Dermatopathology (Martin) Flashcards
1
Q
- macroscopic lesion
- Traumatic lesion breaking the epidermis and causing a raw linear area (i.e., deep scratch); often self-induced
A
excoriation
2
Q
- macroscopic lesion
- Thickened, rough skin (similar to a lichen on a rock); usually the result of repeated rubbing
A
lichenification
3
Q
- macroscopic lesion
- Circumscribed, flat lesion distinguished from surrounding skin by color. Macules are 5 mm in diameter or less, patches are greater than 5 mm
A
macule, patch
4
Q
- macroscopic lesion
- Separation of nail plate from nail bed
A
onycholysis
5
Q
- macroscopic lesion
- Elevated dome-shaped or flat-topped lesion. Papules are 5 mm or less across, while nodules are greater than 5 mm in size.
A
papule, nodule
6
Q
- macroscopic lesion
- Elevated flat-topped lesion, usually greater than 5 mm across (may be caused by coalescent papules)
A
plaque
7
Q
- macroscopic lesion
- Discrete, pus-filled, raised lesion
A
pustule
8
Q
- macroscopic lesion
- Dry, horny, platelike excrescence; usually the result of imperfect cornification
A
scale
9
Q
- macroscopic lesion
- Fluid-filled raised lesion 5 mm or less across (vesicle) or greater than 5 mm across (bulla). Blister is the common term for either.
A
vesicle, bulla, blister
10
Q
- macroscopic lesion
- Itchy, transient, elevated lesion with variable blanching and erythema formed as the result of dermal edema
A
wheal
11
Q
- microscopic lesion
- Diffuse epidermal hyperplasia
A
acanthosis
12
Q
- microscopic lesion
- Abnormal, premature keratinization within cells below the stratum granulosum
A
dyskeratosis
13
Q
- microscopic lesion
- Discontinuity of the skin showing incomplete loss of the epidermis
A
erosion
14
Q
- microscopic lesion
- Infiltration of the epidermis by inflammatory cells
A
exocytosis
15
Q
- microscopic lesion
- Intracellular edema of keratinocytes, often seen in viral infections
A
hydropic swelling (ballooning)
16
Q
- microscopic lesion
- Hyperplasia of the stratum granulosum, often due to intense rubbing
A
hypergranulosis
17
Q
- microscopic lesion
- Thickening of the stratum corneum, often associated with a qualitative abnormality of the keratin
A
hyperkeratosis
18
Q
- microscopic swelling
- A linear pattern of melanocyte proliferation within the epidermal basal cell layer
A
lentiginous
19
Q
- microscopic swelling
- Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae
A
papillomatosis
20
Q
- microscopic swelling
- Keratinization with retained nuclei in the stratum corneum. On mucous membranes, parakeratosis is normal.
A
parakeratosis
21
Q
- microscopic lesion
- Intercellular edema of the epidermis
A
spongiosis
22
Q
- microscopic swelling
- Discontinuity of the skin showing complete loss of the epidermis revealing dermis or subcutis
A
ulceration
23
Q
- microscopic swelling
- Formation of vacuoles within or adjacent to cells; often refers to basal cell-basement membrane zone area
A
vacuolization
24
Q
- “disordered growth”
- loss in uniformity of individual cells and architectural orientation
- pleomorphism
- hyperchromatic
- increased mitoses (nml and abnml)
A
dysplasia
25
Q
Disorders of pigmentation and melanocytes:
A
- freckle
- lentigo
- melanocytic nevus
- dysplastic nevi
- melanoma
26
Q
- most common pigmented lesion of childhood
- 1 mm to several mm, tan-red or light brown macules
- appear after sun exposure
- fade/darken cyclically w/ season changes: hyperpigmentation > increased melanin in basal keratinocytes
A
freckle
(ephelis)
27
Q
- occur in neurofibromatosis
- similar in histology to freckles
- larger, arise independently of sun exposure
- contain aggregated melanosomes (macromelanosomes) in cytoplasm of melanocytes
A
cafe au lait spots
28
Q
- benign localized hyperplasia of melanocytes (no sex or racial predilection, unknown cause)
- initiated in infancy and childhood, occurs at all ages
- mucous membranes and skin
- 5-10 mm, oval, tan-brown macules or patches
- do not darken w/ sun exposure
- histo: linear (nonnested) melanocytic hyperplasia (restricted to cell layer immediately above BM, elongation and thinning of rete ridges common)
A
lentigo
(lentiginous = describe similar proliferations in basal cell layer in melanocytic tumors (i.e. acral lentiginous melanoma, lentigo maligna))
29
Q
- benign, usually acquired by activating mutations in components of RAS or BRAF signaling pathway (limited period of proliferation): p16/INKa inhibitors of CDK4 and CDK6 cause permanent growth arrest (disrupted in melanoma)
- usually < 6 mm, tan-brown, uniformly pigmented
- flat macules or elevated papules, well-defined rounded borders
- different types: junctional nevi, compound nevi, intradermal nevi
- benign histo: superficial (nests, large-round cells, increased melanin), deeper (cords or single cells, smaller cells, decreased pigment), deepest (fusiform, fascicles resembling neural tissue)
- histo helpful in differentiating these lesions from melanoma
A
melanocytic nevus (mole)
30
Q
What are the different types of melanocytic nevi?
A
- junctional nevi: nests at dermoepidermal junction
- compound nevi: nests or cords grow into underlying dermins (nest in epidermis and dermis)
- intradermal nevi: no epidermal nests, usually older lesions
31
Q
- +/- precursors of melanoma, multiple of these may increase risk of melanoma
- familial atypical mole and melanoma syndrome: AD, >50% chance of developing melanoma by 60 y/o, CDKN2A or CDK4 gene
- not all of these types of lesions develop into melanoma, and not all melanoma are derived from these types of lesions
- majority of these lesions are stable and never progress to melanoma
- these lesions often acquire activating mutations in NRAS and BRAF genes
A
dysplastic nevi
32
Q
- familial atypical mole and melanoma syndrome
- autosomal dominant inheritance
- >50% chance of developing melanoma by 60 y/o
- individuals may develop several melanomas at multiple sites
- CDKN2A or CDK4 gene
A
dysplastic nevus syndrome
33
Q
Dysplastic nevus histology:
A
- large than acquired nevi, >5 mm, can be hundreds
- variegated pigmentation, irregular borders of lesions
- enlarged epidermal nests that may coalesce w/ other nests
- lentiginous hyperplasia: single nevus cells replace basal cells along E-D junction
- atypia: Ig nuclei, irregular angulated nuclear contour, hyperchromasia
- lymphocytic infiltration of superficial dermis, melanin incontinence (loose melanin)
- linear fibrosis surrounds epidermal rete ridges
*refer to image*
34
Q
A
35
Q
Describe how dysplatic nevi can progress to melanoma:
A
a) lentiginous melanocytic hyperplasia develops
b) lentiginous junctional nevus develops
c) lentiginous compound nevus w/ abnml architectural and cytologic features (dysplatic nevus)
d) early melanoma (radial growth phase) w/ large dark cells in epidermis
e) advanced melanoma (vertical growth phase) w/ malignant spread into dermis and vessels
36
Q
- most deadly of all skin cancers, strongly linked to acquired mutations caused by exposure to UV radiation in sunlight (DNA damage)
- skin, oropharynx, GI/GU tracts, esophagus, meninges, and uvea of eye
- most cured surgically
- increased incidence: >100,000 cases and >6,800 deaths expected in US in 2020 (lol? it’s 2021 babes)
- despite increased incidence there is decreased death rates in past several years, may reflect effectiveness of immune checkpoint inhibitor therapy
- 10-15% inherited AD w/ variable penetrance
- majority sporadic due to single factor (UV radiation), periodic severe sunburns early in life are an important risk factor
- since melanomas sometimes occur in dark-skinned individuals and at body sites that are not sun-exposed, sunlight is not always an essential predisposing factor, and other environmental factors may also contribute to risk
A
melanoma
37
Q
Risk factors for melanoma:
A
- light complexion, hair, eyes
- hx of blistering subburns
- proximity to the equator
- indoor occupation, outdoor hobies
- fmhx of melanoma or dysplastic nevi
- precursor lesions (congenital or dysplastic nevi)
- xeroderma pigmentosum
38
Q
Most common melanoma sites in white ppl:
A
- upper back (esp men)
- legs (esp women)
39
Q
Most common melanoma sites in blacks and asians:
A
- soles of feet
- mucous membranes
- palms
- nail beds
(among African Americans, avg lifetime risk of melanoma is about 15x lower than in white population)
40
Q
Clinical features of melanoma (ABCDE’s mnemonic):
A
- A: asymmetry
- B: irregular borders
- C: variegated color
- D: increasing diameter
- E: evolution/change over time (esp rapid)
- any pigmented lesion w/ diameter >6mm, any change, itching or pain
41
Q
What are the main drivers/gene mutations in melanoma?
A
- disruption of cell cycle control genes: CDKN2A in 40% AD familial melanomas and 10% sporadic melanomas; encodes 3 tumor suppressor genes (p15, p16, ARF)
- activation of pro-growth signaling pathways: increase RAS and PI-3K/AKT signaling (drug tx target), mutations in BRAF occur in 40-50% of melanomas
- activation of telomerase: TERT in 70% of tumors (most commonly mutated gene in melanoma)
- non-sun-exposed sites: rarely have BRAF or RAS mutations; more likely to have activating mutations in receptor tyrosine kinase, KIT, which sits upstream of both RAS and PI-3K/AKT; PTEN is also silenced in 20% of melanomas arising from non-sun-exposed sites
42
Q
- melanocytic marker
- monoclonal Ab that reacts against an intrinsic antigen known as Pmel-17
- can be detected in only 50-70% of melanomas
- does not react well against intradermal nevi, nml adult melanocytes, spindle cell melanomas, and desmoplastic melanomas
- nonreactive w/ almost all non-melanoma human malignancies, w/ the exception of rare tumors showing evidence of melanogenesis (e.g. pigmented schwannoma, clear cell sarcoma) or tumors a/w tuberous sclerosis complex (angiomyolipoma and lymphangiomyoma)
A
HMB-45
(human melanoma black)
43
Q
How will melanoma cells appear histologically?
A
- usually larger than nml melanocytes or cells found in melanocytic nevi
- have large nuclei w/ irregular contours, chromatin that is clumped at periphery of the nuclear membrane, and prominent red (eosinophilic) nucleoli
44
Q
- horizontal spread of melanoma within the epidermis and superficial dermis
- tumor cells seem to lack the capacity to metastasize
- lentigo maligna: usually an indolent lesion on the face of older men, may remain in this type of growth phase for several decades
- superficial spreading: most common type of melanoma, usually involving sun-exposed skin
- acral/mucosal lentiginous: melanoma that is unrelated to sun-exposure
A
radial growth phase
45
Q
- tumor cells that invade downward into the deeper dermal layers as an expansile mass, after a variable (and unpredictable) period of time following radial phase
- this growth phase is often heralded by the appearance of a nodule and correlates w/ the emergence of a tumor subclone w/ metastatic potential
- unlike melanocytic nevi, “neurotization” is absent
- the probability of metastasis in such lesions correlates w/ the depth of invasion, which by convention is the distance from the superficial epidermal granular cell layer to the deepest intradermal tumor cells, this is known as Breslow thickness
A
vertical growth phase
46
Q
- measurement of the depth of invasion of a melanoma
- distance from the superficial epidermal granular cell layer to the deepest intradermal tumor cells
A
Breslow thickness
47
Q
Factors to consider for melanoma prognosis:
A
- tumor depth (Breslow thickness)
- # of mitoses
- evidence of regression (host immune response)
- ulceration of overlying skin
- presence and # of tumor infiltrating lymphocytes
- gender
- location (central body or extremity)
48
Q
Favorable melanoma prognosis:
A
- thinner tumor depth
- no mitosis (<1 per mm^2)
- brisk tumor infiltrating lymphocyte response
- no regression
- lack of ulceration
49
Q
Poor melanoma prognosis:
A
- deep tumor depth
- mitosis present
- regression present
- ulceration present
- metastases, even micrometastases
- # and degree of LN involvement correlates well w/ overall survival
50
Q
4 common types of benign epithelial tumors:
A
- seborrheic keratoses
- acanthosis nigricans
- fibroepithelial polyp
- epithelial or follicular inclusion cyst (Wen)
51
Q
- occurs typically in middle age or older individual
- arises spontaneously, primarily in trunk but also in extremities, head, and neck
- dermatosis papulosa nigra: people of color, multiple small lesions on face (35% of AA adults)
- round, flat, coin-like, waxy papules, tan-dark brown; velvety or granular suface; pore-like ostia impacted w/ kertain (helps DDx of melanoma); sharply dermacated sheets of small cells resemble nml basal cells; hyperkeratosis, horn cysts (keratin filled cysts)
- activating mutations in fibroblast growth factor receptor-3 (FGFR-3), found in many of these sporadic lesions, thought to drive growth of tumor
- Leser-Trelat sign: paraneoplastic syndrome, sudden appearance of large numbers of Seb K’s, a/w carcinomas of GI tract
A
seborrheic keratoses
52
Q
- subtype of seb k lesion seen in ppl of color
- multiple small lesions on face
- occurs in 35% of AA adults
- Morgan Freeman lesions
A
dermatosis papulosa nigra
53
Q
Seb k mutation:
A
fibroblast growth factor receptor-3 (FGFR-3)
54
Q
- paraneoplastic syndrome
- sudden appearance of large numbers of seb k’s
- a/w carcinomas of GI tract
A
Leser-Trelat sign
55
Q
- cutaneous sign of several underlying benign and malignant conditions
- thickened, hyperpigmented, skin w/ velvet-like texture in flexural/intertriginous areas (two skin surfaces that rub together)
- 80% benign condition that develops gradually during childhood or puberty: AD w/ variable penetrance, a/w obesity/endocrine abnmalities (obesity/diabetes most common), several rare congenital disorders
- remaining cases a/w cancers, commonly GI adenocarcinomas in middle age or older individuals (d/t paraneoplastic process, aka growth factors released from tumors)
- pathogenesis: increased growth factor receptor signaling in skin; familial form (FGFR-3) same as seb k; DM2/hyperinsulinemia believed to increase stimulation of insulin-like growth factor receptor-1 (IGFR-1)
- histo: epidermis and underlying enlarged dermal papillae undulate sharply > numerous repeating peaks/valleys; variable hyperplasia may be seen w/ hyperkeratosis and slight basal cell layer hyperpigmentation (no melanocytic hyperplasia)
A
acanthosis nigricans
56
Q
What cancer is a/w acanthosis nigricans?
A
- most commonly GI adenocarcinomas in middle aged/older individuals
- d/t paraneoplastic process (growth factors released from tumors)
- recall 80% of acanthosis nigricans are benign
57
Q
- aka acrochordon, squamous papilloma, or skin tag
- occurs on head, neck, trunk, face, and intertriginous areas typically in middle aged/elderly
- a/w diabetes, obestity, and intestinal polyposis
- Birt-Hogg-Dubé syndrome: rare, polyps and perifollicular mesenchymal tumors (fibroblasts a/w hair bulb)
- soft, flesh-colored, bad-like tumors often attached by slender stalk
- histo: fibrovascular cores covered by benign squamous epithelium
- torsion > ischemic necrosis > removal
A
fibroepithelial polyp
58
Q
- invagination and cystic expansion of the epidermis or hair follicle
- subject to traumatic rupture, spill keratin into dermis > extensive and painful granulomatous inflammatory response
A
epithelial or follicular inclusion cyst (Wen)
59
Q
- hundreds of neoplasms arising from or showing differentiation toward cutaneous appendages, benign tumors may be confused w/ basal cell carcinoma
- nondescript, flesh-colored, solitary or multiple papules and nodules
- types: Cowden syndrome (trichilemmomas), cylindromas, eccrine poromas, syringomas, sebaceous adenomas, pilomatricomas
A
adnexal (appendage) tumors
61
Q
- a type of adnexal tumor
- ductal differentiation, forehead or scalp, “jigsaw puzzle”
- turban tumor: coalesce, hat-like growth d/t CYLD (tumor suppressor gene)
- CYLD* associated genetic syndromes: familial trichoepithelioma and Brooke-Spiegler
A
cylindroma
64
Q
- a type of adnexal tumor
- Muir-Torre syndrome (internal malignancies)
- hereditary nonpolyposis colorectal carcinoma syndrome (Lynch syndrome)
- DNA mismtach repair proteins
- histo: shows a lobular proliferation of sebocytes with increased peripheral basaloid cells and more mature sebocytes in the central portion that have frothy or bubbly cytoplasm due to the presence of lipid vesicles
A
sebaceous adenoma
70
Q
- occurs predominantly on sun damaged skin w/ hyperkeratosis (face, arms, dorsum of hands)
- risks: light skin individuals, ionizing radiation exposure, industrial hydrocarbons, arsenic
- given enough time progressively worsens > squamous cell carcinoma
- appearance: <1cm, tan-brown, red or skin colored, rough sandpaper-like consistency; cutaneous horn (excessive keratin prod); dyskeratosis (pink cytoplasm), intracellular bridges, blue-gray elastosis (sun damage), parakeratosis
- actinic cheilitis: similar lesions of the lips
A
actinic keratosis
74
Q
Describe the histology presentation of SCC:
A
- in situ: lesions are sharply defined, red, scaling plaques; atypical (enlarged & hypochromatic) nuclei involve all levels of epidermis
- invasive: lesions are nodular, keratin production (hyperkeratotic scale), may ulcerate; anaplastic cells w/ dyskeratosis (single-cell keratinization)
75
Q
- most common invasive cancer, 1 million cases/yr in US
- slow growing, rarely mets, cured by local excision, <0.5% locally aggressive
- risks: sun exposed sites of light skin elderly adults, immunosuppression, xeroderma pigmentosum
- mutation: unbridled Hedgehog signaling, PTCH gene
- nevoid BCC syndrome = Gorlin syndrome = BC nevus syndrome: AD, mult BCC <20 y/o, medulloblastoma, ovarian fibromas, odontogenic keratocytes, pits of palms/soles
- appearance: pearly papules, telangiectasias, rodent ulcers; basophilic/basaloid cells, hyperchromatic nuclei, peripheral palisading (arranged radially w/ long axes in parallel alignment); artificial clefts separate stroma from tumor
A
basal cell carcinoma
76
Q
Describe the role of PTCH mutation in BCC:
A
- Mutations in PTCH , and less often in SMO, allow SMO to signal without SHH binding and produce constitutive activation of GLI1
- GLI signaling is a characteristic feature of sporadic basal cell carcinomas and tumors associated with the nevoid basal cell carcinoma (Gorlin) syndrome
- Mutations that activate Hedgehog signaling are also prevalent in sporadic basal cell carcinomas
- Loss-of-function PTCH mutations are common, and about one-third of these mutations consist of C→T transitions that are hallmarks of UV damage. This insight has paved the way for the development and clinical implementation of small molecule inhibitors of the Hedgehog pathway
78
Q
- benign dermal neoplasm of uncertain origin
- most common in adults, esp legs of young to middle aged women
- the lesions may be asx or tender, +/- size change over time, indolent
- dimple sign: lateral pressure on the skin produces a depression
- many individuals have hx of antecendent trauma, the lesions are abnml response to injury/inflammation
- appearance: firm, tan-brown papules, <1cm, become flattened w/ time
- histo: benign spindle-shaped cells, well defined, non-encapsulated mass in mid dermis; overlying epidermal hyperplasia, downward elongation of hyperpigmented rete ridges (pseudoepitheliomatous hyperplasia)
A
benign fibrous histiocytoma (dermatofibroma)
79
Q
- well differentiated fibrosarcoma of the skin
- slow growing, locally aggressive, can recur, rarely mets (more likely if more cytological atypia)
- mutation: translocation collagen 1A1 (COL1A1) and PDGFB, promoting tumor cell growth
- appearance: “protuberant” nodule, usually on the trunk, firm indurated plaque +/- ulceration
- histo: closely packed fibroblasts arranged radially (i.e. blades of a pinwheel = storiform); rare mitoses, overlying epidermis is thinned (opposite of dermatofibroma); honeycomb pattern = deep extension from dermis into subQ fat
A
dermatofibrosarcoma protuberans (DFSP)
81
Q
- CD4+ helper T-cells in the skin
- remains localized for many years, may eventually evolve into systemic lymphoma
- individuals are usually >40 y/o, w/ truncal lesions (also can present on extremities, face, and scalp)
- appearance: scaly, red-brown patches; raised scaling plaques can be confused w/ psoriasis; fungating nodules
- prognosis: determined by % of body surface involved and progression from patch > plaque > nodule; eczema-like lesions = early stages, multiple tumor nodules = systemic spread
- when the lymphocytes move to the blood, this is Sézary syndrome
- tx: topical steroids or UV light for early skin lesions; more aggressive systemic chemo indicated or advanced dz
A
mycoides fungoides
(cutaneous T-cell lymphoma, CTCL)
82
Q
- cutaneous T-cell lymphoma where the T-cells have moved into the blood
- appearance: erythroderma, diffuse erythema and scaling of entire body surface
- histo: markedly folded nuclear membrane, hyperconvoluted or cerebriform contour; band-like aggregates within superficial dermis; Pautrier microabscesses are small clusters of cells in epidermis
A
Sézary syndrome
(it is unknown whether this is an advanced from of mycosis fungoides or a separate dz)
83
Q
- urticaria pigmentosa (cutaneous form in children) accounts for >50% of all cases: multiple, widely distributed lesions, round-oval, red-brown, nonscaling papula and small plaques
- adults: usually multiple cutaneous lesions, ~10% have systemic dz w/ mast cells infiltrating organs
- solitary mastocytoma: usually seen in young children, pink-tan brown nodule, +/- pruritic or blister formation
- histamine and heparin are released when mast cells degranulate
- Darier sign: localized are of dermal edema and erythema (wheal) when skin is rubbed
- dermatographism: area of dermal edema resembling a hive, result of local stroking of skin w/ pointed instrument
- systemic sx: pruritus/flushing; triggered by certain foods, temp changes, alcohol, drugs (morphine, codeine, aspirin); rhinorrhea; rarely GI or nasal bleeding (anticoagulant effect of heparin); bone pain (mast cell infiltration or osteoporosis); osteoporosis in premenopausal women/men d/t excessive histamine release in BM
- mutation: point mutations in KIT receptor tyrosine kinase > mast cell growth/survival
- histo: spindle-shaped and stellate mast cells, fibrosis, edema, few eosinophils; metachromatic stain (toluidine blue or Giemsa), IHC for mast cell tryptase and KIT
A
mastocytoma
84
Q
- impaired epidermal maturation leading to chronic keratin buildup (hyperkeratosis) that results in clinically fish-like scales
- defective desquamation leads to retention of abnormally formed scale
- buildup of compacted stratum corneum, a/w loss of normal basketweave pattern, generally no inflammation present
- there are multiple different forms of this condition w/ differing inheritance patterns
A
ichthyosis
88
Q
- localized mast cell degranulation > dermal microvascular hyperpermeability (antigen-induced release of vasoactive mediators from mast cells)
- wheals: pruritic edematous plaques
- angioedema: edema of the deeper dermis and subQ fat
- occurs predominantly in 20-40 y/o, usually <24 hrs, sites exposed to pressure (trunk, distal extremities, ears), persistent episodes may herald an underlying dz (e.g. collagen vascular disorders, Hodgkin lymphoma), but usually no underlying case found
- appearance: small, pruritic papules to large edematous plaques; individual lesions may coalesce to form annular, linear, or arciform configurations
- histo: sparse superficial perivenular infiltrate of mononuclear cells and rare neutrophils, +/- eosinophils; collagen bundes more widely spaced than nml skin d/t edema; dermal lymphatics may be dilated d/t absorption of edema fluid
A
urticaria (hives)
90
Q
- literally means “to boil over”, one of the most common skin conditions
- T-cell mediated inflammatory rxn (type IV hypersensitivity)
- external application of Ag (poison ivy) or ingested food/drug (5 different types)
- appearance: red, papulovesicular, oozing/crusted (impetiginization) lesions; if persists, can develop acanthosis and hyperkeratosis > raised scaling plaques; spongiosis (edema in intracellular spaces, splaying them apart, particularly in stratum spinosum)
- tx: no cure, palliative w/ topical steroids
A
acute eczematous dermatitis
91
Q
What are the 5 subtypes of acute eczematous dermatitis?
A
- allergic contact dermatitis
- atopic dermatitis
- drug-related eczematous dermatitis
- photoeczematous dermatitis
- primary irritant dermatitis
- the pattern/composition of infiltrate (on histo) may provide clues to underlying cause
- eczema resulting from certain ingested drugs is marked by perivascular infiltrates that often contain eosinophils in the superficial and deep dermis
- eczema resulting from contact antigens tends to prod a mononuclear inflammatory rxn w/o eosinophils that preferentially affects the superficial dermis
92
Q
- uncommon, self-limited hypersensitivity rxn to certain infections/drugs (infections, drugs, cancer, collagen vascular dz)
- keratinocyte injury mediated CD8+ cytotoxic T-lymphocytes: CD8+ cytotoxic T-cells in center of lesion, CD4+ helper T-cells and Langerhans cells in the periphery; similar to acute graft vs host dz, skin allograft rejection, and fixed drug eruptions
- diverse array of lesions: targetoid lesions, interface dermatitis, Stevens-Johnson condition, toxic epidermal necrolysis
A
erythema multiforme
97
Q
Diverse lesions a/w erythema multiforme:
A
- targetoid lesions, macules, papules, vesicles, and bullae
- interface dermatitis: dermal edema, lymphocyte infiltration along dermoepidermal junction, a/w dermal edema and degenerating keratinocytes
- Stevens-Johnson: predominantly in children, extensive skin involvement plus oral mucosa, conjunctiva, urethra/genital/perianal areas, secondary infections lead to life-threatening sepsis
- toxic epidermal necrolysis: diffuse necrosis/sloughing of cutaneous and mucosal epithelia, resembles extensive burns
99
Q
- chronic inflammatory dermatosis, autoimmune basis
- 1-2% ppl in US, ~15% develop assoc arthritis; may also be a/w myopathy, enteropathy, and AIDS
- Koebner phenomenon: induced psoriatic lesions in susceptible pts by local trauma, starts self-perpetuating local inflammatory response
- appearance/histo: pink to salmon colored plaque covered by loosely adherent silver scale present on elbows, knees, scalp, lumbosacral region, intergluteal clef, and glans penis; nail changes; MKD acanthosis; Munro microabscesses; Auspitz sign; erythroderma
- tx: excellent clinical responses are observed in patients tx w/ TNF & IL-17 inhibitors
A
psoriasis
102
Q
Describe psoriasis gross appearance and histo:
A
appearance
- pink to salmon colored plaque covered by loosely adherent silver scale
- early lesions: dominated by inflammation, marked by presence of small pustules/erythema
- chronic lesions: erythematous and covered by characteristic silver-white scale
- present on elbows, knees, scalp, lumbosacral region, intergluteal cleft, and glans penis
- 30% w/ nail changes: pitting, dimpling, yellow-brown discoloration (oil slick), oncolysis (separation of nail plate from underlying nail bed), thickening, crumbling
- erythroderma: psoriasis one cause of total body erythema/scaling
- Auspitz sign: mult, minute, bleeding points when scale lifted from plaque
histo
- Mkd acanthosis, regular downward elongation of rete ridges “test tubes in rack”
- mitoses above basal cell layer, stratum granulosum thin or absent, extensive parakeratotic scale
- Munro microabscesses: small PMN (polymorphonuclear leukocytes) aggregates in parakeratotic stratum corneum
103
Q
- occurs in 5% of population, more common than psoriasis
- occurs in bodily regions w/ increased sebaceous glands: scalp, forehead, external auditory canal, retroauricular area, nasolabial folds, presternal area
- inflammation of epidermis, not a dz of sebaceous gland
- increased seb prod in response to androgens is a possible contributory factor
- Parkinson’s dz: increased sebum prod secondary to dopamine def, leads to this condition, tx is levodopa which decreases oil prod
- a severe form of this condition that is difficult to tx was once common in individuals w/ HIV w/ low CD4 counts, but its incidence has fallen w/ advent of antiviral therapy
A
seborrheic dermatitis
104
Q
Describe the gross appearance and histo of seborrheic dermatitis:
A
appearance
- individual lesions are macules and papules on an erythematous-yellow, often greay base, typically a/w extensive scaling/crusting
- fissure may also be present, partically behind the ears
- dandruff is common clinical expression of seborrheic derm of scalp
histo
- mounds of parakeratosis containing neutrophils and serum are present at ostia of hair follicles = follicular lipping
106
Q
- 6 P’s: pruritic, purple, polygonal, planar, papules, plaques
- self limited dz of skin/mucosa, resolving spontaneously in 1-2 yrs
- postinflammatory hyperpigmentation left after resolution
- squamous cell carcinoma noted to occur in chronic mucosal and paramucosal lesions of this kind (possibly carcinogenesis in setting of chronic inflammation)
- Koebner phenomenon: also seen in psoriasis
- appearance: itchy violaceous, flat-topped papules that may coalesce, Wickham striae; lesions may be dark brown in darker individuals; 70% of cases have white oral mucosal lesions
- histo: interface dermatitis, sawtoothing, Civatte bodies
A
lichen planus
107
Q
Describe the appearance and histo of lichen planus:
A
appearance
- itchy violaceous, flat-topped papules, that may coalesce
- Wickham striae: pink-purple polygonal papules highlighted w/ lacelike pattern of white lines, created by areas of hypergranulosis
- darker individuals may develop lesions w/ dark brown color d/t release of melanin into dermis as basal cell layer is destroyed
- multiple, symmetrical lesions esp on extremities, wrist, elbows, and glans penis
- 70% of cases have oral mucosal lesions w/ white, reticulated or net-like appearance
histo
- dense cutaneous infiltrate of lymphs, along dermoepidermal junct (interface dermatitis)
- sawtoothing: angulated zigzag contour of dermoepidermal interface
- colloid or Civatte bodies: anucleate, necrotic basal cells incorporated into inflamed papillary dermis
110
Q
- type of inflammatory blistering/bullous dz
- IgG autoantibodies dissolution of intracellular attachments within the epidermis and mucosal epithelium lead to these blisters, may be fatal w/o tx
- net-like pattern of intercellular IgG deposits: vulgaris = all levels; foliaceus = superficial
- occurs predominantly in 40-60 y/o’s, equally affecting sexes
- histo: acantholysis (dissolution of intercellular bridges connecting squamous epithelial cells, these cells become rounded)
- types: vulgaris (most common), vegetans, foliaceus, erythromatosus, paraneoplastic
- tx: immunosuppressives
A
pemphigus
111
Q
- most common type of pemphigus, >80% of cases worldwide
- occurs in mucosa and skin of scalp, face, axilla, groin, trunk and pressure points
- superficial vesicles rupture easily > shallow erosions w/ dried serum/crust
- histo: deposition of immunoglobulin along the plasma membranes of keratinocytes in a reticular or fishnet-like pattern accompanied by suprabasalar loss of cell-to-cell adhesion (acantholysis); single layer of intact basal cells that forms the blister base has been likened to a row of tombstones
A
pemphigus vulgaris
113
Q
- benign subtype of pemphigus
- endemic to Brazil
- occurs on scalp, face, chest, back
- erythema and crusting lesions; delicate superficial (subcorneal) blisters are much less erosive than those seen in pemphigus vulgaris
- histo: subcorneal separation of the epithelium is seen; the immunoglobulin deposits and acantholysis are more superficial
A
pemphigus foliaceus
116
Q
- a type of inflammatory blistering/bullous dz
- occurs in elderly on inner aspect of thighs, flexor surfaces of forearms, axilla, groin, and lower abd; 10-15% are oral lesions
- antibody (IgG) linear deposits at dermoepidermal junction; BPAG’s (antigens a/w dz, components of demidesmosomes)
- do not rupture easily d/t subepidermal nature (nonacantholytic blisters)
- ulcers form when blisters rupture, however they usually heal w/o scarring unless they become secondarily infected
A
bullous pemphigoid
117
Q
- type of inflammatory blistering/bullous dz
- urticarial and grouped vesicles that typically occur in men in their 30-40’s
- bilateral, symmetric, grouped lesions on extensor surfaces of elbows, knees, upper back, and buttocks
- a/w celiac dz d/t IgA Ab’s to gluten (Ab’s cross react w/ reticulin > subepidermal blister)
- histo: granular deposits of IgA at the tips of dermal papillae, a/w acccumulation of neutrophils (microabscesses) at tips of dermal papillae
- tx: some individuals respond to gluten-free diet
A
dermatitis herpetiformis
118
Q
- a type of non-inflammatory blistering/bullous dz
- groups of disorders that are inherited defects in structural proteins
- blisters at sites of pressure, rubbing, or trauma at (or soon after) birth
- electron microscopy differentiates the various types
A
epidermolysis bullosa
119
Q
- a type of non-inflammatory blistering/bullous dz
- group of inborn or acquired disturbances in porphyrin metabolism
- porphyrins: pigments normally present in Hgb, myoglobin, and cytochromes
- sx: urticaria and subepidermal vesicles a/w scarring, exacerbated by sunlight
- histo: rigid dermal papillae at the base that contain abnml superficial vessels; subepidermal vesicles w/ adjacent dermis that contains vessels w/ walls that are thickened by glassy deposits of serum proteins (Ig’s)
A
porphyria
121
Q
- occurs in middle aged and older individuals, 3% of US, predominantly women
- 4 stages: flushing, persistent erythema/telangiectasia, pustules/papules, rhinophyma (permanent thickening of nasal skin)
- a/w high cutaneous levels of antimicrobial peptide cathelicidin
- several microbial triggers have been proposed, but none are proven
A
rosacea
124
Q
- virtually universal in middle-late teens, affects genders equally, more severe dz in men
- occurs in all races, however Asians usually have milder dz
- induced/exacerbated by: corticosteroids, adrenocorticotropic hormone, testosterone, gonadotropins, contraceptives, trimethadione, iodides, bromides; occupational exposure (heaving clothing, cosmetics, tropical climate (blocks sebaceous glands))
- open comedones: central black (oxidation of melanin, not dirt) keratin plug
- closed comedones: keratin plug trapped beneath epidermal surface, potential for follicular rupture and inflammation
- multifactorial dz due to keratin block, puberty, bacteria (Propionibacterium acnes), and inflammation
- acne conglobate: severe variant, sinus tract formation and dermal scarring
- tx: abx for P. acnes, 13-cis-retinoic acid (isoretinoin) for antisebaceous action
A
acne vulgaris
128
Q
- a subtype of panniculitis
- most common form of subacute presentation
- poorly defined, exquisitely tender erythematous plaques and nodules, more readily palpated (ropy) than seen
- over weeks, lesions flatten and become bruise-like, no residual scars
- considered delayed hypersensitivity rxn to microbial or drug related antigens: infectious β-hemolytic streptococcal infection, TB, or less commonly coccidiodomycosis, histoplasmosis, and leprosy; drugs including sulfonamides and oral contraceptives; and inflammatory dz’s including sarcoidosis, inflammatory bowel dz, and certain malignant neoplasms
- histo: in early lesions, the CT septae are widened by edema, fibrin exudation, and neutrophilic infiltration; later, infiltration by lymphocytes, histiocytes, multinucleated giant cells, and eosinophils is a/w septal fibrosis
A
erythema nodosum
135
Q
- squamoproliferative lesions caused by HPV infection
- anogenital: HPV types 6 and 11
- HPV 16: a/w in site SCC of genitalia and bowenoid papulosis (genital lesions of young adults w/ histologic appearance of carcinoma in situ, but usually regresses spontaeously)
- HPV 5 and 8: related to SCC, esp individuals w/ epidermodysplasia verruciformis, develop mult flat warts w/ some that progress to carcinoma
- children/adolescents: direct contact or autoinnoculation; generally self-limited, regressing spontanesouly in 6mo-2yrs
A
verrucae (warts)
140
Q
Histology of verrucae (warts):
A
lesions show papillomatous epidermal hyperplasia and cytopathic alterations, including nuclear pallor and prominent keratohyaline granules
141
Q
- common, self-limited poxvirus infection (virus is brick shaped, w/ dumbbell shaped DNA core)
- spread through direct contact, within children and young adults
- occurs in trunk and anogenital regions
- appearance: firm, pruritic, pink-skin colored umbilicated papules; curd-like material can be expressed from umbilication (smear shows molluscum bodies)
- histo: (Giemsa or H&E) molluscum bodies = ellipsoid, homogenous, cytoplasmic inclusions
A
molluscum contagiosum
142
Q
- common superficial bacterial infection of skin
- highly contagious, occurs in otherwise healthy children and occasionally in adults w/ poor health
- occurs on exposed skin of face/hands
- Staphylococcus aureus > toxin causing epidermal injury (toxin cleaves desmoglein 1)
- appearance: erythematous macule initially, then mult small pustules which break > shallow erosions > honey colored crust (drying serum, if not removed new lesions form around periphery and extensive epidermal damage may occur)
- two forms: contagiosa and bullosa (differ based on size of pustules)
- tx: eliminate bacteria and lesion heals
A
impetigo
145
Q
- common superficial fungal infection of the body surface; occurs in all ages, but esp children
- predisposing factors: excessive heat and humidity, exposure to infected animals, and chronic dermatophytosis of the feet or nails
- most common appearance: expanding, round, slightly erythematous plaque with elevated scaling border
- histo: routine histo shows mild eczematous (spongiotic) dermatitis and focal neutrophilic abscesses, periodic acid–Schiff stain (PAS) reveals deep red hyphae within the stratum corneum
A
tinea corporis
