Diffuse Panbronchiolitis and Thymoma: More Than Just Coincidence?

Abstract

INTRODUCTION: Diffuse panbronchiolitis (DPB) is a rare inflammatory disorder seen almost exclusively in East Asian populations. It can lead to bronchiectasis, recurrent pulmonary infections, progressive respiratory failure and eventually death without appropriate treatment. DPB associated with thymoma is exceedingly rare with 7 previously reported cases from China, Japan and India. We describe the first reported case from the United States. CASE PRESENTATION: A 55-year-old Korean man with asthma, chronic sinusitis and myasthenia gravis, presented with 2 weeks of productive cough, dyspnea, fevers and night sweats. A chest CT demonstrated diffuse tree-in-bud nodularity and bronchiolectasis, calcified granulomas and a 4.1x1.6 cm middle mediastinal mass. CT guided biopsy revealed a low-grade thymoma. An extensive infectious evaluation including bacterial, fungal, mycobacterial and viral investigations from the blood, serum, bronchoalveolar lavage and transbronchial biopsies was only notable for Acinetobacter. Broad spectrum antimicrobials were tailored to sensitivities. Evaluation for an underlying autoimmune disorder was unrevealing. His symptoms recurred one month later. Repeat imaging demonstrated progression of the tree-in-bud nodularity. An extensive infectious evaluation was repeated and negative. Thymectomy and wedge lung biopsy were performed after medical optimization confirming WHO subtype B2 thymoma, Masaoka stage II with focal transcapsular invasion. The lung biopsy demonstrated a diffuse cellular bronchiolitis with obstructive endogenous lipoid pneumonia and bronchiolar dilatation consistent with DPB. Surgical specimen cultures were negative. Oral azithromycin was begun and a course of adjuvant radiation for the thymoma was completed. Significant clinical and radiographic improvement was noted at 3 months with ongoing improvement at one year. DISCUSSION: DPB is an inflammatory disorder of the respiratory bronchioles of unclear etiology. Typical findings of DPB include sinusitis, productive cough, dyspnea, wheezing and diffuse nodularity with bronchiolectasis on imaging. Recent evidence suggests a high correlation with East Asian HLA subtypes supporting a unique genetic susceptibility. Additional studies implicate neutrophils, CD8+ T-cells, macrophages and immune cytokines. Thymomas are classically associated with autoimmune disorders such as myasthenia gravis and red cell aplasia. It is unclear if the reported cases reflect a true relationship. CONCLUSIONS: To our knowledge, this is the first report of DPB and thymoma in Western literature. Surgical biopsy is often required in low prevalence areas for diagnostic confirmation of DPB. Management includes usual treatment of thymoma and chronic macrolide therapy for DPB.