Lymphohistiocytosis: a multi-factorial syndrome of macrophagic activation clinico-pathological study of 38 cases.

Lymphohistiocytosis (LH) is defined by a widespread infiltrate of non-malignant lymphocytes and macrophages, involving principally the liver, spleen and central nervous system and associated with a severe lymphoid atrophy. For this histological study, 38 juvenile cases of LH were selected and reviewed. Morphological and histochemical studies revealed that the macrophages were activated. They appeared to be OKM1, OKT9 and HLA Dr positive and showed a patent or occult erythro and thrombocytophagocytosis. Comparatively, most of the lymphoid cells did not bear any immunoglobulin and did not label with a wide panel of monoclonal antibodies including T3, T4, T6, T8, T11. The review of the clinical and biological data of these 38 cases suggests that LH does not represent a single entity but can be regarded as a non-specific response to various causes. Three different conditions associated with LH can be isolated. The first group consists of patients in whom the disease is characterized by an early onset, high familial incidence and an inevitably fatal course. This category contains the largest number of cases (29 out of 38) and corresponds to the classic description of Familial Erythrophagocytic Reticulosis by Farquhar and Claireaux. The second group includes mainly male patients and children over 2 years old. Inheritance is not a predominant feature. The course of the disease is comparatively long. A viral infection was present in three of the seven cases. This category shares many of the clinico-pathological features of the Virus Hemophagocytic Syndrome and is presumably related to a chronic and latent viral infection. A third group can be identified on the basis of the presence of pigmentation abnormalities and immunodeficiency disorders probably associated with cytoskeletal abnormalities. This group includes Chediak-Higashi disease and Griscelli's disease. The fact that some genetic factors and immunodeficiency disorders are present in these three groups is probably significant and suggests that LH is a condition brought about by multiple factors--of which the common denominator is an apparent activation of the Mononuclear Phagocytic System.