LANGERHANS CELLS IN LANGERHANS CELL GRANULOMATOSIS ARE NOT ACTIVELY PROLIFERATING CELLS

Pulmonary Langerhans cell granulomatosis (LCG), also called histiocyto sis X, is a disorder of unknown etiology characterized by the presence of destructive granulomas containing numerous Langerhans cells (LCs). The process may be localized or multifocal, and it remains unclear wh ether the same pathogenic mechanism is involved in all forms of the di sease. It is often assumed that the massive accumulation of LCs at the sites of the lesions results from the abnormal proliferation of these cells, although it has been suggested that LCG in adults, at least in the lung, could be a reactive disorder initiated by activated LCs. Li ttle is known, however, concerning the mechanisms responsible for the accumulation of large numbers of LCs in the course of the disease, and the relative contribution of recruitment and local proliferation of t hese cells remains to be established. To investigate this question, th e proportion of replicating LCs was evaluated in biopsied granulomas f rom patients with localized or diffuse form of LCG by means of several histopathological techniques currently used in assessment of cell pro liferation. The findings demonstrate that, except for proliferating ce ll nuclear antigen (PCNA), all parameters measured are low in all form s of the disease. They are similar to those of renewing epithelial cel ls and clearly less than those of neoplastic cells. These data strongl y suggest that LCs in LCG granulomas are not a rapidly dividing cell p opulation and that local LC replication makes only a minimal contribut ion to granuloma maintenance. Caution appears to be necessary in the u se of PCNA as a marker of growth fraction.