Pulmonary Eosinophilia
Philip T. Cagle, Timothy C. Allen, Mary Beth Beasley in Diagnostic Pulmonary Pathology, 2008
While the bronchiolocentric distribution and appearance of lesions at low power may suggest pulmonary Langerhans cell histiocytosis, Langerhans cells may be difficult to find, especially in older lesions. In problematic cases, their demonstration may require examination of multiple levels. Immunohistochemical staining for S100 and CD1a may also be helpful in confirming their identity (63–65). In addition to S100 and CD1a, langerin, a Langerhans cell-specific lectin that initiates Birbeck granule formation, has also been shown to be expressed preferentially in this disorder (66). Caution is necessary interpreting these stains, however, as other types of interstitial lung disease may show a mild increase in scattered Langerhans cells. Nonetheless, identification of significant aggregates of these cells is consistent with pulmonary Langerhans cell histiocytosis. In the past, electron microscopy was also helpful for demonstration of Birbeck granules but is usually not necessary in current samples (12, 62–65).
Immunology
M. Alan Menter, Caitriona Ryan in Psoriasis, 2017
Langerhans cells are a type of immature conventional DC that reside in the epidermis.7 They are actively phagocytic and contain large granules known as Birbeck granules. CD1a and langerin (CD207) are used as specific markers to distinguish Langerhans cells from other DC subsets. The main role of Langerhans cells is to take up and process antigens and migrate to local skin-draining lymph nodes where they present to antigen-specific T cells.2 However, the role of Langerhans cells in psoriasis immunopathogenesis is still unclear.3 Recently, attention has focused on the potential importance of Langerhans cells in uninvolved skin sites of psoriasis patients, and it has been demonstrated that Langerhans cell migration is impaired in early onset psoriasis (onset before 40 years of age).31,32 Also, the treatment with TNF-α inhibitors (adalimumab, etanercept) and anti-IL-12p40 antibody (ustekinumab) significantly restored epidermal Langerhans cell migration in uninvolved skin.33 Although the influence of impaired Langerhans cell mobilization on the pathogenesis of psoriasis is uncertain, the loss of Langerhans cell motility may have an impact on the ability of these cells to sense the local antigenic microenvironment and regulate cutaneous immune responses.
Pathology and Epidemiology
John T. Kemshead in Pediatric Tumors: Immunological and Molecular Markers, 2020
A diagnostic finding of great value in histiocytosis X however are the trilaminar and racquet-shaped Birbeck granules; indeed most would agree that the ultrastructural presence of these granules is pathognomonic of this group of disorders. Attempts have been made24 to correlate the presence of these structures with a histological subtype of the disease bearing a particularly good prognosis, and characterized by a mixed population of cells in the tumor infiltrate, including a high proportion of multinucleate giant cells. It is also probable that the identification of Birbeck granules ultrastructurally is at least as reliable, and probably more so, than the use of such immunohistological techniques as S-100 protein or histochemical methods as α-1 mannosidase.
A case of multisystem Langerhans cell histiocytosis presenting as central diabetes insipidus
Published in Journal of Community Hospital Internal Medicine Perspectives, 2019
P. Daniel Nicholas, Ian Garrahy
The label Langerhans cell histiocytosis (LCH) derived from histologic studies of biopsied lesions. It was noted that the malignant histiocytes contain Birbeck granules and the protein langerin (CD207), both associated with Langerhans cells (LC), and it was postulated that the epidermal LC underwent a malignant transformation in LCH. However, a subsequent cytologic study illustrated that the dendritic cells that form LCH lesions are actually precursors from the bone marrow that travel to lesion sites and differentiate into langerin+ cells, a theory termed the ‘Misguided Myeloid Dendritic Cell Precursor’ model [1]. Animal studies confirmed the identity of LCH as a myeloid neoplasia by demonstrating that inducing a point mutation implicated in the disease’s pathogenesis, BRAF-V600E, in bone marrow dendritic cell progenitors resulted in a phenotype mimicking high-risk LCH in humans, while inducing the same mutation in differentiated dendritic cells resulted in a low-risk LCH phenotype [6].
Dendritic Cells Currently under the Spotlight; Classification and Subset Based upon New Markers
Published in Immunological Investigations, 2021
Samaneh Soltani, Mahdi Mahmoudi, Elham Farhadi
Professional APCs in the skin include DCs, monocytes, and macrophages. LCs are antigen-presenting DCs that populates in basal/suprabasal layers of stratified epithelial tissues such as epidermis, urogenital/oral mucosae, and cornea (Strobl et al. 2019). LCs are stable self-renewing cells that are not dependent on CD34+ precursors in the absence of inflammation (Chopin et al. 2013). LCs are considered as the first immunological barrier in the epidermis, which perpetually arises from resident radioresistant precursor cells in steady-state and comprises about 1–3% of all nucleated cells in the human epidermis (Said and Weindl 2015). LCs present a range of TLRs, including TLR 1, 2, 3, 6, 10 (Sehgal et al. 2014), high amount of the CLR, CD207, CD1a, and the invariant MHC class I molecule. In addition, they express HLA-DR, ATPase (CD39), FcεR1 (The high-affinity IgE receptor), and EpCAM (Collin and Bigley 2018; Sparber 2014). E-Cadherin, EpCAM (TROP1), TROP2, AXL, and tight junction proteins, including claudin, occluding, and ZO-1, are involved in tight accretion of LCs in the epithelium (Bauer et al. 2012; Hieronymus et al. 2015). ID2 and Runt-related transcription factor 3 (RUNX3) are the differential TFs, which recognized in LC cells (Collin and Bigley 2018). The expression of CD207 is associated with intra-cytoplasmic vesicles and Birbeck granules (BG) that are two features by which LCs readily distinguished from other DCs (Valladeau et al. 2000). In the human epidermis LCs are the main hematopoietic cells while γδ T cells are central in the murine epidermis (Merad et al. 2013).
Successful cochlear implantation in Langerhans cell histiocytosis: A rare case
Published in Cochlear Implants International, 2018
Gaurav Gupta, Avani Jain, Mohnish Grover
The diagnostic laboratory work up is particularly important in multisystem disease and should include complete blood count, coagulation profile, and liver function tests. Once a clinical diagnosis of LCH is suspected, a radiographic skeletal survey or bone scan is required for detection of bony lesions (Azouz et al., 2005). Typically, osseous involvement is represented by diffuse lytic lesions with well-defined soft-tissue margins without sclerotic margins (Bayazit et al., 2001). For temporal bone involvement, HRCT is the preferred imaging modality both to assess the extent of involvement and for monitoring disease activity and response to treatment. In this case, lytic lesions were confined to the temporal bones bilaterally and the rest of the bone scan was normal. The diagnosis of LCH is established by tissue biopsy, on the basis of pathological and immunohistochemical features. On light microscopy, a reactive infiltration of eosinophils, granulocytes, and immature Langerhans cells can be seen. The presence of Birbeck granules on electron microscopy and immunocytochemical features like CD1a antigen and S100 positivity are specific for diagnosis (Bayazit et al., 2001; Martini et al., 2000).
Related Knowledge Centers
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- Langerhans Cell
- Langerhans Cell Histiocytosis
- Histiocytosis
- Langerin
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