Immunohistochemical comparison of cutaneous histiocytoses and related skin disorders: Diagnostic and histogenetic relevance of MS‐1 high molecular weight protein expression

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Abstract
Twenty‐nine cases of Langerhans cell histiocytosis (LCH), non‐Langerhans cell histiocytoses (N‐LCH), noninfectious granulomas, and fibroblast‐related lesions were examined with a panel of monoclonal and polyclonal antibodies on freshly frozen tissue sections to characterize the macrophage phenotype of N‐LCH syndromes. MS‐1 high molecular weight extracellular protein, specific for sinusoidal endothelial cells and dendritic perivascular macrophages in normal human organs, was expressed by N‐LCH cells but was not found in LCH cells, epithelioid cells in sarcoidosis, or palisading histiocytes in granuloma annulare. The subcellular location of MS‐1 protein, i.e., cytoplasmic vs. peripheral/extracellular, allowed discrimination of small and large (foamy or multinucleated) N‐LCH cells. MS‐1‐positive cells, which were found intermingled in cellular dermatofibromas but not in fibrous dermatofibromas, differed from MS‐1‐positive N‐LCH cells by their dendritic morphology, and thus rather resembled their normal dermal counterparts. A preserved functional relationship of these two MS‐1‐positive cell types was indicated by the fact that N‐LCH and cellular dermatofibromas were the only lesions found to be highly vascularized. As expected, CD1a showed high specificity for LCH, while CD34 was predominantly expressed by fibroblast‐related lesions; in cellular dermatofibromas, CD34 and MS‐1 expression partially overlapped. The other antigens tested showed non‐specific or overlapping patterns of expression. In conclusion, assessment of MS‐1 protein expression (in addition to assessment of CD1a and CD34) promises to be of diagnostic value in the discrimination of N‐LCH from related skin disorders, and it may indicate a common differentiative pathway for most N‐LCH disease entities.