Lymphadenitis caused by infection with cytomegalovirus (CMV).

CMV lymphadenitis.

Cytomegalovirus is a ubiquitous pathogenic agent with worldwide distribution. In the United States, complement-fixing antibodies to CMV are present in 44% to 53% of males over 15 years of age. In homosexual males between 18 and 29 years of age, the presence of anti-CMV antibodies has been reported to be as high as 92% (1).

Cytomegalovirus, the largest of human viruses, is a member of the family of herpesviruses and, as such, a DNA virus that replicates in the cell nucleus (2). It is characterized by its large size (110 to 130 nm in diameter) and is composed of a dense core, an icosahedral capsid, and a surrounding envelope with periodic short projections. Within a population of virions, many particles do not possess envelopes, and others have empty capsids without the internal DNA nucleoid (2,3).

Cytomegalovirus may be transmitted by blood transfusion and transplacental passage and also from person to person through saliva and respiratory secretions. In homosexual males, CMV-infected semen is the main route of transmission (1). In the population at large, CMV infection occurs in childhood and is accompanied by flulike symptoms. Subsequently, the infection becomes clinically occult, and the virus is undetectable by laboratory techniques because the viral genome has been integrated into the host genetic material of various cells. Thus, a latent infection may persist indefinitely and be reactivated under conditions of immune deficiency (4). In the peripheral blood, where atypical lymphocytes are present in up to 20% of cases, CMV has been identified in lymphocytes, particularly T cells, and other mononuclear cells (5). Endothelial cells in all the organs are preferential sites of CMV infection, and the reticular cells of hematolymphoid organs also appear to be a favorable location (6).

In immunocompetent adults, CMV infection, like infectious mononucleosis [an Epstein-Barr viral (EBV) infection] may take the form of an acute, usually benign syndrome of fever, malaise, night sweats, enlarged lymph nodes, and mild hepatitis (7). Transmitted to newborns, CMV infection may result in a severe and frequently lethal syndrome that affects the central nervous system (8). Far more often, CMV affects immunosuppressed persons, such as recipients of organ transplants, patients with neoplastic diseases who are receiving chemotherapy, and particularly people with AIDS, in which a latent infection is reactivated (8,9). In these patients, widespread CMV infection involves a variety of organs, including the regional lymph nodes. Disseminated CMV infection, used by the Centers for Disease Control and Prevention as one of the criteria for the diagnosis of AIDS, most often affects the adrenals, lungs, gastrointestinal tract, eyes, and central nervous system (6,10,11,12,13).

Lymph nodes in various locations may be involved during generalized infection with CMV, both in infants and adults. The lymph node changes are nonspecific and closely resemble those of EBV lymphadenitis. Moderate follicular hyperplasia, aggregates of monocytoid cells, and sheets of immunoblasts admixed with small lymphocytes and monocytoid cells efface the architecture and produce a diffuse paracortical immunoblastic hyperplasia resulting in a mottled appearance (Fig. 10.1). Occasionally, large, atypical lymphoid cells with round lobated nuclei and prominent nucleoli, resembling Hodgkin cells or Reed-Sternberg cells, may be seen (Fig. 10.2). The CMV-infected cells are increased in size (cytomegaly), and the markedly enlarged nuclei contain the characteristic “owl’s eye” viral inclusions (Fig. 10.3). These inclusion bodies, the largest produced by any virus in humans, are up to 15 μm in diameter, strongly acidophilic, and surrounded by a clear vacuolar space (2). Sometimes, minute strands of eosinophilic material are present within the halo. The nucleolus is persistent in CMV-infected cells, unlike the nucleolus in cells infected by other herpesviruses, and nucleolar persistence is a characteristic diagnostic feature (13). The cytoplasmic inclusions are less visible, smaller (2 to 4 μm in diameter), multiple (as many as 20 in a single cell), and basophilic (2). They contain DNA and polysaccharides and therefore stain with the Feulgen method and with periodic acid–Schiff stain (2). Immunohistochemical staining and in situ hybridization of lymph nodes for CMV show that not only the inclusion-containing cells but also numerous normal-looking cells are infected with the virus (8). Such cells are located mostly in the medulla and at the corticomedullary junction. Their mostly elongated appearance in one study led to the suggestion that the CMV-infected cells are not lymphocytes but reticular cells (8). An immunophenotypic study of a lymph node from a patient without immune compromise has shown that CMV infects only T cells, both CD4+ and CD8+ subsets, but not B cells (14). Thus, CMV infection suppresses T-cell proliferation and natural killer cell activity (5).