Letterer-Siwe disease: immunohistochemical evidence for a proliferative disorder involving immature cells of Langerhans lineage.

The morphological, ultrastructural and immunophenotypic properties of Histiocytosis-X (H-X) cells were investigated in a lymph node involved by Letterer-Siwe (L-S) disease. H-X cells were T6+ (CD1a), S-100+, T4+ (CD4) and HLA-DR+; in addition they were consistently T11+ (CD2) and were stained by antibodies directed against receptors for transferrin (T9), C3bi (OKM-1/CD11b), IgG-Fc (Leu-11/CD16) and Interleukin-2 (IL-2R/CD25). On immunostained cytosmears, T6+ cells were highly polymorphic and a prominent fraction (45%) showed immature morphology, characterized by lymphoid appearance. Cells expressing macrophage markers (ANAE, AACT, Leu-M3/CD14, PAM-1) were 10-fold fewer than T6+ cells and did not show a lymphoid morphology. At TEM level, H-X cells were characterized by poor content of LC granules and by the presence of myelin-like laminated bodies and of lysosome-like dense bodies. The immunophenotypic properties of H-X cells were compared to those of epidermal Langerhans cells (LCs) and of LCs present in lymph nodes of three cases of dermatophatic lymphadenitis. Epidermal LCs were T6+/HLA-DR+, and sometimes faintly T4+. Lymph node LCs were T6+, S-100+, T4+, HLA-DR+, and showed the same variety of surface receptors detected in H-X cells; furthermore, in a case with massive infiltration of the paracortex by T6+ cells, lymph node LCs were faintly T11+ and some of the T6+ cells had lymphoid aspect. Our findings suggest that the H-X cell population of L-S disease is not homogeneous, but is composed of discrete cell subsets with distinctive antigenic and morphological traits closely resembling those of cells of LC lineage at different maturational stages.