Skin Pathology

The skin is the largest organ of the body composed of epidermis and dermis. The epidermis is a stratified squamous keratinizing epithelium composed of several layers of keratinocytes 1-basal layer of proliferative cells. 2-Prickle cell layer of polygonal cells 3-granular cell layer of flattened cells rich in granules. 4-Corneal layer of differentiated keratinocytes.

In addition to keratinocytes, the epidermis contains other important cell types 1-Melanocytes: are dendritic cells producing melanin responsible for UV protection. 2-Langerhan’s cells are dendritic cells not identified by light microscope. 3-Merkel cells are neuroendocrine cells responsible for mechanoreception.

The dermis is composed of dermal connective tissue composed of collagen fibers. It has two distinctive areas 1- papillary dermis rich in small nerves and capillaries. 2-reticular dermis rich in skin appendages ( sweet glands, pilosebaceous unit).

Terms used in dermatopathology Macroscopic terms Macule: a circumscribed impalpable colored area. Papule: a small palpable lesion < 5mm in diameter. Nodule ; a large palpable lesion >5mm in diameter. Plaque: a raised flat lesion > 5mm in diameter. Vesicle: a small fluid filled blister < 5mm diameter. Bullae: a large fluid filled blister > 5mm diameter. Pustule: a vesicle containing pus.

Crust: dried plasma protein with inflammatory cells and blood. Scale: dry flaky or powdering surface due to thickened corneal layer. Excoriation: deep ( usually self-induced) scratch. Purpura: extravasations of RBCs into dermis.

Microscopic terms: Acanthosis: epidermal thickening due to hyperplasia of prickle cell layer. Hyperkeratosis: thickened corneal layer. Dyskeratosis: premature keratinization of epidermal cells. parakeratosis: retained nucleus in corneal layer. Spongiosis: intraepidermal edema. Acantholysis: loss of keratinocyte cohesion. Lichenoid : inflammation of the basal layer of epidermis.

Psoriasis Is a common inflammatory dermatosis affecting 1-2% of population. It is characterized by formation of well-defined pinkish plaques with silver scale. Predisposing factors: Local trauma Stress and medications

Psoriasis: well defined scaly plaque

Microscopically Acanthosis Hyperkeratosis Parakeratosis Elongation of ret ridges Neutrophil infiltration of stratum corneum

The vesiculobullous epidermal reactions A range of skin conditions associated with formation of blisters ( vesicles or bullae) Causes 1-thermal injury 2-insect bite reaction 3-drug reaction 4-infection by viruses, bacteria or fungi. 5-primary vesiculobullous disorders e.g pemphigus vulgaris, bullous pemphigoid, dermatitis herpetiformis.

Primary vesiculobullous disorders Pathogenesis Epidermal keratinocytes are held together by adhesion molecules called cadherins that are found within the desmosomes. These desmosomes held keratenocytes together and to basement membrane. Autoantibodies against desmosomal cadherins leads to loss of keratinocyte adhesion and bullous formation.

Mechanisms of epidermal-epidermal adhesion and epidermal-dermal adhesion.

Pemphigus vulgaris Affect middle aged and elderly, bullae develop on the trunk, axillae, groin, scalp and face. The blisters rupture leaving shallow erosions. Pathogenesis: IgG autoantibodies against desmosomal attachment in prickle cell layer with formation of immune complex and complement activation and release of proteases. Microscopically: blisters are suprabasal with intact basal layer of keratinocytes.

Pemphigus vulgaris: the blisters are large and rupture easily leaving shallow erosions

Pemphigus vulgaris: blister cavity lies above the basal layer which remains attached to the basement membrane

Bullous pemphigoid Affects elderly, blisters develop over the abdomen, groin and flexor surfaces of limbs. Oral cavity may be involved. The blisters are larger than in pemphigous vulgaris and more resistant to trauma ( because of their subepidermal location). IgG autoantibodies against desmosomal molecules which fix the basal cells to basement membrane so bullae are subepidermal ( the roof is formed of full thickness epidermis)

Bullous pemphigoid: the blister cavity lies beneath the full thickness of epidermis

Dermatitis herpetiformis Is a rare chronic blistering disease presents in early adulthood. Papules and vesicles develop symmetrically over the elbow and knee. 90% of patients have glutein-sensitive enteropathy due to autoantibodies of IgA type which are deposited into the dermal papillae leading to chemotaxis of neutrophils and formation of microabscesses at the tip of dermal papillae.

Premalignant epithelial lesions of epidermis 1)Actinic keratosis An area of epidermal dysplasia with overlying parakeratosis due to chronic sun exposure. It may progress to carcinoma (BCC or SCC). 2) Bown’s disease Is squamous cell carcinoma in situ. If untreated it may progress to SCC.

Actinic keratosis: the epidermis shows irregular orientation and variation in shape and size of keratinocytes with parakeratosis ( presence of blue staining nuclei in the stratum corneum)

Carcinoma of the skin Majority of carcinomas of skin arise in the epidermis. Basal cell carcinoma Is a slowly growing malignant tumor of keratinocytes It is common in sun exposed skin of white people It is locally aggressive but non- metastesizing (rarely metastasize)

Grossly Pearly nodule with central ulcer(rodent ulcer) An ill defined patches or nodules Microscscopically: It derives its name from histological resemblance of tumor cells to the basal layer of epidermis. It shows nests of small darkly stained cells with peripheral palisading

Basal cell carcinoma: large rounded ulcer with elevated edge & necrotic base at the upper part of the face

BCC forming ill defined pigmented nodule

Basal cell carcinoma: nests of dark blue cells with peripheral palisading

Squamous cell carcinoma Arises from epidermal squamous epithelium in sun-damaged skin, burn scars and chronic ulcers. It differs from BCC morphologically and clinically. It has the potential for distant metastasis. It presents as hyperkeratotic nodule and in more advanced stage it may results in ulceration and destruction of underlying tissue.

Squamous cell carcinoma-Hyperkeratotic nodule with central ulceration

Microscopically: it forms highly irregular strands and nodules of malignant epithelial cells invading into the underlying dermis with variable degree of keratin production.

Slide on left : moderately differentiated squamous cell carcinoma,there is area of cell nest with malignant squamous cells( pleomorphism, hyperchromatism, high nuclear/ cytoplasmic ratios )& keratin formation,the other area lacks keratin slide on right: poorly differentiated squamous cell carcinoma with pleomorphic cells and minimal pink keratinization, increase mitotic activity & prominent nucleoli

Melanocytic naevus ( mole) Benign melanocytic neoplasm arises in the epidermis and extends into the dermis. It is either congenital or acquired, it is important because melanoma usually arises from a preexisting naevus

Common acquired naevus Is very common in white subjects It starts as small brown well circumscribed hyper pigmented macule or papule. Predisposing factors Sunlight exposure sunburns

Compound nevus

Melanocyte proliferation starts in the epidermis at the junction between the epidermis and dermis forming cell nests ( junctional naevus). Later one naevus cells extend to superficial dermis( compound naevus). After many years, the junctional naevus cells disappear, and all naevus cells are now intradermal called intradermal naevus. At the base of the naevus, the melanocytes become smaller and elongated and lose their pigmentation (maturation).

Common acquired nevus: round to oval nests of melanocytes are present at dermoepidermal junction and extend into the upper dermis

Benign intradermal nevus the junctional naevus cells disappear, and all naevus cells are now intradermal :

Malignant melanoma Malignant tumor of melanocytes. 50% arises from melanocytic naevus. Clinically arises as flat or raised irregular lesion which bleeds easily or a sudden change in the size or color of a pre existing naevus.

Histologically : 4 variants of melanoma 1)Superficial spreading melanoma: is the most common variant, malignant melanocytes are seen through out thr thickness of epidermis. 2)Nodular melanoma: grows rapidly forming pigmented nodule. 3)Lentigo maligna melanoma arises in sun-exposed skin in middle age or elderly from atrophic epidermis producing irregular pigmentation. 4)Acral lentiginous melanoma arises from skin of palm of hands, soles of feet.

spreading melanoma: the lesion is irregular in shape with marked variation in color and irregular surface. Superficial

Morphology Melanoma cells have large nuclei, prominent eosinophilic nucleoli, and a typical mitosis and grow in nests or in individual cells at all levels of epidermis and as dermal nodules with variable degree of melanin production. The growth of melanoma is both horizontal and vertical growth.

Melanoma cells extend throughout layers of epidermis and dermis

Horizontal (radial) growth :is horizontal growth of melanoma cells within the epidermis and superficial dermis. Vertical : melanoma cells grow down ward in the deeper dermis. The depth of this invasion can be measured in millimeters (Breslow thickness). This depth of invasion determines the probability of distant metastasis.