Case of the Month

Answer to June's Case of the Month

C. Usual interstitial pneumonia

Usual interstitial pneumonia (UIP) is the most common histopathological pattern of idiopathic pulmonary fibrosis (IPF). IPF is a bilateral, slowly progressive lung disease of unknown cause manifesting with dry cough, slowly worsening dyspnea, and presence of inspiratory basal crackles. It affects older adults, predominantly men 50–70 years old, usually with a history of smoking and gastroesophageal reflux disease.

A pathologic diagnosis of UIP requires four features:

1. A heterogeneous appearance or “patchwork pattern” of interstitial fibrosis with normal and fibrotic lung adjacent to each other (Image 1).
2. Fibroblastic foci that represent areas of active fibrosis and collagen synthesis at the interface between the normal and the fibrotic lung (Image 2).
3. The fibrosis involves the lung in a characteristic subpleural or paraseptal distribution, starting at the periphery of the lobule and eventually involving the entire lobule (Image 3).
4. Honeycomb change represents the final stages of this fibrosis. Honeycomb changes depict reorganized airspaces, partially lined by bronchiolar epithelium; often filled by mucin intermingled with neutrophils, macrophages and lymphocytes; and surrounded by hyperplastic smooth muscle layer within the fibrotic areas (Image 4).

Alveolar wall inflammation and fibrosis is the key event in the etiology of UIP, along with repetitive normal and aberrant wound healing. The most recent evidence suggests that host defense and cell senescence gene variants may be the most important etiologic causes of UIP. In this regard, several genetic alterations have been reported that may contribute to the pathogenesis of UIP. These include mutations in the genes responsible for length of telomerases (TERT and TERC) as well as mutations in the surfactant protein C gene and the mucin 5B promoter region (MUC5B).

Overall, the prognosis for patients with UIP is quite poor, with a median life survival of 3–5 years. In the past, the only known therapy for patients with UIP was lung transplantation. However, new anti-fibrotic therapies have emerged to stop the progression of the fibrosis in UIP. It is important that pathologists are familiar with the histologic criteria for diagnosing UIP so that patients receive the most effective therapy.

Submitted by Ivana Savic, University of Belgrade Faculty of Medicine, Belgrade, Serbia, and Carol Farver, MD, University of Michigan, Ann Arbor, Michigan, USA.