Langerhans Cell Histocytosis
Langerhans Cell Histocytosis
Langerhans cell histiocytosis (LCH) is a clonal disorder believed to be derived from cells of the dendritic system. Fascin, a 55-kd actin-bundling protein, represents a highly selective marker for dendritic cells of lymphoid tissues and peripheral blood and is involved in the formation of dendritic processes in maturing epidermal Langerhans cells. Since lesional cells of LCH may represent Langerhans cells arrested at an early stage of activation, immunohistochemical expression of fascin in epidermal Langerhans cells and in the lesional cells of 34 cases of LCH was evaluated in paraffin sections using an immunoalkaline phosphatase technique. Though epidermal Langerhans cells were nonreactive for fascin, lesional cells in all LCH cases exhibited immunoreactivity for fascin, CD1a, and S-100 protein. Variation in staining intensity was observed in some cases, possibly reflecting differences in cell maturation or activation. Involved tissues included bone, soft tissue, lymph node, thyroid, orbit, and extradural cranial tissue. Immunoreactivity of lesional cells of LCH for fascin supports their derivation from cells of the dendritic system and represents another alteration in the phenotype of Langerhans cells that is associated with maturation, migration, culture, or clonal expansion.
Langerhans cell histiocytosis (LCH) is a unifocal or multifocal disorder characterized by a proliferation of distinctive cells with ovoid, reniform, grooved, or highly convoluted nuclei and pale eosinophilic cytoplasm. Bone is the most frequent site of disease, although skin, lymph node, lung, and other sites may be involved. The lesions contain varying proportions of Langerhans cells, macrophages, eosinophils, lymphocytes, giant cells, and, to a lesser extent, plasma cells and neutrophils. Currently, the term Langerhans cell histiocytosis is used to include a spectrum of disorders previously designated as eosinophilic granuloma, histiocytosis X, Hand-Schüller-Christian disease, and Letterer-Siwe disease. The most specific markers for the lesional cells of LCH are Birbeck granules, identified ultrastructurally, and CD1a glycoprotein, detected immunohistochemically. Although this process has been regarded as a reactive disorder of immune dysregulation, molecular genetic studies have demonstrated that all forms of LCH are clonal. However, based on long-term studies of large numbers of cases, some investigators still consider this lesion to be a disorder of altered immunity, analogous to sarcoidosis, and prefer the term Langerhans cell granulomatosis.
Langerhans cells (LCs), the hallmark of this disease, were first described in 1868 by the investigator whose name they now bear, using a gold chloride staining technique that identified a unique nonpigmented dendritic appearing cell in the epidermis. These cells also are found in lymph nodes and the thymus and in limited numbers in the oral mucosa, esophagus, main bronchi, and distal colon. LCs are believed to be bone marrow-derived from CD34+ precursor cells and to represent part of the dendritic cell system. These cells are potent antigen-presenting cells and, after antigenic stimulation, have the capacity to migrate from the epidermis via afferent lymphatics to the paracortical areas of lymph nodes, where they apparently complete the process of maturation to dendritic cells, including interdigitating reticulum cells. Functional as well as phenotypic and morphologic changes are coincident with this maturation process. LCs express Fc receptors and the nonpolymorphic class I molecule CD1a and ultrastructurally have cytoplasmic Birbeck granules. Following migration from skin, or in culture, these features are lost in association with up-regulation of major histocompatibility complex (MHC) class II and adhesion molecules. The lesional cells of LCH are reactive for a variety of antigens in paraffin sections, with CD1a and S-100 protein representing the most helpful markers. Immunohistochemical studies have demonstrated that dendritic cells in lymphoid tissues may be detected selectively with a monoclonal antibody to fascin, a 55-kd actin-bundling protein. Interdigitating reticulum cells in interfollicular T-cell zones exhibited the strongest reactivity, with weaker staining of follicular dendritic cells and nodal sinus lining cells. Histiocytes (eg, epithelioid, phagocytic) typically are nonreactive. Since LCs are regarded as part of the dendritic system, rather than of the mononuclear phagocytic system, we evaluated the immunohistochemical staining profile for fascin in epidermal LCs and in tissues involved by LCH. The results of these studies potentially may provide information related to the pathogenesis of this disorder and possibly provide another phenotypic marker for these unique lesional cells.
Langerhans cell histiocytosis (LCH) is a clonal disorder believed to be derived from cells of the dendritic system. Fascin, a 55-kd actin-bundling protein, represents a highly selective marker for dendritic cells of lymphoid tissues and peripheral blood and is involved in the formation of dendritic processes in maturing epidermal Langerhans cells. Since lesional cells of LCH may represent Langerhans cells arrested at an early stage of activation, immunohistochemical expression of fascin in epidermal Langerhans cells and in the lesional cells of 34 cases of LCH was evaluated in paraffin sections using an immunoalkaline phosphatase technique. Though epidermal Langerhans cells were nonreactive for fascin, lesional cells in all LCH cases exhibited immunoreactivity for fascin, CD1a, and S-100 protein. Variation in staining intensity was observed in some cases, possibly reflecting differences in cell maturation or activation. Involved tissues included bone, soft tissue, lymph node, thyroid, orbit, and extradural cranial tissue. Immunoreactivity of lesional cells of LCH for fascin supports their derivation from cells of the dendritic system and represents another alteration in the phenotype of Langerhans cells that is associated with maturation, migration, culture, or clonal expansion.
Langerhans cell histiocytosis (LCH) is a unifocal or multifocal disorder characterized by a proliferation of distinctive cells with ovoid, reniform, grooved, or highly convoluted nuclei and pale eosinophilic cytoplasm. Bone is the most frequent site of disease, although skin, lymph node, lung, and other sites may be involved. The lesions contain varying proportions of Langerhans cells, macrophages, eosinophils, lymphocytes, giant cells, and, to a lesser extent, plasma cells and neutrophils. Currently, the term Langerhans cell histiocytosis is used to include a spectrum of disorders previously designated as eosinophilic granuloma, histiocytosis X, Hand-Schüller-Christian disease, and Letterer-Siwe disease. The most specific markers for the lesional cells of LCH are Birbeck granules, identified ultrastructurally, and CD1a glycoprotein, detected immunohistochemically. Although this process has been regarded as a reactive disorder of immune dysregulation, molecular genetic studies have demonstrated that all forms of LCH are clonal. However, based on long-term studies of large numbers of cases, some investigators still consider this lesion to be a disorder of altered immunity, analogous to sarcoidosis, and prefer the term Langerhans cell granulomatosis.
Langerhans cells (LCs), the hallmark of this disease, were first described in 1868 by the investigator whose name they now bear, using a gold chloride staining technique that identified a unique nonpigmented dendritic appearing cell in the epidermis. These cells also are found in lymph nodes and the thymus and in limited numbers in the oral mucosa, esophagus, main bronchi, and distal colon. LCs are believed to be bone marrow-derived from CD34+ precursor cells and to represent part of the dendritic cell system. These cells are potent antigen-presenting cells and, after antigenic stimulation, have the capacity to migrate from the epidermis via afferent lymphatics to the paracortical areas of lymph nodes, where they apparently complete the process of maturation to dendritic cells, including interdigitating reticulum cells. Functional as well as phenotypic and morphologic changes are coincident with this maturation process. LCs express Fc receptors and the nonpolymorphic class I molecule CD1a and ultrastructurally have cytoplasmic Birbeck granules. Following migration from skin, or in culture, these features are lost in association with up-regulation of major histocompatibility complex (MHC) class II and adhesion molecules. The lesional cells of LCH are reactive for a variety of antigens in paraffin sections, with CD1a and S-100 protein representing the most helpful markers. Immunohistochemical studies have demonstrated that dendritic cells in lymphoid tissues may be detected selectively with a monoclonal antibody to fascin, a 55-kd actin-bundling protein. Interdigitating reticulum cells in interfollicular T-cell zones exhibited the strongest reactivity, with weaker staining of follicular dendritic cells and nodal sinus lining cells. Histiocytes (eg, epithelioid, phagocytic) typically are nonreactive. Since LCs are regarded as part of the dendritic system, rather than of the mononuclear phagocytic system, we evaluated the immunohistochemical staining profile for fascin in epidermal LCs and in tissues involved by LCH. The results of these studies potentially may provide information related to the pathogenesis of this disorder and possibly provide another phenotypic marker for these unique lesional cells.
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