Lymphadenitis caused by infection with the protozoan Toxoplasma gondii.

Piringer-Kuchinka lymphadenopathy.

Toxoplasmosis is a common parasitic disease worldwide. The infection, which is mostly asymptomatic, is prevalent in warm and humid climates, where almost all people have antibodies to Toxoplasma; it is infrequent in cold and dry areas (1,2). In the United States, toxoplasmosis is the most common parasitic infection. It is estimated that 50% of Americans have antibodies, indicative of chronic asymptomatic infection, and every year about 3,000 children are infected at birth (3). In France, 70% to 90% of persons >20 years have positive serologic findings (4). Toxoplasma gondii organisms infect a wide variety of mammals and birds, but the definitive host is the cat (3). Rodents may also serve as intermediate hosts, as in a reported case of Toxoplasma lymphadenitis transmitted to a patient by his pet rabbit (5).

The parasite has a complex life cycle. The cat is the definitive host for the sexual stage of reproduction, during which trophozoites multiply in the intestinal epithelium and produce oocysts that are eliminated in the stool. Human beings and other mammals, the intermediate hosts, are infected through the ingestion of oocysts from contaminated soil or infected, undercooked meat (2,3). More unusual modes of infection are transplacental transfer of T. gondii from mother to fetus and transmission of Toxoplasma organisms with a transplanted kidney to a susceptible immunodeficient recipient (6). In intermediate hosts, the ingested oocysts are disrupted by digestive enzymes and the trophozoites are released into the intestine, where they spread through lymphatics and blood vessels and are carried by macrophages into the internal organs (7). Within macrophages, particularly in immunodeficient hosts, the trophozoites multiply rapidly, forming large clusters of small (2 to 6 μm diameter), crescent-shaped entities called tachyzoites. In immunocompetent hosts, as immunity is established, the parasites are segregated in cysts partially synthesized by the host. Protected by the cyst walls, bradyzoites multiply slowly, as their name implies, and may persist for long periods of time. Thus, in humans, Toxoplasma organisms exist in two forms, tachyzoites in the circulation and bradyzoites within intracellular cysts; the third form, the oocyst, is found only in cats.

Toxoplasmosis may occur as one of three major clinical syndromes: Toxoplasma lymphadenitis in the general population, systemic toxoplasmosis in immune-deficient patients, and fetal toxoplasmosis transmitted by transplacental infection.

In immunologically compromised hosts, such as patients who have leukemia, lymphoma, or acquired immune deficiency syndrome (AIDS), or are receiving immunosuppressive therapy, T. gondii infection becomes acutely disseminated, usually progressing to involve the central nervous system (8,9,10,11,12,13,14). In a study of brain biopsy specimens in patients with AIDS, toxoplasmic encephalitis was the diagnosis in 71% of cases (13). When associated with severe immune deficiency, toxoplasmosis often results in death from myocarditis, pneumonitis, chorioretinitis, or encephalitis (15,16). Similar infections may occur in an immunosuppressed host when Toxoplasma organisms are inadvertently transmitted with a transplanted kidney (6). In patients with hematologic malignancies, toxoplasmosis has occurred particularly in those who underwent bone marrow
transplantation (17). Fetal toxoplasmosis, the result of congenital infection, occurs in 1 of every 1,000 live births in the United States. The chance of transmitting the infection transplacentally is greater during the last trimester; however, the damage to the fetus is greater when transmission occurs in early pregnancy (7). It is generally a serious systemic illness that produces symptomatic cerebral and ocular lesions. In affected children, the brain lesions are usually periventricular with characteristic focal calcifications.

In normal adults, the most common manifestation is a localized lymphadenopathy. It may be entirely asymptomatic or accompanied by mild, nonspecific symptoms such as fever and myalgia. Toxoplasma is considered to be the etiologic agent of 15% to 20% of all unexplained lymphadenopathies, particularly those involving cervical lymph nodes (3,18). In children, cervical lymphadenopathies are common, the acute forms caused by viral upper respiratory tract infections, streptococcal or staphylococcal infections, the subacute or chronic by toxoplasmosis, cat-scratch disease, and mycobacteria infections (19,20).

The posterior cervical lymph nodes are most commonly and characteristically involved (21). However, other cervical, supraclavicular, and occipital lymph nodes may be affected, such as an intramammary lymph node in a reported case in which fibroadenoma and lymphoma had been initially considered (22). Occasionally, generalized lymphadenopathy, sometimes accompanied by moderate hepatosplenomegaly, may occur (3,18). The lymph nodes may be tender or painless on palpation, and the enlargement may last from a few days to more than a year, usually resolving spontaneously in a matter of weeks. At palpation, the lymph node is firm but not rock hard, 0.5 to 3 cm in diameter, and not ulcerated (16).

The histologic criteria originally described by Piringer-Kuchinka and colleagues (23) and Saxen and colleagues (24) have been repeatedly confirmed (25,26), and it is generally accepted that Toxoplasma lymphadenitis can be diagnosed histologically and confirmed by serologic assays (25,26,27,28,29).

The lymph node architecture is altered by the lymphoid follicles, which are markedly hyperplastic, comprising reactive germinal centers; by numerous, widely scattered epithelioid cells; and by aggregates of monocytoid cells. The reactive follicles, clusters of epithelioid cells, and patches of monocytoid cells constitute a triad characteristic of Toxoplasma lymphadenitis (Fig. 29.1). The follicles are enlarged mainly by the intensely reactive germinal centers. These include increased numbers of centroblasts, many in mitosis, and macrophages containing nuclear debris (tingible bodies) (Fig. 29.2).

The monocytoid cells are assembled in islands and sheets around and within the nodal sinuses, sometimes adjacent to blood vessels (Fig. 29.3). They are large, flat cells with sharp, visible cell borders, clear cytoplasm, and relatively small, darkly stained nuclei (Fig. 29.4). Nucleoli are inconspicuous, and mitoses are absent (Fig. 29.5). These cells, described as monocytoid because of a morphologic resemblance, are in fact B cells expressing surface immunoglobulins and cytoplasmic B-cell markers (28,30) (Figs. 29.6 and 29.7). Although common in toxoplasmosis, they are not specific and can be seen in other lymphadenitides, notably in the acute stage of human immunodeficiency virus (HIV) infection (31).