Midterm Flashcards
Where are melanocytes found
Epidermis
T cells expressing what home back to the dermis?
CCR and CCR10
What do the efferent nerve fibers do on the skin
Sweating, control erector pili mm
What is excoriation
Traumatic lesions breaking epidermis an causing a raw linear area (often self induced like a scratch)
What is lichenification
Thickened, rough skin; usually resulting from chronic Rubbing
What is a macule or patch
Circumscribed, flat lesion distinguished from skin by color; maccules are 5 mm or less; patches >5mm
What is onycholysis
Separation of nail plate from nail bed
What are papules or nodules
Elevated dome shaped or flat topped lesion; papules <5mm nodules >5mm
What are plaques
Elevated flat topped lesion
What are pustules
Discrete pus filled raised lesion
What are scales
Dry horny platelike excrescences
What are vesicles, bulla, blisters
Fluid filled raised lesion 5mm or less (vesicle) or greater than 5mm (bulla); blister is common term for either
What is a wheal
Itchy transient elevated lesion with variable blanching and erythema formed s result fo dermal edema
What is acanthosis
Diffuse epidermal hyperplasia
What is dyskeratosis
Abnormal premature keritnization within cells below stratum granulosum
What are erosions
Discontinuity of the skin showing incomplete loss of epidermis
What is exocytosis
Infiltration of epidermis by inflammatory cells
What is hydropic swelling (ballooning)
Intracellular edema of keratinocytes; often seen in viral infections
What is hypergranulosis
Hyperplasia of stratum granulosum; often due to intense rubbing
What is hyperkeratosis
Thickening of stratum cornermen
What is lentiginous
Linear pattern of melanocytes proflieration within epidermal basal cell layer
What is papillomatosis
Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae
What is parakeratosis
Keratinization with retained nuclei in stratum Corneum; normal on mucous membranes
What is spongiosis
Intracellular edema of epidermis
What is ulceration
Discontinuity of skin showing complete loss of piper is revealing debris or subcutis
What is vacuolization
Formation of vacuoles within or adjacent to cells
What is ephelis
Freckle; most common pigmented lesions of childhood in light individuals
How do cafe au lait spots differ from freckles
Larger, arise independently of sun exposure and contain aggregated melanosomes (macromlanosomes)
What is lentigo
Benign hyperplasia of melanocytes often in infancy and childhood; no sex or racial predilection; do not darken when exposed to light; histo* linear melanocytic hyperplasia, elongation and thinning of rete ridges
What is melanocytic nevi
Moles; acquired activating mutations in RAS pathway;
What are the different forms of melanocytic nevi
- congenital: deep dermal growth around adnexa, NV bundles, and bv walls; present at birth; large variants have increased melanoma risk
- blue: non-nested dermal infiltration with assoc fibrosis; highly dendritic; black-blue nodule often confused with melanoma
- spindle (spitz): fascicular gwoth; pink-blue cytoplasm and fusiform cells; common in children; red-pink nodule often confused with hemangioma
- halo: lymphocytic infiltration surround nevus;
- dysplastic: coalescing intraepidermal nests; potential marker or precursor of melanoma
What is the progression of morphological changes of melanocytic nevi
-earliest lesions are junctional nevi (aggregates or nests of round cells that grow along dermoepidermal junction)
-then grow into underlying dermis to form compound nevi
-in older lesions, epidermal nests are lost to form pure i trader always nevi
At deepest extent, grow in fascicles and resemble neural tissue (neurotinization) important to distinguish from melanoma
What are dysplastic nevus syndromes
AD; tendency to develop multiple dysplastic nevi and melanoma
What mutations do people with dysplastic nevi syndromes have
RAS/BRAF in addition to CDKN2A
What is the morphology of dysplastic nevi
Larger than most acquired nevi; pebbly surface or target like lesions with darker aided center and irregular flat periphery; variability in pigmentation (variegation); occur in both supposed and protected body surfaces (unlike moles); involve dermis and epidermis; nevus nest cells can fuse with adjacent nests; produces lentiginous hyperplasia; release of melanin from dead nevus cells (melanin incontinence)
What are the most frequent diver mutations in melanoma
- CDKN2A: encodes for p15/INK4b, p16/INK4a, p14/ARF; inhibit CDK4 and 6 (p16), p14 enhances p53 activity by inhibiting MDM2
- RAS and PI3K/AKT; melanomas in non-sun expose areas rarely have mutations in BRAF or NRAS and more likely to have KIT mutations and PTEN
- reactivation of telomerase; TERT*most commonly mutate gene
What is the morphology of melanoma
Variations in color (can sometimes have white areas - where tumor is regressing), bores are irregular and notched; radial growth - horizontal within epidermis and superficial dermis (can’t met here); then vertical growth - appearance of nodule; ability to met measured by Breslow thickness
What are the types of melanoma in radial growth phase
- lentigo maligna: presents as indolent lesion on face of older men that can remain in those phase for decades
- superficial spreading: most common type of melanoma* usually involving sun exposed skin
- acral/mucosal lentiginous melanoma: unrelated to sun exposure*
What is a melanoma marker
HMB-45
What are the prognostic factors of melanoma
Breslow thickness, number of mitosis, evidence of tumor regression, ulceration or skin, presence and number of infiltrating lymphocytes, gender, location
Favorable: thinner, no mitosis, brisk tumor infiltrating response, absence of regression, lack of ulceration
What are the ABCDEs of melanoma
Asymmetry, irregular borders, variegated color, increasing diameter, evolution or change over time
What skin manifestation does cowden have
Trichilemmonomas
What skin manifestation does Muir-torre have
Multiple sebaceous neoplasms
What are sebeorrheic keratoses
Epidermal tumors;; middle to older age; mostly on trunk; in people of color - lesions on face are termed dermatosis papulosa Nigra
What is the pathogenesis of seborrheic keratoses
Activation mutations in FGFR3; can appear is part of paraneoplastic syndrome - Leser-trelat sign (most commonly from GI carcinomas)
What is the morphology of seborrheic keratoses
Coinlike, waxy plaques; velvety to granular surface; pore-like Ostia impacted with keratin; keratin production at the surface and small keratin filled cysts and invaginations of keratin into main mass are characteristic
What are the 2 types of acanthosis Nigricans
- in most cases, assoc with benign conditions and develops gradually during childhood; can occur as AD trait, assoc with obesity or endocrine ab, or part of congenital syndromes
- in remaining cases, arises in assoc with cancers, mostly GI adenocarcinomas in middle aged and older adults; paraneoplastic
What is the pathogensis of acanthosis nigricans
Disturbance that leads to increased GF signaling; familial form assoc with FGFR3 mutation; can be seen in combo with achondroplasia and thanatophhoric dysplasia
Does acanthosis nigricans have melanocytic hyperplasia
No
What is a fibroepithelial polyp
Aka acochordon, squamous papilloma, skin tag; middle aged individuals on neck, trunk, face, and intertriginous areas; can be seen with birt-Hogg-dube syndrome; soft, flesh colored, attached by stalk - can undergo ischemic necrosis; can become more numerous during pregnancy
What is an epithelial or follicular inclusion cyst (wen)
Formed by invagination and cystic expansion of epidermis or a hair follicle; can rupture which can spill keratin into dermis and lead to painful granulomatous response
What are adenxal (appendage) tumors
Fresh colored, solitary or multiple
What are eccrine poromas
Adnexal tumor that occurs predominately on palms and solves where swat glands are numerous
What are cylindromas
Appendage tumor with ductal differentiation; occurs on forehead and scalp; *turban tumor; can be AD inherited (mutation in CYLD); mutations in CYLD also assoc with familial trichoepithelioma and Brooke Spielberg syndrome
What are syringomas
Adnexal tumors with eccrine differentiation; usually on lower eyelids
What are sebaceous adenomas
Can be assoc with internal malignancy in Muir-torre syndrome (HNPCC subset); DNA mismatch mutation
What are pilomatricomas
Adnexal tumor showing follicular differentiation; assoc with CTNNB1 mutations (encodes B catenin); regulates hair growth
What is the morphology of the adnexal tumors
- cylindroma: islands that. Fit together like jigsaw puzzle within fibrous matrix
- trichoepithelioma: forms primitive structures resembling hair follicles
- sebaceous adenoma: lobular proliferation; frothy or bubble cytoplasm
- pilomatrixomas: trichilemmal or hairlike differentation; Ghost cells
What are actinic. Keratoses
Occur in sundamaged skin and exhibit hyperkeratosis; exposure to UV light, hydrocarbons and arsenic; may show progressively worsening dysplastic changes that end in SCC; sandpaper consistency - can produce cutaneous horn from overproduction of keratin; face, arms dorsum of hands most affected; lips can develop similar lesions (cheilitis)
What is the morphology of actinic keratoses
Atypia seen in lowermost layers of epidermis; pink or reddish cytoplasm; intercellular bridges NOT present; superficial dermis contains thickened blue gray elastic fibers (elastosis); stratum corneum is thickened and often retain their nuclei (parakeratosis)
How are actinic keratoses treated
Cut off, frozen off, topical application of imiquimod (activates TLRs)
Is SCC of the skin more common in men or women
Men; except for those on the legs
What is the pathogenesis of SCC of the skin
Lifetime sun exposure; immunosuppression - susceptible to HPV 5 and 8 (also seen in people with epidermodysplasia verruciformis); exposure to tars and oils, chronic ulcers and draining osteomyelitis, old burns, ingestion of aresenicals
What kind of skin cancer are people with xeroderma pigmentosum at risk for
SCC
What is the morphology of SCC of the skin
Involves all levels of epidermis
What is basal cel carcinoma
Locally aggressive tumor assoc with mutations that activate the hedgehog pathway; *most common invasive cancer in humans; occur at sun exposed sights
What syndrome leads to an increased risk of basal cell carcinoma
Nevoid basal cell carcinoma syndrome (NBCCS) aka gorlin syndrome; AD; development of BCC before age 20 accompanied by ot her tumors - medulloblastomas and ovarian fibromas, odontognic keratocytes, pits of palms and soles and developmental abnormalities; mutation is PTCH - leads to excessive GLI1 activation
What is the morphology of basal cell carcinoma
Pearly papules containing prominent dilated subepidermal bv (telangiectasias); “rodent ulcers”; do NOT occur on mucosal surfaces; two patterns: multifocal - originates from epidermis; nodular: goes deeply into dermis; cells at periphery of tumor arranged radially (palisading)
What is benign fibrous histiocytoma (dermatofibroma)
Heterogeneous family of morph and histo related benign dermal neoplasms; sen in adults; occur on legs of young Nd middle aged women; asymptomatic or tender; indolent; composed of factor XIIIa-positive dermal dendritic cells; spindle shaped cells arranged in nonncapsulated mass within mid dermis; some contain pseudoepitheliomatous hyperplasia - downward elongation of hyperpigmented rete ridges
What is dermatofibrosarcoma protuberant
Dermis tumor primary fibrosarcoma; slow growing; rarely met; translocation* involving collagen 1A1 (COL1A1) and platelet deriveed growth factor beta (PDGFB) - overexpression of PDGFB; treat with local excision or those than cant be excised - PDGFB inhibitors (imatinib mesylate) - lifelong use
What is the morphology of dermatofibrosarcoma protuberans
Protuberant nodule most often on t runs firm plaque; composed of fibroblasts, reminiscent of blades of a pinwheel (storiform pattern); rare mitosis; overlying epidermis is thinned (in contrast to dermatofibroma); honeycomb pattern frequently seen; need wide excision; “Swiss cheese” infiltration of subcutis
What are the features of mycosis fungoides
Most involve turn; scaly, red brown patches; can be confused with psoriasis; prognosis related to percentage of body surface involved and progression from patch to plaque to nodular forms; nodules correlates with systemic spread; if diffuse erythema and scarring of entire body surface - Sezary syndrome
What is the morphology of mycosis fungoides
Sezary-lutzner cells - form bandlike aggregates within superficial dermis; invade dermis as singl cells sand small clusters (pautrier microabscesses)
What is mastocytosis
Increased number of mast cells in skin; childhood form called urticaria pigmentosa; prognosis can be poor
What are the signs and sx of mastoytosis
Due to histamine and heparin; Darier sign - localized area of dermal edema and erythema (wheal) that occurs when lesional skin is rubbed; dermatogaphism - area of dermal edema resembling a hive that occurs as a result of localized stroking of normal skin; can cause osteoporosis by excessive histamine release
What is the pathogenesis of mastocytosis
Acquired mutations in KIT
What is ichthyosis
Chronic excessive keratin buildup (hyperkeratosis) that results in fishlike scales
What are the types of ichthyosis
- ichthyosis vulgaris: AD or acquired
- congenital ichthyosiform erythroderma: AR
- lamellar ichthyosis: AR
- x-linked ichthyosis
What is the pathogensis of ichthyosis
Defective deesquamation leading to retention of abnormally formed scale - X linked caused by def of steroid sulfatase (removes proadhesive cholesterol sulfate from intercellular spaces; results in persistent cell to cell adhesion within stratum corneum
What is the morphology of ichthyosis
Buildup of compacted stratum corneum assoc with loss of normal basket-weave pattern
What is angioedema
Edema of deeper dermis and subcutaneous fat
What are the major sites of hives
Areas exposed to pressure - trunk, distal extremities, ears
What is the pathogenesis of urticaria
Antigen induced release of vasoactive mediators is main cause
Other causes:
-mast cell dependent, IgE dependent: follows exposure to antigens; type I reaction
-mast cell dependent, IgE independent: results from substances that directly incidence degranulation of mast cells such as opiates, abx, curare, and contrast
-mast cell independent, IgE independent: triggered by local factors that increase permeability; aspirin; hereditary angioneurotic edema
What is the morphology of urticaria
Collagen bundles more widely spaced than in normal. Skin as a result of superficial dermal edema; no changes in epidermis
What are the categories of acute eczematous dermatitis
- allergic contact dermatitis
- atopic
- drug related
- photoeczematous
- primary irritant
What is the pathogeneis of acute eczematous dermatitis
Results from type IV hypersensitivity; chemicals act as happens and become antigens which are taken up by langerhans cells -> migrate to draining LN -> CD4 cells; on reexposure response within 24 hours
What is the morphology of acute eczematous dermatitis
Red, papulovsicular oozing and crusted lesions; if persist can develop reactive acanthosis and hyperkeratosis; ex: Rhus toxiodendron (poison ivy) - can have superimposed bacterial infection with yellow crust (impetiginization); spongiosis; unlike urticaria, edema seeps into epidermis - shearing of desmosomes can lead to vesicles
What are the stages of morphology of eczema
- superficial perivascular infiltrate with dermal edema and mast cell degranulation
- epidermal spongiosis and microvesicle formation
- abnormal scale, including parakeratosis and acanthosis I
- hyperkeratosis
What is erythema multiforme
Uncommon self limited hypersensitivity reaction; assoc with herpes simplex, mycoplasma infections, histoplasmosis, coccidioidomycosis, typhoid, leprosy, sulfonamides, penicillin, barbiturates, salicylates, hydantoins, antimalarials, cancer, collagen vascular dz
What is the pathogenesis of erythema multiforme
Keratinocytes injury mediated by skin homing CD8 T cells - more prominent in center of lesion; CD4 and langerhans in periphery
What is the morphology of erythema multiforme
Diverse array of lesions - macules, papules, vesicles, Bullae, and characteristic taretoid lesions; *febrile form - Stevens Johnson syndrome - involves skin, lips, oral mucosa, conjunctiva, urethra, and genital and perianal areas; another variant - toxic epidermal necrosis - diffuse necrosis and sloughing
What is the histo of erythema multiforme
Targetoid lesions show infiltrate along dermodepidermal junction here they are assoc with necrotic keratinocytes (interface dermatitis)
What is psoriasis
Chronic inflammatory dermatosis that appears to have autoimmune basis; strong assoc its HLA-Cw*0602; dominated by Th1 and 17 hype cytokines; treat with TNF blockers; can be induced in susceptible individuals by local trauma (koebner phenomennon)
What is the morphology of psoriasis
Most commonly affects skin of elbows, knees, scalp, lumbo-sacral area, intergluteal cleft and glans penis; pink to salmon colored plaque covered by silver-white scales that are loosely adherent; nail changes - yellow-brown discoloration with pitting, dimpling, or separation of nail plate (onycholysis); epidermal thickening with downward elongation of rete ridges (test tubes in a rack) stratum granulosum thinned or absent and extensive parakeratotic scale seen; thinning of layer that lines dermal papillae neutrophils form spongiform pustules and parakeratotic stratum corneum (Munro microabscess)
What is auspitz sign
Pulling back scales of psoriasis results in pinpoint bleeds
What is seborrheic dermatitis
Chronic inflammatory dermatosis; involves regions with high density of sebaceous glands (scalp, forehead especially labella, external auditory canal, retroauricular area, nasolabial olds, presternal area); inflammation of epidermis
What is the pathogenesis of seborrheic dermatitis
Increased sebum production n response to androgens *parkinsons patients have increased likelihood; colonization of skin with fungus - malassezia; severe form seen in AIDs individuals
What is the morphology of seborrheic dermatitis
Individual lesions are macules or papules on erythematous yellow, greasy base assoc with scaling and crusting; fissures can be present, esp behind ears; dandruff is common; parakeratosis containing neutrophils found at Ostia of hair follicles (follicular lipping)
What is lichen planus
Pruritic purple, polygonal, planar, papules, plaques *six Ps; self limited usually (1-2 years); resolution leaves hyperpigmented residue
What is the morphology of lichen planus
Itchy papules tat coalesce; highlighted. By white dots or lines called wick ham striae created by hypergranulosis; interface dermatitis; sawtooth* pattern; anucleate necrotic basal cells may become incorporated into inflamed papillary dermis referred to as colloid or civatte bodies
What is pemphigus
Blistering disorder caused by autoabs that result in dissolution of intercellular attachments within epidermis and mucosal epithelium; most are in 4-6th decade of life; men=women; multiple variants: vulgaris, vegetable, foliaceus, erythematosus, paraneoplastic; usually benign but can become fatal
What is a subcorneal blister
Stratum corneum forms the roof of the bulla (as in pemphigus foliaceus)
What is a suprabasilar blister
Portion of the epidermis including the stratum corneum forms the roof (as in pemphigus vulgaris)
What is a subepidermal blister
Entire epidermis separates from dermis (as in bullous pemphigoid)
What is pemphigus vulgaris
Most common type* involves mucosa and skin, esp scalp, face, axilla, groin, trunk and points of pressure; vesicles and bullae that rupture easily
What is pemphigus vegetans
Rare; presents with large moist verrucous (wart like) vegetating plaques studded wit pustules on groin, axilla and flexural surfaces
What is pemphigus foliaceus
More benign form; endemic in Brazil (fogo selvagem); scalp, face, chest and back; bullae very superficial and present as areas of erythema and crusting
What is pemphigus erytematosus
Localized less severe form of pemphigus foliaceus; may selectively involve malar area of face in lupus erythematosus like fashion
What autoabs are seen in pemphigus vulgaris
Dsg1 and Dsg3 - causes blisters in deep suprabasal epidermis
What abs are seen in pemphigus foliaceus
Dsg1; leads to superficial blisters
What abs are seen in bullous pemphigoid
BPAG2 (component of hemidesmosome) leads to blister formation at level of lamina Lucida of BM
What does paraneoplastic pemphigus occur in assoc with
Non-Hodgkin lymphoma mostly
What is the pathogenesis of all pemphigus dz
Autoimmune IgG abs against desmogleins; net-like partner of IgG deposits
What is the morphology of pemphigus
Acanthosis (dissolution or lysis of intercellular bridges); in vulgaris and vegetans, selectively involves cells immediately above basal layer; in vegetans, their is overlying epidermal hyperplasia; an immediately suprabasal acantholytic blister is characteristic of vulgaris*
What is bullous pemphigoid
Affects elderly; sites of involvement inner thighs, flexor surfaces of forearms, axillae, groin, lower abdomen; oral lesions appear after cutaneous
What is the pathogensis of bullous pemphigoid
Autoabs to proteins that are required for adherence of basal keratinocytes to BM; deposition in continuous linear pattern at dermoepidermal junction
What is the morphology of bullous pemphigoid
Tense bullae filled with clear fluid involving erythematosus or normal appearing skin; do not rupture easily *unlike in pemphigus; heal without scarring; separation of bullous from pemphigus is identification of supepidermal nonacantholytic blisters
What are the characteristics of dermatitis herpetaformis
Mostly males in 3rd-4th decade; very itchy
What is the pathogenesis of dermatitis herpetiformis
IgA abs cross react with reticulum (component of anchoring fibrils that tether epidermal BM to superficial dermis); produces subepidermal blister
What is the morphology of dermatitis herpetiformis
B/l symmetric and grouped involving extensor surfaces, elbow,s knees, upper back and butt; fibrin and neutrophils accumulate selectively at tips of dermal papillae* forming microabscesses; discontinuous granular deposits of IgA that selectively localize to tips of dermal papillae
What are the noninflammatory blistering disorders
Epidermolysis bullosa and porphyria
What is epidermolysis bullosa
Grou pf disorders caused by inherited defects in structural proteins that land mechanical stability to the skin; common feature is proclivity to form blisters at sites of pressure, rubbing or trauma at or soon after birth
What are the types of epidermolysis bullosa
- simplex: defects of basal cell layer of epidermis resulting from mutations in genes encoding keratin 14 or 5; normally pair with one antlers to make keratin fiber; dominant negative activity; AD; most common type
- junctional: blisters occur in otherwise histo normal skin at level of lamina Luisa; AR defect in subunit of lamina (binds hemidsmosomes and anchoring filaments)
- dystrophic: blisters beneath lamina densa in assoc with rudimentary to defective anchoring I rails; mutations in COL7A1 (type VII collagen); AD or AR
- mixed.
What is porphyria
Group of uncommon or acquired disturbances of porphyria metabolism (pigments that are normally present in Hb, myoglobin and cytochromes)
What are the types of porphyria
Congenital erythropoietin porphyria, erythrohepatic protoporphyai, acute intermittent porphyria, porphyria cutanea Garda, mixed
What are the manifestations of porphyria
Urticaria, subepidermal vesicles assoc with scarring exacerbated by sunlight; adjacent dermis contains vessels with walls thickened by glassy depsotis of serum proteins (Igs)
What is acne vulgaris
Males have more severe dz; milder in Asians; inflammatory and noninflammatory type; noninflammatory broken down into
- open comedones: follicular papules containing central black keratin plug; result of oxidation of melanin pigment
- closed comedones:follicular papaules without visible central plug; keratin plug trapped beneath epidermal surface - potential sources of follicular rupture and inflammation
What is the pathogensis of acne
- keratinization of lower portion of follicular infundibulum and development of keratin plug that blocks outflow of sebum to skin surface
- hypertrophy of sebaceous glands during puberty under influence of androgens
- lipase-synthesizing bacteria (propionibaterium acnes) colonizing upper and midportion of hair follicle converting lipids to proinflammatory FA
- secondary inflammation of involved follicle
How doe acutane work
Antisebaceous action
What is the morphology of acne
Erythematous papules, nodules and pustules; severe variants (acne conglobata) result in sinus tract formation and dermal scarring
What is rosacea
Predilection for females; 4 stages
- flushing episodes (prerosacea)
- persistent erythema and telangiectasia
- pustules and papules
- rhinophyma (permanent thickening of nasal skin by confluent erythematous papules and prominent follicles)
What is the pathogenesis of rosacea
High cutaneous levels of antimicrobial peptide cathelicidin;; diff from peptides in individuals without rosacea as a result of alternative processing by kallikrein 5; TLR2 involve
What is panniculitis
Inflammatory reaction in subcutaneous adipose tissue that affects lobules of fat or connective tissue that separates fat into lobules; often involves lower legs; erythema nodosum most common form* erythema induration another form
What is erythema nodosum
Poorly defined, exquisitely tender erythematosus plaques and nodules that may be more palpated rather than seen; assoc with infections (beta hemolytic strep, TB, coccidiomycosis, histo, leprosy), drugs (sulfonamides, OCP), sarcoidosis, IBD; delayed hypersensitivity; over weeks, lesions flatten and become bruiselike leaving no scars while new lesions develop; need deep wedge of tissue bx
What is erythema induratum
Affects adolescents and menopausal women; primary vasculitits of deep vessels supplying the fat lobules of subcutis; leads to fat necrosis and inflammation; presents as erythematous slightly tender nodule that usually ulcerates
What is the morphology of erythema nodosum
In early lesions, connective tissue septae are widened by edema, fibrin exudate, and neutrophils; later infiltration by lymphocytes, histiocytes and giant cells assoc with septal fibrosis; no vasculitis
What is the morphology of erythema induratum
Granulomatous inflammation and zones of caseous necrosis involve fat lobule; early lesions show necrotizing vasculitis affecting small to medium sized arteries and veins in deep dermis and subcutis
What is Weber-Christian dz
Relapsing febrile nodular panniculitis; rare form of lobular nonvasculitits panniculitis seen in kids and adults; crops of erythematous plaque or nodules on the LE created by deep-seated foci of inflammation containing aggregates of foamy macrophages
What is factorial panniculitis
Secondary panniculitis caused by self-inflicted traum or injection of foreign substance
What are verrucae
Squamoproflierative disorders caused by HPV; self limited regress within 6 months to 2 year s
What HPV is assoc with bowenoid papulosis
HPV 16
What is the morphology of verrucae
- verruca vulgaris: most common; occur anywhere but mostly on hands (dorsal surfaces); flat to convex; rough, pebble like surface
- verruca plana: flat wart common on face or dorsal hand; elevated, flat smooth; smaller
- verruca plantaris and palmaris: occur on soles and palms; rough scaly lesions coalesce ; look like calluses
- condyloma acuminatum: penis, female genitalia, urethra, perianal areas and rectum; cauliflower like mass
What are the histo features of verrucae
Epidermal hyperplasia termed verrucous or papillomatous epidermal hyperplasia; halos of pallor surrounding nuclei
What are the characteristics of Molluscum contagiosum
Virus is brick shaped, dumbbell shaped DNA core
What causes impetigo
Staph aureus
What is the pathogensis of impetigo
Bacteria in epidermis evoke innate immune response that causes epidermal injury leading to exudate and formation of a scale crust; bacterial toxin cleaves desmoglein 1 -forms blister; heals without scarring
What is the morphology of impetigo
Starts ad macule, but pustules supervenes; as pustules break, erosions form covered with drying serum giving honey colored crust appearance; need to remove crust or new lesions will form and can damage epidermis; accumulation of neutrophils beneath stratum corneum
What are superficial fungal infections
Confined to stratum corneum and caused primarily by dermatophytes
What is tinea capitis
Occurs in kids; dermatophytosis of scalp - asymptomatic hairless patches of skin assoc with mild erythema, crust formation and scaling
What is tinea Barbae
Dermatophyte infection of beard that affects adult men
What is tinea corporis
Common superficial fungal infection; all ages,but mostly kids; predisposing factors include excessive heat, exposure to infected animals, and chronic dermatophytosis of feet or nails; most common type is expanding round erythematous plaque with scaling border
What is tinea cruris
Inguinal ares of obese men during warm weather
What is tinea pedis
Athletes foot; diffuse erythema and scaling; initially localized to web spaces; most of inflammatory reaction is result of bacterial superinfection and not directly related to primary dermatophytosis; can spread to nail (onychomycosis) - produces discoloration, thickening and deformity of nail plate
What is tinea versicolor
Usually on upper trunk; caused by malassezia furfur (yeast; not dermatophyte); macules of varied size and color with fine peripheral scale
What makes up the bone matrix
Osteoid (mostly type I collagen) and a mineral component
What is a measure of osteoblast activity
Serum osteopontin (osteocalcin)
What makes the bone matrix hard
Hydroxyapatite
What is the cellular component of mature bone
Osteoblasts, osteocytes and bone resorbing osteoclasts
- osteoblast: surface of matrix; synthesize, transport and assemble matrix and regulate mineralization
- osteocytes:interconnected by network of dendritic processes through tunnels known as canaliculi; control calcium nad phosphate levels and detect mechanical forces and translate them into biological activity (mechanotransduction)
- osteoclasts: multinucleated macrophages derived from monocytes that are responsible for bone resorption; attach to bone matrix and create extracellular trench
What is intramembraneous ossification use for
Formation of flat bones; no cartilage anlagen
What is the development of bone controlled by
- growth hormone: acts on resting chondrocyts to induce proliferation
- T3: acting on proliferating chondrocytes to induce hypertrophy
- Indian hedgehog: locally secreted; coordinates chondrocyte proliferation and osteoblast proliferation
- PTHrP: local; expressed by stromal cells
- Wnt: bind to Frizzld and LRP5/6 to activate Bcatenin
- SOX9: TF produced by proliferating chondrocytes essential for differentation into chondrocytes
- RUNX2: chondrycote and osteoblast differentiation; expressed in hypertrophic chondrocytes
- FGFs
- BMPs
Where does bone remodeling take place
Bone multicellular unit BMU
Describe the RANK-RANKl pathway
RANK expressed on osteoclasts precursors; RANKL expressed on osteoblasts; OPG secreted decoy receptor made by osteoblasts (prevents RANKL interaction with RANK); when stimulated by RANKL, RANK activates NFkB -> generation of osteoclasts
What factors promote bone turnover
PTH, IL-1, glucocorticoids
When is peak bone mass achieved
Early adulthood after cessation of skeletal growth
What are dysostosis
Problems in migration and condensation of mesenchyme; most common forms: complete absence of bone or entire digit (aplasia), extra bones or digits (supernumerary digit), and abnormal fusion of bones (syndactyly, craniosynostosis); homeobox mutations most common
What are dysplasias of bone
Caused by global disorganization of bone or cartilage; arise from mutations in genes that control development or remodeling of entire skeleton
What defects in transcription factors can cause diseases of skeleton
- HOXD13: brachydactyly types D and E; short broad terminal phalanges of first digit
- SOX9: camptomelic dysplasia; sex reversal; ab skeleton
- RUNX2: cleidocranial dysplasia; abnormal clavicles, Wormian bones, supernumerary tenth
- TBX5: holt-oral syndrome; congenital ab; forelimb anomalies
- LMX1B: nail-patella syndrome; hypoplastic nails, patellar, dislocated radial head, progressive nephropathy
- PAX3: waardenburg syndrome; hearing loss, abnormal pigmentation, craniofacial abnormalities
What defects in signal transduction proteins can lead to skeletal defects
- FGFR3: achondroplasia; short stature, frontal bossing, midface def
- FGFR3: hypochondroplasia; disproportionately short stature, Micromelia, relative microcephalic
- LRP5: osteopetrosis AD; increased bone density, hearing loss, skeletal fragility
- RANKL: osteopetrosis infantile; increased bone density
- LRP5: osteporosis pseudoglioma syndrome; congenital or infant-onset loss of vision, skeletal fragility
- FGFR3: thanatophoric dysplasia; severe limb shortening and bowing, frontal bossing, depressed nasal bridge
What defects in extracellular structural proteins can cause diseases of skeleton
- COL2A1: achondrogenesis type 2; short trunk
- COL10A1: type x collagen; metaphyseal dysplasia, Schmidt type; mildly short stature
- COL1A1 COL1A2: osteogenesis imperfects; bone fragility
What defects in metabolic enzymes and transporters can cause skeletal disease
- CA2: osteopetrosis with renal tubular acidosis; affects carbonic anhydrase; increased bone density, fragility
- CLCN7: osteopetrosis, late onset type 2; affects chloride channel; increased bone density, fragility
What is cleidocranial dysplasia
AD; patent fontanelles, delayed closure of cranial sutures, Wormian bones (extra bones that occur within cranial suture), delayed eruption of secondary teeth, primitive clavicles, short height
What is the most common skeletal dysplasia
Achondroplasia; AD; retarded cartilage growth; shortened prox extremities; normal trunk; big head with depression of root of nose; GOF in FGFR3
What is thanatophoric dysplasia
Most common lethal for of dwarfism; shortening of limbs, frontal bossing, microcephalic; small chest cavity; bell-shaped abdomen; GOF in FGFR3
What is the most common inherited disorder of connective tissue
OI
What are the features of OI
Blue sclera, hearing loss (sensorineural and conduction), dental imperfections (small misshapen and blue-yellow)
Which type of OI is fatal in utero or during perinatal period
Type 2
What are the features of OI type 1
Decreased synthesis of pro-alpha1chain; AD; postnatal features, blue sclera, normal stature, fragility, dentinogenesis imperecta, hearing impairment, joint laxity, compatible with survival
What are the features of OI type 2
Abnormally short pro-alpha 1 chain, unstable triple helix, abnormal or insufficiency pro-alpha 2 chain; most AR, some AD; death in utero or within days of birth; blue sclera
What are the features of OI type 3
Altered structure of propeptides of pro-alpha2; impaired formation of triple helix; AD or AR; compatible with survival; growth retardation, multiple fractures, progressive kyphoscoliosis, blue sclera at birth that becomes white, hearing impairment, dentinogenesis imperfecta; progressive deforming
What are the features of OI type IV
Short pro-alpha2 chain; unstable triple helix; AD; postnatal fractures; NORMAL sclera; moderate skeletal fragility; short stature; sometimes denitogenesis imperfecta; compatible with survival
What collagens are important in hyaline cartilage
II, IX, X, XI
What is osteopetrosis
Marble bone disease aka albers-schonberg dz; genetic; reduced bone resorption and diffuse symmetric skeletal sclerosis due to impaired function or formation of osteoclasts; stone like quality of bones but they are abnormally brittle and fracture like chalk
What is the pathogenesis of osteopetrosis
Most mutations interfere with process of acidification of osteoclasts resorption pit which is required for dissolution of calcium hydroxyapatite within matrix; ex: AR defect in CA2 (carbonic anhydrase) - also affects ability to acidify urine; another form has mutation in CLCN7 (encodes proton pump located on surface of osteoclasts)
What is the morphology of osteopetrosis
Lack medullary canal; ends of long bones are bulbous (erlenmeyer flask deformity); neural foramina are small and compress exiting nerves; primary spongiosa persists Nd fills medullary cavity leaving not room for hematopoietic marrow; bone is woven
What are the clinical features of osteopetrosis
Severe infantile is AR and becomes evident in utero or soon afte birth; fracture, anemia and hydrocephaly are seen resulting in postpartum mortality; those who survive have CN defects (optic atrophy, deafness, facial paralysis) and repeated infections b/c of leukopenia; HSM; mild AD form may not be detected until adolescence - repeat fractures; mild CN defect and anemia; treat with hematopoietic SC transplant
What are the mucopolysaccharidoses
Lysosomal storage disease caused by def in enzymes that degrade derrmatan sulfate, heparin sulfate and keratin sulfate; accumulate in chondrocytes causing death o cells resulting in defects in cartilage; short stature, chest wall abnormalities, malformed bones
What is the dif between osteopenia and osteoporosis
Osteopenia: decreased bone mass
Osteoporosis: osteopenia severe enough to increase risk of fracture
Other than bone mass 2.5 SD below the mean, what signifies osteoporosis
Presence of atraumatic fracture or vertebral compression fracture
What are the most common forms of osteoporosis
Senile and postmenopausal type
What are the age related changes in bone
Osteoblasts have reduced proliferation and lower response to GF; senile osteoporosis categorized as low-turnover variant
What effect does reduced physical activity have on bone
Increased rate of bone loss (mechanical forces stimulation bone remodeling); lose bone when immobilized or paralyzed extremity, astronauts; higher bone density in athletes; weight training most effective rather than repetitive endurance (ie bicycling)
What genes have been assoc with osteoporosis
RANKL, OPG, PANK
What effect does calcium nutritional state have on bone
Influences peak bone mass
What kind of osteoporosis is postmenopausal
High-turnover; lack of estrogen stimulates both bone resorption and formation but latter cant keep up with the order; lack of estrogen stimulates cytokines which increase RANKL and stimulate osteoclasts recruitment
What is the morphology of osteoporosis
Histological normal bone that is decreased in quantity; loss of horizontal trabecular and thickened vertical trabecular
What are the clinical features of osteoporosis
-fractures of vertebrae causes deformities- lumbar lordosis and kyphosclosiosis
-fractures of femoral neck, pelvis or spine can cause PE and pneumonia
Cannot be detects on plain radio graph until 30% of bone mass lost
What is denosumab
Anti-RANKL ab used for some orbs of postmenopausal osteoporosis
What is paget dz
Aka osteitis deformans; disorder of increased, but disordered and structurally unsound bone mass
What are the stages of paget dz
- initial osteocytes stage
- mixed osteoclastic-osteoblasts stage which ends with predominance of osteoblasts activity and evolves into
- a final burned out quiescent osteosclerotic stage
What are the features of paget dz
Usually begins in late adulthood (average 70 years); common in whites in England, France, Austria, Germany, Australia, and US; most are asymptomatic
What is the pathogenesis of paget dz
Uncertain; familial and some sporadic cases show mutations in SQSTMI - increases activity of NFkB; activating RANk and inactivating OPG mutations account from some juvenile cases; modulation of vit D sensitivity and IL-6 secretion by virally infected osteoclasts - can play a role
What is the morphology of paget dz
Hallmark is mosaic pattern of lamellar bone seen in sclerotic phase; jigsaw puzzle like appearance produced by prominent cement lines
What is the clinical course of paget
Depend on extent and site of dz; most are asymptomatic; mostly polyostotic; axial skeleton or proximal femur involved in most cases; enlargement of craniofacial skeleton can produce leontiasis ossea (lion face) and cranium too heavy to hold head erect; can lead to invagination of skull base (platybasia) and compression of posterior fossa; anterior bowing of femurs and tibia - secondary osteoarthritis; chalk stick fractures; hypervascularitiy warms overlying skin -> can lead to high output heart failure
What tumor and tumor-like conditions develop in pagetic bone
Giant cell tumor, extra osseous massses of hematopoietic tissue; most dreaded complication is sarcoma - usually osteo or fibrosarcoma
How can diagnosis of paget dz be made
Radiograph; bone is enlarged with thick coarsened vortices and cancellous bone; active dz has wedge shaped lyric leading edge; many of elevated serum alk phosphatase but normal calcium and phosphorus
How do you treat paget
Calcitonin and bisphosphonates
What other aspects does renal failure contribute to bone disease besides just secondary hyperPTH
Decreased vit D synth; hyperphosphatemia further inhibits alpha1 hydroxylase; metabolic acidosis and aluminum deposition in bone
What is the morphology of bone in primary hyperPTH
-osteoporosis (most severe in phalanges, vertebrae and prox femur - can produce dissecting osteitis - railroad tracks), brown tumors (reactive mass) and osteitis fibrosa cystica
What is renal osteodystrophy
Seen in chronic renal dz; osteopenia/porosis; osteomalacia; secondary hyperPTH growth retardation
What are the types of bone changes in ESRD
- high turnover osteodystrophy: increased bone resorption and bone formation with the former predominating
- low-turnover or aplastic dz: a dynamic bone (little osteoclasts and osteoblasts activity)
- mixed pattern of dz: areas of high turnover and low turnover
What is the pathogenesis of renal osteodystrophy
- tubular dysfunction: ie renal tubular acidosis; low pH dissolves hydroxyapatite resulting in demineralization of matrix and osteomalacia
- generalized renal failure: reduced phosphate excretion, secondary hyper PTH
- decreased production of secreted factors: decreased BMP-7 (induces osteoblast differentiation)
What are the types of fractures
Simple: overlying skin intact
Compound: bone communicates with skin surface
Comminuted: bone is fragmented
Displaced: ends of bone at fracture site are not aligned
Stress: slowing developing fracture
Green stick: extends only partially through bone; common in infants
Pathological: involving bone weakened by underlying disease
What is involved in the healing of fractures
Immediately after fractures, hematoma forms filling fracture gap; clotted blood provides fibrin mesh and creates framework for influx. Of inflammatory cells; platelets release factors that activate osteoprogenitor cells in periosteum, medullary cavity; en of first week - matrix production and remodeling of fractured ends; soft tissue callus or procallus
What happens after 2 weeks of fracture
Soft tissue callus transformed into bony callus; deposit subperiosteal trabecular of woven bone oriented perpendicular to cortical axis; stabilizes site; undergoes endochonral ossification
How can the healing of a fracture be messed up
Improper immobilization can cause non union, which if persists the callus undergoes cystic degeneration and luminal surface can become lined by synovial like cells creating a false joint (pseudoarthrosis)
What do most cases of bone necrosis stem from
Fractures or corticosteroid administration
What are the sx of avascular necrosis
- subbchondral: pain withactivity that becomes constant as secondary changes supervenes; often collapse and lead to secondary osteoarthritis
- medullary: clinically silent except in gaucher dz, sickle cell, dysbarism
What is osteomyelitis
Inflammation of bone and marrow
What are the features of pyogenic osteomyelitis
In kids, most common hematogenous in origin and develops in long bones
In adults, most commonly from open fractures, surgery or diabetic infections
Staph aureus most common cause
What are the most common causes of osteomyelitis in individuals with UTIs or IV drug users
Klebsiella, E. coli, pseudomonas
What are frequent causes of osteomyelitis in neonatal period
Haemophilus and group B strep
What are the different sites of osteomyelitis in kids vs adults
- neonate: metaphysic, epiphysis or both
- children: meteaphysis
- adults: emphyses and subchondral regions
What is the dead bone in osteomyelitis known as
Sequestrum
What can occur after the first week of osteomyelitis
Chronic inflammatory cells release cytokines that stimulate osteoclastic bone resporption newly deposited bone can form shell of living tissue known as involucrum around segment of devitalized infected bone; Brodie abscess (small intraosseous abscess that involves cortex and walled off by reactive bone); sclerosing osteomyelitis of garre develops in jaw
What is the clincial course of hematogenous osteomyelitis
Unexplained fever in kids; localized bone pain in adults; diagnosis strongly suggested by radiographic findings of lyric focus of bone destruction surrounded by zone of sclerosis
What are the features of chronic osteomyelitis
Can cause flare puts years after initial infection; complications include fracture, secondly amyloidosis, endocarditis, sepsis; development of SCC of draining sinus tract and sarcoma in infected bone
What are complications of tuberculous arthritis
Destruction of discs and vertbrae, sinus tract formation, psoas abscess, amyloidosis
What is skeletal syphilis
Syphilis and yaws (treponema pertenue) can involve bone; in congenital syphilis, bone lesions appear about 5th month of gestation; localize in areas of active endochondral ossification (osteochondritis) and periosteum (periostitis); saber shin produced by massive reactive periosteum bone deposition in medial and anterior surfaces of tibia
What is the morphology of skeletal syphilis
Edematous granulation tissue containing numerous plasma cells and necrotic bone
What age does osteosarcoma incidence peak
Adolescence; most commonly involves the knee
What age does chondrosarcoma incidence peak
Older adults; mostly involves pelvis and proximal extremities
What is the most common primary cancer of bone
Osteosarcoma
What increases the risk of bone neoplasia
Chronic injury: bone infarcts, chronic osteomyelitis, paget dz, radiation, metal prostheses
What are the common locations of hematopoietic bone tumors
Vertebrae, pelvis; age 50-60
What are the cartilage forming tumors in bone and where are they commonly located
Benign:
-osteochondroma: metaphysic of long bones; age 10-30
-chondroma: small bones of hands and feet; 30-50
-chondroblastoma: epiphysis of long bones; 10-20
-chondromyxoid fibroma: tibia, pelvis; 20-30
Malignant:
-chondrosarcoma: pelvis, shoulder; 40-60
What are the bone forming tumors of bone
Benign
-osteoid osteoma: metaphysic of long bones; 10-20
-osteoblastoma: vertebral column 10-20
Malignant:
-osteosarcoma: metaphysic of distal femur, prox tibia; 10-20
Where do notochodral tumors of bone form
Chordoma - malignant; Clivus and sacrum; age 30-60; foamy cells in myxoid matrix
What do bone forming tumors all produce
Unmineralized osteoid or mineralized woven bone
What are osteoid osteomas
By definition, less than 2cm in diameter occur in young men in teens and 20s; predilection for appendicular Skeleton; femur or tibia; arise in cortex, less frequent in medullary cavity; thick rind of reactive cortical bone on XR; severe nocturnal pain relieved by aspirin* - pain caused by PGE2 released by osteoblasts; treated with radiofrequency ablation
What are osteoblastomas
Larger than 2 cm; involves posterior spine (laminate and Pedicles); pain is unresponsive to aspirin* tumor does not induce bony reaction; excised
What is the morphology of osteoid osteoma and osteoblastoma
Both are masses of hemorrhagic gritty tan tissue;composed of interconnecting trabecular of woven bone rimmed by single layer of osteoblasts
What is osteosarcoma
Malignant tumor that produces osteoid matrix or mineralized bone; bimodal age distribution: <20 and older adults who have paget, bone infarcts or prior radiation; more common in men; arise in metaphyseal region of long bones and most occur around the knee; breaks through cortex and lifts periosteum resulting in reactive periosteal bone formation; triangular shadow btw Corte and raised periosteum known as codman triangle and is indicative of aggressive tumor (but not diagnostic of osteosarcoma)
What is the pathogenesis of osteosarcoma
- RB
- TP53
- INK4a
- MDM2 and CDK4
How are the subtypes of osteosarcoma grouped
- site of origin (intramedullary, intracortical, or surface)
- histo grade
- primary (underlying bone is unremarkable) or secondary to preexisting disorders
- histo features (osteoblasts, chondroblastic, fibroblastic, telangiectatic, small cell, giant cell)
