A) Tumors Arising From Keratinocytes Basal Cell Carcinoma

Is the commonest of all malignancies in North America Can be locally destructive but has an extremely low likelihood of metastasis. Pathologists can diagnose the nests of basaloid cells even on small fragmented biopsies

Right: pigmented BCC, sometimes melanin in tumor cells Left:

translucent, pearly appearance: dermal nests of basaloid cells surrounded by rim of mucin Smooth intact surface: epidermis usually

Left: Ulcerated BCC, in more advanced lesions Right: another example of pearly appearance

Left: Demonstrates smooth pearly surface of BCC and also telangiectases Center: Demonstrates peripheral palisading of tumor cells beside tumor cells Right: again demonstrates peripheral palisading From Robbins

Squamous Cell Carcinoma

Nodularity or induration: Penetration of tumour epithelium into dermis Rough Scale: hyperkeratosis (excess surface keratin)

Left: shows nodular ulcerated SCC Center: shows penetration of epithelium into dermis, transgressing basement membrane Right: Invasive tumor cells exhibit enlarged nuclei with angulated contours and prominent nucleoli. Enlargement and pleomorphism of keratinocytes with abundant eosinophilic cytoplasm.

Malignancy most closely linked to long-term sun exposure It has a greater likelihood of metastasis and mortality than basal cell carcinoma. Invasion of the dermis differentiates this tumor from actinic keratosis Since tumor recapitulates the squamous epithelium of the epidermis, pathologists can have difficulty distinguishing it from benign reactive epidermal proliferations on small or fragmented biopses

Actinic Keratosis

Left: Excessive scale formation in this lesion has produced a "cutaneous horn. " Center: sharply demarcated columns of compact hyperkeratosis and parakeratosis: results in sharp demarcation, roughness and scale grossly Right: Progression to full-thickness nuclear atypia, with or without the presence of superficial epidermal maturation, heralds the development of early squamous cell carcinoma in situ.

These extremely common sun-induced premalignant lesions within the epidermis sometimes progress Confinement of proliferation to epidermis: results in lack of nodularity or induration, usually papules or macules Subtle enlargement and pleomorphism of keratinocytes Dermal inflammatory cells: gives rise to red planar papule or plaque

Seborrheic Keratosis

Right: sharply demarcated epidermal thickening with a domed superficial aspect and horizontal deep aspect

Note cysts containing keratin (white plugs), results in comedo-like plugs Left: the pathology (right image) gives rise to a stuck on appearance, that has a warty like texture. Melanin within tumor keratinocytes gives rise to brown colour The prevalence unsightly idiopathic benign tumors increases with age (uniformly present when >60)

Wart

A Multiple papules with rough pebble-like surfaces B (Low Power) Papillomatosis (undulation of the epidermis) producing verrucous or pebble-like surface (A) C (High Power) course keratohyaline granules and perinuclear vacuolation D This shows in situ hybridization showing viral DNA within epidermal cells (FYI)

Also not shown is blood in stratum corneum, resulting in red or black dots on paring Hyperkeratosis (B) and parakeratosis (not shown)produces scale

B)Tumors Arising from Melanocytes Melanocyte Nevus

Nested pale slightly pigmented cells, hence lesion is usually brown in pigmentation Tumor cells a the dermo-epidermal junction and/ or in the dermis hence can be a macule, papule or polyp Small size, symmetry and circumscription results the same characteristics grossly

Melanoma

Nested and singly dispersed cells with pale, slightly pigmented cytoplasm at the dermo-epidermal and in the dermis, produces the varied brown pigmentation. Large size: Diameter often 6mm or greater Asymmetry from side to side: Asymmetry in gross Singly dispersed tumor cells in the epidermis at the edge of the lesion: Border irregular Upward spread of tumor cells above the basal layer of the epidermis, sometimes with melanin in stratum corneum: sometimes black in Color Sometimes melanin in the deep dermis: sometimes areas of blue Colour Sometimes dermal inflammation or vascular proliferation: sometimes areas of red Colour (bottom right image) Sometimes fibrosis: sometimes areas of white Colour (bottom left image)

Blue Nevus

Benign proliferations of melanocytes deep within the dermis, most often occurring as a small single lesion on the face or extremity. The colour comes from alteration of the normally brown or black color of melanin to blue-grey when it is seen through layers of the dermis and epidermis There is an intact epidermis resulting in a smooth macule or papule The heavily pigmented melanocytes in the deep dermis: results in a poorly demarcated border and a blue-grey color.

C) Tumors of Other Dermal Components Dermatofibroma

Intact epidermis: results in a smooth surface of lesion Dermal profliferation of cells with round and angulated nuclei (packed dermis) produces a nodule as in image B. Image C: Note the characteristic overlying epidermal hyperplasia and the tendency of fibroblasts to surround individual collagen bundles. The thick collagen fibers results in firmness upon palpation Image A: Hemorrhage and hemosiderin pigment results in brown/ tan color of the lesion Dermatofibromas resemble small round firm brown scars, but there is usually no injury recalled.

Hemangioma

Image Image Image Image

A: hemangioma on the tongue B: histology of juvenile capillary hemangioma C: image of cavernous hemangioma D: pyogenic granuloma of the lip

Hemangiomas commony present as: large rapidly growing tumors in infancy (strawberry angioma=infantile capillary hemangioma) small rapidly growing ulcerating tumors at any age (pyogenic granuloma) image D small slowly growing tumors in adulthood (senile angioma= cherry angioma= Campbell de morgan spot It is a circumscribed nodule of dermal blood vessels which gives rise it a discrete bright red papule or nodule

Neurofibroma

Image of neurofibromatosis (Cecil Textbook of Medicine) showing caf au lait spots.

Multiple neurofibromas indicate the hereditary systemic disease neurofibromatosis Intact epidermis: results in a smooth surface Dermal proliferation of cells with wavy nuclei having pointed ends : results in papules, nodules or polyps. Delicate collagen fibers produces a soft texture on palpation Presence of numerous mast cells Lack of cells with increased pigment: hence the lesions are usually skin colored

D. Epidermal Infections Tinea Corporis

Image A: characteristic plaque of tinea corporis Image B: shows the picture of mild eczematous (spongiotic) dermatitis, Image C: periodic acid-Schiff stain reveals deep red hyphae and yeast forms within the stratum corneum.

Hyper keratosis and parakeratosis (image B) produces and obvious scale seen in image A Numerous inflammatory cells in the dermis and epidermis results in a pruritic red plaque also seen in image A Sparse fine branching hyphae seen in image C

Caused by Trichophyton, Epidermophyton and Microsporum. Which commonly cause skin, hair and nail diseases but are not present on health skin. Application of KOH to scrapings from diseased skin dissolves keratinocytes allowing identification of the small numbers of fungi On biopsies, the pathologyic features often resemble psoriasis or eczema unless special stains are performed to identify the sparse fungi

Pityriasis Versicolor

Also called tinea versicolor, is caused by Malassezia ( Pityrosporum), which normally lives as a yeast in hair follicles, but in some people, travels out onto the surface of the epidermis as a yeast and hyphae The organism secretes a compound that is toxic to melanocytes (note hypopigmentation in image) A KOH prep shows numerous organisms Hyperkeratosis without parakeratosis results in subtle fine scale Minimal inflammation results in macules or patches with little redness or itching Numberous yeast and plump hyphae, resembling sausages and meatballs

Herpes Simplex and Varicella-Zoster

Top Left: Herpes in a dermatomal distribution Top Right: Herpes Vesicles on Palm Bottom Left: vesicles and erosions on palate Bottom Right: Herpes causing erythema multiforme with typical targetoid papules of palm

Necrosis of all epidermal cell types: results in vesicles and erosions Multinucleated keratinocytes Dermal inflammation: results in redness These viruses cause cold sores, genital herpes, chicken pox (varicella) and shingles (herpes zoster). The pathologic changes are the same in all types of infection. The distinctive multinucleated keratinocytes can be rapidly identified by a Tzanck preparation, performed by smearing scrapings from a vesicle onto a slide, staining and examining, under a microscope

E) Other Epidermal Inflammatory Disorders

Psoriasis
Top Left: Early and eruptive lesions may be dominated by signs of inflammation and erythema Top Right: Established, chronic lesions demonstrate erythema surmounted by characteristic silver-white scale (Robbins) Bottom Left and Right: Pustular psoriasis (from emedicine)

Predisposition to this very common type of cutaneoous inflammation is hereditary, with lesions precipitated by minor trauma, cutaneous or systemic infections or drugs Punctate bleeding when the scales are removed, sometimes helpful in diagnosis, is called Auspitz sign

Elegated rete ridges (epidermal hyperplasia), results in planar papules or plaques Uniform hyperkeratosis and parakeratosis, results in numerous prominent scales Neutrophils in the visible pustules epidermis, hence sometimes

Thinning of the portions of the epidermis directly overlying the dermal papillae, with dilated vessels close to the epidermis: hence bright redness and presence of Auspitz sign

Eczema

Stages of eczema development. A, Initial dermal edema and perivascular infiltration by inflammatory cells is B followed within 24 to 48 hours by epidermal spongiosis and microvesicle formation . C Abnormal scale, including parakeratosis, D follows, along with progressive epidermal hyperplasia and E hyperkeratosis as the lesion enters into a more chronic stage.

Eczema can be triggered by heredity (atopic dermatitis), irritants (irritant contact dermatititis), contact with allergens (allergic contact dermatitis, excessive drying of the skin (asteatotic eczema), or insufficiency of veins in the legs (stasis dermatitis)

A, In an acute allergic contact dermatitis, numerous vesicles appear at the site of antigen exposure B Histologically, intercellular edema produces widened intercellular spaces within the epidermis, eventually resulting in small, fluid-filled intraepidermal vesicles.

Elongated rete ridges (epidermal hyperplasia) results in papules or plaques Variable hyperkeratosis and parakeratosis: hence variable scale Lymphocytes and increased lLangerhans cells, triggering by external agents Increased fluid(serous fluid) space between keratinocytes in the epidermis (spongiosis) : resulting in vesicles, weeping and crusting Lymphocytes surrounding dermal vessels results in redness

Lichen Planus

A A solitary lesion of lichen planus (glistening surface is due to application of mineral oil, rendering the scale transparent). This flat-topped pink-purple, polygonal papule shows prominent Wickham striae that are more easily appreciated through the transparent scale. B Biopsy of one of the lesions demonstrates the bandlike infiltrate of lymphocytes at the dermoepidermal junction and pointed rete ridges (saw-toothing)

Lichen Planus is characterized by 5 Ps: pruritic, purple, planar, polygonal, papules Cutaneous and oral lesions characteristically show superimposed white lines, Wickhams striae Dence band-like infiltrate of lymphocytes at the dermo-epidermal junction results in a pruritic purple papule Wedge-shaped hypergranulosis (thickening of the stratum granulosum) and hyperkeratosis: produces Wickhams stria (image B) Necrotic basal keratinocytes

F. Blistering Disorders Pemphigus Vulgaris

Pemphigus disorder

vulgaris

is

rare

antibody-mediated

Antibodies are directed against an antigen which is important for adherence between keratinocytes Result is separation of the suprabasal portion of the epidermis from the basal layer of the epidermis, which remains attached to the dermis. Fluid accumulates in the intraepidermal leading to clinically apparent bullae. space,

Pemphigus Vulgaris (cont)

The roof of the bulla, because it consists of only a partial thickness of the epidermis, is fragile and ruptures easily, leading to flaccid bullae and erosions. A similar process occurs in the mucosa of the upper aerodigestive tract The cutaneous erosions are functionally similar to seconddegree burns, resulting in fluid and protein loss and bacterial infection Erosions in the mouth and pharynx make eating and drinking difficult because of pain. Before immunosuppressive therapies were pemphigus valgaris was almost always fatal discovered,

Suprabasal intraepidermal cleft: results in fragile, flaccid bullae with many erosions.

Bullous Pemphigoid

A Clinical bullae result from B basal cell layer vacuolization, producing a subepidermal blister. Histopathology of the edge of an early lesion showing the onset of epidermal separation from the underlying dermis. Eosinophils, as well as lymphocytes and occasional neutrophils, may be intimately associated with basal cell layer destruction, creating the subepidermal cleft.

Common blistering disease of the elderly, caused by antibodies to the antigens in the basement membrane. The antibodies induce an inflammatory infiltrate of eosinophils near this zone. Loss of adhesion between the epidermis and dermis allows s ubepidermal fluid accumulation. The full thickness of the epidermis overlying the bulla has enough strength to remain intact long enough that some degree of healing can occur in the base of the bulla before the roof ruptures Mucosal disease does not usually occur, and death from disease is unusual Dermal eosinophils results in pruritic erythematous plaques Subepidermal cleft produces a tense bullae with few erosions (image A)

Acne

A Inflammatory acne is characterized clinically by erythematous papules and pustules, with the possibility of eventual scarring. B A portion of a hair shaft piercing the follicular epithelium and eliciting an inflammatory response and fibrosis.

Initial pathogenetic event is plugging of the superficial portions of haif follicles by excessive keratin. This can result in rupture of the follicle aided by the bacterium Proprionibacterium acnes followed by inflammation and scarring Plugging of hair follicle by keratin resulting in open comodones (black heads) and closed comedones (white heads) Inflammation in and around the follicles results in red follicular papules, pustules and nodules Replacement of normal dermal structures by fibroblasts and excess collagen results in scarring