1.1 Pathology of Skin (pt 1) Flashcards
what is the deadliest of all skin cancers?
provide characterisitics!
malignant melanoma
strongly associated w/ sun exposure
inherently immunogenic (T-cell)
(mutation = cell cycle regulator: p16/INKa, CDK4), growth factor receptors - RAS, BRAF & telomerase)
= vary color, large, irregular, hetergenous, notched borders, pigment incontinence
what is mastocytosis
and what is an example
spectrum of rare disorders due to increased number of mast cels in skin & maybe other organs
-ex: urticaria pigmentosa: predominate in children; could be nodular, diffuse &/or multiple
10% of ind w/ mast cell dz have systemic dz (ex adults: kit mutation in systemic mastocytisis)
What are the ABCDEs of Melanoma
(what does a normal mole look like?)
A: asymmetry
B: border
C: color
D: diameter
E: evolving
normal mole = brown/tan, flat/raised, round/oval, <6mm
what is the difference btn papule and nodule
both - elevated dome shaped/ flat topped lesion
papule = 5 mm
nodule = >5mm
provide the following for Cowden syndrome:
inheritance pattern
chromosomal location/gene/protein
fxn/manifestation of loss
inheritance pattern: AD
chromosomal loaction/gene/protein: 10q23/ PTEN/PTEN
fxn/manifestation of loss = trichilemmomas (lipid phosphatase/benign follicular appendage tumor) & internal adenocarcinoma (breast & endometrial)
how common are skin conditions in the US?
very common!
affect 1/3 of US population
what are examples of tumors of the dermis
benign fibrous histocytoma (dermatofibroma)
Dermatofibrosarcoma protuberans
explain the difference btn epidermal ridges and demal papillae
epidermal ridges (aka rete ridges) that project into the dermis *look different based on location*
dermal papillae - project into the epidermis
What is dermatofibrosarcoma protuberans
= primary fibrosacroma of the skin
==> translocation COL1A1 (collagen 1A1) & PDGF-B –> overexpress PDGF-B –> tumor cells growth through an autocrine loop
= encapsulated, cellular (could involve fat), slow growing & locally aggresive - rarely metastasize
*Storiform pattern (last pic) ; closely packed fibroblasts arranged radially (pinwheel appearance)
This shows a stain that positively stained fro the melanocytic marker, what is the marker?
HMB-45
how do actinic keratosis present histologically
atypical basal cells- pink/red cytoplasm
Intercellular bridges present (not in BCC!)
Parakeratosis - thickened stratum corneum that retain their nuclei
Elastosis: thick, blue-gray elastic fibers of superficial dermis
BM intact (not in SCC!)
how does the basillar layer mature?
bottom to top
columnar cuboidal –> stellae
what is lentigo
localized, circumscribed melanocytic hyperplasia (linear, non-nested)
–>infancy & childhood
-DO NOT darken w/ sun
provide the following for familial melanoma syndrome:
inheritance pattern
chromosomal loaction/gene/protein
fxn/manifestation of loss
inheritance pattern: AD
chromosomal loaction/gene/protein: 9p21 - CDKN/p16/INK4 or CDKN2/p14/ARF
fxn/manifestation of loss: melanoma
what are the disorders of pigmentation and melanocytes
freckles (ephelis)
lentigo
melanocytic nevus
dysplastic nevi
melanoma
how do actinic keratosis present?
who is most suseptible
elderly
= prolif of keratin process make horn (aka hyperkeratosis)
=tan, brown, red or flesh colored < 1cm
what is the word for thickening of the stratum corneum bc qualitative abnormality of keratin
hyperkeratosis
provide the following for Tuberous sclerosis:
inheritance pattern
chromosomal loaction/gene/protein
fxn/manifestation of loss
inheritance pattern: AD
chromosomal loaction/gene/protein: 9p34/TSC1/hamartin & 16p13/TSC2/tuberin
fxn/manifestation of loss: (-)ly regulate mTor, angiofibroma, mental retardation
what is the morphology for acanthosis nigricans
epidermis and underlying enlarged dermal papillae undulate sharply and make numerous peaks/valleys
see hyperplasia, hyperkeratosis & slight basal cell layer hyperpigmentation
what is scale
dry, horny, platelike outgrowth
result from imperfect cornification
Describe the pathogenesis, morphology, presentation of BCC
*rmr BCC = most common invasive CA in humans & most common malignancy worldwide BUT metastasis is rare*
pathogenesis: uncontrolled hedgehog signaling - PTCH LOF mutation
morphology: basal cell prolif; 1. multifocal growth from epidermis & 2. nodular lesion growing downward into dermis ad cords and islands of basophilic cells w/ hyperchromic nuclei
palisading - cells in periphery of tumor cell islands tend to be arranged radially w/ long axes in parallel alignement
present: pearly papules w/ telangictasia, elevated & translucent w/ some sort of central umbilication
define/describe (presentation & microscopicaly):
seborrheic keratoses
= common, benign epidermal tumor; common in elderly
=pigmented or pale/irritated (only bc ppl pick at skin) ; mostly on the trunk, superficial, flat, round/coin-like
=waxy exophytic lesions (stucco keratosis) crumble/scrape off
pseudohorn cysts- keratin on surface- rete pegs proliferate and highly pigmented
what are the components of epidermis
(epidermis = most superficial)
=stratified squamous epithelium
squamous epithelial cells (keratinocytes)
melanocytes
dendritic cells
merkel cells
define excoriation
traumatic lesion breaking the epidermis - cause raw linear area
what is the pathogenesis and morphology of melanocytic nevus
pathogenesis: activating mutation in BRAF, less often NRAS
Morphology:
- junctional : flat; nest of nevus cells at dermoepidermal jxn (common in kids) - larger cells & produce melanin
- compound: rounded/raised; nests/cords of melanocytes that extend into underlying dermis - smaller, produce little pigment
older adults: intradermal nevi
what is onycholysis
separation of nail plate
what is Leser Trelat sign?
sudden appearance of multiple seborrheic keratosies & paraneoplastic syndrome
b/c keratnocyte stimulation via TGFalpha made by visceral cancers
what is the mnemonic for painful skin lesions
GLEN-DAB
Glomus tumor (typically under nail)
Leiomyoma (angio-type)
Eccrine spirademona
Neurofibroma
Dermatofibroma
Angiolipoma
Blue rubber bled nevus
describe the following for blue nevus
diagnostic architectural features,
cytologic feature
clinical significance
diagnostic architectural features: non-nested dermal inflitration, often have fibrosis
cytologic feature: highly dendritic, heavily pigmented cells
clinical significance: black/blue nodule; confused w/ melanoma CAN BE PAINFUL
This shows vertical growth phase of a tumor, what are favorable factors in relation to this??
surface of skin to tumor depth < 1 mm = good!
describe the following for spindle & epitheliod cells (spitz nevus):
diagnostic architectural features,
cytologic feature
clinical significance
diagnostic architectural features: fascicular growth
cytologic feature: large, plump, pink-blue cytoplasm; fusifrom cells
clinical significance: common in kids; confused w/ hemangioma (bc are red & pink nodules)
what is benign fibrous histiocytoma (dermatofibroma)
= adults (esp legs of young/middle aged women)
-asymptomatic; increase/decrease in size over time
=indolent
*may have Hx of antecedent trauma –> abnormal response to injury/inflam –> increased ammount of altered collagen in hypertrophic scar or keloid
lenticular cells present on biopsy
what is the word for thickened, rough skin (esp due to repeated rubbing)
lichenification
what pigmented lesion is most common in children
how do they present?
freckles (epheis)
1-10mm tans-red-brown macules ==> fade depending on sun exposure
due to focal melanin overproduction w/i basal keratinocytes
describe the following for congenital nevus:
diagnostic architectural features,
cytologic feature
clinical significance
diagnostic architectural features: deep dermal, maybe subQ growth around adnexa, neurovascular bundles and BV walls
cytologic feature: look like ordinary acquired nevi
clinical significance: present @ birth, increased melanoma risk
provide the following for xeroderma pigmentosum:
inheritance pattern
chromosomal loaction/gene/protein
fxn/manifestation of loss
inheritance pattern: AR!!!
chromosomal loaction/gene/protein: 9q22 & others; XPA/XPA & others
fxn/manifestation of loss: melanoma & nonmelanoma skin cancer (malfxn of NER)
what is vacuolization
vacuoles w/i or adjacent to cells
often = basal cell basement membrane zone area
when do you usuallly see hydropic swelling (ballooning)
intracellular edema bc viral infxn
what are adnexal (appendage tumors)
= hundreds of neoplasms arising from showing differentiation toward cutaneous appendages
ex: eccrine poroma, cylindroma, syringoma, sebaceous adenoma, pilomatricoma, etc
why is it that some areas of the skin have 4 layers and others have 5
stratum lucidum - only seen in places w/ thick layers of skin (palm/soles)
layers mneumonic: “Come, Lets Get Sun Burned”
what is a wheal
itchy, transient, elevated lesion w/ variable blanching & erythema formed as result of dermal edema
what is the relationship of melanocytes and keratinocytes
melanocyte makes melanin and delivers it to keratinocytes
-melanin in keratinocyte help protect skin from UV
what is darier sign
see in acute hypersensitivity rxn
-localized are of dermal edema & wheal when lesional skin is rubbed
what is the function of keratinocytes
tough, durable physical layer
attached via desmosomes
make keratin: intermediate filaments proteins making up the cytoskeleton of cells (Ab in cytokeratine used to identify pathology in keratin)
make cytokines and defensins
what are epithelial inclusion cysts
slight elevation & nodular cyst
“sebaceous cyst” = sebaceous material - can ooze if ruptured (foul smell)
“wen”
provide the following for Muir-Torre Syndrome
inheritance pattern
chromosomal loaction/gene/protein
fxn/manifestation of loss
inheritance pattern: AD
chromosomal loaction/gene/protein: 2p22/MSH2/MSH2 & 3p21/MLH1/MLH1
fxn/manifestation of loss: sebaceous neoplasia( DNA match repair) & internal malignancy (colon & others)
what are tumors of cellular migrants to the skin
mycosis fungoides (cutaneous T cell lymphoma)
mastocytosis
what are the components of dermis
Connective tissue:
lymphocytes: (primarily T)
lymphatics
small BVs
afferent & sensory N. fibers
adnexal components (hair follicle, sebaceous glands, & sweat glands)
what is dermatographism
dermal edema - looks like hives due to localized stroking or apparently normal skin w/ pointed instument
what is the fxn of the arrector pili M
attached to hair shaft
-constrict and cause “goose bumps”
what is Spongiosis
edema causing intercellular bridges btn cells to become prominent
what are the types of benign epithelial tumors
=SAFE
Seborrheic keratoses
Acanthosis nigricans
Fibroepithelial polyps
Epithelial or follicular inclusion cyst
what are warning signs of melanoma that don’t follow the ABCDE rule
sore that doesnt heal
spread of pigment from border of the spot to surrounding skin
redness/ new swelling beyond border
change in sensation (itchy, tender, pain)
change in surface (scaliness, oozing, bleeding, lump/bump)
what is the word for elevated flat-topped lesion, >5 mm
plaque
describe the following for dysplastic nevus
diagnostic architectural features,
cytologic feature
clinical significance
- diagnostic architectural features: coalescent intraepigermal nests; larger than other nevi (>5mm)
- cytologic feature: irregular shaped, dark stained nuclei= cytologic atypia &
lamellar fibrosis in dermis–> melanin incontinence (melanin lost and eaten by macrophage:
; lentiginous melanocyte hyperplasia
- clinical significance: *potential precursor for melanoma*
_(_germline mutation of gene encoding cell cycle regulators - p16/INKa, CDK4 & telomerase)
what are premalignant epidermal tumors
& what factors increase risk of getting these
actinic keratosis
outdoor,sun exposure & light skin
describe the following for Halo nevus
diagnostic architectural features,
cytologic feature
clinical significance
diagnostic architectural features: lymphocytic infiltration around nevus cell
cytologic feature: like ordinary acquired nevus
clinical significance: host immune response against nevus cell &&& surrounding normal melanocytes
Describe the pathogenesis and morphology of SCC
pathogenesis - come from precursor actinic keratosis; greater risk with sun exposure–> acquired mutation form UV light affect pyrimidine dimers; also associated w/ immunosuppression (chemo/organ transplant)
morphology: well demarcated, red, scaly plaque, solar elastosis (nodular and ulcerated) (BM lost)
what is lentiginous
linear pattern of melanocyte proliferation w/i epidermal basal cell layer
what is the difference btn macule and patch
both = circumscribed, flat lesion; distinguished by color
macule = 5 mm
patch = >5 mm
what another word for subcutaneous tissue layer
hypodermis
what are skin adnexa (appendages)
derived from skin and usually next to it - include hair follicle, sebaceous and sweat glands
macroscopic: appendages = specialized structures like nails of fingers and toes
What is acanthosis nigricans & what causes it?
dark, thick skin in creases of flexual areas/ velvet like texture
80% - benign; acquired (obesity, DM, pineal/pituitary tumor, autoimmune endocrinopathy) & inherited (rare, auto dom)
20%- associated w/ malignancy - solid cancers (most common GI carcinoma); paraneoplastic phenomenon
what is the difference btn erosin and exocytosis
erosion: discontinuity, complete loss of epidermis
exocytosis: infiltration of epidermis by inflam cells
what is a fibroepithelial polyp and associated morphology
common sporadic, cutaneous lesion on (axilla & soft tissue) neck, trunk, face and intertriginous areas
morphology: soft flesh colored tumor attached by fibrovascular salk; covered in benign epidermis
may be associated w/ DM, obesity, intestinal polyposis & increase during pregnancy
what is dyskeratosis
abn/premature keratinization w/i cells below stratum granulosum
what is the word for diffuse epidermal hyperplasia
acanthosis
differentiate vesicle, bulla and blister
all = fluid filled
vesicle: <5 mm
bulla: >5 mm
blister: either!
What tumor may evolve and involve ceribroform nuclei?
describe presentation
mycosis fungoides = local T4 cutaneous lymphoma –> evolve to system lymphoma =sezary syndrome (express ceribroform nuclei)
(indolent –> aggressive)
> 40 yr
=scaly, red-brown patches, raised, scaling plaque
-prognosis depends on % body surface involved and progression of patch
(nodule –> plaque –> ulcerations)
provide the following for nevoid BCC syndrome:
inheritance pattern
chromosomal location/gene/protein
fxn/manifestation of loss
inheritance pattern: AD
chromosomal location/gene/protein: 9q22/PTCH
fxn/manifestation of loss: multiple BCC, jaw cyst
