Chronic Hypersensitivity Pneumonitis-Morphology of the Explanted Lungs

Dear Editor, For many years, hypersensitivity pneumonitis is a recognized form of interstitial lung disease. Usual interstitial pneumonia (UIP) is a pattern of interstitial pneumonia which is characterized by heterogeneous fibrosis in the lung parenchyma along with architectural distortion, fibroblast foci, and honeycombing of the lungs.[1,2] Histologic UIP pattern without any etiology is primary UIP and is referred to as idiopathic pulmonary fibrosis (IPF). UIP pattern can be seen secondary to connective tissue disease-related, hypersensitivity pneumonitis-related and asbestos-related interstitial lung disease.[2] In 2020, American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) defined hypersensitivity pneumonitis (HP) as an inflammatory and/or fibrotic disease affecting lung parenchyma and small airways.[3] It typically results from an immune-mediated reaction provoked by an overt or occult inhaled antigen in susceptible individuals. More than 50 occupations/exposures associated with HP have been described.[4] Traditionally, HP has been divided into acute, subacute and chronic forms. Many authors reserve chronic HP in which there is radiological or pathological evidence of fibrosis. The new ATS guidelines recommended simply separating HP into non-fibrotic and fibrotic forms. However, there has been disagreement about features which do or do not allow a diagnosis of fibrotic form of HP and particularly those that separate fibrotic HP from IPF.[3,5,6] There is a scarcity of data on secondary UIP types, especially HP. We are tempted to report the morphology of both the lungs of a 45-year-old male, who was known case of chronic HP diagnosed at an outside hospital. He was referred for bilateral lung transplant at our transplant centre. On gross examination, both the lungs were slightly smaller in size and firm in consistency. The right lung was 580 gm while the left lung was 560 gm in weight. There was no pleural thickening or exudative pleuritis [Figure 1a]. On the cut section, both lungs were solid and firm in consistency [Figure 1b]. There were no cavities or military tubercles. Multiple sections were taken, fixed in 10% formalin and processed. Then, 2–4 μm thick sections were cut and stained with hematoxylin and eosin.Figure 1: (a) Both the lungs are small in size and firm, and (b) cut section is firmOn microscopic examination, it was found that alveolar walls were thickened and infiltrated by moderate lymphocytic infiltrate, and there was interstitial fibrosis [Figure 2a]. Alveolar walls and lumen also showed histiocytes with eosinophilic cytoplasm [Figure 2b]. Fibrosis was mainly bronchiolocentric. It was seen in more than 60% of bronchioles. Peribronchiolar metaplasia was seen as fine interstitial fibrosis with overlying metaplastic bronchiolar epithelium. Occasional giant cell was seen. There were no epithelioid granulomas or caseous necrosis. Fibroblastic foci were seen at many places [Figure 3a]. Cystic spaces were filled with eosinophilic mucinous fluid and histiocytes with pink cytoplasm. Honeycombing was seen as many cystic spaces lined by respiratory epithelium and filled with mucus [Figure 3b]. Honeycombing represents the end-stage lung disease. There were no fungal hyphae on fungal stains such as GMS and PAS. There were no acid-fast bacilli on ZN stain.Figure 2: Lung parenchyma (a) interstitial inflammation and fibrosis (Hematoxylin and Eosin × 100) and (b) interstitial fibrosis and many macrophages in alveolar lumen (Hematoxylin and Eosin × 400)Figure 3: (a) Lung parenchyma with Fibroblastic foci (Hematoxylin and eosin × 400, arrows), and (b) honeycombing and cystic spaces with mucin and macrophages. (Hematoxylin and eosin × 100)There was no pleural fibrosis or extensive interstitial fibrosis and minimal inflammation, which was against the diagnosis of IPF. There was no lymphoid hyperplasia, secondary follicles, chronic pleuritis, or organizing pneumonia, which favor the diagnosis of connective tissue disorder related UIP. A final diagnosis of chronic fibrotic HP was made. Bronchiolocentric fibrosis and peribronchiolar metaplasia with radiological fibrosis in the lungs are diagnostic of the chronic form of HP. Data availability statement All data generated or analyzed during this study are included in this published article. Further details are available from the corresponding author upon reasonable request. Author contribution SSC: Conceptualization, Data collection, Writing original draft. MS: Clinical management, Supervision, AR: review and editing. ACB: Literature review, Manuscript editing. AR: Literature review. SSC: Manuscript proofreading. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.