ETAS_05 dermatopath

Dermatopathology 153

5 DermatopathologyChristine J. Ko, MD

C o n t e n t s5.1 Normal Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

5.2 Stains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

5.3 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . 157

5.4 Acantholytic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . 158

5.5 Adnexal/Epithelial Neoplasms . . . . . . . . . . . . . . . . . .160

5.6 Alopecias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168

5.7 Bullous Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168

5.8 Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169

5.9 Deposition Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

5.10 Drug Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

5.11 Fat Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

5.12 Fibrous/Fibrohistiocytic Disorders. . . . . . . . . . . . . . 175

5.13 Genodermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

5.14 Granulomatous Disorders. . . . . . . . . . . . . . . . . . . . . . .180

5.15 Histiocytoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181

5.16 Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182

5.17 Inflammatory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186

5.18 Lymphomas and Markers . . . . . . . . . . . . . . . . . . . . . . . 192

5.19 Melanocytic Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

5.20 Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198

5.21 Neural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199

5.22 Pagetoid Spread . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .201

5.23 Palisading Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . 202

5.24 Vascular. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203

5.25 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206

5.26 Clues for Board Purposes. . . . . . . . . . . . . . . . . . . . . . .210

5.27 “Bodies” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212

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5.1 NORMAL SKINApocrine Glands

• Decapitationsecretion• Foundinaxillae,anogenital,externalearcanal(ceruminous),eyelid(Moll’s),breast(mammary)

• Apocrineglandshaveaninnerlayerofsecretorycellsthatvaryinheightanddemonstrate“snouts”ofapocrinesecretionwithalayerofmyoepithelialcellssurroundingtheglands

• Stainwithgrosscysticdiseasefluidprotein15(GCDFP-15)• AlsostainwithkeratinAE1(stainsducts),CAM5.2,EMA

Eccrine Glands• Merocrinesecretion• Eccrineglandsarecomposedofonedistinctlayerofcellswith2populations,clearcellsanddarkercells;myoepithelialcellssurroundglands,butareoftendifficulttoappreciate

• StainwithS100,CEA,CAM5.2

Sebaceous Glands• Holocrinesecretion

• MeibomianandWolf(oneyelid),Fordyce(onvermilion,oral/mucosae),Tyson(onpenis),Montgomery(onnipple)

Hair Follicle• Infundibulum=portionaboveinsertionofsebaceousduct;identicaltonormalepidermisinkeratinizationpattern;desmoglein-3positiveinbasallayer

• Isthmus=portionbetweeninsertionsofsebaceousductandarrectorpili;trichilemmalkeratinization;desmoglein-3positiveinalllayers

• Lowerportion=fromarrectortothebaseoffollicle• Innerrootsheathnotpresentatisthmus• Epidermisandinfundibulumundergoeskeratinizationwithkeratohyalinegranules(basophilic);outerrootsheathundergotrichilemmalkeratinization(withoutforminggranules)intheisthmus;lowerpartofthefollicle’sinnerrootsheathundergoeskeratinizationwithtrichohyalinegranules(eosinophilic);hairkeratinizeswithoutforminggranulesandformshardkeratin

• Trichilemmalcarcinomastainswithkeratin17andc-erb-b2• Proliferatingtrichilemmalcyststainswithcytokeratin7

Nail Bed• Expresseskeratin6,16,17

uTIPa�Seenectopicallyinnevus

sebaceus(aniceclue)

uTIPa Present all over the body

except on vermilion of lips, glans, labia minora, nail beds, inner prepuce

uTIPaLayersofthelowerportion(from

outertoinner):fibrousrootsheath,glassy/vitreouslayer,outerrootsheath,innerrootsheath(Henle,Huxley,cuticleofinnerrootsheath),haircuticle,haircortex,hairmedulla;desmoglein-1positiveininnerrootsheathandinnermostpartofouterrootsheath

uTIPaInpachyonychiacongenitatypeI

(Jadassohn-Lewandowsky),keratins6aand16aremutated

aInpachyonychiacongenitatypeII(Jackson-Lawler),keratins6band17aremutated,andpatientshavemultiplesteatocysts

156 2011/2012DermatologyIn-ReviewlCommittedtoYourFuture

5.2 STAINSBodian

• Nervefibersblack

Feulgen• DNAmagenta

Fontana Masson• Melanin

Foote’s or Snook’s • Reticulinfibersblack

Giemsa• Mastcellgranulespurple(itistheheparininthemastcellsthatisstaining)• Leishmania

Leder• Mastcellgranulesred

Masson Trichrome• Collagenblue/green,muscle/nerve/keratinred

Methyl-green Pyronin• RNApink,DNAgreen

Perls (PrussianBlue)• Iron/hemosiderinbrightblue

PTAH (PhosphotungsticAcidHematoxylin)• Stainsfibrin

For Amyloid• Congored(stainsred,greenbirefringenceonpolarization)• Crystalviolet(morespecific;stainspurple)• ThioflavinT(fluorescesgreen-blue)• AcidorceinGiemsa(stainsskyblue)

For Bacteria• McCallum-Goodpasture• Brown-Brenn• Brown-Hopps• Ziehl-NeelsenandFite-Faracoforacid-fastbacteria

For Calcium• VonKossa(blue-black)• Alizarinred(red)• Pentahydroxyflavanol(fluoresces)• Aldehydefuchsin(brown)

uTIPa Stains the inclusions in

infantile digital fibromatosis


For Elastic Tissue• VerhoeffvonGieson(blue-black)• Gomori’saldehyde-fuchsin(purple)• Orcein-Giemsa(black)

For Fat (NeedFresh/FrozenTissue)• Scarletred• OilredO• Sudanblack(alsostainslipofuscin)• Osmiumtetroxide(differentiatesanimalfatfrommineraloil)

For Fungi• PAS• GMS(Gomorimethenaminesilver)

For Mucin/Mucopolysaccharides (MPS)• AlcianBlue2.5(blue)-acidMPS• AlcianBlue0.5(blue)-sulfatedMPS• Colloidaliron(blue)-acidMPS• Mucicarmine(pink)• Toluidineblue(blue)-acidMPS

For Mycobacteria• Ziehl-Neelsen• Fite-Faraco

For Nerve Fibers• Bodian(nervefibersblack)• PGP9.5• Neurofilament

For Ochronosis• Cresylvioletormethylenebluestainsthepigmentblack

For Spirochetes• SilverstainslikeWarthinStarryorDieterleorSteiner

5.3 IMMUNOHISTOCHEMISTRY

Table5-1.CommonlyUsedImmunohistochemicalStains

Antigen Major Targets

Cytokeratin(AE1/AE3,34BE12,MNF116,5/6,etc.)

NORMAL:EpidermisandadnexalepitheliumUSEFULFOR:Squamouscellcarcinoma

S-100protein NORMAL:Melanocytes,Langerhanscells,eccrineglands,chondrocytes,adiposetissue,nervesUSEFULFOR:Melanoma,adnexaltumors,neuraltumors

HMB-45 NORMAL:MelanocytesUSEFULFOR:Somemelanomas,nevi


Antigen Major Targets

MelanA/MART-1 NORMAL:MelanocytesUSEFULFOR:Melanoma,somenevi

Mel-5 NORMAL:MelanocytesUSEFULFOR:Somemelanomas/nevi,vitiligo

Vimentin NORMAL:TissuewithmesenchymalderivationUSEFULFOR:Atypicalfibroxanthoma,sarcomas,melanomas,somesquamouscellcarcinomas

Desmin NORMAL:Smooth/skeletalmuscleUSEFULFOR:Muscletumors

Smoothmuscleactin(SMA) NORMAL:Smoothmuscle,myofibroblasticcellsUSEFULFOR:Smoothmuscletumors,someatypicalfibroxanthomas

Carcinoembryonicantigen(CEA)

NORMAL:Eccrine/apocrineglandsUSEFULFOR:Adnexaltumors,Paget’sdiseaseofthebreast,extramammaryPaget’s

Epithelialmembraneantigen(EMA)

NORMAL:Sebaceous,eccrine,apocrineglandsUSEFULFOR:Sebaceoustumors,squamouscellcarcinoma,epithelioidsarcoma,systemic(nodal)anaplasticlargecelllymphoma

Neuron-specificenolase(NSE)

NORMAL:Non-specificneuroendocrinemarkerUSEFULFOR:Merkelcellcarcinoma

Chromogranin NORMAL:NeuroendocrinecellsUSEFULFOR:Merkelcellcarcinoma

Synaptophysin NORMAL:NeuroendocrinecellsUSEFULFOR:Merkelcellcarcinoma

Cytokeratin20 NORMAL:NeuroendocrinecellsUSEFULFOR:Merkelcellcarcinoma,trichoepithelioma

FactorVIII-relatedAntigen NORMAL:Endothelialcells,platelets,megakaryocytesUSEFULFOR:Vasculartumors

CD31 NORMAL:Endothelialcells,stemcellsUSEFULFOR:Dermatofibrosarcomaprotuberans,vasculartumors

FactorXIIIa NORMAL:DermaldendrocytesUSEFULFOR:Dermatofibroma

Cytokeratin5/6P63

NORMAL:EpithelialcellsP63USEFULFOR:Primarycutaneousadnexaltumors;negativeinmetastaticadenocarcinomas

TTF-1 NORMAL:ThyroidtissueUSEFULFOR:Lungcarcinoma;negativeinMerkelcellcarcinoma

5.4 ACANTHOLYTIC DISORDERS Darier’s Disease (KeratosisFollicularis)

• Columnofparakeratosisaboveafocusofacantholyticdyskeratosis(corpsrondsandgrains)

Table5-1.CommonlyUsedImmunohistochemicalStains(cont)

uTIPa�Autosomal dominant, ATP2A2 gene that encodes the

sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA)


Grover’s Disease• OftensmallerfocithanthoseinDarier’s,withoutthecolumnofparakeratosis

Hailey-Hailey• “Full-thicknessacantholysis,”theso-calleddilapidatedbrickwall,althoughsometimestheupperlayersoftheepidermisarenotacantholytic

Paraneoplastic Pemphigus• Clinicalpresentationiswithintractableoralulcers/erosions,conjunctivitis,target-likelesions(EM-like)

• Suprabasilaracantholysis(likePV)andEM-likechanges(necrotickeratinocytesandvacuolarchangeofthebasallayer)

Pemphigus Foliaceus (PF)• Intraepidermalacantholyticblister,throughthesubcorneal/granularlayer,granularcellsoftenappearmoreprominent

• Differentialincludesbullousimpetigo,subcornealpustulardermatosis,pemphiguserythematosus

• CluestoPFratherthanbullousimpetigoare“cling-ons,”whichareacantholyticcellsthatarestillattachedtothestratumcorneumontheroofoftheblister,andlessneutrophilsintheblistercavity

• Intercellularantibodiesagainstdesmoglein1, 160kDa

Pemphigus Vegetans• Variantofpemphigusvulgaris

• Markedhyperplasiaoftheepidermis withcharacteristiceosinophilicabscesses, acantholysismaybeminimal

uTIPa Oftenthereareseveralfociofacantholyticdyskeratosis,

sometimeswithdifferentpatternsindifferentfoci,forexample,onefocusthatappearsmorespongioticwithanotherthatlookslikePVandanotherthatlookslikeDarier'sorHailey-Haileyorsuperficialpemphigus

uTIPaAutosomal dominant, ATP2C1 gene

uTIPa Intercellular and linear DEJ antibodies against desmoplakins

(250 kDa, 230 kDa bullous pemphigoid antigen 1), envoplakin (210 kDa), periplakin (190 kDa), 170 kDa antigen, PV Ag (130 kDa)

Figure 5-1. Darier’s Disease

Figure 5-2. Hailey-Hailey

Figure 5-3. Pemphigus Foliaceus


Pemphigus Vulgaris (PV)• Intraepidermalacantholyticsuprabasalblister,non-dyskeratotic,withtombstoningofthebasallayer

• Acantholysisextendsdownadnexae,unlike inHaileyHailey

• Intercellularantibodiesagainstdesmoglein 3,130kDa

Squamous Cell Carcinoma, Adenoid Type• AlsocalledacantholyticSCC• Becauseofdyskeratosisandsubsequentacantholysis,SCC’smayshowtubularandalveolarformationsonhistology;often,anAKoftheacantholytictypeisseenoverlyingthelesion

Warty Dyskeratoma• CanlookexactlylikeDarier’s,butideallyitisalargerlesion(solitaryclinically)thatsometimeshasacyst-likearchitecture

5.5 ADNEXAL/EPITHELIAL NEOPLASMSAcrospiroma

• Includeshidroacanthomasimplex(locatedintraepidermally)(seeFigureunderHidroacanthomaSimplex),poroma,dermalducttumor,hidradenoma(deeperdermis)

• Poroma:Uniformbluecellscomingoffinaplate-likefashionoffoftheepidermis,ductalareaswithin

• Hidradenoma:Clearcellsandmorebasaloid/cuboidalcellsperipherally,ductalareas

Adenoid Cystic Carcinoma• Alsofairlycharacteristicpattern• Cribiformpatternofepitheliumandductalareas

Clear Cell Hidradenoma (EccrineHidradenoma,EccrineAcrospiroma,NodularHidradenoma,Solid-cysticHidradenomia)

• Large,circumscribed,butnotencapsulated• Occasionallyconnectstooverlyingepidermisorextendsintosubcutis

• Biphasiccellularpopulation:roundcellswitheosinophiliccytoplasmandovalvesicularnucleusorcellswithclearcytoplasmwithsmalldarkeccentricallylocatednucleus

Figure 5-4. Pemphigus Vegetans

Figure 5-5. Warty Dyskeratoma

Figure 5-6. Adenoid Cystic Carcinoma


• Maycontainsomeducts;veryfewdistinguishingfeaturesandmaybeadiagnosisofexclusion;distinguishfrommetastaticrenalcellcarcinoma

Cylindroma• Thoughttobeapocrineinorigin• Upperdermiswithoutconnectionto overlyingepidermis• Multiple,puzzle-likelobulesinjigsawormosaicpattern,eachlobulehasbasementmembrane(PASpositive,densepinkstroma)aroundit

• CYLDgene • Brooke-Spieglersyndrome:multiple trichoepitheliomas,cylindromas, spiradenomas

Desmoplastic Trichoepithelioma• Quitedifferentfromconventionaltrichoepithelioma

• Slightindentationoftheepidermis;smallareaslooklikesyringomas

• Narrowepithelialstrandsembeddedindensecollagenousstroma,horncysts,calcificationfrequentlyseen,symmetric;roundedbase

• Doesn’tpenetratelikemorpheaformBCC;lotsofhorncystsandcalciumdeposits;noretractionartefact

Dilated Pore of Winer• Keratin-plugged,cysticallydilatedhairfollicle,usuallysuperficial,butcanextendintosubcutaneousfat

• Linedbyacanthoticepithelium,withbudsofproliferationextendingawayasirregularstrands

Fibroepithelioma of Pinkus• Polypoidshape;basaloidepithelialstrands,2-3cellsthick,arisingfrommanyfocialongtheepidermisandanastomosingtocompartmentalizethefibrousstroma

Figure 5-7. Clear Cell Hidradenoma

Figure 5-8. Desmoplastic Trichoepithelioma

Figure 5-9. Fibroepithelioma of Pinkus


Hidradenoma Papilliferum• Vulvararea• Well-demarcatednoduleindermisandmaybecontinuouswithoverlyingepithelium

• Papillatedprojectionsintocysticspaces,decapitationsecretion

Hidroacanthoma Simplex (IntraepidermalPoroma)

• Hyperkeratosiswithacanthosis• Epidermisshowsdiscretecollectionsofregulartumorcellsthatresemblethoseofaneccrineporoma

• Tumorcellscanbespindleshapedalso;thedermisisunaffected

Inverted Follicular Keratosis• Endophyticwithwhorlsofmaturingsquamousepithelium(squamouseddies)nearhairfollicleostium;somelesionscontainhorncysts;nokoilocytes

Irritated Seborrheic Keratosis• Characteristicsquamouseddiesofeosinophilicsquamouscellsinadownwardproliferation(endophytic)withminimaltomildinflammationatthebase

• Somesaythatthisisthesameasaninvertedfollicularkeratosis

Keratoacanthoma• Crateriformarchitecture,symmetric,largecentralkeratinplug,well-formedflankingcollarette

• Well-differentiated,oftenpale-staining,eosinophilic,glassycytoplasmwithtendencytowardkeratinization,noabnormalmitoticfigures

Microcystic Adnexal Carcinoma• “Syringomagonemad”;growsdeepwithoutmetastasizing

• Roundballs(syringoma-like)uphigh,andmorelinearandcord-likedownlow

Figure 5-10. Hidradenoma Papilliferum

Figure 5-11. Hidroacanthoma Simplex

Figure 5-12. Inverted Follicular Keratosis


• Numeroussmalltomedium-sizedsquamousmicrocysts,superficiallylocated,andsolidstrandsofcells,manywithductularlumina,densefibrousstromasurroundsallcomponentsandismorescleroticininfiltrativeareas

• Perineuralinvasionfrequentlyobserved

Mixed Tumor of the Skin (ChondroidSyringoma)

• Areasthatlooklikecartilagewithductal/adnexalstructure-likecords/strandsofcells

• Multilobulatedwithindeepdermisand/orsubcutaneousfat

• Abundantstromawithbasophilicpseudocartilaginousappearance

• Lobulesseparatedbyfibroussepta• Nestsandcordsofcuboidalcellswithcopiouseosinophiliccytoplasmandbasophilicnuclei,tubuloalveolarstructureslinedbytwoormorerowsofepithelialcells

Morpheaform Basal Cell Carcinoma (BCC)• Thincordsofbasaloidcells,gettingthinnerasthecordsgodeeper;someretractionartefactmaybepresent

• Haphazarddownwardgrowththatinfiltrates

• Canresembledesmoplastictrichoepithelioma,butofteninfiltratesdeeperintothedermis

• Bcl-2stainsBCCsdiffusely

Mucinous Carcinoma• Dermaltumorthatmayextendintosubcutaneousfat,withverycharacteristic,“floating”compartmentalizedislandsoftumorcellssuspendedinalakeofmucin

• Tumorcellsaresometimesvacuolatedwitheosinophiliccytoplasmandsmallhyperchromaticnuclei

•MUSTruleoutmetastaticcancer

Nevus Sebaceus of Jadassohn• Epidermalacanthosisandpapillomatosis• Fociofabortivehairpapillae• Sebaceousglandslocatedabnormallyhighindermis,openingdirectlyontosurface,andcanappearunrelatedtohairfollicle

Figure 5-13. Mixed Tumor of the Skin

Figure 5-14. Nevus Sebaceus of Jadassohn


• Hasadifferentlookpre-pubertal(smallersebaceousglands)andpost-pubertal(largersebaceousglands)

• Aclueisapocrineglandsinthereticulardermis

• Tumorscanarisewithinnevussebaceus,withtrichoblastomathoughttobethemostcommon,followedbysyringocystadenomapapilliferum,BCC

Pilomatricoma (CalcifyingEpitheliomaofMalherbe)

• Basaloidbluecells(matricalcells)andpalepinkamorphousareasthatonhigherpowerhave“shadows”ofnuclei(shadowcells),areasofcalcificationorsometimesossification

• Mutationsfoundinbeta-catenin

Proliferating Trichilemmal Tumor• Lookslikeapilarcystgonewild• Lobulatedintradermalmassofsquamousepithelium

• Individuallobuleswithsharplydefinedandnon-infiltratingborder

• Maybesurroundedbyathickenedbasementmembrane

• Strikingperipheralpalisadingoflobuleedges

• Tricholemmalkeratinizationwithabsentgranularlayer

Sebaceous Adenoma• Lobulesofsebocyteswithrimsofbasalcells

• Mayreplacesurfaceepithelium• Individuallobulesmirrorstructureofnormalsebaceousgland,peripheryoflobuleshowssmallgerminativecellswithscantycytoplasm

PEARLw Multiplepilomatricomasseenin

Rubinstein-Taybi,Gardner’s(cyst-likepilomatricomas),Turner’s,

sarcoidosis,sternalcleftandcoagulation defects,myotonicdystrophy(Steinert’s)

Figure 5-15. Pilomatricoma

Figure 5-16. Proliferating Trichilemmal Tumor

Figure 5-17. Sebaceous Adenoma


• >50%lobulecontainsmaturesebaceouscells

• Sebaceousepitheliomasaremoreasymmetricanddisorganizedwith>50%ofcellsbeingbasaloidgerminativecells

• Iftherearemitoses,aninfiltrativegrowthpattern,andatypicalcells,thinkofsebaceouscarcinoma

• AssociatedwithMuir-Torresyndrome

Spiradenoma• “Blueballsinthedermis”(noepidermalconnection)→tumorlobulesindermisandoccasionallyintosubcutaneousfat

• Lobulesareintenselybasophilicwithcellsarrangedinintertwiningcords,darkandlightcells

•Aclueisfocalpocketsofhyalinematerial withinthecellularareasandlymphocytes pepperingtheislands

• Nowthoughttobeapocrine

Syringocystadenoma Papilliferum• Papillatedtumorwithabundantplasmacellsinthestroma

• Invaginationfromoverlyingepidermis• Double-layeredepitheliumwithouterzoneofsmallcellsandinnerzoneoftallcolumnarcells

• Mayshowdecapitationsecretion

Syringoma• Duct-like“tadpoles”andcordsofperipheralbluecellsaroundcentralclearcellsinafibrousstroma

• Increasedincidenceinpatientswith Down’s

• Clear-cellvariantisassociatedwithdiabetes

Figure 5-18. Spiradenoma

Figure 5-19. Syringocystadenoma Papilliferum

Figure 5-20. Syringoma


Trichilemmoma• Proliferationofouterrootsheath• Smallsolitarylobuleorgroupoflobulesconnectedtoepidermiswithverticalgrowth

• Peripheralpalisadingoflobules• Manyofthetumorcellscontainglycogenandhaveaclearcellappearance(PAS-positive)

• Atthebaseofeachlesionisathinredlinemimickingthevitreoussheathofhair

• MultipleonesseeninCowden’s

Trichoadenoma• Indermis,numeroushorncystssurroundedbyeosinophilicepithelium

• Well-definedfibroepithelialtumorcomposedofhorncystsandconspicuousfibrovascularstroma

• Scatteredislandsoftumorcells• Midwaybetweenatrichoepitheliomaandatrichofolliculomaintermsofdifferentiation

Trichoblastoma• Moreprimitivethantrichoepithelioma;usuallylackshorncysts

• Featuressimilartotrichoepithelioma,butcenteredinmiddermisandcaninvolvesubcutaneousfat

• Lobulesofbasaloidcellsintimatelyassociatedwithconspicuousfibromyxoidstroma

• Clueisthepapillarymesenchymalbody,whichresemblesaveryearlyhairbulb(folliculargerm)surroundedbyloosespindlecells,althoughthiscanbeseenintrichoepitheliomas

Trichodiscoma• Flattenedepidermis,withlateralcollarette• Unencapsulated,elliptical,looselywovenadmixtureofcollagen,reticulin,andthinelasticfibers

• Alwaystopographicallyrelatedtohairfollicle

• SeeninBirt-Hogg-Dube

Figure 5-21. Trichilemmoma

Figure 5-22. Trichoadenoma


Trichoepithelioma•Numeroushorncystsbothindermisandwithinlobulesofbasaloidcells,completekeratinization,tumorcellsindistinguishablefromthoseofBCC,showingperipheralpalisading,perilobularconnectivetissuesheathmoreconspicuous(morefibrotic)andassociatedwithformationofpapillarymesenchymalbodies(primitivehairbulbs),foreignbodygiantcellreactiontofreekeratin,cleftsbetweenstromaandstroma,andnocleftsbetweencellsandstroma;horncystsoccur

Trichofolliculoma• Dilatedhairfollicle(cysticcavity)withgranularlayerandcontainingkeratinousdebrisandhairshaftfragments

• Arisesfromsurfaceepithelium• Numeroushairfolliclesarisefromitswall,eachsurroundedbyaclearlydefinedperifollicularsheath

• Clinicallyhasoneormoresilkywhitehairsextendingoutfromlesion

Verrucous Carcinoma• “Condylomagonewild”;takesupone-halfthesizeoftheslide• Acanthoticpapillaryprocesseswithmassivehyperkeratosisandoftenparakeratosis• Endophyticcomponenthaswell-differentiatedsquamousepitheliumgrowingdownintotheunderlyingtissuesasdeeplypenetrating,bulbousprocessesshowingacharacteristic“pushing”margin(incontrasttotheinfiltrativeborderofanordinarySCC)

• Keratinizationismassive,withaccompanyingsinuses;nocytologicatypia

Figure 5-23. Trichoepithelioma

Figure 5-24. Trichofolliculoma

PEARL

wRasmussen'ssyndrome:multipletrichoepitheliomas,cylindromas,andmilia

wRombosyndrome:multipletrichoepitheliomas,milia,vermiculateatrophy,BCC,peripheralvasodilationandcyanosis


5.6 ALOPECIASAlopecia Areata

• Peribulbarlymphohistiocyticinfiltratearoundanagenfolliclesneardermal/subcutaneousjunction(“swarmofbees”)

• Theremaybeincreasedcatagenhairsandminiaturizedhairs

Androgenetic Alopecia• Scalpskin• Manyfolliclesshowdiminishedsize(miniaturization)

• Lackofinflammation

Discoid Lupus Erythematosus• Scalpskinoften• Epidermalatrophy,follicularplugging,denselymphohistiocyticperiadnexalinfiltrate,areaofscarring

• VacuolarchangeatDEjunction• Basementmembranethickening• Mucinincollagenbundles• Pigmentaryincontinence

Lichen Planopilaris• Focallydenseperivascularandperiadnexallymphohistiocyticinfiltrate• Focalareasofhypergranulosis,keratinplugging,vacuolarchangesofbasallayerofthefollicularepithelium

• Advanceddiseaseshowsfibrousscarsverticallyoriented• Adjacentinterfollicularepitheliummayshowtypicallichenoidinfiltrate• Basalcellhydropicdegenerationmayormaynotbepresent• DifferentialdiagnosisisLE,whichwouldnotshownormalepidermisbetweenthefollicles

Pseudopelade of Brocq• Presenceofnormalepidermisandreducednumbersorabsenceofsebaceousglands• Noevidenceofinflammatoryfolliculitis• Vertically-orientedfibrousscarringreplaceshairfollicles,witharrectorpilistillattached

Trichotillomania• Trichomalacia→hairshaftsfragmented,bent,anddistorted• Pigmentedcasts

5.7 BULLOUS DISORDERSBullous Pemphigoid (BP)

• Subepidermalseparationwitheosinophils(butsometimesthereisre-epithelializationatthebase,sotheblistercanlookintraepidermal)

• AcluetoearlyBPiseosinophilicspongiosisandeosinophilslinedupalongtheDEJ• RarelyBPcanbeneutrophilicor“cell-poor”(non-inflammatory)

Figure 5-25. Discoid Lupus Erythematosus

uTIPaA clue to early BP is eosinophilic spongiosis and eosinophils lined up along the DEJ


• LinearIgGandC3attheDEJondirectimmunofluorescence(DIF)• Twoantigens:Bullouspemphigoidantigen-1(BPAg-1)(230kDa)andBullouspemphigoidantigen-2(BPAg-2)(180kDa);theBPAg-2isthoughttobethepathogenicantigen

• HerpesgestationiscanbeindistinguishablefromBPonbiopsybutonDIFhaslinearC3andlesscommonlyIgG

Cicatricial Pemphigoid (CP)• Sparseinflammation,subepidermalseparation,scarringofpapillarydermis• Lookforplasmacellstoindicateamucosalsurface• Anti-epiligrinCPisassociatedwithmalignancy,especiallyadenocarcinomas(epiligrinisanothernameforlaminin5)

Dermatitis Herpetiformis• DIFshowsgranularIgAindermalpapillae• LinearIgAdisease(orchronicbullousdiseaseofchildhood)canlookhistologicallythesame,butDIFshowslinearIgAattheDEJ

• DifferentialdiagnosisincludesbullousSLE,EBA,neutrophil-richBP,cicatricialpemphigoid

Epidermolysis Bullosa Acquisita (EBA)• Subepidermalseparation• CanlookhistologicallylikeBPorlikeDH(withneutrophils)ornon-inflammatory• Salt-splitskindifferentiatesEBAfromBP• AntibodiestotypeVIIcollagen(290kDa)

Porphyria Cutanea Tarda (PCT)• Subepidermalblisterwithcleanbreak• Minimallymphocyticinfiltrate,prominentsolarelastosis,slightlyeosinophilicnecrotickeratinocytes,erythrocyteswithinblister

• Festooningofdermalpapillae• “Caterpillarbodies”→eosinophilicelongated,wavystructuresinlowerandmidepidermislyingparalleltoBMzone

• DIFwithIgG,IgM,IgA,C3atDEJandaroundvessels

• PseudoporphyriacanlookhistologicallyexactlylikePCT

5.8 CYSTS

Apocrine Hidrocystoma• Thecystliningshowsapocrine-typedecapitationsecretion

• Fibrouspseudocapsule• Linedbyadoublelayerofepithelialcells:outerflattenedvacuolatedmyoepithelialcells,andinnertallcolumnarcells

• Unilocularormultilocular

Figure 5-26. Apocrine Hidrocystoma

uTIPaClue is neutrophils clustered in dermal papillae adjacent to a subepidermal split


Branchial Cyst• Mostcommonsiteisalongthesideoftheneck• Thecystliningisstratifiedsquamousorpseudo-stratifiedcolumnarwithcilia• Prominentlymphoidfolliclesdeeptothewall

Bronchogenic Cyst• Majoritypresentonprecordiumorsuprasternal• Indermisorsubcutis,epithelialliningthrownintofolds→pseudostratifiedcuboidalorcolumnarandciliatedwithmucussecretinggobletcells,whichdistinguishthiscystfromothers

Cutaneous Ciliated Cyst• Majoritypresentonthethighsofwomen• Epithelialliningiscuboidalorcolumnarwithciliaonthesurfaceandcollagen/vesselsdeeptothewall

Dermoid Cyst• Mostcommonsiteisthelateraleyebrowarea• Theepithelialliningisstratifiedsquamouswithadnexalstructures(hairfollicles,sebaceousglands,eccrine/apocrineglands)

Epidermoid Cyst (InfundibularCyst)• Punctumusuallypresent,unilocularandspherical,linedbyepidermis-likeepitheliumwithagranularlayer

• Ruptureassociatedwithaforeignbodygranulomatousreaction

Median Raphe Cyst• Majoritypresentontheventralpenis;sometimesventralscrotumorperineum• Epithelialliningpseudostratifiedcolumnar+/-mucinouscells

Pilar (Trichilemmal)Cyst• Fibrouscapsulesurroundinglayerofdark-stainingbasalcells• Keratinizationwithoutgranularlayer,mostsuperficialcystcellsarelargerwithmoreabundantcytoplasm

• Cholesterolcleftsseeninmostlesions,andsomeshowcalcification

Steatocystoma• Thekeratininsidethecystcanresemblethekeratinofanepidermalinclusioncyst,buttheliningofthecystismorecorrugatedwithabrightpinkribbon-likesurface;sebaceousglandsareseenconnectingtooradjacenttothewall

• Multiplesteatocystsassociatedwith pachyonychiacongenitatypeII(Jackson- Lawler) Figure 5-27. Steatocystoma


Thyroglossal Duct Cyst• Cystliningisstratifiedsquamousorpseudostratifiedcuboidal/columnar+/-cilia

• Deeptothewallaremucousglands,thyroidfollicles,lymphocyticinfiltrate

Vellus Hair Cysts• Mid-dermalcystwithfollicularlining,containinglaminatedkeratinandmanyvellushairs

• Occasionallyincontinuitywithepidermis,telogenfollicle,orapilomotormuscle

5.9 DEPOSITION DISORDERSCalcinosis Cutis

• Chunkydarkbluematerialinthedermis• Maybeidiopathic,dystrophic,ormetastatic

Colloid Milium• Depositsgenerallylarger(canextendfromthepapillarydermisintothereticular)thaninmacularorlichenamyloidosus,withacracked/cleftedappearance

• Theremaybesolarelastosis• Juvenilecolloidmiliumishistochemicallyindistinguishablefromamyloidderivedfromkeratin

Focal Cutaneous Mucinosis• Papuleorpolypoid(unlikepretibialmyxedema)

• Locationshowsnothickenedstratumcorneum• Lesionlocatedinmidandupperdermis

Follicular Mucinosis (AlopeciaMucinosis)• Mucinousdegenerationoftheexternalrootsheathandsebaceousglands,accompaniedbyvariableinflammatoryinfiltrate

• Mucininthefollicle• Follicularinfundibulumshowsvacuolaralteration• Ifassociatedwithmycosisfungoides,mayshowatypicallymphocytesandPautriermicroabscesses

• Mucinstainspositivewithalcianblue;perifollicularscarringcanbeafeature

Figure 5-29. Calcinosis Cutis

Figure 5-28. Vellus Hair Cysts


Macular and Lichen Amyloidosus• Lichenamyloidosushasahyperplasticepidermiscomparedtothemacularform

• Bothconditionshavepinkglobsofmaterialwithinthepapillarydermishighupagainsttherete

• AssociatedwithMENIIa

Mucocele• Onmucousmembranes• Ifintactitcanlooklikeasubepidermalvesicle

• Oftenruptured,sothereislightbluematerialwithnumerousinflammatorycellsandmuciphagesandgranulationtissue

• Clueisthepresenceofsalivaryglands

Myxoid Cyst• Notatruecyst;devoidoflining• Consistsoflargepoolofmucincontainingspindle/stellatefibroblasts• Compressedcollagenattheperiphery• Overlyingepitheliumisatrophicandhyperkeratotic

•Lookforacrallocation• Poolofmucinwithspindlecells,oftenwithanepidermalcollarette

Nodular Amyloid• Depositsofamyloidinpapillaryandreticulardermisandmayinvolvesubcutaneousfat• Plasmacellsaroundbloodvesselsatmarginofamyloiddeposits• Amyloiddepositsmaythickenbloodvesselwalls• Colloidmiliumismorefocalandinvolvesonlytheupperdermis

Osteoma Cutis• Withinthedermis,well-circumscribednoduleofmaturelamellarbone,oftencontainingnarrowspaces

• Noghostcellsseen,sodon’tconfusewithossifiedpilomatricoma

Papular Mucinosis (lichenmyxedematosus)• Collagenfiberswidelyseparatedbymucindeposits,increasednumbersoffibroblasts• Epidermismaybenormal,acanthotic,oratrophic• Inscleromyxedemavariant,fibroblastsarenumerous(increasedinnumber)withconsequentfibrosis(increasedcollagen)andthickeningofdermiswithmucin

• Morecellularthanpretibialmyxedema

Pretibial Myxedema• Epidermisoftenhyperkeratoticwithfollicularplugging• Dermisshowsseparationofcollagenbundlesbylargequantitiesofmucin

Figure 5-30. Macular and Lichen Amyloidosus


• Stellatefibroblastsareevident;relativelyacellularandnon-inflammatory• Noincreaseinfibroblasts• Squarebiopsy• AssociatedwithGrave’sdiseaseandthyroidacropachy

Scleredema• Reticulardermisgreatlythickened,oftenwithlossofsubcutaneousfat• Eccrinetrapping,broadenedcollagenfibers• MucindemonstratedbyAlcianblueorcolloidalironstain

•Associatedwithdiabetes,streptococcalinfection,paraproteinemia

Scleromyxedema• Fibroblastsaregreatlyincreasedwithconsequentfibrosis(increasedcollagen)andthickeningofdermis

• Mucinisincreased• Morecellularthanpretibialmyxedema

•Associatedwithparaproteinemia,generallyIgGlambda• Squarebiopsy

5.10 DRUG REACTIONSFixed Drug Eruption

• Basketweavestratumcorneum• Interfacedermatitis• Necroticepidermiswithpossiblesubepidermalblister

• Civattebodies• Superficialanddeeplymphohistiocyticinfiltratewithscatteredeosinophilsandneutrophils(beforeyouchooseEM,checkforeos)

• Pigmentincontinencewithmelanophages

Lichenoid Drug• Band-likelichenoidinfiltrateattheDEjunction• Basalcellhydropicdegenerationatthebasallayeroftheepidermis

• Presenceofeosinophilsandparakeratosis

Minocycline-induced Pigmentation• Theblue-blackcolorinscarsonthefacestainslikehemosiderin(Perls-positive)• Blue-grayonlegsstainslikeironandmelanin(stainswithPerlsandFontanaMasson)• Muddy-browncoloronsun-exposedareasshowsincreasedbasalmelanizationandmelanophages(probablysecondarytophototoxicity)

uTIPa Remember: PLEVA has parakeratosis and lacks

the eosinophils

Figure 5-31. Fixed Drug Eruption

uTIPa 3 types: blue-black in scars on the

face, blue-gray on legs, muddy-brown on sun-exposed areas; first 2 may be secondary to a drug metabolite-protein complex


Neutrophilic Eccrine Hidradenitis

• Mostcommonlysecondarytochemotherapy,especiallycytarabine• Onbiopsythereisadenseneutrophilicinfiltratearoundtheeccrineglands

5.11 FAT DISORDERSAlpha-1-Antitrypsin Deficiency Panniculitis

• Lobularpanniculitis• Focalinflammationwithlargenumbersofneutrophilsthatpourintothedermis• Fatnecrosisiscommon• Lossofelastictissueonspecialstaining,novasculitis• Lipid-ladenfoamymacrophagessometimesevident

Angiolipoma• Alipomawithbloodvessels• Usuallyencapsulated,matureadipocytesadmixedwithanastomosingsmallbloodvessels• Luminalmicrothrombialwayspresent

Erythema Induratum (NodularVasculitis)• “Messy-looking,”diffuseprocess• Nodulargranulomatouspanniculitis,predominantlylobularwithspilloverintothefibroussepta

• Fatnecrosis,withdenseneutrophilicinfiltrate• Infiltrateconsistsofneutrophils,lymphocytes,histiocytes,epithelioidcellsandgiantcells,lipid-ladenfoamyhistiocytes

• Vasculitis(oftenatdermal/SCjunction)withendothelialswelling

Erythema Nodosum• Septalpanniculitis,withwidenedfibroussepta

• Lymphohistiocyticinfiltratewithmultinucleatedgiantcells(Toutongiantcells),scatteredeosinophils

• Noevidenceofeithervasculitisornecrosis

• Sparselymphohistiocyticinfiltratealsoaroundbloodvesselsindermis

Hibernoma• Deepbenigntumor,resemblesnormalbrownfat

• “Pingpongballs”stuffedintocells→admixtureofmatureunivacuolatedadipocytesandmultivacuolatedlargeadipocyteswithcentralnucleiandgranulareosinophiliccytoplasm

• Highlyvascularizedsepta;don’tmistakeforagranularcelltumor• “Mulberrycells”withscallopednucleisecondarytovacuoles(cellshaveincreasedmitochondria)

Figure 5-32. Erythema Nodosum


Lipodermatosclerosis (LipomembranousPanniculitis)

• Lobularpanniculitis• Fattycystslinedbyeosinophilichyalinemembranesthatpresenta“raggedborder”→lipomembranouschange

• Superimposedvenousstasischangesinthedermis

Lupus Profundus• OverlyingepitheliumandsuperficialdermismayshowfeaturesofDLE,orbeunaffected

• Withindeepdermisandextendingintowidenedseptaeofsubcutaneousfatisadensechronicinflammatorycellinfiltrateofplasmacellsandlymphocytes

• Hyalinenecrosisoffatwithamostlylobularpanniculitis• Lymphoidfolliclessometimespresent

Pancreatic Panniculitis • Lobularpanniculitis,fatnecrosiswith“ghostcells”havingnonuclei• Adipocytescontaingranulareosinophilicorbasophilic(calcified)debris• Neutrophilinfiltratearoundfocioffatnecrosis,hemorrhage,uninvolvedsurroundingfatisheavilyinfiltratedbyinflammatorycells,someofwhicharefoamyduetoingestedlipid,oftentherearemultinucleatedgiantcells

Polyarteritis Nodosa• Septalpanniculitiswithmedium-sizedvesselvasculitis• Inflammationtightlylocalizedaroundvessel• MorefibrinouschangeandthusREDDERthanthrombophlebitis

Subcutaneous Fat Necrosis of the Newborn• Intensenecrosis• Adipocytesswollenandcontainradiallyarrangedeosinophiliccrystallinecrystals• Heavyinflammatorycellinfiltrateincludingforeignbodygiantcells• Olderlesionsmayshowcalcificationandfibrosis

• Similarfindingsinpost-steroidpanniculitis

5.12 FIBROUS/FIBROHISTIOCYCTIC DISORDERSAcrochordon

• Normalorhyperplasticepidermissurroundingacoreoffibrovasculartissuewithlooseordensecollagenfibers

• Absenceofadnexalstructures• Fatcellsmaybepresent→nevuslipomatosussuperficialis

Figure 5-33. Lupus Profundus


Acquired Digital Fibrokeratoma• Acrallocation• Pedunculatedandcoveredbyvariablyacanthoticandhyperkeratoticskin

• Corecomposedofdensecollagenfibersorientedinthedirectionoftheverticalaxisofthelesion

• Nonervebundlesandnokoilocytes

Angiofibroma (FibrousPapuleoftheFace,PearlyPenilePapules,Koenen’sTumor)

• Fibrosis,sometimesinan“onion-skin”patternaroundvessels

• Scatteredstellatefibroblastsandincreasedvascularity

• Localizedareaoffibroplasiaandvascularproliferationintheupperdermis

• Hypocellular• Fibrousbandingaroundfollicles• StainspositiveforfactorXIIIa• MultiplelesionsseenintuberoussclerosisandMENI

Atrophie Blanche (SegmentalHyalinizingVasculitis)

• Increasednumberofdermalvesselscontainingfibrinoidplugs

• Thickredwallsofthevessels• Frankvasculitisisnotafeature• Variabledegreeofpurpurawithhemosiderinpigment

• Infullyestablishedplaquesthereisepidermalatrophywithscleroderma-likescarring

Atypical Fibroxanthoma• Well-defined,dermallesion• Often,epidermalcollarette;thedeepmarginpushesratherthaninvades

• High-gradeatypia;composedofapleiomorphicmixofspindlecells,histiocyte-likecells,atypicalxanthomatouscells(classicallyseen),andmultinucleatedgiantcells

• Mitoticactivityandhyperchromasiacanbepresent

Figure 5-35. Angiofibroma

Figure 5-36. Atypical Fibroxanthoma

Figure 5-34. Acquired Digital Fibrokeratoma


uTIPaMake sure there isn’t an overt malignant melanoma in situ or SCC at epidermis

• StainspositiveforCD68,alpha-1antitrypsin,muscle-specificactin,CD10,CD99

Dermatofibroma(FibrousHistiocytoma,DF)

• Interlacingfasciclesofslenderspindlecells(runninghaphazardly)

• Oftenstoriform,withinaloosecollagenousormyxoidstroma,scatteredfoamyhistiocytes,multinucleatedgiantcells

• Peripheryoflesionshowshyalinecollagenbundlessurroundedbytumorcells,grenzzoneseen;don’tcountonpigmentedepidermalhyperplasia

• MultipleDFsseeninlupuserythematosus andimmunosuppression/HIV

• FactorXIIIa-positiveandstromelysin-3 positive

Dermatofibrosarcoma Protuberans (DFSP)• Dermaltumor,morecellularthanDFwithsmallercells,irregularinfiltrationofsubcutaneousfat

• Uniformspindlecellswithelongatednucleishowinglittleornopleiomorphism• Storiformpatternwithwhorls;thereisamyxoidvariant• CD34-positive• GiantcellfibroblastomaisalsoCD34-positive,andisusuallyseeninmalechildrenontheneck/trunk→thoughttobeajuvenilecounterpartofDFSP

• Translocationt(17;22)(q22;q13)hasbeendemonstrated;thistranslocationresultsinthefusionoftwogenes:collagentypeIalpha1(COL1A1)andplatelet-derivedgrowthfactorB-chain(PDGFB)

Epithelioid Sarcoma• Forearmsofyoungadults• Epithelioidcellsmixedwithspindlecellswithgranulomatousinflammationinfibroticstromawithnecrosis(canlooklikeapalisadinggranulomatousdisorder),atypia,mitoses,andvascularinvasion

Figure 5-38. Dermatofibrosarcoma Protuberans

Figure 5-37. Dermatofibroma (Fibrous Histiocytoma)

uTIPaNot well-circumscribed on low power (don’t go to high power)


• Mustruleoutinfectiouscauses(therefore,unlikelyyouwouldmakethisdiagnosisontheBoardswithoutclinicalhistory)

• Vimentin+,lowmolecularweightcytokeratin+

Giant Cell Epulis• Exactcounterpartofthegiantcelltumoroftendonsheathbutmoresuperficialandwithmucousmembraneepithelium

Giant Cell Tumor of Tendon Sheath• Deeptumor;lobulatedandwell-defined,oftenwithafibrouspseudocapsule• Xanthomatouscells,siderophages,andconspicuousgiantcells(osteoclasticgiantcells→purpleandangulated)

• Prominentcollagenousstroma,mitoticfiguresmaybenumerous,CD68positivestaining

Infantile Digital Fibromatosis• Irregularmassofproliferatingspindle-shapedmyofibroblastsembeddedinadensecollagenousstromaextendingdeeplyfromthedermis

• Findingbrightlyeosinophilic,PAS+,pinkcircularintracytoplasmicinclusionsinthemyofibroblastsisdiagnostic→thoughttobeaggregatesofactin

Keloid• Nodularfibroblasticproliferationandthepresenceofhypocellular,glassy,eosinophilic,hyalinizedanddisorderedcollagenfibersindermis

• Rubinstein-Taybi,Noonan’s,andTurner’ssyndromescanhavemultiplekeloids

Nodular Fasciitis• Clinicallypresentsasarapidly-growingtumorinayoungerperson

• Unencapsulated,deepmassofplumpspindlecellssetinaloosemyxoidandcollagenousstroma

• Thin-walledbloodvessels,ramifythroughlesioninaradialarrangement;fociofextravasatedRBC’s

• Mitoticcellsbutwithoutatypia• MoreheterogeneousthanaDFSP• Immunohistochemistrypositiveformuscleactin,butdesminisnegative

Hypertrophic Scar• Nonspecificdermalfibroblasticproliferation,oftenwithepidermalatrophy Figure 5-40. Nodular Fascilitis

Figure 5-39. Keloid


• Morecellularthankeloids• Hyalinizedcollagenfiberslessprominent;fasciclesandbundlesseen

Scar• Spindle-shapedcellsintermixedwithvaryingamountsofcollagen(dependentontheageofthescar)withvesselsorientedperpendicularlytotheepidermis

• Lackofadnexae

5.13 GENODERMATOSESBirt-Hogg-Dube

• Triadoffibrofolliculomas,skintags,andtrichodiscomas

• Increasedriskofrenalcancerandspontaneouspneumothorax• Autosomaldominant,moleculardefectinfolliculin

Cowden’s Disease• Multipletrichilemmomas,scleroticfibromas(storiformcollagenoma),acralkeratoses,oralfibromas

• Increasedriskofbreast/thyroidcancer• Autosomaldominant,mutationinPTEN gene

Epidermolytic Hyperkeratosis (BullousCongenitalIchthyosiformErythroderma)

• Hypergranulosis• Prominentvacuolizationofthesuperficialepidermalcells

• Stippledkeratohyalinegranules;higherupthereis“dropout”ofnuclei• SeeninbullousCIE,benignkeratoses,epidermalnevi,orincidental

• Autosomaldominant,defectinkeratins1/10

Ichthyosis Vulgaris• Orthokeratosiswithhypogranulosis/absentgranularlayer

• Autosomaldominant,defectinfilaggrin/profilaggrin

Incontinentia Pigmenti

• Eosinophilicspongiosiswithdyskeratoticcells• Pigmentincontinencewithmelanophagesindermisinlaterstages• Verrucouslesionsshowhyperkeratosis,acanthosis,papillomatosisandfocaldyskeratosis

• X-linkeddominant,mutationinNEMOgene

Figure 5-41. Cowden’s Disease


Porokeratosis• Keratin-filledepidermalinvaginationwithanangulatedparakeratotictier,thecornoidlamella

• Epitheliumdeeptotierisdevoidofgranularcelllayer,adjacentepitheliumtowardlesion’scenterisoftenatrophic

• Alwayslooktoperipheryofalichenoid infiltratetocheckforthecornoidlamella

Pseudoxanthoma Elasticum• Degenerativechangesofelasticfibersofmiddleandlowerdermis

• ElasticfibersreadilyidentifiableonH&E,appearing“pinkandsquiggly”→widelydispersedgranularmaterialamidstnormalcollagenfibers

• ElasticfibersstainpositivewithvonKossastain

• Transepidermaleliminationofdegenerateelastictissuemaybeseen;calcificationseeninolderlesions

• Autosomalrecessiveordominant

5.14 GRANULOMATOUS DISORDERSLeprosy, Borderline

• Multiplenodulesconsistingofepithelioidtuberclesinthesuperficialanddeepdermis• Nodulesarenotrounded,butmoreirregularandelliptical• Theinfiltratewithinthesenodulesislymphohistiocytic• Infiltratefoundaroundnervebundles

Leprosy, Lepromatous• Histiocytesinpoorlycircumscribedmassesinthedermiswithfew,ifany,lymphocytes• Histiocytesareoftenfoamy(dermisshowslotsofpallor),anddistended(termedvirchowcells)withlargegroups(globi)ofleprosybacilli(revealedbyZiehl-NeelsenorFitestain)

• Grenzzoneseen→maydestroycutaneousappendagesandextendintosubcutaneousfat

Leprosy, Tuberculoid• Epithelioidnon-caseatinggranulomatousresponsearoundsmallcutaneousnerves• Oftenextendingintoadjacentdermis• Langerhansgiantcells,scarcebacilli

Lichen Nitidus• Atrophicepidermiscoveredbyaparakeratotictier• Interfacedermatitis• Claw-likeextensionoftheepidermalridgesmarklateralboundariesofanlymphohistiocyticinfiltrate(“ballandclaw”)

• Giantcellsandgranulomatamaybeseen

Figure 5-42. Porokeratosis


Sarcoidosis• Fairlynormalepidermis• “Naked,”noncaseatingepithelioidtubercles(sparselymphocyticinfiltrate)locatedthroughoutthemidanddeepdermis

• Diagnosisofexclusion;canbeidenticaltoforeignbodyreaction(silica,beryllium,etc.)andgranulomatousrosacea

• Schaumannbody(basophilic,roundedstructurecomposedofcalciumcarbon-ate,phosphate,andiron)andasteroidbody(lipoprotein,eosinophilic,star-shaped),neitherbodyisspecificforsar-coid(seenalsoinTB,leprosy,berylliosis)

5.15 HISTIOCYTOSESJuvenile Xanthogranuloma

• Intradermalcollectionofuniformlipid-ladenhistiocytes,admixedwithmultinucleatedgiantcellsofToutonandforeignbodytypes(butToutongiantcellsnotspecificforJXG,andcanbeseeninanyxanthomatousprocess)

• Variablenumbersofneutrophils,eosinophils,mastcells,andlymphocytes,noepidermalinvolvement

• MultipleJXGsareassociatedwithocularinvolvement;even1JXGassociatedwithneurofibromatosisandCML

Langerhans Cell Histiocytosis• Infiltrateinupperdermis→uniformcellswithpalereniformvesicularnucleiandpale-stainingoreosinophiliccytoplasm

• Anedematouszoneof“floatingcells”intheupperdermis→eachcellseenindividually

• EpidermotropismischaracteristicasarePautriermicroabscesses;scatteredeosinophils

• Birbeckgranules• S100andCD1apositive;langerin(CD207) positive(mostspecific)

Figure 5-44. Sarcoidosis

Figure 5-45. Juvenile Xanthogranuloma

Figure 5-43. Lichen Nitidus


Reticulohistiocytosis

• Multicentrictypeseenmoreofteninolderwomen,associatedwitharthritismutilans,oftenseenclusteredaroundthenail→“coralbeadsign,”associatedwithbreastcancer

• Well-definedcollectionofuniformpinkhistiocytesandmultinucleatedgiantcellswith“groundglass”(notfoamy)cytoplasm→locatedpredominantlyindermis

Verruciform Xanthoma• Clinicallyoftenonoralmucosaeorgenitalarea• Regularacanthosis,parakeratosis,andhyperkeratosis• Bulbousepidermalridgespenetratetosamedepth,givinglevellowerborder,expandedridgeswithmarkedcentralkeratinocytenecrosisandheavyneutrophilinfiltrate

• Papillarydermisbetweenelongatedepidermalridgescontainslargenumbersofeosinophilicfoamyxanthomacells,butnoToutoncellspresent

5.16 INFECTIONSActinomycosis

• Containssulfurgranule(organismtangledtogetherinmattedcolony)withaneosinophicrim–Splendore-Hoeppliphenomenon–withdensesurroundingneutrophilicinfiltrate

Blastomycosis• Pseudoepitheliomatoushyperplasiaoverlyingabscesses

• Organisms(8-15microns)withbroad-basedbudding

Chromoblastomycosis• Pseudoepitheliomatoushyperplasiaoverlyingabscesseswithpresenceof“copperpennies”=scleroticbodies=medlarbodies=hotcrossbuns(6-12microns)

Coccidioidomycosis• Spherules(whichcontainandcancollapsetoreleaseendospores→10-80microns)

• Combinationofsuppurationwithpseudoepitheliomatoushyperplasia

• Rhinosporidiosissporangiumisbigger

Condyloma Acuminatum• Markedacanthosis,papillomatosis,withhyperkeratosisandparakeratosis

Figure 5-46. Actinomycosis

Figure 5-47. Chromoblastomycosis


• Sharpmargination,superficialvacuolatedkeratinocytes(koilocytes)

Cryptococcosis• Sphericalyeast,narrow-basedsinglebudding

• Mucinouscapsuleshowinggelatinousclearing

• Maybeagranulomatouspatternthathasrareorganisms

• Mucicarminepositivityofcapsuledis-criminatesbetweencryptococcusandothertissuefungalinfectionssuchashis-toplasmosisandblastomycosis

• Gelatinouspatternshowsnumerousvacuolated-likeareascontainingabundantencapsulatedorganisms4-20microns(largerthanhistoplasmosis)

Epidermodysplasia Verruciformis• Bluishchangeinthegranularlayer(thoughttoberibosomes)

• AssociatedwithHPVtypes5,8• Associatedwithimmunosuppression/HIVinsporadicformandisalsoinheritedinanautosomalrecessiveform

• MutationshavebeenfoundintheEVER1andEVER2genes;thesegenesareon17q25,thelocationofthePSORS2gene(oneofthegenesimplicatedintheinheritanceofpsoriasis)

Herpes Simplex Virus Infection• Suprabasilarintraepidermalbullae(ballooning)

• Mixedcellinfiltrateconsistingofneutrophilsandeosinophils

• Multinucleatedgiantcellswithmarginatedchromatin,steel-graynuclei,reticulardegenerationwithstrandsofcytoplasm

• Mayhavesubepidermalbullae;canlookidenticaltoerythemamultiformeinthelateralaspectsoflesion

• MayseeCowdryAbodies(Lipschutzbodies)

Figure 5-49. Cryptococcosis

Figure 5-50. Herpes Simplex Virus Infection

Figure 5-48. Condyloma Acuminatum


Histoplasmosis• Notencapsulated;2-4micronsyeastwithindistendedmacrophagesasabasophilicdotwithsurroundingartefactualhalo(pseudocapsule)

• SimilartoLeishmania,butlackinginthekinetoplast

• StainspositivewithPASandmethenaminesilver

Leishmaniasis• Amastigotes(littledots)withinmacrophages(Leishman-Donovanbodies),2-4microns,kinetoplastpresent

• Acanthoticepithelium,withfrequentlyulceration

• Epidermismayshowpseudoepithelio-matoushyperplasiaandintraepidermalneutrophilicabscesses,dermiscontainsintenseinfiltrateofhistiocytes,lympho-cytes,andplasmacells

• OrganismsbestseenwithGiemsastain• Lookslikehistoplasmosis,buthistoplasmosishasatiny“halo”aroundtheorganism

Molluscum Contagiosum• Lobulated,endophytichyperplasia• Keratinocytescontainverylargeintracytoplasmicinclusions,thatcompressthenucleusagainstthecellmembrane(Henderson-Pattersonbodies)→fillthecellsinacup-shapedinvaginationoftheepidermis,oftenatthehairfollicle

Orf (EcthymaContagiosum)• Acralskin;symmetricnodule• Parakeratosisandacanthosis;earlylesionshowsintracytoplasmiceosinophilicinclusionbodiesintheupper1/3oftheepidermis

• Ballooningwithoutmultinucleatedcells• Epidermiscanbehyperplasticwithdown-growingrete,dermalinflammationandvasodilationofvessels

• Mayshownecrosis;cowpoxisidentical

Protothecosis• Causedbyanalgae,mostcommonlyPrototheca wickerhamii• Organismlookslikeasoccerballonhistopathology(6-10mm)→themorula

Figure 5-52. Leishmaniasis

Figure 5-51. Histoplasmosis


Scabies• Burrowwithinhornylayer,withonlyblindend(withfemalemite)locatedinstratummalpighii

• Spongiosisinstratummalpighiinearmite• Dermalinfiltrateofeosinophilsandlymphocytesinlesionscontainingmites• Occasionallyscybala(feces)canbeseen

Syphilis, Primary Chancre• Epidermalhyperplasiawithintenselymphohistiocyticandneutrophilinfiltrateindermis• Plasmacellspresent• Overlyingepidermisulcerated,withadjacentepidermisshowingpseudoepiltheliomatoushyperplasia

Syphilis, Secondary• Papularlesionsshowsuperficialanddeepperivascularinfiltratesthatmaybecomeband-like;plasmacells(whichareoftendeep)andhistiocytes(paleinfiltrate)

• Parakeratosis,acanthosis,spongiosis,andexocytosis

• Thick-walledbloodvesselswithswollenenthothelialcellscharacteristic

• Psoriasiformsyphilidesshowparakeratosisandacanthosiswithextendedepidermalridges

• Spirochetescanbeseeninlowerepidermisandinbloodvessels

Tinea Versicolor • Minimalspongiosis;organismseasilyseenonH&E(unlikedermatophyte)instratumcorneumasspaghettiandmeatballs(mustseeboth)

Verruca Plana• Relativelyflatlesionwiththecellsofthegranularlayerappearingtobeclearerthanusual(vacuolized)

Figure 5-53. Syphilis, SecondaryuTIPaExtravasated RBCs may be a feature of both papular and papulosquamous vari- ants; most commonly the infiltrate will be

lichenoid → if you see lichenoid pattern, look for plasma cells

uTIPaThink of this diagnosis when skin appears normal or mildly inflamed

Figure 5-54. Verruca Plana


Verruca Vulgaris• Hyperkeratosis,papillomatosis,tiersofparakeratosisovertipsofexophyticcomponent• Prominentgranularcelllayerwithinwhicharevacuolatedcellscontainingenlargedclumpsofirregularkeratohyalingranules(“owl’seyes”orkoilocytes)(seeninupper1/3ofepidermis)

• Dilatedbloodvesselsinthedermalpapilla

5.17 INFLAMMATORYAcne Keloidalis

• Early:Dilatedfolliclemaycontainpusextendingthroughepithelium,surroundedbyneutrophils,lymphocytes,andperhapsplasmacells

• Later:Markedfibrosis/scarring,freebrokenhairshaftswithforeignbodygiantcellreaction;possiblelaterallymphoplasmacyticinfiltrate

• Identicalfindingsinhidradenitissuppurativa,butthisconditionalsolikelyshowssinustractslinedbystratifiedsquamousepitheliumandsurroundedbyfibrosisandinflammation

Chronic Radiodermatitis• Hyperkeratosis,fociofparakeratosis,acanthosisoratrophywithflattenedreteridges• Spongiosisorbasalcellliquefactiondegeneration• Dermisisfibrotic,paleandsickly,andlacksinflammation(notsquareandredlikemorphea)• Bizarre(radiation)fibroblasts,thickenedbloodvesselswithfibrointimalhyperplasia,ortelangiectasia

• Lossofappendages

Cryoglobulinemia• Vasculardilatation,endothelialswelling,andpluggingofvascularluminabyhyalinematerial(microthrombi)→reddeposits

• SamepatternforDIC,cryoglobulinemia,lupusanticoagulant,proteinSandCdeficiency,antithrombinIIIdeficiency,coumadinandheparinnecrosis,PNH

Lichen Planus-like Keratosis (BenignLichenoidKeratosis)• Hyperkeratosis,hypergranulosis,variableacanthosis,andbasalcellliquefactiondegeneration(worsethanLP)

• Parakeratosiscommonlypresent(unlikeLP)• Broadened,widenedandirregularepidermalridges(ratherthansawtooth),denseband-likelymphohisticyticinfiltrateinsuperficialdermisthatmaycontaineosinophilsandplasmacells;seennearlentigoorseborrheickeratoses

Erythema Annulare Centrifugum (GyrateErythema)• Well-demarcatedperivascularinfiltrateoflymphocytesandhistiocytes→cuffing,butnotalwayslikethis

• Epidermisusuallynormal,butfocalspongiosiscanbeseen• Makesurethatthereisnointerfacedermatitisoflupus,nopapillarydermaledemaofPMLE

Erythema Elevatum Diutinum• Leukocytoclasticvasculitis• Epidermismayshowacanthosisandparakeratosis

uTIPaBig clue → hyperpigmentation of the basal layer; no dysplasia like a lichenoid actinic keratosis


• Fibrinoidnecrosisandneutrophilinfiltrationofvessels

• Olderlesionsshowgranulomatoustissueandfibrousscarring

Erythema Multiforme• Subepidermalblister,withnecrotickeratinocytesatalllevelsofepidermis

• Vacuolarinterfacechange• Basketweavestratumcorneum(PLEVAdoesn’tshowthis)

• LymphohistiocyticinfiltrateespeciallyatDEjunction

• Usuallynoeosinophils(butnotahard-and-fastrule)

• Infiltratecanbedeep

Granuloma Faciale• Dense,oftennodularinfiltrateinmiddermis

• Grenzzone;involvesbothepidermisandhairfollicles

• Infiltrateinvolveseosinophils,neutrophils,plasmacells,mastcells,andlymphocytes,extravasatedRBCs

• Dilatedbloodvesselswithfibrindepositionintheirwalls

Graft Versus Host Disease (GVHD)• Acutediseaseshowswidespreadbasalcellhydropicdegenerationwithscatterednecrotickeratinocytesthatarefoundinadnexae

• Lymphocyticexocytosiswithsatellitecellnecrosis(notalwayspresent)• Dermaledemawithdilatedbloodvessels• Pigmentaryincontinence

Leukocytoclastic Vasculitis• Subepidermalorintraepidermalblisterwithneutrophils,necrotickeratinocytes,basketweavestratumcorneum

• Edemaofpapillarydermis,withcollectionofneutrophilsandnucleardustaroundandobliterationofvessels

• Fibrinoiddegenerationofvessels,fibrin“blendsinto”surroundingcollagen• ExtravasatedRBC’s

Lichen Simplex Chronicus• Psoriasiformhyperplasiawithorthokeratosis,prominentgranularlayer,focalparakeratosis• Verticallyorientedcollagenfibersinelongateddermalpapillae

Figure 5-55. Erythema Multiforme

Figure 5-56. Granuloma Faciale


• Superficialperivascularlymphohistiocyticinfiltrate

• DifferentialdiagnosisincludeshypertrophicLP,whichshowsalichenoidinfiltrate

Lichen Planus• Prototypicallichenoidinflammatoryconditionwithaband-likeinfiltrateoflymphocytessometimesobscuringtheDEJ,withhyperkeratosis,wedge-shapedareasofhypergranulosis,irregularacanthosis,saw-toothingofthebasallayerwithsquamotizationofbasalcells

• Colloid/Civattebodies• Parakeratosisandeosinophilsshouldbeabsent

• LPonmucosa:Plasmacellswithouthypergranulosis(oftenontheBoards)

Lichen Sclerosus et Atrophicus• Often,epidermalatrophywithconfluentorthokeratosis,follicularplugging

• SubepidermalbullacontainingRBC’s• Superficialperivascularandband-likelymphohistiocyticinfiltrateunderapaleandscleroticzone

• Telangiectasesinpapillarydermis,homogeneouscollageninupperdermis,dermaledema

• Sameasbalanitisxeroticaobliterans(BXO)

• PatientsmayhavecirculatoryautoantibodiestoECM-1

Lichen Striatus• Mildparakeratosis,spongiosis;superficialperivascularinflammatoryinfiltrateofpredominantlylymphocytes(rareplasmacellsoreosinophils)thatmaybealmostband-likesuperficially

• Lowpowershowsanearlyemptydermis,butdeepdermisshowsadenseinfiltratearoundtheadnexalstructures→veryuniquetothisentity

Figure 5-58. Lichen Sclerosus et Atrophicus

Figure 5-59. Lichen Striatus

Figure 5-57. Lichen Planus


Lupus Erythematosus• Follicularplugging,mildhyperkeratosis,vacuolarchangeofbasallayer,basementmembranethickening,pigmentincontinence,increaseddermalmucin

• Superficialanddeepperivascularinfiltrateoflymphocytesandhistiocytesthatisperiadnexalaswell

Morphea • Squarebiopsythatisveryred• Papillarydermisunaffectedusually• Reticulardermishasswollencollagenbundlesthatareintenselyeosinophilicandorientedparalleltosurface,alsoseptaofsubcutaneousfatinvolvedwithatrophyofadipocytesandfibrosis,folliclesandsebaceousglandsareatrophicorabsent

• Eccrinetrapping,dense,chronicinflammatorycellinfiltrateoflymphocytesandplasmacells,mucinisnotalargefeature;therearenogiantcells

Perforating Folliculitis• Widelydilatedhairfolliclecontainingortho-andparakeratotickeratin,basophilicnecroticdebris

• Connectivetissueelementsandinflammatorycells• Acurleduphairsometimesisfoundwithinthekeratinousplug

Perniosis• Acrallocation,withinterfacedermatitis,occasionally• Papillarydermaledema;infiltrateisdiffuseanddeep• SimilartoPMLE

Pigmented Purpuric Dermatosis• Chroniccapillaritis;superficialvesselsdilatedwithendothelialcellhypertrophyandsurroundingextravasatedredbloodcells

• Perivascularlymphocyticinfiltrate(noeosinophilsorneutrophils)thatmaylooklichenoid

• Purpurainearlylesions,andhemosiderin-ladenmacrophages(siderophages)seeninolderlesions;pigmentisdeep(stainwithPerlsPrussianblue)

Figure 5-60. Pigmented Purpuric Dermatosis

uTIPaVariants include: progressive pigmentary dermsis of

Schamberg, lichen aureus (clinically usually asymmetrical), eczematid-like purpura of Doucas and Kapetenakis, lichenoid dermatitis of Gougerot and Blum, purpura annularis telangiectoides of Majocchi


Pityriasis Lichenoides et Varioliformis Acuta (PLEVA)

• Parakeratosis,pallorofupperepidermis• Spongiosisandvacuolaralterationofthebasallayerwithsomenecrotickeratinocytesatdifferentlevels

• Papillarydermaledema• Band-likeinterfaceinfiltrateanddeepinfiltratecomposedofmostlylymphocyteswithexocytosisoflymphocytes

• ExtravasatedRBC’sinupperdermis• CanlookjustlikeLyPbutLyPhaseosinophilsandneutrophilsandPLEVAdoesn’t

• Erythemamultiformedoesn’tshowparakeratosis

Pityriasis Rosea• Moundsofparakeratosisoverslightacanthosis,andslightspongiosis

• Superficialperivascularinfiltratepredominantlylymphocytes

• ExtravasatedRBC’sinpapillarydermiswithextensionintotheepidermis

• Papillarydermaledema

Pityriasis Rubra Pilaris• Acanthosiswithbroadandshortreteridgeswithslightspongiosis

• Thicksuprapapillaryplates,focalorconfluenthypergranulosis(variable)

• Alternatingorthokeratosisandparakeratosisbothverticallyandhorizontally

• Dermisshowsmildsuperficialperivascularlymphocyticinfiltrate

• Uniquefeature→conicalhyperkeratoticfollicularplugisfarabovetheepidermis

Polymorphous Light Eruption (PMLE)• Variableepidermalspongiosis• Dermal,perivascularlymphocyticcellinfiltratewithmarkedpapillarydermaledema

Figure 5-62. Pityriasis Rosea

Figure 5-61. Pityriasis Lichenoides et Varioliformis Acuta

Figure 5-63. Pityriasis Rubra Pilaris


• MayresembleSCLE,butinfiltratemorecommonlyaroundbloodvesselsthanpilosebaceousunits,andnovacuolarinterfacechanges

• InfiltrategoesdeeperthanSCLE

Psoriasis• Lengthenedandmultilayeredparakeratosiswithneutrophils(Munro’smicroabscesses)

• Palloroftheupperepidermis• Hypogranulosis• Regularacanthosisofepidermis• Spiraleddilatedvesselsunderthinnedsuprapapillaryplates

• Earlylesionsmayshowspongiosis

Rosacea, Granulomatous • Perifollicular• Telangiectasesandroundepithelioidtuberclesthatmaycaseateinsuperficialdermis

• Surroundinglymphocytes

Sweet’s• Densenodularinfiltrate,composedprimarilyofneutrophils,histiocytes,andsomelymphocytes

•Maybeprimarilyhistiocytoid• Nucleardust(leukocytoclasis)ismarked,thepapillarydermisisedematous

• Focaldegenerationofcollagen,extravasatedRBC’s

• Novasculiticchanges;dermaledemashouldalsomakeyouthinkofPMLE,whichhaslymphocytes

Stasis Dermatitis• Hyperkeratoticepidermiswithareasofparakeratosis,acanthosis,andfocalspongiosis• Superficial,perivascularlymphohistiocyticinfiltratethatsurroundsplump,thickenedcapillariesandvenules

• Superficialdermalvesselsmaybearrangedinlobularaggregates• Reticulardermisisoftenfibroticandhemosiderinisusuallypresentdeep

Toxic Epidermal Necrolysis• Confluentwipe-outoftheepithelium,full-thicknessnecrosis,subepidermalvesiculation,sparseinflammation

Figure 5-64. Polymorphous Light Eruption

Figure 5-65. Psoriasis


5.18 LYMPHOMAS AND MARKERSB-cell Lymphoma

• Oftenadiffuse,deepinfiltrate• Germinalcentersmaybepresent(especiallyinprimarycutaneousfolliclecenterlymphomawithafolliculargrowthpattern)

• Oftencanbe“bottomheavy”involvingsubcutaneousfatlobules• Epidermisgenerallyspared• CD20+

Leukemia Cutis• AMMListhemostcommon(acutemyelomonocyticleukemia;myeloidprecursors);grenzzonepresent

• Densediffuseinfiltrateindermisandextendingintosubcutaneousfat;cellssplayedoutthroughthestroma→someIndian-filing;notalwayshighlyatypical,darklystainingsmall-tomedium-sizedcells

• Infiltratemaybesparseordense• NeoplasticcellsstainpositiveforLeder,lysozyme,myeloperoxidase

Lymphoma Cutis• Diffuseinfiltrate• Nogerminalcenters;infiltrategoesdeepwithoutapattern• Oftencanbe“bottomheavy”involvingsubcutaneousfatlobules• Epidermisspared• CD20+

Lymphomatoid Papulosis (LyP)• PLEVA-likearchitecturally,butcellsmoreatypical;infiltrateiswedged-shapedwithbaseofwedgeincloseappositiontotheepidermis

• Earlylesionsmaynotaffectepidermis,whileinolderlesionstheinfiltratemaybelichenoid;interfacemightbeobscuredbyinfiltrate

• LyPhaseosinophilsandneutrophilsintermixedwithatypicallymphocytesthatlooklike“chunksofcoal”

• MostcellsareCD3positiveandCD4positive

Figure 5-66. Lymphomatoid Papulosis

uTIPaType A: CD30-positive; pleomorphic cells are

large with vesicular nuclei; Reed-Sternberg-like multinucleate giant cells; neutrophils, eosinophils, and plasma cells

a Type B: MF type with preponderance of Sezary-type cells

aType C: like anaplastic large cell lymphoma

aType D: like aggressive epidermotropic CD8+ cytotoxic T=cell lymphoma

uTIPaThe 2005 WHO-EORTC and 2008 WHO Classification of

primary cutaneous B-cell lymphomas has 4 main categories: follicle center lymphoma; marginal zone lymphoma; diffuse large B-cell lymphoma, leg type or other/NOS


Mantle Cell Lymphoma• Clinically:Mostpatientshavedisseminateddiseaseattheoutset,1/3haveleukemicinvolvement;cutaneouslesionshavebeenreportedtoprecedeinternaldisease

• Characteristicallybcl-1(CyclinD1)positive[t(11;14)translocationinvolvingbcl-1andtheimmunoglobulinheavychaingene]

• AlsopositivewithCD19,CD20,CD5(likeCLL),CD43,bcl-2• LackCD23(unlikeCLL)• Mantlecellshavecellsurfaceimmunoglobulins(oftenIgMandIgD)• Oftenhaslambdalightchainrestriction

Mycosis Fungoides (MF)• ForBoardpurposes,aslideofMFshouldhavemostofthesecriteria:– Largerintraepidermallymphocytescomparedwithsmallerdermallymphocytes

– Pautrier’sabscesses–Disproportionateexocytosisinrelationtospongiosis

– BasilarlymphocyteslinedupagainsttheDEJ(“toysoldiers,"“stringsofpearls”)

– Pagetoidspreadoflymphocytesintotheepidermis

– 7-9micronconvolutedlymphocytes(abasalkeratinocyteisabout7-9microns)

–Halo’dlymphocytesintheepidermis– Papillarydermalfibrosis,so-called“fettucine”collagen–CD4+cellsintheepidermisthathaveoftenlostCD5andCD7

• NotethattypeBlymphomatoidpapulosiscanlookexactlylikeMFhistologically

Pseudolymphoma (ReactiveLymphoidHyperplasia)• Densenodulesconsistingofsmalllymphocytesandhistiocytes• Germinalcenter(centrocytesandcentroblasts)morphologywithsurroundingmantleandthenmarginalzone,surroundingT-cells→nodulesinvolveboththeupperandlowerdermis(more“topheavy”)

• Lymphocytes,eosinophils,ectopicadipocytes• Incenterofreactivefollicleare“tingiblebodymacrophages”

Subcutaneous Panniculitis-like T-cell Lymphoma • Clinicallypatientspresentwithsubcutaneousnodulesontheextremities,canhaveafatalhemophagocyticsyndrome

• Biopsycanbesubtle;shouldseeaseptalandlobularpanniculitiswithmediumtolargeatypicallymphocytes,rimmingoffatcellswithatypicallymphocytes,necrosis;theremaybephagocytosisoflymphocytes/debris/erythrocytes

Figure 5-67. Mycosis Fungoides


uTIP Cell Markers

w Markers • CD1a

– Langerhanscells

• CD2,CD3

– PanT-cell

• CD4

– HelperT-cell

– Alsoexpressedbyhistiocytes(Langerhanscells)

• CD5

– PanT-cell

– MarkerofCLL,mantlecelllymphoma

– LostinMF

• CD7

– T-cells

– LostinMF

• CD8

– CytotoxicT-cell

• CD10

– Markerforprimarycutaneousfolliclecenterlymphomas

• CD16

– NKcellmarker

• CD19,CD20,CD79a

– Bcellmarker

• CD23

– PositivemarkerinCLL

– NegativemarkerinMantlecelllymphoma

• CD30

– Markerforanaplasticlargecelllymphoma,lymphomatoidpapulosis,Hodgkin’s,transformedMF

• CD45(akaLCA=leukocytecommonantigen)

– T-cells,B-cells,myeloidcells,histiocytes

• CD56

– NKcellmarker

• CD57

– T-cellswithNKactivity

• CD138

– Plasmacellmarker,CD79a

• Bcl-1

– Markerformantlecelllymphoma

• Bcl-2

– Anti-apoptotic

– Markerforfollicularcelllymphoma(nodal)

– Primarycutaneousfolliclecenterlymphomasaregenerallybcl-2negative

– StainsBCCsdiffuselywhereasstainsonlytheouterrimofepitheliumintrichoepitheliomas

• Bcl-6

– Markerforprimarycutaneousfolliclecenterlymphomas

• MUM-1/IRF4

– MarkerfordiffuselargeB-celllymphomas,legtype

• Twogroups:1.)Alpha-betaT-cells(bydefinition)thatareCD8+,moreindolentclinically2.)Gamma-deltaT-cellsthatareCD56+,moreaggressive(fatal)withsystemichemophagocytosis-thissubsetisnowconsideredasubsetofcutaneousgamma-deltaT-celllymphomas(aprovisionaldiagnosis)


Figure 5-68. Immunohistochemical Stains for the Diagnosis of Some Cutaneous Lymphomas

5.19 MELANOCYTIC LESIONSAtypical Nevus (DysplasticNevus,NevuswithArchitecturalDisorder,Clark’sNevus)

• Maybejunctionalorcompound;incompoundlesions,theepidermalcomponentextendsbeyondthelateralborderofthedermalnevuscells(shoulderphenomenon),littleornopagetoidspread,lentiginousmelanocytichyperplasiawithelongationofreteridges

• Melanocyteshaveincreasednuclearsize,nuclearmembraneirregularity,prominentnucleoli,andpleomorphismandarerandomlydistributedalongbasallayer;markedfixationartefact,fusionofadjacentnests,raremitoses

• Periepidermalfibroblasticresponse→lamellarfibroplasia;randomatypia(notuniform)

Balloon Cell Nevus• Roundorovalcellswithabundantpale-stainingorclearcytoplasm• Thecellscontainacentralhyperchromaticorvesicularnucleuswithveryconspicuousnucleolus

• Lookslikeaxanthoma,butdistinguishbylookinghighindermisascellsmaygointoepidermis(compoundorintradermal),containmelanin,orshownesting

Blue Nevus, Cellular• Large,oftenwell-circumscribed,nodularmassthatfillsthedermisandmaypenetrateintosubcutaneousfat

• Getsmorecellularasyoulooklowerindermis


• Composedofadualcellpopulation:largenumbersofcloselyaggregatedlargespindleandepithelioidcellsadmixedwithheavilypigmentedcells

• Melanophages• Tumorcellsmaybedividedintonestsandcordsbycollagenousseptae,noatypiaandrarelymitoticfigurespresent

• Veryrarely,melanomamaydevelopwithin

Blue Nevus, Common• Typicallyinupperdermis,heavilypigmenteddendriticspindlecellswithassociatedhost-deriveddensefibroblasticandcollagenousspindlecellresponse

• Oftenassociatedheavilypigmentedmelanophages

• Nomitoticfiguresandnopleomorphism• Overlyingepidemisisnormal• Completelybenignlesion

Blue Nevus, Combined• Associationofacommonbluenevuswithanoverlyingmelanocyticnevus

Nevus, Congenital• Frequentlyhyperkeratosis,acanthosis,andpapillomatosis

• Neonatallesionsarecompoundanddevelopwithinacanthosis

• Melanocytesmaypresentaswell-circumscribednestsorassinglecellsscatteredthroughalllayersofepidermis

• Nevususuallyisadiffuseinfiltrateofmelanocytesfrompapillarydermisintodeepreticulardermisandpossiblysubcutaneousfat

• Nevuscellsensheathepidermalappendagesandcanbefoundwithinarrectorpilimuscles,hairfollicles,sebaceousglandsandthewallsofeccrinesweatducts

• Withincreasingdepththenevuscellsadoptasingle-cellarrayandIndian-filepattern

Deep Penetrating Nevus• Maybeavariantofbluenevusorcongenitalnevus• Symmetrical,wedge-shaped,conglomerateofspindleandepithelioidcellsthatextendintodeepreticulardermis/fat

• Noupwardextensionofmelanocytes(Pagetoidspread)• Oftensurroundsfollicles/nerves/glands

Figure 5-69. Blue Nevus, Common

Figure 5-70. Blue Nevus, Combined


Halo Nevus• Raiseddermalnodule,acanthoticandfrequentlyhyperkeratoticepidermis• Nevusisusuallycompoundandinfiltratedextensivelybylymphocytesandhistiocyteswithoccasionalmastandplasmacells,itlookslichenoidbutit’sadeeperinfiltratethanlichenplanus

• Fontana-Massonshowsanabsenceofmelaninattheperiphery

Malignant Melanoma, Superficial Spreading• Asymmetricproliferationofatypicalmelanocytesscatteredsinglyandinclustersatalllevelsofepidermis(buckshotscatter,orpagetoidspread)

• Singlecells>nests;cellsareepithelioidwithabundantcytoplasm• Vesicularnucleiwithprominentnucleoli,scatteredmitoticfigures,atypia,tumorgrowthspreadsfromoneepidermalridgetoanother

• Epidermisoftenacanthoticwithpartial/completeeffacementofreteridges

• Associatedwithmutationsinp16,CDKN4a,BRAF,sometimesp53,ras

Malignant Melanoma, Desmoplastic Variant• Diffuselyinfiltrative,sometimespaucicellular,markedlyfibroticdermis• Proliferationofatypicalspindle-shapedmelanocyteswithhyperchromaticnucleiandoccasionalmitoticfigures

• Atypicalmelanocytesassingleunitsandirregularnestsintheoverlyingepidermis• Neurotropism• S100+,butHMB45negative

Malignant Melanoma, in Situ• BroadpoorlycircumscribedasymmetricalproliferationofenlargedatypicalmelanocytesassingleunitsandirregularnestsatDEjunction

• Manyatypicalmelanocytesextendingintotheupperlevelsoftheepidermis• Noatypicalmelanocytesinthedermis

Malignant Melanoma, Lentigo Maligna• Atypicaldendriticmelanocytesatbasalepidermisshowingmarkedcytoplasmicvacuolationandpleomorphicirregularhyperchromaticnuclei

• Littletendencytoinvolveupperepidermis• Cellscaninvolveadnexae→goesupanddownhairfollicles• Pigmentoftenabundantinvolvingfull-thicknessofepidermisandstratumcorneum• Epidermisoftenatrophicandthereissolarelastosis(actinicdamage)• Desmoplasticmelanomasderivefromthese,usually

Nevus of Ito/Ota/Mongolian Spot• Nojunctionalactivity• Inupperandmiddermisareelongated,dendritic,highlypigmentedmelanocytesscatteredamongthecollagenbundles

• Lesscellularorevenacellular,veryfewtonomelanophages

Pigmented Spindle Cell Nevus of Reed• Lesionoftenshowsbreadthgreaterthanheight• Symmetric,cellsareuniform,narrow,elongated,spindle-shaped,oftenheavilypigmented


• Typicallyjunctionalorconfinedtoepidermisandpapillarydermis,mayblendinwithadjacentkeratinocytes

• Arrangedinnests(>singlecells)andverticallyoriented• Nevuscellsformcompactclusterthatpushestheconnectivetissueaside• Associatedwithpigmentedparakeratosis

Recurrent Nevus• Directlyoverlyingascar,remnantsofapreviouslyexcisednevus• AtypicalmelanocytesattheDEJinalentiginouspattern,sharplycircumscribed• Nomitoticfigures• Sharplateraldemarcation,buttherecanbesomeupwardspread

Spitz Nevus• Symmetriclesionthatiswedge-shaped• Presenceofjunctionalcleavageartifact• Noinvolvementofoverlyingepidermis• Kaminobodies(butnotnecessary)• Epidermalnestsofspindlecellsarrangedvertically,withlackofcellularcohesionbetweenadjacentcells

• Nonuclearpleomorphism,alittlemitoticactivityisokay

• Littletonopigmentationclassically• Presenceofvascularectasia• Maturationoflesionindeeperlevels(decreaseinthesizeofnestsandmelanocytes)

• Associatedwithgainofchromose11pinrarecases

5.20 MUSCLEAngioleiomyoma

• Onlowpower,adeeptumorthatisredandwell-circumscribed• Highpower:Interlacingbundlesofuniformsmoothmusclecellsdistributedaroundnumeroussmallvessels

• Fewlesionsaresowell-circumscribed

Figure 5-71. Pigmented Spindle Cell Nevus of Reed

Figure 5-72. Spitz Nevus


Leiomyoma

• Familialmultiplecutaneous leiomyomatosis–genedefectfumarate hydratase

• Reddish/orangecolor→derivedfromarrectorpilimuscle

• Uniforminterlacingbundlesorirregularcollectionsofelongatedcellswithbrightlyeosinophiliccytoplasmandblunt-endedorcigar-shapednuclei,mitosesareabsent

• StainspositivefordesminandSMA

Leiomyosarcoma• Ill-defineddiffuselesion,interlacingbundlesofsmoothmusclecellswitheosinophiliccytoplasmandblunt-ended,cigar-shapednuclei

• Pleiomorphisminsubcutaneousvariantmorecommon

• Necroticareascanbeseen• PositiveforSMAanddesmin

5.21 NEURALCellular Neurothekeoma (DermalNerveSheathMyxoma)

• Unencapsulated,lobulatedmassindermiswithsparingofsuperficialpapillarydermis

• Tumorlobulesseparatedbyfibroussepta,andcomposedofstellateandspindlecellswithpaleindistinctcytoplasmsetinanabundantmyxoidmatrix;occasionallythereareblandmultinucleatedgiantcells

• NegativeforS-100,positiveforNKIC3• Differentialdiagnosisincludesdesmoplasticmelanoma,dermalSpitz,epithelioidcellhistiocytoma

Granular Cell Tumor • 40%locatedonthetongue• Ill-defined,composedofnestsoflargeroundcellswithbrightlyeosinophilicgranularcytoplasm

Figure 5-75. Cellular Neurothekeoma

Figure 5-74. Leiomyoma

Figure 5-73. Angioleiomyoma

uTIPaAn important clue is pseudoepitheliomatous/epidermal hyperplasia at surface (reminiscent of the epidermis above a dermatofibroma)


• Cellbordersareindistinctgivingasyncytialappearance

• Nucleiareuniformlysmall;commonly,pseudoepitheliomatoushyperplasiaofoverlyingepitheliumintumorsofdermisortongue

• S-100+,Vimentin+,NSE+

Neurofibroma• Lowpowerdiagnosis• Well-defined,butunencapsulateddermalorsubcutaneous;“bubblegumpink”collagenousstroma,nucleiare“tinydots”

• Engorgedvesselsthroughoutthetumor;scatteredmastcells(aclue)andotherinflammatorycellsaprominentfeature

• NocollagentrappingasseeninDF• MayconfusewithDFSP,butDFSPgoesthroughthefat

• Aplexiformneurofibromaishighlysuggestiveofneurofibromatosis

Palisaded Encapsulated Neuroma (PEN)• Higherindermis,awell-circumscribeddermalnodule,typically,butmaybemultinodularorplexiform

• Encapsulationisincompleteandsuperficialpartoftumorappearstomergeoftenwithsurroundingdermis

• Cellsarearrangedinshortfasciclesseparatedbyartefactualcleftingandcomposedofwavyhyperchromaticnucleiandill-definedpaleeosinophiliccytoplasm

• MostcellsS-100positive• MucosalneuromasinMENIIbresemblePENs

Schwannoma (Neurilemmoma)• Invariablyencapsulated,insubcutaneousordeepertissues;biphasicAntoniAandAntoniBareas

• AntoniA→cellularcomponent,closelypackedspindlecellswithtapering,elongated,wavynuclei;nuclearpalisadingproducesVerocaybodies;“fenceofcells”oneithersideofacentralpinkarea

Figure 5-76. Granular Cell Tumor

Figure 5-77. Neurofibroma

Figure 5-78. Palisaded Encapsulated Neuroma


• AntoniB→irregularlyscatteredspindleorstellatecellsinloosemyxoidstromaatperiphery;withinarescatteredinflammatorycellsandsmallbloodvesselswithhyalinizedwalls

• ComposedofSchwanncellsandareS-100positive

Supernumerary Digit• Clinicallylocatednearthebaseofthefifthfinger• Architectureatlowpowerlookslikeanacquireddigitalfibrokeratoma,buttherearenumerousnervebundlesinthedermis;sometimesthereisbone/cartilageaswell

Traumatic Neuroma• UnencapsulatedmassofnumerousaxonsandSchwanncellsembeddedinscartissueadjacenttothecutendofadamagednerve

• Nervefasciclesdispersedhaphazardly

5.22 PAGETOID SPREADBowen’s Disease

• Full-thicknessdysplasiaincludingintraepidermalportionsofthecutaneousadnexae

• Parakeratosis,markedacanthosis,withcompletedisorganizationoftheepidermalarchitecture,lossofmaturation,andlackofpolarityofcells

• Nuclearpleomorphismandmitoticfiguresseen;clear-cellvariantshowsmarkedcytoplasmicvacuolizationinupperlayers

• SometimeswithlargekeratinocytesthatresemblethecellsinPaget’sdiseaseofthebreast

• Dyskeratoticcellsandacantholysismaybeseen(Paget’sdiseaseshowsnodyskeratosisandnoclearcells)

• Thebasallayerismoreuniformandlookslikeeyeliner(i.e.,“eyelinersign”)• Stainforhigh-molecularweightkeratins(cytokeratin+)

Metastatic Breast Carcinoma with Epidermotropism• EpidermiscanlooklikePaget’sdisease• Keyisinthedermis,wherethereareneoplasticcellsinfiltratingsingle-filethroughcollagen,withsomeaggregationintoduct-likestructures

• Lotsofatypia(unlikemicrocysticadnexalcarcinoma,whichshowsnoatypia)• NogrenzzonelikeAMML

• CEA+,CK7+

Pagetoid Melanoma• Thebasallayershouldhaveatypicalmelanocytes• CEA-negative,S100+

Figure 5-79. Bowen’s Disease


Paget’s Disease of the Breast/Extramammary Paget’s• Allvariantsshowidenticalhistology• Epidermisoftenacanthotic,withvaryingamountsofparakeratosisorhyperkeratosis• Infiltrationwithlargecellswithabundantpale-stainingcytoplasmcontaininglargevesicularnuclei;theuniquefeatureisthegray/bluecytoplasm

• Cellscanbescatteredthroughoutalllayersofepidermis• Unlikemelanoma,thereareareaswhereproliferationisstrictlyabovethebasallayer• FrequentlypositivewithAlcianbluepH2.5,colloidaliron,ormucicarminestains;stainspositiveforPAS,CEA,EMA,CAM5.2,andlowmolecularweightkeratin

Much Rarer• Pagetoidreticulosis(Woringer-Kolopp:localizeddiseaseinyoungerpatientsonacralareas;Ketron-Goodman:widespreaddisease)

• IntraepidermalspreadofsebaceouscarcinomaorMerkelcellcarcinoma

5.23 PALISADING REACTIONSGout

• Histiocytes,somepalisaded,surroundingabasophilicaggregate,whichonhigherpowerhassomecrystallinefeatures(silveryneedle-likeclefts)

• Formalinfixationcandestroyuratecrytals(needalcoholfixation)

Granuloma Annulare (GA)• Palisadinggranuloma,sometimesinterstitial,withhistiocytessurroundingafocusofalteredcollagenthatoftenhasabluishtingesecondarytomucin;thepalisadinggranulomasareindiscretefociinthedermis

• Notethatgiantcellsandplasmacellsaremorecommonlyseeninnecrobiosislipoidicadiabeticorum

• NotethatdeepGAcanlookexactlylikearheumatoidnodule,andtheslidemaylackepidermis

Necrobiosis Lipoidica Diabeticorum (NLD)• Squarebiopsy,thinepidermiswithnoreteridges

uTIPaA clue to Paget’s disease of the breast is recognizing nipple (smooth muscle bundles in the dermis, sometimes ducts)

Figure 5-80. Gout

Figure 5-81. Granuloma Annulare


• “Layered”superficialanddeepdermalinfiltrates(multifocal),separatedbyareasofdegeneratedcollagen(necrobiosis,drippingofredareasthroughthedermis),infiltrateconsistsoflymphocytes,histiocytes,andplasmacells

• Elastic-van-Giesonstainshowscompleteabsenceofelastictissue• PlasmacellsandgiantcellsaremorenumerousthaninGA

Necrobiotic Xanthogranuloma• Granulomatousinflammationsurroundingcentralnecrobiosisandcholesterolclefts,mayseelymphoidfollicles

• Largeareasofmarkednecrobiosisalternatewithfociofxanthogranulomatousinfiltrateinreticulardermisintosubcutaneousfat

• Necrobioticcollagenappearsasamorphouseosinophilicdebris• Infiltratecomposedoflymphocytes,epithelioidcells,foamyhistiocytes,andconspicuousgiantcells,manyofwhichareToutontype,andothersarebizarreandangulated

• ComparedwithNLDandsubcutaneousGA,thenecrobiosisofNXGisfarmoreextensive,occurringinbroadbandswithextensiveinfiltratesofToutongiantcellsandfoamyhistiocytes

• Associatedwithparaproteinemia

Rheumatoid Nodule• Epidermisisoftennotrepresentedontheslide(adeeplesion)

• Densedepositoffibrin(confluent,large,eosinophilic)withsurroundingpalisading(“picketfence”)ofhistiocytes–palisadeistight,typicallylocatedinsubcutaneousfatorindeepreticulardermis

• ConsiderdeepGA,especiallyifthespecimenisfromachild

5.24 VASCULARAcroangiodermatitis of Mali

• CanlooklikeKaposi’sclinically• Biopsyshowsexaggeratedstasischangeswiththick“reduplicated”vessels,extravasatedRBCs,hemosiderin,fibrosis

Angiokeratoma• Numerousdilatedandcongestedcapillariesinthepapillarydermiswithoverlyingacanthosisandhyperkeratosisoftheepidermis

• Thrombosisiscommon• InFabry’sdiseasetherearecytoplasmicvacuolesrepresentinglipids

Angiolymphoid Hyperplasia • Oftenontheface• Intradermalill-defined,lobulatedmassofnumerousvascularchannelslinedbylargeroundedendothelialcellswithcopiouseosinophiliccytoplasm→theendothelialcellsareprotuberantandextendintothevessellumen

uTIPa5 types: Mibelli Corporis diffusum Circumscripta Papular Fordyce

Figure 5-82. Rheumatoid Nodule


• Eachvesselisseparate;sometimesprominentinflammatorycellinfiltrateoflymphocytes,eosinophilsandhistiocytes

Angiosarcoma• Oftenonscalp/sunexposedareasofelderly

• Ill-definedinfiltrativeintradermalmassofnumerousanastomosing,cleftingvascularchannelsofvaryingcaliberthatdissect(carve)throughthecollagen

• Endotheliumthatissingle-ordouble-layeredandplump,pleomorphicandmitoticallyactive(highlyatypical)→formingpapillaeorsolidnestswithinvascularlumina

• StainswithCD31• UnderEMthereareWeibel-Paladebodies

• Stewart-Treves:angiosarcomadevel- opinginlymphedematousarea (originallydescribedinpost-mastectomy

lymphedema)

Bacillary Angiomatosis• Lobulesofcapillarieswithprominentvascularendothelialcellswith“blueclouds”oforganismslocatedadjacenttovessels

• Neutrophilicinfiltratewithleukocytoclasis• Lookforulceration• NeedtostainorganismswithWarthin-Starry

Glomus Tumor• Commonacrally(subungual),canbeparoxysmallypainful

• DerivedfromcontractilecellsoftheSucquet-Hoyercanalandaredesmin-positive

• Veryuniformroundcellsaroundvascularspaces(thespacescanbequitedilatedandresembleacysticstructure)

• Solidtumorsarecomposedofsheetsofuniformcellsthatmightonlybetwocellsthick;don’tconfusewitheccrinespiradenoma

• Stainspositiveforsmoothmuscleactin,muscle-specificactin,andmyosin• Aninheritedformisautosomaldominantwithnumeroustumorsthatarenon-painfulandlocatedonthetrunk/extremities;histologicallyareoftenglomangiomas

Figure 5-83. Angiolymphoid Hyperplasia

Figure 5-85. Glomus Tumor

Figure 5-84. Angiosarcoma


Intravascular Papillary Endothelial Hyperplasia (Masson’s)• Thrombosedvessel(circularspacewithpinkfibrinwithin)withpapillatedfrondsprojectingintothecenter;thefrondsarelinedbyasinglelayerofendothelialcells

• Noatypia

Kaposi’s Sarcoma• Earlypatch:Increaseindermalvesselsshowingminimalatypiaandadmixtureoflymphocytesandplasmacellsassociatedwithhemosiderindepositsandpurpura;vesselsorientedparalleltoepidermisandmaydissectbetweencollagenbundles;trappingofRBC’s;aclueisthepromontorysignwheretherearenewvessels(clefts)formingaroundothervessels/adnexae

• Plaquestage:Obviousandextensivedermalvascularproliferationwithluminavaryingconsiderablyincaliber;prominentinflammation

• Nodularstage:Well-circumscribeddermalmassofvariablyeosinophilicspindlecells,scatteredbetweencellsarenumerousirregular,slit-like,vascularspaceslackingendotheliallining

• SpindlecellsareCD34-positiveandfocallypositiveforCD31;Ulex–positive;FactorVIIIpositive

• HHV-8positive

Liposarcoma, Myxoid• Complexplexiformnetworkofsmallthin-walledcapillariesinapatternresemblingchicken-wire

• Myxoidstroma• Deeplesion

Lymphangioma, Cavernous• Widely-dilated,irregularlyshapedspacesindermisandsubcutaneoustissuelinedbysinglelayerofblandendothelialcells

• Milkywhitesubstanceinvessels

Pyogenic Granuloma• Exophytic,lobulated,dermalmassofnumeroussmallcapillaries• Verycellular;oftenradiatingfromlarger,morecentralvessels,inalooseedematouscollagenousmatrix

• Mitosescommonlypresent,adjacentepidermisoftenacanthoticandformscollarette• NotrappingofRBC’s

Figure 5-86. Kaposi’s Sarcoma

Figure 5-87. Kaposi’s Sarcoma


Sclerosing Hemangioma• Likeafibroushistiocytomawithhemosiderinthrownin

• TheperipheryofthetumorresemblesaDFwithcollagentrapping;therecanbefoamycellsandmultinucleatedgiantcells

• LookforRBC’strappedbetweenspindlecells

5.25 MISCELLANEOUSAcanthosis Nigricans

• Elongatedpapillomatosis• Hyperkeratosis• Slightacanthosis• Occasionalkeratin-filledcysts

Accessory Tragus• Polypoidpapule• Peripheryrimmedbyvellushairs(nearepidermis)

• Cartilagemightnotbepresent;ifcartilagepresentitisatcenterofpolypandsurroundedbyabundantadiposetissue

Amalgam Tattoo• Mucosalsurface• Dermalpigmentwhichisdepositedinaveryfine,wigglypattern

• Occasionalclumping

Chloroma• Greenishtumor(grossly)inacutegranulocyticleukemia

• Greencolorsecondarytomyeloperoxidase

• Diffuseinfiltrateindermiswithmanyblastcells

• Chloracetateesterase-positive

Chondrodermatitis Nodularis Helicis• Notalwaysanulcer;thekeyisfibrosisordegeneratedcollagenbeneathanulcerorhyperplasticepidermis

• Granulationtissueflanksthefibrosis• Basecontainsabundantgranulationtissueandheavychronicinflammatorycellinfiltrate,oftendegenerativechangesincartilagewithhyalinizationorcalcification

Figure 5-88. Pyogenic Granuloma

Figure 5-89. Accessory Tragus

Figure 5-90. Chondrodermatitis Nodularis Helicis


Clear Cell Acanthoma• Clueisthatitlookslikepsoriasis,withregularacanthosis,butthecellsareclear/pale,andatlowpoweryoucanseeanabruptchangeoneachlateralmarginfromclear/palecellstonormal-appearing,lessacanthoticepidermis

• Associatedwithichthyosis

• Clear/palecellssecondarytoincreasedglycogencontentsecondarytoadeficiencyof phosphorylase

• PAS-positive

Coma Blister• Akintoerythemamultiformeofthesweatglands→eccrineglandsareredandnecrotic• Bothintra-andsubepidermalblistercanform• Causedbyhypoxemia

Elastosis Perforans Serpiginosa (EPS)• Perforatingdisorderwitheliminationofbasophilicelasticfibersthroughtheepidermis

• Increasedelastictissueindermisandpapillaefilledwithhomogeneouscoarseelasticfibers

• Centerofpapulehasaplugthatfillsawindingorstraightcanalunrelatedtopilosebaceousunit,extendingfrompapillarydermistoskinsurface

• Surroundingepidermishyperplasticandacanthoticandsometimespseudoepitheliomatous,growingdownwardtoengulfabnormalelasticfibersinaclaw-likefashion

Electrodessication Artefact• Epithelialcellsbecomeelongatedandspindledlike“chafsofwheat”

• Streamingofnuclei• Collagenamorphousandblue

Endometriosis, Cutaneous • Dilatedducts,endometrialglandslinedbytallcolumnarepithelium

• Fibrovascularcore(stroma)aroundductsthatappearapocrine• Oftendeeperindermiswithassociatedhemorrhage

PEARL

wAssociatedwithDown’ssyndrome,Ehlers-DanlostypeIV,Osteogenesisimperfecta,RothmundThompson,Marfan’s,Werner’s,acrogeria,penicillamine

Figure 5-91. Electrodessication Artefact

Figure 5-92. Endometriosis, Cutaneous


Eosinophilic (Pustular)Folliculitis• Histologicallythethreeformslooksimilar:eosinophil-richpustule,spongiosisofouterrootsheathofhairfollicle,superficialanddeepperifollicularandperivascularlymphocyticinfiltratewitheosinophils,neutrophils

Erythema Dyschromicum Perstans• Hyperkeratosiswithnormaloratrophicepidermis;basalcellvacuolardegenerationandcytoidbodyformation

• Markedpigmentaryincontinence• Mildperivascularorlichenoidinflammatorycellinfiltrateinsuperficialdermis

Freeze Artefact• Emptyvacuolesthroughoutepidermis

Gel Foam Artefact • Wavyforeignsubstance

Ochronosis• Exogenousandendogenoushistopathologyidentical

• Banana-shapedbrownishtoorange-yellowthickened,discoloredcollagen

Merkel Cell Carcinoma• Veryblueonlowpowerbutcellsareverypaleonhighpower

• Showsnodulesandsheetsofbasophiliccellswithvesicularnucleicontainingsmallnucleoliandinconspicuouscytoplasm

• Tumorcellscandissectthroughcollagen,markedmitoticactivity;tumorsstainpositiveforneuronspecificenolase,EMA,Ber-EP4,CAM5.2,CD57

PEARL

w Clinicallythereareprobablythreedifferentforms,oneseenascrustedpapulesontheoccipitalscalpofbabies,anotherseenmoreinJapanesepatientsontheface,andanotherconsistingofpruriticpapulesonthetrunkofHIVpatients

Figure 5-93. Eosinophilic (Pustular) Folliculitis

Figure 5-94. Erythema Dyschromicum Perstans

Figure 5-95. Gel Foam Artefact


• Characteristicparanuclearglobularcoexpressionofsimpleepithelialcytokeratins(CK20)andneurofilamentproteins

• Metastaticoatcellcarcinomalooksthesamebutstainsnegativeforcytokeratin20andispositivewithTTF-1

•AssociatedwithMerkelcellpolyomavirus

Necrolytic Migratory Erythema• Necrosisofthesuperficialepidermis(relativesparingofthelowerepidermis)(thenecrosiscanlooklikeconfluentparakeratosis)

• Intraepidermalcleftingandvesiculation• Differentialincludesothernutritionaldeficiencieslikezincdeficiency(acrodermatitisenteropathica),pellagra,biotindeficiency

Paraffinoma• Roundorovalspaceswithinthedermisandsubcutaneousfatina“swisscheese”pattern

• Foamyhistiocytesorgiantcellsmaylineedgesofthesecysticspaces,anddensefibrousscarringmaybeevident

Reactive Perforating Collagenosis• Wideneddermalpapillacontainsbasophilicdebriswithoutinflammation–“volcanoeffect”

• Overlyingepidermisthinned,andperilesionalepidermisacanthoticandenvelopsalteredcollagen

• Lookslikeanulcer,andfiberscarriedtosurfacebywidenedintercellularspaces• Inumbilicatedlesionsepidermisformsacup-shapeddepressionwithparakeratotickeratinocyticdebrisanddegeneratedverticallyorientedcollagen

Renal Carcinoma, Metastatic• Bloodvesselsarethecluetothediagnosis→veryvascular;bubbly,clearcellswithsomemitosesandcytologicatypia

Storiform Collagenoma (ScleroticFibroma)• Well-circumscribeddermalnodulecomposedofhyalinizedcollagenbundlesseparatedbycleftsandarrangedinastoriformpattern

• Hypocellular• Cowden’ssyndromeorGardner’ssyndrome

Figure 5-96. Ochronosis

Figure 5-97. Merkel Cell Carcinoma


Urticaria Pigmentosa• Mastcellsseenpredominantlyinpapillarydermis• Eosinophilspresentoften,basalcellhyperpigmentationofoverlyingepidermiscommonly,blisteringcanoccursubepidermally

• CanstainwithGiemsa,Leder,ortoluidineblue;aswellastryptaseandc-kit• Monomorphiccelldifferentialdiagnosis,whichincludesmastocytosis,glomustumor,and

poroma

Xanthelasma• Importantclueisrecognizingeyelidskin,eitherbyvellushairfolliclesorskeletalmuscleatthebaseofthebiopsy

• Lipidladenfoamcellswithinsuperficialdermis

Xanthoma, Eruptive• Foamyhistiocyteswithinsuperficialreticulardermis• Lymphocytesandneutrophilsmayinfiltrate• AlwayscheckforfoamcellsifyouarethinkingGA

5.26 CLUES FOR BOARD PURPOSES If the epidermis is absent, think of:

• Angioleiomyoma• Giantcelltumoroftendonsheath• Nodularfasciitis• Rheumatoidnodule• Gout• Hibernoma

If the section looks normal at low power, think of:• Macularamyloidosis• Anetoderma• Argyria• Atrophoderma• Café-au-laitspot• Connectivetissuenevus• Cutislaxa• Dermatophyteinfection• Tineaversicolor• GVHD• Ichthyosisvulgaris• Myxedema• Parapsoriasis• Porokeratosis• Scleroderma• Scleromyxedema• Urticaria• TMEP• Vitiligo


If there is necrosis in the epidermis, think of:• Nutritionaldeficiency(ifconfluentsuperficialnecrosisbelowstratumcorneum,withsparingoflowerepidermis)

• Erythemamultiforme(iffull-thicknessnecrosiswithanormalbasket-weavestratumcorneum)

• Herpes(ifnecrosisinsmallfociorassociatedwithafollicleandintermixedwithballooncells/giantcells/cellswithbasophilicviralchanges)

• Comabullae(lookfornecrosisofeccrineglands)

If you see giant cells, think of:• Reticulohistiocytosis(ifpalepinkand“oncocytic”)• Juvenilexanthogranuloma(ifTouton)• Xanthoma(ifmanyToutonwithfoamycells)• Tuberculosis(ifLanghansandforeign-body)• Herpes(ifassociatedwithnecrosisandballooncells)• Scar(ifforeign-body)• Rupturedcyst(ifforeign-body)• Giantcelltumoroftendonsheath(ifosteoclast-like)

If you see regular acanthosis at low power, think of:• Psoriasis• Bowen’s(lookforatypia/mitoses)• Clearcellacanthoma(lookforpalecellswithabruptdemarcationtonormal)• Dermatophytosis(hyphaewithinstratumcorneum)

If you see neutrophils in the stratum corneum, think of:• Psoriasis• Dermatophytosis• Pityriasislichenoides• Verruciformxanthoma

If you see parakeratosis above basket-weave stratum corneum, think of:• Dermatophytosis• Resolvingspongioticdisorder

If you see pseudoepitheliomatous hyperplasia overlying abscesses, think of:• Blastomycosis(lookforbroad-basedbuddingorganisms8-15microns)• Paracoccidioidomycosis(lookfor60micronmariner’swheel;singleyeastcellswillbe6-20microns)

• Chromoblastomycosis(lookforpigmented6-12micron“copperpennies”)• Coccidioidomycosis(lookfor10-80micronspherules)• Sporotrichosis(cigar-shapedorganismsthatareveryrareonbiopsy)• Halogenoderma/Bromoderma(notethatthisdiagnosisishistory-dependentandneedsexclusionofinfections,soitisunlikelythatyouwillmakethisdiagnosisontheBoards)

If you see grains, think of:• Botryomycosis(lookfor“blueclouds”ofbacteriasurroundedbyeosinophilicmaterialintheSplendore-Hoepplireaction)


• Actinomycosis/Nocardiosis(lookforthinfilamentsatperipheryofgrain)• Eumycetoma(lookforthickhyphaeatperipheryofgrain)

Gram-positive sulfur granules differential:• Staphylococcalabscess• Actinomycosis(pinkandfilamentousattheedgeoflesion)• Nocardia(canvisualizeorganismswithFitestain)

If you see hyperkeratosis over an atrophic epidermis, think of:• Lichensclerosusetatrophicus• Flegel’sdisease• Discoidlupuserythematosus

If you see a dome-shaped/cone-shaped silhouette at low power, think of:• Accessorydigit(lookfornervesindermis)• Acquireddigitalfibrokeratoma(hyperkeratosis,dermalfibrosis)• Accessorynipple(hyperpigmentedacanthosis,smoothmusclebundlesindermis,ductsindeepdermis)

• Accessorytragus(numerousvellus/smallhairfolliclesindermis/cartilagemaybepresent)

If you see a very rectangular-shaped punch biopsy “i.e., square biopsy sign,” think of:• Scleromyxedema• Scleredema• Scleroderma• Necrobiosislipoidicadiabeticorum

If you see clear cells, think of:• Metastaticrenalcellcarcinoma(lookforhemorrhage)• Clearcellsquamouscellcarcinoma/Bowen’s(lookforatypia/mitoses/squamouspearls)• Trichilemmoma(lookforpalisadingofbasallayerandthickbasementmembrane)• Clearcellacanthoma• Hidradenoma• Note:makesurethecellsareclearcells,notballooncellsorsebaceouscells

If you see eosinophilic spongiosis, think of:• Incontinentiapigmenti,pemphigus,BP,chronicbullousdiseaseofchildhood,pemphigoidgestationis,PUPPP,insect-bitereactions,atopicdermatitis,contactdermatitis,Grover’sdisease,drugreaction

• Thereisclearingofkeratinocyteswithindwellingeosinophils,butnoabscessformation

5.27 “BODIES”Asteroid Body

• EosinophilicamorphousmaterialseeninsporotrichosisOR• Stellateinclusionsseeninsarcoid,berylliosis

Birbeck Granules• Seenonelectronmicroscopy• Tennis-racquet-shapedcytoplasmicbodiesinLangerhanscells


Caterpillar Body• Paleamorphouspinklinearstructuresintheepidermisofporphyriacutaneoustarda• RepresentstypeIVcollagen

Civatte Body• Apoptoticcellremnantsinepidermis

Colloid Body• Apoptoticcellremnantsinpapillarydermis

Comma-shaped Body• Seenonelectronmicroscopy• Associatedwithhistiocytoseslikebenigncephalichistiocytosis(non-specific)

Cowdry A body (LipschutzBody)• Intranucleareosinophilicglobulesseeninherpesinfection

Cowdry B Body• Intranuclearinclusionsseeninadenovirusandpoliovirusinfection

Donovan Body• Intracytoplasmicbacteriaingranulomainguinale

Dutcher Body• “Pseudo”-nuclearinclusionssecondarytocollectionsofimmunoglobulininthecytoplasmthatpushintothenucleusofplasmacells

Guarnieri Body• Eosinophiliccytoplasmicinclusionsseeninsmallpox

Henderson-Paterson Body• LargeeosinophiliccytoplasmicinclusionsthatfillthecellseeninMolluscumlesions

Kamino Body• EosinophilicglobularmassesofvaryingsizesseenatandaboveDEJ• ConsideredtobeahelpfulmarkerforSpitznevus

Leishman-Donovan Body• Intracytoplasmic,nonflagellatedparasiteseeninleishmaniasis

Lipschutz Body (CowdryABody)• Intranuclearinclusionsinepithelialorneuronalcellsseeninherpesinfection

Medlar Body• a.k.a.scleroticbody,“copperpenny,”hotcrossbun• Seeninchromoblastomycosis

Michaelis-Gutman Body• Concentric,laminated,calcifiedbodieswithinandexternaltocellsseeninmalakoplakia


Negri Body• Cytoplasmicinclusions(neuronal)seeninrabies

Papillary Mesenchymal Body• Structurethoughttobeanabortiveattemptoffibroblaststoformmesenchymenecessaryforhairinduction,reminiscentofearlyhairgerm

• Seenintrichoblastomaandtrichoepithelioma

Psammoma Body• Concentric,laminated,calcifiedbodiesseeninpapillarythyroidcarcinoma,benignnevi,meningiomas,andotherconditions

Russell Body• Inclusionssecondarytocollectionsofimmunoglobulininthecytoplasmofplasmacells• Seeninrhinoscleroma,granulomainguinale,syphilis

Schaumann Body• Concentric,laminated,calcifiedinclusionsseeninsarcoidandothergranulomatousdisorders

Verocay Body• Palisadednucleioneithersideofacentralpinkareainschwannoma

Weibel-palade Body• Cytoplasmicmarkerofendothelialcells

Worm-shaped Body• Seenonelectronmicroscopy• Associatedwithhistiocytoseslikebenigncephalichistiocytosis(non-specific)

Zebra Body• Seenonelectronmicroscopyinmucopolysaccharidoses

ACKNOWLEDGMENTS

RonaldBarr,MDScottBinder,MDBruceE.Strober,MD,PhD

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NOTES


NOTES


NOTES

Health & Medicine

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