Electron Microscopy Identifies Virus in Cells Lifted from Microscopic Slides: A Useful Method for a Unique Circumstance

Abstract

Electron microscopy (EM) using a "lift technique" (EM-lift) of suspect cells has been used when a question of viral infection is raised by light microscopy and is not otherwise confirmed. We demonstrate how, in this unique circumstance, EM can complement or even supersede immunohistochemistry (IHC) and culture studies. Cases with suspected viral inclusions followed by EM-lift were collected over 25 years; hematoxylin and eosin, IHC, and culture findings were reviewed. Immunohistochemistry results were not available in 15 of the 30 samples found; tissue blocks were obtained in 6 of the samples, and additional IHC studies were performed. Nine cases had viral cultures. The usual clinical question was "rejection versus infection" in a transplant setting (56%). The gastrointestinal tract/liver was most frequently sampled (76%). The EM-lift technique confirmed virus in 18 cases, including adenovirus (58%), cytomegalovirus, herpes, papillomavirus, and parvovirus. Twenty-one cases had informative EM but IHC findings were positive in 8. Both EM-lift and IHC findings were positive in 5 cases and negative in 8 cases. All IHC-positive cases were positive by EM-lift. Of the 6 cases with new IHC, 2 negative cases stained with a newer antibody (EM-positive for adenovirus) and 4 remained negative. Nine had culture findings; 1 was positive, with positive EM-lift. Eight were culture-negative; 4 of these were EM-positive. We conclude that in clinical settings in which virus identification is critical and infection is not otherwise confirmed, the lift technique can be more sensitive than IHC (missed inclusions) and culture studies (often not done) or polymerase chain reaction test, which can be overly sensitive.