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to 100 microns) with rounded to oblong shapes. The plane of sectioning may not always reveal
the intranuclear inclusion completely, so the finding of large cells alone should prompt a careful
search for diagnostic inclusions elsewhere. Vascular endothelium, epithelial surfaces, adrenal
medulla, and cortex near ependymal or meningeal surfaces of the brain are particularly good
places to look for inclusions.
The tissue responses to CMV are quite varied. Often when there are infrequent and/or
widely scattered inclusions, there is little appreciable inflammatory reaction accompanying the
inclusions. In these cases, the presence of CMV may not be associated with clinical disease. In
other cases, the cytomegalic cells are accompanied by the presence of small focal areas of
inflammation, hemorrhage, or necrosis. In a few cases, there are large numbers of inclusions and
the surrounding tissues are markedly inflamed, hemorrhagic, or necrotic. The inflammation can
range from clusters of small lymphocytes to mixed infiltrates with lymphocytes and neutrophils
to diffuse neutrophilic infiltrates. A granulomatous response is not seen and calcification does
not occur.[419] In persons starting antiretroviral therapy (ART) there can be an immune
restoration syndrome (IRD) marked by more florid inflammation, including an immune recovery
uveitis with CMV infection.[285]
Cytomegalovirus-infected cells must be distinguished from macrophages and ganglion
cells, which may also be large, have prominent nucleoli, and have basophilic stippling of the
cytoplasm. Nucleoli of such cells are smaller and basophilic stippling is finer than in
cytomegalic cells. Toxoplasma gondii pseudocysts have bradyzoites that resemble the basophilic
inclusions of CMV, but the pseudocyst wall is thicker than the CMV cell membrane and the
basophilic inclusions of CMV are coarser and more variable than bradyzoites. Both in situ
hybridization and immunoperoxidase methods are useful for detection of cytomegalovirus,
particularly when classic intranuclear inclusions are not present.[420]
Cytomegalovirus infection is the immediate cause of death in only 10% of AIDS cases
overall and in 20% of cases in which CMV infection is present at autopsy. Usually, CMV is an
indolent infection. Deaths from CMV infection result from pulmonary involvement in two thirds
of cases, central nervous system involvement in one fourth, and gastrointestinal tract
involvement in one eighth. Despite the high number of cases with adrenal involvement, death
from adrenal failure is rare.[419]
Ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl] guanine, abbreviated DHPG), the first
drug of choice, and Foscavir (foscarnet, trisodium phosphonoformate) have been used to treat
patients with CMV, particularly those with retinitis. The agent, valacyclovir, is an acyclovir
congener that is rapidly metabolized to acyclovir in vivo. Another agent requiring no
intracellular viral activation is cidofovir, a nucleoside analogue of cytosine with potent activity
against herpesviruses. Ganciclovir, foscarnet, or valacyclovir may provide symptomatic relief in
AIDS patients with CMV, and the infection is often slowed or tissue destruction diminished and
survival is increased. Prophylaxis with ganciclovir or cidofovir may be used in selected
patients. In treated patients who later die, residual CMV infection can usually be found at
autopsy in one or more organ sites.[208,419,208,421]