The phenotypic spectrum of histiocytosis X cells

Proliferating cells in histiocytosis X (histiocytosis X cells) share many structural and immunophenotypic features with Langerhans cells, leading to the assumption that histiocytosis X represents a proliferative disorder of Langerhans cells. Because, depending on their state of activation and/or differentiation, Langerhans cells exhibit a varying immunophenotype, we investigated whether histiocytosis X cells display a similar phenotypic heterogeneity and, if so, whether the heterogenous biological behavior of histiocytosis X is reflected by differences in the immunophenotype of the proliferating cells. In 21 patients suffering from different clinical manifestations of histiocytosis X, proliferating cells uniformly expressed class I and II alloantigens, T200, CD1, CD4, and S100 protein. In 12 of 21 cases, histiocytosis X cells additionally exhibited immunocytochemically detectable amounts of C3b and C3bi receptors and certain monocyte/macrophage antigens (CDw14, Ki-M1, Ki-M6). This immunophenotypic heterogeneity of histiocytosis X cells could not be correlated with clinical course, prognosis, and final outcome of the disease in a given patient. The capacity of histiocytosis X cells to immunophenotypically mimic various states of Langerhans cell activation and/or differentiation, however, underscores the concept of histiocytosis X as a proliferative disorder of Langerhans cell origin.