1. T Cell Low Grade Lymphomas

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

3. 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

4. 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

5. 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

6. 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

7. 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

8. MF Staging TNMB Ia 1000-1 Ia 1000-1 Ib 20 00-1 Ib 20 00-1 IIa1-21-200-1 IIa1-21-200-1 IIb3 0-2 00-1 IIb3 0-2 00-1 IIIa40-2 0 0-1 IIIa40-2 0 0-1 IIIb40-201 IIIb40-201 IVa 1 1-40-202 IVa 1 1-40-202 IVa 2 1-4300-2 IVa 2 1-4300-2 IVb 1-40-310-2 IVb 1-40-310-2

9. MF Prognosis Low Risk Low Risk  Ia / IIa  Med Surv 10-12 yrs (age matched) Intermediate Risk Intermediate Risk  Stage III  Med Surv 5 yrs High Risk High Risk  Nodal/visceral IV  Med Surv 2 yrs

10. 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

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

12. 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

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

14. 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

15. 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

16. 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

17. 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

18. 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