A tentative diagnosis of lymphoma was made, based on the gross findings. However, microscopic examination of lymph nodes (H&E, x 3.3) revealed lymphodepletion, with edema, reticulin fibrosis, and abundant yeast forms (H&E, x66) with prominent capsules. Similar yeast forms were also evident in the spleen, lungs, liver, bone marrow, brain, kidneys, and adrenal glands. A colloidal iron stain and methenamine silver stain (lung, x33) highlight the yeast, some of which demonstrate budding. These morphologic characteristics are diagnostic of infection with Cryptococcus neoformans.

Although the patient had no previous history of significant illness or immunosuppression, human immunodeficiency virus RNA was detected in lymph nodes by in situ hybridization (x 132, hematoxylin counterstain. Black silver grains denote a positive hybridization signal).

Cryptococcus neoformans is a yeast found in nature, most commonly associated with pigeon droppings. Infection is usually by inhalation of aerosolized organisms. Cryptococcal yeast forms vary from 2 - 15 mm in diameter, and are usually spherical. The thick capsule, which stains brightly with periodic acid-Schiff (PAS) stain in histologic sections and is highlighted by India ink staining of wet preparations, allows presumptive identification of Cryptoccus neoformans. A positive latex agglutination or ELISA test for specific Cryptcoccus polysaccharide surface antigens is diagnostic.