A 62-year-old man comes to the clinic due to a 6-month history of progressive exertional dyspnea. The patient has an occasional cough but has no palpitations, orthopnea, chest pain, or lower extremity swelling. Past medical history is insignificant. He works as an attorney, does not use tobacco, and drinks alcohol only on social occasions. His symptoms continue to progress, and the patient dies of respiratory failure 3 years after the initial clinic visit. Autopsy findings include heterogenous lung parenchyma with predominantly subpleural areas of dense collagen deposition, lymphocyte infiltration, and fibroblast proliferation intermixed with areas of normal lung tissue. Which of the following is the most likely diagnosis?

Question

A 62-year-old man comes to the clinic due to a 6-month history of progressive exertional dyspnea.  The patient has an occasional cough but has no palpitations, orthopnea, chest pain, or lower extremity swelling.  Past medical history is insignificant.  He works as an attorney, does not use tobacco, and drinks alcohol only on social occasions.  His symptoms continue to progress, and the patient dies of respiratory failure 3 years after the initial clinic visit.  Autopsy findings include heterogenous lung parenchyma with predominantly subpleural areas of dense collagen deposition, lymphocyte infiltration, and fibroblast proliferation intermixed with areas of normal lung tissue.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

The described histopathologic findings are consistent with idiopathic pulmonary fibrosis (IPF). Microscopic findings are heterogeneous and include: Importantly, there should also be no other findings consistent with another disease process (eg, granulomas). The precise etiology of IPF is unclear, but risk factors include cigarette smoking, environmental pollutants, chronic aspiration, older age, and certain genetic factors (eg, telomerase mutations). Patients typically have dyspnea, nonproductive cough, finger clubbing, and inspiratory crackles. The onset is insidious, prognosis is poor, and no curative treatment exists. (Choice A) Alpha-1 antitrypsin deficiency causes alveolar wall destruction, resulting in panacinar emphysema. Patients tend to present at a young age with dyspnea, productive cough, and wheezing. Emphysematous changes (eg, bullae) are seen predominantly at the lung bases, and histologic findings include large alveoli with thin septa. (Choice B) Asbestosis usually occurs in patients with occupational exposures (eg, shipbuilding). Microscopy may show fibrosis and honeycombing, but asbestosis can be differentiated from IPF by the presence of asbestos bodies (brown, beaded rods coated with iron-containing material) and ferruginous bodies (inorganic particles with a similar ferrous material). Pleural plaques are also common. (Choice C) Chronic bronchitis causes significant sputum production over a prolonged period and is often related to smoking. Histologic findings include mild lymphocytic infiltrates and mucous gland hyperplasia with mucus-filled bronchioles. (Choice D) Chronic hypersensitivity pneumonitis is due to repeated exposure to an inciting agent (eg, birds, fungi, chemicals). Cough and dyspnea occur shortly after exposure to the antigen and may progress to respiratory failure. Histologic findings include noncaseating granulomas, peribronchiolar fibrosis, and patchy lymphocytic infiltrates. (Choice E) Cryptogenic organizing pneumonia is another interstitial lung disease of unclear etiology that typically presents with dry cough, dyspnea, and fatigue. However, histologic findings include fibroblastic plugs in the alveolar sacs and ducts, often extending into adjacent alveoli in a characteristic butterfly pattern. Educational objective: Histologic findings of idiopathic pulmonary fibrosis are most prominent in the lung periphery and include a heterogeneous mixture of chronic inflammation and patchy interstitial fibrosis, focal fibroblast proliferation, and formation of fibrotic cystic spaces in a honeycomb pattern. __________ References: Idiopathic pulmonary fibrosis: evolving concepts. (http://www.ncbi.nlm.nih.gov/pubmed/24867394)

A 62-Year-Old Man Comes to the Clinic Due to a 6-Month