Prognostic markers are important in hematologic oncology for predicting patient survival, selecting optimal treatment, monitoring treatment response, and detecting relapse. Key prognostic markers in acute myeloid leukemia (AML) include age, white blood cell count, percentage of blasts after treatment, cytogenetics such as inv(16) and t(15;17), mutations such as FLT3 and NPM1, and minimal residual disease levels. The French-American-British classification and World Health Organization classification further categorize AML based on morphology and genetics. Prognosis is favorable in AML subgroups like acute promyelocytic leukemia and those with t(8;21) or inv(16), and adverse with complex

1. PROGNOSTIC MARKERSPROGNOSTIC MARKERS
ININ
HEMATOLOGIC ONCOLOGYHEMATOLOGIC ONCOLOGY
Dr. Reshama NirmaleDr. Reshama Nirmale

2. Introduction to Prognostic MarkersIntroduction to Prognostic Markers
Leukemias :-Leukemias :-
 AML,AML,
 ALL,ALL,
 CML,CML,
 CLL,CLL,
Lymphomas :-Lymphomas :-
 HLHL
 NHL :-NHL :-
B cellB cell
T cellT cell
MDSMDS
Other CMPDsOther CMPDs

3. Prognostic MarkersPrognostic Markers
Imp - not only inImp - not only in diagnosisdiagnosis but also inbut also in
 PredictingPredicting survivalsurvival of pt.of pt.
 Selection ofSelection of proper t/tproper t/t,,
 MonitoringMonitoring responseresponse to t/t ,to t/t ,
 Detection ofDetection of relapserelapse – MRD by FISH ,RQ- PCR– MRD by FISH ,RQ- PCR
Prognostic indicesPrognostic indices
 Ann-Arbor classification -HLAnn-Arbor classification -HL
 Prognostic indicesPrognostic indices
- B-CLL - Rai & BINET staging system- B-CLL - Rai & BINET staging system
- IPI for malignant lymphoma- IPI for malignant lymphoma
- IPSS for MDS- IPSS for MDS

4. Age :-Age :- e.g – ALL ,NHL ,DLBCLe.g – ALL ,NHL ,DLBCL
Morphology :-Morphology :- e. g.e. g.
- AML - M0 ,M6,M7- AML - M0 ,M6,M7
- Grades (NHL) - low vs high- Grades (NHL) - low vs high
- Follicular lymphoma grading,- Follicular lymphoma grading,
Histologic subtypes :Histologic subtypes :- e.g.- e.g.
- DLBCL- immuno / centro- DLBCL- immuno / centro
TransformationTransformation – e.g. B-CLL – DLBCL– e.g. B-CLL – DLBCL
AngiogenesisAngiogenesis - Ki-67 – e.g. AML, ALL, MDS- Ki-67 – e.g. AML, ALL, MDS
Apoptosis :Apoptosis : – e.g.- overexpression of Bcl-2 –– e.g.- overexpression of Bcl-2 – FLFL
- c-FLIP express - ALL- c-FLIP express - ALL
Prognostic MarkersPrognostic Markers

5. Prognostic MarkersPrognostic Markers
Serum Markers :-Serum Markers :- β2 - microglobulin, LDH (2, 3)β2 - microglobulin, LDH (2, 3)
- Cytokines - IL-6, 18- Cytokines - IL-6, 18
Chromosomal & genetic abn.Chromosomal & genetic abn. :-:- by FISHby FISH
-- t (9;22) & t (15;17)t (9;22) & t (15;17)
Phenotypic markersPhenotypic markers :-:-
-- ALK +ve ALCLALK +ve ALCL
MRDMRD - FISH,- FISH,
- Immunophenotyping –FCM & PCR,- Immunophenotyping –FCM & PCR,
- B-CLL & NHL ,MM, AML,CML- B-CLL & NHL ,MM, AML,CML

6. LEUKEMIASLEUKEMIAS

7. ACUTE LEUKEMIAACUTE LEUKEMIA
World wide incidence :- 4 per 1 lakhWorld wide incidence :- 4 per 1 lakh
80 % : AML80 % : AML
BlastsBlasts ≥≥ 20 %20 %

8. FAB CLASSIFICATION OF AMLFAB CLASSIFICATION OF AML
M0 : Minimally differentiatedM0 : Minimally differentiated
M1 : Myeloblastic leukemia without maturationM1 : Myeloblastic leukemia without maturation
M2 : Myeloblastic leukemia with maturationM2 : Myeloblastic leukemia with maturation
M3 : Hypergranular promyelocytic leukemiaM3 : Hypergranular promyelocytic leukemia
M3 variant : hypogranular promyelocytic leukemiaM3 variant : hypogranular promyelocytic leukemia
M4 : myelomonocytic leukemiaM4 : myelomonocytic leukemia
M4E0 : variant, increase in marrow eosinophilsM4E0 : variant, increase in marrow eosinophils
M5 : Monocytic leukemiaM5 : Monocytic leukemia
M5a ; without maturationM5a ; without maturation
M5b : with maturationM5b : with maturation
M6 : Erythroleukemia (DiGuglielmo’s disease)M6 : Erythroleukemia (DiGuglielmo’s disease)
M7 : Megakaryoblastic leukemiaM7 : Megakaryoblastic leukemia

9. WHO CLASSIFICATION OF AMLWHO CLASSIFICATION OF AML
AML WITH RECURRENT CYTOGENETICAML WITH RECURRENT CYTOGENETIC
ABNORMALITIESABNORMALITIES (85% of AML in young)(85% of AML in young)
-- AML with t (8;21)(q22;q22) - AML1/ETO ( M2 )AML with t (8;21)(q22;q22) - AML1/ETO ( M2 )
- Acute promyelocytic leukemia :AML with- Acute promyelocytic leukemia :AML with
t(15;17)(q22:q12) and variant PML/RARa (M3)t(15;17)(q22:q12) and variant PML/RARa (M3)
- AML with abnormal bone marrow eosinophils inv(16)- AML with abnormal bone marrow eosinophils inv(16)
(p13;q22) , t(16;16)(p13;q22)- CBF(p13;q22) , t(16;16)(p13;q22)- CBFββ/MYH1 –(M4Eo)/MYH1 –(M4Eo)
- AML with 11q23 MLL abnormalities (M5)- AML with 11q23 MLL abnormalities (M5)
AML WITH MULTILINEAGE DYSPLASIAAML WITH MULTILINEAGE DYSPLASIA:(-7, -5, +8, +9, +11):(-7, -5, +8, +9, +11)
-- With prior MDSWith prior MDS
- Without prior MDS- Without prior MDS

10. WHO CLASSIFICATION OF AMLWHO CLASSIFICATION OF AML
AML THERAPY RELATEDAML THERAPY RELATED :-:-
– Alkylating agent relatedAlkylating agent related
– Topoisomerase II inhibitor relatedTopoisomerase II inhibitor related
AML NOT OTHERWISE CATEGORIZEDAML NOT OTHERWISE CATEGORIZED :-:-
– AML minimally differentiatedAML minimally differentiated
– AML without maturationAML without maturation
– AML with maturationAML with maturation
– Acute myelomonocytic leukemiaAcute myelomonocytic leukemia
– Acute monocytic leukemiaAcute monocytic leukemia
– Acute erythroid leukemiaAcute erythroid leukemia
– Acute megekaryoblastic leukemiaAcute megekaryoblastic leukemia
– Acute basophilic leukemiaAcute basophilic leukemia
– Acute panmyelosis with myelofibrosisAcute panmyelosis with myelofibrosis

11. AMLAML
Clonal malignancy of transformedClonal malignancy of transformed
multipotent Haematopoieticmultipotent Haematopoietic
progenitor cellprogenitor cell →→ accumulation ofaccumulation of
immature cells in BMimmature cells in BM →→ cytopeniacytopenia
& complications,& complications,
3.4 / 1 lakh, 80-90% acute leukemia3.4 / 1 lakh, 80-90% acute leukemia

12. AMLAML
A)A) ClinicalClinical :-:-
Bad prognosisBad prognosis :-:-
-- Age : < 2 yrs & elderly pts.Age : < 2 yrs & elderly pts.
- Hyperleucocytosis ( bl.blasts > 1 Lakh)- Hyperleucocytosis ( bl.blasts > 1 Lakh)
- BM blast % after T/t 5 yr survival- BM blast % after T/t 5 yr survival
< 5 % 56 %< 5 % 56 %
> 5 % 27 %> 5 % 27 %
Good prognosisGood prognosis ::
– Early response to therapy, rapid cytoreductionEarly response to therapy, rapid cytoreduction
– Down SyndromeDown Syndrome
Younger & FAB M7Younger & FAB M7

13. FAVOURABLEFAVOURABLE :-:-
+nce of Auer rods+nce of Auer rods
(M1 - M4)(M1 - M4)
+nce of Eosinophils+nce of Eosinophils
(M2 - M4Eo)(M2 - M4Eo)
UNFAVOURABLEUNFAVOURABLE :-:-
M0, M6, M7M0, M6, M7
Megaloblastic features in M6, M7 &Megaloblastic features in M6, M7 &
AML from MDS,AML from MDS,
Trilineage dysplasia,Trilineage dysplasia,
Extramedullary myeloid tumoursExtramedullary myeloid tumours
(Granulocytic Sarcoma) - AML-M5,(Granulocytic Sarcoma) - AML-M5,
CD 56 +ve,CD 56 +ve, Platelets < 1 lakh,Platelets < 1 lakh,
Neutrophils < 1000 / μlNeutrophils < 1000 / μl
Acute Panmyelosis & MyelofibrosisAcute Panmyelosis & Myelofibrosis
+nce of Leucocyte Function Ag+nce of Leucocyte Function Ag
(CD11b & CD 11c)(CD11b & CD 11c)
Leukemia of ambiguous lineage,Leukemia of ambiguous lineage,
Morphologic & Phenotypic :-

14. • Cytogenetic & Molecular :-
FAVORABLEFAVORABLE :-:-
t (8;21)(q22;q22) -t (8;21)(q22;q22) -
ETO / RUNX1 (AML-1)ETO / RUNX1 (AML-1)
Inv 16 / t (16;16)Inv 16 / t (16;16)
t (15;17)(q22;q11) -t (15;17)(q22;q11) -
PML / RARάPML / RARά
t (11;17)(q13;q21) -t (11;17)(q13;q21) -
NUMA / RARάNUMA / RARά
ADVERSEADVERSE :-:-
Complex karyotype (>/=Complex karyotype (>/=
3),3),
Inv 3,-7Inv 3,-7
t (6;9),t (6;9),
t (6;11),t (6;11),
INTERMEDIATEINTERMEDIATE :-:-
Normal karyotype,Normal karyotype,
-Y,-Y,
Del 5q,Del 5q,
t (9;11)t (9;11)
Del 11qDel 11q
+13+13

15. AMLAML
Somatic mutationsSomatic mutations --
FLT 3FLT 3 genegene && N-RASN-RAS genegene mutation - MCmutation - MC
FLT 3FLT 3 mut. - predict relapse - poormut. - predict relapse - poor
prognosisprognosis
p53 mutation ,CD 34+ , BCL 2 & WT 1p53 mutation ,CD 34+ , BCL 2 & WT 1
coexpr. - poor prognosiscoexpr. - poor prognosis
Expression of MDR geneExpression of MDR gene

16. Minimal Residual DiseaseMinimal Residual Disease :-:-
 Detected by FCM, FISH, RQ-PCRDetected by FCM, FISH, RQ-PCR
 Target translocations- t (15;17), t (9;22), t (8;21)Target translocations- t (15;17), t (9;22), t (8;21)
inv 16 / t (16;16),inv 16 / t (16;16),
 Pts with < 5 % blasts - Low relapse rate - GoodPts with < 5 % blasts - Low relapse rate - Good
survival,survival,
 Depending on no. of tumour cells / normal cell, 4 riskDepending on no. of tumour cells / normal cell, 4 risk
strategies (San Miguel et al ),strategies (San Miguel et al ),
< 10< 10-4-4
cells - very low risk - No relapsecells - very low risk - No relapse
1010-4-4
--1010-3-3
cells - Low risk - 3 yr relapse 14 %cells - Low risk - 3 yr relapse 14 %
1010-3-3
--1010-2-2
cells - Intermediate - 3 yr relapse 50 %,cells - Intermediate - 3 yr relapse 50 %,
> 10> 10-2-2
cells - High risk - 3 yr relapse 84 %,cells - High risk - 3 yr relapse 84 %,

17. Pts with relapsed diseasePts with relapsed disease
– Platelets < 50,000 / μlPlatelets < 50,000 / μl
– Leococyte count > 50,000 / μlLeococyte count > 50,000 / μl
– Past h/o MDS or MPDPast h/o MDS or MPD
– NonNon inv 16inv 16
– Therapy relatedTherapy related
AMLAML

18. APML :-APML :-
– 10 % AML,10 % AML,
– c/b Leucopenia, Abnormal promyelocytes, DICc/b Leucopenia, Abnormal promyelocytes, DIC
– t (15;17) : 95 % of APMLt (15;17) : 95 % of APML
– Relapse :Relapse :
Old pts, increased WBC & platelet count - CD 56Old pts, increased WBC & platelet count - CD 56
+ve, +nce of FLT 3 gene mut.+ve, +nce of FLT 3 gene mut.
+ve RQ-PCR after consolidation+ve RQ-PCR after consolidation
AMLAML

19. t (15;17)(q22;q21)t (15;17)(q22;q21)
Chr 17 (RARChr 17 (RAR ά))Chr 15 (PML)Chr 15 (PML)
PML / RARPML / RARά
• Impaired growth suppressorImpaired growth suppressor
& Proapoptotic activities& Proapoptotic activities
• Responsive to ATRAResponsive to ATRA
RARRARά / PML/ PML
 Other Translocations :-Other Translocations :-
• t (5;17)(q35;q21) = RARt (5;17)(q35;q21) = RARά + NPM+ NPM
• t (11;17)(q13;q21) = RARt (11;17)(q13;q21) = RARά + NUMA+ NUMA
• t (11;17)(q23;q21) = RARt (11;17)(q23;q21) = RARά + PLZF :
Resistant to ATRA

20.  WHO CLASSIFICATIONWHO CLASSIFICATION
Precursor B lymphoblastic leukemia / lymphomaPrecursor B lymphoblastic leukemia / lymphoma
Precursor T lymphoblastic lymphoma / leukemiaPrecursor T lymphoblastic lymphoma / leukemia
Leukemic phase of Burkitt lymphomaLeukemic phase of Burkitt lymphoma
 FAB CLASSIFICATIONFAB CLASSIFICATION :-:-
 L1 – Small blastsL1 – Small blasts
 L2 - Large homogenousL2 - Large homogenous
 L3 – Large heterogenousL3 – Large heterogenous
ALLALL

21. CHILDHOOD ALLCHILDHOOD ALL
FAVOURABLEFAVOURABLE UNFAVOURABLEUNFAVOURABLE
AgeAge 3-7 yr3-7 yr <1; >10<1; >10
GenderGender FF MM
WBC countWBC count <10,000 / μl<10,000 / μl > 2lakh> 2lakh
FAB FeaturesFAB Features L1L1 L2L2
PloidyPloidy HyperHyper HypoHypo
Time to remissionTime to remission <14 days<14 days >28 days>28 days
MRDMRD <10<10-4-4
>10>10-3-3
CytogeneticCytogenetic Trisomies 4,10,17Trisomies 4,10,17 t(9:22)t(9:22)

22. ADULT ALLADULT ALL
FEATURESFEATURES FAVOURABLEFAVOURABLE UNFAVOURABLEUNFAVOURABLE
AgeAge <30 yrs<30 yrs >30 yrs>30 yrs
WBC countWBC count < 30,000< 30,000 >/= 30,000>/= 30,000
ImmunophenotypeImmunophenotype T- cell ALLT- cell ALL Mature B- cell ALL,Mature B- cell ALL,
Early T-cell ALLEarly T-cell ALL
CytogeneticsCytogenetics 12p abn. t(10;14)12p abn. t(10;14)
(q24;q11)(q24;q11)
T(9;22), t(4;11),T(9;22), t(4;11),
t(1;19),hypoploid,t(1;19),hypoploid,
-7,+8-7,+8
Response to therapyResponse to therapy CR <4 wksCR <4 wks Persistent MRDPersistent MRD

23. CMLCML
Stem cell & MCStem cell & MC MPDMPD disorderdisorder
Asso. with t(9;22)(q34;q11)Asso. with t(9;22)(q34;q11)
Bi or TriphasicBi or Triphasic
IPT :-IPT :-
– CP - CD 15 & HLA-DR weakly +veCP - CD 15 & HLA-DR weakly +ve
– BP - a / w myeloid CD 13;14;15;33 +veBP - a / w myeloid CD 13;14;15;33 +ve
megakaryocytic CDw4, CD 61 +vemegakaryocytic CDw4, CD 61 +ve
Erythrocytic Glycophorin-A, Hb A +veErythrocytic Glycophorin-A, Hb A +ve

24. Clinical & Lab featuresClinical & Lab features :-:-
POOR PROGNOSISPOOR PROGNOSIS
– Males, Blacks, Old age,Males, Blacks, Old age,
– High WBC count (1 lakh )High WBC count (1 lakh )
– Basophils + Eosinophils > 15 %,Basophils + Eosinophils > 15 %,
– > 5 % Blasts in BM,> 5 % Blasts in BM,
– Massive Hepatosplenomegaly,Massive Hepatosplenomegaly,
– Platelets > 7 lakhs,Platelets > 7 lakhs,
– Additional Chromosomal abnormalities -Additional Chromosomal abnormalities -
+8 ,19+8 ,19
– Marrow fibrosisMarrow fibrosis
CMLCML

25. Risk of Relapse :-Risk of Relapse :-
– Hb < 12 gm %,Hb < 12 gm %,
– Thrombocytosis,Thrombocytosis,
– Increased bands in PBS,Increased bands in PBS,
– No T/t response within 6 months,No T/t response within 6 months,
– +nce of clonal evolution,+nce of clonal evolution,
Sokal & Hasford scoring system,Sokal & Hasford scoring system,
CMLCML

26. HasfordHasford SokalSokal
• AgeAge
• Spleen sizeSpleen size
• Peripheral blood -Peripheral blood -
- Blasts- Blasts
- Eosinophils- Eosinophils
- Basophils- Basophils
- Platelets- Platelets
• ScoreScore : [O.66 age + O.04: [O.66 age + O.04
spleen + O.05 blasts(%) +spleen + O.05 blasts(%) +
O.04 eo(%) + O.20 baso +1.09O.04 eo(%) + O.20 baso +1.09
Plat] x 1000Plat] x 1000
• Risk cat.:-Risk cat.:-
Low :- </= 780Low :- </= 780
Interm. :- 781 - 1480Interm. :- 781 - 1480
High :- > 1480High :- > 1480
• AgeAge
• Spleen sizeSpleen size
• Peripheral blood -Peripheral blood -
- Blasts- Blasts
- Platelets- Platelets
• ScoreScore : exp[O.011(age - 43.4): exp[O.011(age - 43.4)
+ O.03(spleen - 7.51) + O.188+ O.03(spleen - 7.51) + O.188
[(Plat / 700)[(Plat / 700)22
- O.56] + O.08- O.56] + O.08
(blast - 2.1)](blast - 2.1)]
• Risk cat.:-Risk cat.:-
Low :- < O.8Low :- < O.8
Interm. :- O.8 - 1.2Interm. :- O.8 - 1.2
High :- > 1.2High :- > 1.2

27. MorphologyMorphology :-:-
– Marked diffuse Reticulin fibrosis & > 15 megakaryocytes /Marked diffuse Reticulin fibrosis & > 15 megakaryocytes /
cmm of BMcmm of BM
– Disappearance of Fibrosis :- High dose IF ά + Low doseDisappearance of Fibrosis :- High dose IF ά + Low dose
Cytosine arabinocydeCytosine arabinocyde
CML progressionCML progression :-:-
– In untreated pts.,In untreated pts.,
– Preceded or accompanied by sec. chr. abn.Preceded or accompanied by sec. chr. abn.
- Ph duplication, Trisomy 8, 19 & loss of Y; p53 mut,- Ph duplication, Trisomy 8, 19 & loss of Y; p53 mut,
- c-MYC & RAS gene mut.- c-MYC & RAS gene mut.
– Rate of transformation - 5 % in 1st yr.Rate of transformation - 5 % in 1st yr.
- Increased to 20-25% / yr thereafter- Increased to 20-25% / yr thereafter
CMLCML

28. APAP :-:-
Basophils > 20 % (PBS)Basophils > 20 % (PBS)
Blasts 10 - 19 % (BM),Blasts 10 - 19 % (BM),
Platelets < 1 lakh,Platelets < 1 lakh,
Marrow fibrosis,Marrow fibrosis,
Cytogenetic evolutionCytogenetic evolution,,
BCBC :-:-
Marrow or Blood Blasts > 20 %,Marrow or Blood Blasts > 20 %,
Clumps of blasts in BMClumps of blasts in BM
Increased LAP scoreIncreased LAP score
Extramedullary myeloid tumourExtramedullary myeloid tumour
Median survival 2 - 6 monthsMedian survival 2 - 6 months
Lymphoblastic transformation :Lymphoblastic transformation :
Better prognosisBetter prognosis
CMLCML

29. RemissionRemission :- indicated by:- indicated by
– Normal WBC count & BM morphology,Normal WBC count & BM morphology,
– Disappearance of Ph chr. & BCR/ABLDisappearance of Ph chr. & BCR/ABL
fusion transcript after Imatinib t/t,fusion transcript after Imatinib t/t,
– Cytogenetic response in CP :- 58 %, AP :-Cytogenetic response in CP :- 58 %, AP :-
48 % & BP :- 22 %48 % & BP :- 22 %
CMLCML

30. CLLCLL
Males, > 50 yrs,Males, > 50 yrs,
Lymphocytes : > 10,000 / μlLymphocytes : > 10,000 / μl
IPT :- Weakly +ve IgM, IgD,IPT :- Weakly +ve IgM, IgD,
CD5, 19, 20, 22CD5, 19, 20, 22
- CD 38 +ve unmutated- CD 38 +ve unmutated
IgVH gene,IgVH gene,

31. Rai & Binet staging systemRai & Binet staging system
STAGINGSTAGING
SYSTEMSYSTEM
RISKRISK STAGESTAGE CLINICAL FEATURESCLINICAL FEATURES
RAIRAI LowLow 00 LymphocytosisLymphocytosis
Interm.Interm. II Lymphocytosis ;LNpathyLymphocytosis ;LNpathy
IIII Lymphocytosis, spleno /Lymphocytosis, spleno /
hepatomegalyhepatomegaly
HighHigh IIIIII Lymphocytosis, Hb <11gm/dlLymphocytosis, Hb <11gm/dl
IVIV Lymphocytosis, plat < 1 lakhLymphocytosis, plat < 1 lakh
BINETBINET LowLow AA No cytopenia ,<3 LN enlargedNo cytopenia ,<3 LN enlarged
Interm.Interm. BB No cytopenia ,>/= 3 LN enlargedNo cytopenia ,>/= 3 LN enlarged
HighHigh CC Hb<10 gm/dl, plat <1lakhHb<10 gm/dl, plat <1lakh

32. Serum markersSerum markers :-:-
– β2 microglobulinβ2 microglobulin
– LDH,LDH,
– CD 23,CD 23,
Increased - progressive dis.Increased - progressive dis.
 Morphological featuresMorphological features :-:-
• Atypical morphology of cells (MC in Trisomy 12) :Atypical morphology of cells (MC in Trisomy 12) :
• > 10 % prolymphocytes> 10 % prolymphocytes
• > 15 % lymph. with cleaved nuclei or> 15 % lymph. with cleaved nuclei or
lymphoplasmacytoid cells,lymphoplasmacytoid cells,
• BM inv. > 70 %BM inv. > 70 %
CLLCLL

33. Molecular featuresMolecular features :-:-
 B cells withB cells with IgVH mutIgVH mut. - benign cond.. - benign cond.
 Unmut. IgVH gene - poor prognosisUnmut. IgVH gene - poor prognosis
 p53 abn. - poor prognosisp53 abn. - poor prognosis
Phenotypic featuresPhenotypic features :-:-
 ZAP 70 geneZAP 70 gene expression - good pognosisexpression - good pognosis
Encodes intracellular Tyrosine kinase for TCREncodes intracellular Tyrosine kinase for TCR
signaling,signaling,
Represents IgVH mutation,Represents IgVH mutation,
– CD 38 :- Unmutated IgVHCD 38 :- Unmutated IgVH
CLLCLL

34. Chromosomal aberrationsChromosomal aberrations :-:-
– MC del 13q, 11q, 14q, 6q & Trisomy 12MC del 13q, 11q, 14q, 6q & Trisomy 12
– Sole 13q14 del :- good prognosisSole 13q14 del :- good prognosis
– 17p, Trisomy 12 :- poor prognosis17p, Trisomy 12 :- poor prognosis
Disease progressionDisease progression :-:-
– in 5 - 10 % of pts,in 5 - 10 % of pts,
– C/F :- Gen. LNpathy, Syst. Symptoms like Fatigue,C/F :- Gen. LNpathy, Syst. Symptoms like Fatigue,
Fever, Wt loss, Cytopenia, Increased LDH,Fever, Wt loss, Cytopenia, Increased LDH,
Hypercalcemia, Monoclonal gammopathy,Hypercalcemia, Monoclonal gammopathy,
– Prolymphocytic transformationProlymphocytic transformation
CLLCLL

35. Richter’s synd.Richter’s synd. (5 %) :-(5 %) :-
– DLBCL (3 %), HD (O.5 %),DLBCL (3 %), HD (O.5 %),
– Occur in both Mut. & Unmut. variant,Occur in both Mut. & Unmut. variant,
– a/w del 11q, overexpression of C-MYC gene, p53 mut,a/w del 11q, overexpression of C-MYC gene, p53 mut,
– Median survival 5 - 8 months,Median survival 5 - 8 months,
– MC seen in pts t/t with Purine Nucleotide AnalogueMC seen in pts t/t with Purine Nucleotide Analogue
CLLCLL

36. LYMPHOMALYMPHOMA

37. Classical HL :-Classical HL :-
– Nodular Sclerosis,Nodular Sclerosis,
– Mixed Cellularity,Mixed Cellularity,
– Lymphocyte Rich,Lymphocyte Rich,
– Lymphocyte DepletionLymphocyte Depletion
Lymphocyte PredominantLymphocyte Predominant
HODGKINS LYMPHOMAHODGKINS LYMPHOMA

38. HODGKINS LYMPHOMAHODGKINS LYMPHOMA
Lymphoma of B –cells c/b RS cells & Hodgkin cellsLymphoma of B –cells c/b RS cells & Hodgkin cells
accompanied by reactive lymphocytes, granulocytes,accompanied by reactive lymphocytes, granulocytes,
eosinophils, histiocytes & plasma cells.eosinophils, histiocytes & plasma cells.
CD20 +, CD15 & 30 +ve, PAX-5 +ve, EBV/EBVERCD20 +, CD15 & 30 +ve, PAX-5 +ve, EBV/EBVER
& Bcl-2 +& Bcl-2 +
With modern therapies favorable prognosisWith modern therapies favorable prognosis
Secondary malignancies – AL, NHL MC cause ofSecondary malignancies – AL, NHL MC cause of
death in long term survivors.death in long term survivors.

39. Ann –Arbor Costwold staging systemAnn –Arbor Costwold staging system
STAGEISTAGEI Single LN region or Lymphoid structureSingle LN region or Lymphoid structure
STAGE IISTAGE II ≥≥ 2 LN regions on same side of diaphragm2 LN regions on same side of diaphragm
STAGE IIISTAGE III Both sides of diaphragmBoth sides of diaphragm
III1III1 With or without splenic, hilar, portal ,celiac nodesWith or without splenic, hilar, portal ,celiac nodes
III2III2 With para-aortic, iliac or mesentric nodesWith para-aortic, iliac or mesentric nodes
STAGE IVSTAGE IV Extranodal sites (not due to direct extension fromExtranodal sites (not due to direct extension from
nodal site)nodal site)
AA No symptomsNo symptoms
BB Fever ,Sweats, Wt lossFever ,Sweats, Wt loss
XX Bulky disease (10 cm LN;>1/3Bulky disease (10 cm LN;>1/3rdrd
widening ofwidening of
mediasinummediasinum
EE Single extranodal site contiguous or proximal toSingle extranodal site contiguous or proximal to
known nodal siteknown nodal site

40. WORSEWORSE :–:–
 AGE > 60 YRSAGE > 60 YRS
 STAGE III – IV – extranodal inv +veSTAGE III – IV – extranodal inv +ve
 Mediastinal massMediastinal mass
 Bulky disease (> 10 cm)Bulky disease (> 10 cm)
 B – symptomsB – symptoms
HODGKINS LYMPHOMAHODGKINS LYMPHOMA

41. Good prognosisGood prognosis :-:-
 CD15 + ; EBV LMP + ;CD15 + ; EBV LMP + ;
 NS HL - NS1NS HL - NS1 (low grade)(low grade)
Poor prognosisPoor prognosis :-:-
 AgeAge ≥≥ 45 yrs45 yrs
 Ann- Arbor stage IVAnn- Arbor stage IV
 ↓↓ S. Alb ,S. Alb , ↑↑ S. LDHS. LDH
 High proliferation indexHigh proliferation index
(( ↑↑ Ki-67 & loss of pRb)Ki-67 & loss of pRb)
 High mast cell proliferationHigh mast cell proliferation
 CD20 +CD20 +
 ↑↑ Exp of Bcl -2,Bcl-XExp of Bcl -2,Bcl-XLL & loss& loss
of BAX exp.of BAX exp.
 NS HL - NS2NS HL - NS2 (High grade)(High grade)
 MORPHOLOGIC & PHENOTYPICMORPHOLOGIC & PHENOTYPIC :-:-

42. NLPHLNLPHL --
 5 % of HL5 % of HL
 Nodular architecture & popcorn cellsNodular architecture & popcorn cells
 Stage IA & IIA - Excellent prognosisStage IA & IIA - Excellent prognosis
 Poor prognosisPoor prognosis
- +nce of diffuse T cell & increased Histiocytes- +nce of diffuse T cell & increased Histiocytes
- BM inv.- BM inv.
 NLPHLNLPHL  DLBCL (Median dur. - 1 yr)DLBCL (Median dur. - 1 yr)
Age 18 - 72 yrsAge 18 - 72 yrs
M > F,M > F,
Median Overall Survival = 35 Months,Median Overall Survival = 35 Months,
HODGKINS LYMPHOMAHODGKINS LYMPHOMA

43. NON - HODGKINNON - HODGKIN
LYMPHOMASLYMPHOMAS

44. Peripheral (Mature)Peripheral (Mature)
B cell neoplasmsB cell neoplasms :-:-
CLL / SLL,CLL / SLL,
B cell Prolymphocytic leukemia,B cell Prolymphocytic leukemia,
Lymphoplasmacytic lymphoma,Lymphoplasmacytic lymphoma,
Splenic & Nodal Marginal zoneSplenic & Nodal Marginal zone
lymphoma,lymphoma,
Mantle cell lymphoma,Mantle cell lymphoma,
Follicular lymphoma,Follicular lymphoma,
Marginal zone lymphoma,Marginal zone lymphoma,
Hairy cell leukemia,Hairy cell leukemia,
Plasma cell Myeloma,Plasma cell Myeloma,
Diffuse Large B cell lymphoma,Diffuse Large B cell lymphoma,
Burkitt’s Lymphoma,Burkitt’s Lymphoma,
Peripheral T cell NeoplasmsPeripheral T cell Neoplasms :-:-
T cell Prolymphocytic Leukemia,T cell Prolymphocytic Leukemia,
Large Granular Lymphocytic Leukemia,Large Granular Lymphocytic Leukemia,
Mycosis Fungoids / Sezary syndrome,Mycosis Fungoids / Sezary syndrome,
Peripheral T cell Lymphoma, Unspecified,Peripheral T cell Lymphoma, Unspecified,
Anaplstic Large cell Lymphoma,Anaplstic Large cell Lymphoma,
Angioimmunoblastic T cell Lymphoma,Angioimmunoblastic T cell Lymphoma,
Adult T cell Leukemia or Lymphoma,Adult T cell Leukemia or Lymphoma,
Enteropathy Asso. T cell Lymphoma,Enteropathy Asso. T cell Lymphoma,
Panniculitis like T cell Lymphoma,Panniculitis like T cell Lymphoma,
Hepatosplenic γδ T cell LymphomaHepatosplenic γδ T cell Lymphoma
NK/T cell Lymphoma, Nasal type,NK/T cell Lymphoma, Nasal type,
NK cell LeukemiaNK cell Leukemia

45. IPI for Malignant LymphomaIPI for Malignant Lymphoma
Adverse FactorsAdverse Factors
Age > 60 yrsAge > 60 yrs
Performance StatusPerformance Status
LDH > NormalLDH > Normal
≥≥ 22 Extranodal sitesExtranodal sites
Stage 3 & 4 diseaseStage 3 & 4 disease
5 year survival5 year survival
83 %83 %
69 %69 %
46 %46 %
32 %32 %
No. of FactorsNo. of Factors
0,10,1
22
33
4,54,5
Risk GroupsRisk Groups
LowLow
Low intermediateLow intermediate
HighHigh
intermediateintermediate

46. Adverse PredictorsAdverse Predictors :-:-
Age > 60 yrsAge > 60 yrs
B symptomsB symptoms
Hb < 11 gm / dl,Hb < 11 gm / dl,
 Sr. LDH,Sr. LDH,
High IPI score ( 3 - 5 )High IPI score ( 3 - 5 )
Bcl 2, c-MYC, p53 +veBcl 2, c-MYC, p53 +ve
B - Small Lymphocytic LymphomaB - Small Lymphocytic Lymphoma

47.  Disorder of Mature B cells with Medium sizedDisorder of Mature B cells with Medium sized
lymphocytes with nucleoli with Prolymphocyteslymphocytes with nucleoli with Prolymphocytes
> 55 %,> 55 %,
 Poor prognosisPoor prognosis--
Advanced age,Advanced age,
Hb < 11 gm%Hb < 11 gm%
Lymphocyte count > 1 lakh / μl,Lymphocyte count > 1 lakh / μl,
 Median overall survival = 5 yrsMedian overall survival = 5 yrs
 Event free survival = 37 months,Event free survival = 37 months,
B - Prolymphocytic Leukemia

48.  B cell disorder c / b Hairy cells in PB & BM,B cell disorder c / b Hairy cells in PB & BM,
Splenomegaly & Pancytopenia,Splenomegaly & Pancytopenia,
 CD 11c,19, 20, 22, 25, 103 +ve,CD 11c,19, 20, 22, 25, 103 +ve,
  Hb,Hb,
  WBC count,WBC count, Poor OutcomePoor Outcome
 SplenomegalySplenomegaly
 Newer t / t like Rituximab & BL-22 immunotoxin -Newer t / t like Rituximab & BL-22 immunotoxin -
5 yr survival from 58.9 % to 87.5 %,5 yr survival from 58.9 % to 87.5 %,
 Risk of sec. malignancies & opportunistic inf. - PoorRisk of sec. malignancies & opportunistic inf. - Poor
prognosisprognosis
Hairy cell Leukemia

49.  c / b indolent clinical course, nodular growthc / b indolent clinical course, nodular growth
pattern,pattern,
 t (14;18)(q32;q22) & Coexpression of CD 10,t (14;18)(q32;q22) & Coexpression of CD 10,
Bcl-2 & Bcl-6Bcl-2 & Bcl-6
 Inv BM with characteristic ParatrabecularInv BM with characteristic Paratrabecular
distribution,distribution,
Follicular Lymphoma

50. Poor prognostic markersPoor prognostic markers :-:-
– Age > 60 yrs,Age > 60 yrs,
– Hb < 12 gm / dl,Hb < 12 gm / dl,
– B symptoms,B symptoms,
– Hepatosplenomegaly,Hepatosplenomegaly,
– Ann-Arbor stage III / IV,Ann-Arbor stage III / IV,
– Bulky disease,Bulky disease,
–  β2 microglobulin,β2 microglobulin,
–  Sr. LDH,Sr. LDH,
–  ESRESR
Follicular Lymphoma

51. FL IPI :FL IPI :
 Age (> 60 yrs Vs < 60 yrs)Age (> 60 yrs Vs < 60 yrs)
 Hb (<12 Vs > 12)Hb (<12 Vs > 12)
 Ann Arbor stage (III, IV Vs I, II)Ann Arbor stage (III, IV Vs I, II)
 No. of nodal areas involved (> 4 Vs < 4)No. of nodal areas involved (> 4 Vs < 4)
 S. LDH > n Vs < nS. LDH > n Vs < n
 Risk groupsRisk groups --
 Low risk (O-1) = 85 % 5 yr survivalLow risk (O-1) = 85 % 5 yr survival
 Intermediate (2) = 79 %Intermediate (2) = 79 %
 Poor riskPoor risk ≥ 3≥ 3 == 28%28%
Follicular Lymphoma

52. Morphological phenotypicMorphological phenotypic :-:-
 Based on Absolute no. ofBased on Absolute no. of CentroblastsCentroblasts / 10 neoplastic/ 10 neoplastic
follicles / hpffollicles / hpf
Grade I = O - 5 / hpf,Grade I = O - 5 / hpf,
Grade II = 6 - 15 / hpfGrade II = 6 - 15 / hpf
Grade IIIaGrade IIIa ≥≥ 15 / hpf + Centrocytes +nt,15 / hpf + Centrocytes +nt,
Grade IIIbGrade IIIb ≥≥ 15 / hpf + Centrocytes -nt15 / hpf + Centrocytes -nt
 FL with Diffuse component - > 50 % large cells = PoorFL with Diffuse component - > 50 % large cells = Poor
survival,survival,
Follicular Lymphoma

53. Chromosomal AberrationsChromosomal Aberrations :-:-
 t (14 ;18)( q32 , q21 ) - 80 - 90 % -CD 10+, Bcl-6t (14 ;18)( q32 , q21 ) - 80 - 90 % -CD 10+, Bcl-6
+ve - favourable+ve - favourable
 Changes that correlate with morpho. progression toChanges that correlate with morpho. progression to
DLBCL - del (1) (p36) ,del (6q) , del (10), +7 &DLBCL - del (1) (p36) ,del (6q) , del (10), +7 &
polyploidy.polyploidy.
Follicular Lymphoma

54. TRANSFORMATIONTRANSFORMATION :-:-
 25-80%25-80%
 Increased no. ofIncreased no. of centroblastscentroblasts - DLBCL,- DLBCL,
Blastic transformation in Burkitt’sBlastic transformation in Burkitt’s
Lymphoma, Precurser B lymphoblasticLymphoma, Precurser B lymphoblastic
lymphoma or Leukemialymphoma or Leukemia
 a / w Sec. genetic abn., c-MYC genea / w Sec. genetic abn., c-MYC gene
rearrangement, p53 mut,rearrangement, p53 mut,
Follicular Lymphoma

55. Mantle cell lymphomaMantle cell lymphoma
– c / b Monomorphic app. cells with irregularc / b Monomorphic app. cells with irregular
indented nuclei +ve for CD 5, 20, 43, &indented nuclei +ve for CD 5, 20, 43, &
CD 23 -ve,CD 23 -ve,
– t (11;14)(q13;q32), Bcl locus coding cyclin D1 -t (11;14)(q13;q32), Bcl locus coding cyclin D1 -
IgH gene,IgH gene,
– 5 yr survival < 10 %,5 yr survival < 10 %,
– Those with relapse after SCT - Rituximab addedThose with relapse after SCT - Rituximab added

56. Poor prognosisPoor prognosis :-:-
 Splenomegaly,Splenomegaly,
 B symptoms,B symptoms,
 WBC count > 10,000 / µl,WBC count > 10,000 / µl,
 High LDH level,High LDH level,
 Blastic variant,Blastic variant,
 High / intermediate or High risk IPI,High / intermediate or High risk IPI,
Chromosomal AberrationsChromosomal Aberrations :-:-
 +12, Complex karyotype - Poor outcome+12, Complex karyotype - Poor outcome
Mantle cell lymphomaMantle cell lymphoma

57. Morphologic progressionMorphologic progression :-:-
– Blastoid variant,Blastoid variant,
– Median survival - 14.5 months,Median survival - 14.5 months,
– c / b - increased Mitotic count,c / b - increased Mitotic count,
- increased Proliferation indices,- increased Proliferation indices,
- Bcl-1 +ve,- Bcl-1 +ve,
- Overexpression of p53,- Overexpression of p53,
- Loss of p21 & p61 gene - Aggressive,- Loss of p21 & p61 gene - Aggressive,
Mantle cell lymphomaMantle cell lymphoma

58. Diffuse Large B cell LymphomaDiffuse Large B cell Lymphoma
 Aggressive lymphoma of mature B cellsAggressive lymphoma of mature B cells
 WHO SUBTYPESWHO SUBTYPES --
-- Centroblastic (MC > 80 %), - Thymic,Centroblastic (MC > 80 %), - Thymic,
- Immunoblastic, - ALK +ve- Immunoblastic, - ALK +ve
- Anaplastic, - Plasmablastic- Anaplastic, - Plasmablastic,,
- Intravascular,- Intravascular,
 +ve for CD 19, 20, 22, 79a, PAX 5,+ve for CD 19, 20, 22, 79a, PAX 5,
 CHOP / Dose intense CHOP / R-CHOP used.CHOP / Dose intense CHOP / R-CHOP used.

59. FavorableFavorable :-:-
 Low stage (I , II),Low stage (I , II),
 Lack of B symptoms,Lack of B symptoms,
 BM < 50 % Large cells,BM < 50 % Large cells,
 Focal inv.,Focal inv.,
 IgR -ve (CR - 71 %)IgR -ve (CR - 71 %)
UnfavorableUnfavorable :-:-
 Age > 60 yrs,Age > 60 yrs,
 Poor performancePoor performance
status,status,
 ↑↑ Sr. LDH & β2Sr. LDH & β2
microglobulin,microglobulin,
 > 50 % Large cells,> 50 % Large cells,
 Diffuse pattern,Diffuse pattern,
 IgR +ve (CR - 51%),IgR +ve (CR - 51%),
• Clinical & Lab parametersClinical & Lab parameters :-
Diffuse Large B cell LymphomaDiffuse Large B cell Lymphoma

60. Morphological & PhenotypicMorphological & Phenotypic :-:-
Poor PrognosisPoor Prognosis :-:-
– T cell rich Large B cell lymphoma - AggressiveT cell rich Large B cell lymphoma - Aggressive
– High proliferation index by Ki-67 - Adverse,High proliferation index by Ki-67 - Adverse,
– c-MYC overexpression, Loss of pRbc-MYC overexpression, Loss of pRb
Molecular MarkersMolecular Markers :-:-
– t (14;18) - Bcl-2 amplification - good prognosist (14;18) - Bcl-2 amplification - good prognosis
Diffuse Large B cell LymphomaDiffuse Large B cell Lymphoma

61. IPTIPT
Germinal center B cellGerminal center B cell
like pattern (A)like pattern (A)
CD10 & Bcl-6 +veCD10 & Bcl-6 +ve
Better survivalBetter survival
Activated B cell likeActivated B cell like
pattern (1 GCM + 1 0fpattern (1 GCM + 1 0f
CD 138, MUM-1 / IRF-4CD 138, MUM-1 / IRF-4
))
WorseWorse
Activated nonActivated non
germinal centergerminal center
(( FOXP-1 +veFOXP-1 +ve))
PoorPoor
Diffuse Large B cell LymphomaDiffuse Large B cell Lymphoma

62.  Specific clinical variantsSpecific clinical variants :-:-
1) Extranodal DLBCL1) Extranodal DLBCL
2) Intravascular - Poor survival < 12 mths.2) Intravascular - Poor survival < 12 mths.
3) Cut. DLBCL - Location on leg aw Bcl-2 &3) Cut. DLBCL - Location on leg aw Bcl-2 &
older age - poor survivalolder age - poor survival
4) Primary testicular DLBCL,4) Primary testicular DLBCL,
5) Primary CNS DLBCL5) Primary CNS DLBCL
6) Mediastinal DLBCL6) Mediastinal DLBCL
Diffuse Large B cell LymphomaDiffuse Large B cell Lymphoma

63. Multiple MyelomaMultiple Myeloma
 Clonal Disorder of B cell at last stage ofClonal Disorder of B cell at last stage of
differentiation c /b BM infiltration by Plasmadifferentiation c /b BM infiltration by Plasma
cells & Monoclonal immunoglobulin production,cells & Monoclonal immunoglobulin production,
 From MGUS or De-novo,From MGUS or De-novo,
 MajorMajor :-:-
• Marrow Plasmacytosis (> 30%)Marrow Plasmacytosis (> 30%)
• Plasmacytoma on biopsy,Plasmacytoma on biopsy,
• M- component -M- component -
• Serum - IgG > 3.5 g / dl,Serum - IgG > 3.5 g / dl,
IgA > 2 g / dlIgA > 2 g / dl
• Urine > 1 g / 24 hr of BJUrine > 1 g / 24 hr of BJ
prot.prot.
 MinorMinor :-:-
• Marrow PlasmacytosisMarrow Plasmacytosis
(10 - 30%),(10 - 30%),
• M component +nt But < Major,M component +nt But < Major,
• Lytic Bone Lesions,Lytic Bone Lesions,
• Reduced normal Ig (< 50 %)Reduced normal Ig (< 50 %)

64. Clinical & Lab parametersClinical & Lab parameters :-:-
 High Plasma cell labeling indexHigh Plasma cell labeling index ≥ 1 %≥ 1 %
- Poor prognosis,- Poor prognosis,
 Decreased Sr monoclonal proteins byDecreased Sr monoclonal proteins by
30 % - Better prognosis,30 % - Better prognosis,
Multiple MyelomaMultiple Myeloma

65. Stage I :-Stage I :- Median survival > 5 yrsMedian survival > 5 yrs..
– LowLow M component levels : IgG < 5 g /dl, IgA < 3 g/dl,M component levels : IgG < 5 g /dl, IgA < 3 g/dl,
Urine BJ < 4 g / 24hrUrine BJ < 4 g / 24hr
– Absent or Solitary Bone Lesion,Absent or Solitary Bone Lesion,
– Normal Hb, Sr. Ca, Ig levels (Non M comp.),Normal Hb, Sr. Ca, Ig levels (Non M comp.),
Stage III :-Stage III :- Any 1 or More,Any 1 or More, Median survival = 2 yrsMedian survival = 2 yrs..
– HighHigh M component : IgG > 7 g/dl, IgA > 5 g/dl,M component : IgG > 7 g/dl, IgA > 5 g/dl,
Urine BJ > 12 g / 24 hr,Urine BJ > 12 g / 24 hr,
– Advanced Multiple Lytic Bone Lesions,Advanced Multiple Lytic Bone Lesions,
– Hb < 8.5 g / dl, Sr. Ca. > 12 mg / dl,Hb < 8.5 g / dl, Sr. Ca. > 12 mg / dl,
Stage II :- Values between I & III,Stage II :- Values between I & III, Median survival > 3 yrMedian survival > 3 yr
Multiple MyelomaMultiple Myeloma

66. Chromosomal AberrationsChromosomal Aberrations :-:-
 70 % numerical aberrations70 % numerical aberrations  MC monosomy 13 -MC monosomy 13 -
High relapse & progression to MMHigh relapse & progression to MM
 MC - t (11;14)(q13;q32)MC - t (11;14)(q13;q32)  Upregulation ofUpregulation of
Cyclin D1Cyclin D1
Trisomy 6, 9, 17Trisomy 6, 9, 17  Prolong survivalProlong survival
Multiple MyelomaMultiple Myeloma

67. Molecular MarkersMolecular Markers :-:-
 Activating mutation of Ki-RAS - Adverse prognosis,Activating mutation of Ki-RAS - Adverse prognosis,
 Based on recurrent Ig translocations & Cyclin DBased on recurrent Ig translocations & Cyclin D
expression,expression,
TC1TC1 - High levels of Cyclin D1 / D3 + t (11;14),- High levels of Cyclin D1 / D3 + t (11;14),
TC2 - Low to mod. Cyclin D1 - t (11;14),TC2 - Low to mod. Cyclin D1 - t (11;14),
TC3 - Mixture of tumours, Cyclin D2,TC3 - Mixture of tumours, Cyclin D2,
TC4TC4 - High levels of Cyclin D2 + t (4;14),- High levels of Cyclin D2 + t (4;14),
TC5TC5 - High levels of Cyclin D2 + t (14;16)- High levels of Cyclin D2 + t (14;16)
Multiple MyelomaMultiple Myeloma

68. Lymphoplasmacytic LymphomaLymphoplasmacytic Lymphoma
 Low grade lymphoma c / b mixture of smallLow grade lymphoma c / b mixture of small
lymphocytes, lymphocytes with plasmacytoidlymphocytes, lymphocytes with plasmacytoid
features & plasma cells,features & plasma cells,
 Occ. cell showOcc. cell show Dutcher’s bodiesDutcher’s bodies,,
 c / b : t (9;14)(q13;q32) - PAX-5 gene on chr. 9c / b : t (9;14)(q13;q32) - PAX-5 gene on chr. 9
 4 - 15 %4 - 15 %  DLBCL,DLBCL,

69. Waldenstrom’s MacroglobulinemiaWaldenstrom’s Macroglobulinemia
  IgM paraprotein (> 30 gm / L), AccumulationIgM paraprotein (> 30 gm / L), Accumulation
of clonal lymphoplasmacytic cells in BM,of clonal lymphoplasmacytic cells in BM,
 AdverseAdverse :- Advanced age,:- Advanced age,
 Hb < 12 gm/dl,Hb < 12 gm/dl,
Cytopenias,Cytopenias,
 Sr. β2 microglobulin levelSr. β2 microglobulin level ≥ 3 mg/L≥ 3 mg/L
 Median survival = 5 - 6 yrs,Median survival = 5 - 6 yrs,

70. Marginal Zone B cell lymphomaMarginal Zone B cell lymphoma
SPLENICSPLENIC MARGINAL ZONE LYMPHOMAMARGINAL ZONE LYMPHOMA :-:-
 Elderly, median age 65 yrs,Elderly, median age 65 yrs,
 Poor prognosisPoor prognosis
- Age > 70 yr, - Hb < 11 gm / dl,- Age > 70 yr, - Hb < 11 gm / dl,
- Lymphocytes > 16,000 /µl - Platelets < 1 lakh,- Lymphocytes > 16,000 /µl - Platelets < 1 lakh,
-- ↑↑ Sr. β2 microglobulin - 7q31 delSr. β2 microglobulin - 7q31 del
 Median survival 8 - 13 yrs, Death - transformationMedian survival 8 - 13 yrs, Death - transformation
 Large cell transformation a/w del (10), del(19) &Large cell transformation a/w del (10), del(19) &
trisomy 3,trisomy 3,

71. EXTRANODAL MARGINAL ZONE B CELLEXTRANODAL MARGINAL ZONE B CELL
LYMPHOMA OFLYMPHOMA OF MALT TYPEMALT TYPE
 Low grade, Stomach, Salivary gland, Thyroid, Skin & inLow grade, Stomach, Salivary gland, Thyroid, Skin & in
acquired lymphoid tissue after chronic infla. Events - H.acquired lymphoid tissue after chronic infla. Events - H.
pylori gastritis, Hashimoto’s & Sjogren’s synd.pylori gastritis, Hashimoto’s & Sjogren’s synd.
 Poor prognosisPoor prognosis
Increased LDH,Increased LDH,
Advanced stage,Advanced stage,
IPI - High riskIPI - High risk
Transformation to High grade lymphoma inTransformation to High grade lymphoma in
8 %, a/w Trisomy 3, 7 & 188 %, a/w Trisomy 3, 7 & 18
 5 yr survival -5 yr survival - without nodal inv. - 97 %,without nodal inv. - 97 %,
- with nodal inv. - 75 %- with nodal inv. - 75 %

72. API2-MALT fusion geneAPI2-MALT fusion gene
Group AGroup A
Fusion -veFusion -ve
EradicationEradication
responsiveresponsive
MCMC
• Low clinical stageLow clinical stage
• SuperficialSuperficial
gastric inv.gastric inv.
Group BGroup B
Fusion -veFusion -ve
EradicationEradication
Non responsiveNon responsive
• Nodal inv.Nodal inv.
• Deep gastric wall inv.Deep gastric wall inv.
• Adv. Clinical stageAdv. Clinical stage
Group CGroup C
Fusion +veFusion +ve
EradicationEradication
Non responsiveNon responsive
• Low H.pylori inf. rateLow H.pylori inf. rate
• Low grade histo.Low grade histo.
• Adv. Clinical stageAdv. Clinical stage
• Bcl-10 +veBcl-10 +ve

73. Nodal Marginal Zone B cellNodal Marginal Zone B cell
LymphomaLymphoma
 MC in Cervical LN,MC in Cervical LN,
 More aggressive than MALT,More aggressive than MALT,
 +nts with Advanced stage (III / IV),+nts with Advanced stage (III / IV),
 Lower survival,Lower survival,
 Transformation to Large cell - 20 % - atTransformation to Large cell - 20 % - at
time of diagnosistime of diagnosis

74. Burkitt’s LymphomaBurkitt’s Lymphoma
 c/b Bulky disease, Extranodal location & Aggressive course,c/b Bulky disease, Extranodal location & Aggressive course,
 3 variants :3 variants :
EndemicEndemic :- 4 - 7 yrs, 100 % EBV asso.:- 4 - 7 yrs, 100 % EBV asso.
- Mandible, Maxilla,- Mandible, Maxilla,
Sporadic / SpontaneousSporadic / Spontaneous :- Young adults, Abd. Organs:- Young adults, Abd. Organs
a/w Immunodefa/w Immunodef. :- HIV. :- HIV
 HistoHisto :- Medium sized cells with numerous mitotic cells:- Medium sized cells with numerous mitotic cells
with scattered Macrophages - “with scattered Macrophages - “Starry sky appStarry sky app.”.”

75.  t (8;14)(q24;q32) :- Aggressive diseaset (8;14)(q24;q32) :- Aggressive disease
 Poor PrognosisPoor Prognosis
 AgeAge ≥ 15 yr,≥ 15 yr,
 BM inv.,BM inv.,
 Initial Sr. LDH > 500 IU / L,Initial Sr. LDH > 500 IU / L,
 Expression of C-FLIPExpression of C-FLIP
 High dose therapy + SCT = Good survival,.High dose therapy + SCT = Good survival,.
Burkitt’s LymphomaBurkitt’s Lymphoma

76. NodalNodal :-:-
– Angio-immunoblastic TAngio-immunoblastic T
cell lymphoma (AILT),cell lymphoma (AILT),
– Peripheral T cellPeripheral T cell
lymphoma, Unspecifiedlymphoma, Unspecified
(PTCL),(PTCL),
– Anaplastic large cellAnaplastic large cell
lymphoma (ALCL),lymphoma (ALCL),
Peripheral (Mature) T-cell NeoplasmPeripheral (Mature) T-cell Neoplasm
ExtranodalExtranodal :-:-
– Mycosis fungoides (MF)Mycosis fungoides (MF)
– Cutaneous ALCL,Cutaneous ALCL,
– Extranodal NK/T cellExtranodal NK/T cell
lymphoma (Nasal type),lymphoma (Nasal type),
– Enteropathy type,Enteropathy type,
– Hepatosplenic,Hepatosplenic,
– SubcutaneousSubcutaneous
panniculitis like,panniculitis like,
10 % of NHL10 % of NHL
• Poor prognosis comp. to B cell lymphomasPoor prognosis comp. to B cell lymphomas

77. T CELL PROLYMPHOCYTICT CELL PROLYMPHOCYTIC
LEUKEMIALEUKEMIA
– Affects adult malesAffects adult males
– Aggressive clinical course,Aggressive clinical course,
– Poor prognosis -Poor prognosis -
Hb < 11g/dlHb < 11g/dl
Advanced ageAdvanced age
Lymphocytosis > 1 lakh / µl,Lymphocytosis > 1 lakh / µl,
Involving Chr. 14 :- inv (14)(q11;q32), t (14;14)(q11;q32)Involving Chr. 14 :- inv (14)(q11;q32), t (14;14)(q11;q32)
& i(8)(q10),- TCL-1 gene activation& i(8)(q10),- TCL-1 gene activation
Complex karyotypeComplex karyotype
– Improved with Alemtuzumab (Anti-CD52)Improved with Alemtuzumab (Anti-CD52)

78. T LARGE GRANULART LARGE GRANULAR
LYMPHOCYTE LEUKEMIALYMPHOCYTE LEUKEMIA
– Indolent courseIndolent course
– Median age 60 yrs,Median age 60 yrs,
– Poor Prognostic Factors :-Poor Prognostic Factors :-
Fever at diagnosis,Fever at diagnosis,
Low % of CD 57 +ve cellsLow % of CD 57 +ve cells
Severe Neutropenia & B symptomsSevere Neutropenia & B symptoms
NK cell phenotypeNK cell phenotype

79. CUTANEOUS T- CELL LYMPHOMASCUTANEOUS T- CELL LYMPHOMAS
– MC- MF, ALCL & Lymphomatoid papulosis.MC- MF, ALCL & Lymphomatoid papulosis.
– Poor prognostic factorsPoor prognostic factors ––
Blood eosinophiliaBlood eosinophilia
Increaesd S.LDH levelsIncreaesd S.LDH levels
High no of chromo. Abn. (>5) - (gain in 8q & loss ofHigh no of chromo. Abn. (>5) - (gain in 8q & loss of
6q &13q)6q &13q)
Dual CD4/CD8 -ve T cellsDual CD4/CD8 -ve T cells

80. MYCOSIS FUNGOIDESMYCOSIS FUNGOIDES
– 10 yr survival 40 - 100 %, depending on degree of10 yr survival 40 - 100 %, depending on degree of
skin inv.,skin inv.,
– Large cell transformationLarge cell transformation
- early in disease (< 2 yrs),- early in disease (< 2 yrs),
- Large cells > 25 %- Large cells > 25 %
- CD 25 +ve,- CD 25 +ve,
- extracutaneous - Shorter survival,- extracutaneous - Shorter survival,

81. SEZARY’S SYNDROMESEZARY’S SYNDROME :-:-
– Aggressive T cell lymphoma with poor prognosis,Aggressive T cell lymphoma with poor prognosis,
– Median survival :- 2 - 3 yrs,Median survival :- 2 - 3 yrs,
– Poor prognosisPoor prognosis
- Past evolution of disease,- Past evolution of disease,
- Increased level of LDH & β2 microglobulin- Increased level of LDH & β2 microglobulin
PRIMARY CUT. ANAPLASTIC LARGE CELLPRIMARY CUT. ANAPLASTIC LARGE CELL
LYMPHOMALYMPHOMA :-:-
– Older pts, ALK -ve,Older pts, ALK -ve,
– Favorable prognosisFavorable prognosis
- CD 30 +ve - Localized skin disease- CD 30 +ve - Localized skin disease
– Poor prognosisPoor prognosis
- Disseminated skin inv. - Extracutaneous disease- Disseminated skin inv. - Extracutaneous disease

82. ANGIO-IMMUNOBLASTICANGIO-IMMUNOBLASTIC
T CELL LYMPHOMAT CELL LYMPHOMA
– LN - polymorphous infiltrate c/o Atypical ,SmallLN - polymorphous infiltrate c/o Atypical ,Small
lymphocytes, Histiocytes, Eosinophils, Plasma cells,lymphocytes, Histiocytes, Eosinophils, Plasma cells,
 no. of arborising vessels & scattered EBV +ve B-no. of arborising vessels & scattered EBV +ve B-
immunoblasts,immunoblasts,
– Aggressive clinical courseAggressive clinical course
– Poor prognosis with conventional t/t, but, High dosePoor prognosis with conventional t/t, but, High dose
chemotherapy +/- SCT - Long term survivalchemotherapy +/- SCT - Long term survival

83. ANAPLASTIC LARGE CELL LYMPHOMAANAPLASTIC LARGE CELL LYMPHOMA
– c/b large pleomorphic cells with irregular nucleic/b large pleomorphic cells with irregular nuclei
((Hallmark cellsHallmark cells), Paracortical & Intrasinusoidal LN inv.), Paracortical & Intrasinusoidal LN inv.
& CD 30 +ve,& CD 30 +ve,
NPM gene
at 5q35
ALK gene
at 2p23
t (2;5)(p23;q35)t (2;5)(p23;q35)
NPM-ALK geneNPM-ALK gene
80 kDa Protein - p80 &80 kDa Protein - p80 &
variant ALK prot.variant ALK prot.
Subcellular LocalisationSubcellular Localisation

84. – Unfavorable factorsUnfavorable factors :-:-
Age > 60 yrs ,Age > 60 yrs ,
CD 56 +ve,CD 56 +ve,
Stage III / IV,Stage III / IV,
ALK -ve,ALK -ve,
Extranodal disease > 2 sites,Extranodal disease > 2 sites,
Increased LDH,Increased LDH,
Leukemic blood inv. - Early relapseLeukemic blood inv. - Early relapse
Children with Lung, Skin & Mediastinal invChildren with Lung, Skin & Mediastinal inv
ANAPLASTIC LARGE CELL LYMPHOMAANAPLASTIC LARGE CELL LYMPHOMA

85. – Favorable prognosisFavorable prognosis --
- ALK +ve cases +- ALK +ve cases +
- IPI - Low / Intermediate risk group- IPI - Low / Intermediate risk group
- 94 % 5 yr survival rate,- 94 % 5 yr survival rate,
ANAPLASTIC LARGE CELLANAPLASTIC LARGE CELL
LYMPHOMALYMPHOMA

86. MYELODYSPLASTIC SYNDROMESMYELODYSPLASTIC SYNDROMES
WHO Classification :-WHO Classification :-
Refractory Anaemia,Refractory Anaemia,
Refractory Anaemia with Ringed Sideroblasts,Refractory Anaemia with Ringed Sideroblasts,
Refractory cytopenia with Multilineage Dyspalsia,Refractory cytopenia with Multilineage Dyspalsia,
Refractory cytopenia with Multilineage Dyspalsia &Refractory cytopenia with Multilineage Dyspalsia &
ringed sideroblastsringed sideroblasts
Refractory Anaemia with Excess blasts -1Refractory Anaemia with Excess blasts -1
Refractory Anaemia with Excess blasts -2Refractory Anaemia with Excess blasts -2
Myelodysplastic synd. a/w isolated del (5q) chr. Abn.Myelodysplastic synd. a/w isolated del (5q) chr. Abn.
Myelodysplastic synd. unclassifiableMyelodysplastic synd. unclassifiable

87. MYELODYSPLASTIC SYNDROMESMYELODYSPLASTIC SYNDROMES
– c / b ineffective haematopoiesis & dyspoiesis leading to BMc / b ineffective haematopoiesis & dyspoiesis leading to BM
failure, Cytopeniafailure, Cytopenia
– De-novo or following chemo-/ radiotherapy,De-novo or following chemo-/ radiotherapy,
– Based on survival duration & incidence of progression toBased on survival duration & incidence of progression to
Ac. Leukemia, divided into:-Ac. Leukemia, divided into:-
Low risk :- Isolated 5q del, RA, RARSLow risk :- Isolated 5q del, RA, RARS
(High- Bad, Bak & Bcl-Xs)(High- Bad, Bak & Bcl-Xs)
High risk :- RCMD & RAEB (Bcl-2, BclXHigh risk :- RCMD & RAEB (Bcl-2, BclXLL))
25 - 38 % of RAEB progress to Ac. Leukemia25 - 38 % of RAEB progress to Ac. Leukemia

88. IPSS FOR MDSIPSS FOR MDS
ScoresScores
PrognosticPrognostic
VariableVariable
00 0.50.5 11 1.51.5 22
BM blastsblasts <5 5-105-10 -- 11-2011-20 21-3021-30
KaryotypeKaryotype GoodGood Intermed.Intermed. PoorPoor
CytopeniasCytopenias 0/10/1 2/32/3
Low risk - 0 (9.4 yrs)Low risk - 0 (9.4 yrs)
INT-1 - 0.5 - 1 (3.3 yrs)INT-1 - 0.5 - 1 (3.3 yrs)
INT-2 - 1.5 - 2 (1.1yrs)INT-2 - 1.5 - 2 (1.1yrs)
HIGH -HIGH - ≥ 2.5≥ 2.5
• Good – normal, monoY,Good – normal, monoY,
del (5q),del (20q)del (5q),del (20q)
• Poor – complex (Poor – complex ( ≥ 3 abn.),
chr.7 abn.
• Intermediate - other

89. CHRONIC MYELOMONOCYTICCHRONIC MYELOMONOCYTIC
LEUKEMIALEUKEMIA
– C/B Persistent Monocytosis > 1000 / µl ,<20% blasts inC/B Persistent Monocytosis > 1000 / µl ,<20% blasts in
BM & PB,BM & PB,
– Majority - Proliferative type c/b WBC count > 13000 / µl -Majority - Proliferative type c/b WBC count > 13000 / µl -
– Dysplastic type :- WBC count < 13000 / µl + CytogeneticDysplastic type :- WBC count < 13000 / µl + Cytogenetic
abn. - Worse prognosis,abn. - Worse prognosis,
– Poor prognosisPoor prognosis ::
Hb < 12 gm / dl,Hb < 12 gm / dl,
+nce of circulating immature myeloid cells,+nce of circulating immature myeloid cells,
Abs. Lymphocyte count > 2500 / µl,Abs. Lymphocyte count > 2500 / µl,
Marrow blastsMarrow blasts ≥≥10 %10 %

90. OTHER CMPD’SOTHER CMPD’S
POLYCYTHEMIA VERAPOLYCYTHEMIA VERA ––
– c/b incr. no of red blood cells, total blood volume,c/b incr. no of red blood cells, total blood volume,
leucocytosos ,thrombocytosis & splenomegalyleucocytosos ,thrombocytosis & splenomegaly
– Progression to myelofibrosis , MDS & AML (20%).Progression to myelofibrosis , MDS & AML (20%).
– Aggressive therapy – MDS & ac. LeukemiaAggressive therapy – MDS & ac. Leukemia
 ESSENTIAL THROMBOCYTHEMIAESSENTIAL THROMBOCYTHEMIA :-:-
• Clonal MPD of megakaryocyte ( ≥ 6 lakh/ µl ) &Clonal MPD of megakaryocyte ( ≥ 6 lakh/ µl ) &
megakaryoctosis with atypia & clustring in BMmegakaryoctosis with atypia & clustring in BM
• Indolent disease c/b median survival -10-15 YrsIndolent disease c/b median survival -10-15 Yrs

91. CHRONIC IDIOPATHICCHRONIC IDIOPATHIC
MYELOFIBROSISMYELOFIBROSIS
– c/b proliferation of megakaryocyte & granulocyticc/b proliferation of megakaryocyte & granulocytic
elements with deposition of excess collagen in BMelements with deposition of excess collagen in BM
– Median survival- 3-7 yrsMedian survival- 3-7 yrs
– Blast crisis - 5to 30 % -Blast crisis - 5to 30 % - poorpoor
– 5q- ,+8, 13q- ,20q- a/w good prognosis5q- ,+8, 13q- ,20q- a/w good prognosis

92. LILLE SCORING SYSTEMLILLE SCORING SYSTEM
Risk groupsRisk groups Hb gm %Hb gm % WBC count / μlWBC count / μl
MedianMedian
survivalsurvival
>10>10
<10 OR<10 OR
<10 &<10 &
LowLow
IntermediateIntermediate
HighHigh
4000-30,0004000-30,000
< 4000/< 4000/
>30,000>30,000
< 4000/< 4000/
>30,000>30,000
93 mths93 mths
26 mths26 mths
13 mths13 mths
CHRONIC IDIOPATHICCHRONIC IDIOPATHIC
MYELOFIBROSISMYELOFIBROSIS

93. Poor prognostic factorsPoor prognostic factors --
– Age > 60 yearAge > 60 year
– MalesMales
– Hepatomegaly,Hepatomegaly,
– Incr. LDH,Incr. LDH,
– platelets < 1 Lakh,platelets < 1 Lakh,
– abnormal karyotype,abnormal karyotype,
– > 10 % granulocyte precursors in blood> 10 % granulocyte precursors in blood
CHRONIC IDIOPATHICCHRONIC IDIOPATHIC
MYELOFIBROSISMYELOFIBROSIS

94. SUMMARYSUMMARY
MC malignancies in haematopoietic system areMC malignancies in haematopoietic system are
Acute Leukemias, CLL, DLBCL, CML & MDS,Acute Leukemias, CLL, DLBCL, CML & MDS,
Classification & Diagnosis from both Clinical &Classification & Diagnosis from both Clinical &
Pathological point of view are complicated &Pathological point of view are complicated &
require multimethodology approach,require multimethodology approach,
Establishing diagnosis is just first step.Establishing diagnosis is just first step.
Selection of proper treatment, monitoring response,Selection of proper treatment, monitoring response,
MRD detection & detection of relapse at early stageMRD detection & detection of relapse at early stage
are also equally important.are also equally important.

95. THANKTHANK YOUYOU

96. PERIPHERAL T CELL LYMPHOMA -PERIPHERAL T CELL LYMPHOMA -
UNSPECIFIED :-UNSPECIFIED :-
– Prognosis poor with overall 5 yr survival 41 - 49 %,Prognosis poor with overall 5 yr survival 41 - 49 %,
– Acc. to IPI :-Acc. to IPI :-
Low risk group ( O - 1 ) :- 64 - 75 % - 5 yr survival,Low risk group ( O - 1 ) :- 64 - 75 % - 5 yr survival,
High risk group ( >/= 2 ) :- 30 %,High risk group ( >/= 2 ) :- 30 %,
– Age > 60 yrs, increased LDH, BM inv. - Poor prognosisAge > 60 yrs, increased LDH, BM inv. - Poor prognosis
– Relapsed or refractory to conventional t/t - Poor prognosisRelapsed or refractory to conventional t/t - Poor prognosis

97. HEPATOSPLENIC γδ-T CELL LYMPHOMA :-HEPATOSPLENIC γδ-T CELL LYMPHOMA :-
– Poor prognosis,Poor prognosis,
– i (7q) +ve,i (7q) +ve,
– Better results with Platinum, Cytarabine based CHOPBetter results with Platinum, Cytarabine based CHOP
regimen,regimen,
– Median survival 16 months,Median survival 16 months,
NK/T CELL LYMPHOMA (Nasal type) :-NK/T CELL LYMPHOMA (Nasal type) :-
– Aggressive tumor,Aggressive tumor,
– May occur at Testis, Bone, Skin, Subcut. Tissue,May occur at Testis, Bone, Skin, Subcut. Tissue,
– 5 yr survival - O %,5 yr survival - O %,