From Histiocytosis X to Langerhans Cell Histiocytosis: A Personal Account

It has always been the aim of pathologists to identify the nature of the stem cell of a given tumoral process and establish a classification on the firm basis of its histogenesis. Modern methods of investigation such as electron microscopy, cytochemistry, and tissue culture have greatly contributed to the identification of the origins of various types of cell proliferations and have provided invaluable data in the study of tumors of uncertain nature such as primitive neuroectodermal tumor (PNET), Ewing's sarcoma, granular cell tumors, and many others. The history of Langerhans cell histiocytosis (LCH) research represents a good and unexpected example of this technical approach. Because we have been implicated both in the initial phase of this investigation as well as in the postulation, dating back to 1973, that the stem cell of Histiocytosis X (HX) [1] could well be the clear, argyrophilic cell described in the epidermis by Paul Langerhans [2], we would like in this paper, in a somewhat more anecdotal manner than in previous publications [3], to describe the data and events, including our hesitations and uncertainties, that led us to propose this histogenesis. In the 1960s, HX was generally regarded as a generic entity, lumping together the various clinicopathologic conditions previously designated by the terms of Hand-Schiiller-Christian disease, Abt-Letterer-Siwe disease, and eosinophilic granuloma of bone. It should be remembered that this unifying concept was initially suggested and proposed by pediatric oncologists: A. Walgren in Sweden and S. Farber in the United States. This unifying view was not, at that time, widely accepted, especially by pediatricians. Nevertheless L. Lichtenstein, a bone pathologist, pointed out the morphologic similarities of the proliferating cells in these 3 conditions and thought that they could share a histiocytic origin. In 1953, he coined the term HX to designate this entity [4]. Because it provided a tumoral counterpart to the recently individualized reticuloendothelial system (RES) and emphasized the enigmatic X (as in the algebraic unknown factor) nature of this proliferation, this provocative name, despite

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