LANGERHANS CELL (EOSINOPHILIC) GRANULOMATOSIS - A CLINICOPATHOLOGICALSTUDY ENCOMPASSING 50 YEARS

We summarize our experience with 238 cases of Langerhans cell granulom atosis (LCG), 198 of whom were followed for a median period of 10.5 ye ars. Our patients did well unless overtreated, and no deaths were attr ibuted to the disorder itself. The disease may appear in unifocal or m ultifocal form, and treatment is based on this fact. Virtually all pat ients recovered completely except for occasional residual orthopedic p roblems or residual diabetes insipidus. Several of the patients underw ent subsequent pregnancies without difficulty. The granulomas primaril y occur in bone, but lung, skin, and lymph nodal involvement is not un common. Involvement of thyroid, thymus, and other sites is rare. The h allmark of the disease is the accumulation of Langerhans cells (LCs). We review the pathology of LCG by histology, electron microscopy, and immunolabeling. LCs originally were identified in squamous epithelium, but these cells are part of the widespread system of dendritic cells. The latter cells, which arise from CD34+ progenitors, are specialized and efficient antigen-presenting cells for T-cell-mediated immunity. In LCG, however, the major associated cells are not T cells, but matur e eosinophils: hence the original name eosinophilic granuloma. Confusi on about terminology has been based upon the scanty and rather crude p athology reports in the original literature. The term histiocytosis X was meant to cover a spectrum of three diseases-eosinophilic granuloma , Hand-Schuller-Christian disease (HSC), and Letterer-Siwe disease (LS )-but HSC and LS have no basis in pathology and hence the terms are me aningless. The term HSC has become a synonym for multifocal eosinophil ic granuloma (LCG). The term LS has been used in reporting a number of benign, malignant, or unknown conditions. We prefer the term LCG to a void confusion with the term histiocytosis X because there is evidence that the LC is not a member of the mononuclear phagocyte system and h ence not a tissue macrophage, and because the use of the term ''histio cyte'' has become a convenience in much of the literature when reporti ng incompletely understood diseases.