Stacey Mills_Histology for Pathologists_9781496398949

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CHAPTER 1:  Skin

The color of the skin is determined by the number and size of melanosomes present both in keratinocytes and melanocytes—and not by the number of melanocytes. The number of melanocytes decreases with age. As a result, the availability of melanin to keratinocytes diminishes, so the skin becomes lighter in color and the incidence of skin can- cer increases because of the lack of protection that melanin provides. Melanin is both argentaffin and argyrophilic. It can be recognized by Fontana–Masson silver stains. In addition, melanocytes and their dendritic processes are identified by the dopa reaction in histologic slides prepared from frozen sections and in paraffin-embedded sections with immuno- histochemical stains with S100 protein. The latter is highly sensitive but not specific for cells of melanocytic lineage. The S100 protein can be detected in various types of cells, such as Langerhans cells, Schwann cells, eccrine, and apocrine gland cells. Melanocytes can also be identified with monoclonal antibodies Melan-A/MART-1 (Melanoma Antigens Recog- nized by T cells-1), a melanocytic differentiation marker. The Melan-A/MART-1 antigen is expressed in normal melano- cytes, common nevi, Spitz nevi, and malignant melanoma. Under normal conditions, the melanoma-associated antigen HMB-45 does not react with adult melanocytes (54). It is expressed in embryonic melanocytes, hair bulb melanocytes and activated melanocytes (55). It is usually seen reacting with most melanoma cells, Spitz nevi, the junctional compo- nent of common nevi, and dysplastic nevi. An absence or significant decrease in the number of melanocytes is seen in vitiligo. In albinism, there is a defect in the synthesis of melanin, but the number of melanocytes is normal in a skin biopsy. Melanocytic hyperplasia is seen in lentigo, benign, and malignant melanocytic neoplasms, and as a reaction pattern in a variety of neoplastic and non- neoplastic conditions (e.g., dermatofibroma). In a freckle, there is an increase in pigment donation to adjacent kerati- nocytes rather than melanocytic hyperplasia. Langerhans Cells Langerhans cells (LCs), discovered by Paul Langerhans in 1868, are mobile, dendritic, antigen-presenting cells pres- ent in all stratified epithelium and predominantly in the mid to upper parts of the squamous layer. In H&E-stained sections, LCs can be suggested as they appear to lie within lacunae having darkly stained nuclei with indented, reni- form shape at high magnification (Fig. 1.10). As with mela- nocytes, their dendritic nature cannot be seen in routine sections. Langerhans cells can be recognized by histoen- zymatic stains for adenosine triphosphatase (ATPase); they can also be detected in formalin-fixed, paraffin-embedded tissue using immunoreactivity for S100 protein and, more specifically, the antibody to the CD1a antigen (Fig. 1.11). With histoenzymatic and immunohistochemical stains, the extensive dendritic nature of LCs becomes evident. By electron microscopy, LCs show no desmosomes, tonofilaments, or melanosomes. They contain small vesicles,

FIGURE 1.10  H&E section of possible Langerhans cells composed of elongated nuclei surrounded by a clear space in the mid epidermis.

multivesicular bodies, lysosomes, and the characteristic Birbeck granule (Fig. 1.12) (56), a rod-shaped organelle varying in size from 100 nm to 1 μ m (57). It has a centrally striated density and an occasional bulb at one end with a unique tennis-racket appearance. Langerhans cells are also present in epithelia, lymphoid organs, and dermis and are increased in the skin in a variety of inflammatory conditions, such as contact dermatitis, where they can be seen as min- ute nodular aggregates in the epidermis. Langerhans cell granulomatosis is a reactive lesion most commonly seen in bones but also appearing at other sites. Merkel Cells Merkel cells (MCs), first described by F.S. Merkel in 1875, are scattered and irregularly distributed in the basal cell layer in the epidermis. They may group together in clusters coupled with enlarged terminal sensory nerve fibers to form slowly adapting mechanoreceptors; within the epidermis, they mediate tactile sensation (58–60). They are located in higher concentration in the glabrous skin of the digits, lips, and oral cavity, in the outer root sheath of hair follicles (61), and in the tactile hair disks (62).

FIGURE 1.11  CD1a-specific reaction of Langerhans cells. Note the dendritic processes. Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this content is prohibited.

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