1. LYMPHOPROLIFERATIVE DISORDERS
FARIDA OESMAN
DEPARTMENT OF CLINICAL PATHOLOGY
FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA

2. LYMPHOPROLIFERATIVE DISORDERS
HEMATOPOETIC
CHRONIC LYMPHOCYTIC LEUKEMIA
HAIRY CELL LEUKEMIA
PLASMA CELL MYELOMA
MACROGLOBULINEMIA WALDENSTROM’S
LYMPHORETICULAR
HODGKIN’S DISEASE
NON HODGKIN’S LYMPHOMA

3. CHRONIC LYMPHOCYTIC LEUKEMIA
CHARACTERIZED BY ACUMULATION OF
MATURE B LYMPHOCYTES USUALLY COEXPRESS CD5 & CD23
IN PERIPHERAL BLOOD, BONE MARROW SPLEEN, LIVER, LYMPH NODES

4. CLASSIFICATION OF CLL ACCORDING TO FRENCH AMERICAN BRITISH (FAB)
CLASSICAL CLL
>90% SMALL LYMPHO-CYTES
CLL/PLL
11-54% PROLYMPHO-CYTES
ATYPICAL CLL
>15% LYMPHOPLAS-MOCYTOID
<10% PROLYMPHO-CYTES

5. EPIDEMIOLOGY A PEAK AT 60 - 80 YEARS RARELY OCCUR AT <40 YEARS
IS THE MOST COMMON LEUKEMIA OF ADULTS
A PEAK AT YEARS RARELY OCCUR AT <40 YEARS
MALE TO FEMALE RATIO IS 2 : 1

6. CLINICAL FeatureS MOST PATIENTS ARE ASYMPTOMATIC,
BUT SOME PRESENT WITH
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

7. LABORATORY FINDING PERIPHERAL BLOOD BONE MARROW
ABSOLUTE LYMPHOCYTOSIS
AT LEAST /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+

8. PERIPHERAL BLOOD

9. DIAGNOSIS OF CLL ACCORDING TO INTERNATIONAL CLL WORKSHOP
NATIONAL CANCER INSTITUTE WORKING GROUP 1989
1. LYMPHOCYTES ≥10.000/uL
ESPECIALLY MATURE LYMPHOCYTES
2. LYMPHOCYTES IN BONE MARROW ≥30%
3. LYMPHOCYTES IN PERIPHERAL BLOOD
SHOWED B CELL PHENOTYPE (CD19, CD20, CD23, CD5)
DIAGNOSIS IS ESTABLISHED IF
1 + 2 or or 2 + 3

10. LEUKEMIC RETICULOENDOTHELIOSIS
HAIRY CELL LEUKEMIA
IS ORIGINALLY REFERRED TO A
LEUKEMIC RETICULOENDOTHELIOSIS
IS AN UNCOMMON B CELL LYMPHOPROLIFERATIVE DISORDERS
MATURE B CELL WITH OVAL NUCLEI, ABUNDANT CYTOPLASM WITH HAIRY PROJECTIONS  HAIRY CELLS
INVOLVING PERIPHERAL BLOOD DIFFUSELY INFILTRATING IN BONE MARROW AND SPLEEN

11. MALE TO FEMALE RATIO IS 5 : 1
EPIDEMIOLOGY
IS A RARE DISEASE COMPRISING 2% OF LYMPHOCYTIC LEUKEMIA
PREDOMINANTLY IN MIDDLE-AGED TO ELDERLY ADULT WITH A MEDIAN AGE OF 50 YEARS
MALE TO FEMALE RATIO IS 5 : 1

12. CLINICAL FeatureS TYPICALLY PRESENT WITH FEATURES OF
RECURRENT OPPORTUNISTIC INFECTIONS  FEVER
ANEMIA  WEAKNESS & FATIGUE
SPLENOMEGALY  LEFT UPPER QUADRANT PAIN

13. LABORATORY FINDING 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)

14. LABORATORY FINDING BONE MARROW
FOCALLY OR DIFUSELY INFILTRATED
BY HAIRY CELLS WITH
B CELL ORIGIN (CD19+, CD20+)
POSITIVE TARTRATE RESISTANT ACID
PHOSPHATASE (TRAP) STAINING
INCREASE OF RETICULIN FIBRES
CAUSING DRY TAP WITH MARROW ASPIRATION
IN PROPORTION OF PATIENTS, THE BM IS
HYPOCELLULAR WITH A LOSS OF HEMATOPOETIC
CELLS ESPECIALLY GRANULOCYTIC LINEAGE

15. PERIPHERAL BLOOD

16. PLASMA CELL MYELOMA
CHARACTERIZED BY
CLONAL PROLIFERATION OF PLASMA CELLS IN BONE MARROW
PRESENCE OF MONOCLONAL (M) PROTEIN IN BLOOD AND OR URINE
ASSOCIATED WITH ORGAN DYSFUNCTION

17. MALE TO FEMALE RATIO IS 1.5 : 1
EPIDEMIOLOGY
COMPRISES 10-15% OF HEMATOPOETIC NEOPLASM USUALLY SEEN IN OLDER ADULTS
90% OF CASES OCCUR AT >50 YEARS A PEAK AT 70 YEARS
MALE TO FEMALE RATIO IS 1.5 : 1

18. CLINICAL VARIANT SYMPTOMATIC MYELOMA DEFINED BY ORGAN DAMAGE
ASYMPTOMATIC (SMOLDERING) MYELOMA
SYMPTOMATIC MYELOMA DEFINED BY ORGAN DAMAGE
 CRAB
NON SECRETORY MYELOMA (3%)

19. CLINICAL FeatureS
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)

20. CLINICAL FeatureS 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

21. LABORATORY FINDING PERIPHERAL BLOOD BONE MARROW
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

22. BONE MARROW

23. LABORATORY FINDING 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

24. SERUM PROTEIN ELECTROPHORESIS
NORMAL
M SPIKE
MONOCLONAL PROTEIN
IN GAMMA REGION
 MONOCLONAL
GAMMOPATHY

25. EVIDENCE OF SURROUNDING OSTEOBLASTIC REACTION
RADIOLOGICAL FINDING
REVEAL A BONE LESIONS
OSTEOLYTIC AREAS
WITHOUT
EVIDENCE OF SURROUNDING
OSTEOBLASTIC REACTION
OSTEOPOROSIS

26. DIAGNOTIC CRITERIA ASYMPTOMATIC MYELOMA SYMPTOMATIC MYELOMA
CLONAL PLASMA CELLS IN BONE
MARROW ≥10% OR PLASMACYTOMA
AND /OR
M PROTEIN IN SERUM >30g/L
SYMPTOMATIC 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

27. MYELOMA STAGING SYSTEM
MODIFIED FROM DURIE & SALMON
STAGE I
LOW 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 & II
STAGE III
HIGH M PROTEIN  IgG >70g/L, IgA >50g/L
URINE LIGHT CHAIN >12g/24 hours
ADVANCED, MULTIPLE BONE LESIONS
Hb <8.5g/dL, SERUM CALCIUM >12 mg/dL
SUBCLASSIFICATION BASED ON RENAL FUNCTION
A: SERUM CREATININE <2mg/dL
B: SERUM CREATININE =>2mg/dL

28. MYELOMA STAGING SYSTEM
INTERNATIONAL STAGING SYSTEM
STAGE I
SERUM β2-MICROGOBULIN <3.5mg/L
SERUM ALBUMIN >3.5g/dL
STAGE II
SERUM ALBUMIN <3.5g/dL OR
SERUM β2-MICROGOBULIN mg/L
IRRESPECTIVE OF SERUM ALBUMIN LEVEL
STAGE III
SERUM β2-MICROGOBULIN >5.5mg/L

29. WALDENSTROM’S MACROGLOBULINEMIA
WHO CLASSIFICATION OF TUMORS HAEMATOPOIETIC AND LYMPHOID TISSUE (2008)
DEFINES AS A TYPE OF LYMPHOPLASMACYTIC LYMPHOMA
IS A NEOPLASM OF B LYMPHOCYTE, PLASMACYTOID LYMPHOCYTE AND PLASMA CELL, USUALLY INVOLVED THE BONE MARROW

30. WALDENSTROM’S MACROGLOBULINEMIA
INFILTRATION OF LYMPHOPLASMOCYTIC CELLS IN BONE MARROW
OCCURANCE OF MONOCLONAL IgM PROTEIN IN THE BLOOD
IS UNCOMMON CONDITION FREQUENTLY IN MEN >50 YEARS

31. CLINICAL FeatureS 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

32. LABORATORY FINDING PERIPHERAL BLOOD BONE MARROW OTHERS
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

33. MYELOMA WALDENSROM’S
CLINICAL FEATURES
Bone lesion (+) (-)
Recurrent infection (+) (-)
Bleeding tendency (+) (++)
Organomegaly (+) (++)
Hyperviscosity (+) (++)
Renal failure (+) (-)
LABORATORY FINDING
Anemia (++) (+)
LeucopenIa (+) / (-) (+) / (-)
Thrombocytopenia (+) / (-) (+) / (-)
Hypercalcemia (+) (-)
Increase serum viscosity (+) (++)

34. THANK YOU