Lymphoma 2023 PDF

Lymphoma Dr. Mekoya D. Mengistu (MD, Internist, Assistant professor of Internal Medicine)  Questions?  What are the types of lymphoma?  What are the major risk factors?  What are the clinical presentation of a patient with lymphoma?  What are the major diagnostic modalities?  Staging of...

Lymphoma Dr. Mekoya D. Mengistu (MD, Internist, Assistant professor of Internal Medicine)  Questions?  What are the types of lymphoma?  What are the major risk factors?  What are the clinical presentation of a patient with lymphoma?  What are the major diagnostic modalities?  Staging of Lymphoma?  What are the major management options of a patient with lymphoma?  What are the major side effects of chemotherapies?  Defin: Lymphoma  Clonal malignant disorders that are derived from lymphoid cells: either precursor or mature T-cell or B-cell  usually originate in the lymph nodes, but they may originate in any organ of the body  There are two types of lymphoma  Hodgkins Lymphoma  Non hodgkins Lymphoma  This two lymphomas differ in how they behave, spread and respond to treatment.  Epidemiology of lymphomas  5th most frequently diagnosed cancer in both sexes  males > females  incidence  Hodgkin lymphoma stable  NHL increasing(NHL—8-10XHL) Fig. Incidence of lymphomas in comparison with other cancers in Canada 4  Hodgkin's Lymphoma  Named after Thomas Hodgkin's.  It’s a cancer of lymphocytes almost in all cases they starts from the B subtype.  It can start at any lymphoid tissues mostly the LN and usually in the upper part of the body  it spreads in contiguous manner and rarely hematogenous. Thomas hodgkins (1898-1966)  Course of the disease is variable, but the prognosis has improved with modern treatment  The prototype cell is the Reed Sternberg's cells.  cell of origin: germinal centre B-cell  Because It has high proliferative activity  Etiology: ? Infection – EBV  ?EBV sometimes causes DNA changes in B lymphocytes.  this leads to the development of Reed-Sternberg cells, which are the cancer cells in HL.  Reed-Sternberg cells (or RS variants) in the affected tissues 6 Reed-Sternberg cell: are the hallmark cells of Hodgkin's lymphoma (HL). 7 A possible model of pathogenesis of HL Reed Sternberg cells  Classifications of HL  Classification is based on microscopic features.  Different types & may be treated differently.  All types are malignant and there is no benign type.  Generally there are two types ◦ Classic HD: are of four types  Nodular sclerosis (70%)  Mixed cellularity (25%)  Lymphocytic rich (5%)  Lymphocytic depletion (1%) ◦ Nodular lymphocytic predominant (5%) HL  Risk factors for HL  Infections eg: EBV, HIV  Age bimodal distribution  Gender: more common in males  Socioeconomic status: higher status  Geographic location: more in westerns and less in Asians  Family history: accounts for 5%, twins has higher risk. Fig. Bimodal age distribution of HL  Clinical manifestations of HL: Clinical manifestation is variable  severity: asymptomatic to extremely ill  time course: evolution over weeks, months, or years  Most patients present with palpable, non-tender Lymphadenopathy 70% localize to cervical or supraclavicular area or Axilla The LAP is Firm, non tender, discrete contiguous spread The size may change spontanously Alcohol induced pain at the site  More than 50% pts have anterior mediastinal mass: can be initial manifestation  Extranodal sites relatively uncommon except in advanced disease 14   Subdiaphramatic presentation of cHL is unusual and more common in older males Only 4% of HL are limited to below the diaphragm 25% of normal spleens harbour tumor  30-40% of HL patients have B-symptoms [70% in Ethiopia]  B symptoms generally correlate with advanced stage and portend a worse prognosis.  Unexplained wt loss of more than 10% in 6months  Unexplained persistent or recurrent fever above 38°C in previous month  Recurrent drenching night sweats during the previous month 15 Classic hodgkins Lymphoma  Occasionally HL presents with unusual manifestation:  Severe and unexplained itching/pruritis  Cutaneous disorders like erythema nodusum, ichthyosiform atrophy  Paraneoplastic cerebellar degeneration, nephrotic syndrome, Hypercalcaemia,  Immune hemolytic anemia and thrombocytopenia, Pain in LN on alcohol ingestion  Staging of HL  Used to determine the extent of spread, to see prognosis and decide treatment options.  Its based on Medical history P/E Blood tests Biopsy of LAP, BM aspiration and biopsies Imaging :CXR, CT SCAN, MRI, PET , GALLIUM SCAN, BONE SCAN  Investigation  CBC: Mild to moderate NCNC anemia is common in HL  ESR, serum ferritin, haptoglobulin  CXR: demonstrate mediastenal mass, hilar LAP, Pleural effusion, parenchymal lung lesions  CT scan/Pet scan: for staging  Biopsy: Excisional/incisional biopsy  preferred and most common type of biopsy for an enlarged LN Core needle biopsy: Eg Mediastinal mass or Hilar LAP BM aspiration/biopsies: BM involvement of cHL is patchy and can be missed  Immuno-histocompatability  Ann arbor(with costs wold modification) staging  Stage I: HD is found in only 1 lymph node area or lymphoid tissues/organ such as thymus  The cancer is only in one extra-nodal organ  Stage II: HD found in 2 or more LN areas on the same side(above or below) of diaphragm  The cancer extends locally from one lymph node area in to near by organs  Stage III: HD found on LN area on both side of the diaphragm  III-1 subdiaphragmatic involvement limited to spleen, splenic hilar LN, ciliac LN, portal LN  III-2: extends to paraortic, iliac or mesentric LN  Stage 4: Diffuse or desiminated involvement of ≥1extranodal organs beyond that designated as E  Any involvement of Liver ,bone marrow, lung ,CSF involvement  BULKY DISEASE(X) : If present, needs intensive therapy.  Defined as Mediatinal mass 1/3 of the chest, nodal mass >10cm across the largest dimension.  All stages are classified as (A)Absent or B-presence of B SYMPTOMS  Add E-for localized, solitary involvement of extranodal deposit excluding liver and bone  Add S: If spleen is involved, IF both use ES.  Clinical staging Stage I Stage II Stage III Stage IV Signs of poor prognosis: A. For limited stages: include all asymptomatic stage I or II supradiaphragmatic disease without bulky  the presence of any of the following factors is considered unfavorable  Age ≥50  Bulky disease(Eg. Mediatinal mass ratio(MMR)> 0.3)  ESR >30 with B symptoms or >50 with out B symptoms  >2 Ann Arbor sites  Massive splenic disease  Extranodal site B. For advanced stages: Bad prognostic signs are  Age ≥45years  Male gender  Anemia Hgb 60, Gender: most are common in males  Exposure to chemicals: such as benzene  Radiation exposure  Immune system deficiencies  Certain infections ◦ Infections that directly transform lymphoma: EBV, HTLV-1, HHV-8 ◦ Infections that weakens immune system: HIV ◦ Infections that causes chronic immune stimulations: H. pylori, C. jejuni, HCV etc 35  Types of B cell NHL Diffuse large B cell lymphoma(DLBCL)  The most common histologic type of NHL: 1/3rd of NHL.  Appear large under microscope,  Average age is 60.  Majority of patient present in advanced stage: III or IV  40% of patients have B-symptoms and 50% have raised LDH  40% of patients have non-nodal sites including BM, CNS, GIT, thyroid, liver and skin  Involvement of BM, testis, breast, kidney, thyroid, liver and skin are at increased risk of CNS involvement  Responds well for Rx: 3/4th are symptoms free after initial Rx and more than half (60-65%) of all cured.  Has sub types  Primary meditational B cell lymphoma  Intravascular large B cell lymphoma  is a rare subtype of DLBCL in which lymphoma cells proliferate within the lumen of small blood vessels.  most often presents with CNS and skin signs. The cutaneous variant of intravascular lymphoma is limited to the skin  Primary CNS lyphoma (PCNSL)- common in immune compromised(Eg. HIV), poor prognosis Follicular lymphoma:  2nd leading cause of NHL: 1 in 5  it means it tends to grow in a circular pattern in LNs.  Occurs painless LAP at multiple sites and bone marrows.  average age is 60  Is slow growing, most patients have no raised LDH, and no B symptoms  treatment may not be required until it starts to cause symptoms.  It responds well to treatment (sensitive to chemo) but cure is hard to achieve  Rx: Observe the asymptomatic patients b/c treatment has no mortality benefit[but Recurs]  Rx if Symptomatic: Rituximab or if large volume disease: R-CHOP  Marginal zone B cell lymphoma- o 2nd most common indolent lymphoma o 3 types: splenic MZL, Extranodal MZL of MALT(MALT Lymphoma), nodal MZL o MALT lyphoma is most commonly in stomach-cause is associated with H. pylori  Chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma: ◦ 5-10% of all NHL ◦ in CLL cancer cells found in the blood and BM while in SLL cells are found mainly in the LN and spleen. ◦ It is a slow growing, no cure but most live >10 years. Burkett's lymphoma: accounts for 0.3-1.3% of NHL  Highly active, aggressive form of NHL but cure rate 95% if treated  The cells have Starry sky appearance, Vacuolated cytoplasm  presents with rapidly enlarging LN with explosive growth involving jaw, chest &/or abdomen  More common in children and immune suppressed patients  Endemic form: is common in equatorial Africa and tropical region  Children, malaria endemic area  Associated with the EBV in ~100% of cases unlike 30% in sporadic form  sporadic forms that occur in Western countries, EBV in 30% of cases  Immunodeficiency-associated cases: EBV in 40% of cases  Diagnosis of NHL  History: Progressively enlarged LN can be in the neck, abdomen, chest, skin and the brain. swollen abdomen, early satiety, chest pain or pressure, SOB B symptoms and extreme tiredness  P/E focus on LN, spleen examinations.  Biopsies: is the only way to diagnose non- Hodgkin lymphoma ◦ Excisional/ incisional biopsies ◦ Fine/core needle biopsies ◦ Bone marrow aspiration/biopsies, LP, effusion analysis  Lab tests: ◦ Immuno-histochemistry tests ◦ Flow cytometer ◦ Cytogenetic ◦ Molecular genetic tests  Blood tests  Imaging:  CXR  CT SCAN, MRI, PET  GALLIUM SCAN  BONE SCAN Staging of NHL  Tests for staging:  Hx, P/E  Biopsies  Blood tests  Imaging tests  Bone marrow studies  Ann-arbor staging was also adopted for NHL  International Prognostic Index  Depend on ◦ Age ◦ Stage ◦ Extension from the lymph node ◦ Performance in daily activities ◦ Serum LDH level  Good prognostic indicators ◦ Age