B15 - Lymphoma and Myeloma Flashcards

Question

burrito lymphoma aiteology

Answer 1

◊ Aetiology: sporadic and endemic } African variety: jaw tumour, EBV driven (endemic) } Commonest childhood tumour in sub-saharan Africa } Sporadic in western population in lymph nodes in abdomen or be behind the eye } common in older population to be orbital tumour

Answer 2

◊ Biology: rapidly growing } Nearly all cells are actively in cell cycle } When chemotherapy is done cell all rapidly die because they're in cell cycle

Answer 3

◊ Genetics: 90% t(8;14) MYC-IGH } Translocation of proto-oncogene c-MYC from chromosome 8 to IGH gene on chromosome 14 } Up regulation of oncogene

Answer 4

} Monotonous B cell infiltrate } Moderately sized cells with very blue cytoplasm and distinctive vacuoles - white holes in cytoplasm } "starry sky" - high mitotic rate – Tissue at low magnification - the tumour cells with while gaps which are the macrophages trying to remove cells that are dying due to very high turnover rate } Derived from germinal centre B-cells

Answer 5

Treatment: aggressive chemotherapy | ◊ Potentially curable - treated aggressively with chemo to try and eradicate

Answer 6

◊ Most common lymphoma - 30% NHL } Incidence is increasing because it is a disease of older people and our population is aging ◊ Disease of adults: median age 65 years ◊ Presents with rapidly enlarging masses } May be in the lymph nodes (primary lymphoid tissue) or other lymphoid sites

Answer 7

} Diffuse infiltration by large cells (usually B cells) } Diverse histology; high proliferation rate – Many of the cells are in active cell cycle meaning they will respond well to chemo

Answer 8

◊ Rx: combination chemotherapy (e.g. CHOP-R) } Rituximab targeting CD20 molecules generally expressed by these tumours (B cell antigen) } Complete remission rates: 60-70% } Approximately 30% curable } Cure rate is higher in younger patients, older patients suffer side effects of treatment } Stem cell transplant in younger patients <65 – Very high dose chemotherapy to eradicate all cells in haemopoietic system (bone marrow and lymphoid tissue) – Replace with new stem cells which will result in reconstitution of haemopoietic system – Only done when disease relapses

Answer 9

} Aggressive NHL: international prognostic index – Age: <60 vs >60 years – Performance status: 0 or 1 vs. 2-4 – LDH: <1x normal vs. >1x normal w Enzyme lactate dehydrogenase w In lymphoid and red blood cells – Disease stage: 1,2 vs. 3,4 w From radiological imaging – Extra-nodal involvement: <1 vs >1 site w Sites outside the lymph nodes that are involved } Assigned 1 point for each bad feature – The more points, the worse prognosis } Rx: depends on site, extent, age – Combination chemotherapy + CD20; DXRT – Young: stem cell transplant } Radiological monitoring: CT, PET/CT

Answer 10

§ Thomas Hodgkin 1798-1866 § Hodgkin lymphoma (Hodgkin's disease) is characterised by the Reed-Sternberg cell: □ Minor cell component found in the appropriate microscopic cellular background □ □ This cells indicates it MUST be hodgkin lymphoma □ These cells only make up a subpopulation of the entire enlarged lymph node because there is a big inflammatory cell background - indicates the tumour cell turning on an immune response to try and repress the disease

Answer 11

§ Bimodal age incidence: □ Young adults (20-30 years); >50 years □ Not extremely common □ Biology differs between younger and older population

Answer 12

§ Clinical features □ Lymphadenopathy □ Painless, non-tender, rubbery lymph nodes (different from lymph nodes following infection which are sore and cancer that metastasise and go to lymph nodes and are hard) ® Cervical: 60-70% (neck) ® Axillary: 10-15% (under arms) □ Dyspnoea - mediastinal involvement: ® Young patients (nodular sclerosing subtype) - because they have a mass in the anterior of the chest ® Shortness of breath □ Splenomegaly: rare at presentation □ Constitutional symptoms (B): ® Fever (30%; cyclic), pruritis, weight loss, night sweats

Answer 13

§ Other features □ FBC: reactive blood count and film features ® Normochromic normocytic anaemia ® Leucocytosis: mild neutrophilia; mild eosinophilia ® Look like a patient with an infection □ ESR: elevated □ Bone marrow: usually reactive changes ® May be performed as staging procedure ® Rarely involved at presentation ® Granulocytic hyperplasia, increase in eosinophils - showing immune response □ Reduced cell mediated immunity: ® Loss of immunologically competent T cells ® Largely unknown why this happens

Answer 14

§ Diagnostic investigations □ Mass in anterior mediastinum □ Pathology: lymphoid tissue with thick fibrotic bands

Answer 15

® Chest: CT image showing grey area in anterior chest wall - Hodgkin lymphoma, enlarged lymph nodes against the vertebrae and the aorta ® Top right: pathology of the lesion, follicles and bands of scar tissues (fibrotic bands), nodular sclerosing hodgkin lymphoma, cellular nodular areas contain reed sternberg cell (bottom right) ® Cells in the background are lymphocytes within the lymph node □ Diagnosis on histology of LN or tissue: ® Reed-sternberg cell: large, bi- or multi-nucleate; prominent nucleoli ("owl eye") ® Inflammatory cells: lymphocytes, histiocytes, plasma cells, eosinophils ® Variable fibrosis □ Sub-types based on histology: ® Classified by pathologist - sub classify different pathological appearance ® Not of major clinical significance - staging is more important □ Ancillary pathology studies ® Immunophenotyping: ◊ Reed-sternberg cells express CD15 and CD30 antigens and are CD45 negative

Answer 16

□ Clinical staging: CT, MRI, PET ® Same clinical staging 1,2,3,4 as non-hodgkin ® A: No B (systemic) symptoms ® B: B symptoms (fever, night sweats, weight loss)

Answer 17

□ Potentially curable 85-90% cured, especially the younger patients □ Early stage favourable: stage 1 and 2 ® Currently combined modality preferred ◊ Short duration chemotherapy ◊ ABVD: doxorubicin, bleomycin, vinblastine and dacarbazine ◊ Involved field radiotherapy - pointing radiotherapy beams at the site where the disease exists □ Advanced disease: stage 3 and 4 ® More intensive combined chemotherapy □ Late effects of therapy ® Second malignancies ◊ Lung cancer (from radiotherapy to the chest) - most common ◊ Acute myeloid leukaemia (from cumulative dose of akylating agents) ◊ Breast cancer (DXRT (radiotherapy) to mediastinum / axilla(under the arm)) } Adolescent or young women } Dose-response relation exists } Overall risk is 20-50% } Happens 5-10 years after

Answer 18

® Currently combined modality preferred ◊ Short duration chemotherapy ◊ ABVD: doxorubicin, bleomycin, vinblastine and dacarbazine ◊ Involved field radiotherapy - pointing radiotherapy beams at the site where the disease exists

Answer 19

□ Advanced disease: stage 3 and 4 | ® More intensive combined chemotherapy

Answer 20

® Second malignancies ◊ Lung cancer (from radiotherapy to the chest) - most common ◊ Acute myeloid leukaemia (from cumulative dose of akylating agents) ◊ Breast cancer (DXRT (radiotherapy) to mediastinum / axilla(under the arm)) } Adolescent or young women } Dose-response relation exists } Overall risk is 20-50% } Happens 5-10 years after

Answer 21

□ Hodgkin lymphoma is a curable malignancy □ Overall cure rate approximately 80% □ Prognosis based on staging and bulk of disease □ Common presentation usually stage 2 disease in young people □ Infections: reduced cell-mediated T cell immunity □ Relapsed disease: difficult to treat ® Autologous bone marrow transplant ◊ Drugs needed to eradicate the Hodgkin lymphoma, but all these drugs would have already been used to try and treat the lymphoma before ® Second malignancies can occur 5%

Answer 22

§ BM neoplasm of end stage differentiated B cells □ B cells undergo further differentiation from a lymphocyte to a plasma cell with makes immunoglobulins. □ If that cell becomes malignant due to genetic abnormality they will look abnormal and will make immunoglobulin □ Because they are all derived from the same cell (clone) they all make the same immunoglobulin molecule (called a monoclonal immunoglobulin or paraprotein or M protein) § Tumour cells produce a monoclonal immunoglobulin: paraprotein or "M protein" § Free Ig light chains (Bence Jones proteins): small enough to be cleared in the kidney § IgG is most common, but Ig can be any class heavy chain of Ig (e.g. IgA myeloma) § Lytic bone lesions: cause pathological fractures □ Plasma cells eat away at bone and cause pathological fractures § Painful tumour, most painful of all blood cancers § Renal failure is common □ Abnormal protein can precipitate in the kidneys and cause acute renal failure § Peak age >60 years § Clinical problems from organ infiltration by neoplastic plasma cells: especially BM § Production of excess Ig ("M protein" or paraprotein) § Bleeding from platelet dysfunction (Ig coating) § Calcium loss and bone wastage

Answer 23

§ Recurrent infections are common: □ Strep; staph; E. coli □ Marrow failure and hypo-gammaglobulinaemia □ May present with pneumonia □ Paraprotein does not function normally □ Neoplastic plasma cells are suppressing normal plasma cell production, levels of normal immunoglobulins are low

Answer 24

§ Symptoms □ Bone pain □ Bone (pathological) fracture without obvious injury □ Frequent infections or an infection difficult to overcome (pnuemonia is common presenting feature) □ Tiredness, shortness of breath (anaemia, leukopenia, thrombocytopaenia) □ Kidney problems; renal failure □ Epistaxis (heavy nosebleeds) or easy bruising □ Drowsiness or confusion (high serum protein)

Answer 25

□ Immunoglobulins (quantitative): ® Total plasma immunoglobulins (Ig): elevated ® Reduced levels of normal immunoglobulins ® Overall increase due to paraprotein □ Serum protein electrophoresis: ® Identifies and quantifies monoclonal proteins ® Monoclonal protein in the gamma region ◊ "M" spike or paraprotein ® Blood count and film: Hb 100; WCC 3; Plt 100 ® Bone marrow examination

Answer 26

§ Other bone imaging methods □ Skeletal survey: (because it eats bone and makes holes) ® Plain x-rays of skull, long bones and axial skeleton ® Detects "lytic lesions" (local loss bone) ® Includes ◊ Lateral skull ◊ Frontal chest film ◊ Cervical-thoracolumbar spine ◊ Shoulders ◊ Pelvis, femur ® Majority of lesions are sharply defined and lytic ® ® 'pepper pot skull' - lesions where plasma cells eat into hard bone and leaches calcium into circulation causing high blood calcium ® Calvarium: top of the skull □ Magnetic resonance imaging: ® More sensitive than skeletal survey (especially for vertebral disease) □ CT scan: size of local lesions □ Radionuclide imaging (bone scan): ® Unable to detect lytic lesions ("cold spot") ® No new bone formation ("hot spot")

Answer 27

□ Common □ Large amount of protein cleared in the urine □ Lambda light chains (Bence Jones protein) are toxic to renal epithelium □ Amyloid deposits in the glomeruli □ Hypercalcemia □ Monitoring serum calcium and renal function is essential □ Paraprotein (especially the light chains) are toxic to the renal epithelium, get stuck and poison the renal cells causing acute renal failure □ Monitoring renal function and calcium level (which is toxic to kidneys)

Answer 28

□ Not curable, but patients are living longer □ Median survival approximately 5 years □ Therapy ® Hydrations: to prevent myeloma kidney - fluids to prevent acute renal failure ® Alkylating agents: remission in 50-70% ® Bisphosphonates to inhibit bone resorption ® Chemotherapy: melphalan, vincristine, cyclophosphamide ® Immunomodulators: thalidomide, lenalidomide ® Proteasome inhibitors: bortezomib ® Young: autologous stem cell (marrow) transplantation

Answer 29

□ Causes of death ® Renal failure, infections and haemorrhage (less common) ® They will relapse