USMF



The skin diseases

Introduction

Definitions of macroscopic terms

Definitions of microscopic terms

Disorders of Pigmentation and Melanocytes

Benign Epithelial Tumors

Premalignant and Malignant Epidermal Tumors

Tumors of the Dermis

Disorders of Epidermal Maturation

Acute Inflammatory Dermatoses

Chronic Inflammatory Dermatoses

Disorders of Epidermal Appendages

Introduction

Accurate description of the clinical appearance of the skin at a macroscopic level is critical, since lesions before biopsy are, in effect, the gross pathology. Correlation between the gross and histologic appearances is often essential in formulating diagnoses and in understanding pathogenesis. Accordingly, efforts are made in the following pages to depict and describe clinical lesions whenever possible and to relate these findings to the microscopic appearance of lesions.

Objectives:

1. Define a nevus in terms of its clinical manifestations.

2. Describe the non-nevoid pigmented disorders of the skin.

3. List the variant forms of nevocellular nevi.

4. Define a dysplastic nevus in terms of its architectural and cytological features and its clinical significance.

5. Discuss the evidence for the concept that some dysplastic nevi are precursors of malignant melanomas.

6. Define a malignant melanoma in terms of its architectural difference from a nevocellular nevus.

7. Describe the risk factors for the development of a malignant melanoma.

8. List the clinical warning signals of melanoma.

9. Know what factor is thought to be responsible for the numerous seborrheic keratoses sometimes seen as a paraneoplastic syndrome.

10. Know the common tumors arising from these adnexal structures.

11. Define squamous cell carcinoma of the skin in terms of etiology, pathogenesis, and prognosis.

12. Define a basal cell carcinoma in terms of frequency, pathogenesis, localization, and clinical outcome.

13. Know which other disease is closely related to urticaria and how it differs from urticaria.

14. Name some clinical features in patients with psoriasis and describe the areas of the skin that are most commonly affected.

Key words: Macule, patch, papule, vesicle, dysplastic nevus, melanoma, seborrheic keratoses, urticaria, psoriasis, verrucae, acanthosis, vitiligo.

clinical objectives:

1. Know the most important histological factor that determines the prognosis of a melanoma

2. Describe the gross and histological features of seborrheic keratoses.

3. Describe the two most frequent histological growth patterns of basal cell carcinoma

4. Describe the typical epidermal changes in psoriasis.

5. Describe the anatomic classification of verrucae.

Definitions of macroscopic terms

Macule Circumscribed lesion of up to 5 mm* in diameter characterized by flatness and usually distinguished from surrounding skin by its coloration.

Patch Circumscribed lesion of more than 5 mm in diameter characterized by flatness and usually distinguished from surrounding skin by its coloration.

Papule Elevated dome-shaped or flat-topped lesion 5 mm or less across.

Nodule Elevated lesion with spherical contour greater than 5 mm across.

Plaque Elevated flat-topped lesion, usually greater than 5 mm across (may be caused by coalescent papules).

Vesicle Fluid-filled raised lesion 5 mm or less across.

Bulla Fluid-filled raised lesion greater than 5 mm across.

Blister Common term used for vesicle or bulla.

Pustule Discrete, pus-filled, raised lesion.

Wheal Itchy, transient, elevated lesion with variable blanching and erythema formed as the result of dermal edema.

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).

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.

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). 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., postinflammatory 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 melanocytes7 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 skin9 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.

Melasma

Melasma is a mask-like zone of facial hyperpigmentation commonly seen in association with pregnancy-hence its designation as the "mask of pregnancy." It also may occur in some individuals taking oral contraceptives. It presents as poorly defined, blotchy, tan-brown macules and patches involving the cheeks, temples, and forehead bilaterally. Sunlight may accentuate this pigmentation, which often resolves spontaneously, particularly with cessation of hormonal stimulation.

Morphology. Three histologic patterns have been recognized: an epidermal type, in which there is increased melanin deposition in the basal layers; a dermal type, characterized by macrophages in the superficial (papillary) dermis that have phagocytosed melanin from the adjacent epidermal layer (a process referred to as melanin pigment incontinence); and a mixed type, characterized by a combination of the changes seen in the epidermal and dermal types. These three types may be distinguished by the use of a Wood's light ("black light"), which permits distinction between epidermal versus dermal pigmentation on clinical inspection. This is important because melasma of the epidermal type, and partially of the mixed type, may respond to the topical bleaching agent hydroquinone.

The pathogenesis of melasma appears to relate to functional alterations in melanocytes resulting in enhanced pigment transfer to basal keratinocytes or to dermal macrophages. Apart from its association with pregnancy and oral contraceptives, melasma may occur during the administration of hydantoins, or it may be idiopathic.

Lentigo

Until now, we have been addressing disorders of pigmentation that do not involve proliferation of melanocytes. The term lentigo (plural, lentigines) refers to a common benign localized hyperplasia of melanocytes occurring at all ages but often in infancy and childhood. There is no sex or racial predilection, and the cause and pathogenesis are unknown. These lesions may involve mucous membranes as well as the skin, and they appear as small (5 to 10 mm across), oval, tan-brown patches. Unlike freckles, lentigines do not darken when they are exposed to sunlight.

Morphology. The essential histologic feature of the lentigo is linear (non-nested) melanocytic hyperplasia (hyperplasia restricted to the cell layer immediately above the basement membrane) that produces a hyperpigmented basal cell layer. So characteristic is this linear melanocytic hyperplasia that the term lentiginous is often used to describe similar patterns of cellular proliferation within the basal cell layer in melanocytic tumors, such as in lentiginous nevi and in certain melanomas (termed acral lentiginous melanomas). Elongation and thinning of the rete ridges are also commonly seen in a lentigo. In contrast to ordinary lentigo (lentigo simplex) a variant termed solar or actinic lentigo occurs in sun-damaged skin in older adults and is associated with subtle alteration in keratinocyte maturation.

Melanocytic nevus (pigmented nevus, mole)

Most of us have at least a few moles and probably regard them as mundane and uninteresting. It may be surprising to learn, then, that moles or nevi represent one of the most diverse, dynamic, and biologically intriguing tumors of the skin! Strictly speaking, the term nevus denotes any congenital lesion of the skin (e.g., birthmark). Melanocytic nevus, however, refers to any congenital or acquired neoplasm of melanocytes, and hence is somewhat of a misnomer.

In clinical appearance, common acquired melanocytic nevi are tan to brown, uniformly pigmented, small (usually ................
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