limfoproliferari cronice maligne

Download LIMFOPROLIFERARI CRONICE MALIGNE

Post on 16-Sep-2015

29 views

Category:

Documents

2 download

Embed Size (px)

DESCRIPTION

curs hematologie

TRANSCRIPT

  • LIMFOPROLIFERARI CRONICE MALIGNE Definitie Proliferari clonale ale limfocitelor mature si imature in diferite stadii de diferentiere Etapele de diferentiere corespund fazei postmedulare Grupul limfoamelor este divers. Distinctia intre diferitele tipuri de limfoame se bazeaza pe caracteristicile diferite ale celulelor tumorale. Revised European-American Classification of Lymphoid Neoplasms (REAL): introdus in 1994, REAL descrie diferitele tipuri de limfoame ca entitati cu fiecare tip clasificate in functie de originea celulara, bazat pe apectul

    morfologic, imunologic si criteriile genetice

    Tratamentul pacientilor cu limfom a fost afectat de lipsa uniformitatii dintre aceste sisteme de clasificare. Clasificarea REAL este prima care introduce liniile limfoide celulare in diferentiere: linia B, T si NK. Clasificarea WHO a limfoproliferarilor cornice - moderna B-Cell Neoplasms I. Precursor B-cell neoplasm: Precursor B-lymphoblastic leukemia/lymphoma II. Mature (peripheral) B-cell neoplasms

    B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma

    B-cell prolymphocytic leukemia Lymphoplasmacytic lymphoma Splenic marginal zone B-cell lymphoma (+/- villous lymphocytes) Nodal marginal zone lymphoma (+/- monocytoid B-cells) Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid

    tissue (MALT) type Hairy cell leuekmia Plasma cell myeloma/plasmacytoma Follicular lymphoma, follicle center Mantle cell lymphoma Diffuse large cell B-cell lymphoma

    Mediastinal large B-cell lymphoma Intravascular large B-cell lymphoma Primary effusion lymphoma

    Burkitt's lymphoma/Burkitt's cell leukemia B-cell proliferations of uncertain malignant potential Lymphomatoid granulomatosis Post-transplant lymphoproliferative disorder

    T-Cell and Natural Killer Cell Neoplasms

  • I. Precursor T cell neoplasm: a.Precursor T-lymphoblastic lymphoma/leukemia b. Blastic NK lymphoma (new) II. Mature (peripheral) T cell and NK-cell neoplasms

    T cell prolymphocytic leukemia T-cell granular lymphocytic leukemia Aggressive NK Cell leukemia Adult T cell lymphoma/leukemia (HTLV1+) Extranodal NK/T-cell lymphoma, nasal type (new) Enteropathy-type T-cell lymphoma Hepatosplenic gamma-delta T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides/Szary's syndrome Primary Cutaneous Anaplastic large cell lymphoma T/null cell Peripheral T cell lymphoma, unspecified Angioimmunoblastic T cell lymphoma Primary Systemic Anaplastic large cell lymphoma, T/null cell T-cell proliferation of uncertain malignant potential Lymphomatoid papulosis

    Hodgkin's Lymphoma (Hodgkin's Disease) (B Cell Origin) Nodular lymphocyte predominance Hodgkin's lymphoma Classical Hodgkin's lymphoma

    Nodular sclerosis Hodgkin's lymphoma Lymphocyte-rich classical Hodgkin's lymphoma Mixed cellularity Hodgkin's lymphoma Lymphocyte depletion Hodgkin's lymphoma

    Factori predispozanti

    Imunodeficiente Infectii cronice Sex masculin Varsta Istoric familial de limfom Istoric de cancer Expunere medicamente: imunosupresive, antiepileptice, MTX OCUPATIE:

    Ierbicide, pesticide, solventi, adezivi Alti factori: Coloranti de par

    Factori nutritionali Transfuzii sanguine

    Factori infectiosi

  • Conditii prelimfomatoase

  • Scor de prognostic international:

  • Mai frecvente la barbati Mai frecvente la adult, incidenta creste cu varsta Varsta medie de diagnostic este 45-55 ani

  • Clasificarea limfoproliferarilor cornice in functie de agresivitate: - indolente - agresive - inalt agresive

  • Stadializarea Ann Arbor a limfoamelor:

    Tabloul clinic comun al limfoproliferarilor cornice:

    Semne constitutionale: sindrom febril Transpiratii Scadere ponderala

    Semne clinice: Adenopatii Hepatomegalie Splenomegalie Eruptii cutanate (in limfoame cu celula T)

  • Limfoproliferarile cornice cu celula B

    Limfomul de manta

    Limfoproliferare cronica rara (4-8% dintre LMNH) descris iniial la mijlocul anilor 1970 Limfocitoza cu limfocite polimorfe, unele cu nucleu clivat Frecvent la varstnici 60-65 ani M/F 2/3

    Asociat cu determinare de tract digestiv (polipoza gastric) Supravietuire medie 3-5 ani Clinic:

    adenopatii generalizate Hepatosplenomegalie

    Frecvent cu determinare medulara Tipuri histologice:

    De zona de Manta nodular difuz blastoid sau limfoblastoid mimeaza LAL

    Imunofenotip: Igs+ (IgM>IgD) CD19+ CD20+ CD5+ CD23- FMC7+ CD79b+ CD43+ CD10- Restrictie lanturi usoare Lambda>kappa

    Aberatii cromozomiale specific t(11;14)(q13;q32) care produce gena PRAD1 si proteina cyclin

    D1 (antiapoptotica) Tratament:

    "watch and wait" pentru pacienti asimptomatici Alchilanti orali +/- coticosteroizi:

    Cyclophosphamide Chlorambucil.

    Chimioterapie combinata : R-CVP: ciclofosfamide + vincristine + prednisone R-CHOP: ciclofosfamide + doxorubicin + vincristine + prednisone FND: fludarabine + mitoxantrone dexamethasone Hyper-CVAD in varianta blastica

    anti-CD20 (rituximab) in monoterapie si imunochimioterapie Radioimunoterapie cu 90Y-ibritumomab

    LMNH folicular

    Relativ frecvent - 30% dintre LMNH Media de varsta 60 ani Peste 40% in stadiul IV Origine in centrul folicular

    Celule mici centrocite cu nucleu clivat Celule mai mari centrocite mari cu nucleu clivat Celule mari centroblaste cu nucleu regulat, 2 sau mai multi nucleoli

    periferici

  • Imunofenotip: CD19+ CD20+ CD22+ CD79a+ CD10+ CD5- CD43- bcl-6+ Citogenetic: t(14;18), bcl-2+

    Scor prognostic: FLIPI Tratament:

    watch and wait Rituximab monoterapie pacienti cu risc mic Rituximab + combinatii (CHOP, CVelHP) Pentru recaderi cure de salvare Mentinere cu rituximab, IFN-alfa BMT, RIT

    LMNH de zona marginala

    1. Ganglionar 2. Extraganglionar 3. Splenic Imunofenotipic: CD19+ CD20+, CD22+ CD5- CD23- CD10- FMC7+ CD24-

    Igs+

    1. LMNH ganglionar (monocitoid) Este cel mai rar limfom marginal Varsta medie 60 ani Morfologic: heterogenitate celulara celula cu nucleu clivat, de tip centrocitic, plasmocite, celule viloase Frecventa afectare mediastinala, fara descarcare leucemica

    2. MALT In tubul digestiv, din placile Peyer Poate disemina local si la distanta (bronhii) si medular, piele, anexe oculare, glandesalivare, plamani, cai respiratorii superioare, san, tiroida, mucoase Asociere cu stimulare antigenica cronica si boli autoimune Helicobacter pylori, tiroidita autoimuna Hashimoto Tratament cu antibiotice +/- chimioterapie +/- imunoterapie, RIT gastrectomie

    3. LMNH splenic de zona marginala Origine in pulpa alba a splinei Asociere cu HCV, EBV Clinic: splenomegalie importanta, fara adenopatii Morfologic: limfocite cu citoplasma viloasa cu prelungiri Determinare medulara cu descarcare leucemica in peste 50% din cazuri Poate avea secretie monoclonala de Ig Imunofenotip: asociere frecv, expresie IgD Factori de prognostic:

    Hb < 12 g/dl LDH crescut Albumina scazuta sub 3,5 g/dl

    Tratament Splenectomie Imunochimoterapie (RCVP, RCHOP)

  • RIT

    LMNH DIFUZ CU CELULA MARE Cel mai frecvent LMNH 35-40% Morfologic: limfocite mari cu pattern de infiltrare difuza

    Centroblastic Imunoblastic Bogat in limfocite T/histiocite CD30+ CD15- EMA+/- Oct+ Bob-1+ Anaplazic CD30+ CD15- ALK- Plasmablastic CD45- CD20- CD79a+ CD138+ Cu expresia ALK CD45-/+ CD20- CD79a- CD30- EMA+ cIgA+ Mediastinal (timic) CD45+ CD20+ CD79a+ BCL-6+ CD10- CD30+

    EMA+ CD23+ Intravscular CD45+ CD20+ CD79a+ CD10+/- CD5+/- CD34-

    Clinic: agresive mase tumorale voluminoase tendinta la det. extraganglionare, SNC

    Tratament: Chimioterapie combinata tip agresiv Imunochimioterapie cu anticorpi monoclonali: R-CHOP standard de prima

    linie Administrare intratecala chimioterapie profilactic sau curativa daca se

    dovedeste determinarea neurologica Radioterapie pe masele tumorale mari Consolidare: SCT

    LIMFOM LIMFOBLASTIC SI BURKITT

    inalt agresive BURKIT Infiltrare difuza cu limfocite intermediare, polimorfe CD45+ CD20+ CD79a+ CD10+ BCL-6+ BCL-2- CD5- CD23- CD30+ TdT-

    LIMFOBLASTIC B infiltrare difuza cu limfocite medii, cu putina citoplasma, cromatina in sare si

    piper CD45- CD20- CD79a+ CD10+ BCL-2+ TdT+ CD99+ CD34+ CD117+ Aspecte genetice: Burkitt Endemie EBV t(8;14) cu gena MYC Limfoblastic B t(12;21) cu gena TEL-AML1 t(9;22) cu gena BCR-ABL t(4;11)q23 cu gena MLL si expresia receptorului tirozinkinazic FLT3 Clinic:

    Burkitt F. endemica copii (sex masculin)

    Tumori faciale si mandibulare (Africa de Nord)

  • F. sporadica frecvent afectare abdominala F. epidemica in SIDA

    Limfomul limfoblastic B 5-15% dintre l. limfoblastice Nu au determinare periferica la diagnostic Au sub 25% infiltrare medulara

    Limfoame cu celula T

    Limfomul T periferic (PTCL)

    15% dintre limfoproliferarile T Deseori asociate cu sindroame paraneoplazice

    Rash cutanat, AHAI, hypergammaglobulinemia, eozinofilie, hipercalcemia, vasculita, hemofagocitoza

    tratament: Chimioterapie alchilanti (CVP, CHOP, CHOEP) IFN-alfa PUVA-terapie pentru leziunile cutanate

    Adult T-cell Lymphoma/leukemia sau Leucemia/Limfomul cu celula T a adultului

    (ATLL) Asociata cu infectia HTLV-1 2% dezvolta boala maligna Forme de prezentare: Limfom primitiv extranodal

    5% dintre prezentarile limfomatoase au determinari cutanate, inelul Waldeyer, tract gastrointestinal, si