2. Introduction to Prognostic Markers
Introduction to Prognostic Markers
Leukemias :-
Leukemias :-
AML,
AML,
ALL,
ALL,
CML,
CML,
CLL,
CLL,
Lymphomas :-
Lymphomas :-
HL
HL
NHL :-
NHL :-
B cell
B cell
T cell
T cell
MDS
MDS
Other CMPDs
Other CMPDs
3. Prognostic Markers
Prognostic Markers
Imp - not only in
Imp - not only in diagnosis
diagnosis but also in
but also in
Predicting
Predicting survival
survival of pt.
of pt.
Selection of
Selection of proper t/t
proper t/t,
,
Monitoring
Monitoring response
response to t/t ,
to t/t ,
Detection of
Detection of relapse
relapse – MRD by FISH ,RQ- PCR
– MRD by FISH ,RQ- PCR
Prognostic indices
Prognostic indices
Ann-Arbor classification -HL
Ann-Arbor classification -HL
Prognostic indices
Prognostic 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 ,DLBCL
e.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
Transformation
Transformation – e.g. B-CLL – DLBCL
– e.g. B-CLL – DLBCL
Angiogenesis
Angiogenesis - 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 – FL
FL
- c-FLIP express - ALL
- c-FLIP express - ALL
Prognostic Markers
Prognostic Markers
7. ACUTE LEUKEMIA
ACUTE LEUKEMIA
World wide incidence :- 4 per 1 lakh
World wide incidence :- 4 per 1 lakh
80 % : AML
80 % : AML
Blasts
Blasts ≥
≥ 20 %
20 %
8. FAB CLASSIFICATION OF AML
FAB CLASSIFICATION OF AML
M0 : Minimally differentiated
M0 : Minimally differentiated
M1 : Myeloblastic leukemia without maturation
M1 : Myeloblastic leukemia without maturation
M2 : Myeloblastic leukemia with maturation
M2 : Myeloblastic leukemia with maturation
M3 : Hypergranular promyelocytic leukemia
M3 : Hypergranular promyelocytic leukemia
M3 variant : hypogranular promyelocytic leukemia
M3 variant : hypogranular promyelocytic leukemia
M4 : myelomonocytic leukemia
M4 : myelomonocytic leukemia
M4E0 : variant, increase in marrow eosinophils
M4E0 : variant, increase in marrow eosinophils
M5 : Monocytic leukemia
M5 : Monocytic leukemia
M5a ; without maturation
M5a ; without maturation
M5b : with maturation
M5b : with maturation
M6 : Erythroleukemia (DiGuglielmo’s disease)
M6 : Erythroleukemia (DiGuglielmo’s disease)
M7 : Megakaryoblastic leukemia
M7 : Megakaryoblastic leukemia
9. WHO CLASSIFICATION OF AML
WHO CLASSIFICATION OF AML
AML WITH RECURRENT CYTOGENETIC
AML WITH RECURRENT CYTOGENETIC
ABNORMALITIES
ABNORMALITIES (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)- CBFβ
β/MYH1 –(M4Eo)
/MYH1 –(M4Eo)
- AML with 11q23 MLL abnormalities (M5)
- AML with 11q23 MLL abnormalities (M5)
AML WITH MULTILINEAGE DYSPLASIA
AML WITH MULTILINEAGE DYSPLASIA:(-7, -5, +8, +9, +11)
:(-7, -5, +8, +9, +11)
-
- With prior MDS
With prior MDS
- Without prior MDS
- Without prior MDS
10. WHO CLASSIFICATION OF AML
WHO CLASSIFICATION OF AML
AML THERAPY RELATED
AML THERAPY RELATED :-
:-
– Alkylating agent related
Alkylating agent related
– Topoisomerase II inhibitor related
Topoisomerase II inhibitor related
AML NOT OTHERWISE CATEGORIZED
AML NOT OTHERWISE CATEGORIZED :-
:-
– AML minimally differentiated
AML minimally differentiated
– AML without maturation
AML without maturation
– AML with maturation
AML with maturation
– Acute myelomonocytic leukemia
Acute myelomonocytic leukemia
– Acute monocytic leukemia
Acute monocytic leukemia
– Acute erythroid leukemia
Acute erythroid leukemia
– Acute megekaryoblastic leukemia
Acute megekaryoblastic leukemia
– Acute basophilic leukemia
Acute basophilic leukemia
– Acute panmyelosis with myelofibrosis
Acute panmyelosis with myelofibrosis
11. AML
AML
Clonal malignancy of transformed
Clonal malignancy of transformed
multipotent Haematopoietic
multipotent Haematopoietic
progenitor cell
progenitor cell →
→ accumulation of
accumulation of
immature cells in BM
immature cells in BM →
→ cytopenia
cytopenia
& complications,
& complications,
3.4 / 1 lakh, 80-90% acute leukemia
3.4 / 1 lakh, 80-90% acute leukemia
12. AML
AML
A)
A) Clinical
Clinical :-
:-
Bad prognosis
Bad 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 prognosis
Good prognosis :
:
– Early response to therapy, rapid cytoreduction
Early response to therapy, rapid cytoreduction
– Down Syndrome
Down Syndrome
Younger & FAB M7
Younger & FAB M7
13. FAVOURABLE
FAVOURABLE :-
:-
+nce of Auer rods
+nce of Auer rods
(M1 - M4)
(M1 - M4)
+nce of Eosinophils
+nce of Eosinophils
(M2 - M4Eo)
(M2 - M4Eo)
UNFAVOURABLE
UNFAVOURABLE :-
:-
M0, M6, M7
M0, M6, M7
Megaloblastic features in M6, M7 &
Megaloblastic features in M6, M7 &
AML from MDS,
AML from MDS,
Trilineage dysplasia,
Trilineage dysplasia,
Extramedullary myeloid tumours
Extramedullary myeloid tumours
(Granulocytic Sarcoma) - AML-M5,
(Granulocytic Sarcoma) - AML-M5,
CD 56 +ve,
CD 56 +ve, Platelets < 1 lakh,
Platelets < 1 lakh,
Neutrophils < 1000 / μl
Neutrophils < 1000 / μl
Acute Panmyelosis & Myelofibrosis
Acute 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 :-
FAVORABLE
FAVORABLE :-
:-
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 / RARά
PML / RARά
t (11;17)(q13;q21) -
t (11;17)(q13;q21) -
NUMA / RARά
NUMA / RARά
ADVERSE
ADVERSE :-
:-
Complex karyotype (>/=
Complex karyotype (>/=
3),
3),
Inv 3,-7
Inv 3,-7
t (6;9),
t (6;9),
t (6;11),
t (6;11),
INTERMEDIATE
INTERMEDIATE :-
:-
Normal karyotype,
Normal karyotype,
-Y,
-Y,
Del 5q,
Del 5q,
t (9;11)
t (9;11)
Del 11q
Del 11q
+13
+13
16. Minimal Residual Disease
Minimal Residual Disease :-
:-
Detected by FCM, FISH, RQ-PCR
Detected 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 - Good
Pts with < 5 % blasts - Low relapse rate - Good
survival,
survival,
Depending on no. of tumour cells / normal cell, 4 risk
Depending 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 relapse
cells - very low risk - No relapse
10
10-4
-4
-
-10
10-3
-3
cells - Low risk - 3 yr relapse 14 %
cells - Low risk - 3 yr relapse 14 %
10
10-3
-3
-
-10
10-2
-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 disease
Pts with relapsed disease
– Platelets < 50,000 / μl
Platelets < 50,000 / μl
– Leococyte count > 50,000 / μl
Leococyte count > 50,000 / μl
– Past h/o MDS or MPD
Past h/o MDS or MPD
– Non
Non inv 16
inv 16
– Therapy related
Therapy related
AML
AML
18. APML :-
APML :-
– 10 % AML,
10 % AML,
– c/b Leucopenia, Abnormal promyelocytes, DIC
c/b Leucopenia, Abnormal promyelocytes, DIC
– t (15;17) : 95 % of APML
t (15;17) : 95 % of APML
– Relapse :
Relapse :
Old pts, increased WBC & platelet count - CD 56
Old 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
AML
AML
19. t (15;17)(q22;q21)
t (15;17)(q22;q21)
Chr 17 (RAR
Chr 17 (RAR ά)
)
Chr 15 (PML)
Chr 15 (PML)
PML / RAR
PML / RARά
• Impaired growth suppressor
Impaired growth suppressor
& Proapoptotic activities
& Proapoptotic activities
• Responsive to ATRA
Responsive to ATRA
RAR
RARά / PML
/ PML
Other Translocations :-
Other Translocations :-
• t (5;17)(q35;q21) = RAR
t (5;17)(q35;q21) = RARά + NPM
+ NPM
• t (11;17)(q13;q21) = RAR
t (11;17)(q13;q21) = RARά + NUMA
+ NUMA
• t (11;17)(q23;q21) = RAR
t (11;17)(q23;q21) = RARά + PLZF :
Resistant to ATRA
20. WHO CLASSIFICATION
WHO CLASSIFICATION
Precursor B lymphoblastic leukemia / lymphoma
Precursor B lymphoblastic leukemia / lymphoma
Precursor T lymphoblastic lymphoma / leukemia
Precursor T lymphoblastic lymphoma / leukemia
Leukemic phase of Burkitt lymphoma
Leukemic phase of Burkitt lymphoma
FAB CLASSIFICATION
FAB CLASSIFICATION :-
:-
L1 – Small blasts
L1 – Small blasts
L2 - Large homogenous
L2 - Large homogenous
L3 – Large heterogenous
L3 – Large heterogenous
ALL
ALL
21. CHILDHOOD ALL
CHILDHOOD ALL
FAVOURABLE
FAVOURABLE UNFAVOURABLE
UNFAVOURABLE
Age
Age 3-7 yr
3-7 yr <1; >10
<1; >10
Gender
Gender F
F M
M
WBC count
WBC count <10,000 / μl
<10,000 / μl > 2lakh
> 2lakh
FAB Features
FAB Features L1
L1 L2
L2
Ploidy
Ploidy Hyper
Hyper Hypo
Hypo
Time to remission
Time to remission <14 days
<14 days >28 days
>28 days
MRD
MRD <10
<10-4
-4
>10
>10-3
-3
Cytogenetic
Cytogenetic Trisomies 4,10,17
Trisomies 4,10,17 t(9:22)
t(9:22)
22. ADULT ALL
ADULT ALL
FEATURES
FEATURES FAVOURABLE
FAVOURABLE UNFAVOURABLE
UNFAVOURABLE
Age
Age <30 yrs
<30 yrs >30 yrs
>30 yrs
WBC count
WBC count < 30,000
< 30,000 >/= 30,000
>/= 30,000
Immunophenotype
Immunophenotype T- cell ALL
T- cell ALL Mature B- cell ALL,
Mature B- cell ALL,
Early T-cell ALL
Early T-cell ALL
Cytogenetics
Cytogenetics 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 therapy
Response to therapy CR <4 wks
CR <4 wks Persistent MRD
Persistent MRD
23. CML
CML
Stem cell & MC
Stem cell & MC MPD
MPD disorder
disorder
Asso. with t(9;22)(q34;q11)
Asso. with t(9;22)(q34;q11)
Bi or Triphasic
Bi or Triphasic
IPT :-
IPT :-
– CP - CD 15 & HLA-DR weakly +ve
CP - CD 15 & HLA-DR weakly +ve
– BP - a / w myeloid CD 13;14;15;33 +ve
BP - a / w myeloid CD 13;14;15;33 +ve
megakaryocytic CDw4, CD 61 +ve
megakaryocytic CDw4, CD 61 +ve
Erythrocytic Glycophorin-A, Hb A +ve
Erythrocytic Glycophorin-A, Hb A +ve
27. Morphology
Morphology :-
:-
– Marked diffuse Reticulin fibrosis & > 15 megakaryocytes /
Marked diffuse Reticulin fibrosis & > 15 megakaryocytes /
cmm of BM
cmm of BM
– Disappearance of Fibrosis :- High dose IF ά + Low dose
Disappearance of Fibrosis :- High dose IF ά + Low dose
Cytosine arabinocyde
Cytosine arabinocyde
CML progression
CML 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
CML
CML
28. AP
AP :-
:-
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 evolution
Cytogenetic evolution,
,
BC
BC :-
:-
Marrow or Blood Blasts > 20 %,
Marrow or Blood Blasts > 20 %,
Clumps of blasts in BM
Clumps of blasts in BM
Increased LAP score
Increased LAP score
Extramedullary myeloid tumour
Extramedullary myeloid tumour
Median survival 2 - 6 months
Median survival 2 - 6 months
Lymphoblastic transformation :
Lymphoblastic transformation :
Better prognosis
Better prognosis
CML
CML
29. Remission
Remission :- indicated by
:- indicated by
– Normal WBC count & BM morphology,
Normal WBC count & BM morphology,
– Disappearance of Ph chr. & BCR/ABL
Disappearance 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 %
CML
CML
31. Rai & Binet staging system
Rai & Binet staging system
STAGING
STAGING
SYSTEM
SYSTEM
RISK
RISK STAGE
STAGE CLINICAL FEATURES
CLINICAL FEATURES
RAI
RAI Low
Low 0
0 Lymphocytosis
Lymphocytosis
Interm.
Interm. I
I Lymphocytosis ;LNpathy
Lymphocytosis ;LNpathy
II
II Lymphocytosis, spleno /
Lymphocytosis, spleno /
hepatomegaly
hepatomegaly
High
High III
III Lymphocytosis, Hb <11gm/dl
Lymphocytosis, Hb <11gm/dl
IV
IV Lymphocytosis, plat < 1 lakh
Lymphocytosis, plat < 1 lakh
BINET
BINET Low
Low A
A No cytopenia ,<3 LN enlarged
No cytopenia ,<3 LN enlarged
Interm.
Interm. B
B No cytopenia ,>/= 3 LN enlarged
No cytopenia ,>/= 3 LN enlarged
High
High C
C Hb<10 gm/dl, plat <1lakh
Hb<10 gm/dl, plat <1lakh
32. Serum markers
Serum markers :-
:-
– β2 microglobulin
β2 microglobulin
– LDH,
LDH,
– CD 23,
CD 23,
Increased - progressive dis.
Increased - progressive dis.
Morphological features
Morphological 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 %
CLL
CLL
33. Molecular features
Molecular features :-
:-
B cells with
B cells with IgVH mut
IgVH mut. - benign cond.
. - benign cond.
Unmut. IgVH gene - poor prognosis
Unmut. IgVH gene - poor prognosis
p53 abn. - poor prognosis
p53 abn. - poor prognosis
Phenotypic features
Phenotypic features :-
:-
ZAP 70 gene
ZAP 70 gene expression - good pognosis
expression - good pognosis
Encodes intracellular Tyrosine kinase for TCR
Encodes intracellular Tyrosine kinase for TCR
signaling,
signaling,
Represents IgVH mutation,
Represents IgVH mutation,
– CD 38 :- Unmutated IgVH
CD 38 :- Unmutated IgVH
CLL
CLL
34. Chromosomal aberrations
Chromosomal aberrations :-
:-
– MC del 13q, 11q, 14q, 6q & Trisomy 12
MC del 13q, 11q, 14q, 6q & Trisomy 12
– Sole 13q14 del :- good prognosis
Sole 13q14 del :- good prognosis
– 17p, Trisomy 12 :- poor prognosis
17p, Trisomy 12 :- poor prognosis
Disease progression
Disease 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 transformation
Prolymphocytic transformation
CLL
CLL
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 Analogue
MC seen in pts t/t with Purine Nucleotide Analogue
CLL
CLL
38. HODGKINS LYMPHOMA
HODGKINS LYMPHOMA
Lymphoma of B –cells c/b RS cells & Hodgkin cells
Lymphoma 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/EBVER
CD20 +, CD15 & 30 +ve, PAX-5 +ve, EBV/EBVER
& Bcl-2 +
& Bcl-2 +
With modern therapies favorable prognosis
With modern therapies favorable prognosis
Secondary malignancies – AL, NHL MC cause of
Secondary malignancies – AL, NHL MC cause of
death in long term survivors.
death in long term survivors.
39. Ann –Arbor Costwold staging system
Ann –Arbor Costwold staging system
STAGEI
STAGEI Single LN region or Lymphoid structure
Single LN region or Lymphoid structure
STAGE II
STAGE II ≥
≥ 2 LN regions on same side of diaphragm
2 LN regions on same side of diaphragm
STAGE III
STAGE III Both sides of diaphragm
Both sides of diaphragm
III1
III1 With or without splenic, hilar, portal ,celiac nodes
With or without splenic, hilar, portal ,celiac nodes
III2
III2 With para-aortic, iliac or mesentric nodes
With para-aortic, iliac or mesentric nodes
STAGE IV
STAGE IV Extranodal sites (not due to direct extension from
Extranodal sites (not due to direct extension from
nodal site)
nodal site)
A
A No symptoms
No symptoms
B
B Fever ,Sweats, Wt loss
Fever ,Sweats, Wt loss
X
X Bulky disease (10 cm LN;>1/3
Bulky disease (10 cm LN;>1/3rd
rd
widening of
widening of
mediasinum
mediasinum
E
E Single extranodal site contiguous or proximal to
Single extranodal site contiguous or proximal to
known nodal site
known nodal site
40. WORSE
WORSE :–
:–
AGE > 60 YRS
AGE > 60 YRS
STAGE III – IV – extranodal inv +ve
STAGE III – IV – extranodal inv +ve
Mediastinal mass
Mediastinal mass
Bulky disease (> 10 cm)
Bulky disease (> 10 cm)
B – symptoms
B – symptoms
HODGKINS LYMPHOMA
HODGKINS LYMPHOMA
41. Good prognosis
Good prognosis :-
:-
CD15 + ; EBV LMP + ;
CD15 + ; EBV LMP + ;
NS HL - NS1
NS HL - NS1 (low grade)
(low grade)
Poor prognosis
Poor prognosis :-
:-
Age
Age ≥
≥ 45 yrs
45 yrs
Ann- Arbor stage IV
Ann- Arbor stage IV
↓
↓ S. Alb ,
S. Alb , ↑
↑ S. LDH
S. LDH
High proliferation index
High proliferation index
(
( ↑
↑ Ki-67 & loss of pRb)
Ki-67 & loss of pRb)
High mast cell proliferation
High mast cell proliferation
CD20 +
CD20 +
↑
↑ Exp of Bcl -2,Bcl-X
Exp of Bcl -2,Bcl-XL
L & loss
& loss
of BAX exp.
of BAX exp.
NS HL - NS2
NS HL - NS2 (High grade)
(High grade)
MORPHOLOGIC & PHENOTYPIC
MORPHOLOGIC & PHENOTYPIC :-
:-
42. NLPHL
NLPHL -
-
5 % of HL
5 % of HL
Nodular architecture & popcorn cells
Nodular architecture & popcorn cells
Stage IA & IIA - Excellent prognosis
Stage IA & IIA - Excellent prognosis
Poor prognosis
Poor prognosis
- +nce of diffuse T cell & increased Histiocytes
- +nce of diffuse T cell & increased Histiocytes
- BM inv.
- BM inv.
NLPHL
NLPHL
DLBCL (Median dur. - 1 yr)
DLBCL (Median dur. - 1 yr)
Age 18 - 72 yrs
Age 18 - 72 yrs
M > F,
M > F,
Median Overall Survival = 35 Months,
Median Overall Survival = 35 Months,
HODGKINS LYMPHOMA
HODGKINS LYMPHOMA
44. Peripheral (Mature)
Peripheral (Mature)
B cell neoplasms
B cell neoplasms :-
:-
CLL / SLL,
CLL / SLL,
B cell Prolymphocytic leukemia,
B cell Prolymphocytic leukemia,
Lymphoplasmacytic lymphoma,
Lymphoplasmacytic lymphoma,
Splenic & Nodal Marginal zone
Splenic & 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 Neoplasms
Peripheral 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 Lymphoma
Hepatosplenic γδ T cell Lymphoma
NK/T cell Lymphoma, Nasal type,
NK/T cell Lymphoma, Nasal type,
NK cell Leukemia
NK cell Leukemia
45. IPI for Malignant Lymphoma
IPI for Malignant Lymphoma
Adverse Factors
Adverse Factors
Age > 60 yrs
Age > 60 yrs
Performance Status
Performance Status
LDH > Normal
LDH > Normal
≥
≥ 2
2 Extranodal sites
Extranodal sites
Stage 3 & 4 disease
Stage 3 & 4 disease
5 year survival
5 year survival
83 %
83 %
69 %
69 %
46 %
46 %
32 %
32 %
No. of Factors
No. of Factors
0,1
0,1
2
2
3
3
4,5
4,5
Risk Groups
Risk Groups
Low
Low
Low intermediate
Low intermediate
High
High
intermediate
intermediate
46. Adverse Predictors
Adverse Predictors :-
:-
Age > 60 yrs
Age > 60 yrs
B symptoms
B 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 +ve
Bcl 2, c-MYC, p53 +ve
B - Small Lymphocytic Lymphoma
B - Small Lymphocytic Lymphoma
47. Disorder of Mature B cells with Medium sized
Disorder of Mature B cells with Medium sized
lymphocytes with nucleoli with Prolymphocytes
lymphocytes with nucleoli with Prolymphocytes
> 55 %,
> 55 %,
Poor prognosis
Poor 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 yrs
Median 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 Outcome
Poor Outcome
Splenomegaly
Splenomegaly
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. - Poor
Risk of sec. malignancies & opportunistic inf. - Poor
prognosis
prognosis
Hairy cell Leukemia
49. c / b indolent clinical course, nodular growth
c / 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-6
Bcl-2 & Bcl-6
Inv BM with characteristic Paratrabecular
Inv BM with characteristic Paratrabecular
distribution,
distribution,
Follicular Lymphoma
50. Poor prognostic markers
Poor 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,
–
ESR
ESR
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 < n
S. LDH > n Vs < n
Risk groups
Risk groups -
-
Low risk (O-1) = 85 % 5 yr survival
Low risk (O-1) = 85 % 5 yr survival
Intermediate (2) = 79 %
Intermediate (2) = 79 %
Poor risk
Poor risk ≥ 3
≥ 3 =
= 28%
28%
Follicular Lymphoma
52. Morphological phenotypic
Morphological phenotypic :-
:-
Based on Absolute no. of
Based on Absolute no. of Centroblasts
Centroblasts / 10 neoplastic
/ 10 neoplastic
follicles / hpf
follicles / hpf
Grade I = O - 5 / hpf,
Grade I = O - 5 / hpf,
Grade II = 6 - 15 / hpf
Grade II = 6 - 15 / hpf
Grade IIIa
Grade IIIa ≥
≥ 15 / hpf + Centrocytes +nt,
15 / hpf + Centrocytes +nt,
Grade IIIb
Grade IIIb ≥
≥ 15 / hpf + Centrocytes -nt
15 / hpf + Centrocytes -nt
FL with Diffuse component - > 50 % large cells = Poor
FL with Diffuse component - > 50 % large cells = Poor
survival,
survival,
Follicular Lymphoma
53. Chromosomal Aberrations
Chromosomal Aberrations :-
:-
t (14 ;18)( q32 , q21 ) - 80 - 90 % -CD 10+, Bcl-6
t (14 ;18)( q32 , q21 ) - 80 - 90 % -CD 10+, Bcl-6
+ve - favourable
+ve - favourable
Changes that correlate with morpho. progression to
Changes 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. TRANSFORMATION
TRANSFORMATION :-
:-
25-80%
25-80%
Increased no. of
Increased no. of centroblasts
centroblasts - DLBCL,
- DLBCL,
Blastic transformation in Burkitt’s
Blastic transformation in Burkitt’s
Lymphoma, Precurser B lymphoblastic
Lymphoma, Precurser B lymphoblastic
lymphoma or Leukemia
lymphoma or Leukemia
a / w Sec. genetic abn., c-MYC gene
a / w Sec. genetic abn., c-MYC gene
rearrangement, p53 mut,
rearrangement, p53 mut,
Follicular Lymphoma
55. Mantle cell lymphoma
Mantle cell lymphoma
– c / b Monomorphic app. cells with irregular
c / 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 added
Those with relapse after SCT - Rituximab added
56. Poor prognosis
Poor 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 Aberrations
Chromosomal Aberrations :-
:-
+12, Complex karyotype - Poor outcome
+12, Complex karyotype - Poor outcome
Mantle cell lymphoma
Mantle cell lymphoma
57. Morphologic progression
Morphologic 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 lymphoma
Mantle cell lymphoma
58. Diffuse Large B cell Lymphoma
Diffuse Large B cell Lymphoma
Aggressive lymphoma of mature B cells
Aggressive lymphoma of mature B cells
WHO SUBTYPES
WHO 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. Favorable
Favorable :-
:-
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 %)
Unfavorable
Unfavorable :-
:-
Age > 60 yrs,
Age > 60 yrs,
Poor performance
Poor performance
status,
status,
↑
↑ Sr. LDH & β2
Sr. LDH & β2
microglobulin,
microglobulin,
> 50 % Large cells,
> 50 % Large cells,
Diffuse pattern,
Diffuse pattern,
IgR +ve (CR - 51%),
IgR +ve (CR - 51%),
• Clinical & Lab parameters
Clinical & Lab parameters :-
Diffuse Large B cell Lymphoma
Diffuse Large B cell Lymphoma
60. Morphological & Phenotypic
Morphological & Phenotypic :-
:-
Poor Prognosis
Poor Prognosis :-
:-
– T cell rich Large B cell lymphoma - Aggressive
T 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 pRb
c-MYC overexpression, Loss of pRb
Molecular Markers
Molecular Markers :-
:-
– t (14;18) - Bcl-2 amplification - good prognosis
t (14;18) - Bcl-2 amplification - good prognosis
Diffuse Large B cell Lymphoma
Diffuse Large B cell Lymphoma
61. IPT
IPT
Germinal center B cell
Germinal center B cell
like pattern (A)
like pattern (A)
CD10 & Bcl-6 +ve
CD10 & Bcl-6 +ve
Better survival
Better survival
Activated B cell like
Activated B cell like
pattern (1 GCM + 1 0f
pattern (1 GCM + 1 0f
CD 138, MUM-1 / IRF-4
CD 138, MUM-1 / IRF-4
)
)
Worse
Worse
Activated non
Activated non
germinal center
germinal center
(
( FOXP-1 +ve
FOXP-1 +ve)
)
Poor
Poor
Diffuse Large B cell Lymphoma
Diffuse Large B cell Lymphoma
62. Specific clinical variants
Specific clinical variants :-
:-
1) Extranodal DLBCL
1) 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 survival
older age - poor survival
4) Primary testicular DLBCL,
4) Primary testicular DLBCL,
5) Primary CNS DLBCL
5) Primary CNS DLBCL
6) Mediastinal DLBCL
6) Mediastinal DLBCL
Diffuse Large B cell Lymphoma
Diffuse Large B cell Lymphoma
63. Multiple Myeloma
Multiple Myeloma
Clonal Disorder of B cell at last stage of
Clonal Disorder of B cell at last stage of
differentiation c /b BM infiltration by Plasma
differentiation c /b BM infiltration by Plasma
cells & Monoclonal immunoglobulin production,
cells & Monoclonal immunoglobulin production,
From MGUS or De-novo,
From MGUS or De-novo,
Major
Major :-
:-
• 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 / dl
IgA > 2 g / dl
• Urine > 1 g / 24 hr of BJ
Urine > 1 g / 24 hr of BJ
prot.
prot.
Minor
Minor :-
:-
• Marrow Plasmacytosis
Marrow 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 parameters
Clinical & Lab parameters :-
:-
High Plasma cell labeling index
High Plasma cell labeling index ≥ 1 %
≥ 1 %
- Poor prognosis,
- Poor prognosis,
Decreased Sr monoclonal proteins by
Decreased Sr monoclonal proteins by
30 % - Better prognosis,
30 % - Better prognosis,
Multiple Myeloma
Multiple Myeloma
65. Stage I :-
Stage I :- Median survival > 5 yrs
Median survival > 5 yrs.
.
– Low
Low 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 / 24hr
Urine 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 yrs
Median survival = 2 yrs.
.
– High
High 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 yr
Median survival > 3 yr
Multiple Myeloma
Multiple Myeloma
66. Chromosomal Aberrations
Chromosomal Aberrations :-
:-
70 % numerical aberrations
70 % numerical aberrations
MC monosomy 13 -
MC monosomy 13 -
High relapse & progression to MM
High relapse & progression to MM
MC - t (11;14)(q13;q32)
MC - t (11;14)(q13;q32)
Upregulation of
Upregulation of
Cyclin D1
Cyclin D1
Trisomy 6, 9, 17
Trisomy 6, 9, 17
Prolong survival
Prolong survival
Multiple Myeloma
Multiple Myeloma
67. Molecular Markers
Molecular Markers :-
:-
Activating mutation of Ki-RAS - Adverse prognosis,
Activating mutation of Ki-RAS - Adverse prognosis,
Based on recurrent Ig translocations & Cyclin D
Based on recurrent Ig translocations & Cyclin D
expression,
expression,
TC1
TC1 - 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,
TC4
TC4 - High levels of Cyclin D2 + t (4;14),
- High levels of Cyclin D2 + t (4;14),
TC5
TC5 - High levels of Cyclin D2 + t (14;16)
- High levels of Cyclin D2 + t (14;16)
Multiple Myeloma
Multiple Myeloma
68. Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma
Low grade lymphoma c / b mixture of small
Low grade lymphoma c / b mixture of small
lymphocytes, lymphocytes with plasmacytoid
lymphocytes, lymphocytes with plasmacytoid
features & plasma cells,
features & plasma cells,
Occ. cell show
Occ. cell show Dutcher’s bodies
Dutcher’s bodies,
,
c / b : t (9;14)(q13;q32) - PAX-5 gene on chr. 9
c / b : t (9;14)(q13;q32) - PAX-5 gene on chr. 9
4 - 15 %
4 - 15 %
DLBCL,
DLBCL,
70. Marginal Zone B cell lymphoma
Marginal Zone B cell lymphoma
SPLENIC
SPLENIC MARGINAL ZONE LYMPHOMA
MARGINAL ZONE LYMPHOMA :-
:-
Elderly, median age 65 yrs,
Elderly, median age 65 yrs,
Poor prognosis
Poor 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 del
Sr. β2 microglobulin - 7q31 del
Median survival 8 - 13 yrs, Death - transformation
Median 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 CELL
EXTRANODAL MARGINAL ZONE B CELL
LYMPHOMA OF
LYMPHOMA OF MALT TYPE
MALT TYPE
Low grade, Stomach, Salivary gland, Thyroid, Skin & in
Low 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 prognosis
Poor prognosis
Increased LDH,
Increased LDH,
Advanced stage,
Advanced stage,
IPI - High risk
IPI - High risk
Transformation to High grade lymphoma in
Transformation to High grade lymphoma in
8 %, a/w Trisomy 3, 7 & 18
8 %, 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 gene
API2-MALT fusion gene
Group A
Group A
Fusion -ve
Fusion -ve
Eradication
Eradication
responsive
responsive
MC
MC
• Low clinical stage
Low clinical stage
• Superficial
Superficial
gastric inv.
gastric inv.
Group B
Group B
Fusion -ve
Fusion -ve
Eradication
Eradication
Non responsive
Non responsive
• Nodal inv.
Nodal inv.
• Deep gastric wall inv.
Deep gastric wall inv.
• Adv. Clinical stage
Adv. Clinical stage
Group C
Group C
Fusion +ve
Fusion +ve
Eradication
Eradication
Non responsive
Non responsive
• Low H.pylori inf. rate
Low H.pylori inf. rate
• Low grade histo.
Low grade histo.
• Adv. Clinical stage
Adv. Clinical stage
• Bcl-10 +ve
Bcl-10 +ve
73. Nodal Marginal Zone B cell
Nodal Marginal Zone B cell
Lymphoma
Lymphoma
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 % - at
Transformation to Large cell - 20 % - at
time of diagnosis
time of diagnosis
75. t (8;14)(q24;q32) :- Aggressive disease
t (8;14)(q24;q32) :- Aggressive disease
Poor Prognosis
Poor Prognosis
Age
Age ≥ 15 yr,
≥ 15 yr,
BM inv.,
BM inv.,
Initial Sr. LDH > 500 IU / L,
Initial Sr. LDH > 500 IU / L,
Expression of C-FLIP
Expression of C-FLIP
High dose therapy + SCT = Good survival,.
High dose therapy + SCT = Good survival,.
Burkitt’s Lymphoma
Burkitt’s Lymphoma
76. Nodal
Nodal :-
:-
– Angio-immunoblastic T
Angio-immunoblastic T
cell lymphoma (AILT),
cell lymphoma (AILT),
– Peripheral T cell
Peripheral T cell
lymphoma, Unspecified
lymphoma, Unspecified
(PTCL),
(PTCL),
– Anaplastic large cell
Anaplastic large cell
lymphoma (ALCL),
lymphoma (ALCL),
Peripheral (Mature) T-cell Neoplasm
Peripheral (Mature) T-cell Neoplasm
Extranodal
Extranodal :-
:-
– Mycosis fungoides (MF)
Mycosis fungoides (MF)
– Cutaneous ALCL,
Cutaneous ALCL,
– Extranodal NK/T cell
Extranodal NK/T cell
lymphoma (Nasal type),
lymphoma (Nasal type),
– Enteropathy type,
Enteropathy type,
– Hepatosplenic,
Hepatosplenic,
– Subcutaneous
Subcutaneous
panniculitis like,
panniculitis like,
10 % of NHL
10 % of NHL
• Poor prognosis comp. to B cell lymphomas
Poor prognosis comp. to B cell lymphomas
77. T CELL PROLYMPHOCYTIC
T CELL PROLYMPHOCYTIC
LEUKEMIA
LEUKEMIA
– Affects adult males
Affects adult males
– Aggressive clinical course,
Aggressive clinical course,
– Poor prognosis -
Poor prognosis -
Hb < 11g/dl
Hb < 11g/dl
Advanced age
Advanced 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 karyotype
Complex karyotype
– Improved with Alemtuzumab (Anti-CD52)
Improved with Alemtuzumab (Anti-CD52)
78. T LARGE GRANULAR
T LARGE GRANULAR
LYMPHOCYTE LEUKEMIA
LYMPHOCYTE LEUKEMIA
– Indolent course
Indolent 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 cells
Low % of CD 57 +ve cells
Severe Neutropenia & B symptoms
Severe Neutropenia & B symptoms
NK cell phenotype
NK cell phenotype
79. CUTANEOUS T- CELL LYMPHOMAS
CUTANEOUS T- CELL LYMPHOMAS
– MC- MF, ALCL & Lymphomatoid papulosis.
MC- MF, ALCL & Lymphomatoid papulosis.
– Poor prognostic factors
Poor prognostic factors –
–
Blood eosinophilia
Blood eosinophilia
Increaesd S.LDH levels
Increaesd S.LDH levels
High no of chromo. Abn. (>5) - (gain in 8q & loss of
High no of chromo. Abn. (>5) - (gain in 8q & loss of
6q &13q)
6q &13q)
Dual CD4/CD8 -ve T cells
Dual CD4/CD8 -ve T cells
80. MYCOSIS FUNGOIDES
MYCOSIS FUNGOIDES
– 10 yr survival 40 - 100 %, depending on degree of
10 yr survival 40 - 100 %, depending on degree of
skin inv.,
skin inv.,
– Large cell transformation
Large 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 SYNDROME
SEZARY’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 prognosis
Poor 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 CELL
PRIMARY CUT. ANAPLASTIC LARGE CELL
LYMPHOMA
LYMPHOMA :-
:-
– Older pts, ALK -ve,
Older pts, ALK -ve,
– Favorable prognosis
Favorable prognosis
- CD 30 +ve - Localized skin disease
- CD 30 +ve - Localized skin disease
– Poor prognosis
Poor prognosis
- Disseminated skin inv. - Extracutaneous disease
- Disseminated skin inv. - Extracutaneous disease
82. ANGIO-IMMUNOBLASTIC
ANGIO-IMMUNOBLASTIC
T CELL LYMPHOMA
T CELL LYMPHOMA
– LN - polymorphous infiltrate c/o Atypical ,Small
LN - 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 course
Aggressive clinical course
– Poor prognosis with conventional t/t, but, High dose
Poor prognosis with conventional t/t, but, High dose
chemotherapy +/- SCT - Long term survival
chemotherapy +/- SCT - Long term survival
83. ANAPLASTIC LARGE CELL LYMPHOMA
ANAPLASTIC LARGE CELL LYMPHOMA
– c/b large pleomorphic cells with irregular nuclei
c/b large pleomorphic cells with irregular nuclei
(
(Hallmark cells
Hallmark 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 gene
NPM-ALK gene
80 kDa Protein - p80 &
80 kDa Protein - p80 &
variant ALK prot.
variant ALK prot.
Subcellular Localisation
Subcellular Localisation
84. – Unfavorable factors
Unfavorable 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 relapse
Leukemic blood inv. - Early relapse
Children with Lung, Skin & Mediastinal inv
Children with Lung, Skin & Mediastinal inv
ANAPLASTIC LARGE CELL LYMPHOMA
ANAPLASTIC LARGE CELL LYMPHOMA
85. – Favorable prognosis
Favorable 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 CELL
ANAPLASTIC LARGE CELL
LYMPHOMA
LYMPHOMA
86. MYELODYSPLASTIC SYNDROMES
MYELODYSPLASTIC 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 sideroblasts
ringed sideroblasts
Refractory Anaemia with Excess blasts -1
Refractory Anaemia with Excess blasts -1
Refractory Anaemia with Excess blasts -2
Refractory 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. unclassifiable
Myelodysplastic synd. unclassifiable
87. MYELODYSPLASTIC SYNDROMES
MYELODYSPLASTIC SYNDROMES
– c / b ineffective haematopoiesis & dyspoiesis leading to BM
c / b ineffective haematopoiesis & dyspoiesis leading to BM
failure, Cytopenia
failure, Cytopenia
– De-novo or following chemo-/ radiotherapy,
De-novo or following chemo-/ radiotherapy,
– Based on survival duration & incidence of progression to
Based on survival duration & incidence of progression to
Ac. Leukemia, divided into:-
Ac. Leukemia, divided into:-
Low risk :- Isolated 5q del, RA, RARS
Low risk :- Isolated 5q del, RA, RARS
(High- Bad, Bak & Bcl-Xs)
(High- Bad, Bak & Bcl-Xs)
High risk :- RCMD & RAEB (Bcl-2, BclX
High risk :- RCMD & RAEB (Bcl-2, BclXL
L)
)
25 - 38 % of RAEB progress to Ac. Leukemia
25 - 38 % of RAEB progress to Ac. Leukemia
94. SUMMARY
SUMMARY
MC malignancies in haematopoietic system are
MC 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 stage
MRD detection & detection of relapse at early stage
are also equally important.
are also equally important.
