Answer: D.

A. Disorders of Pigmentation

1. Vitiligo a. Irregular, completely depigmented patches b. Common; may affect any race; familial predisposition c. Unknown etiology; possibly autoimmune d. Micro: affected areas are devoid of melanocytes

2. Melasma a. Irregular blotchy patches of hyperpigmentation on the face b. Associated with oral contraceptive use and pregnancy ("mask of pregnancy")

c. May regress after pregnancy

3. Freckles (ephelides)

a. Common in fair-skinned children b. Light brown macules on face, shoulders, and chest c. Darken and fade with the seasons (exposure to sunlight)

d. Micro i. Increased melanin deposition in the basal cell layer of the epidermis ii. Normal number of melanocytes

4. Benign lentigo a. Benign, localized proliferation of melanocytes b. Small, oval, light brown macules c. Micro: linear melanocytic hyperplasia

B. Melanocytic Tumors

1. Congenital nevi (birthmarks)

a. Present at birth b. Giant congenital nevi have increased risk of melanoma

2. Nevocellular nevus (mole)

a. Benign tumor of melanocytes (nevus cells)

b. Clearly related to sun exposure c. Types: junctional, compound, and intradermal d. Gross i. Uniform tan to brown color ii. Sharp, well circumscribed borders iii. Tend to be stable in shape and size e. Malignant transformation is uncommon

3. Dysplastic nevi (BK moles)

a. Nevi are larger and irregular and may have pigment variation b. Micro: the nevus exhibits cytological and architectural atypia c. Dysplastic nevus syndrome i. Autosomal dominant (CMM1 gene on chromosome 1)

ii. Often have multiple dysplastic nevi iii. Increased risk of melanoma

4. Malignant melanoma a. Incidence i. Increasing at a rapid rate ii. Melanoma peaks in ages 40-70

b. Risk factors i. Chronic sun exposure, sunburns ii. Fair-skinned individuals iii. Dysplastic nevus syndrome c. Gross i. Asymmetric, irregular borders, variegated color, large diameter, enlarging, macule, papule, or nodule ii. Males: upper back; females: back and legs d. Lentigo maligna melanoma i. Older age; usually on the face or neck ii. Best prognosis e. Superficial spreading melanoma i. Overall, most common type ii. Primarily horizontal growth pattern f. Acral-lentiginous melanoma i. Most common melanoma in dark-skinned individuals ii. Affects palms, soles, and subungual area g. Nodular melanoma i. Nodular tumor with a vertical growth pattern ii. Worst prognosis of the melanomas h. Prognosis i. Staging is by depth of invasion (vertical growth) ■ Breslow's thickness * Clark's levels i. Treatment i. Wide surgical excision ii. Systemic disease is treated with chemotherapy or immunotherapy iii. May resolve spontaneously

C. Benign Epidermal and Dermal Lesions 1. Acanthosis nigricans a. Thickened, hyperpigmented skin in axillae and groin b. Associated with internal malignancy

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2. Seborrheic keratoses a. Benign squamo proliferative neoplasm b. Very common in middle-aged and elderly individuals c. Distribution: trunk, head, neck, and extremities d. Gross i. Tan to brown coin-shaped plaques with a granular surface ii. "Stuck on" appearance e. Micro i. Basaloid epidermal hyperplasia ii. "Horn cysts" (keratin-filled epidermal pseudocysts)

f. Treatment i. Usually left untreated ii, May be removed if they become irritated or for cosmetic purposes g. Sign of Leser-Trélat (paraneoplastic syndrome): sudden development of multiple lesions may accompany an underlying malignancy

3. Psoriasis a. Epidemiology i. Affects 1% of the U.S. population ii. Most common form is psoriasis vulgaris iii. Unknown etiology iv. Clear genetic component v. May be associated with arthritis, enteropathy, and myopathy b. Gross i. Common sites: knees, elbows, and scalp ii. Gross: well demarcated erythematous plaques with a silvery scale iii. Auspitz sign: removal of scale results in pinpoint bleeding iv. Nail beds show pitting and discoloration c. Pathogenesis: increased epidermal turnover d. Micro i. Epidermal hyperplasia (acanthosis)

ii. Patchy hyperkeratinization with parakeratosis iii. Uniform elongation and thickening of the rete ridges iv. Thinning of the epidermis over the dermal papillae v. Munro microabscesses e. Treatment i. Topical steroids and ultraviolet irradiation ii. Severe systemic disease may be treated with methotrexate Malignant Tumors

1. Squamous cell carcinoma (SCC)

a. Incidence: the tumor peaks at 60 years of age b. Risk factors i. Chronic sun exposure (ultraviolet UV-B)

ii. Fair complexion iii. Chronic skin ulcers or sinus tracts ; iv. Long-term exposure to hydrocarbons, arsenic, burns, radiation v. Immunosuppression vi. Xeroderma pigmentosa c. Precursors i. Actinic keratosis

• Sun-induced dysplasia of the keratinocytes ■ Gross: rough, red papules on the face, arms, and hands ii. Bowen disease: squamous cell carcinoma in situ d. Gross

; i. Occurs on sun-exposed areas (face and hands)

ii. Tan nodular mass, which commonly ulcerates e. Micro i. Nests of atypical keratinocytes invade the dermis ii. Formation of keratin pearls iii. Intercellular bridges (desmosomes) between tumor cells f. Prognosis i. Rarely metastasizes ii. Complete excision is usually curative g. Variant: keratoacanthoma (well differentiated SCC)

i. Rapidly growing, dome-shaped nodules with a central keratin-filled crater ii. Often self-limited and regresses spontaneously 2. Basal cell carcinoma a. Most common tumor in adults in the United States b. Most common in middle-aged or elderly individuals c. Risk factors i. Chronic sun exposure ii. Fair complexion iii. Immunosuppression iv. Xeroderma pigmentosum d. Gross i. Occurs on sun-exposed, hair-bearing areas (face)

ii. Pearly papules iii. Nodules with heaped-up, translucent borders iv. Telangiectasia v. Ulceration (rodent ulcer)

e. Micro: invasive nests of basaloid cells with a palisading growth pattern I f. Prognosis

: i. Grows slowly but may be locally aggressive ii. Rarely metastasizes g. Treatment i. Shave biopsies have a 50% recurrence rate ii. Complete excision is usually curative

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3. Histiocytosis X (Langerhaiis cell histiocytosis)

a. Proliferation of Langerhans cells (histiocytes), which are normally found within the epidermis b. Three clinical variants i. Unifocal (eosinophilic granuloma)

ii. Multifocal (Hand-Schiiller-Christian disease)

iii. Acute disseminated (Letterer-Siwe syndrome)

c. Langerhans cells are CD la positive d. Electron microscopy: cytoplasmic Birbeck granules (tennis-racket-shaped)

4. Mycosis fungoides (cutaneous T-ceU lymphoma)

b. Gross: rash of scaly red patches, plaques, or nodules c. Common sites: trunk, extremities, face d. Micro i. Superficial dermal infiltrate of T lymphocytes ii. Epidermotropism: tendency to invade the epidermis iii. Pautrier microabscesses: collections of lymphocytes within the epidermis e. Sézary syndrome: blood involvement

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