medicine.Lymphomas.(dr.sabir)
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    medicine.Lymphomas.(dr.sabir) medicine.Lymphomas.(dr.sabir) Presentation Transcript

    • Lymphomas Dr. Sabir M. Amin
    • Definition
      • collection of lymphoid malignancies in which malignant lymphocytes accumulate in lymph nodes and
      • lymphoid tissues, leading to lymphadenopathy, extranodal disease, and constitutional symptoms
    • Classification
      • Stage I
      • .. involvement of a single lymph node region or extra lymphatic organ or site
      • • Stage II
      • .. involvement of two or more lymph node regions or an extra lymphatic site and one or more lymph node regions on same side of diaphragm
      • • Stage III
      • .. involvement of lymph node regions on both sides of the diaphragm; may or may not be accompanied by single extra lymphatic site or splenic involvement
    • Classification…cont
      • Stage IV
      • • diffuse involvement of one or more cxtralymphatic organs including BM
      • • subtypes:
      • A = absence of B symptoms
      • B = presence of B symptoms
      • • unexplained fever >38°C
      • • unexplained weight loss (>10% of body weight in 6 months)
      • • night sweats
    • Hodgkin’s disease
      • malignant proliferation of lymphoid cells with Reed-Sternberg cells (thought to arise from germinal center B-cells)
      • Bimodal distribution with peaks at the age of 20 years and >50 years
      • .. association with Epstein-Barr virus in up to 50% of cases
    • Clinical features
      • asymptomatic lymphadenopathy (70%)
      • • non-tender, rubbery consistency
      • • cervical/supraclavicular (60-80%), axillary (10-20%), inguinal (6-12%) • splenomegaly (50%) ± hepatomegaly
      • • mediastinal mass found on routine CXR, may be symptomatic (cough) rarely may present with SVC syndrome, pleural effusion
    • Cl. Features…cont
      • B symptoms (especially in widespread disease; fever in 30%), pruritus
      • • alcohol-induced pain in nodes. nephrotic syndrome
      • .. starts at a single site in lymphatic system (node), spreads first to adjacent nodes disease progresses in contiguity with lymphatic system
    • Investigation
      • CBC
      • .. anemia (chronic disease, rarely hemolytic), eosinophilia, leukocytosis, platelets normal or increased early, decreased in advanced disease
      • Biochemistry
      • LFTs (liver involvement)
      • RFTs (prior to initiating chemotherapy)
      • .. ALP, Ca (bone involvement)
      • • ESR, LDH (monitor disease progression)
    • Investigation
      • i maging
      • .. CXR, CT chest (lymph nodes, mediastinal mass), CT abdomen/pelvis (liver or spleen involvement), gallium scan (assess treatment response)
      • cardiac function assessment - ( Echo for EF) for pts at high risk of pre-treatment cardiac disease (age :>60, history of HT, CHF, CAD, MI, CVA)
      • .. PFTs - if history of lung disease (COPD. smoking. previous radiation to lung)
      • .. excisional lymph node biopsy confirms diagnosis
      • .. bone marrow biopsy to assess marrow infiltration (only necessary if B symptoms, stage III or IV, bulky disease or cytopenia)
    • Diagnosis
      • Diagnosis can be made with lymph node biopsy. There are four main histologic subtypes based on the No. of lymphocytes, Reed - Sternberg cells, and the presence of fibrous tissue:
      •     1.Lymphocyte predominance       ( after age 50 ) 2.Mixed cellularity     most common, young)   ) 3.Nodular sclerosis       4.Lymphocyte depletion
    • Treatment
      • 1) stage I-II : chemotherapy (ABVD) followed by involved field XRT ( Adriamycin, Bleomycin, Vinblastin, Dacarbazine)
      • 2) stage III-IV : chemotherapy (ABVD, BEACOPP), with XRT for bulky disease
      • 3) Relapse, resistant to therapy: high dose chemotherapy, bone marrow transplant
      • BEACOPP( bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisolone)
    • Complications of treatment
      • cardiac disease - 2° to XRT, adriamycin is cardiotoxic
      • pulmonary disease - secondary to bleomycin( interstitial pneumonitis)
      • infertility - recommend sperm banking
      • secondary malignancy in irradiated field
      • .. <2% risk of MDS, AML (2° to treatment, usually within 8 years)
      • • solid tumours of lung, breast, >10 years after treatment
      • • non-Hodgkin's lymphoma
      • hypothyroidism - post XRT
      • infection - post splenectomy (give Pneumovax, HiB, and pneumococcal conjugate vaccines), during treatment
    • Adverse prognostic factors
      • 1. serum albumin <4 gm/dL
      • 2. hemoglobin <10.5 gm/dL
      • 3. male
      • 4. stage IV disease
      • 5. age:<45 years
      • 6. leukocytosis (WBC >15000)
      • 7. lymphocytopenia (lymphocytes <8% of WBC )
    • Non-Hodgkin’s lymphoma
      • malignant proliferation of lymphoid cells without Reed-Sternberg cells.
      • Originates from both B- (85%) and T- or NK- (15%) cells
      • • B cell NHL - e.g. Burkitt&quot;s lymphoma, mantle cell lymphoma. follicular lymphoma
      • • T cell NHL - e.g. mycosis fungoides. anaplastic large cell lymphoma
    • Grade
      • WHO/REAL classification system - 3 categories of NHLs based on natural history:
      • 1) Low-grade ( indolent ) 35-40% - e.g. follicular lymphoma, small lymphocytic Iymphoma/CLL, mantle cell lymphoma
      • 2) Intermediate-grade ( aggressive ) 50% - e.g. diffuse large B-cell lymphoma
      • 3) High-grade ( highly aggressive ) 5% - e.g. Burkitt's lymphoma
    • Clinical features
      • painless superficial lymphadenopathy, usually >1 lymph region
      • • usually presents as widespread disease
      • • B symptoms (fever, weight loss, night sweats) not as common as in Hodgkin's disease
      • • cytopenia: anemia ± neutropenia ± thrombocytopenia if BM fails
    • Clinical features
      • • hepatosplenomegaly
      • • retroperitoneal and mesenteric involvement (2nd most common site of involvement)
      • • oropharyngeal involvement in 5-10% with sore throat and obstructive apnea
      • • extranodal involvement - most commonly Gl tract, also testes. bone. kidney
      • • CNS involvement in 1% (often with HIV)
    • Investigation
      • CBC
      • normocytic normochromic anemia
      • • autoimmune hemolytic anemia
      • • advanced disease: thrombocytopenia, neutropenia, and leukoerythroblastic anemia
      • peripheral blood film sometimes shows lymphoma cells
      • Biochemistry
      • increase in uric acid
      • • abnormal LFTs in liver metastases
      • • increased LDH (rapidly progressing disease. poor prognostic factor)
    • Imaging
      • CXR and CT for thoracic involvement
      • • CT for abdominal and pelvic involvement
      • • gallium scan is useful for monitoring response to treatment and evaluation of residual tumour following therapy
      • Diagnosed by lymph node biopsy
      • • fine needle aspiration occasionally sufficient. excisional biopsy preferred
      • bone marrow biopsy
    • Treatment
      • Localized disease (e.g. Gl. brain, bone, head and neck)
      • surgery (if applicable)
      • • radiotherapy to primary site and adjacent nodal areas
      • • adjuvant chemotherapy
    • Treatment..con
      • indolent lymphoma - goal of treatment is symptom management
      • watchful waiting
      • radiation therapy for localized disease
      • chemotherapy (single agent, combination or rituximab/ Rituxan, an anti-CD20 Ab)
    • Treatment..con
      • Aggressive lymphoma - goal of treatment is curative
      • -combination chemotherapy: CHOP is mainstay. plus rituximab if B-cell lymphoma
      • -radiation for localized /bulky disease
      • -CNS prophylaxis with high-dose methotrexate (intrathecal or systemic) if certain sites involved
      • -relapse, resistant to therapy: high dose chemotherapy, BMT
    • Treatment…con
      • Highly aggressive lymphoma
      • -Burkitt&quot;s Lymphoma - short bursts of intensive chemotherapy
      • -'CODOX-M&quot;' chemotherapy regimen also often used ± IVAC
      • -CNS prophylaxis and tumour lysis syndrome prophylaxis
    • Complication
      • 1)Hypersplenism
      • 2) infection
      • 3) autoimmune hemolytic anemia and thrombocytopenia
      • 4)vascular obstruction (from enlarged nodes)
      • 5) tumour lysis syndrome (particularly in very aggressive lymphoma)
    • Prognosis
      • poor prognostic factors
      • • >60 years old
      • • poor response to therapy
      • • multiple nodal regions
      • • elevated LDH
      • nodes >5 cm
      • • previous history of low-grade disease or AIDS
    • Chronic lymphocytic leukemia (CLL)
      • indolent disease characterized by clonal malignancy of mature B-cells
      • most common leukemia in Western world
      • • mainly older patient; median age 65 years
      • • M>F
    • Pathophysiology
      • accumulation of neoplastic lymphocytes in blood, bone marrow, lymph nodes and spleen
    • Clinical features
      • 25% asymptomatic (incidental finding)
      • • 5-10% present with B symptoms (≥1 of: unintentional weight loss ≥10% of body weight within previous 6 months, fevers >38°C or night sweats for ≥2 weeks without evidence of infection, extreme fatigue)
      • • lymphadenopathy (75%), splenomegaly (35%), hepatomegaly (20%)
      • • immune dysregulation - autoimmune hemolytic anemia (Coombs +), immune thrombocytopenia purpura (ITP), hypogammaglobulinemia ± neutropenia
      • • BM failure - late, secondary to marrow involvement by CLL cells
    • Investigation
      • CBC : absolute lymphocytosis >5000
      • • peripheral blood film
      • • lymphocytes are small and mature
      • • smudge cells
      • flow cytometry
      • cytogenetics - FISH
      • bone marrow aspirate
      • lymphocytes >30% of all nucleated cells
    • Natural history and treatment
      • natural history - indolent but incurable, with slow progression; thus select gentlest treatment that will control symptoms
      • observation if early, stable, asymptomatic
      • intermittent chlorambucil or fludarabine
      • corticosteroids, IVIG - especially for autoimmune phenomena
      • • radiotherapy
      • • chemotherapy - including Rituximab (anti-CD20 mAb)
      • • small minority present with aggressive disease usually associated with chromosomal abnormalities (e.g. p53 deletion)
      • • 9 year median survival, but varies greatly
    • Complications
      • 1) 5% undergo Richter's Transformation - aggressive transformation to Diffuse Large B-Cell Lymphoma
      • 2) hyperuricemia with treatment