A 65-year-old man dies while hospitalized for severe breathing difficulty. The patient had several prior episodes of dyspnea and cough requiring hospitalization. He had a history of hypertension and chronic kidney disease. The patient smoked a pack of cigarettes daily for 38 years and immigrated to the United States 20 years ago. Autopsy is performed, and microscopic examination of the lungs reveals alveolar macrophages containing aggregates of golden-brown cytoplasmic granules that turn dark blue with Prussian blue staining. Which of the following conditions is most likely associated with this patient's microscopic findings?
This patient most likely had heart failure due to left ventricular dysfunction. Impaired forward pumping by the left ventricle causes increased pulmonary capillary pressure that can lead to pulmonary edema and dyspnea. The rise in hydrostatic pressure also disrupts the integrity of the pulmonary capillaries, leading to extravasation of red blood cells and alveolar hemorrhage. The red blood cells are eventually phagocytosed by macrophages, and the iron from hemoglobin is converted to hemosiderin.
Prussian blue stain detects ferric iron stores (eg, ferritin and hemosiderin). In the Prussian blue reaction, colorless potassium ferrocyanide is converted by iron to blue-black ferric ferrocyanide. Macrophages containing golden-brown cytoplasmic granules that turn blue with Prussian blue staining represent hemosiderin-laden macrophages (siderophages). These cells may be found in any tissue where macrophages encounter extravasated red blood cells; in the alveolar parenchyma, they are often called "heart failure cells."
(Choice A) Airway hyperreactivity occurs in asthma or chronic obstructive pulmonary disease, neither of which is associated with hemosiderin-laden macrophages.
(Choice B) Coal worker's pneumoconiosis results from chronic inhalation of coal dust and is associated with alveolar macrophages containing black intracytoplasmic aggregates, so-called carbon-laden macrophages. These carbon aggregates do not stain blue with Prussian blue staining.
(Choice C) A number of infectious organisms (eg, Mycobacterium tuberculosis, Histoplasma capsulatum) can survive within macrophages and produce a granulomatous response in the lungs; however, these organisms are typically visualized using other special staining methods (eg, acid-fast staining) and would not stain blue with Prussian blue staining.
(Choices E and F) Pulmonary arterial hypertension (primary pulmonary hypertension) and pulmonary thromboembolism both involve an elevation in pulmonary arterial pressure; however, pulmonary edema with extravasation of red blood cells does not occur as pulmonary capillary and pulmonary venous pressures are not elevated.
Educational objective:
Alveolar hemosiderin-laden macrophages indicate alveolar hemorrhage. They most commonly result from chronic elevation of pulmonary capillary hydrostatic pressure in the setting of left-sided heart failure.