The American Thoracic Society and the European Respiratory Society define usual interstitial pneumonia (UIP) as the pathologic abnormality essential to the diagnosis of the distinct clinical disorder idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis. IPF is a chronic progressive form of interstitial pulmonary fibrosis that occurs in middle-aged to elderly patients and does not respond to immunosuppressive therapy, unlike many other interstitial lung diseases. The patient classically presents with insidious onset of shortness of breath. Over months or years, as increasingly more lung tissue is gradually replaced by scar, large areas (especially in the lower zones and subpleurally) become end-stage honeycomb lung, and the disease becomes progressively more clinically severe, eventually resulting in respiratory failure. The great majority of patients with IPF are smokers, and it is probable that smoking has a causative role in IPF. In comparison to many other forms of interstitial pneumonia, including most other idiopathic interstitial pneumonias, the prognosis of UIP is poor, and as noted, UIP does not respond to steroids. Therefore, it is important to correctly diagnose UIP versus other interstitial pneumonias.

UIP is characterized histologically by a patchy pattern of chronic interstitial fibrosis (mature collagen) with relatively minimal to mild interstitial chronic inflammation. This patchy pattern results in areas of variable interstitial fibrosis mixed with areas of normal or nearly normal lung parenchyma and areas of architectural distortion consisting of honeycomb lung or solid scars. Radiologically, grossly, and microscopically, the fibrosis and honeycombing of UIP are more prominent in lower lung zones and in the periphery of the lung. Microscopically, the fibrosis is also worse in the periphery of the lobule. Essential to the concept and diagnosis of UIP is temporal heterogeneity (the process is ongoing and not of the “same age” or same duration throughout the biopsy). The temporal heterogeneity is demonstrated by the presence of active fibroblast foci representing “younger” foci of active ongoing disease compared to the more abundant “older” mature scarring. Fibroblast foci consist of small tufts of granulation tissue (fibroblasts in a myxoid or edematous stroma), typically on the fibrotic walls at the interface between fibrotic and normal lung.

Honeycomb areas may show lymphoid aggregates, smooth-muscle hyperplasia, bronchiolar or squamous metaplasia of cyst linings and neutrophils, macrophages, or debris in the cystic spaces (see Chapter 89). Desquamative interstitial pneumonia-like reactions with collections of macrophages containing granular brown cytoplasmic material may be seen in the honeycomb areas (see Chapter 75). Infections or other superimposed pathologies are possible. There is an increased risk of lung cancer in patients with UIP. Whether or not this is due to the UIP itself or to smoking as an etiologic agent common to both diseases is not known.