Dermatopathology Flashcards
clinical word for freckles?
ephelis
acantholysis definition?
the breaking of intercellular connections between keratinocytes
acanthosis definition?
epidermal hyperplasia
dyskeratosis definition?
the atypical keratinization below the stratum granulosum
erosion definition?
focal incomplete epidermal loss
exocytosis definition?
epidermal inflammatory cells
hydropic swelling?
intracellular keratinocyte edema
hypergranulosis definition?
hyperplasia of the SG layer
hyperkeratosis definition?
hyperplasia of the SC layer
lentigenous definition?
linear (non-nested) melanocyte proliferation within SB layer
papillomatosis definition?
hyperplasia of dermal papillae; causes surface elevation
parakeratosis definition?
SC layer retains their nuclei
spongiosis definition?
epidermal intercellular edema
vaculoization defintion?
formation of vacuoles within keratinocytes
what is a melanocytic nevus?
it is a congenital or acquired melanocytic neoplasm
what are the three types of melanocytic nevi?
junctional, compound, and intradermal
what is a junctional nevus?
where there are nests of melanocytic cells/nevus cells at the dermoepidermal junction; they are usually flat and brown to black
what is a compound nevus?
when there are nests of nevus cells/melanocytes dipping into the dermis level as well as at the dermoepidermal junction; they are slightly raise and colored
what is an intradermal nevus?
it is one in which melanocytic nevus cells are located only in the dermis, they are raised and normally flesh colored
what types of mutation can cause nevi?
activating mutations in BRAF that cause proliferation of melanocytes
what is a dysplastic nevus?
often a compound nevus with atypical growth
what are three ways a dysplastic nevus is different from a regular nevus?
- basal cell layer replacement via lentigenous hyperplasia
- papillary dermal fibrosis
- pigment incontinence
what is pigment incontinence?
when dead melanocytes release melanin into dermis
what mutation can be attributed to some dysplastic nevi?
BRAF or NRAS - activating
what is dysplastic nevus syndrome?
an AD familial disorder characterized by hundres of nevi; strongly associated with melanoma and can result from familial mutation of CDK4
acquired mutations of BRAF and NRAS are commo
where can you get melanoma?
SMEMEA
skin, mucosal surfaces, esophagus, meninges, eyes, anogenital area
what is the microscopic histology of melanoma?
large nuclei with irregular contours, chromatin clumped at periphery of nuclear membrane; cherry red color to nuclei
what are the two types of growth you see with melanoma?
radial and vertical
what is radial growth?
horizontal spread of melanoma within the epidermal and superficial dermal layer, dont metastasize
what are some examples of radial growth?
lentigo maligna - an indolent lesion on the face that may not progress for decades
superficial spreading melanoma - sun-exposed skin; most common
acral/mucosal lentigenous - not from sun-exposure
what is vertical growth?
the invasion of the melanoma into the dermis, involving formation of a nodule
cells lack maturation and have the capability to metastasize
what is the Breslow thickness?
it is a measure of the melanoma from stratum granulosum to the deepest layer of penetration - it correlates with ability/likelihood of metastasis - the deeper, the more likely it is to metastasize
what are some mutations that may lead to melanoma?
BRAF, NRAS, PI3K/AKT
RB mutations that affect CDK inihibitors
telomerase activators (mutations of TERT promoter)
how does melanoma metastasize?
hematogenously
what is a seborrheic keratosis?
it is a uniform, round, brown lesion with keratin plugs or horn cysts
what mutation leads to seborrheic keratosis?
mutations in FGFR2 which increase the Ras and PI3K/AKT pathways - leading to epidermal proliferation
what can be one cause of seborrheic keratosis?
paraneoplastic syndrome indicative of a GI malignancy - the cancer produced TGF-alpha which stimulates epidermal proliferation
what is the microscopic morphology of seborrheic keratosis?
exophytic, monotonous sheets of small cells with variable pigmentation; hyperkeratosis
what is acanthosis nigricans?
it is a hyperpigmented velvety lesion that occurs in flexural areas
what are some microscopic morphologies of acanthosis nigricans?
prominent rete ridges and hyperkeratosis, basal cell hyperpigmentation (BUT no basal cell hyperplasia)
what are the two types of acanthosis nigricans?
benign and malignant
what is benign acanthosis nigricans?
it is familial AD and usually develops in childhood due to inheritance of FGFR-3 mutation
can also be related to obesity or endocrine disorders
what is malignant acanthosis nigricans?
it develops in adulthood and is usually associated with occult adenocarcinoma
what is the proper term for a skin tag?
fibroepithelial polyp
what is a fibroepithelial polyp?
it is a tumor with a fibrovascular stalk that is covered in benign epidermis
what is an epithelial cyst?
aka wen
it is a lesion filled with keratin, lipid, and sebaceous secretions
what are some types of epithelial cysts?
epithelial inclusion cyst, pilar (trichilemmal) cysts, dermoid cyst, streatocystoma multiplex
what is an epithelial inclusion cyst?
it contains keratin, wall is made of normal epidermis
what is a pilar (trichilemmal) cyst?
wall is made of follicular epithelium
what is a dermoid cyst?
wall is similar to epidermis but has lots of hair follicles
what is a steatocystoma multiplex
wall resembles sebaceous gland ductal epithelium with numerous compressed sebaceous lobules
what are adnexal tummors?
tumors arising from skin appendages like sebaceous glands, hair follicles etc
what is Cowden syndrome?
a malignancy that can have adnexal tumors as markers
what is actinic keratosis?
a brown/red lesion due to sun-exposure and hyperkeratosis
what is the morphology of actinic keratosis?
cutaneous horns, basal cell hyperplasia, dyskeratosis, parakeratosis; blue-gray elastic fibers due to abberant fibroblast action due to UV exposure
what mutation causes actinic keratoses?
TP53 due to UV
what is actinic keratosis a precursor for?
squamous cell carcinoma
what is squamous cell carcinoma morphology?
red scaling plaques to more developed nodular ucleractions with complete epidermal atypia
what is a keratocanthoma?
it is a type of SCC (maybe) that presents as a cup shaped nodule with keratin filled crater
what mutations are responsible for scc?
TP53 mutation (with actinic keratosis precursor) HRAS mutation (activating) lof Notch signaling responsible for epidermal differentiation
what genetic disease predisposes people to SCC?
xeroderma pigmentosa - involves loss of nucleotide base excision repair mechanism for pyrimidine dimers
what are other potential causes of SCC?
immunosuppression (HPV infection?) and industrial carcinogens
what is basal cell carcinoma?
hyperproliferation of basal cells
what is the morphology of BCC?
pearly, telangiectatic nodules that dont metastasize and are locally invasive
what are the two ways BCC can occur?
multifocal and nodular
what is multifocal BCC?
it is only in the epidermis and consists of superficial spreading
what is nodular BCC?
characterized by islands of basal cells in the dermis that are hyperchromatic and in a mucinous matrix with stroma retracting from the cells
what is nevoid basal cell carcinoma syndrome?
aka Gorlin syndrome; an AD disorder consisting of multuple BCCs early in life
what is the main mutation causing BCC?
unbridled Hedgehog signaling
SHH normally binds to its receptor PTCH which causes it to release SMO which goes on to activate GLI1 which increases cell proliferation - when SHH is unbridled, you get lots of cell proliferation
what is dermatofibroma?
a benign neoplasm characterized by dermal fibroblast proliferation and trapping of collagen; it includes epidermal hyperplasia over the region and downward elongation of rete ridges because of this
spindle cells are characteristic of these too
what is dermatofibrosarcoma protuberans?
a well-defined fibrosarcoma characterized by closely packed fibroblasts in a pinwheel shape
what mutations can cause dermatofibrosarcoma protuberans?
a translocation of the collagen 1A1 gene and PDGFbeta genes in which the collagen promoter is put in front of the PDGFbeta gene, overexpressing it, leading to tumor cell growth
what is mycosis fungoides?
a cutaneous CD4+ cell lymphoma characterized by red scaling plaques, fungating nodules
what is Sezary syndrome?
a type of mycosis fungoides that involves diffuse erythema and scaling across entire body
what are histologic characteristics of mycosis fungoides?
the presence of Sezary-Lutzner cells which form band-like aggregates in the superficial dermis; they can invade into the epidermis, forming Pautrier microabscesses
what is mastocytosis?
an accumulation of mast cells in the skin causing a brown-pink nodule that may be prurituc
what causes the symptoms of mastocytosis?
release of histamine and heparin; systemic symptoms include gi bleeding, nasal discharge, and osteoporosis)
what stains would you use to visualize mastocytosis microscopically?
Giemsa or toludine blue (in case the mast cells are degranulated)
what mutation causes mastocytosis?
activating mutation in the Kit receptor tyrosine kinase which drives cell growth and survival
what is urticaria?
the formation of hives due to introduction of something into body; get edmeatous wheals often due to mast cell degranulaiton
what layer of skin does the urticaria edema occur in?
the dermis
what are the three types of urticaria?
IgE and mast cell dependent
IgE independent and mast cell dependent
IgE and mast cell independent
how do you get IgE and mast cell dependent urticaria?
type 1 hypersensitivity reaction to allergens like food, drugs, pollen
how do you get IgE independent, mast cells dependent urticaria?
direct stimulation of mast cells without IgE by things like antibiotics, opiates, and curare
how do you get IgE and mast cell independent urticaria?
local increase of vascular permeability by things like aspirin which inhibits the cyclooxygenase pathway
what is acute eczematous dermatitis?
a type IV hypersensitivity that involves reactive chemicals reacting with self-proteins to make haptens that act as neoantigens and cause an inflammatory response via Langerhans cells - then upon reexposure you get a reaction
what is allergic contact dermatitis?
when you additionally have spongiosis (intercellular epidermal edema) that splays apart keratinocytes via desomosomes in SS
what do lesions in acute eczematous dermatitis look like?
oozing, crusting, red, vesicles that can eventually become scaling red plaques
what is erythema multiforme?
a type IV hypersensitivity reaction that is CD8+ T cell mediated and causes blisters and targetoid lesions
what are some causes of erythema multiforme?
infections like HSV and typhoid, antibiotics (sulfonamides, penicillin, etc) or cancer and collagen vascular diseases (lupus and dermatomyositis)
what are the three types of erythema multiforme?
EM minor, EM major (Steven’s Johnson syndrome), and toxic epidermal necrolysis
what are the manifestations of EM minor?
blisters and targetoid lesions, dermoepidermal lymphocytic infiltrate, dermal edema; self-limiting
what are the manifestations of Stevens-Johnson syndrome (EM major)?
febrile form with diffuse blisters all over skin and other surfaces like conjunctiva, mucosal surface, and genitals
what are the manifestations of toxic epidermal necrolysis?
full thickness, diffuse necrosis and sloughing of cutaneous and mucosal epithelia
what does psoriasis look like?
salmon-pink lesions with silvery scales; often get nail dysfiguration
what are some diseases associated with psoriasis?
arthritis, myopathy, enteropathy, joint diseases, AIDS
what can psoriasis lead to increased risks of?
CV disease and stroke
what are microscopic manifestations of psoriasis?
acanthosis and increases rete ridges increased mitoses above SB parakeratosis auspitz sign spongiosis in SS layer munro microabscesses
what is the Auspitz sign?
due to epidermal thinning over dermal papillae, you get pinpoint bleeding from dermal bv’s when scale is removed
what is a munro microabscess?
accumulation of neutrophils in the stratum corneum
what is the pathogenesis of psoriasis?
type IV hypersensitivity mediated by CD4+ Th1 cells, Th17 cells and CD8+ cells
what cytokines cause hyperkeratosis in psoriasis?
INF-gamma, IL-17, and TNF
what is the Koebner phenomenon?
genesis of new lesions at sites of trauma
what is seborrheic dermatitis?
CID common in areas with lots of sebaceous glands - macules and papules on erythematous-yellow, greasy base
what are the six P’s of Lichen Planus?
pruritic, purple, polygonal, planar, papules, plaques
what are other characteristics of Lichen Planus?
self-limited, can cause SCC if chronic, koebner happens, wickham striae; dense continuous infiltrate of lymphocytes at DE jxn
what is pemphigous?
an inflammatory blistering disorder that is a type II hypersensitivity rxn
what are morphologic hallmarks of pemphigous?
acantholysis with intercellular clefting and intraepithelial blisters
what is the morphology of pemphigous vulgaris?
involves places other than skin inlcuing mucosa; have easily ruptured blisters due to separation occurring right above basal layer (suprabasal blister)
against what is the antibody against in pemphigous vulgaris?
desmoglein 1 and 3
what is the morphology of pemphigous foliaceus?
superficial blisters that present at erythema and crusting - subcorneal blister (desmoglein 1 antibody)
what class of antibodies is involved in pemphigous?
IgG - it disrupts cellular adhesion and activates intercellular proteases
what do you see in immunofluorescence with pemphigous?
netlike structures composed of desmoglein antibodies
what is bullous pemphigoid?
an autoimmune disorder characterized by tense blisters that arent easily ruptured that are sub-epidermal (i.e. at DE jxn)
what are the autoantibodies in bollus pemphigoid against?
BPAG2 autoantibodies (hemidesmosomes - which is what holds epidermis to dermis)
what is the Nikolsky sign?
when you rub the skin and you get immediate exfoliation and blister formation - positive in P. vulgaris and negative in bullous pemphigoid
what is dermatitis herpetiformis?
a rare disorder characterized by urticaria and grouped vesciles - people develop IgA ab’s to gluten and these cross-react with reticulin in epidermal basement memrbane - subdermal blister,
what is epidermolysis bullosa?
inherited disorders in structural proteins - when you rub the skin you get blisters
what are the three types of epidermylosis bullosa?
simplex, junctional, dystrophic
what is simplex epidermylosis bullosa?
defects in the basal layer (mutation in keratin 14 or 5) dominant negative
what is junctional epidermylosis bullosa?
lamina lucida level blisters, AR defects in laminin which normally binds to hemidesmosomes
what is dystrophic epidermylosis bullosa?
blisters develop beneath lamina densa in association with rudimentary or defective anchoring fibrils - mutation in type VII collagen
what are the two types of acne vulgaris?
noninflamm and inflamm
what are open comedones?
small follicular papules containing a central black keratin plug
what are closed comedones?
follicular papules without visible central plaques
what is rosacea?
non-specific perifollicular infiltrate with dermal edema due to high cutaneous levels of antimicrobial peptide cathelicidin
what is panniculitis?
inflammation of subcutaneous fat
what are two types of panniculitis?
erythema nodosum (very painful); erythema induratum
what is erythema nodosum?
veyr tender erythematous nodules that affects connective tissues between fat lobules and lobules themselves
what is erythema induratum?
primary vasculitis of subcutaneous fat with subsequent inflammation and necrosis of adipose tissue
what is molluscum contagiousum?
a poxvirus that causes firm, prurituc, pink umbilicated papules that has a cheesy material containg molluscum bodies; microscopically see lots of virions
what is impetigo?
superficial bacterial infection (s. aureus and Group A step) that is super contagious and can be bollus in kids
“honey colored crust” - pustules have lots of neutrophils and G+ cocci
