medicine.Lymphomas.(dr.sabir)

1,224 views

Published on

Published in: Health & Medicine
1 Comment
2 Likes
Statistics
Notes
No Downloads
Views
Total views
1,224
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
81
Comments
1
Likes
2
Embeds 0
No embeds

No notes for slide

medicine.Lymphomas.(dr.sabir)

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

×