It is unclear how closely related the two types are. It is possible that they are different forms of the same disease. Malignant histiocytosis is the more aggressive form and usually leads to death in a matter of weeks. It frequently involves the spleen, liver, and lymph nodes. It can also invade other tissues including the lungs and skin.
Systemic histiocytosis can have episodes that come and go with varying severity.
It invades the skin and peripheral lymph nodes in almost every case but also involves other tissues particularly in later stages of the disease. The appearance of the histiocytes themselves also differs between the two forms. Malignant histiocytes are abnormal. Neither form of histiocytosis should not be confused with benign histiocytomas. Benign histiocytomas are common in dogs.