Disorders of Pigmentation and Melanocytes

Chapter 25 - The Skin

George F. Murphy MD

Klaus Sellheyer MD

Martin C. Mihm Jr. MD

Normal

The Skin: More Than a Mechanical Barrier

Little more than 100 years ago, the noted pathologist Rudolph Virchow understood the skin as a protective covering for more delicate and functionally sophisticated internal viscera.[1]

Then, and for the century that followed, the skin was considered primarily a passive barrier to fluid loss and mechanical injury. During the past three decades, however, enormously

productive avenues of scientific inquiry have demonstrated the skin to be a complex organ in which precisely

Figure 25-1 A, The skin is composed of an epidermal layer (e) from which specialized adnexa (hair follicles, h; sweat glands, g; and sebaceous glands, s) descend into the underlying

dermis (d). B, This projection of the epidermal layer (e) and underlying superficial dermis demonstrates the progressive upward maturation of basal cells (b) into cornified squamous

epithelial cells of the stratum corneum (sc). Melanin-containing dendritic melanocytes (m) (and rare Merkel cells containing neurosecretory granules) and midepidermal dendritic

Langerhans cells (lc) are also present. The underlying dermis contains small vessels (v), fibroblasts (f), perivascular mast cells (mc), and dendrocytes (dc), potentially important in

dermal immunity and repair.

Figure 25-2Schematic representation of dynamic interaction between the epidermal layer and the dermal layer. Keratinocytes at the edge of an ulcer (A) produce cytokines and factors

that influence both keratinization and the function of underlying dermal cells (B). In turn, dermal cells (B), such as mast cells, also release cytokines (green granules) and proteases (red

granules), which may regulate both endothelial cells and overlying keratinocytes. Perturbations in these interactions between epidermal cells and dermal cells may contribute to

pathologic processes, such as psoriasis (C), in which both compartments become morphologically abnormal.

Scale

Dry, horny, platelike excrescence; usually the result of imperfect cornification.

Lichenification

Thickened and rough skin characterized by prominent skin markings; usually the result of repeated rubbing in susceptible persons.

Excoriation

Traumatic lesion characterized by breakage of the epidermis, causing a raw linear area (i.e., a deep scratch); often self-induced.

Onycholysis

Separation of nail plate from nail bed.

DEFINITIONS OF MICROSCOPIC TERMS

Hyperkeratosis

Thickening of the stratum corneum, often associated with a qualitative abnormality of the keratin.

Parakeratosis

Modes of keratinization characterized by the retention of the nuclei in the stratum corneum. On mucous membranes, parakeratosis is normal.

Hypergranulosis

Hyperplasia of the stratum granulosum, often due to intense rubbing.

Acanthosis

Diffuse epidermal hyperplasia.

Papillomatosis

Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae.

Dyskeratosis

Abnormal keratinization occurring prematurely within individual cells or groups of cells below the stratum granulosum.

Acantholysis

Loss of intercellular connections resulting in loss of cohesion between keratinocytes.

Spongiosis

Intercellular edema of the epidermis.

Hydropic swelling (ballooning)

Intracellular edema of keratinocytes, often seen in viral infections.

Exocytosis

Infiltration of the epidermis by inflammatory or circulating blood cells.

Erosion

Discontinuity of the skin exhibiting incomplete loss of the epidermis.

Ulceration

Discontinuity of the skin exhibiting complete loss of the epidermis and often of portions of the dermis and even subcutaneous fat.

Vacuolization

Formation of vacuoles within or adjacent to cells; often refers to basal cell-basement membrane zone area.

Lentiginous

Referring to a linear pattern of melanocyte proliferation within the epidermal basal cell layer. Lentiginous melanocytic hyperplasia can occur as a reactive change or as part of a

neoplasm of melanocytes.

Disorders of Pigmentation and Melanocytes

Skin pigmentation has historically had major societal implications. Cosmetic desire for increased pigmentation (tanning) has resulted in many deleterious alterations that are described in

the pages that follow. Focal or widespread loss of normal protective pigmentation not only renders individuals extraordinarily vulnerable to the harmful effects of sunlight (as in

albinism), but has also resulted in severe emotional stress and, in some cultures, profound social and economic discrimination (as in vitiligo). Change in preexisting skin pigmentation

may signify important primary events in the skin (e.g., malignant transformation of a mole) or disorders of internal viscera (e.g., in Addison disease, see Chapter 24 ).

VITILIGO

Vitiligo is a common disorder characterized by partial or complete loss of pigment-producing melanocytes within the epidermis. All ages and races are affected, but lesions are most

noticeable in darkly pigmented individuals. Vitiligo may be entirely unapparent in lightly pigmented skin until tanning occurs in the surrounding normal skin. In darkly pigmented

individuals with extensive involvement, residual zones of normal skin may at first appear to represent hyperpigmented lesions ( Fig. 25-3A ).

Clinical lesions are asymptomatic, flat, well-demarcated macules and patches of pigment loss; their size varies from few to many centimeters. Vitiligo often involves the hands and

wrists; axillae; and perioral, periorbital, and anogenital skin. A curious phenomenon called koebnerization often occurs in vitiligo (as well as in certain other conditions; see lichen

planus), where lesions develop primarily at sites of repeated trauma.

Morphology.

On histologic examination, vitiligo usually appears indistinguishable from normal skin. However, it is characterized by loss of melanocytes, as revealed by electron microscopy; it also

may be diagnosed by immunohistochemistry for melanocyte-associated proteins (e.g., tyrosinase or Melan-A, or S-100; Fig. 25-3B ). This is in contrast to some forms of albinism,in

which melanocytes are present but melanin pigment is not produced because of a lack of or defect in tyrosinase. There are other causes of hypopigmentation that are unrelated to

diminished expression of melanin or melanocytes (e.g., post-inflammatory hypopigmentation, which represents redistribution of existing pigment within skin possibly coupled with

diminished transfer of pigment to keratinocytes).

Pathogenesis.

Why are melanocytes progressively lost or destroyed in vitiligo? Theories of pathogenesis include (1) autoimmunity, (2) neurohumoral factors toxic to melanocytes and released by

nearby nerve endings, and (3) self-destruction of melanocytes by toxic intermediates of melanin synthesis. Most evidence supports autoimmune causation, focusing on the presence of

circulating antibodies against melanocytes[7] and the association of vitiligo with other autoimmune disorders, such as pernicious anemia, Addison disease, and autoimmune thyroiditis.

Abnormalities in macrophages,[8] and in T lymphocytes in skin[9] and in the peripheral blood have been described recently, suggesting that aberrations in cell-mediated immunity may

also be operative in the pathogenesis of vitiligo. Another interesting facet of vitiligo is its response to therapy with UV light of the A wavelength coupled with use of the photosensitizing

drug, psoralen (a therapy known as PUVA). Lesions so treated may regain pigment initially at the ostia of hair follicles, suggesting that melanocyte precursors harbored within the

uppermost follicular epithelium are stimulated by this therapeutic approach.

Figure 25-3 A, Clinical appearance of vitiligo. Well-demarcated zones of pigment loss result from depletion of melanocytes that produce small melanin granules. Note small macules of

normal pigment within the patches of vitiligo; Some of these appear to surround follicular ostia. B, Immunochemistry for S-100 protein revealing positively stained melanocytes within

the basal cell layer of the epidermis; these cells are decreased or absent in vitiligo.

Figure 25-4Nevocellular nevus, junctional type. A, In clinical appearance, lesions are small, relatively flat, symmetric, and uniform. B, On histologic examination, junctional nevi are

characterized by rounded nests of nevus cells originating at the tips of rete ridges along the dermoepidermal junction.

Figure 25-5Nevocellular nevus, compound type. In contrast to the junctional nevus, the compound nevus (A) is more raised and dome shaped. The symmetry and uniform pigment

distribution suggest a benign process. Histologically (B), compound nevi combine the features of junctional nevi (intraepidermal nevus cell nests) with nests and cords of nevus cells in

the underlying dermis.

TABLE 25-1-- Variant Forms of Nevocellular Nevi

Date: 2016-04-22; view: 875