Langerhans cell histiocytosis in children

Forty children who had Langerhanscell histiocytosis were followed for an average of six years (range, excluding patients who died of the disease, two to fifteen years). The patients were divided into two diagnostic groups: those who had localized disease (involving one bone or more only) and those who had multifocal disease (an osseous lesion and a soft-tissue mass, a skin rash, diabetes insipidus, or generalized disease). Methods of treatment included curettage, bone-grafting, chemotherapy, local or systemic corticosteroids, and radiotherapy. Nineteen of the thirty patients who had localized disease had a complete response to the therapy, four had a partial response, and seven had no response. Twenty-one of these thirty patients had not had a recurrence by the time of the latest follow-up examination; nine had a local recurrence within four years after the initial therapy but had no additional recurrences after treatment of the local recurrence. No recurrence occurred more than four years after the time that the initial diagnosis had been made. Five of the ten patients who had multifocal disease had a complete response to the therapy, two had a partial response, and three had no response. Six patients had a recurrence; four did not. Two patients died of the disease. As a result of this study, we recommend the avoidance of intensive measures of treatment, if possible, and we advise long-term follow-up of these patients. Langerhans-cell histiocytosis 3. formerly known as histiocytosis X”, denotes an enigmatic group of disorders of unknown etiology. variable clinical forms, and uncertain outcome. Langenhans-cell histiocytosis is a non-neoplastic lesion characterized by infiltration of tissue by cells of the monocyte-macrophage lineage. The cytoplasm of these cells contains specific inclusion X bodies. identical to the Birbeck granules in a Langer*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study. t39, Avenue Georges Pompidou. 92300 Levallois-Perret. France. Please address requests for reprints to Dr. Sessa. lChildren’s Hospital. 11. all#{235}e du Morvan. 54511 Vandoeuvreles-Nancv C#{233}dex.France. hans cell, that are visible under an electron microscope and are characterized by positive immunostaining for 5-100 protein and OKT6 antigen’24. Multiple organ systems may be involved in this disorder, and the disease may appear in several forms, from the mildest (a solitary eosinophilic granuloma of bone) to the most severe (multiple granulomas of bone and soft tissue). The hallmark of Langerhans-cell histiocytosis in most patients (70 to 90 per cent in various series9’5243’37) is an osseous lesion. When an osseous lesion (or several) is the only manifestation, the disease is referred to as eosinophilic granuloma29. When the granulomas are more widespread. causing cranial lesions, diabetes insipidus. and exophthalmos. the disease is referred to as Hand-SchUller-Chnistian disease5. The disseminated form of Langerhans-cell histiocytosis is called Letterer-Siwe disease29. This last presentation is more commonly seen in infants and in children who are less than three years old, and it is characterized by wasting, hepatosplenomegaly. a skin rash, generalized multiplc lesions, and a poor prognosis’537. Among these three types, there are many intermediate forms and one form may change into another5’ 5. Lichtenstein29 first used the term histiocytosis X in 1953 for the three different forms, to indicate that the histiocytes were always present. although the etiology remained obscure. The principal difficulty in the establishment of a definite protocol for treatment is the absence of reliable prognostic criteria. despite attempts to score factors at the initial assessment2’. Lahey2’ described a young age at the onset of the disease; involvement of multiple organ systems; rapidity of progression of the disease; and, especially, dysfunction of the liver, respiratory. or hematopoietic systems as signs of a poor prognosis. Newton and Hamoudi3 accorded a prognostic value to histological findings: type I. or malignant histological findings. is characterized by a disordered histiocytic proliferation without a reactionary granuloma and has an unfavonable outcome; type II. or benign histological findings. is characterized by a granuloma in which histiocytes appear in syncytial sheets with indistinct cell margins and has a favorable prognosis. Lavin and Osband29 stated that the intensity and rapidity of the response to therapy are critical factors for a successful outcome. Sex. Osseous Site of Recurrence Additional Case Age Lesions Biopsy Treatment Response (Site/Time) Therapy Current Status (Yrs.) (Most) 1 F. 6 Parietal bone Observation 2 F. 14 Frontal bone Skull Curettage 3 M, 6 Occipital bone Skull Curettage 4 M. 8 Frontal bone Skull Observation 5 M, 7 Occipital bone Skull Observation 6 M. 5 Orbit Orbit Curettage 7 M.2 CS CS Curettage. graft. cast . Complete