Respiratory Bronchiolitis-Interstitial Lung Disease Combined With Lung Cancer:Case Report And Literature Review

Objective: Respiratory bronchiolitis-asociated interstitial lung disease(RBILD)is closely related to smoking.Its main pathological feature is the accumulation of numerous pigmented alveolar macrophages in patchy centering around respiratory bronchiole.Insidious onset,and the disease may be worse with progressive exertional dyspnea and cough.It can also be complicated with pulmonary infection and hypoxemia.Most case reports suggest a good prognosis,but patients complicated with lung cancer are extremely rare.This article reported a case of respiratory bronchiolitis-associated interstitial lung disease combined with lung cancer(RBILD-LC),so we can observe its clinical diagnosis and treatment during the whole process.Method: A retrospective analysis of a patient with RBILD-LC in the First Affiliated Hospital of Guang Xi Medical College and the related literature were reviewed by the pathogenesis,clinical manifestations,laboratory examination,imaging,diagnosis,antidiastole,treatment and efficacy.Result: 1.The patient was a 65-year-old man,whose main symptoms were repeating cough,expectoration,hemoptysis.He had a long history of smoking for over 30 years.And he had no special occupational exposure history or familial lung cancer.Physical examination: clubbing of fingers and toes could be seen.The patient began to develop symptoms of dry cough,chest discomfort and occasional expectoration in 2011.Since then,his symptoms have gradually gotten worse.So he took a computed tomography(CT)scan which showed diffuse ground glass opacity in both lungs,paraseptal emphysema and pulmonary bullae mainly distributed in the upper lungs in November 2013,and Repeatedly pulmonary function examinations suggested mild obstructive ventilation dysfunction and normal diffusion dysfunction.The pathological changes showed the accumulation of brownish pigmented macrophages within respiratory bronchioles and extended into neighboring alveoli.The lesion was centrally distributed along the peripheral bronchioles,respiratory bronchiole wall thickened with alveolar septum widened and interstitial fibrosis,there was focal lymphocyte infiltration.Some of the alveoli showed compensatory emphysema.He was diagnosed with RBILD.There was no better therapeutic effect after inhaled and oral glucocorticoid therapy for 3 months.Thus corticosteroids were gradually withdrawn.And no significant improvement in imaging or lung function during follow-up.Finally the patient was stopped to be followed up in 2015.In July 2018,the patient developed a cough producing yellow sputum mixed with blood,but he didn’t take any measures,and the symptoms lasted for a long time.Until January 2019,he took a CT scan of chest showed a new onset of huge space-occupying lesion in the upper lobe and the dorsal segment of the lower lobes of the right lung,with marginal lobulation and patchy calcification shadow inside.But no significant progression of interstitial lung lesions was observed.Lung biopsy was consistent with the diagnosis of right lung adenocarcinoma at stage IVB(T4N3M1c).He received chemotherapy with carboplatin and pemetrexed.After 2 cycles of chemotherapy,the patient achieved partial remission(PR)and continued to be treated with original chemotherapy for another 12 cycles.During chemotherapy,he developed a symptom of hand-foot syndrome(HFS)when added with the Cabozantinib by RET positive,a driver gene of lung cancer,so cabozantinib was stopped.Unfortunately,the disease progressed after being diagnosed with lung cancer for14 months.He received chemotherapy by carboplatin and docetaxel for 2 cycles,which was still being followed up until now.2.Literature review results: There were only 2 cases of RBILD-LC with complete data at home and abroad.Both of them were male with a history of heavy smoking.The main symptoms were cough,sputum and dyspnea.The physical examination showed velcro rales audible in both lungs and clubbed-fingers.The pathology showed typical RBILD manifestations.The imaging findings of 1 case were mainly ground glass opacities,mesh shadows and parastatal emphysema.Pathological biopsy showed adenocarcinoma.Due to the tumor that had been removed during biopsy,he received glucocorticoid treatment and quit smoking.And he was in stable condition.Another case showed ground glass opacities and fibrosis in imaging.His pathological biopsy proved to be squamous cell carcinoma,and the patient died after 18 months of chemotherapy.Conclusion: 1.The onset of RBILD is hidden.With Chronic progression,it would develop symptoms of exertional dyspnea and cough.Physical examinations can be found velcro rales audible in both lungs and clubbing of fingers and toes.Radiographic findings show varying degrees of diffuse ground glass opacity,centrilobular nodules,emphysema,bronchial wall thickening,mesh shadows,The pathological manifestations show the accumulation of pigmented macrophages within respiratory bronchioles and extended into the adjacent alveoli surrounding chronic inflammatory cell infiltration,with mild bronchiolar fibrosi sand alveolar septa thickened by fibrosis.2.RBILD combined with lung cancer are two independent diseases.The pathogenesis of RBILD-LC is still unclear,and long-term cigarette smoking exposure is a common risk factor.Therefore the patients with RBILD should be followed up intensively in clinic.3.RBILD-LC treated by the standard regimen of primary lung cancer,and the similarities and differences of therapy for RBILD-LC and primary lung cancer were not clear at present.