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MYCOSIS FUNGOIDES

MYCOSIS FUNGOIDES SHEIKHA. MYCOSIS FUNGOIDES. Professor Anwar Sheikha MD, FRCP, FRCPath., FCAP, FRCPA, FRCPI, FACP Senior Consultant Clinical & Lab. Hematologist Clinical Professor of Hematology

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MYCOSIS FUNGOIDES

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  1. MYCOSIS FUNGOIDES SHEIKHA MYCOSIS FUNGOIDES

  2. Professor Anwar Sheikha MD, FRCP, FRCPath., FCAP, FRCPA, FRCPI, FACP Senior Consultant Clinical & Lab. Hematologist Clinical Professor of Hematology University of Mississippi Medical Center, Jackson, Mississippi Professor of Hematology, University of Salahaddin, Erbil, Kurdistan, IRAQ Owner & C.E.O., Raziana Company for Health Services, Hawler, IRAQ

  3. MYCOSIS FUNGOIDES SHEIKHA MF is a cutaneous lymphoma of mature CD4+ T cells The commonest cutaneous T-cell lymphoma It has unique clinical & histologic features Not all cutaneous T-cell lymphomas are MF MYCOSIS FUNGOIDES SEZARY SYNDROME MF/SZ

  4. MYCOSIS FUNGOIDES SHEIKHA Professor Lennert, Keil Classification

  5. MYCOSIS FUNGOIDES SHEIKHA

  6. W.H.O. CLASSIFICATION OF LYMPHOID NEOPLASMS B T& NK NHL Precursor T-cell neoplasms Precursor B-cell neoplasms * Mature (Peripheral) B-cell neoplasms Mature (Peripheral) T-cell neoplasms Nodular Lymphocyte-Predominant Hodgkin Lymphoma Classical Hodgkin Lymphoma HD

  7. W.H.O. CLASSIFICATION OF LYMPHOID NEOPLASMS *T-cell Prolymphocytic Leukemia *T-cell Granular Lymphocytic Leukemia *Aggressive NK-cell Leukemia *Adult T-cell Leukemia/Lymphoma (HTLV1) *Extranodal NK/T-cell Lymphoma. Nasal type *Entropathy-type T-cell Lymphoma *Hepatosplenic γδ T-cell Lymphoma *Subcutaneous Panniculitis-like T Lymphoma *Mycosis Fungoides /Sézary Syndrome *Anaplastic Large-cell Lymphoma/T/null, skin type *Peripheral T-cell Lymphoma, not otherwise characterized *Angioimmunoblastic T-cell Lymphoma *Anaplastic Large-cell Lymphoma/T/null, systemic type NHL T& NK Mature (Peripheral) T-cell neoplasms *

  8. MYCOSIS FUNGOIDES SHEIKHA

  9. MYCOSIS FUNGOIDES SHEIKHA Incidence: 3 per million (0.29 per 100,000 population in USA) 2% of all new cases of NHL Age: Older adults (55 to 60) Male/Female: 2/1 TUMOR STAGE PATCH STAGE PLAQUE STAGE ERYTHRODERMA “SEZARY” Cerebriform “Sezary” Cells Epidermo- tropism

  10. MYCOSIS FUNGOIDES SHEIKHA Patch Plaque Tumor Stage MF patches are usually distributed in sun-shielded areas such as those covered by a bathing suit or intertriginous regions. Sézary Syndrome

  11. Various Cutaneous Manifestations of Mycosis Fungoides

  12. MYCOSIS FUNGOIDES SHEIKHA EPIDERMOTROPIC The cardinal features of MF is infiltration of epidermis and then dermis by Atypical Cerebriform Lymphoid Cells

  13. Mycosis Fungoides: A Cancer of Skin-Homing T Cells Girardi M et al. N Engl J Med 2004;350:1978-1988

  14. Multiple discrete & confluent plaques of cutaneous T-cell lymphoma “MF”

  15. Multiple plaques of cutaneous T-cell lymphoma with tumor formation “MF”

  16. PATCH STAGE • Mild epidermal hyperplasia with • perivascular or band-like infiltrate • of small- to medium-sized atypical • lymphocytes with cerebriform nuclear • convolution. • EPIDERMOTROPISM: • Cerebriform lymphocytes exhibit • epidermotropism and are arranged • along the dermal-epidermal junction • in a single-file pattern or scattered • in the epidermis. • Pautrier’s microabscesses are small • intra-epidermal collections of cerebriform • lymphocytes & are pathognomonic for • MF. They might not be present in early • stages of MF MF PATCHES Eczematoid

  17. 2. PLAQUE STAGE: The density of the neoplastic cells within dermis increases Exaggerated epidermotropism Psoriasiform

  18. 2. PLAQUE STAGE: The density of the neoplastic cells within dermis increases Exaggerated epidermotropism Plaque Stage: A broad band-like cellular infiltrate in the upper dermis Pautrier Psoriasiform

  19. 3. TUMOR STAGE: VERTICAL GROWTH Very dense dermal infiltrate involving the full breadth of the dermis & extending to the subcutaneous fat. Epidermotropism diminishes de novo tumor “d’emblee” ﺩﻮﻤﻪﻞ Tumors could get infected  sepsis  death

  20. ERYTHRODERMA Pathology similar to Patch stage but infiltrate is more sparse Generalized erythroderma with Sézary cells “with cerebriform nuclei” in blood of >1,000/uL  Sézary Syndrome ↑CD4 to CD8 ratio >10:1 T-cell Receptor gene rearrangement

  21. Intensely symptomatic from pruritus & scaling Usually have lymphadenitis Sézary Syndrome = Generalized erythroderma Lympha- denopathy Sézary cells

  22. MYCOSIS FUNGOIDES SHEIKHA

  23. Pautrier Abscesses

  24. MYCOSIS FUNGOIDES SHEIKHA LYMPH NODE INVOLVEMENT IN MF or SZS DERMATOPATHIC LYMPHADENITIS = DL

  25. MYCOSIS FUNGOIDES SHEIKHA IMMUNOPHENOTYPE in MF/SZS CD2+ CD7- CD30- CD3+ CD4+ Molecular Diagnosis: PCR of T-cell Receptor γ rearrangement, especially in early patch stages CD5+ CD25 -/+ Cell of Origin: CD4+ T lymphocyte with skin homing “epidermotropic” properties

  26. MYCOSIS FUNGOIDES SHEIKHA CLINICAL PRESENTATION OF MF MF often has a long natural history Median duration from onset to diagnosis may be 5 years or more Usually starts with scaly skin lesions that wax & wane over years Biopsy at this stage is usually non-diagnostic Patient may respond at this stage to topical steroid Repeated biopsy is warranted if MF is suspected and biopsy is negative

  27. MYCOSIS FUNGOIDES SHEIKHA CLINICAL PRESENTATION OF MF 30% Limited patch or plaque stage <10% BSA T1 35-40% Generalized patch or plaque stage >10% BSA T2 15-20% Tumorous stage <10% BSA T3 PRURITUS Commonest symptom of MF 15% Erythro- derma T4 Only 15% of MF patients show extracutaneous disease. Lymph nodes; Visceral disease, etc

  28. MYCOSIS FUNGOIDES SHEIKHA OTHER FEATURES OF MF Skin Hair Follicles could be extensively infiltrated. Mucin might be deposited  Follicular MF Pagetoid reticulosis is a verrucous variant of MF Affecting acral sites like hands & feet. Extreme atypical LC epidermotropism verrucae Granulomatous slack skin pendulous folds of slack or lax skin “macrophage-mediated destruction of dermal elastic fibers” Many MF have only skin problems. 15% have extracutaneous disease; LN, Visceral sites “Lung, Oral cavity, CNS, etc” could be affected.

  29. Various Cutaneous Manifestations of Mycosis Fungoides

  30. MYCOSIS FUNGOIDES SHEIKHA STAGING OF MF

  31. MYCOSIS FUNGOIDES SHEIKHA Tumor- Node- Metastasis- Blood Classification For MF

  32. MYCOSIS FUNGOIDES SHEIKHA CLINICAL STAGING SYSTEM FOR MF B CLASSIFICATION (SEZARY CELLS) DOES NOT ALTER CLINICAL STAGE

  33. MYCOSIS FUNGOIDES SHEIKHA Tumor-Node-Metastasis-Blood & Clinical Staging Classification

  34. MYCOSIS FUNGOIDES SHEIKHA

  35. MYCOSIS FUNGOIDES SHEIKHA TOPICAL CHEMO- THERAPY TREATMENT OF MF Effective TOPICAL NITROGEN MUSTARD“MECHLORETHAMINE" Mechanism ?? AQUEOUS SOLUTION OINTMENT 10 to 20 mg Per 100 cc = Choice of aqueous or ointment depends on convenience, preference & cost Hypersensitivity is 30% with Aqueous solution & < 5% with ointment

  36. MYCOSIS FUNGOIDES SHEIKHA Topical N2-Mustard is applied locally or to the entire skin at least daily during the clearing phase. After few weeks treatment may be applied to the affected region. N2-Mustard may only be applied to the affected anatomical site if the disease is really limited. Treatment is continued on daily basis until the lesions are cleared (6 months+)  3 to 6 months of maintenance therapy If response is slow; increase N2-Mustard concentration or frequency of application Half will relapse after discontinuation of R/ but respond again CR rate for limited patch or plaque stage “T1” is 70% to 80% The median time to skin clearance is 6 to 8 months 20% to 25% have durable CR of > 10 years Local Radiation to Refractory local lesions

  37. MYCOSIS FUNGOIDES SHEIKHA TOPICAL CHEMO- THERAPY TREATMENT OF MF TOPICAL Carmustine“BCNU" Similar efficacy to N2- Mustard but it could be absorbed & cause myelosuppression, thus limiting its long-term use. BCNU use could cause telangiectasias in areas exposed to the drug

  38. MYCOSIS FUNGOIDES SHEIKHA TREATMENT OF MF PHOTO- THERAPY Ultraviolet Light (UV)  UVA or UVB wavelength ± Psoralen = PUVA Psoralen is a photosensitizing agent The long-wave UVA has greater dermal penetration power For early Limited disease UVB alone or Home UV phototherapy (UVA & UVB) could be effective PUVA is the most commonly used form of therapy for MF & SZS It is effective in Psoriasis but has also been found to be effective in MF PUVA is used 2-3 times/week during the clearance phase ( >6 months) Reduce frequency in maintenance phase. For recurrence ↑ frequency again Complete clearance rate with PUVA is 50% to 90% for patch & plaque stage Less response for erythrodermic or tumor stage

  39. MYCOSIS FUNGOIDES SHEIKHA PUVA COMPLICATIONS ACUTE: Nausea Phototoxic reactions such as erythroderma, blistering & dryness Shield eyes & skin from sun for 24 hrs after Psoralen ingestion LONG TERM: Cataract (use UVA opaque goggles during therapy) Secondary cutaneous malignancy

  40. MYCOSIS FUNGOIDES SHEIKHA TOPICAL RETINOIDS Bexarotene “Targretin” 1% Gel Overall Response Rate is 63% Complete Response rate is 21% Because of the irritant effect, it is only used for discrete patch or plaque stage Not applicable in generalized disease Apply thin over the lesions twice daily Irritation is a rule. Withhold for few weeks if erythema

  41. MYCOSIS FUNGOIDES SHEIKHA TREATMENT OF MF RADIATION THERAPY MF is an exquisitely radiosensitive neoplasm Irradiation may be exploited in several ways Individual plaques or tumors of MF may be treated to total doses of 15 to 25 Gy in 1 to 3 weeks, with a high likelihood of achieving long-term local control. For the unusual patient with with unilesional or localized MF, local electron beam therapy achieves the most efficient & complete clearance of the disease Depth of penetration of electrons is controllable; this is of major advantage in MF Depth of R/ with TSEBT is better than N2-Mustard or PUVA

  42. MYCOSIS FUNGOIDES SHEIKHA TOTAL SKIN ELECTRON BEAM THERAPY “Stanford Technique” A full cycle takes 2 days 2 Gy is given per cycle Total dose of around 36 Gy is given over 10 weeks; Give a week rest in middle to give relief from erythema OVERALL RESPONSE RATE 100% COMPLETE RESPONSE RATE 98% 50% OF T1 & 25% OF T2 ARE FREE OF DISEASE 5 YEARS AFTER A SINGLE COURSE Local N2-Mustard is indicated for 6 months after TSEBT Complications: Erythema Dry desquamation Alopecia Nail loss Sweating problems Indications: Very thick plaques Recent rapid progression Other local therapy are ineffective

  43. MYCOSIS FUNGOIDES SHEIKHA

  44. MYCOSIS FUNGOIDES SHEIKHA TREATMENT OF MF SYSTEMIC CHEMO- THERAPY Only for Extracutaneous MF 80% to 100% Complete or Partial Response Duration of Response is usually < 1 year CHOP COP CAVE COMP

  45. MYCOSIS FUNGOIDES SHEIKHA TREATMENT OF MF OTHER TREATMENTS Extracorporeal Photopheresis Interferon-α Systemic Retinoids Recombinant Fusion Proteins IL-2-diphtheria toxin (Ontak; denileukin diftitox) For IL-2 receptor “CD25+” MF

  46. MYCOSIS FUNGOIDES SHEIKHA

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