Stacey Mills_Histology for Pathologists_9781496398949

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SECTION I : CutaneousTissue

trimester, the dermoepidermal junction with its compo- nents is ultrastructurally similar to that of mature skin (10). Thus, the characteristic neonatal epidermis is well devel- oped by the 4th month. Keratinocytes constitute 90% to 95% of the cells in the epidermis. The rest of the epidermal cells are nonkerati- nocytes, and they include melanocytes, Langerhans cells, and Merkel cells. The nonkeratinocytes are seen in the epidermis of 8- to 10-week-old embryos. The precursor cells of melanocytes migrate from the neural crest to the dermis and then to the epidermis, where they differentiate into melanocytes during the first 3 months of development. During this migration, melanocytes can reside in other organs and tissues. Ultrastructurally, recognizable melano- somes in melanocytes may be seen in the fetal epidermis at 8 to 10 weeks of gestational age (11). Langerhans cells are derived from the CD34 + hema- topoietic precursor cell of the bone marrow. The charac- teristic cytoplasmic marker, the Birbeck granule, is seen ultrastructurally in 10-week-old embryos (12). The expres- sion of a more characteristic immunohistochemical marker, CD1a, is completed by 12 to 13 weeks of estimated gesta- tional age (12,13). Merkel cells can also be seen in the epidermis of 8- to 10-week-old embryos. The origin of Merkel cells is debat- able. Some have suggested a neural crest derivation (14), whereas others suggest epidermal origin through a process of differentiation from neighboring keratinocytes (15,16,17). Merkel cells in the epidermis are initially numerous and later diminish with increasing gestational age (18). Dermis The dermis is derived from the primitive mesenchyme underlying the surface ectoderm. The papillary and reticu- lar dermis are recognized by 15 weeks of intrauterine life (19,20). As described by Breathnach (19), three types of cells are recognized in 6- to 14-week-old embryos. Type I cells are stellate-dendritic cells with long, slender processes. These are the most numerous primitive mesenchymal cells and probably give rise to the endothelial cells and the pericytes. Type II cells have less extensive cell pro- cesses; the nucleus is round and the cytoplasm contains large vacuoles. They are classified as phagocytic macro- phages of yolk-sac origin. Type III cells are round with little or no membrane extension, but they contain numer- ous vesicles, some with an internal content suggestive of granule secretory type of cells. These cells could be mela- noblasts on their way to the epidermis, or they could be precursors of mast cells; Schwann cells associated with neuroaxons, but lacking basal lamina, are also identified during this period. The type II mesenchymal cells are rarely seen after week 14 of development. However, another cell type with ultrastructure of histiocyte or macrophage is frequently

seen during this time. Well-formed mast cells are also seen in the dermis. In 14 to 21 weeks of development, fibroblasts are numer- ous and active. Fibroblasts are recognized as elongated spin- dle cells with abundant rough endoplasmic reticulum. They are the fundamental cells of the dermis and synthesize all types of fibers and ground substance (1). Type III collagen fibers are abundantly present in the matrix of fetus, whereas type I collagen fibers are more prominent in adult skin (20). Elastic fibers appear in the dermis after the collagen fiber during the 22nd week of gestational age; and, by week 32, a well-developed network of elastic fibers is formed in the dermis. Initially, the dermis is organized into somites, but soon this segmental organization ends and the dermis of the head and neck and extremities organizes into dermatomes along the segmental nerves that are being formed (21). From the 24th week to term, fat cells develop in the subcutaneous tissue from the primitive mesenchymal cells. Epithelial Skin Appendages Most epithelial cells of skin appendages derive from fol- licular epithelial stem cells localized in the basal layer of epidermis at the prominent bulge region of the develop- ing human fetal hair follicles. Furthermore, such multipo- tent stem cells may represent the ultimate epidermal stem cell (22). In 10-week-old embryos, mesenchymal cells of the developing dermis interact with epidermal basal cells. These epidermal cells grow both downward to the dermis and upward through the epidermis to form the opening of the hair canal. As the growing epithelial cells reach the subcutaneous fat, the lower portion becomes bulbous and partially encloses the mesenchymal cells descending with them to form the dermal papillae of the hair follicle, this structure plays an important role in the future processes of hair follicle regeneration (23). The descending epider- mal cells around the dermal papillae constitute the matrix cells from which the hair layers and inner root sheath will develop. The outer root sheath derives from downward growth of the epidermis. The first hairs appear by the end of the 3rd gestational month as lanugo hair around the eyebrow and the upper lip. The lanugo hair is shed around the time of birth. The developing hair follicle gives rise to the sebaceous and apocrine glands. The sebaceous glands originate as epithelial buds from the outer root sheath of the hair follicles and are developed at approximately the 13th to 15th gestational weeks (24). Differentiated sebaceous glands with a hair protruding through the skin surface are present at the 18th week of gestational age (25). They respond to maternal hormones and are well developed at the time of birth. The apocrine glands also develop as epithelial buds from the outer sheath of the hair follicles in 5- to 6-month- old fetuses (21) and continue into late embryonic life as long as new hair follicles develop.

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