Pathology Skin PIGMENTATION DISORDERS Vitiligo o o Dark Skinned Individual with loss of pigmentation
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For Skin: First Aid and Class has a bunch more diseases. Dr. Wang tells you about many more than included here. To be honest, Skin is a small section of this block and has many diseases, so we tried to limit the amount of memorization in the skin section that you had to do. I built this after‐the‐fact, during my Board Review.
Autoimmune destruction of the melanocytes causing a lack of pigmentation Obvious on African Americans (who’s scan is patchy and white), apparent on Caucasians when they try to tan Irregular areas of complete depigmentation
Melasma ‐ ‐ ‐
Hyperpigmentation around the eye Commonly occurs in pregnancy, called the “mask of pregnancy” Lesions regress when pregnancy is completed
Freckles (Ephelis) ‐ ‐
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Regions of pigmentation, commonly on the sun‐exposed areas Macules of focal hyperpigmentation o Melanocytes Normal is Number o Melanin concentration is greater Get darker during the summer, lighter in the winter (dependent on sun exposure)
Albinism ‐ ‐ ‐
Deficiency of tyrosinase prevents the formation of melanin within the melanocytes Presents with white skin, white hair, and translucent corneas ↑risk for skin cancers, highly susceptible to sunburn
Congenital Nevus (birthmark) o o o A birthmark
Represent the most benign lesion of melanocytes Flat macules of hyperpigmentation that are present at birth and have no risk of tumorigenesis The presence of hair lets you know they are normal
Nevocellular Mole o
o o A Mole
Benign tumor of the melanocytes that are strongly associated with sunlight Very well circumscribed = Benign Consistent Pigmentation = Benign Carry a small risk of turning to cancer if not monitored and allowed sun exposure This made Cindy Crawford world famous
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Pathology Skin Dysplastic Nevus o
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The evil, more malignant version of a mole Poorly demarcated, not well circumscribed Inconsistent pigmentation Still small risk of transformation to cancer, but greater than a mole These should be examined and excised by a dermatologist
Malignant Melanoma (Cancer) o
o o o
This is the most evil, most malignant version of the mole Very poorly demarcated, not well circumscribed Very inconsistent pigmentation Tend to be very large and generally flat Elevated risk with sunburns and from the presence of dysplastic nevus Fair‐Skinned, Blonde, Blue‐eyes are all at ↑ risk These are going to spread both along the epidermis (↑surface area) and into the epidermis (depth and raising above the skin) The only treatment is radical resection with complete surgical excision with complete margins and chemo if has already spread May spontaneous regress on its own!
Disease Vitiligo Melasma Albinism
Freckles Congenital Nevus Nevocellular Mole Dysplastic Nevus Melanoma
DISEASES OF PIGMENTATION Character Autoimmune destruction of the melanocytes (once they are gone, they are gone) Produces patchy distribution of complete depigmentation Hyperpigmentation of the skin around the orbits (called the mask of pregnancy) Sets in with oral contraceptive use or pregnancy, disappears with termination of underlying cause Tyrosinase Deficiency causes there to be no melanin made in melanocytes Produces a white skin, white hair, and translucent corneas ↑ Risk for sunburn and cancers of the skin Discrete regions of normal # of melanocytes with ↑concentration of melanin A birthmark, a lesion of melanocytes that are present from birth There is no risk of transformation to cancer A benign lesion of the melanocytes (well circumscribed and consistently pigmented) Are usually raised, so are considered a papule or a plaque A more malignant lesion of the melanocytes (poorly circumscribed and inconsistently pigmented) Are usually raised or flat (papules), and contain dysplastic cells on histology The most malignant lesion of the melanocytes Grow horizontally and vertically (depth of invasion is the best indicator for metastasis) Is a cancer that is strongly associated with congenital syndromes and sunburns Despite being an “oma,” this is actually a malignant cancer, so should be called melanocarcinoma
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Pathology Skin EPIDERMAL/DERMAL LESIONS Acanthosis Nigracans o o
Hyperpigmentation and thickening of the skin (leather‐like appearance) Found in the axilla and groin Indicates an internal malignancy Usually gastric and pulmonary cancer
Darkening of the Armpit
Seborrheic Keratosis o o o o o
Benign hyperproliferative disorders of the elderly Commonly found on the face, they look as though they can be “plucked off” Under the scope you will see a proliferative epidermis into the dermis with the formation of keratin horn cysts Cyst‐like spaces within the epidermis that are filled with keratin Is benign, and you remove them only if they get infected If the vignette is very old and it is a benign lesion, pick this
Psoriasis o
o Silvery scaly lesions with erythema (red) that bleed when picked
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This is a largely raised papules and plaques that have a characteristic appearance Occur on the pressure point areas (knees, elbows, scalp) There is an Erythmatous plaque with Silver Scaly Lesions Attempts to remove these plaques produces pinpoint bleeding Mechanism ↑Turnover of the epidermis, undergoing epidermal hyperplasia (Acanthosis) Hyperkeratinization (extra keratin on top of the scales) Look for Monroe Microabscesses Treatment Topical Steroids or ultraviolet radiation
Erythema Multiforme o o
Presents as a target lesion with a central region of redness, surrounded by nothing, with an expanding region of red inflammation Associated with a number of conditions including infection, drugs and cancer
Erythema Nodosum ‐ ‐
Erythmatous nodules of subcutaneous fat that occur on the shins and knees Areas of redness associated with various inflammatory disorders, common in women
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Pathology Skin Uticaria ‐ ‐
Hives, generated from mast cell degranulation Present as red macules (short) that may raise up to papules, or even to translucent wheals
Atopic Dermatitis / Contact Dermatitis ‐ ‐ ‐
Type 4 Hypersensitivity reaction that follows exposure of an allergen Lesion normally presents hours to days after exposure in the shape of the object o Watch band, sandal, shoe, latex glove May itch, but is generally not problematic
Impetigo ‐ ‐ ‐
Disease Acanthosis Nigracans Seborrheic Keratosis Psoriasis
Erythema Multiforme Erythema Nodosum Uticaria Contact Dermatitis
Honey‐colored crusting lesion caused by infection Common in young children Causative agent is a Strep Pyogenes or Staph Aureus EPIDERMAL/DERMAL DISEASES Character This is a paraneoplastic syndrome caused by a visceral malignancy (gastric, lung, intestines) Is a thickening and a darkening of the skin in the axilla and/or groin Benign, hyperprolific disorder of the elderly that is not preneoplastic Look for keratin horn cysts or the appearance of being able to “pluck” it off Erythematous red plaques with silvery scales that bleed when picked found on extensor surfaces Causes a hyperkeratosis and hyperproliferation of the epithelium Treat with topical corticosteroids Target Lesion with central red mark, surrounded by a ring of clear, then an ring of red Red lesion on the fronts of shins and knees Wheals caused by mast cell degranulation (hives) Type 4 hypersenstivity reaction that develops hours to days after contact in the pattern of the object touching the skin
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Pathology Skin BLISTERING DISEASES Pemphigus Vulgaris o
o IgG Immunofluorescence showing net‐like distribution throughout epidermis
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Fatal autoimmune disease with IgG against desmosomes that hold the epidermis together, targeting the link between epithelial cells Intracytoplasmic bridges are destroyed, but the basal layer stays intact Basal layer forms tombstones after the rest of the cells shear off Creates easily ripped blisters on the skin and mouth These easily get ripped off, ↑risk of infection They can heal without scarring Look for Antibodies in a net‐like distribution across the epidermis
Bullous Pemphigoid o
o IgG Immunofluorescence showing linear deposition at dermal‐epidermal junction
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Autoimmune disease with IgG against hemidesmosomes that holds the basal layer to the epidermis Intracytoplasmic bridges are intact, but the basal layer rips Smooth surface is left behind, while the epidermis holds tightly to itself Because tightly held, they are turgid and do not tear easily These do no get easily ripped off, there is no ↑risk for infection Do not occur on the mouth Antibodies will be only at the dermal‐epidermal junction
Dermatitis Herpatiformis o o IgA Immunofluorescence showing deposition at tips of papillae
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Is an IgA Autoimmune Disease against Gluten and Gliadin This is the same target and antibody as in Celiac Sprue (GI Block) Antibody‐Antigen complexes deposit at tips of dermal papillae Type III hypersensitivity reaction Deposition of complexes at tips cause elevation of epidermis, resulting in blister Responds to a Gluten‐Free Diet
Phemphigus is the real thing, and is the worse one to have; it kills you, so it leaves Tombstones. Pemphigoid is pemphigus‐like, and isn’t as bad; it doesn’t kill you, so its nice and smooth Disease Phemphigus Vulgaris Bullous Pemphigoid Dermatitis Herpatiformis
BLISTERING DISEASES Character IgG Autoimmune disease against desmosomes that hold epithelial cells to each other Presents with tombstone histology and a net‐like immunofluorescence Flaccid Blisters that teat easily and are present in the mouth IgG Autoimmune disease against hemidesmosomes that hold the basal layer to basement membrane Presents with a smooth surface on histology and a linear immunofluorescence Turgid Blisters that do not tear easily and are not present in the mouth IgA Immune Complex deposition at the tips of dermal papillae inducing an elevation of epidermis Associated with Celiac Sprue and a reaction to Gluten/Gliadin found in wheat products
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Pathology Skin MALIGNANT TUMORS Sqaumous Cell Carcinoma Sqaumous Cell Carcinoma, wherever it is in the body, will have a carcinoma in situ phase, and can be identified by cytoplasmic bridges and keratin pearls. You will see this again in GI and in Lung
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Tumor that occurs in older individuals on sun‐exposed areas Caused by exposure to UVB radiation Fair skin, Hydrocarbons, Burns, and radiations ↑risk Xeroderma Pigmentosum (absence of the enzymes required to repair thymidine dimers created by UVB radiation) significantly ↑risk Has a premalignant condition called Actinic Keratosis Sun‐exposed areas generate cutaneous horns These are brown‐black rough nodules on the skin Premalignant and essentially means “here comes the cancer” Has another premalignant condition called Bowen’s Disease Is just a carcinoma in situ Often does not metastasize though can invade locally Key Associations Keratin Pearls – whorls of pink material within the tumor Cytoplasmic Bridges – look for these in vignette, they are desmosomes Carcinoma in Situ – tumor is entire width of epithelium without invasion
Basal Cell Carcinoma The history and incidence is o almost the same as SCC. Look for Pearly or Greasy description with o a central ulceration to o differentiate from SCC
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It is the single most common tumor in humans Occurs in the elderly and in sun‐exposed areas Described as a raised papules with translucent, pearly lesion of hair‐bearing skin May ulcerate in the center of the lesion (not shown) Under the scope we will see a basaloid proliferation Invasive nests in the dermis that are lined with deeply staining cells Because they line up, we call them palisading Because they are dark, they look like basal cells, thus basaloid Very rarely metastasizes but is horribly locally invasive
Pearly papule
MALIGNANT TUMORS
Disease Sqaumous Cell Carcinoma Basal Cell Carcinoma
Character Occurs on sun‐exposed areas in patients with fair skin or Xeroderma Pigmentosum Look for S‐100 positivity, keratin pearls, cytoplasmic bridges, and a carcinoma in situ Has a premalignant lesion called actinic keratosis Occurs on sun‐exposed areas in patients with fair skin or Xeroderma Pigmentosum Look for pearly papules with central ulceration They are invasive nests of deeply staining cells (basaloid) that line up in a circle (palisading)
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