LYMPHOMA

Topic of presentation: Lymphoma. Pathology of Lymphoma, stages of Lymphoma, types of Lymphoma. Hodgkin and Non-Hodgkin lymphoma are discussed along with their sub types clinical features, diagnosis, treatment and prognosis.

1. Lymphoma Dr.Muhammad Zaid Shaukat Lymphoma Disease 1

2. Collection of lymphoid malignancies in which malignant lymphocytes accumulate at lymph nodes and lymphoid tissues  leading to lymphadenopathy, extranodal disease, and constitutional symptoms, “B” symptoms . Lymphoma Lymphoma 2

3. 3 STAGING Of LYMPHOMAS

4. 4 SUB-TYPES  A = absence of B-symptoms  B = presence of B-symptoms  “B” symptoms: fever, weight loss, drenching night sweats CHROMOSOMAL TRANSLOCATIONS TRANSLOCATION GENE ACTIVATION ASSOCIATED NEOPLASM t(8;14) c-myc activation Burkitt’s lymphoma t(14;18) bcl-2 activation Follicular lymphoma t(9;22) Philadelphia chromosome (bcr-abl hybrid) CML, ALL in adults (25% of the time) t(11;14) Overexpression of cyclin D1 protein Mantle Cell Lymphoma

5. Hodgkin’s Lymphoma Hodgkin’s Lymphoma 5 Malignant proliferation of lymphoid cells with Reed-Sternberg cells (thought to arise from germinal centre B-cells) Epidemiology • bimodal distribution with peaks at 20 yr and >50 yr • association with Epstein-Barr virus in up to 50% of cases, causal role not determined Band of fibrosis (left), lacunar cells (a variant of Reed sternberg cells – right)

6. Pathology Large B cells (CD 15 and CD 30 +ve) with multilobed nuclei and prominent nucleoli that looks like “Owl eye” They produce cytokines which attract inflammatory cells and cause fibrosis  Due to cytokine release: B symptoms – fever, chills, wt loss, night cells Presence of reactive inflammatory cells that make bulk of tumor Fibrosis HODGKIN’S LYMPHOMA 6 Reed-Sternberg Cells Cytokines release

7. Types of Hodgkin’s Lymphoma Hodgkin Lymphoma 7 Type Characteristics Nodular sclerosis  Most common type of HL - Classic pt is young adult female - Presents as enlarged cervical or mediastinal lymph nodes  Lymph node is divided by band of fibrosis  Reed sternberg cells are present in lake like spaces (lacunar cells) Mixed cellularity Associated with abundant eosinophils (reed sternberg cells produce IL-5) Lymphocyte rich Best prognosis of all types Lymphocyte depleted - Most aggressive of all types -Usually seen in HIV pt or old pt

8. HODGKIN’S LYMPHOMA 8 CLINICAL FEATURES  Asymptomatic lymphadenopathy (70%) ƒ non-tender, rubbery consistency ƒ cervical/supraclavicular (60-80%), axillary (10-20%), inguinal (6-12%) S plenomegaly (50%) ± hepatomegaly M ediastinal mass ƒ found on routine CXR, may be symptomatic (cough) ƒ rarely may present with SVC syndrome, pleural efusion S ystemic symptoms ƒ B symptoms (especially in widespread disease; fever in 30%), pruritus No n-specifc/paraneoplastic ƒ alcohol-induced pain in nodes, nephrotic syndrome S tarts at a single site in lymphatic system (node), spreads frst to adjacent nodes ƒ disease progresses in contiguity with lymphatic system

9. Lymphoma 9 SVC syndrome Slow healing of wounds Easy bruising Pale skin Pleural effusion Shortness of breath Fever Joint Pain Swollen lymph nodes in neck, armpit and groin

10. HODGKIN’S LYMPHOMA 10

11. INVESTIGATIONS HODGKIN’S LYMPHOMA 11  CBC ƒ Anemia (chronic disease, rarely hemolytic), eosinophilia, leukocytosis, platelets normal or increased early, decreased in advanced disease  B iochemistry ƒ HIV serologyƒ LFTs (liver involvement) ƒ renal function tests (prior to initiating chemotherapy) ƒ ALP, Ca2+ (bone involvement) ƒ ESR, LDH (monitor disease progression)  I maging ƒ CXR, CT chest (lymph nodes, mediastinal mass), CT abdomen/pelvis (liver or spleen involvement), gallium scan (assess treatment response), PET scans ƒ Cardiac function assessment (MUGA scan or echocardiography): for patients at high risk of pre-treatment cardiac disease (age >60, history of HTN, CHF, PUD, CAD, MI, CVA), treatment can be cardiotoxic  PFTs : if history of lung disease (COPD, smoking, previous radiation to lung) • excisional lymph node biopsy confrms diagnosis  B one marrow biopsy to assess marrow infltration (only necessary if B-symptoms, stage III or IV, bulky disease or cytopenia)

12. TREATMENT Stage Ia and IIa: local radiation with a small course of chemotherapy Stage III and IV or anyone with “B” symptoms: ABVD A = adriamycin (doxorubicin) B = bleomycin V = vinblastine D = dacarbazine Lymphoma Disease 12

13. 13 Radiation increases the risk of solid tumors such as breast, thyroid, or lung cancer. Screening for breast cancer is recommended 8 years or more after treatment. Radiation also increases the chance of premature coronary artery disease. The risk of acute leukemia, MDS, and NHL as a complication of chemotherapy is about 1% per year. COMPLICATIONS OF CHEMOTHERAPY AND RADIATION

14. NON-HODGKIN LYMPHOMA Non-Hodgkin lymphoma (NHL) is a proliferation of lymphocytes in the lymph nodes and spleen. NHL is most often widespread at presentation and can affect any lymph node or organ that has lymphoid tissue. Malignant proliferation of lymphoid cells of progenitor or mature B- or T-cells. Non-Hodgkin Lymphoma 14

15. Small B-cells  Follicular lymphoma - enlarged and too many follicles-Can progress to diffuse large B cell lymphoma  Mantle cell lymphoma - cancer of mantle (area around follicle)-Often present in late adulthood with painless lymphadenopathy Marginal zone lymphoma - cancer of marginal zone (area around mantle)-Marginal zone made of postgerminal B cells  Small lymphocytic lymphoma (CLL that involve tissue) CLASSIFICATION Intermediate B cell lymphoma  Burkitt lymphoma Often present in child or young adult as extranodal mass •African form – in jaws •Sporadic form – in abdomen Large B cells  Diffuse large B-cell lymphoma  Most common NHL -High grade (aggressive) Present in late adulthood as extranodal mass or enlarging lymph nodes NON-HODGKIN LYMPHOMA 15

16. NON-HODGKIN LYMPHOMA 16 CLINICAL FEATURES P ainless superfcial lymphadenopathy, usually >1 lymph node region U sually presents as widespread disease (exception is aggressive lymphoma) C onstitutional symptoms not as common as in Hodgkin lymphoma  C ytopenia : anemia ± neutropenia ± thrombocytopenia can occur when bone marrow is involved  A bdominal signs ƒ hepatosplenomegaly ƒ retroperitoneal and mesenteric involvement (second most common site of involvement)  O ropharyngeal involvement in 5-10% with sore throat and obstructive apnea  E xtranodal involvement : most commonly GI tract; also testes, bone, kidney  CNS involvement in 1% (ofen with HIV)

17. 17 INVESTIGATIONS  CBC ƒ normocytic normochromic anemia ƒ autoimmune hemolytic anemia ƒ advanced disease: thrombocytopenia, neutropenia, and leukoerythroblastic anemia  P eripheral blood flm may show lymphoma cells  Fl ow cytometry of peripheral blood is valuable for low-grade NHL  BIOCHEMISTRY ƒ increase in uric acid ƒ abnormal LFTs in liver metastases ƒ increased LDH (rapidly progressing disease, poor prognostic factor)  CXR , CT neck, abdomen, pelvis for staging  PET is useful for monitoring response to treatment and evaluation of residual tumour following therapy in aggressive histological disease DIAGNOSIS  Lymph node biopsy: excisional biopsy preferred, FNA unreliable  B one marrow biopsy: not optimal for diagnosis as BM may not be involved

18. NON-HODGKIN LYMPHOMA 18 Treatment Local disease (stage Ia and IIa) Advanced disease (stage III and IV, any “B” symptoms) Local radiation and small dose/course of chemotherapy Combination chemotherapy with CHOP and rituximab, an antibody against CD20 C = cyclophosphamide H = adriamycin (doxorubicin or “hydroxydaunorubicin”) O = vincristine (Oncovin) P = prednisone

19. 19 Hodgkin Lymphoma Non-Hodgkin Lymphoma Frequency 40% 60% Malignant Cells Reed-Sternberg cells (owl eye cells) – B cells –induce inflammation and fibrosis Lymphoid cells – many subtypes – most are B cell than T cells Mass Composition Inflammatory cells and fibrosis (reactive cells) Lymphoid cells Clinical Painless lymphadenopathy - B symptoms Bimodal: classically seen in young adult and >55 yrs - Painless lymphadenopathy - Classically seen in late adults Spread Contiguous (touching); rarely extranodal Diffuse; often extranodal Staging Guides therapy Radiation mainstray treatment Limited importance Leukemic Phase Doesn’t occur Occurs Prognosis Much better prognosis than non-Hodgkins

20. Thanks! 20 Lymphoma Please keep this slide for attribution