Cryptococcus Lymphadenitis
Definition
Lymphadenitis caused by infection with Cryptococcus neoformans.
Epidemiology
Cryptococcus neoformans has worldwide distribution. It is found in aged pigeon feces and bird nests, where it remains viable for >2 years. Transmission is by aerosols via the pulmonary route, but not from person to person. Infection by transplanted organs is also possible (1). Cryptococcal disease was rare before the acquired immune deficiency syndrome (AIDS) epidemic. Today 7% to 15% of AIDS patients in the United States develop cryptococcal infections (1,2). In Africa, the infection rate average is 15% to 30%, and up to 88% in some areas such as Zimbabwe (1).
Etiology
Cryptococcus neoformans is a saprophytic, monomorphic fungus that forms yeasts but not hyphae. The yeasts are round, about 3 to 6 μm in diameter, refractile, and surrounded by a thick mucopolysaccharide capsule. Budding is more common in Cryptococcus organisms than in any other yeasts. Single or double buds with narrow bases form that detach easily, reproducing the mother cell. Rapidly growing organisms may form chains of budding cells resembling hyphae (3,4). They are easily isolated from clinical specimens, forming moist, mucoid white colonies on Sabouraud agar. The cell walls stain with Grocott methenamine silver (GMS) and characteristically with mucicarmine and periodic acid–Schiff (PAS) stains.
Pathogenesis
Cryptococcus neoformans is not highly pathogenic. The virulence factors are related to the capsule and include proteases, phospholipases, melanin, mannitol, and others, which interfere with phagocytosis and destruction of the organism (5). However, virulence plays a far lesser role than the immune status of the host (1). The infection is acquired by inhaling yeasts. In the lung, these generate a primary focus; lymphangitis and involvement of a regional lymph node follow, resulting in what is called a primary pulmonary-lymph node complex of cryptococcosis (6). In normal, immunocompetent persons, this remains clinically occult and eventually undergoes fibrosis. Immunodeficient persons may acquire a new aerogenous infection, or an old, occult lesion may be reactivated. The most severe infections occur in patients with deficient cellular immunity, particularly patients with AIDS, leukemias, lymphomas, and Hodgkin disease. Cytotoxic treatments, specifically fludarabine, favor the spread of cryptococcal infection (7,8,9).
Clinical Syndrome
Cryptococcosis is one of the few fungal infections that affects both immunocompetent and immunodeficient persons (10). It may cause an asymptomatic pulmonary infection, sometimes followed by meningitis, pneumonia, pulmonary nodules, or mass lesions (1). Generally, it starts as a primary pulmonary lymph node complex, which in immunocompetent persons becomes fibrosed and occult. In people susceptible to the infection because of diabetes, renal insufficiency, or corticosteroid therapy, cryptococcosis may become disseminated, with predominant organ localization, and involve the meninges and central nervous system (6,11,12). In AIDS, cryptococcosis may be the presenting manifestation or appear together with other opportunistic infections. The lymph nodes may be affected in relation to an occult focus of cryptococcosis or as part of the disseminated form (13). Involved lymph nodes show multiple nodular, confluent lesions that may be visible on radiologic examination (11). An unusual case of cryptococcal mesenteric lymphadenitis misdiagnosed as acute appendicitis in a child was reported (14).