Melanocytes, Langherhans, and Merkel CellsMelanocyte- Pigment-producing dendritic cell derived from neural crest; found in skin, hair, uveal tract of eye (choroid, iris, ciliary body), leptomeninges, and inner ear (striae vascularis of cochlea)
- Survival/migration during embryogenesis depends on specific interactions such as c-kit activation contributing to migration and development of melanocytes and melanoblasts
- Resides in basal layer with ratio of one melanocyte to ten basal keratinocytes (do not confuse with epidermal melanin unit where one melanocyte in contact with 36 keratinocytes)
- Melanocytes do not form junctions with keratinocytes (hence, artifactual halo on H&E)
- Function: production of melanin pigment with subsequent transfer to keratinocytes, absorption of UV radiation, and protection from UV-induced mutations
- Melanin: synthesized in melanosome (specialized type of lysosome) and passes through series of stages (I–IV) before melanosome transferred to keratinocyte via phagocytosis of melanocyte tips (apocopation); melanin precursors acted upon by copper-dependent enzyme tyrosinase; two types of pigment (Figure 1.4)
| | Figure 1.4 Melanin biosynthetic pathway |
- Eumelanin: brown or black in color, eumelanosome (oval-shaped, longitudinally oriented with lamellar internal structure)
- Melanin stimulated by melanocyte-stimulating hormone (MSH), which is derived from larger precursor propiomelanocortin (POMC); POMC also a precursor for ACTH, which is why ↑ hyperpigmentation seen in Addison’s disease
- Melanocortin-1 receptor (MC1R) controls which type of melanin is produced by melanocytes; loss of function in MC1R results in ↑ pheomelanin (red hair) and ↓ eumelanin; thus, fair skin without the more protective pigment and more prone to damage from UV radiation with subsequent ↑ risk for melanoma
- Hair melanocytes: one melanocyte to five keratinocytes; graying caused by gradual decrease in number of follicular melanocytes
- Chronic sun exposure results in melanocytes creating larger melanosomes
- Racial differences NOT due to differences in number of melanocytes, but rather the size, distribution, and number of melanosomes (all races have SAME melanocyte density)
- Dark-skinned: larger melanosomes, ↑ melanization, ↓ melanosome degradation, and melanosomes transferred as individual organelles
- Light-skinned: smaller melanosomes and transferred as membrane-bound clusters (with 3–6 melanosomes)
| | | | | | Be able to identify EM image of Langerhans cell | | | | | |
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- Bone marrow-derived dendritic cell with monocyte-macrophage lineage found in stratum spinosum; constitutes 3–5% of cells of epidermis; contains actin and vimentin
- Critical in recognizing and presenting foreign antigens to specific T lymphocytes
- Connected to keratinocytes via E-cadherin receptors
- On EM, Langherhans cell with folded nucleus and distinct intracytoplasmic organelles (Birbeck granules: rod-shaped or tennis racquet-shaped with striated appearance)
- Exposure to UV radiation causes depletion of LC and decreases ability to present antigen
| | | | | | Langerhans cell histiocytosis:
Letterer-Siwe – acute disseminated
Eosinophilic granuloma – bone (cranium)
Hand-Schuller-Christian – diabetes insipidus, exophthalmos, bone lesions
Hashimoto-Pritzker – self-healing | | | | | |
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Merkel Cell- Ectoderm-derived cell (less likely neural crest-derived) functioning as mechanoreceptor (slow adapting, type I); found among basal keratinocytes and positive for S100 immunostain
- Found in areas with high tactile sensitivity (lips, fingers, ORS of hair follicle, oral mucosa)
- EM shows microvilli at cell surface with dense core granules, lobulated nucleus, and intermediate filaments assuming whorled arrangement near nucleus (dot-like pattern)
- Markers: cytokeratin (CK) 20 (specific for merkel cells in skin), also contain CK8, 18, and 19
- Contain battery of neuropeptides and neurotransmitter-like substances:
- Neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), chromogranin A, synaptophysin, and met-enkephalin
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