Haematological Malignancies PDF

The Overview Leukaemia: Malignancy of the progenitor cells Acute Chronic Myeloid AML CML Lymphoid ALL CLL Myeloproliferative Neoplasms: Malignancy of myeloid cells Thrombocytes: Essential thrombocythemia RBC: Polycythaemia rubra vera...

The Overview Leukaemia: Malignancy of the progenitor cells Acute Chronic Myeloid AML CML Lymphoid ALL CLL Myeloproliferative Neoplasms: Malignancy of myeloid cells Thrombocytes: Essential thrombocythemia RBC: Polycythaemia rubra vera Leukocytes: Chronic myeloid leukaemia (CML) Everything: Primary myelofibrosis Lymphoma: Malignancy of lymphoid cells Hodgkin’s Non-Hodgkin’s Multiple Myeloma: Malignancy of plasma cells The Overview Leukaemia: Malignancy of the progenitor cells Acute Chronic Myeloid AML CML Lymphoid ALL CLL Myeloproliferative Neoplasms: Malignancy of myeloid cells Thrombocytes: Essential thrombocythemia RBC: Polycythaemia rubra vera Leukocytes: Chronic myeloid leukaemia (CML) Everything: Primary myelofibrosis Lymphoma: Malignancy of lymphoid cells Hodgkin’s Non-Hodgkin’s Multiple Myeloma Malignancy of plasma cells Leukaemia Neoplastic lesion of the cellular precursors (common myeloid/lymphoid progenitor) arising in the bone marrow Acute = large, poorly differentiated, non-functional blasts = more aggressive Chronic = smaller, well differentiated, poorly functional cells Lymphoid = B cells, T cells, NK cells Myeloid = Everything, mainly neutrophils Relative prevalence: CLL (very indolent) > AML > CML > ALL Relative mortality: AML (very aggressive) > ALL > CML > CLL Diagnosis: 1. Bone marrow biopsy and trephine - normal marrow will be replaced by leukemic cells 2. Blood smear and FBE - anaemia, thrombocytopenia, neutropenia, abnormal cells 3. Immunophenotyping - looking for specific mutations Acute Myeloid Leukaemia Demographic: Older adults >65 yrs, often with a history of myelodysplastic syndromes Peripheral blood film: >20% blasts + Auer rods Bone marrow biopsy: +++ Hypercellularity of myeloid lineages, blasts Key Features: Anaemia: Pallor, fatigue, dyspnoea, palpitations, dizziness Thrombocytopenia: Petechiae, epistaxis, bleeding gums Neutropenia: Frequent, severe infections B symptoms (fever, fatigue, weight loss, night sweats) Other Features (because of blasts depositing in peripheral areas) Gum hypertrophy Skin deposition Large hepatosplenomegaly Bony tenderness Lymphadenopathy Prognosis: Very bad (65 yrs, Philadelphia chromosome (9:22 BCR-ABL) mutation Peripheral blood film: Left shift with normal lymphocytes Bone marrow biopsy: Moderate hypercellularity with left shift and increased granulocytes Key Features: 1. Chronic phase = Asymptomatic (often an incidental finding) or ○ Vague fever, fatigue, weight loss ○ Massive splenomegaly (early satiety, LUQ pain, shoulder tip pain) 2. Accelerated phase ○ Anaemia ○ Thrombocytopenia ○ Basophilia → Pruritus ○ Leukocytosis 3. Blastic phase (basically AML) Prognosis: Variable (5-50yrs), essentially treatable now with Imatinib (tyrosine kinase inhibitor)- less deadly Acute Lymphoid Leukaemia Demographic: Children 80yrs Peripheral blood film: >20% blasts, very immature lymphocytes with minimal cytoplasm Bone marrow biopsy: +++ Hypercellularity with invasion by blastic lymphoid cells Key Features: Anaemia: Pallor, fatigue, dyspnoea, palpitations, dizziness Thrombocytopenia: Petechiae, epistaxis, bleeding gums Neutropenia: Frequent, severe infections Hepatosplenomegaly Sites of Spread (high vascularity) Brain Bones (= marrow failure and compression fractures) Balls (testes) Prognosis: Very good in children (90%), not bad in adults (60%) Children tolerate chemotherapy better than elderly adults Chronic Lymphoid Leukaemia Demographic: Elderly >80yrs Peripheral blood film: Small, mostly mature lymphocytosis (95% originate from B cell lineages), smear cells Bone marrow biopsy: Hypercellular but not a problem until late Key Features: Early disease: Lymphadenopathy ○ Painless, rubbery lymphadenopathy with atypical lymphocytes ○ Resembles lymphoma but originates in the bone marrow Late or aggressive disease: ○ Hepatosplenomegaly ○ Anaemia ○ Thrombocytopenia Only 5-10% present with the classic fever, sweats, weight loss Prognosis: Very good (>25 years), patients often die with the condition - most common leukaemia in adults and elderly The Overview Leukaemia: Malignancy of the progenitor cells Acute Chronic Myeloid AML CML Lymphoid ALL CLL Myeloproliferative Neoplasms: Malignancy of myeloid cells Platelets only: Essential thrombocythemia RBC (+ others): Polycythaemia rubra vera Leukocytes: Chronic myeloid leukaemia (CML) Everything: Primary myelofibrosis Lymphoma: Malignancy of lymphoid cells Hodgkin’s Non-Hodgkin’s Multiple Myeloma Malignancy of plasma cells Essential Thrombocytopenia Overproduction of platelets for no good reason (>450 x 10⁹/L) Associated with JAK2 or calreticulin mutations Peripheral blood film: Large clusters of irregular platelets, giant platelets Bone marrow biopsy: Hypercellular with large immature megakaryocytes Key Features: Paradoxical poor clotting → Haemorrhage, often GIT origin Thrombosis: TIAs (visual disturbance), strokes, MIs, PVD, DVT etc. Erythromelalgia (small, episodic microvascular thrombosis → red painful extremities “Secondary thrombocytosis” is overproduction of platelets when there is a good reason (e.g. infection, inflammation, bleeding) Polycythaemia Rubra Vera Overproduction of RBC, 97% are heterozygous for the JAK2 mutation Peripheral blood film: Lots of microcytic hypochromic RBC +/- elevated platelets Bone marrow biopsy: Hypercellular with elevated everything (panmyelosis) Key Features: Erythrocytosis ○ Facial, conjunctival, palmar flushing ○ Pruritus after heat (itchy after a hot shower) ○ Gout (increased RBC turnover) Thrombotic (platelets also increased) ○ Paradoxical poor clotting → Haemorrhage, often GIT origin, peptic ulcer disease ○ Thrombosis: TIAs (visual disturbance), strokes, MIs, PVD, DVT etc. ○ Erythromelalgia (small, episodic microvascular thrombosis → red painful extremities Patients will have decreased serum EPO (negative feedback) Primary Myelofibrosis Rare global bone marrow fibrosis leading to failure Associated with JAK2 mutation in 50% Leucoerythroblastic peripheral blood film: Immature RBC (anisocytosis, poikilocytosis, nucleated) and WBC, tear drop RBCs Bone marrow biopsy: “Dry tap” - nothing comes out Key Features: A → G Anaemia Bone and joint pain (loss of marrow) Constitutional symptoms Dry BM aspirate Extramedulllary haematopoiesis (hepatosplenomegaly) Fatigue (most common presenting complaint) Gout The Overview Leukaemia: Malignancy of the progenitor cells Acute Chronic Myeloid AML CML Lymphoid ALL CLL Myeloproliferative Neoplasms: Malignancy of myeloid cells Thrombocytes: Essential thrombocythemia RBC: Polycythaemia rubra vera Leukocytes: Chronic myeloid leukaemia (CML) Everything: Primary myelofibrosis Lymphoma: Malignancy of lymphoid cells Hodgkin’s Non-Hodgkin’s Multiple Myeloma Malignancy of plasma cells Hodgkin’s Lymphoma Malignant proliferation of lymphoid cells with Reed Sternberg cells Key features: Painless lymphadenopathy: Rubbery, mobile, enlarged lymph nodes ○ Cervical/supraclavicular most common ○ Rarely can present with SVC syndrome or pleural effusion B symptoms (fever, fatigue, night sweats, weight loss) Hepatosplenomegaly Tender LN with EtOH consumption Associated with a past history of EBV infection Non-Hodgkin’s Lymphoma Malignant proliferation of lymphoid cells with no Reed Sternberg cells The vast majority arise from B cells and there are multiple types: Burkitt’s lymphoma ○ Very aggressive ○ Caused by mutation of the c-myc gene, most commonly t(8;14) ○ Associated with EBV (endemic variant, also associated with chronic malaria) and HIV (immunodeficient variant) ○ Submental and submandibular lymphadenopathy Follicular lymphoma ○ Indolent ○ Caused by mutation of the bcl-2 gene, t(14;18) ○ Often presents with widespread lymphadenopathy Diffuse large B cell lymphoma ○ Aggressive, can be a progression of follicular lymphoma ○ More rapid lymphadenopathy Mantle cell lymphoma ○ Indolent ○ Caused by overexpression of cyclin D1 ○ Causes mucosal polyps in the GIT, mainly around the ileocaecal valve Multiple Myeloma Monoclonal expansion of plasma cells (secreting antibodies) Peripheral blood film: Rouleaux bodies Key Features: CRAB HyperCalcemia Renal failure Anaemia Bony lesions (lower back pain) Urinalysis will show Bence Jones protein