Dermatology Flashcards
Childhood pigmented lesion 1-10mm. tan-brown macules that fades and is recurring dependent on sun-exposure. melanocytes density is normal. hyper pigmentation is based on overproduction of melanin what is this?
freckles (ephelis)
cafe au lait spots larger than freckles, independent of sun-exposure and contain aggregated melanosomes) what is the classic condition that this could be?
neurofibromatosis type 1
benign hyper pigmented macules (tan-brown) in infancy and children and involves mucous membrane independent of sun-exposure (does not get darker) characterized by hyper pigmented, non-basal melanocytes hyperplasia (restricted to cell layer immediately above the basement membrane) with rete ridges and thinning
what is this?
lentigo
lentiginous = describe similar proliferation just in the basal layer in melanocytic tumors
well-demarcated, uniformly round tan-brown papules <6mm acquired mutation of BRAF, NRASm p16/INK4a (the RAS pathway)
three categories
junction nevi
compound nevi
dermal nevi
what condition am I describing and describe the three categories describe neurotization
the moles starts out flat, but then the papules with age
melanocytic nevus (nevi, mole)
junction nevi-nest of nevus cells at dermoepidemeral junction -earliest lesions
compound nevi- nest or cords of melanocytes that extend into the underlying dermis
intradermal nevi- the epidermal component is lost
neurotization- nevi cells that enter the dermis can mature (become smaller, nonpigmented and resembling neural tissue)
moles that are larger than acquired moles (>5mm) flat macules to slight raise plaques with variegated pigmentation and irregular borders that occur in sun-exposed as well as protected skin can be in the hundreds (what is this syndrome called)
pathogenesis of the syndrome are mutation of the CDKN2A (normally encode p16 or CDK4) acquired mutation NRAS, BRAF, and TERT over-expression most are compound nevi with enlarged and fused nest of nevus cells, lentiginous melanocytes hyperplasia, linear papillary dermal fibrosis surround the rete ridges and pigment incontinence (release of melanin from dead melanocytes)
typically have shouldering (typical junction nevi extend 2 rete ridges from the nevi if it extends >2 rete ridges than we worry about dysplastic/melanoma
is there a risk for melanomas?
dysplasic nevi
the syndrome is dysplastic nevus syndrome half of the patients with this syndrome develop melanoma by age 60, but most are clinically stable and sporadic with low risk of malignant transformation
malignant tumor most commonly arises from skin.
pathogenesis- sun-exposure, light skin dysplastic nevi syndrome, mutations that increase RAS and PI3K/AKT pathway (NRAS and BRAF),
mutations that reduces retinoblastoma protein activities or CDK inhibitors (CDKN2A, p16/INK2a, p14/ARF), TERT mutation
morphology: large cells with expanded irregular nuclei containing peripheral clumped chromatin and prominent eosinophilic nucleoli what is this lesion?
progress in radial pattern (describe it)
- lentigo meligna-indolent lesion on the face that may not progress for years
- superficial spreading- most common form of melanoma in sun-exposed spots
- acral ( pertaining to peripheral body parts, such as toes and fingers. Acral melanoma is a type of skin cancer that occurs on fingers, palms, soles, and nail beds. Acral distribution of a dermatosis means it affects distal portions of limbs (hand, foot) and head (ears, nose)) and mucosal lentiginous melanoma unrelated to skin exposure
vertical growth (describe it)
what are the favorable prognostic factors? what are the ABCDE signs?
melanoma (majority are sporadic)
radial growth is non-metastatic horizontal growth at the dermoepidermal
junction vertical growth is metastatic potential growth invading the dermis with the probability of metastasis correlates with depth of invasion. breslow thickness is measured from the epidermal granular layer to the deepest intradermal tumor cells
favorable prognostic factors
- breslow thickness (thinner is better)
- number of mitoses (<1 per mm2) evidence of regression (absent)
- ulceration (absent)
- presence of tumbor infiltrating lymphocytes (many)
- gender (female)
- location (extremities)
- sentinel node micrometastasis (absent)
ABCDE -asymmetries, irregular borders, variegated color, increasing diameter, and evolution over time
xeroderma pigmentosum (nucleotide excision repair is mutated)
neurotization is absent unlike in melanocyte nevi
gross: lesion are uniform, waxy, tan-brown, velvety or granular, round plaques most commonly on the trunk.
if a smaller facial lesion in non-whites are present then that is called dermatosis papulosa nigra
microscopic: lesion are sharply demarcated with exophytic with hyperplasia of pigmented basaloid cells and hyperkeratosis; keratin-filled horn cysts are common large number indicate paraneoplastic syndrome (leser-Trelat sign) due to elaboration of TNF alpha and FGFR3 (found in many seb K and drive growth factors)
also contains pore-like ostia impacted with keratin (differentiate from melanoma)
what is this condition?
seborrheic keratoses
thick lesion with velvety hyperpigmented plaques in flexural areas
benign type arises in childhood-puberty, autosomal dominant, associated with FGFR3 mutation, obesity or diabetes
malignant type: middle age-older individuals associated with adenocarcinoma morphology: hyperkeratosis with prominent rete ridges and basal hyperpigmentation (without melanocyte hyperplasia)
what is this condition?
acanthosis nigricans
known as acrohordon, squamous papilloma or skin tag found on neck, trunk, face, or intertriginous zones in middle age-older individuals described as soft fresh-colored tumors attached to slender fibrovascular stalk covered by benign epidermis associated with pregnancy, diabetes, or intestinal polyposis
what is the condition?
fibroepithelial polyp
cyst commonly presented as well-circumscribed firm, subcutaneous nodules rupture can spill keratin into the dermis, leading often to painful granulomatous inflammation
what is this condition?
epithelial cyst (Wen)
lesion on the scalp and forehead composing of islands of basaloid cells and apocrine or eccrine differentiation to form a hat-like growths (tubans tumor), mutation of CYLD tumor suppressor “jagsaw puzzle” C
multiple small tan papules near the lower eyelids composed of basaloid epithelium with eccrine differentiation S
lobar proliferation of sebocytes with frothy lipid filled cytoplasm associated with muir-Torre syndrome (subset of HNPCC), linked to germline deficit in DNA mismatch S
proliferation of basaloid cells that form hair follicles-like structures T
proliferation of basaloid cells that show hair-like differentiation associated with mutation of CTNNB1 gene encoding beta-catenin P
apocrine carcinomas occurring inthe axilla and scalp and exhibit ducal differentiation showing prominent apocrine secretion A
palm and sole where sweat glands are numerous E
cylindroma
syringoma
sebaceous adenomas
trichoepitheliomas
pilomatrixomas
apocrine carcinoma
eccrine poroma
premalignant dysplastic lesion associated with chronic sun-exposure in light-skinned individuals
caused by sun exposure, ionizing radiation, industrial hydrocarbon, arensic
gross: <1cm tan-brown, red, flesh colored with rough sandpaper-like consistency that can form cutaneous horns
microscopic: hyperkeratosis and parakeratosis (parakeratosis have retained nuclei). dermis exhibits thickened blue-gray elastic (elastosis) due to aberrant synthesis by sun damaged fibroblasts
eosinophilic (pink cytoplasm) due to dyskeratosis, intracellular bridges
can progress to SCC if given enough time
can get actinic cheilitis
what is the condition?
actinic keratosis
second most common tumor of sun-exposed skin of older individuals UV radiation inducing DNA damage and dampening the immune function of langerhan cells this increase of infection to HPV subtype 5 and 8 acquired or germline (xeroderma pigmentosum) p53 mutation allows rapid accumulation of mutation that increase RAS signaling or that decrease Notch signaling
gross: well-demarcated, red, scaling plaques; invasive lesions are nodular and prone to ulceration
microscopic: full-thickness epidermal atypia invasive tumors vary from well differentiated (with prominent keratinization) to highly anaplastic with necrosis
risk factor: industrial carcinogens (tars/oil) chronic ulcers and draining osteomyelitis, burn scar, ingestion of arsenicals, ionizing radiation, tobacco and betel nut
in situ: lesion appear as sharply defined, red, scaling plaques (enlarged & hyperchromatic nuclei)
invasive: lesions are nodular, keratin production (hyperkeratotic scale) may ulcerate
- anaplastic cells, dyskeratosis (single-cell keratinization)
squamous cell carcinoma
most common invasive human cancer of the skin PTCH absence or PTCH and SMO mutation leading to SMO activation and development of BCC
slow growing , sun-exposed sites of lightly pigmented elderly adults, immunosuppression, xeroderma pigmentosum
most BCC mutation resulting in unfettered hedgehog signaling
gross: pearly papules with prominent telangiectatic (rodent ulcers), peripheral palisading
microscopic: monotonous basal cell proliferation either as multifocal superficial growths over large area of skin or as nodules extending deeply into the dermis
gorlin syndrom=nevoid basal cell carcinoma syndrome
-AD, mult BCC <20yo + medulloblastoma, ovarian fibromas, dontogenic keratocyts, pits in palms and soles
Basal cell carcinoma
group of dermal fibroblasts and histiocytes occurring in adults and frequently in the legs of young women.
benign
gross: firm tan-brown occasionally tender papules, become flat over time and inward dimpling with lateral compression (dimple sign), hx of antecedent trauma due to abn response to injury
composed at least patially of factor XIIIa-positive dermal dendritic cells
microscopic: spindle-shaped fibroblast with well-defined middermal nonencapsulated mass many cases have overlying epidermal hyperplasia
benign fibrous histiocytoma
1. cutaneous T-cell lymphoma (CTCL) -generalized LAD in individual over 40 and remain localized for year before evolving into systemic lymphoma
- if there is seeding of the blood by malignant T cells accompanied by diffuse erythema and scaling (erythroderma) that is this condition called?
the proliferating cells are CD4+ with clonal T cell receptor gene rearrangements and CLA is responsible for cutaneous homing behavior
gross: Mycosis Funoides have early lesion resemble eczema in the trunk (also extremities, face, scalp), progressive scaly red-brown patches, scaling plaques (similar to psoriasis) or fungating nodules over various body surfaces correlate with systemic spread
microscopic: hall mark of the original condition is sezary cells-malignant CD4 + (T-helper) markedly folded nuclear membrane, hyperconvoluted or cerebriform- sezary cells
-pautrier microabscesses- small clusters of cells in epidermis could be seen
-band-like aggregates within superficial dermis
- mycosis fungoides
- sezary syndrome
this is a spectrum disorder of epidermal maturation leading to chronic excessice keatin accumulation (hyperkeratosis) resembing fish scales x-linked recessive, autosomal dominant and autosomal recessive forms
primary defect in most forms is increased cell-cell adhesion resulting in abnormal (insufficiency) desquamation
the x-linked disease is caused by steroid sulfatase deficiency leading to increased amounts of proadhesive cholesterol sulfate in intercellular spaces and persistent adhesion in the stratum corneum
microscopically: compacted stratum corneum with minimal inflammation the thickness of the epidermis or granulosum is use to subclassify the disorder
ichthyosis
acquired form (ichthyosis vulgaris)
delayed hypersensitive response driven by langerhans cell proliferation
gross: pruritic, red, papulovesicular to blistered, oozing and crusted, chronic exposure can evolve into psoriasis-like scaling plaques or form yellow crust (impetiginization)
microscopic: early spongiosis (particularly in stratum spinosum) progresses to frank fluid accumulation to form vesicles in chronic condition the vesicular phase is replaced by acanthosis and hyperkeratosis
external application of Ag (poison ivy) or igested food
-usuhiol in poison ivy/oak (Rhus toxicodendron)
acute eczematous dermatitis
gross: salmon-pink plaques with silvery scaling
commonly effects elbows, knees, scalp, lumboscral, nail changes can be seen with yellow-brown discoloration (oncolysis)
microscopic: marked acanthosis with downward rete elongation and mitoses well above the basal layer
Koebner phenomenon- induce psoriatic lesion in suscepible pts with local trauma, start a self-perpetuating local inflammatory response
thin straum granulosum or absent with extensive overlying parakeratosis, dilated vessels in the underlying dermal papillae yield pinpoint bleeds when scales is removed
munro microabscesses: small PMN aggregates in parakeratotic stratum corneum
Auspitz sign- multiple, minute, bleeding points when the scales lifed from the plagues
psoriasis
gross: pruritic, purple, polygonal planar papules that turns into plaques.
itchy, violaceous, flat-topped papules that coalesce-often highlighted by white dots or lines in darkly pigmented people (wickham striae) multiple and symmetrically on wrist and elbows and glans penis, oral mucosal lesions are generally white and netlike
microscopic: SCC noted to occur
koebner phenomenon seen
-wickham striae: papules highlighted with white dots, created by areas of hypergranulosis in darkly pigmented individuals
dense cutaneous infiltrate of lymphs, along dermoepidermal junct (interface dermatitis)
- saw toothing of dermoepidermal interface
- colloid or civatte bodies: anucleate, necrotic basal cell incorpated into inflamed papillary dermis
lichen planus (self-limiting)
autoimmune blistering affecting 30-40 patients- autoantibodies dissolution of intracellular attachement within epidermis and mucosal epithelium and can be fatal with tx
multiple variant:
-most common oral mucosa, scalp, face, interiginous zone, trunk, and pressure points. lesions are superifical easily ruptured blisters that leave shallow, crusted erosion. can be fatal if untreated, what is it?
–suprabasal split
-rare large moist verrucous plaques (wart-like), studded with pustules, typically flexural and interitriginous zones
-more benign form occurring epidemically in south america (Brazil) mainly on face, scalp, and upper trunk. bullae are extremely superficial, leaving slight erythema and crusting after rupture
–subcorneal split
-localized milder variant of pemphigus foliaceus involving only malar distribution
-blistering disorder associated with non-hodgkin lymphoma
all variants have characterized acantholysis with intercellular clefting and intraepithelial blister
pemphigus vulgaris
pemphigus vegetans
pemphigus foliaceus
pemphigus erythematosus
paraneoplastic pemphigus
describe the separation of pemphigus vulgaris and vegetans and foliaceus
separation occurs immediately above the basal layer (suprabasal blister leaving an intact layer of tombstone like basal cells in the vegetans variant.
in the foliaceus variant, only the stratum granulosum is involved and anti-Ig or anti-complement immunofluorescence, netlike reticular staining may be seen in epidermis, outlining each keratinocytes
group of noninflammatory disorders that have blistering at pressure sites or trauma due to defect in structural proteins forming the dermoepidermal junction.
simplex type-mutation of keratin 5 or 14 leading to structural defects in epidermal basal cell layer
junctional type: defect in either BPAG2 or laminin, the latter is protein that links hemidesmosomes and anchoring fibrils; the resulting is blistering at the lamina lucida in otherwise normal skin
dystrophic type: blistering beneath the lamina densa due to to type 7 collagen mutations this form typically leads to cutaneous scarring
NOTE: blisters at site of pressure, rubbing, trauma
electron microscopy can differentiate the various types
epidermolysis bullosa
group of inborn or acquired disturbances of porphyrin metabolism porphyrin are ring structures that bind metal in hemoglobin, myoglobin, cytochromes, cutaneous lesions consist of urticaria and scarring that exacerbated by sun exposure
histology: subepidermal vesicles with marked thickening of the walls of the superficial dermal vessels
porphyria
self-limiting poxvirus infection transmitted by direct contact
gross: firm, pruritic, pink to skin -colored, umbilicated papules seen on trunk or anogenital regions; cheesy material containing diagnostic molluscum bodies can be expressed on central umbilication
microscopic: lesion exhibit cuplike verrucous epidermal hyperplasa with pathognompnic molluscum bodies- eosinophilic cyptoplasmic inclusion in stratum granulosum or stratum corneum
molluscum contagiosum
what are some histology features to note when looking for melanomas?
describe
