Mononucleosis, caused by the Epstein-Barr virus, can produce a very severe, reactive presentation. The vacuoles in both lymphocytes and monocytes are a striking feature, as is the deep blue cytoplasm in some lymphocytes with large shoots. The active cells are fragile and can easily be smudged. It can be tricky to distinguish lymphocytes from monocytes, due to their sometimes bizarre shapes.