Diagnosis of interstitial lung diseases: from Averill A. Liebow to artificial intelligence

Abstract

Histopathologic criteria of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) were defined over the years and endorsed by leading organizations decades after Dr. Averill A. Liebow first coined the term UIP in the 1960s as a distinct pathologic pattern of fibrotic interstitial lung disease. Novel technology and recent research on interstitial lung diseases with genetic component shed light on molecular pathogenesis of UIP/IPF. Two antifibrotic agents introduced in the mid-2010s opened a new era of therapeutic approaches to UIP/IPF, albeit contentious issues regarding their efficacy, side effects, and costs. Recently, the concept of progressive pulmonary fibrosis was introduced to acknowledge additional types of progressive fibrosing interstitial lung diseases with the clinical and pathologic phenotypes comparable to those of UIP/IPF. Likewise, some authors have proposed a paradigm shift by considering UIP as a stand-alone diagnostic entity to encompass other fibrosing interstitial lung diseases that manifest a relentless progression as in IPF. These trends signal a pendulum moving toward the tendency of lumping diagnoses, which poses a risk of obscuring potentially important information crucial to both clinical and research purposes. Recent advances in whole slide imaging for digital pathology and artificial intelligence technology could offer an unprecedented opportunity to enhance histopathologic evaluation of interstitial lung diseases. However, current clinical practice trends of moving away from surgical lung biopsies in interstitial lung disease patients may become a limiting factor in this endeavor as it would be difficult to build a large histopathologic database with correlative clinical data required for artificial intelligence models.

Keywords: Artificial intelligence; Digital pathology; Familial pulmonary fibrosis; Idiopathic pulmonary fibrosis; Progressive pulmonary fibrosis; Usual interstitial pneumonia.

Fig. 1.

(A) Usual interstitial pneumonia (UIP), the prototype of interstitial lung disease, showing patchy interstitial fibrosis with subpleural accentuation, marked architectural distortion of alveolar architecture with scarring and microscopic honeycomb changes, and temporal heterogeneity of fibrosis evidenced by scattered fibroblastic foci with dome-shaped myofibroblastic/fibroblastic proliferation over scarred areas (arrows), which likely implies an ongoing acute lung injury in already scarred lung tissue causing progressive clinical course. (B) Nonspecific interstitial pneumonia (NSIP) shows diffuse and uniform fibrous interstitial thickening. In contrast to UIP, NSIP shows relatively well-preserved alveolar architecture without honeycomb changes or fibroblastic foci, which likely explains a more favorable prognosis of NSIP than UIP. (C) Desquamative interstitial pneumonia (DIP) characterized by diffuse collection of pigmented macrophages in the alveolar spaces with mild to moderate interstitial fibrosis. DIP in the original classification by Dr. Liebow is included in the current American Thoracic Society classification. (D) Giant cell interstitial pneumonia (GIP) showing many scattered multinucleated giant cells in the alveolar spaces or septa. GIP was included in the Dr. Liebow’s original classification of interstitial lung diseases but dropped in the current idiopathic interstitial pneumonia classification as GIP is now primarily regarded as a hard metal pneumoconiosis (e.g., cobalt).

Fig. 2.

An axial view of high-resolution computed tomography demonstrates a portion of lower lung fields with classific findings of usual interstitial pneumonia characterized by peripherally accentuated reticular densities and honeycomb changes.

Fig. 3.

The idiopathic interstitial pneumonia (IIP) classification established in 2000s is evolved from the less well-defined idiopathic pulmonary fibrosis (IPF) that encompassed various histologic patterns. Progressive pulmonary fibrosis in the current official practice guideline by American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) can be the manifestion by many fibrotic lung diseases other than IPF. AIP, acute interstitial pneumonia; CFA, cryptogenic fibrosing alveolitis; CiOP, cicatricial organizing pneumonia; COP, cryptogenic organizing pneumonia; CTD-ILD, connective tissue disease–associated interstitial lung disease; DIP, desquamative interstitial pneumonia; F-HP, fibrotic hypersensitivity pneumonitis; F-NSIP, fibrotic nonspecific interstitial pneumonia; FOP, fibrotic organizing pneumonia; LCH, Langerhans cell histiocytosis; PPFE, pleuroparenchymal fibroelastosis; RBILD, respiratory bronchiolitis interstitial lung disease; UIP, usual interstitial pneumonia.