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Because type II pneumocytes function as alveolar reserve cells, they proliferate after lung injury, such as pneumonia, sepsis, pulmonary embolus with infarction, chemotherapeutic drugs, radiation therapy, interstitial lung disease.

In cytologic smears they appear as single cells or clusters of cells with large nuclei, coarse chromatin and prominent nucleoli, with scant to abundant cytoplasm. These cells may resemble an adenocarcinoma when floridly hyperplastic, as in diffuse alveolar damage; it is therefore helpful the clinical history of respiratory distress. Type II pneumocytes are not present in BAL specimens more than 1 month after the onset of acute lung injury.