Skin Pathology Flashcards
Traumatic lesion breaking the epidermis and causing a raw linear area (i.e., deep scratch); often self induced
Excoriation
5 Disorders of pigmentation and melanocytes
Freckle Lentigo Melanocytic nevus Dysplastic nevus Melanoma
Most common pigmented lesion of childhood; appear after sun exposure, typically fading and darkening cyclically with season changes and are caused by increased melanin pigment in basal keratinocytes
Freckle (ephelis)
_________, which are seen in neurofibromatosis, have similar histoogy to freckles but are larger and arise independently of sun exposure
Cafe au lait spots
Benign localized hyperplasia of melanocytes initiated in infancy and childhood but can occur in all ages; do NOT darken when exposed to sunlight. Histologically characterized by linear melanocytic hyperplasia restricted to cell layer immediately above basement membrane
Lentigo
_______ is a term describing linear melanocytic hyperplasia in the basal cell layer in melanocytic tumors
Lentiginous
[i.e., acral lentiginous melanoma]
Melanocytic nevi are benign growths usually acquired by activating mutations in components of the ______ signaling pathway
They are usually <6mm, tan-brown, and _____ pigmented; consisting of flat macules or elevated papules with well-defined rounded borders
Ras
Uniformly
3 types of nevi include:
________ = nests at dermoepidermal junction
________ = nests or cords grow into underlying dermis w/ nests in dermis and epidermis
_______ =no epidermal nests; usually older lesions
Junctional
Compound
Intradermal
Describe histology of melanocytic nevi (moles)
Benign histology with superficial nests of large-round cells with increased melanin
Deeper than that are cords or single cells, smaller cells, and decreased pigment
Deepest are fusiform, fascicles resembling neural tissue
[she explains it as maturing in opposite direction from normal epithelium— with larger more heavily pigmented cells being more superficially located, and smaller less pigmented cells as nevus goes deeper into dermis]
Autosomal dominant syndrome with 50% chance of progression to melanoma by age 60
Dysplastic nevus syndrome
T/F: all melanoma were at one time dysplastic nevi
False — not all dysplastic nevi become melanoma, and not all melanoma come from dysplastic nevi
Dysplastic nevi often acquire activating mutations in ____ and ____ genes
NRAS; BRAF
Histologically, dysplastic nevi are _____ than acquired nevi. They have ______ pigmentation with irregular borders. They have enlarged epidermal nests that may coalesce with other nests. _____ _____ occurs when single nevus cells replace basal cells along the epidermal-dermal junction. Atypia is signified by large nuclei, irregular angulated nuclear contour, and hyperchromasia. Lymphocytic infiltrate of superficial dermis may occur, as well as melanin incontinence. Linear ____ surrounds the epidermal rete ridges
Larger
Variegated
Lentiginous hyperplasia
Fibrosis
Melanoma is the most deadly of all skin cancers and is strongly linked to acquired mutations caused by exposure to __________ which causes _________
UV radiation in sunlight; DNA damage
Risk factors for melanoma
Light complexion, hair, eyes
History of blistering sunburn(s)
Proximity to the equator
Indoor occupation; outdoor hobbies
Family hx of melanoma or dysplastic nevi
Precursor lesions (congenital or dysplastic nevi)
Xeroderma pigmentosum
Most common sites of melanoma in men vs. women
Men — upper back
Women — legs
Although it is rare in blacks and asians, where is malignant melanoma most commonly found in these pt populations?
Soles
Mucous membranes
Palms
Nail beds
Clinical features of melanoma: ABCDEs
Asymmetry Irregular Borders Variegated Color Increasing Diameter Evolution/change over time (rapid)
Any pigmented lesion with diameter >6mm, any change, itching, or pain should raise suspicion for _____
Melanoma
Driver mutations in melanoma
Disruption in cell cycle control genes: CDKN2A, tumor suppressor genes p15/INK4b, p16/INK4a, p14/ARF
Activation of pro-growth signaling pathways: mutations in BRAF 40-50%, NRAS
Activation of telomerase: TERT in 70% of tumors (MOST COMMON)
Morphologic findings associated with melanoma
Epidermis: single abnormal cells and nests with aggregates of lymphocytic infiltration
Prominent red nucleoli
HMB-45+ staining = indicator of melanoma
The _____ growth phase of melanoma consists of horizontal spread within the epidermis and superficial dermis; tumor cells seem to lack the capacity to ________
Radial; metastasize
Radial growth melanoma; usually an indolent lesion on the face of older men, may remain in the radial growth phase for several decades
Lentigo maligna
Most common type of melanoma, usually involving sun exposed skin; radial growth phase
Superficial spreading melanoma
Type of radial growth melanoma that is UNRELATED to sun exposure
Acral/mucosal lentiginous melanoma
During _____ growth phase of melanoma, tumor cells invade downward into deeper dermal layers as an expansile mass, after a variable and unpredictable period of time following radial phase.
This phase is often heralded by the appearance of a _____ and correlates with the emergence of a tumor subclone with _______ potential. Unlike melanocytic nevi, “______” is absent
Vertical
Nodule; metastatic; neurotization
What indicates the probability of metastasis in melanoma?
Correlated with depth of invasion, which is the distance from superficial epidermal granular cell layer to the deepest intradermal tumor cells — aka the BRESLOW THICKNESS
No mitosis, brisk tumor infiltrating lymphocyte response, no regression, and lack of ulceration are indications of a _____ prognosis in melanoma
Favorable
4 types of benign epithelial tumors
Seborrheic keratoses
Acanthosis nigricans
Fibroepithelial polyp
Epithelial or Follicular Inclusion Cyst (Wen)
Benign epithelial tumors arising in middle age, or older individuals, forming round flat waxy papules with tan-brown color that have velvety or granular surface, pore-like ostia impacted with keratin, and possibly hyperkeratosis with horn cysts
Seborrheic keratoses
[dermatosis papulosa nigra when there are multiple small lesions on face — think morgan freeman]
________ = paraneoplastic syndrome in which there is sudden appearance of large numbers of seborrheic keratoses
Leser-trelat sign
Adnexal (appendage) tumors may consist of hundreds of neoplasms arising from or showing differentiation toward cutaneous appendages. They are benign, nondescript, flesh-colored, solitary or multiple papules and nodules.
________ _______ consists of multiple trichilemmomas d/t loss of function in PTEN leading to increased risk for endometrial cancer, breast cancer, etc
Cowden syndrome
Adnexal tumor with ductal differentiation on forehead or scalpe showing “jigsaw puzzle” pattern
Cylindroma
[turban tumor is when these coalesce with hat-like growth; related to CYLD]
Adnexal tumor found on palms and soles where sweat glands are numerous
Eccrine poroma
Adnexal tumor with eccrine differentiation of lower eyelids
Syringoma
Sebaceous adenoma is associated with ________ syndrome — hereditary nonpolyposis colorectal carcinoma syndrome with DNA mismatch repair protein defects
Muir-Torre
Adnexal tumor with follicular differentiation, CTNNB1 encodes Beta catenin
Pilomatricoma
Inheritance and gene/protein affected in neurofibromatosis I
AD inheritance
Loss of NF1/neurofibromin (normally negatively regulates RAS signaling/neurofibromas)
Inheritance and gene/protein affected in neurofibromatosis II
AD inheritance
NF2/merlin (normally integrates signaling/neurofibromas and acoustic neuromas)
Inheritance and gene/protein affected in xeroderma pigmentosum
AR inheritance
Affects XPA (normally participates in nucleotide excision repair — loss may result in melanoma and nonmelanoma skin cancers)
_____ _____ occurs with sun damaged skin, particularly in lightly pigmented individuals, ionizing radiation exposure, industrial hydrocarbons, arsenic, etc. and progressively worsen with the potential to become ________ with time. They tend to be <1cm, tan-brown, red, or skin colored with rough sandpaper-like consistency
Actinic keratosis; SCC
Actinic keratosis may present grossly as a ______ _______ due to excessive keratin production. Morphologic features include ______ (single-cell keratinization, pink cytoplasm), intracellular bridges, blue-gray _______ (sun damage), and parakeratosis
Cutaneous horn; dyskeratosis; elastosis
Lesions of actinic keratosis that develop on the lips
Actinic cheilitis
Second most common tumor arising in sun exposed sites in older people; occurring more frequently in males than females (except on the legs), and <5% metastasize to regional LNs
SCC
Pathogenesis of SCC
DNA damage induced by UV light; incidence is proportional to degree of lifetime sun exposure
Other factors include immunosuppression (including oncogenic viruses, especially HPV 5 and 8), industrial carcinogen exposure, chronic ulcers and draining osteomyelitis, old burns, tobacco and betel nut chewing, etc
AD inherited condition in which HPV is implicated, leading to increased risk of cutaneous SCC
Epidermodysplasia verruciformis
SCC may be associated with acquired defects in precursor AK, ______ mutations high in caucasions, suggesting dysfunction in this gene is an early event leading to improper repair of UV damage. Mutations in _______ and _______ signaling have also been implicated
TP53; RAS; Notch
Condition characterized by inherited mutation in nucleotide excision repair pathway, leading to improper repair of pyrimidine dimers and increased risk of SCC
Xeroderma pigmentosum
Describe appearance of SCC as an in situ lesion vs. invasive lesion
In situ lesions appear as sharply defined, red, scaling plaques [atypical enlarged and hyperchromatic nuclei involve all levels of the epidermis]
Invasive lesions are nodular, keratin production (hyperkeratotic scale), may ulcerate [anaplastic cells, dyskeratosis]
Most common invasive skin cancer that is slow growing, rarely metastasizes, cured by local excision, and risk factors include sun exposed sites of lightly pigmented elderly adults, immunosuppression, and xeroderma pigmentosum
Basal cell carcinoma (BCC)
Gene mutation(s) associated with BCC
Unbridled Hedgehog signaling, PTCH
AD inherited syndrome resulting in multiple BCC <20 y/o + medulloblastoma, ovarian fibromas, odontogenic keratocysts, pits of palms and soles
Nevoid basal cell carcinoma syndrome (NBCCS) aka Gorlin syndrome aka basal cell nevus syndrome
Gross description and morphology associated with BCC
Pearly papules, telangiectatic vessels, rodent ulcers
Basophilic/basaloid cells, hyperchromatic nuclei, peripheral palisading, artificial clefts separate stroma from tumor
2 tumors of the dermis
Benign fibrous histiocytoma (dermatofibroma)
Dermatofibrosarcoma protuberans
Benign dermal neoplasm of uncertain origin, occurs in adults - esp the legs of young to middle aged women, described as firm, tan-brown papules <1cm that become flattened with time
Dermatofibroma (benign fibrous histiocytoma)
Clinical presentation of dermatofibroma
May be asymptomatic or tender, increase or decrease in size over time, and are considered indolent
Dimple sign = lateral pressure on skin produces a depression
Many present with hx of antecedent trauma w/abnormal response to injury and inflammation
Dermatofibromas are composed of at least partially _______-positive dermal dendritic cells. They consist of benign _______-shaped cells as a well defined _________ (encapsulated or nonencapsulated) mass in mid dermis. There is _________ ________ which consists of overlying epidermal hyperplasia and downward elongation of hyperpigmented rete ridges
Factor XIIIa
Spindle
Non-encapsulated
Pseudoepitheliomatous hyperplasia
Well differentiated primary fibrosarcoma of the skin that is slow growing, locally aggressive, can recur but rarely metastasizes, and is associated with a translocation collagen 1A1 (COL1A1) and PDGFB
Dermatofibrosarcoma protruberans (DFSP)
Dermatofibrosarcoma protruberans is described as a protruberant nodule, usually of the trunk, firm indurated plaque that may or may not ulcerate. What is the morphology of this lesion?
Storiform appearance — closely packed fibroblasts arranged radially, reminiscent of blades of a pinwheel
Rare mitoses, overlying epidermis is thinned
Honeycomb pattern = deep extension from the dermis into the subQ fat
2 types of tumors of cellular migrants to the skin
Mycosis fungoides (cutaneous T-cell lymphoma)
Mastocytosis
Tumor of CD4+ T helper cells in the skin that may eventually evolve into a systemic lymphoma
Mycosis fungoides (CTCL)
Clinical presentation of mycosis fungoides
Usually >40 y/o, truncal lesions (also extremities, face, and scalp)
Scaly red-brown patches, Raised scaling plaques, Fungating nodules
_________ syndrome = erythroderma, diffuse erythema and scaling of entire body surface; composed of ______ cells which have markedly folded nuclear membrane, hyperconvoluted or cerebriform contour, band-like aggregates within the superficial dermis, and _______ ______ which consist of small clusters of cells in the epidermis
Sezary; sezary; pautrier microabscesses
Cutaneous form of mastocytosis often seen in children, characterized by multiple, widely distributed lesions, round-oval, red-brown, nonscaling papules and small plaques
Urticaria pigmentosa
Manifestations of mastocytosis include:
_____ ____= pink-tan brown nodule, +/- pruritis or blister formation
______ sign = localized area of dermal edema and erythema (wheal) when skin is rubbed
_______ = area of dermal edema resembling a hive, result of local stroking skin with pointed instrument
Solitary mastocytoma
Darier sign
Dermatographism
2 mediators released when mast cells degranulate that are implicated in mastocytosis
Histamine
Heparin
Systemic symptoms associated with mastocytosis include pruritis and flushing d/t certain foods, temp changes, alcohol, drugs (morphine, codeine, asa), rhinorrhea, rarely GI or nasal bleeding (AC effects of heparin); and bone pain.
One sign of mastocytosis is __________ in premenopausal women and men d/t excessive histamine release on the bone marrow
Osteoporosis
Mastocytosis is associated with point mutations in _____ RTK leading to mast cell growth and survival. Cells are described as ______-shaped and _____ mast cells, associated with fibrosis, edema, and few eosinophils
KIT; spindle; stellate
Impaired epidermal maturation, chronic excessive keratin buildup (hyperkeratosis) that results in clinically fish-like scales
Ichthyosis
3 types of acute inflammatory dermatoses
Urticaria
Acute eczematous dermatitis
Erythema multiforme
Condition characterized by localized mast cell degranulation, wheals (pruritic edematous plaques), angioedema due to antigen-induced release of vasoactive mediators from mast cells
Urticaria (hives)
Dermatitis caused by external application of antigen (urushiol in poison ivy/oak aka Rhus toxicodendron) or ingested food or drug
Acute eczematous dermatitis
What type of HSR is acute eczematous dermatitis?
Type IV (T-cell mediated inflammatory rxn)
_______ = acute eczematous dermatitis, edema in intracellular spaces splaying them apart, particularly in stratum spinosum
Spongiosis
Acute eczematous dermatitis is described as red, papulovesicular, oozing, and crusted (impetiginization) lesions that, when persistent, may develop ______ and _______ which present as raised scaling plaques
Acanthosis; hyperkeratosis
Erythema multiforme is an uncommon, self-limited hypersensitivity reaction to certain infections and drugs. It is characterized by keratinocyte injury mediated by ___________
CD8+ CTLs
Examples of causes of erythema multiforme
Infections — HSV, mycoplasma, histoplasmosis, coccidiodomycosis, typhoid, leprosy
Drugs — sulfonamides, PCN, barbiturates, salicylates, hydantoins, antimalarials
Cancer — carcinomas, lymphomas
Collagen vascular dz — SLE, dermatomyositis, polyarteritis nodosa
Erythema multiforme leads to a diverse array of lesions including macules, papules, vesicles, bullae, and ______ lesions
______ dermatitis = dermal edema, lymphocyte infiltration along dermoepidermal junction associated with degenerating keratinocytes
________ _______ syndrome = occurs in children, extensive skin involvement + oral mucosa, conjunctiva, urethra, genital, and perianal areas
______ _____ ______ = diffuse necrosis and sloughing of cutaneous and mucosal epithelial
Targetoid
Interface
Stevens-johnson
Toxic epidermal necrolysis
3 types of chronic inflammatory dermatoses
Psoriasis
Seborrheic dermatitis
Lichen planus
Psoriasis is a chronic inflammatory dermatosis with autoimmune basis and may also be associated with myopathy, enteropathy, and AIDS. What genes are implicated in the development of this condition?
HLA-C, HLA-Cw*0602 allele
[homozygous 2.5x increased risk than heterozygotes]
What is the koebner phenomenon as it relates to psoriasis?
Induction of psoriatic lesions in susceptible pts by local trauma, which starts a self-perpetuating local inflammatory response
[this also occurs in lichen planus]
Describe the gross appearance of psoriasis including the significance of auspitz sign
Pink to salmon colored plaques covered loosely by adherent silver scale; often on elbows, knees, scalp, and lumbosacral region
May see pitting and dimpling of nails along with yellow-brown discoloration and oncolysis
Auspitz sign = multiple minute bleeding points when scale is lifted from plaque
Morphologic appearance of psoriasis
Marked acanthosis, regular downward elongation of rete ridges “test tubes in a rack”
Mitoses above basal cell layer, stratum granulosum thin or absent, extensive parakeratotic scale
Munro microabscesses = small PMN aggregates in parakeratotic stratum corneum
The 6 P’s of _____ _____ include pruritic, purple, polygonal, planar, papules, and plaques
Lichen planus
Lichen planus is a self limited disorder of skin and mucosa, resolving spontaneously in 1-2 years. There is often postinflammatory hyperpigmentation left after resolution. ________ is noted to occur in chronic mucosal and paramucosal lesions of lichen planus — possibly due to carcinogenesis in the setting of chronic inflammation. The _______ phenomenon is seen in lichen planus and psoriasis
SCC; koebner
Describe gross appearance of lichen planus
Itchy violaceous, flat-topped papules that may coalesce
Wickham striae — papules highlighted with white dots, created by areas of hypergranulosis in darkly pigmented individuals
Describe morphology of lichen planus
Dense cutaneous infiltrate of lymphs, along dermoepidermal junction (interface dermatitis)
Saw-toothing of dermoepidermal interface
Colloid or civatte bodies: anucleate, necrotic basal cells incorporated into inflamed papillary dermis
3 Inflammatory blistering disorders, and 2 noninflammatory blistering disorders
Inflammatory:
Pemphigus
Bullous pemphigoid
Dermatitis herpetiformis
Noninflammatory:
Epidermolysis bullosa
Porphyria
________ is characterized by IgG autoantibody dissolution of intracellular attachments within the epidermis and mucosal epithelium leading to net-like pattern of intercellular IgG deposits and may be fatal without treatment; occurs in 4-6th decade, M= F
Pemphigus
Most common form of pemphigus, accounting for >80% of the cases worldwide, often affecting the scalp, face, axilla, groin, trunk, and pressure points; presents as shallow erosions with dried serum and crust; affects suprabasal region
Pemphigus vulgaris
Rare form of pemphigus characterized by large moist verrucous vegetating plaques that are studded with pustules; occurs in groin, axilla, and flexural surfaces
Pemphigus vegetans
Benign form of pemphigus mostly found in Brazil; characterized by erythema and crusting on scalp, face, chest, and back; affects subcorneal region
Pemphigus foliaceus
Localized type of pemphigus that is a less severe form of foliaceous, affecting the malar area of the face
Pemphigus erythromatosus
Paraneoplastic pemphigus is associated with malignancies, namely ____ and other _______ neoplasms
NHL; lymphoid
Type of pemphigoid affecting the elderly, esp along inner aspects of thighs, flexor surfaces of forearms, axilla, groin, and lower abdomen; involves subepidermal region
Bullous pemphigoid
With bullous pemphigoid, antibody deposits at dermoepidermal junction. _____ are the bullous pemphigoid antigens which are components of __________ of cells. They do NOT rupture easily, as they are subepidermal nonacantholytic blisters
BPAGs; hemidesmosomes
Dermatitis herpetiformis consists of urticarial and grouped vesicles, usually occurs in men in 3-4th decade. What is the pathogenesis of this condition?
Celiac disease —> development of IgA Abs to gluten which cross reacts with reticulin —> subepidermal blister
Group of disorders due to inherited defects in structural proteins resulting in blisters at sites of pressure, rubbing, or trauma at (or soon after) birth; electron microscopy is used to differentiate among various types
Epidermolysis bullosa
Group of inborn or acquired disturbances in metabolism of pigments normally present in Hgb, myoglobin, and cytochromes; manifestations include urticaria and vesicles associated with scarring, exacerbated by sunlight
Porphyria
The 4 stages of ______ include flushing, persistent erythema and telangiectasia, pustules and papules, and may be associated with _______ which is a permanent thickening of nasal skin; this condition is associated with high cutaneous levels of antimicrobial peptide cathelicidin
Rosacea; rhinophyma
Types of acne vulgaris
Open comedones — central black keratin plug
Closed comedones — keratin plug trapped beneath epidermal surface, potential for follicular rupture
Acne conglobate —severe variant, sinus tract formation and dermal scarring
Bacteria implicated and 2 major Rx treatment options for acne vulgaris
Propionibacterium acnes
Tx: abx for P acnes, 13-cis-retinoic acid (isoretinoin)
The histopathology of _____ _____ is distinctive. In early lesions, the CT septae are widened by edema, fibrin exudation, and neutrophilic infiltration. Later, infiltration by lymphocytes, histiocytes, multinucleated giant cells, and occasional eosinophils is associated with septal fibrosis
Erythema nodosum
Erythema nodosum and erythema induratum are forms of _______, which is an inflammatory reaction in subcutaneous adipose tissue
Panniculitis
Most common form of subacute presentation of panniculitis that is defined as erythematous plaques and nodules that are more readily palpated than seen; lesions usually flatten and become bruise-like over a period of weeks
Erythema nodosum
Erythema nodosum is considered a delayed hypersensitivity rxn to microbial or drug related antigens. What are some specific causes of EN?
Infectious beta-hemolytic streptococcal infection, TB, or less commonly coccidiodomycosis, histoplasmosis, and leprosy
Drugs: sulfonamides, OCPs
Sarcoidosis, IBD, certain malignancies
Uncommon type of panniculitis seen in adolescents and menopausal females, defined as a primary vasculitis of deep vessels supplying fat lobules of subcutaneous region resulting in fat necrosis, granulomatous inflammation, and eventual ulceration with zones of caseous necrosis
Erythema induratum
Verrucae (warts) are squamoproliferative disorders caused by ….
HPV
[anogenital warts = 6,11. In situ SCC and bowenoid papulosis = 16. SCC also associated with types 5 and 8]
Common, self-limited pox virus infection transmitted via direct contact; often affects trunk and anogenital regions as firm and often pruritic pink-skin colored umbilicated papules that appear as ellipsoid homogenous cytoplasmic inclusions with giemsa stain
Molluscum contagiosum
Pathogenesis of impetigo
Staph aureus releases toxin causing epidermal injury — toxin cleaves desmoglein 1
Erythematous macule initially, then multiple small pustules which break causing shallow erosions (honey colored crust)
Tinea pedis may lead to ______ which is discoloration, thickening, and deformity of the nail plate
Onychomycosis
Tinea versicolor occurs on the upper trunk and is highly distinctive in appearance. It is caused by ____________, which is a yeast, not a dermatophyte like the other tinea’s. The lesions consist of groups of macules of varied size and color with a fine peripheral scale
Malassezia furfur
5 potentially life-threatening disorders that have skin rash as a primary feature
Pemphigus vulgaris
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Toxic shock syndrome
Staphylococcal scalded skin syndrome
