2011-07-PATHO-Skin Oncology

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PIGMENTARY,INFLAMMATORY ANDNEOPLASTIC LESIONS OFTHE SKIN

I.DISORDERS OF PIGMENTATIONAND MELANOCYTES

A. VITILIGO

Partial or complete loss ofpigment-producing melanocyteswithin epidermis

All races affected

Asymptomatic, flat, well-demarcated macules of pigmentloss

Few centimeters to large lesions

involving wrists, axillae, extensorsurfaces, perioral, periorbital andanogenital skin

Rarely: total body involvement

Docs example is The King ofPop, The Genius, The Main Man,Michael Jackson (RIP)

HISTOLOGY :

Characterized as loss ofmelanocytes

In albinism, melanocytesare present but NO melaninis produced due to lack ofenzyme tyrosinase

THEORIES:

Autommunity

Neurohumoral factors

Self-destruction ofmelanocytes by toxicintermediates

B. FRECKLE

Common pigmented lesions in

childhood

Change not in the number ofmelanocytes but in degree ofpigmentation

Fade then darken

1-10 mm

Tan-red to light brown maculeswhich appear after sun exposure

HISTOLOGY:

Increase in melaninpigment within basalkeratinocytes

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Subject: PathologyTopic: Skin OncologyLecturer: Dr. CagampanDate of Lecture: July 21, 2011

Transcriptionist: Benjie ParasEditor: Robin PadillaPages: 14

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C. MELASMA

Mask-like zone of facialhyperpigmentation commonlyseen in pregnancy

Poorly defined, blotchy maculesinvolving cheeks, temples and

forehead

May resolve spontaneously at endof pregnancy

HISTOLOGY:

Epidermal type- increasemelanin deposition in basallayer

Dermal type- melanin

incontinence

D. LENTIGO

In infancy and childhood; no sexpredilection

Common benign localizedhyperplasia of melanocytes

May involve skin, mucousmembrane as 5-10 mmoval, tan macules

HISTOLOGY:

Melanocytic hyperplasiaproducing a

hyperpigmented basallayer accompanied byelongation and thinning ofrete ridges

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E. NEVOCELLULAR NEVUS(mole)

Congenital or acquired

Tan to brown pigmented, small

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spindle-shaped atlower dermis

F. DYSPLASTIC NEVI

BK moles : precursor ofmalignant melanoma

Larger than most acquired nevi(>6mm) and occur in hundreds;on sunlight or unexposed areas ofthe body

Flat macules to raised plaqueswith variable color and contour

Imply an increased risk that thepatient will develop malignantmelanoma in an affected skin andpre-existing nevi

Undergo malignanttransformation at a higherfrequency than ordinary moles

Documented in family memberswith Heritable melanomasyndrome

HISTOLOGY:

Enlarged, irregular nevuscells with cytologic atypia

Occupying the dermis withcoalescence of nevus nestand lentiginous hyperplasia

G. MALIGNANTMELANOMA

Lightly pigmented individuals athigher risk

Docs example is BOB MARLEY.He died due to a malignantmelanoma on his toe. He didnt

amputate the toe due to hisRastafarian beliefs.

Predisposing factors:

Sunlight

Dysplastic nevus

Hereditary factors

Carcinogens

Signs and Symptoms:

Usually asymptomatic

Itching or pain may beearly manifestations

Change in color, shape,size of pigmented lesionare most consistent signs

Gross:

Variegated in color: shadesof black, brown, blue, red,gray with areas ofhypopigmentation,irregular notched borders

May occur in scalp,mucosal surfaces, nailbeds,conjunctiva, orbit,esophagus, meninges

GROWTH CHARACTERISTICS:

Radial growth

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Grow horizontallywithin the epidermaland superficialdermal layers

Does not yetmetastasize (Clarklevel 4)

Vertical growth

Melanoma growsinto deeper dermisas an expansilemass Metastaticpotential (Clark level5)

HISTOLOGY:

Large, irregular cells withhyperchromatic nuclei andprominent nucleoli

Must indicate depth of invasion(Clark level):

Level I: confinement ofmelanoma cells toepidermis and appendages

Level II:extension to

papillary dermis

Level III: throughoutpapillary dermis and fillingit; impinging upon reticulardermis

Level IV: invasion ofreticular dermis

Level V: invasion ofsubcutaneous fat

Prognosis depends on tumorthickness:

5-yr survival rate: 83%

II. BENIGN EPITHILIAL TUMORS

A.SEBORRHEICKERATOSIS

In middle age and older

Arise spontaneously in trunk,head and neck, extremities

Round, flat, coin-like plaques, fewmm. to several cm., dark brown,velvety to granular surface

HISTOLOGY:

Sheets of small, basaloidcells in tracts sharplydemarcated fromepidermis

Variable pigment

Numerous horn cysts

Laser-Trelat sign

numerous

occurrence ofseborrheic keratosisas part of a

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paraneoplasticsyndrome

B.ACANTHOSISNIGRICANS

Hyperpigmented skin lesion offlexural areas

like axillae, skin folds of neck,groin and anogenital region

Benign Type

80% of cases

In childhood or puberty

Malignant Type

in middle age and older

In association withunderlyingadenocarcinoma

HISTOLOGY

Undulating epidermalacanthosis with peaks andvalleys

Basal layerhyperpigmentation,hyperkeratosis

C.FIBROEPITHELIALPOLYP

Skin tag, bag-like, fleshy, softtumor

Soft, flesh-colored, bag-like tumoroften attached by a slender stalk

In middle age and older

Neck, trunk and face

HISTOLOGY:

Fibrovascular core coveredby squamous epithelium

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D.EPITHELIAL CYST(WEN)

Epidermal Inclusion cyst

(Sebaceous cyst)

Dormed by down growth andcystic expansion of epidermis orepithelium of hair follicle,subcutaneous, wellcircumscribed, firm, movablenodules

HISTOLOGY:

Cyst wall lined by stratifiedsquamous epitheliumcontaining keratinousmaterial.

E. KERATOCANTHOMA

Flesh colored, dome-shapednodules with a keratin-filled plug

imparting a crater-likeappearance

1-several cm., cheeks, nose, ears,dorsa of hands, may mimicsquamous cell carcinoma

Rapidly develops but healsspontaneously without treatment

HISTOLOGY:

Central, keratin-filled cratersurrounded byproliferating, large, atypicalepithelial cells thatextended upward in a lip-like fashion and downwardinto dermis as irregulartongues

F. ADNEXAL TUMORS

Solitary or multiple papules andnodules

Eccrine poroma : on palms

and soles

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Cylindroma : forehead andscalp; turban tumors; islandsof basaloid cells like pieces f

jigsaw puzzle

Tricoepitheliomas : face,scalp, neck, and upper trunk;proliferation of basaloid cellswith formation of hair follicle-like structures

III. PREMALIGNANT ANDMALIGNANT EPIDERMAL TUMORS

A.ACTINIC KERATOSIS

Dysplastic epithelial changes dueto chronic sun exposure

In lightly pigmented individuals

1 cm, tan-red, brown with a roughsandpaper consistency

Cutaneous horn

Face, arms, dorsal part of hands

HISTOLOGY:

Hyperkeratosis,parakeratosis, basal layerhyperplasia with cytologicatypia or early atrophy ofepidermis

Dermis shows thickenedand elastic fibers

B.SQUAMOUS CELLCARCINOMA

PREDISPOSING FACTORS:

Sunlight exposure

Industrial carcinogens (tarsand oils)

Chronic ulcers

Draining osteomyelitis

Old burn scars

Arsenical ingestion

Ionizing radiation

Tobacco and betel nutchewing (oral cavity)

Presents as plaques, nodules,ulcer, leukoplakia

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HISTOLOGY:

Range from well to poorlydifferentiated lesions

Low potential formetastasis

C.BASAL CELLCARCINOMA

Occurs in sun-exposed areas, andin lightly pigmented individuals

Incidence rises in patients with

inherited defects in DNAreplication or repair andimmunosuppression

Pearly papules; may ulcerate

Indolent behavior but maybedeeply ulcerative (invasive);rarely metastasize

Has different types:

1. Nodular type

2. Rodent ulcer

3. Keratotic type

4. Pigmented

5. Extensive ulceratedtype

HISTOLOGY:

Cords and islands ofbasaloid cells withhyperchromatic nucleiembedded in a mucinousmatrix and oftensurrounded by manyfibroblasts andlymphocytes

Peripheral palisading ofcells in tumor islands

IV. TUMORS OF THE DERMIS

A.BENIGN FIBROUSHISTIOCYTOMA(DERMATOFIBROMA)

In adults, few to several cm

Firm papules/ nodules

Proliferation of benign spindlefibroblasts, collagen andhistiocyte-like cells in intertwiningbundles within the dermis

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V. TUMORS OF CELLULARIMMIGRANTS TO SKIN

A. HISTIOCYTOSIS X(LANGERHANS CELLHISTIOCYTOSIS)

Solitary or multiple lesionsranging from papules to nodulesto scaling plaques

HISTOLOGY:

Diffuse dermal infiltrate oflarge, round cells with palecytoplasm and indentednuclei

Appear in cell aggregatesor as dermal infiltrates ofcells with foamy cytoplasm

B. MYCOSIS FUNGOIDES(CUTANEOUS T-CELLLYMPHOMA)

Greater than 40 y/o

Scaly red-brown patches, raised,scaling plaques and fungatingnodules : eczema-like lesions

Sezary syndrome : seeding ofblood by malignant T-cells

HISTOLOGY :

Band-like aggregateswithin the superficialdermis and invade theepidermis singly or inclusters

(PAUTRIERSMICROABSCESSES)

Sezary- Lutner cells

T-helper cells (CD4antigen-positive) withmarkedly unfolded nuclearmembrane imparting acerebriform contour

Histologic hallmark

D.MASTOCYTOSIS

Proliferation of mast cells in skin

or viscera

Urticaria pigmentosa

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Localized cutaneous formthat predominantly affectschildren

Solitary mastocytosis

Multiple, round, red-brown,non-scaling papules and

plaques or nodules

May have multi-organinfiltration

Signs and Symptoms dueto effects ofhistamine/heparin

VI. ACUTE INFLAMMATORYDERMATOSES

A.URTICARIA (HIVES)

Common between 20-40 y/o butcan occur in any age; trunk,extremities, ears

Localized mast cell degranulationand resultant dermal micro-vascular hyperpermeability (IgEdependent) culminating in pruritic

wheals

Lesions develop and fade withinhours; may last for days ormonths due to inability toeliminate the antigen;

Pruritic papules to largeedematous plaques

HISTOLOGY:

Superficial perivenularinfiltrate consisting ofmononuclear cells

Superficial dermal edema

Dilated lymphatics

B.ACUTE ECZEMATOUSDERMATITIS

Red, papulovesicular, oozing andcrusted lesions to scaling

plaques; very pruritic

to boil over

HISTOLOGY:

Spongiosis : accumulationof edema fluid within theepidermis (stratumspinosum);

Superficial perivascularlymphocytic infiltrateassociated with papillary

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dermal edema and mastcell degranulation

C.ERYTHEMAMULTIFORME

Cytotoxic reaction pattern

Self-limited disorder resultingfrom hypersensitivity response tocertain infection and drugs

multiform lesions : macules,papules, vesicles, bullae

target lesions : red macules, orpapules with eroded center

Associated with the following:

Infections- herpes simplex,mycoplasma infections,typhoid, etc.

Drugs- sulfonamides, PCN,barbiturates, salicylates,hydantoins and anti-malarials

Malignancies

Collagen-vascular diseases

VARIANTS:

Stevens Johnsons

Extensive febrileform in children witherosions andhemorrhagic crustsin lips and mucosalsurfaces

Toxic EpidermalNecrolysis

Diffuse necrosis andsloughing off ofcutaneous andmucosal epithelialsurface

HISTOLOGY:

zones ofepidermalnecrosis;blister

formation

erosion target lesion

lymphocyticinfiltrates near

necrotic basalepidermalcells andmicrovascularinjury to theunderlyingnutrientvessels

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D.ERYTHEMANODOSUM

Poorly defined, tender,erythematous nodules

Form of panniculitis-inflammatoryreaction involving subcutaneousfat, lower legs.

Associated with infections, drugadministration, sarcoidosis,inflammatory bowel disease andmalignancies.

HISTOLOGY :

edema, widenedconnective tissue septa,fibrin and neutrophilicexudation

Later mononuclear infiltrates septal fibrosis

VII. CHRONIC INFLAMMATORYDERMATOSES

A.PSORIASIS

1-2% of the population in US; anyage (mean: 27 y/o)

Elbows, knees, scalp,lumbosacral, interglutealcleavage, glans penis, nails

Well demarcated, pink andsalmon-colored plaques coveredby loosely adherent silvery-whitescales

Annular, linear, gyrate, orserpiginous lesions

Erythroderma : total bodyerythema and scaling , postularpsoriasis

HISTOLOGY:

Acanthosis due toincreased epidermal cells

Cell turn over

Elongation of rete ridgesand mitosis above basallayer

Thick parakeratosis scale

Absent granular cell layer

Dilated papillary dermalvessels

Auspitz sign

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multiple bleeding pointswhen a scale is lifted fromthe plaque due to proximityof dermal vessels withinthe papilla to overlyingscale

Munros microabscesses

Neutophilic aggregates

Kogoj phenomenon

Genesis of new lesions atsites of trauma

B.SEBORRHEICDERMATITIS

1 3% of general population

In regions with high density ofsebaceous glands

Macules, papules on anerythematous base with scalingand crusting

Unknown cause, responds toketoconazole

HISTOLOGY:

Spongiotic dermatitis

Follicular lipping parakeratotic mounds withneutrophils at ostia of hairfollicles

Superficial perivascularinfiltrate

C.LICHEN PLANUS

Pruritic, purple, polygonalpapules: skin and mucousmembranes

Self-limiting and resolvesspontaneously (1-2 yrs)

Wickhams striae: white dots orlines highlightening papules

Symmetric distribution alongextremities, wrist, elbows, glanspenis and oral cavity

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D.LUPUSERYTHEMATOSUS(LE) (DLE)

Malar erythema or large, sharplydemarcated

erythematous scaling plaques

Skin lesions are shiny, atrophic,wrinkled, telangiectasia orvessels, keratotic plugs

LUPUS BAND TEST:

(+) granular band of Ig andcomplement along dermo-epidermal junction

Humoral and cell mediatedmechanisms

HISTOLOGY:

Epidermal atrophy with lossof normal rete ridges

hyperkeratosis; basal layervacuolation;

lymphocytic infiltration ofdermal-follicular epithelial

junction, perivascular andperiadnexal;

Thickening of basementmembrane

E. ACNE VULGARIS

Affects hair follicles: mid to lateteenage years, male or female; allraces;

Result from physiologic hormonalvariations and alterations in hairfollicle maturation

Heritable and endocrine factors

Induced or exacerbated by drugs,occupational contactants andocclusive conditions

Open comedones: smallfollicular papules containing a

central black keratin plug(oxidation of melanin pigment;Known as black heads

Closed comedones:follicularpapules without a visible centralplug

Inflammatory acne:erythematous, papules, nodules,pustules

Propionebacterium acne:bacterial lipases that break downsebaceous oils

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VIII. BLISTERING DISEASES

A.PEMPHIGUS(VULGARIS)

Caused by

autoantibodydissolution ofintercellular

attachmentsacantholysis

4th to 6th decade of life, men =women

Cause by IgG autoantibodiesagainst desmogleins

Mucosa and skin of scalp, face,axilla, groin, trunk, pressurepoints

HISTOLOGY:

Acantholysis; suprabasal

blister

Superficial dermalinfiltration of chronicinflammatory cells

Immunofluorescence

Net-like pattern ofintercellular IgG deposits

B.BULLOUSPEMPHIGOID

Caused by autoantibodies againstBullous Pemphigoid Antigen

(BPAG); involved indermoepidermal bonding

Affects elderly; skin and mucosalmembranes

Tense bulla 2-8 cm in diameter

Inner thighs, flexor surfaces offorearms, axillae, groin and lowerabdomen

HISTOLOGY:

Subepidermal,nonacantholytic blisters

Superficial perivascularinfiltrate of lymphocytesand eosinophils; basal celllayer vacuolization

Immunofluorescence:

Continuous and lineardeposition of IgG

Basement atdermoepidermal junction

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C.DERMATITISHERPETIFORMIS

IgA antibodies to dietary glutenwhich cross-react with reticulin:component of anchoring fibrils

epidermal basement membraneto superficial dermis

Urticaria and grouped vesicles

Males 3rd and 4th decade

Occurs in association with celiacdisease

Responds to gluten-free diet

HISTOLOGY:

Microabscesses at tips ofdermal papillae

Subepidermal blister

Immunofluorescence:

Granular deposits of IgA attips of dermal papillae

-END-

Kobe =5 champ rings

Lebron= 0, zero, none, waley

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2011-07-PATHO-Skin Oncology