WBC neoplastic disorders for MBChB students.pptx

Wbc neoplastic disoders

1. NEOPLASTIC DISORDERS OF WHITE BLOOD CELLS These include Leukemias Lymphomas Myelomatosis and related conditions 1

2. Leukemias These are neoplastic clonal disorders of hematopoietic tissues in which a stem cell or other precursor blood cell in the bone marrow or lymphoid tissue proliferates Clonal proliferation of the leukemic cells and tissue infiltration lead to the impairment or suppression of normal blood cell production Leukemic cells do not function or mature normally 2

3. Classification of Leukemia This is based on whether the disease is acute (rapidly progressive) or chronic (slowly progressive) and whether the leukemic cells are of myeloid or lymphoid in origin. Leukemias can therefore be broadly divided into : Acute myeloid leukemia (AML) Acute lymphoid leukemia (ALL) Chronic myeloid leukemia (CML) Chronic lymphoid leukemia (CLL 3

4. Features of acute leukemias Features Acute myeloid leukemia (AML) A cute lymphoblastic leukemia (ALL) abnormality Clonal proliferation of myeloblasts Clonal proliferation of lymphoblasts Age incidence More common in adults in Tropical Africa. but generally have similar frequency as ALL in children below 15yrs. Most often found in children (males more than females) Clinical findings Bone pain, fever, anaemic ,bleeding purpura, thrombosis and hepatosplenomegally. There is often inflammation of the gums, skin involvement and coagulation defects Bone pain, fever, anaemia, bleeding, purpura, thrombosis and hepatosplenomegally. Lymphadenopathy and Central nervous system involvement ( late stages of the disease) Laboratory Findings Increased WBC count but can be normal. Reduced platelets Haemoglobin level is reduced or normal Myeloblasts seen in PBF Presence of Auer rods is diagnostic. Bone marrow is hypercellular with myeloblast. Increased WBC count but can be normal. Reduced platelets Haemoglobin level is reduced or normal Lymphoblasts seen in PBF Auer rods absent. Bone marrow is hypercellular with lymphoblasts and lymphocytes. 4

5. Features of chronic leukemias Features Chronic myeloid leukemia (CML) Chronic lymphoid leukemia (CLL) abnormality Clonal proliferation of myeloid cells Clonal proliferation of B lymphocytes occasionally of T lymphocytes Age incidence In developing countries CML is common in younger people and children More often found in older people >60yrs of age, with more men affected than females. In Tropical Africa CLL is also found in younger people Clinical findings Splenomegaly, lethargy, and weight loss in early stages. CML develops into AML which is preceded with an accelerated stage. The spleen and liver enlarge. There is anaemia, thrombocytopenia with bleeding tendency, fever, sweats and bone pain . Weight loss, lymphadenopathy and hepatosplenomegally. In late stages inadequate immune responses resulting in infections .Anaemia from hypersplenomegally and autoimmune haemolysis. Laboratory findings WBC increased Platelets increased or normal HB reduced or normal PBF shows increased neutrophils, marked left shift with all stages of neutrophilic cell maturation seen Bone marrow hypercellular with mature and immature myeloid cells seen WBC increased Platelets reduced in late stages HB moderately reduced PBF shows absolute lymphocytosis Bone marrow hypercellular with lymphoid cells. 5

6. Investigations: TBC and : 60% of pts have an elevated WBC. Most are anemic Most are thrombocytopenic PBF - 90%have blast in the peripheral blood film. Bone marrow aspirate and biopsy : 20% or more of all nucleated cells are blast. 6

7. Cytochemical staining Sudan Black – ALL Myeloperoxidase - AML Cytogenetic studies T(15;17), T(8;21), Inv(16). Radiology: CXR: Mediastinal mass(T-cell ALL) Osteopenia or lytic lesion 50% of patients with ALL.(intractable pain). 7

8. DIC: Most common with promyelocytic leukemia,small% monocytic leukemia&ALL Electrolytes: Hypo/hyperkalemia Hypomagnesimia hyperphosphatemia Hypermetabolism :  LDH. uric acid 8

9. The Philadelphia chromosome It is characterized by a cytogenetic aberration consisting of a reciprocal translocation between the long arms of chromosomes 22 and 9; t(9;22 ). 9

10. Lymphoblast/myeloblast 10

11. PBF from a pt with CML 11

12. Management: A-Supportive measure : -Isolation -Oropharynx/GIT decontamination to prevent fungal infection -IV antibiotics for infection -Blood transfusion if anemia and thrombocytopenia. 12

13. Therapeutic option B-Curative intent : - O nly allogenic bone marrow transplant . C_Classical approch (curative/palliative) Induction chemotherapy Consolidation of remission Maintenance chemotherapy 13

14. LYMPHOMAS Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and other lymphoid tissues and cause the clinical feature of lymphadenopathy. They can be divided into Hodgkins lymphoma (HL) and non Hodgkins lymphoma (NHL) based on the presence of Reed-Sternberg (RS) cells in Hodgkins lymphoma The most important of the NHL found in tropical A frica is the Burkitt's lymphoma It is found mainly in children aged 4-9yrs as a solid tumour of the face and jaw or abdomen. It is associated with Epstein Barr virus (EBV). RS cell is thought to be from the B cell lineage with abnormal synthesis of full length immunoglobulin chain Severe Hodgkins lymphoma is also associated with Epstein-Barr virus but its role in the pathogenesis is not clear. 14

15. Clinical presentation and findings Can present at any age but rare in children with peak incidence in young adults Male to female predominance ratio is 2:1 Common presentation is firm discrete lymphadenopathy superficial mainly of the cervical area Starts with a single group of lymph nodes, weight loss, night sweats. Lymphadenopathy may spread to other groups of nodes as the disease progresses Constitutional symptoms are common in patients with widespread disease and may include fever , pruritis , alcohol induced pain in areas where the disease is present, weight loss, night sweats, weakness and fatigue. 15

16. Laboratory findings Normocytic-normochromic anaemia In advanced disease bone marrow involvement may occur with bone marrow failure One third of patients have neutrophilia, eosinophilia is frequent Advanced disease is associated with lymphopenia and loss of cell mediated immunity Serum lactate dehydrogenase (LDH) is initially raised in 30-40% of cases The diagnosis is made by histological examination of excised lymph node 16

17. MULTIPLE MYELOMA This is a monoclonal proliferation of plasma cells (myeloma cells) in bone marrow, arising from the malignant transformation of a B lymphocyte The malignant plasma cells replace normal haemopoetic tissue, destroy bone and secrete monoclonal ( single type) immunoglobulin usually IgA or IgG referred to as paraprotein Most myelomas also produce immunoglobulin fragments ( light chains or parts of heavy chains) Light chain fragments filter through kidney glomeruli and can be found in the urine ( Bence Jones proteins) 17

18. Clinical presentation and findings This is mainly a disease of the elderly , but in developing countries, it is also found in those between 30-60yrs. Presents with anaemia, bone pain. May present with fracture ,renal disease, thrombosis or haemorrhage. Laboratory findings will include Normocytic normochromic anaemia, Raised ESR, Bence Jones proteins is found in urine and P lasma cells may be seen in PBF and Bone marrow films. 18