WHOEORTCClassification,2005

Mycosisfungoides MFvariants
FolliculotropicMF(includesfollicularmucinosis) Pagetoidreticulosis Granulomatousslackskin Szarysyndrome AdultTcellleukemia/lymphoma(ATLL) PrimarycutaneousCD30+lymphoproliferative disorders

WHOEORTCClassification,2005
SubcutaneouspanniculitislikeTcelllymphoma ExtranodalNK/Tcelllymphoma,nasaltype Primarycutaneousaggressiveepidermotropic CD8+Tcelllymphoma Cutaneous/ Tcelllymphoma PrimarycutaneousCD4+small/mediumsized pleomorphicTcelllymphoma

CutaneousTcelllymphoma
ThetermCTCLshouldnotbeusedasa synonymformycosisfungoides Pathologyrequestformshouldalwaysinclude clinicalinformationincludingprovisional diagnosis Manydiseases,malignantandotherwisemay showfeaturesidenticaltomycosisfungoides

Mycosisfungoides:epidemiology
0.360.46per105 ofpopulation 103 newcasesperyearinUS 2M:1F Blacks>whites(2:1) 4th6th decades Rarelypresentsinchildren

Mycosisfungoides Majorsubtypes
Patchstage Plaquestage Poikilodermaatrophicansvasculare Tumorstage Mycosisfungoidesintransformation Erythrodermicmycosisfungoides

Raresubtypesofmycosisfungoides
Bullous Hypopigmented/hyperpigmented Verrucous/hyperkeratotic Pustular Lichenoidpapular Palmoplantarpsoriasiform Granulomatous Necrobioticmycosisfungoides Acanthosisnigricanslike Mycosisfungoides&ichthyosis Vesiculobullousmycosisfungoides Purpuricmycosisfungoides Unilesionalmycosisfungoides Syringotropic Mycosisfungoideswithdermalmucin

Mycosisfungoides Generalhistologicalfeatures
Lymphocyteswithhalos Linearepidermotropism EpidermalSzarycells Pautriers microabscesses Epidermallymphocytes largerthandermalones Lymphocyteatypia

Patchstagemycosisfungoides
Irregular,asymmetricalslightlyscalypatches Trunk,limbs,breastsandflexures Canbewidespread Clinicaldifferentialincludessuperficialscaly dermatitis(digitatedermatosis),psoriasis, eczemaetc

Patchstagemycosisfungoides
Featuresoftensubtle Mayrequiremultiple biopsies Oftenonlyfocal epidermotropism Pautriermicro abscessesrare Featuresmaybe maskedbytreatment

Patchstagemycosisfungoides
Acanthosisoratrophy Variableparakeratosis atypicallymphocytes withhalo Palisadinghelpful feature FewSzarycells Pautriermicroabscess variablypresent

Plaquestagemycosisfungoides
Induratedplaques Oftenbizarremorphology Centralclearingleadstoannularor serpiginouslesions Hyperkeratosissometimesmarkede.g.on palmsandsoles

Plaquestagemycosisfungoides
Featuresmoreobvious Psoriasiformhyperplasia Markedepidermotropism Pautriermicroabscesses common Szarycellsconspicuous Atypicaldermalinfiltrate Dermalscarringcommon

Poikilodermaatrophicans vasculare
Smallnumbersofplaquesonbreasts, buttocks,hips,abdomen,majorflexures Atrophy,telangiectasia,hypopigmentation, hyperpigmentation Perhapsfewerprogresstotumorstage disease

Poikilodermaatrophicans vasculare
Hyperkeratosis Epidermalatrophy Interfacechange Cytoidbodies Pigmentincontinence Epidermotropism Szarycellscommon Bandlikedermal infiltrate

Tumorstagemycosisfungoides
Smallpercentageofpatientsprogressto tumorstagedisease Tumornodulesofteninabackgroundof plaquestagedisease Face,scalp,intertriginoussitesoftenaffected butcanbeanywhere

Tumorstagemycosisfungoides
Epidermotropismoften lost Densedermalinfiltrate Szarycellsmaybe inconspicuous Markedpleomorphism Markedmitoticactivity Tumorgiantcellsmay mimicRScells

Mycosisfungoides immunohistochemistry
CD2+,CD4+,CD45RO+, CLA+ VariableCD5&CD7 CD25+/ (IL2receptor) CD30expression correlateswith transformation RareCD8+variants TCRgene rearrangement

Transformation
1023% Survival1136months >/=25%composedof largecellsoradistinct nodule Vesicularor hyperchromaticnuclei Prominentnucleoli Markedpleomorphism Mitosesabundant

Folliculotropicmycosisfungoides (Follicularmucinosis)
Rarevariantwithfollicularinvolvement Variablemucinosis(follicularmucinosis) Middleagedtoelderlymales Head&neck(particularlyface&scalp),trunk

Folliculotropicmycosisfungoides (Follicularmucinosis)
Patches,plaquesorgroupedfollicular papules Alopecia&pruritus Acneiformlesionssuchascomedonelike cysts,pustules&milia Mucinorrhea Difficulttotreat
Poorer prognosis than classic MF

Folliculotropicmycosisfungoides
Follicularinfiltrationby mediumtolarge atypicallymphocytes ?MediatedbyICAM1 Variablemucin Basaloidfollicular hyperplasia Variableepidermal involvement

Folliculotropicmycosisfungoides
Follicularinterface change Syringotropism Blastcells Giantcells Variableeosinophilia Largecell transformationwith CD30expression

Folliculotropicmycosisfungoides Differentialdiagnosis
Lichenplanopilaris Pseudolymphomatousfolliculitis Eosinophilicfolliculitis Follicularlymphomatoidpapulosis Alopeciamucinosa

Alopeciamucinosa
Noreliablefeaturesdistinguishbetween idiopathicalopeciamucinosa&folliculotropic MF >50%showaTCRgenerearrangementbyPCR

Causesoffollicularmucinosis
Folliculotropicmycosisfungoides Ofujisdisease HIVassociatedeosinophilicfolliculitis Angiolymphoidhyperplasiawitheosinophilia Pityrosporumfolliculitis Arthropodbite

Syringotropicmycosisfungoides
Exceedinglyrare Papulesonpatchesorplaques Localizedhairloss GenerallyaccompaniesfolliculotropicMF Scarring&ulceration 2m:1F Difficulttotreat

Granulomatousmycosisfungoides
4%ofcasesofMF Rareassociations: sarcoidosis,generalized GAandanichthyosis presentation Sarcoidal Tuberculoid GAlike,NLlike Elastophagocytosis Lymphophagocytosis

Lymphomaswhichmaybe associatedwithgranulomata
Mycosisfungoides Granulomatousslackskin CD4+small/mediumTcell lymphoma ATLL Subcutaneouspanniculitis likeTcelllymphoma Cutaneousmarginalzone Bcelllymphoma

Granulomatousslackskin
<50documentedcases Caucasians Predilectionformales 3rd5th decades Pendulousfoldsinflexures +/ backgroundMF 2nd lymphomain50%ofcases

Granulomatousslackskin
Denseinfiltrateof pleomorphic lymphocytes +/ MFcells Granulomata Giantcells Elastophagocytosis Lymphophagocytosis +/ Epidermalchanges

Histologicaldifferentialdiagnosis ofmycosisfungoides
Superficialscalydermatitis Tcellpseudolymphoma Szarysyndrome AdultTcellleukemia/lymphoma(ATLL) CD8+primarycutaneousepidermotropicT celllymphoma Primarycutaneous/ Tcelllymphoma Actinicreticuloid

Superficialscalydermatitis
AKAdigitatedermatosisorsmallplaque parapsoriasis Middleagedadults Persistentpink,scalypatchesoftenwithadigitate appearance Trunk&arms+ Uniforminsize,shape&color

Superficialscalydermatitis
Parakeratosisor hyperkeratosis Focalmildspongiosis Superficial perivascular lymphocyticinfiltrate Noatypia CD4>CD8,CD2+, CD3+,CD5+,CD7+/

CutaneousTcellpseudolymphoma
Lymphomatoiddrugreactions Lymphomatoidcontactdermatitis Chronicactinicdermatitis(actinicreticuloid) Pseudolymphomatousangiokeratoma Tcellrichangiomatoidpolypoid pseudolymphoma Pseudolymphomatousfolliculitis AtypicalLPDofHIVinfection

Tcellpseudolymphomatous DrugReactions
Superficialperivascular, bandlikeordiffuse atypicalinfiltrate Eosinophilsoften conspicuous Epidermotropism Szarycells Microabscessesrare Histiocytes,giantcells& granulomata+/

TcellPseudolymphomatous DrugReactions
Immunohistochemistry CD3+,CD4+mostcommon CD8+variantsrare CD30+exceptional Tcellreceptorrearrangementsareusually polyclonal

Tcellrichangiomatoidpolypoid pseudolymphoma(TRAPP)
Solitary <1.0cmpolypoidangiomatouspapule Head&trunk Resemblespyogenicgranuloma Youngadults Predilectionforfemales

Tcellrichangiomatoidpolypoid pseudolymphoma(TRAPP)
Nonulcerated polypoidlesion Grenzzone Conspicuous vasculature Maturelymphocytes Eosinophils,plasma cells

CD3

PrimarycutaneousCD8+aggressive epidermotropiccytotoxicTcelllymphoma
<1%ofCTCL Adults Generalized,rapidlyprogressive Patches,plaques,nodules,tumors Metastasescommon Meansurvival32months

Histologicalfeatures
Epidermotropic medium/large pleomorphicT cells Immunoblasts Bandlikedermal component Necrosiscommon

Immunohistochemistry
CD3+,CD8+,CD7+ CD4,CD2,CD5 TIA1+ Perforin&granzymeB variable EBV TIA1

AdultTcellleukemia/lymphoma
HTLV1infection Transfusion Bloodproducts IVdrugabuse Sexualintercourse Transplacentally Breastmilk Characteristiclonglatentperiod

AdultTcellleukemia/lymphoma
AcuteATLL ChronicATLL SmolderingATLL LymphomatousATLL Skinlesions(4372%) Papules,plaques,nodules,tumors Erythroderma M(6.6%),F(2.1%)

AdultTcellleukemia/lymphoma
Perivascular,nodular, diffuseinfiltrates Small/mediumirregular pleomorphicnuclei Blastforms,Mycosis, ReedSternberglikecells Epidermotropism Pautriermicroabscesses Granulomatavariable

AdultTcellleukemia/lymphoma
CD2+,CD3+,CD4+, CD5+,CD25+ CCR4+,FoxP3+ CD7 CD8+variantrare CD4+/CD8+rare CD30variable ALK1

Primarycutaneouspleomorphic small/mediumsizedTcelllymphoma
2%ofallCTCL Singletumornodule Lessoftenmultiple lesions Head,neck,upper trunk F>M Elderlymostlyaffected 5yearsurvival 80%

Primarycutaneouspleomorphic small/mediumsizedTcelllymphoma
Uniformsmall/medium lymphocytes Hyperchromaticnuclei MFcellsabsent Mitosesuncommon Epidermotropismrare Folliculotropismrare Variableinflammatory cells

Primarycutaneouspleomorphic small/mediumsizedTcelllymphoma
CD3+,CD4+ PD.1+,CXCl13+, BCL6+,CD10+ (follicularTcell markers) VariableCD2,CD7 VariableBcells CD30variable

/ Tcelllymphoma
1%CTCL Medianage60years Plaques,nodules&subcutaneouslesions Trunk&limbs Hemophagocyticsyndromein25% Mediansurvival15/12

/ Tcelllymphoma
Threevariants:Plaques MFlike,tumorsare diffuse&involve subcutis,subcutaneous panniculitislikeTcell lymphoma Medium/largecells Necrosiscommon Angioinvasioncommon

/ Tcelllymphoma
CD2+,CD3+,CD7+ CD56usuallypositive CD5 CD4&CD8generallyabsent TIA1+,perforin+,granzymeB+ EBV / surface expression TCR- & TCR- clonal rearrangement