Langerhans Cell Histiocytosis (LCH) Is Characterized by a Distinct Cytoplasmic HLA-DR Staining Pattern Consistent with a Trafficking Pathway Defect
Lucas Redd, Monika Schmelz, Lisa Rimsza. University of Arizona, Tucson, AZ
Background: LCH is a clonal proliferation of antigen presenting Langerhans cells most commonly occurring in children in bone and soft tissue locations. The neoplastic cells characteristically express CD1a, S100, CD45, and sometimes CD68. However, exceptions to this immunophenotype are found. Major Histocompatibility Class II (MHCII) antigens are characteristically present on antigen presenting cells of the immune system and are reportedly expressed in LCH. In antigen presenting cells, antigen loading occurs in the MIIC lysozomal compartment of the endocytic pathway followed by transport of the MHCII-antigen complex to the cell surface. The pattern of MHCII staining in LCH is not previously described. We hypothesized that MHCII molecules would be present on the cell surface of LCH cells and might serve as an additional diagnostic marker.
Design: We searched for cases between 1980-2012 with LCH and for normal tissues known to contain Langerhans or histiocytic cell populations and which had sufficient material remaining in for additional IHC. Using an established clinical protocol, we performed IHC for the representative MHCII isoform, HLA-DR. Cases were reviewed for staining pattern (cell surface, cytoplasmic granular, or cytoplasmic globules) and intensity of staining (0 to 3+).
Results: Fourteen (14) cases of LCH were identified and stained along with 1 each of normal tonsil, lymph node, spleen, bone marrow, thymus, lung, skin, and liver. The pattern of staining was markedly different between the cell populations. Strong HLA-DR cell surface expression was seen on benign B cells, a subset of T cells, interdigitating reticulum cells, and pulmonary macrophages. A granular cytoplasmic staining pattern (without surface) was seen in benign Langerhans cells in the skin and histiocytic populations (spleen, lymph node, BM, lung, liver, thymus). Strikingly, 14 of 14 LCH cases demonstrated a strong cytoplasmic granular and globular staining pattern with no surface staining, a pattern not seen in any of the benign populations.
Conclusions: This is the first report describing a distinct coarsely granular and/or globular staining pattern of HLA-DR in LCH. The cytoplasmic accumulation of the protein is compatible with recent data indicating a possible defect in the MHCII trafficking pathway in LCH. The distinct staining pattern may be a useful tool for diagnosis.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 230, Monday Morning