Langerhans cell histiocytosis shows distinct cytoplasmic expression of major histocompatibility class II antigens

Langerhans cell histiocytosis (LCH) is a monoclonal proliferation of antigen presenting cells (APC). In benign APCs, antigen loading occurs in the major histocompatibility class II (MHCII)-lysosomal compartment of the endocytic pathway followed by transport to the cell surface upon antigen stimulation. The pattern of MHCII expression in LCH is not well characterized. The cellular localization of MHCII was determined using immunohistochemistry (IHC). Staining pattern for the representative MHCII molecule, HLA-DR, (cell surface, cytoplasmic granular, or cytoplasmic globular), and intensity (0 to 3+) was recorded for normal tissues and 44 LCH samples along with available clinicopathologic features. Results were confirmed with a different antibody to confirm the appearance. In the normal tissue survey, strong HLA-DR cell surface expression was present on APCs, benign B cells, and some T cells. A granular cytoplasmic staining pattern (without surface expression) was seen in benign Langerhans cells (LCs) in the skin and histiocytes. Strikingly, all 44 LCH samples demonstrated both cytoplasmic granular and an unusual “globular” staining pattern with no surface staining. This is the first report of a highly specific HLA-DR staining pattern in LCH detected by IHC. The cytoplasmic perinuclear globular localization of MHCII may possibly be useful in diagnostics and may result from an immature/antigen-naïve differentiation state of the neoplastic cell.