What does the X in histiocytosis X mean?

It expresses the common etiologic link among the three clinical forms of the disease: eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease. When Louis Lichtenstein coined the name histiocytosis X in 1953, he chose the X to represent the then-undetermined cause of the disorders. He wrote that the suffix X “has the advantage of brevity and, by implication, emphasizes the necessity for an intensive search for the etiologic agent.” We now know that the common link is a proliferation of dendritic cells that are ultrastructurally and immunologically similar to Langerhans cells. Indeed, they probably are Langerhans cells, as reflected in the current name for histiocytosis X—Langerhans cell histiocytosis. Much about the disorder is still unknown, so perhaps Langerhans cell histiocytosis deserves to keep an X-designation.

Lichtenstein L: Histiocytosis X, Arch Pathol 56:84–102, 1953.