Download - FARIDA OESMAN DEPARTMENT OF CLINICAL PATHOLOGY FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA
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FARIDA OESMAN DEPARTMENT OF CLINICAL PATHOLOGY
FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA
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• SYMETRICAL ENLARGMENT OF LYMPH NODES• SPLENOMEGALY & HEPATOMEGALY
ARE COMMON IN LATER STAGES• FEATURES OF ANEMIA (PALLOR, WEAKNES)
AND FEATURES OF THROMBOCYTOPENIA (BRUISING, PURPURA)
DUE TO MARROW REPLACEMENT• RECURRENT INFECTIONS
BACTERIAL INF IN EARLY DISEASE VIRAL & FUNGAL INF IN ADVANCED DISEASE
DUE T0 IMMUNOSUPRESSION AS RESULTS OF HYPOGAMMAGLOBULINEMIA
CELLULAR IMMUNE DYSFUNCTION
MOST PATIENTS ARE ASYMPTOMATIC,BUT SOME PRESENT WITH
MOST PATIENTS ARE ASYMPTOMATIC,BUT SOME PRESENT WITH
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PERIPHERAL BLOOD • ABSOLUTE LYMPHOCYTOSIS
AT LEAST 10.000/uL• 70-99% OF WBC ARE SMALL LYMPHOCYTES• VARYING NUMBERS OF SMUDGE CELLS• NORMOCYTIC NORMOCHROME ANEMIA, NEUTROPENIA & THROMBOCYTOPENIA
DEVELOP WITH DISEASE PROGRESSION• AUTOIMMUNE HEMOLYTIC ANEMIA IN
10%POSITIVE DIRECT COOMB’S TEST
BONE MARROW• FOCALLY OR DIFUSELY INFILTRATED
BY LYMPHOCYTES• >90% OF CASE ARE B CELL ORIGIN
CD19+, CD20+, CD23+, CD5+
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ACCORDING TO INTERNATIONAL CLL WORKSHOP
NATIONAL CANCER INSTITUTE WORKING GROUP 1989
1. LYMPHOCYTES ≥10.000/uL ESPECIALLY MATURE LYMPHOCYTES2. LYMPHOCYTES IN BONE MARROW
≥30%3. LYMPHOCYTES IN PERIPHERAL BLOOD SHOWED B CELL PHENOTYPE
(CD19, CD20, CD23, CD5)
1. LYMPHOCYTES ≥10.000/uL ESPECIALLY MATURE LYMPHOCYTES2. LYMPHOCYTES IN BONE MARROW
≥30%3. LYMPHOCYTES IN PERIPHERAL BLOOD SHOWED B CELL PHENOTYPE
(CD19, CD20, CD23, CD5)
DIAGNOSIS IS ESTABLISHED IF1 + 2 or 1 + 3 or 2 + 3
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IS ORIGINALLY REFERRED TO A LEUKEMIC RETICULOENDOTHELIOSIS
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• RECURRENT OPPORTUNISTIC INFECTIONS FEVER
• ANEMIA WEAKNESS & FATIGUE• SPLENOMEGALY LEFT UPPER
QUADRANT PAIN
TYPICALLY PRESENT WITH FEATURES OF
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PERIPHERAL BLOOD• PANCYTOPENIA IS USUAL
AT PRESENTATION• LYMPHOCYTE COUNT IS
RARELY >20.000/uL• MONOCYTOPENIA IS
A DISTINCTIVE FEATURES• A VARIABLE NUMBER OF
LARGE LYMPHOCYTES WITH VILLOUS CYTOPLASMIC PROJECTIONS
(HAIRY CELLS)
PERIPHERAL BLOOD• PANCYTOPENIA IS USUAL
AT PRESENTATION• LYMPHOCYTE COUNT IS
RARELY >20.000/uL• MONOCYTOPENIA IS
A DISTINCTIVE FEATURES• A VARIABLE NUMBER OF
LARGE LYMPHOCYTES WITH VILLOUS CYTOPLASMIC PROJECTIONS
(HAIRY CELLS)
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BONE MARROW• FOCALLY OR DIFUSELY INFILTRATED
BY HAIRY CELLS WITH B CELL ORIGIN (CD19+, CD20+)
POSITIVE TARTRATE RESISTANT ACIDPHOSPHATASE (TRAP) STAINING
• INCREASE OF RETICULIN FIBRES CAUSING DRY TAP WITH MARROW ASPIRATION
• IN PROPORTION OF PATIENTS, THE BM ISHYPOCELLULAR WITH A LOSS OF HEMATOPOETIC
CELLS ESPECIALLY GRANULOCYTIC LINEAGE
BONE MARROW• FOCALLY OR DIFUSELY INFILTRATED
BY HAIRY CELLS WITH B CELL ORIGIN (CD19+, CD20+)
POSITIVE TARTRATE RESISTANT ACIDPHOSPHATASE (TRAP) STAINING
• INCREASE OF RETICULIN FIBRES CAUSING DRY TAP WITH MARROW ASPIRATION
• IN PROPORTION OF PATIENTS, THE BM ISHYPOCELLULAR WITH A LOSS OF HEMATOPOETIC
CELLS ESPECIALLY GRANULOCYTIC LINEAGE
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CHARACTERIZED BY
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• BONE PAIN AND PATHOLOGICAL FRACTURES DUE TO INFILTRATION OF
PLASMA CELL INTO BONE• FEATURES OF ANEMIA DUE TO BONE MARROW REPLACEMENT BY PLASMA
CELLS • RECURRENT INFECTION DUE TO
DEPRESSSED OF NORMAL IMMUNOGLOBULIN PRODUCTION
• FEATURES OF RENAL FAILURE DUE TO TUBULAR DAMAGE RESULTING FROM
MONOCLONAL LIGHT CHAIN PROTEINURIA (BENCE JONES PROTEIN)
• BONE PAIN AND PATHOLOGICAL FRACTURES DUE TO INFILTRATION OF
PLASMA CELL INTO BONE• FEATURES OF ANEMIA DUE TO BONE MARROW REPLACEMENT BY PLASMA
CELLS • RECURRENT INFECTION DUE TO
DEPRESSSED OF NORMAL IMMUNOGLOBULIN PRODUCTION
• FEATURES OF RENAL FAILURE DUE TO TUBULAR DAMAGE RESULTING FROM
MONOCLONAL LIGHT CHAIN PROTEINURIA (BENCE JONES PROTEIN)
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• ABNORMAL BLEEDING TENDENCY DUE TO M PROTEIN INTERFERE WITH PLATELET FUNCTION OR COAGULATION FACTORS THROMBOCYTOPENIA IN ADVANCED DISEASE
• HYPERVISCOSITY SYNDROME IN 2% CASES VISUAL FAILURE, CNS SYMPTOMS, NEUROPATHIES
• ABNORMAL BLEEDING TENDENCY DUE TO M PROTEIN INTERFERE WITH PLATELET FUNCTION OR COAGULATION FACTORS THROMBOCYTOPENIA IN ADVANCED DISEASE
• HYPERVISCOSITY SYNDROME IN 2% CASES VISUAL FAILURE, CNS SYMPTOMS, NEUROPATHIES
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PERIPHERAL BLOOD• NORMOCYTIC NORMOCHROMIC ANEMIA
• ROULEAUX FORMATION• NEUTROPENIA & THROMBOCYTOPENIA
OCCURS IN ADVANCED DISEASE• PLASMA CELLS IN 15% OF CASES
• HIGH ERYTHROCYTE SEDIMENTATION RATE
BONE MARROW• INCREASE PLASMA CELLS USUALLY >20%
OFTEN WITH ABNORMAL FORMS
PERIPHERAL BLOOD• NORMOCYTIC NORMOCHROMIC ANEMIA
• ROULEAUX FORMATION• NEUTROPENIA & THROMBOCYTOPENIA
OCCURS IN ADVANCED DISEASE• PLASMA CELLS IN 15% OF CASES
• HIGH ERYTHROCYTE SEDIMENTATION RATE
BONE MARROW• INCREASE PLASMA CELLS USUALLY >20%
OFTEN WITH ABNORMAL FORMS
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OTHERS• PRESENCE OF M PROTEIN IN SERUM M SPIKE IN SERUM ELECTROPHORESIS IgG 50%, IgA 20%, LIGHT CHAIN 20%, IgM, IgD, IgE <10% URINE BENCE JONES PROTEIN (2/3 CASES)• INCREASED SERUM M PROTEIN LEVELS IgG >30g/L, IgA >20g/L• INCREASED OF SERUM CALCIUM (20%)• INCREASED OF SERUM CREATININE (20-30%)• DECREASE OF SERUM ALBUMIN IN ADVANCED DISEASE• INCREASED OF SERUM 2 MICROGLOBULIN, USEFUL INDICATOR OF PROGNOSIS <4 mg/L A RELATIVELY GOOD PROGNOSIS
OTHERS• PRESENCE OF M PROTEIN IN SERUM M SPIKE IN SERUM ELECTROPHORESIS IgG 50%, IgA 20%, LIGHT CHAIN 20%, IgM, IgD, IgE <10% URINE BENCE JONES PROTEIN (2/3 CASES)• INCREASED SERUM M PROTEIN LEVELS IgG >30g/L, IgA >20g/L• INCREASED OF SERUM CALCIUM (20%)• INCREASED OF SERUM CREATININE (20-30%)• DECREASE OF SERUM ALBUMIN IN ADVANCED DISEASE• INCREASED OF SERUM 2 MICROGLOBULIN, USEFUL INDICATOR OF PROGNOSIS <4 mg/L A RELATIVELY GOOD PROGNOSIS
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NORMAL
MONOCLONAL PROTEININ GAMMA REGION MONOCLONALGAMMOPATHY
M SPIKE
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• OSTEOLYTIC AREAS WITHOUT
EVIDENCE OF SURROUNDING OSTEOBLASTIC REACTION
• OSTEOPOROSIS
• OSTEOLYTIC AREAS WITHOUT
EVIDENCE OF SURROUNDING OSTEOBLASTIC REACTION
• OSTEOPOROSIS
REVEAL A BONE LESIONS
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ASYMPTOMATIC MYELOMACLONAL PLASMA CELLS IN BONE
MARROW ≥10% OR PLASMACYTOMAAND /OR
M PROTEIN IN SERUM >30g/LSYMPTOMATIC MYELOMA
CLONAL PLASMA CELLS IN BONE MARROW ≥10%M PROTEIN IN SERUM OR URINE
HYPERCALCEMIA, RENAL INSUFFICIENCY,ANEMIA, BONE LESIONS (CRAB)NON SECRETORY MYELOMA
CLONAL PLASMA CELLS IN BONE MARROW ≥30%OR
BIOPSY PROVEN PLASMACYTOMA
ASYMPTOMATIC MYELOMACLONAL PLASMA CELLS IN BONE
MARROW ≥10% OR PLASMACYTOMAAND /OR
M PROTEIN IN SERUM >30g/LSYMPTOMATIC MYELOMA
CLONAL PLASMA CELLS IN BONE MARROW ≥10%M PROTEIN IN SERUM OR URINE
HYPERCALCEMIA, RENAL INSUFFICIENCY,ANEMIA, BONE LESIONS (CRAB)NON SECRETORY MYELOMA
CLONAL PLASMA CELLS IN BONE MARROW ≥30%OR
BIOPSY PROVEN PLASMACYTOMA
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MODIFIED FROM DURIE & SALMON
STAGE ILOW M PROTEIN IgG <50g/L, IgA <30g/L
URINE BENCE JONES <4g/24 hours ABSENT OR SOLITARY BONE LESIONS
NORMAL Hb, SERUM CALCIUM, Ig LEVEL (NON M)STAGE II
OVERALL VALUES BETWEEN I & IISTAGE III
HIGH M PROTEIN IgG >70g/L, IgA >50g/LURINE LIGHT CHAIN >12g/24 hours
ADVANCED, MULTIPLE BONE LESIONSHb <8.5g/dL, SERUM CALCIUM >12 mg/dL
STAGE ILOW M PROTEIN IgG <50g/L, IgA <30g/L
URINE BENCE JONES <4g/24 hours ABSENT OR SOLITARY BONE LESIONS
NORMAL Hb, SERUM CALCIUM, Ig LEVEL (NON M)STAGE II
OVERALL VALUES BETWEEN I & IISTAGE III
HIGH M PROTEIN IgG >70g/L, IgA >50g/LURINE LIGHT CHAIN >12g/24 hours
ADVANCED, MULTIPLE BONE LESIONSHb <8.5g/dL, SERUM CALCIUM >12 mg/dL
SUBCLASSIFICATION BASED ON RENAL FUNCTIONA: SERUM CREATININE <2mg/dLB: SERUM CREATININE =>2mg/dL
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INTERNATIONAL STAGING SYSTEM
STAGE ISERUM β2-MICROGOBULIN <3.5mg/L
SERUM ALBUMIN >3.5g/dL
STAGE IISERUM β2-MICROGOBULIN <3.5mg/L
SERUM ALBUMIN <3.5g/dLOR
SERUM β2-MICROGOBULIN 3.5-5.5mg/LIRRESPECTIVE OF SERUM ALBUMIN LEVEL
STAGE IIISERUM β2-MICROGOBULIN >5.5mg/L
STAGE ISERUM β2-MICROGOBULIN <3.5mg/L
SERUM ALBUMIN >3.5g/dL
STAGE IISERUM β2-MICROGOBULIN <3.5mg/L
SERUM ALBUMIN <3.5g/dLOR
SERUM β2-MICROGOBULIN 3.5-5.5mg/LIRRESPECTIVE OF SERUM ALBUMIN LEVEL
STAGE IIISERUM β2-MICROGOBULIN >5.5mg/L
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• USUALLY INCIDIOUS ONSET WITH FATIGUE AND WEIGHT LOSS
• HYPERVISCOSITY SYNDROME (20-30%) OCULAR & NEUROLOGIC MANIFESTATION
• IF MACROGLOBULIN IS CRYOGLOBULIN FEATURES OF CRYOPRECIPITATION (5%)
SUCH AS RAYNAUD PHENOMENON• ANEMIA DUE TO INCREASED PLASMA VOLUME
• A BLEEDING TENDENCY DUE TO MACROGLOBULIN INTERFERENCE WITH
PLATELET FUNCTION COAGULATION FACTORS
• USUALLY INCIDIOUS ONSET WITH FATIGUE AND WEIGHT LOSS
• HYPERVISCOSITY SYNDROME (20-30%) OCULAR & NEUROLOGIC MANIFESTATION
• IF MACROGLOBULIN IS CRYOGLOBULIN FEATURES OF CRYOPRECIPITATION (5%)
SUCH AS RAYNAUD PHENOMENON• ANEMIA DUE TO INCREASED PLASMA VOLUME
• A BLEEDING TENDENCY DUE TO MACROGLOBULIN INTERFERENCE WITH
PLATELET FUNCTION COAGULATION FACTORS
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PERIPHERAL BLOOD• NORMOCYTIC NORMOCHROMIC ANEMIA
• ROULEAUX FORMATION• NEUTROPENIA, LYMPHOCYTOSIS AND
LYMPHOPLASMOCYTOID CELLS• HIGH ERYTHROCYTE SEDIMENTATION RATE
BONE MARROW• INFILTRATION OF LYMPHOPLASMOCYTOID CELLS
OTHERS• M SPIKE IN PROTEIN ELECTROPHORESIS
IgM • BENCE JONES PROTEIN IN 10% CASES
• INCREASED SERUM/PLASMA VISCOSITY
PERIPHERAL BLOOD• NORMOCYTIC NORMOCHROMIC ANEMIA
• ROULEAUX FORMATION• NEUTROPENIA, LYMPHOCYTOSIS AND
LYMPHOPLASMOCYTOID CELLS• HIGH ERYTHROCYTE SEDIMENTATION RATE
BONE MARROW• INFILTRATION OF LYMPHOPLASMOCYTOID CELLS
OTHERS• M SPIKE IN PROTEIN ELECTROPHORESIS
IgM • BENCE JONES PROTEIN IN 10% CASES
• INCREASED SERUM/PLASMA VISCOSITY
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MYELOMA WALDENSROM’S
CLINICAL FEATURES• Bone lesion (+) (-)• Recurrent infection (+) (-)• Bleeding tendency (+) (++)• Organomegaly (+) (++)• Hyperviscosity (+) (++)• Renal failure (+) (-)
LABORATORY FINDING• Anemia (++) (+)• LeucopenIa (+) / (-) (+) / (-)• Thrombocytopenia (+) / (-) (+) / (-)• Hypercalcemia (+) (-)• Increase serum viscosity (+) (++)
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