In Reply.—Dr Green's letter raises a question that has been confusing in the medical literature. As noted by Dr Green, histiocytosis is associated with a variety of infectious and hemolytic states. However, in HMR, the histiocytes have cytologic atypia consistent with a malignant process. Although none of the seven cases of HMR that occurred after ALL reported in our article had serologic tests performed to rule out Epstein-Barr virus, cytomegalovirus, or toxoplasmosis, each case met the criteria of a malignant histiocytic proliferation.
Risdall et al1 emphasized that histiocyte proliferation with viral infection is benign. Cohen and colleagues2 linked HMR and Epstein-Barr virus infection without any qualifiers.
In discussing Dr Green's letter and questions with Karcher et al,3 who reported two cases of HMR occurring after ALL quoted in our article, Karcher et al3 emphasized that cytologically atypical histiocytes are required for a diagnosis of HMR,