. Materials and methods We reviewed 139 charts of patients with lymphangitic carcinomatosis of the lung who had CT and X-ray exams with a maximum interval of 7 days. The presence of Kerley A-lines on X-ray was assessed by a radiologist. The A-lines on X-ray were defined as follows: dense; fine (< 1 mm thick); ≥ 2 cm in length, radiating from the hilum; no bifurcation; and not adjacent to the pleura. For cases with Kerley A-lines on X-ray, three radiologists agreed that the lines on CT corresponded with Kerley A-lines. The incidence of A-lines and the characteristics of the lines were investigated. The septal lines between lung segments were identified using a 3D-CT lung segmentation analysis workstation. The percentage of agreement between the A-lines on CT and lung segmental lines was assessed. Results On chest X-ray, 37 Kerley A-lines (right, 16; left, 21) were identified in the 22 cases (16%). Of these, 4 lungs with 12 lines were excluded from analysis due to technical reasons. Nineteen of the 25 lines (76%) corresponded to the septal lines on CT. Of these, 11 lines matched with automatically segmented lines (intersegmental septa, 4; intersubsegmental septa, 7) by the workstation. Two lines (8%) represented fissures. Four lines corresponded to the bronchial wall/artery (3 lines, 12%) or vein (1 line, 4%). Conclusion Kerley A-lines primarily represented thickened and continued interlobular septal lines that corresponded to the septa between lung segments and subsegments.

Clinical and Imaging Features of Non-Small Cell Lung Cancer with G12C KRAS Mutation

KRAS G12C mutations are important oncogenic mutations that confer sensitivity to direct G12C inhibitors. We retrospectively identified patients with KRAS+ NSCLC from 2015 to 2019 and assessed the imaging features of the primary tumor and the distribution of metastases of G12C NSCLC compared to those of non-G12C KRAS NSCLC and NSCLC driven by oncogenic fusion events (RET, ALK, ROS1) and EGFR mutations at the time of initial diagnosis. Two hundred fifteen patients with KRAS+ NSCLC (G12C: 83; non-G12C: 132) were included. On single variate analysis, the G12C group was more likely than the non-G12C KRAS group to have cavitation (13% vs. 5%, p = 0.04) and lung metastasis (38% vs. 21%; p = 0.043). Compared to the fusion rearrangement group, the G12C group had a lower frequency of pleural metastasis (21% vs. 41%, p = 0.01) and lymphangitic carcinomatosis (4% vs. 39%, p = 0.0001) and a higher frequency of brain metastasis (42% vs. 22%, p = 0.005). Compared to the EGFR+ group, the G12C group had a lower frequency of lung metastasis (38% vs. 67%, p = 0.0008) and a higher frequency of distant nodal metastasis (10% vs. 2%, p = 0.02). KRAS G12C NSCLC may have distinct primary tumor imaging features and patterns of metastasis when compared to those of NSCLC driven by other genetic alterations.

Successful treatment of pulmonary lymphangitic carcinomatosis by anlotinib in 14 Chinese patients with advanced non-small cell lung cancer.

e21064 Background: Pulmonary lymphangitic carcinomatosis (PLC) occurs in 6%-8% of intrathoracic metastases among malignant tumor. The median survival was only 2.0 months from time of pulmonary symptoms to death in cases during 2000-2018, which is a poor prognosis. Effective interventions were needed besides standard chemotherapy and symptomatic support. Anlotinib showed a critical effect on lymphangiogenesis, and lymphatic metastasis in mouse models of lung adenocarcinoma, it might be a therapeutic option for tumor lymphatic metastasis. In this study, we retrospectively analyzed the efficacy and safety of anlotinib for PLC in patients with Non-small Cell Lung Cancer (NSCLC). Methods: We retrospectively investigated NSCLC patients with PLC at our hospital between May 2018 and November 2020, who received anlotinib monotherapy or combined therapy for PLC. Data were analyzed for progression-free survival (PFS), overall survival (OS), objective response rate(ORR), disease control rate(DCR) and adverse events (AE). The impact of clinical and genomic factors on PFS and OS were also assessed. Results: A total of 14 patients were enrolled with a median age of 64 years. 10(71.4%) were male, 4(28.6%) has smoking history, 10(71.4%) of patients had a performance status of 2-3. 9, 3, 2 patients had TP53 mutation, EGFR mutation, ALK fusion respectively. 9(64.3%) patients received anlotinib monotherapy. Of 14 patients, 8 achieved partial response (PR), 5 presented stable disease (SD), 1 had progressed disease. The ORR and DCR were 57.1% and 92.9% respectively. The median PFS was 3.1 months (95% CI: 2.0-4.2), the median OS for 1, 2, ≥3 line were 13 months, 7.2 months, 5.2 months, respectively. Median PFS and OS (≥3 line) were significantly longer for patients with TP53-mutant tumors compared with those with TP53–wild-type tumors (median PFS: 7 vs. 1.1 months, median OS (≥3 line): 6.8 vs. 1.9 months). No difference of PFS and OS (≥3 line) was found between EGFR or ALK alteration and the corresponding wild type patients. The most frequently reported AEs were high blood pressure (11, 78.6%), hand foot syndrome (6, 42.9%), diarrhea (5, 35.7%), fatigue (4, 28.6%), hoarseness (3, 21.4%), proteinuria (2, 14.3%) and stomatitis (2, 14.3%). Conclusions: Anlotinib presented favorable efficacy in patients with pulmonary lymphangitic carcinomatosis and conferred considerable survival benefit compared with previous studies, especially in patients harboring TP53 mutations. The AEs were manageable. These indicated that anlotinib can be a promising therapeutic treatment of PLC. More clinical data is needed to validate this finding.

Pulmonary Lymphangitic Carcinomatosis as the Initial and Only Presentation of Gastric Cancer in a Young Male and Literature Review

BackgroundPulmonary lymphangitic carcinomatosis (PLC) is a malignant lung disease characterized by metastatic tumor lesions in the lung lymphatic vessels with a poor prognosis. Early diagnosis is the key to improve the outcome. However, when PLC is the first manifestation of patients without a known malignancy, it often leads to delayed diagnosis and treatment, and even fatal consequences due to non-specific symptoms. Here, we describe a young male presenting PLC as the first and only manifestation followed by diagnosis of gastric adenocarcinoma and systemically summarized previously reported clinical properties of PLC cases in the literature.Case presentationA 32 years old male presented nonproductive cough for 20 days and progressive exertional dyspnea in a week. He was diagnosed with pneumonia and received antibiotics for almost 3 weeks without any improvement. Chest computed tomography showed multiple nodules and thickened interlobular septa in bilateral lung. PET/CT revealed a primary gastric tumor with PLC and the biopsy of the cervical lymph node confirmed a poorly metastatic differentiated gastric adenocarcinoma. The patient’s general condition deteriorated rapidly and he developed respiratory failure, requiring non-invasive mechanical ventilation on day 9 after admission. Chemotherapy was given to the patient on the tenth day. However, few hours after receiving the first dose, the patient died of respiratory failure. It was only one month from the onset of symptoms to death of our case.ConclusionsPatients presenting PLC as the first manifestation of an unknown malignancy carry a bleak prognosis. PLC be considered for differential diagnosis in patients who present with dyspnea, dry cough with or without loss of weight. Particular attentions need to be given to patients, especially young ones without histories of malignancy, whose chest imaging exhibits thickened interlobular septa. While the stomach, lung and prostate are the most likely origins of the primary tumors, patients with PLC derived from prostate cancer may have a better prognosis after anti-cancer treatment.