T Cell Low Grade LymphomasT Cell Low Grade Lymphomas

T Cell Low Grade Lymphomas

General PrinciplesGeneral Principles Usually Primary Skin lymphomasUsually Primary Skin lymphomas Typically indolent CourseTypically indolent Course Conservative managementConservative management

Usually skin basedUsually skin based Not curableNot curable

T Cell Low Grade Lymphomas Cutaneous T cell LymphomasCutaneous T cell Lymphomas

Mycoses FungoidesMycoses Fungoides Classic MFClassic MF Granulomatous Slack SkinGranulomatous Slack Skin Pagetoid Reticulosis (epidermal)Pagetoid Reticulosis (epidermal) Follicular Mucinosis MFFollicular Mucinosis MF

Sezary SyndromeSezary Syndrome Primary cutaneous CD 30 + T cell LymphPrimary cutaneous CD 30 + T cell Lymph

Lymphomatoid PapulosisLymphomatoid Papulosis Primary Cutaneous Anaplastic Large Cell Primary Cutaneous Anaplastic Large Cell

lymphoma lymphoma

Mycoses Fungoides

0.5% NHL0.5% NHL 50% of all primary skin lymphomas50% of all primary skin lymphomas Long Natural HistoryLong Natural History WHO – EORTC Classification of Skin WHO – EORTC Classification of Skin

LymphomasLymphomas

Copyright ©2003 American Society of Hematology. Copyright restrictions may apply.

Maslak, P. ASH Image Bank 2003;2003:100636

Figure 3. Sezary cell in the peripheral blood with a deep nuclear cleft

MF ClinicalClinical

Patches, non sun exposed, atrophy / scaling, Patches, non sun exposed, atrophy / scaling, salmon pink, hyepr/hypo pigmentsalmon pink, hyepr/hypo pigment

DiagnosisDiagnosis Proper Skin BiopsyProper Skin Biopsy

Atypical lymphs papillary dermisAtypical lymphs papillary dermisEpidermotropismEpidermotropismPautrier microabscessPautrier microabscess

ImmunohistochemistryImmunohistochemistry+ CD 3, 4, 45RO+ CD 3, 4, 45RO- CD 8, 30- CD 8, 30Loss of T cell antigens – CD7Loss of T cell antigens – CD7

TCR gene rearrangementTCR gene rearrangement

MF – Staging TMN T0 - clinical/ histological suspicious lesions T0 - clinical/ histological suspicious lesions T1- limited patches < 10%T1- limited patches < 10% T2 - generalized > 10%T2 - generalized > 10% T3 – tumours >1cmT3 – tumours >1cm T4 - generalized erythroderma >80%T4 - generalized erythroderma >80%

N0 - no abnormal lymph nodesN0 - no abnormal lymph nodes N1 – clinically abnormal, histology negativeN1 – clinically abnormal, histology negative

• N1a clone - / N1b clone +N1a clone - / N1b clone + N2 – clinically abnormal, histology positiveN2 – clinically abnormal, histology positive

• N2a clone - / N2b clone +N2a clone - / N2b clone + N3 – clinically abnormal, effacement of lymph nodeN3 – clinically abnormal, effacement of lymph node

PB0 - atypical circulating cells < 5%PB0 - atypical circulating cells < 5% PB1 – atypical circulating cells > 5% PB1 – atypical circulating cells > 5% PB2 – high blood tumour burdenPB2 – high blood tumour burden

• >= 1000/>= 1000/μμl or CD4/CD8 ratio >10l or CD4/CD8 ratio >10

M0 – no visceral organ involvedM0 – no visceral organ involved M1 – path confirmed visceral organ involvedM1 – path confirmed visceral organ involved

MF Staging

TT NN MM BB Ia Ia 11 00 00 0-10-1 Ib Ib 22 0 0 00 0-10-1 IIaIIa 1-21-2 1-21-2 00 0-10-1 IIbIIb 3 3 0-20-2 00 0-10-1 IIIaIIIa 44 0-2 0-2 0 0 0-10-1 IIIbIIIb 44 0-20-2 00 11 IVaIVa11 1-41-4 0-20-2 00 22 IVaIVa22 1-41-4 33 00 0-20-2 IVb IVb 1-41-4 0-30-3 11 0-20-2

MF Prognosis Low RiskLow Risk

Ia / IIaIa / IIa Med Surv 10-12 yrs (age matched)Med Surv 10-12 yrs (age matched)

Intermediate RiskIntermediate Risk Stage IIIStage III Med Surv 5 yrsMed Surv 5 yrs

High RiskHigh Risk Nodal/visceral IVNodal/visceral IV Med Surv 2 yrsMed Surv 2 yrs

Sezary Syndrome ErythrodermaErythroderma

>90%>90% Thick, edematousThick, edematous Thermal dysregulationThermal dysregulation

Generalized lymphadenopathyGeneralized lymphadenopathy Blood involvementBlood involvement

1x101x1099/L/L 5% of Lymphs5% of Lymphs CD4:CD8 ratio >10 (n<3)CD4:CD8 ratio >10 (n<3) High LDH / CaHigh LDH / Ca

Median Survival <2 yrsMedian Survival <2 yrs

Therapeutic Options Skin Based TreatmentsSkin Based Treatments

PUVAPUVA Focused radiationFocused radiation TSEBTSEB

Narrow Band UVBNarrow Band UVB Topical SteroidsTopical Steroids Topical RetinoidsTopical Retinoids Topical ImiquimodTopical Imiquimod Topical Nitrogen MustardTopical Nitrogen Mustard

Radiation

Local RadsLocal Rads Local controlLocal control Tumour stage diseaseTumour stage disease Stage 1a disease in one rad fieldStage 1a disease in one rad field

Potentially curativePotentially curative

Total Skin Electron Beam RadiationTotal Skin Electron Beam Radiation 6 week course, 6 week course, Hamilton Juravinski Cancer CentreHamilton Juravinski Cancer Centre

Therapeutic Options SystemicSystemic

Interferon alphaInterferon alpha Oral RetinoidsOral Retinoids Extracorporeal Photophoresis (ECP)Extracorporeal Photophoresis (ECP)

ChemotherapyChemotherapy

OtherOther HiDAC inhibitors - vorinostatHiDAC inhibitors - vorinostat Low dose MethotrexateLow dose Methotrexate Dinileukin diftitoxDinileukin diftitox PentostatinPentostatin IL12IL12 CampathCampath

Principles of Management

Immune based therapyImmune based therapy

Progressive disease associated with immune Progressive disease associated with immune dysregulationdysregulation

Decreases in Th1 responseDecreases in Th1 response• IL 12 , INFalpha, NKcells, CD8 TcellsIL 12 , INFalpha, NKcells, CD8 Tcells

Therapies that add to immunosuppression Therapies that add to immunosuppression can produce more rapid disease progressioncan produce more rapid disease progression

Principles of Management

Early Stage DiseaseEarly Stage Disease Survival is similar to age matched controlsSurvival is similar to age matched controls

Skin based treatments to startSkin based treatments to start Add immunomodulatory agents if neededAdd immunomodulatory agents if needed

Interferon has best evidenceInterferon has best evidence Maintenance therapyMaintenance therapy No change in OSNo change in OS

Principles of Management

Advanced Stage DiseaseAdvanced Stage Disease Multiple immunomodulatory agentsMultiple immunomodulatory agents Systemic and Skin based therapies combinedSystemic and Skin based therapies combined Maintenance TherapyMaintenance Therapy Stay away from systemic chemo if possibleStay away from systemic chemo if possible

if pushed – purine analogues, MTXif pushed – purine analogues, MTX ? Change in overall survival? Change in overall survival

Primary Cutaneous CD30 + Lymphomas Lymphomatoid PapulosisLymphomatoid Papulosis

Chronic recurrent self healing papulonudular Chronic recurrent self healing papulonudular skin eruption with histologic features of skin eruption with histologic features of lymphomalymphoma

Large CD30 cells & inflammatory cellsLarge CD30 cells & inflammatory cells Benign courseBenign course TreatmentTreatment

ObservationObservationLocal radsLocal radsLow dose methotrexateLow dose methotrexate

Primary Cutaneous CD30 + Lymphomas Anaplastic Large Cell lymphoma of SkinAnaplastic Large Cell lymphoma of Skin

CD 30 + large cells, CD4+, ALK1-CD 30 + large cells, CD4+, ALK1- Can be solitary of mulitifocalCan be solitary of mulitifocal Need to be sure no systemic diseaseNeed to be sure no systemic disease Prognosis – 5 yr survival 95%Prognosis – 5 yr survival 95% TreatmentTreatment

Solitary – local radsSolitary – local radsMultifocal – CHOP / methotrexateMultifocal – CHOP / methotrexate