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

Abstract

Objectives 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 MHC II expression in LCH is not well characterized. Methods The cellular localization of MHCII was determined using immunohistochemisty (IHC). Staining pattern for the representative MHCII molecule, HLA-DR, (cell surface, cytoplasmic granular, or cytoplasmic globular) and intensity (0 to 3+) were recorded for normal tissues and 44 LCH samples along with available clinicopathologic features. Results were confirmed with a different antibody to confirm the appearance. Results In the normal tissue survey, strong HLA-DR cell surface expression was present on APCs, benign B cells, some T cells, and pulmonary macrophages. 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. Conclusion 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.

Ovol1/2 loss‐induced epidermal defects elicit skin immune activation and alter global metabolism

“…Furthermore, flow cytometry revealed significantly higher mean fluorescent intensity of MHC II on LCs from iDKO epidermis compared with control counterparts, while relative abundance of LCs and DETCs remained similar (Figs 4C and D, and EV3A–C). Taken together, these data show that LCs in iDKO epidermis are in a preciously “activated” state (Nishibu et al , 2006; Kubo et al , 2009; Van den Bossche & Van Ginderachter, 2013; Redd et al , 2016; Yan et al , 2020; Yang et al , 2021).…”

Cutaneous Melanomas: A Single Center Experience on the Usage of Immunohistochemistry Applied for the Diagnosis

“…S100 is probably the most historically known and commonly used melanocytic differentiation marker in surgical pathology laboratories, with it being expressed in almost all cN and cM (as well as desmoplastic cM) [ 17 , 18 , 19 , 20 ]. Its sensitivity ranges between 93% and 100% in the published series, with a characteristic staining pattern in both the nucleus and cell cytoplasm; however, S100 is not highly specific, with it also being expressed by several soft tissue tumors (nerve sheath tumors, adipocytic tumors, chondroid tumors, notochordal tumors, and many others), hematopoietic disorders (Langerhans cell histiocytosis), and others tumors (glial tumors, sex cord-stromal tumors, myoepithelial carcinoma, and other salivary gland tumors) [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. For this reason, we always recommend using S100 in conjunction with other melanocytic (HMB-45 and MART-1) and case-by-case selected immunohistochemical markers, in specific diagnostic settings (metastasis of unknown primary cutaneous tumors with undifferentiated morphology).…”

Langerhans cell histiocytosis: A malignant myeloid neoplasm or disorder of immune regulation?

“…Langerhans cell histiocytosis cells make up 4–70 per cent of cells within lesions. Although they share common features with epidermal Langerhans cells and activated Langerhans cells, they differ by the low cell‐surface expression and intracytoplasmic localisation of HLA‐DR, 19,20 and their inability to respond to allogeneic T‐cell stimulation 21 . Additionally, intralesional LCH cells have recently been shown to be heterogeneous at the cellular, transcriptomic and epigenomic level, with a shared developmental hierarchy across all lesions studied 22 .…”

“…T cells are involved in immune surveillance, and it is known that LCH cells have low expression of HLA‐DR, CD83, CD86 and CD208, which play an important role in antigen‐dependent T‐cell activation. 19 , 20 An interesting clinical observation is the regression of LCH lesions following biopsy or injection of low‐dose steroids into the lesion, indicating that the possible disruption of the LCH microenvironment leads to immune responses that lead to resolution of the lesion. LCH lesions have been shown to have high numbers of Foxp3 Tregs, which are a regulatory T‐cell subset that expresses the forkhead box P3 transcription factor.…”