T Cell Low Grade Lymphomas

General Principles General Principles  Usually Primary Skin lymphomas  Typically indolent Course  Conservative management  Usually skin based  Not curable

T Cell Low Grade Lymphomas Cutaneous T cell Lymphomas Cutaneous T cell Lymphomas Mycoses Fungoides Mycoses Fungoides  Classic MF  Granulomatous Slack Skin  Pagetoid Reticulosis (epidermal)  Follicular Mucinosis MF Sezary Syndrome Sezary Syndrome Primary cutaneous CD 30 + T cell Lymph Primary cutaneous CD 30 + T cell Lymph  Lymphomatoid Papulosis  Primary Cutaneous Anaplastic Large Cell lymphoma

Mycoses Fungoides 0.5% NHL 0.5% NHL 50% of all primary skin lymphomas 50% of all primary skin lymphomas Long Natural History Long Natural History WHO – EORTC Classification of Skin Lymphomas WHO – EORTC Classification of Skin Lymphomas

Copyright ©2003 American Society of Hematology. Copyright restrictions may apply. Maslak, P. ASH Image Bank 2003;2003: Figure 3. Sezary cell in the peripheral blood with a deep nuclear cleft

MF Clinical Clinical  Patches, non sun exposed, atrophy / scaling, salmon pink, hyepr/hypo pigment Diagnosis Diagnosis  Proper Skin Biopsy  Atypical lymphs papillary dermis  Epidermotropism  Pautrier microabscess  Immunohistochemistry  + CD 3, 4, 45RO  - CD 8, 30  Loss of T cell antigens – CD7  TCR 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 >1cm T3 – tumours >1cm T4 - generalized erythroderma >80% T4 - generalized erythroderma >80% N0 - no abnormal lymph nodes N0 - no abnormal lymph nodes N1 – clinically abnormal, histology negative N1 – clinically abnormal, histology negative N1a clone - / N1b clone +N1a clone - / N1b clone + N2 – clinically abnormal, histology positive N2 – clinically abnormal, histology positive N2a clone - / N2b clone +N2a clone - / N2b clone + N3 – clinically abnormal, effacement of lymph node N3 – 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 burden PB2 – high blood tumour burden >= 1000/μl or CD4/CD8 ratio >10>= 1000/μl or CD4/CD8 ratio >10 M0 – no visceral organ involved M0 – no visceral organ involved M1 – path confirmed visceral organ involved M1 – path confirmed visceral organ involved

MF Staging TNMB Ia Ia Ib Ib IIa IIa IIb IIb IIIa IIIa IIIb IIIb IVa IVa IVa IVa IVb IVb

MF Prognosis Low Risk Low Risk  Ia / IIa  Med Surv yrs (age matched) Intermediate Risk Intermediate Risk  Stage III  Med Surv 5 yrs High Risk High Risk  Nodal/visceral IV  Med Surv 2 yrs

Sezary Syndrome Erythroderma Erythroderma  >90%  Thick, edematous  Thermal dysregulation Generalized lymphadenopathy Generalized lymphadenopathy Blood involvement Blood involvement  1x10 9 /L  5% of Lymphs  CD4:CD8 ratio >10 (n 10 (n<3)  High LDH / Ca Median Survival <2 yrs Median Survival <2 yrs

Therapeutic Options Skin Based Treatments Skin Based Treatments  PUVA  Focused radiation  TSEB  Narrow Band UVB  Topical Steroids  Topical Retinoids  Topical Imiquimod  Topical Nitrogen Mustard

Radiation Local Rads Local Rads  Local control  Tumour stage disease  Stage 1a disease in one rad field  Potentially curative Total Skin Electron Beam Radiation Total Skin Electron Beam Radiation  6 week course,  Hamilton Juravinski Cancer Centre

Therapeutic Options Systemic Systemic  Interferon alpha  Oral Retinoids  Extracorporeal Photophoresis (ECP)  Chemotherapy  Other  HiDAC inhibitors - vorinostat  Low dose Methotrexate  Dinileukin diftitox  Pentostatin  IL12  Campath

Principles of Management Immune based therapy Immune based therapy  Progressive disease associated with immune dysregulation  Decreases in Th1 response IL 12, INFalpha, NKcells, CD8 TcellsIL 12, INFalpha, NKcells, CD8 Tcells  Therapies that add to immunosuppression can produce more rapid disease progression

Principles of Management Early Stage Disease Early Stage Disease  Survival is similar to age matched controls  Skin based treatments to start  Add immunomodulatory agents if needed  Interferon has best evidence  Maintenance therapy  No change in OS

Principles of Management Advanced Stage Disease Advanced Stage Disease  Multiple immunomodulatory agents  Systemic and Skin based therapies combined  Maintenance Therapy  Stay away from systemic chemo if possible  if pushed – purine analogues, MTX  ? Change in overall survival

Primary Cutaneous CD30 + Lymphomas Lymphomatoid Papulosis Lymphomatoid Papulosis  Chronic recurrent self healing papulonudular skin eruption with histologic features of lymphoma  Large CD30 cells & inflammatory cells  Benign course  Treatment  Observation  Local rads  Low dose methotrexate

Primary Cutaneous CD30 + Lymphomas Anaplastic Large Cell lymphoma of Skin Anaplastic Large Cell lymphoma of Skin  CD 30 + large cells, CD4+, ALK1-  Can be solitary of mulitifocal  Need to be sure no systemic disease  Prognosis – 5 yr survival 95%  Treatment  Solitary – local rads  Multifocal – CHOP / methotrexate