LUKEMIA
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  • 1.
    • Golden rules in science & medicine:
    • Start strong stay strong ; start loose become more loose
    • Look for fundamentals & let the details look for themselves
    • ( so, after study of each subject
    • do a subject skeleton /mind map for it )
    • Truly, one picture is worth ,at least, a thousand words.
    • Do not rush in your diagnosis.
    • Common is common.
    • Golden rules in genetics:
    • Each human character is controlled by
    • 2 genes / gene clusters on 2 homologous chromosomes
    • so, gene is the unit of inheritance.
    • Each specific gene encodes for a specific antigen or protein.
    HEMATOLOGICAL MALIGNANCIES
  • 2. Hematological Malignancies
    • Definition:-
    • Group of haematological disorders characterized by
    • clonal expansion of
    • haemopoietic cells which has undergone
    • genetic mutation
    Haemopoietic cells :in the marrow or peripheral lymphoid tissue Clonal :derived from a single cell proliferation ( N.B. it is autonomous & uncontrolled) compare with normal haemopoiesis
  • 3. Clonal evolution of malignancy Most malignancies r the result of several sequentially acquired mutations rather than single catastrophic mutation.
  • 4.
    • POINTS OF INTEREST IN NORMAL HEMOPOIESIS
    Stromal cells are the major source of growth factors except for : a. Erythropoietin , 90 % of which is synthesized in the kidney. b. Thrombopoietin , made largely in the liver .
  • 5.  
  • 6. Cell cycle CDK p53 is known as the ‘ guardian of the genome ‘
  • 7.  
  • 8.
    • The genes involved in the development of Haematological malignancies
    • can be broadly divided into 2 groups :
    • 1. Oncogenes 2. anti-oncogenes / Tumour Suppressor Genes (TSG)
  • 9. Usually point mutation or gene deletion (del.) One of the striking features of haemat.malign. ( in contrast to most solid tumours ) is high frequency of translocations ( t ) p53 the { guardian of the genome } is The most significant TSG in human cancer It is mutated or inactivated in > 50 % of malignant diseases including many haematological malignancies Examples of chromosomal translocations in haematological malignancies will be mentioned later on TSG may acquire loss-of-function mutation malignant transformation e.g. p53 (at 17p13 ) & Rb (at 13q14 ) Oncogenes arise because of gain-of-function mutation in the normal cellular genes ( proto-oncogenes ) TSG act in Cell cycle control (Checkpoint) ( G-1 S G-2 M ) DNA damage cell-cycle arrest for 1 of 2 1.DNA repair & continuation of cell cycle 2.Apoptosis by activating pro-apoptotic genes proto-oncogenes are often involved in transduction ( transfer of external signals to the nucleus to activate genes ) Tumour Suppressor Genes (TSG) (anti-oncogenes) Oncogenes
  • 10. The aetiology of Haematological Malignancies
    • It is a combination of
    • genetic background &
    • environmental influence
    • that determines the risk of developing
    • haematological malignancy
    • I. Inherited factors :- see next page
    • II. Environmental influence:
    • #. Chemicals
    • #. Drugs
    • #. Radiation
    • #. Infections
  • 11. I. Inherited factors
    • The incidence of leukaemia is greatly increased in some genetic diseases , particularly :
    • D W - F A B
    • D Down’s syndrome:
    • 20-30-fold increased frequency of AL ( M-7)
    • W Wiskott - Aldrich syndrome ( WAS ):
    • F Fanconi’s anaemia
    • 10% of cases develop AML
    • A Ataxia telangiectasia
    • B Bloom’s syndrome
    • Ashkenazi Jewish with TID
    • T elangiectasia +
    • life-threatening i nfections +
    • d warfism
    • Autosomal recessive
    • characterized by :
    • Defective DNA repair &
    • Hypersensitivity to
    • other
    • DNA damaging agents
    X-linked recessive ( T hrombocytopenia & BLEEDING with small plt & defective plt. Aggr. + recurrent i nfections-due to COMBINED IMMUNE-PARESIS in i nfancy) Tri- somy- 21
  • 12.
    • #. Chemicals : chronic exposure to benzene may cause
    • BM hypoplasia , dysplasia & chromosomal abnormalities
    • & is unusual cause of MDS or AML
    • #. Drugs : The alkylating agent (e.g. chlorambucil ; Melphalan)
    • predispose to AML,
    • especially if combined with radiotherapy
    • or if used to treat patients with
    • lymphocytic or plasmacytic disorders
    • #. Radiation : Radiation ,especially to the BM, is leukaemogenic see fig.--
    • #. Infections: Pls, refer to lymphoma Fig.10-2
    II. Environmental influence
    • Alkylating agent express reactive alkyl group
    • which make covalent bond with cell molecules (particularly purine in DNA) DNA damage
  • 13. The most common Specific abnormality in childhood ALL is the t ( 12 ; 21 )
  • 14.  
  • 15. HAEMOPOIETIC STEM CELLS (HSC) (CD34+ ; CD38-) LYMPHOID STEM CELLS MYELOID STEM CELLS LYMPHOCYTES OTHER BLOOD CELLS
  • 16. HAEMOPOIETIC STEM CELLS (HSC) LYMPHOID STEM CELLS MYELOID STEM CELLS LYMPHOCYTES RBC OTHER WBC PLATELET
  • 17. HAEMOPOIETIC STEM CELLS LYMPHOID STEM cell MYELOID STEM CELLS LYMPHOCYTES ACUTE CHRONIC OTHER BLOOD CELLS
  • 18. ACUTE CHRONIC HSC or early progenitors Maturing & mature cells usually aggressive & rapidly fatal if not rapidly treated x x some has high cure rate e.g. ALL( L1) in children X
  • 19. HAEMOPOIETIC STEM CELLS LYMPHOID STEM CELL Lymphoblast MYELOID STEM CELL Myeloblast LYMPHOCYTES ACUTE CHRONIC M Y E L O I D L Y M P H O I D OTHER BLOOD CELLS
  • 20. Lymphoblasts Lymphocytes Granulocytes Myeloblasts ALL AML CML CLL
  • 21. LYMPHOID STEM CELLS Pre-T Thymocyte Peripheral T Cells T- Helper T- Supp. Pro-B Pre-B B- Virgin B- Mature LPC PLASMA CELL ALL CLL
  • 22. MYELOID STEM CELLS PRO - NORMOBLAST RBC MONO- BLAST MONO- CYTE MYELOBLAST PRO-MYELOCYTE MYELOCYTE META-MYELOCYTE BAND or STAB GRANULOCYTES MEGA- KARYO- BLAST PLATELET AML CML
  • 23. Acute Leukemia means Maturation Arrest Sustained SELF-RENEWAL at the expense of DIFFERENTIATION accumulation of BLAST CELLS Differentiation (Maturation) Self-renewal Maturation Arrest Sustained self-renewal Differentiation (Maturation) Acute Leukemia Normal
  • 24. ACUTE LEUKEMIAS Types& Sub-types INCIDENCE Age Clinical presentation & Lab. Data B.M. failure Anaemia symptoms & signs of anaemia Neutropenia recurrent infections NB Total WBC count ( High; Normal or low ) Thrombocytopenia bleeding tendency Tissue Infiltration
  • 25. Clinical presentation & Lab. Data Anaemia symptoms & signs of anaemia Neutropenia recurrent infections Thrombocytopenia bleeding tendency Tissue Infiltration: e.g. organomegaly (hepatosplenomegaly) ; lymphadenopathy ; meningeal syndrome ( headache, nausea, vomiting, blurring of vision & diplopia with blast cells in CSF) ; skin lesions ; testicular swelling -------- etc. B.M. failure caused by accumulation of BLAST cells
  • 26. ALL AML TYPES & AGE mainly children ~ 4 yr mainly adults ALL the most common malignancy of childhood ( 25-30 % ) a second rise after the age of 40 yr AML incidence increase with age
  • 27.
    • LAB DIAGNOSIS OF ACUTE LEUKAEMIA
    • Complete Blood Count (CBC) & smear
    • BM aspiration & trephine Biopsy
    • Special (cyto-chemical) Stains
    • Immunological markers
    • (Immuno-pheno-type “ IPT”) by
    • Flow cyto metry “FCM”
    • Chromosomal studies
    • Cyto-genetic analysis
    • Molecular genetic analysis including FISH
    • Storage of BM smears wrapped in aluminum foil at -20˚C
    • Others: microbiological ; Biochemical .........etc.
  • 28. CBC ;Smear & BM aspiration
    • Acute Leukaemia (AL) is defined as
    • the presence of
    • over 20 % of blast cells in
    • the peripheral blood or
    • bone marrow
    • at clinical presentation
    • Q: Could we diagnose AL with less than 20 % blasts ?
    • A: YES , if s pecific leukaemia - a ss ociated
    • cytogenetic or molecular genetics abnormalities
    • are present
  • 29. AML FAB SUB-TYPES OF AL M0 M1 M2 M3 M4 M5 M6 M7 L1 L2 L3 ALL Morphological classification of AL
  • 30. Burkitt’s Lymphoma is the Lymphomatous correlate of L- 3 ALL
  • 31. LYMPHOBLASTS IN ALL FAB SUBTYPES large & homogeneous é marked Cy. basophilia & Cy. vacuoles Larger& heterogeneous é more abundant Cy. & more prominent Ni. small & monomorphic é large N/C ratio L3 L2 L1
  • 32. ACUTE LEUKEMIAS SPECIAL STAINS M1-M4 M5 L2 LYMPHOBLAST MYELOBLAST MONOBLAST PAS Periodic acid- Schiff *Sudan Black-B’ SBB ’ * Myeloperoxidase’ MPO ’ * Specific Esterase Non-Specific Esterase
  • 33. IPT of AL male predominance & Mediastinal mass CD14&CD15: M4 & M5 Glycophorin -A : M6 CD41a(GpIIb/IIIa) : M7 CD 14 & !% in M4& M5 Glycophorin A in M6 CD41a in( Myeloperoxidae in M0 CD14 &CD15 in M4 & M5 Glycophorin-A in M6 CD41a in M7 TdT ; Terminal deoxynucleotidyl transferase ~12% L1 or L2 ~ 3% L3 ~85% L1 or L2 ± ++ - cIg +ve Commonly child often infant CD 10 ( CALLA ) Pre-B common Pro-B sIg +v e B-ALL
  • 34. Prognostic factors in ALL ( still + ve) at 3 - 6 months (- ve) at 1-3 months Minimal residual disease (MRD) > 4 week < 4 week Time to remission > 1 week < 1 week Time to clear b l asts from bl ood P h + ve , or P seudo-diploid Normal or Hyperdiploid Cytogenetics T-ALL ( in children ) C ALLA IPT High (> 50.000 /µL) Low WBC count ( + ) ( - ) CNS disease at presentation b oys (?) testes is a common site for relapse G irls Sex Adult ( or infant < 2 yr ) C hild Age P oor G ood
  • 35. Myeloblast M0-M1 Monoblast M5 Pro-normoblast Megakaryo - blast M7 Promyelocyte M3 AML FAB-sub-types M0 - M7 M2 M4 M6 N.B. odd No.:- single cell even No.:- double cell Auer rods
  • 36. M5a (monoblastic) M5b (monocytic) Pro-normoblast M7 Megakaryo - blastic M3 Ac. Promyelocytic L. (APL) AML FAB-sub-types M2 with granulocytic maturation M4 with granulocytic & monocytic maturation M6 ( Erythroleukaemia ) N.B. odd No.:- single cell even No.:- double cell M0 un differentiated M1 without maturation
  • 37. M5 Megakaryo- blast M7 Promyelocyte M3 & M-3v AML Specific clinical. features M4 tissue infiltration Acute MF (no splenomegaly BM MK—blasts) DD:- MMM Myelofibrosis é Myeloid Metaplasia DIC
  • 38. 0 0
  • 39. ACUTE LEUKEMIAS SPECIAL STAINS M4 M5 MYELOBLAST MONOBLAST *Sudan Black-B’ SBB ’ * Myeloperoxidase’ MPO ’ *Specific Esterase Non-Specific Esterase DE M2-SBB+ve Auer rod M2-SBB+ve CG M2-MPO+ve CG M4-SBB+ve My Mo-ve
  • 40. AML é. out M aturation M1 M2 AML é granulocytic Maturation
  • 41. Myeloblast Promyelocyte C: Heavy azurophilic granulation (hypergranular) & Auer rods (rod-shaped granules) strongly positive for MPO Faggot cells : cells with bundles of Auer rods N: with nucleoli ( Ni ) APL M3 Classical
  • 42. APL M3 Faggot cell
  • 43. APL (M-3v) micro-granular variant Characterized by: paucity of myeloid granules & dumb-bell nucleus M-3v
  • 44. AML (AMML) M4 AML with granulocytic & monocytic maturation Monoblast Myeloblast +
  • 45. M5
  • 46. Myeloblast Pro- normoblast > 50% of the nucleated marrow cells r erythroid &Myeloblasts < 30% BM NEC M6 AML Erythroleukemia M6
  • 47. Myeloblast Megakaryo- blast Large and small megakaryoblasts with high N/C ratio C: is pale & a granular with blebs EM Platelets Peroxidase +ve AML M7 Megakaryoblastic L.
  • 48. IPT of AL male predominance & Mediastinal mass CD14&CD15: M4 & M5 Glycophorin -A : M6 CD41a(GpIIb/IIIa) : M7 CD 14 & !% in M4& M5 Glycophorin A in M6 CD41a in( Myeloperoxidae in M0 CD14 &CD15 in M4 & M5 Glycophorin-A in M6 CD41a in M7 TdT ; Terminal deoxynucleotidyl transferase ~12% L1 or L2 ~ 3% L3 ~85% L1 or L2 ± ++ - cIg +ve Commonly child often infant CD 10 ( CALLA ) Pre-B common Pro-B sIg +v e B-ALL
  • 49. M5 t ( 9 ; 11 ) t ( 11 ; 19 ) del (11q) M3 t ( 15 ; 17 ) AML Translocations (t) & other chromosomal changes M2 t ( 8 ; 21 ) M4-Eo inv ( 16 ) del ( 16q ) 11q23 abnormalities detected in 85 % of secondary AML
  • 50. Prognostic factors in AML No Yes Complete remission after 1 course ? myeloid lymphoid CML-BC ( + ) ( - ) T rilineage Dysplasia ( + ) ( - ) Multi-drug resistance (MDR) del ( 5 or7 ) ; ( 11q23 ) t(8,21) ; t(15,17) & inv(16) T ranslocations ( + ve ) ( - ve ) IPT ( CD-34 ; HLA-DR & TdT ) High (> 50.000 µL) Low WBC count ( + ) ( - ) CNS or extra med. Disease at presentation ( + ) ( - ) i.e. denovo Previous MDS / MPD / Chemotherapy Adult ( > 60 yr ) or (infant < 2 yr ) Aged 40-60 yr induction remission 80% Age Poor Good
  • 51. Hybrid Acute Leukaemia (Hybrid AL)
    • AL with blast cells showing
    • features of both ALL & AML
    Bi-phenotypic Bi-lineal Blasts with features of ALL Blasts with features of both ALL & AML on the same cell Blasts with features of AML 2 separate cell populations
  • 52. Up to 1993, the reported cases are 160 The 1 st reported case in Arab countries AML is the type often found in Cong. Leukaemia particularly M5&M7 Prognosis is extremely poor The Practitioner.Vol.10,No12,Dec.1999
  • 53. Clinical presentation & Lab. Data Anaemia symptoms & signs of anaemia Neutropenia recurrent infections Thrombocytopenia bleeding tendency Tissue Infiltration: e.g. organomegaly (hepatosplenomegaly) ; lymphadenopathy ; meningeal syndrome ( headache, nausea, vomiting, blurring of vision & diplopia with blast cells in CSF) ; skin lesions ; testicular swelling -------- etc. B.M. failure caused by accumulation of BLAST cells
  • 54. Pallor
  • 55. Infections Pneumonia
  • 56. Bleeding Tendency Extensive Bruising Mucosal Bleeding Purpura
  • 57. Bleeding Tendency Retina Cerebral
  • 58. Gum Hypertrophy Lymphadenopathy
  • 59. Leukemic Skin Infiltrate Testicular Leukemia Leukemic Infiltrate
  • 60. Mediastinal Involvement
  • 61. Therapy of AL
    • Supportive: for BM failure
    • Specific: Chemotherapy ± Radiotherapy
    • *. Induction of remission
    • *. Intensification (consolidation)
    • *. Cranial prophylaxis
    • *. Maintenance therapy
    • Stem Cell Transplantation: allogeneic SCT
  • 62. Myelodysplastic Syndrome (MDS) Myelodysplasia of Haemopoietic cells Ineffective Haemopoiesis Anaemia symptoms & signs of anaemia Neutropenia recurrent infections Thrombocytopenia bleeding tendency ANT in various combinations : RA : Refractory anaemia RN : Refractory Neutropenia RT : Refractory Thrombocytopenia R Bicytopenia : ( e.g. A + N ; A + T ; N + T etc.---------------)
  • 63. M D S L O W R I S K H I G H R I S K Any of the above with Promonocytes As any of the above with Persistent monocytosis > 1.0 X 10 3 / µL Chronic myelo-monocytic leuk. ( CMML ) 20% of MDS Tissue infiltr . ( gum hypertrophy; splenomeg.; skin rash & LAP) Blasts over 20 % or Auer rods present Blasts >5 % RAEB in transformation ( RAEB-t ) Blasts 5 - 20 % Blasts < 5 % RA with excess blasts ( RAEB ) Blasts < 5 % Ring sideroblasts > 15 % of total erythroblasts Blasts < 1 % RA with ring sideroblast ( RARS ) Blasts < 5 % Blasts < 1 % Refractory anaemia ( RA ) BM PB
  • 64. Chronic Lymphocytic Leukaemia (CLL) Chronic Myeloid Leukaemia (CML) TYPES & AGE Peak incidence 70 ± 10 yr Male : female 2 : 1 Any age but most frequently at the age of 50 ± 10 yr Male : female 1.4 : 1 Only 15 % before the age of 50 yr
  • 65. C hronic M yeloid L eukaemia (CML)
  • 66. Anaemia symptoms & signs of anaemia High total WBC count : 50 – 500 X 10 3 / µL Hyper-Leucocytosis *..In up to 50 % of cases Dx. is made incidentally from the routine CBC bleeding tendency inspite thrombocytosis(?) Plt.dysfunction Clinical Presentation of CML Huge spleen Discomfort& Indigestion (small meals) Hyper-metabolism: #.weight loss #. Lassitude #.night sweat #.anorexia (?) mimic hyper-thyroidism Gout & Renal impairment Visual disturbances & Priapism 2ry to hyperleucocytosis & leuco-stasis with impaired microcirculation Urticaria
  • 67. Anaemia Normocytic Normochromic High total WBC count e.g. 50 - 500X10 3 / µL Hyper-Leucocytosis Smear: complete spectrum of myeloid cells (myeloblast in the chronic phase: less than 5 %) with eosinophilia & basophilia #. Most frequent thrombocytosis but, may be normal or low #. Plt.dysfunction Laboratory features of CML
    • Ph’ pos .: over 95 %
    • NB: Ph’ neg. BCR-ABL pos. CML
    • behaves clinically like Ph’ pos. CML
    • Hyperuricaemia
    • High B12& B12 binding capacity
    • (due to increased TC-1 from neutrophil)
    • False hyperkalaemia
    • (K + released from leucocytes)
    • & false hypoglycemia
    • ( glucose consumed by leucocytes)
    • Low NAP score ( N :20-100 )
    • (neutrophil alkaline phosphatase)
    BM: Hypercellular with granulocytic predominance
  • 68.  
  • 69. NAP score CML P regnancy Myelo p roliferative Disorders (MPD) - Polycythaemia (rubra) vera - PRV - Myelofibrosis ( MF ) P olymorphnuclear Leucocytosis ( Myeloid Leukaemoid Reaction ; Neutrophilia ; Neutrophil leucocytosis) Low Raised
  • 70.  
  • 71. The Philadelphia ( Ph’ ) chromosome: reciprocal translocation
  • 72. BCR-ABL oncoprotein : 210 KDa in CML & some Ph’+ve ALL due to M-BCR: Major-BCR 190 KDa in other Ph’+ve ALL due to m-BCR: minor-BCR BCR-ABL = Breakpoint Cluster Region- Abelson Leukaemia
  • 73. Chronic Myeloid Leukaemias (CML)
    • CML , Ph + ( CGL- Chronic Granulocytic Leukaemia )
    • CML , Ph – ( atypical ) <5% poor prognosis
    • Juvenile myelomonocytic leukaemia (Juvenile CML)
    • Chronic neutrophilic leukaemia
    • Eosinophilic leukaemia
    • Chronic myelomonocytic leukaemia (CMML )
    • refer to Myelodysplastic Syndrome (MDS)
  • 74. Chronic Phase Accelerated Phase CML Blast Crisis ( 70 % of CML ) inbetween more than 20 % less than 5 % BLAST CELLS
  • 75.  
  • 76.  
  • 77.  
  • 78.  
  • 79.  
  • 80. Glivec is the first line drug in the management of CML-chronic phase C omplete haematological response in virtually all patients , but the aim of treatment is C omplete c ytogenetic response { (-) Ph’ chromosome in BM in cytogenetic analysis }
  • 81. Juvenile CML
    • Young Children (1 st 4 yr of life) boys: girls (2:1)
    • Tissue infiltrations ( Skin rash ; HSM & LAP )
    • Blasts & promonocytes < 20% in PB & BM
    • Monocytosis > 1X10 3 / µL hence, the name JMML
    • No BCR-ABL fusion gene
    • Hb-F high for age (a useful diagnostic feature)
    • Poor prognosis (if untreated BC& death usually occur within 4 yr)
    • Treatment of choice is SCT
    Juvenile myelo-monocytic leukaemia (JMML)
  • 82. Chronic Lymphocytic Leukaemia(s) *. B-Chronic Lymphocytic Leukaemia ( CLL ) The most common of Chronic Lymphoid Leukaemias
  • 83. Chronic Lymphocytic Leukaemia (CLL) Chronic Myeloid Leukaemia (CML) TYPES & AGE Peak incidence 70 ± 10 yr Any age but most frequently at the age of 50 ± 10 yr only 15 % before the age of 50 yr Male : female 2 : 1 Male : female 1.4 : 1
  • 84. Chronic Lymphocytic Leukaemia (CLL)
    • Etiology : Un known
    • No higher incidence after chemo-therapy or radio-therapy
    • ( in contrast to CML:
    • incresed incidence in survivors of atom bomb in Japan)
    • The most common leukaemia in the western world
    • ( ? due to increased routine medical check-up )
    • 7 fold increased risk of CLL in the close relatives of the patient
    • CLL is characterized by proliferation and accumulation of
    • mature-looking but b iologically immature B lymphocytes
    • ( weak surface expression of Ig-M & Ig-D ).
    • #. Accumulation ; where & why ?
    • PB ; BM ; LN ; liver & spleen
    • as a result of impaired apoptosis i.e. elderly lymphocytes
  • 85. Early: Bacterial infections Advanced Disease: viral & fungal infections Immuno suppression is significant Due to: 1. Hypo- gamma- globulin- aemia 2. Cellular immune dys- function Anaemia: Hb < 10 g/dL Thrombocytopenia: Plt < 100 x10 3 / µL Lymphadenopathy Symmetrical ; discrete & not tender (cervical ; axillary or inguinal) The most frequent clinical sign Hepatosplenomegaly Absolute Lymphocytosis ( > 5x10 3 /µL & sustained ) most cases Dx in routine CBC
  • 86. Stage III : As stage 0 + Anaemia (Hb < 10 g/dL) ± Adenopathy ± Organomegaly Stage IV: As stage 0 + Thrombocytopenia (Plt < 100 x 10 3 / µL) ± Adenopathy ± Organomegaly Stage I : As stage 0 + Adeno-pathy Stage II: Stage 0: Absolute Lymphocytosis As stage 0 + Organomegaly ( Enlarged liver & / or spleen) ± Adeno-pathy Rai classification of CLL
  • 87. Early: Bacterial infections Advanced Disease: viral & fungal infections reduced S. Ig conc. Anaemia Hb < 10 g/dL normocytic &normochromic Thrombocytopenia: Plt < 100 x10 3 / µL Lymphocytosis (5-300 x10 3 /µL) Smear: 70-99% small mature-looking lymphocytes with smudge (smear) cells BM aspiration : Lymphocytic replacement of normal marrow elements Lymphocytes comprise 60 ± 35 % Lab. Dx
  • 88. Causes of anemia in CLL Primary ( Marrow Infiltration ) Hyper- splenism Immune Chemotherapy Folate Deficiency Elderly Nutritional Deficiency SECONDARY
  • 89. Causes of thrombocytopenia in CLL Primary ( Marrow Infiltration ) Hyper- splenism Immune Chemotherapy SECONDARY
  • 90. The most common Chromosomal Abnormalities in CLL
    • Deletion 11q23
    • Trisomy 12
    • Deletion 17p
    • involving the p53
    deletion 13q14 good prognosis Bad prognosis
  • 91. Bilateral inguinal lymphadenopathy Gross enlargement of the lymph nodes in both axillary regions in a 70-year-old female
  • 92.  
  • 93. C L L
  • 94. Richter’s Syndrome (Large cell transformation) ( Immuno- blastic transformation)
    • 5 % of CLL
    • with fever & weight loss
    • Large blast cell
    • (previously termed Immuno-blast)
    • spillover to the blood
    • with monoclonal protein in serum &
    • free light chain in urine
    • BM & LN examination reveals
    • the same cells
    • ( Large cell lymphoma)
    PBS showing large blast cells (immunoblasts)