Lymphadenitis caused by infection with vaccinia virus.

Postvaccinial lymphadenitis, smallpox vaccination adenitis.

Vaccinia virus infections usually do not occur naturally, being generally induced as vaccination against smallpox infection (1). Vaccinia is a poxvirus, considerably less virulent and with a broader host range than smallpox (2). The two DNA poxviruses are antigenically similar, so vaccinia virus is used to vaccinate against smallpox virus. From 1 to 3 weeks after the administration of vaccinia virus, a regional lymphadenopathy may develop in lymph nodes draining the vaccination site. The most common locations are the supraclavicular, cervical, and axillary lymph nodes. Lymphadenitis occurs in response to the vaccinia virus, usually present in the affected lymph nodes. Vaccinia lymphadenitis was experimentally reproduced in monkeys and rabbits (3). Eight days after the injection, the regional lymph nodes were diffusely hyperplastic and showed a typically mottled appearance, whereas at 15 days, the changes in the lymph nodes were characterized by follicular hyperplasia. Vaccinia virus was detected in the lymph nodes of monkeys at 8 and 10 days, and the maximal antibody response was reached at 15 days (3,4,5). Postvaccinial lymphadenitis is rarely seen nowadays because vaccination against smallpox is no longer required for travel to most parts of the world (6).

The morphologic changes may be of variable intensity and are generally similar to those produced by infection with other viruses, notably herpesvirus, measles virus, and other unidentified viral agents (5). The basic architecture of the lymph nodes is preserved, although marked hyperplasia is present with a follicular, diffuse, or combined follicular and diffuse patterns (4,5,6,7,8) (Fig. 13.1). The characteristically mottled (moth-eaten) appearance is caused by a marked proliferation of immunoblasts, which are scattered throughout the lymph node parenchyma (4). Intermingled with these cells in the parafollicular areas are mature lymphocytes, plasma cells, eosinophils, and mast cells. Proliferating vessels and distended sinuses filled with immunoblasts and plasma cells floating in abundant proteinaceous fluid are other features. Immunoblasts, which represent the predominant cell type, are two to three times larger than mature lymphocytes and have large nuclei with thick nuclear membranes, one to three prominent nucleoli, and frequent mitoses. The immunoblasts in mitosis are more numerous in the first 10 days after vaccination, whereas plasma cells become more common after the first 10 days (4). Not infrequently, very large immunoblasts with bizarre, multilobate nuclei and prominent nucleoli are present (9). Some of these unusual immunoblasts that are seen occasionally in other viral lymphadenitides closely resemble “popcorn cells,” mononuclear Hodgkin cells, or multilobated Reed-Sternberg cells and may lead to an erroneous diagnosis of Hodgkin disease.