Embed Size (px)
Citation preview
FARIDA OESMAN DEPARTMENT OF CLINICAL PATHOLOGY
FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA
• 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
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+
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
IS ORIGINALLY REFERRED TO A LEUKEMIC RETICULOENDOTHELIOSIS
• RECURRENT OPPORTUNISTIC INFECTIONS FEVER
• ANEMIA WEAKNESS & FATIGUE• SPLENOMEGALY LEFT UPPER
QUADRANT PAIN
TYPICALLY PRESENT WITH FEATURES OF
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)
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
CHARACTERIZED BY
• 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)
• 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
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
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
NORMAL
MONOCLONAL PROTEININ GAMMA REGION MONOCLONALGAMMOPATHY
M SPIKE
• OSTEOLYTIC AREAS WITHOUT
EVIDENCE OF SURROUNDING OSTEOBLASTIC REACTION
• OSTEOPOROSIS
• OSTEOLYTIC AREAS WITHOUT
EVIDENCE OF SURROUNDING OSTEOBLASTIC REACTION
• OSTEOPOROSIS
REVEAL A BONE LESIONS
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
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
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
• 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
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
MYELOMA WALDENSROM’S
CLINICAL FEATURES• Bone lesion (+) (-)• Recurrent infection (+) (-)• Bleeding tendency (+) (++)• Organomegaly (+) (++)• Hyperviscosity (+) (++)• Renal failure (+) (-)
LABORATORY FINDING• Anemia (++) (+)• LeucopenIa (+) / (-) (+) / (-)• Thrombocytopenia (+) / (-) (+) / (-)• Hypercalcemia (+) (-)• Increase serum viscosity (+) (++)
