Abstract: Background: While the incidence of malignant tumor-associated interstitial lung disease (MT-ILD) is low, the median survival rate at 6 months is only 58.1% and few studies on MT-ILD in children (MT-chILD) has been previously reported. Objective: To explore clinical features, imaging, pathological features, disease burden and prognosis of MT-chILD, thus providing clinical evidence for early identification, diagnosis and treatment of the MT-chILD. Design: Retrospective cohort study. Methods: Cases of MT-chILD diagnosed by the MDT team in Children's Hospital of Fudan University from February 2014 to February 2021 were retrospectively included. Clinical manifestations, imaging, pathology, treatment, disease burden and follow-up information were collected. Main outcome measures: Factors affecting the 5-year survival of MT-chILD. Results: Fifteen cases were firstly diagnosed in our respiratory department with the following symptoms: cough or shortness of breath (13 cases), fever (9 cases), hemoptysis (4 cases), chest pain or chest tightness (4 cases), fatigue(1 case), abdominal pain(1 case), and diarrhea(1 case). There were 9 cases with normal tumor markers. Lung images showed diffuse nodules, cystic shadows in both lungs, exudation in both lungs with multi-window cord shadows, and uneven brightness of both lungs with ground-glass opacity. The basic pathological classification of MT-chILD were 5 cases of Langerhans histiocytosis (LCH), 4 cases of neuroblastoma, and 1 case of pulmonary mucinous adenocarcinoma, pulmonary papillary adenocarcinoma, T lymphoblastoma, rhabdomyosarcoma, pulmonary fibroblastoma or acinar soft tissue sarcoma, respectively. The median time from onset to diagnosis of MT-chILD was 6.9 months, with 9 cases(60%) misdiagnosed as infections. The average hospitalization cost was RMB 70,000. While 10 cases received chemotherapy after diagnosis, 5 patients gave up treatment. The median survival time after diagnosis was 14 months. There were several independent risk factors affecting the 5-year survival rate of MT-chILD: treatment abandonment (OR=1.754, 95%CI: 1.535~2.519), malnutrition (OR=1.231, 95%CI: 1.020~1.428), combined with fungal infection (OR=1.232, 95%CI: 1.018~1.492), combined with mediastinal emphysema (OR=1.298, 95%CI: 1.002~1.681), combined with sepsis (OR=1251, 95%CI: 1.035~1.787). Chemotherapy (OR=0.658, 95%CI: 0.525~0.993) was a protective factor for 5-year survival of MT-chILD. Conclusion: The onset of MT-chILD presents atypical respiratory symptoms and signs, non-specific laboratory indicators, leading to high misdiagnosis rates and high medical costs. Lung imaging and biopsy pathology are important for the final diagnosis. Active treatment without giving up, receiving chemotherapy and preventing complications are beneficial to long-term survival.

Key words: Children, Interstitial lung disease, Malignant tumors, Risk factors, Survival rate