Blood Disorders 5 PDF

 Blood disorders 5 Small lymphocytic lymphoma / chronic lymphocytic leukemia = Mainly from B cells > It is a low grade malignancy and it is an indolent tumor Manifests with bone marrow and lymph node involvement The leukemia involves...

 Blood disorders 5 Small lymphocytic lymphoma / chronic lymphocytic leukemia = Mainly from B cells > It is a low grade malignancy and it is an indolent tumor Manifests with bone marrow and lymph node involvement The leukemia involves bone Marrow and peripheral blood Lymphoma involves tissues like lymph nodes or extranodular tissue The chronic lymphatic leukemia → bone marrow The small lymphatic lymphoma → lymph nodes. chronic lymphatic leukemia most common leukemia of adults. High levels of expression of BCL2 (antiapoptatic gene) Up regulation of this gene like in ① diffuse large B cell lymphoma and ② follicular lymphoma Half life of the cells is prolonged ( will stay and Proliferate ) Associated with immune abnormalities (decreased immunity and increased susceptibility of infection and autoimmune disorders. ) Involved lymph nodes are effaced by sheets of small mature B lymphocyles. ( it is not characterized by nodular proliferation like follicular lymphoma) In most patients there is an absolute lymphocytosis in the peripheral blood ( increased lymphocytes. ) Indolent course (low grade) Small fraction transform to aggressive tumors (aggressive diffuse large B cell lymphoma) DLBL This transformation is named (richter transformation) - Lymph nodes with small lymphocytic lymphoma. - At lower magnification →The architecture is diffusely effaced with no nodules or nodular pattern ( distinguishing feature of follicular lymphoma) > - at higher magnification → diffusely infiltrated by the small mature B lymphocytes  Acute lymphoblastic Leukemia /lymphoma => Acute: because it is characterized by sudden Onset with aggressive behavior => Lymphoblastic: because it is characterized by the proliferation of lymphoblast or precursors of B (pre-b) or T (pre-t) cells that are immature and we call them lymphoblast → characterized by the earliest stage of the maturation of the lymphocytes Immature B or T calls (lymphoblasts) 85% are B- ALLs, the rest is T-ALLs B cell origin are commonly encountered in childhood and they present as leukemia, so they involve the marrow and we call them acute lymphoblastic leukemia T cell we call it acute lymphoblastic lymphomas because they occur in the thymus in the mediastinum and they affect the adolescent. Both come at younger age group. ALL is the most common type in children ( WBCs may be greater than 100,000 cell /ml (elevated) We use immune histo chemical stain to Subtype ALLs (B and T) Differentiate ALL from AML(acute myeloid leukemia) (which is characterized by the presence of myloblast rather than lymphoblasts) Anemia, neutropenia, and thrombocytopenia Because the proliferation of blasts suppresses normal hematopoiesis in bone marrow the patient presents with pancytopenia Hb → low Neutrophils → low → because the WBC count is mainly lymphocytes and lymphoblasts. → the patient is susceptible fo infections Thrombocytopenia → patient susceptible to bleeding tendencies CNS manifestation from maningeal spread or irritation Hepatosplenomegaly, and lymphoadenopathy → Extramedullary hematopoiesis Aggressive clinical behavior ( whether lymphoma or leukemia ) 95% of children obtain a remission / 75-85% are cured → aggressive tumor but cure rate is high (compaired to indolent tumors → usually cannot be cured) Scant basophilic cytoplasm fine chromatin with small nucleoli Lymphoblasts in the peripheral blood E Large cells large nucleus. Fine chromatin. Small Prominent nucleolus Cytoplasm is very scant → form a small rim around a large nucleus These are the characteristics of acute lymphoblastic leukemia Plasma cell myeloma /Multiple myeloma Plasma cell tumor ( Included in B cell neoplasm ) Why is it considered related to B cells? Because plasma cells derived from B cells. ( produce immunoglobulins ) Multiple lyric bone lesions with pathologic fractures, pain and hyper calcemia ( released calcium will go into the blood Median age → 70 yr Neoplastic plasma cells Suppress normal humoral immunity ( more susceptible to infections ) Secrete light chains immunoglobulins (bence jones proteins) U Bence jones protiens →detected in the urine (abnormal) Effects on bone, kidney and immunity (For diagnostic purposes) Factors by plasma cells Defects in humoral Renal dysfunction = Lytic lesion immunity => Deposition of proteinceous material in the > Major feature of - S Compromise kidney tubules → obstructive multible myloma function of proteinaceous casts => Mediate bone normal B cells : Deposition of light chains or bence jones destruction protein in the glumeruli → hypercalcemia Lytic lesions and renal faliure Hypondense bone Taking a biopsy from the bone will lesions give A definite diagnosis Most commonly in → BM microscopic examination vertebral column ribs, skull, pelvis femur ' & Increased numbers of plasma clavicle and scapula cells → > 30% of BM cellularitiy Pathologic fractures Bone marrow aspirate ( multiple myeloma patient) Normal marrow cells are largely replaced by neoplastic plasma cells Anemia →BM elements will be suppressed such as RBC 02 Sometimes with moderate leukopenia and thrombocytopenia Neoplastic cells exhibit bi/multinucleation Eccentric nucleus They may show vacuoles cytoplasm Peripheral cytoplasm Ou Sometimes they resemble normal cells with Perinuclear hof or clear area Myeloid neoplasm Derived from the myeloid series which give the granulocytes in the BM Devided into S A- acute myeloid leukemia Myeloblasts Different from lymphoblast Immature myeloid cells ( myeloblasts) accumulate Nuclei contains Many nucleoli in BM and PB → that's why we call them leukemia. not only small one Myeloblasts make up > 20% of BM cells. Granular cytoplasm ( it is the precursor of granulocytes Median age → 50yr Fatigue pallor (anemia) Very similar to ALL Abnormal bleeding (thrompocylopenia) Infections (other elements than myeloblasts are supressed) May cause peripheral extramedullary hematopoiesis (splendmegaly and lymphoadenopathy ) but less prominent than ALL Devastating aggressive disease (the management will be similar to aggressive tumors. ) The cure rate is less than ALL B- myeloproliferative neoplasms Overproduction of blood cells (hypercellular marrow ) with normal maturation With exception of myelofibrosis → fibrosis in the bone marrow and hypocellularity in later stages -next page Group of disorders: Chronic myeloid leukemia. Polycythemia vera Primary mylofibrosis. Essential thrombocythemia Hebatesplenomegaly (Elevated platelets count ) Characterized by normal maturation of the calls, so they reach the mature levels All without the exception can transform to AML at any stage Chronic myeloid leukemia (CML) Adults (25-60 yrs) Philadelphia (ph) chromosome is highly characteristic of CML Harbor bcr/abl fusion gene in 95% of cases →due to balanced (9:22) chromosomes translocation → This gene has tyrosine kinase activity (can be used to detect the presence of bcr /abl ) → can be treated with tyrosine kinase inhibitors. Leukocyte count is elevated >>>> 100,000 cell/ul → mostly in myeloid series → granulocytes (in different stages of maturation) 3 · Platelet are elevated + anemia It is chronic so it has insidious onset, slowly progressive Blast crisis → transform to (AML or ALL) → (from go chronic to acute )at any time es Polycythemia Vera Excessive proliferation of erythroid, granulocytic and megakaryocitic elements Most signs and symptoms related to increase in red cell mass (blood volume and vescocity) Must be distinguished from relative polycythemia, which results from hemoconcentration ( like in dehydration condition it will give false impression that the hemoglobin levels is high ) →caused by reduced plasma volume (hb is normal) Low levels of serum erythropoietin ( to differentiate from it secondary polycythemia → which is due to high erythropoietin levels ) →erythropoietin independent proliferation Harbors JAK2 mutation (imp in diagnosis) Splenomegaly Plethora → the skin looks hyperemic and red / and cyanosis Clinical features (congestion) → due to increased volume und viscosity Thrombosis Bleeding → high but dysfunctional platelets Pruritic → itching (histamine from basophils ) Hypertension (high blood volume) Headache and dizziness Gout → increased turn over of the cells and uric acid production Primary myelofibrosis Myloproliferative neoplasm of megakaryocytes (thrombocytosis) and myeloid cells (leukocytosis ) BM fibrosis caused by inappropriate release of fibrogenic factors from neoplastic megakaryocytes  Hallmark: Obliterative BM fibrosis → will reduce hematopoiesis and leads to cytopenia in last stages Extensive extramedullary hematopoiesis → Massive splenomegaly (may reach 4kg ) Harbor JAK2 mutations Red cells often exhibit bizarre shapes (tear drop cells ) On peripheral blood: Nucleated erythroid precursors and immature WBC ↳ S (leukoerythroblastosis) ~ The appearance of immature elements in the Pb because of the increased proliferation (Normally exists in BM ) C- myelodysplastic syndromes (MDS) → tumor of myeloid series Maturation defect associated with ineffective hematopoiesis There is proliferation in BM and production of RBCs but it is ineffective → associated with cylopenia as the cell will die in BM → problem in the maturation High risk of transformation to AML Transformed stem cells retain the capacity to differential into red cells granulocytes, panel platelets → but in an ineffective and disordered manner Marrow is hyper cellular PB show one or more cytopenia ( anemia, neutropenia, thrombocytopenia) May develop after chemotheraply or radiotheraply It can arise de novo, primarily without any predisposing factors) Age → 50-70 yrs End of lec.