follicular lymphoma

2. Definition
• Follicular lymphoma is a neoplasm of a follicle
center B cell that is composed of a mixture of
cleaved follicle center cells (centrocytes) and
large non cleaved follicle center cells
(centroblasts).

3. • MC human B cell neoplasm.
• Primarily affecting adults, Rare in childrens.
• Median age of presentation is 59 years.
• male : female – 1:1.7
• 45% of all NHL, 80% of all Indolent
Lymphomas.
• Stage I & II – 33% ( Low grade)
• Stage III & IV – 67% (High grade).

4. Clinical presentation
• New painless lymphadenopathy
• Non tender, firm, rubbery in consistancy
• Mostly involves
retroauricular,cervical,supraclvicular,axillary,in
guinal,popiletial rarely epitrochlear node.
• Extra nodal sites includes
spleen,liver,bonemarrow.
• CNS disease is rare.

5. • B symptoms,
Fever >38˚
Night sweats
Weight loss >10% of body weight in
preceding month.
• Asthenia
• Anemia,leukopenia,thrombocytopenia due to
BM suppression
• FL follows Waxing n Waning course.

6. CAUSES
• Genetics – chromosomal translocations
• Viruses- EBV, HTLT I, HHV 8.
• Immunodeficiency state :
Congenital
Acquired- hiv,immunosupprasant drugs
• Autoimmune disorders

7. Follicular Lymphoma
Bcl2 Chromosome 18
Mbr (major breakpoint region, 150 bp)
JH
C
Double strand DNA break by RAG1/2
Chromosome 14
Bcl2 C t(14;18) translocation
bcl2 CE C 3’E
Unregulation of Bcl2 expression by IgH enhancers
Translocation takes place in B cell precursors.
Transformation takes place
during B cell activation in GC.

8. Bcl2 inhibits apoptosis
cytochrome c
Apaf-1
dATP or ATP
mitochondrion
Apaf-1
Pro-caspase-9
Caspase-9
Pro-caspase-3 Caspase-3
Apoptosis
Bcl-2, Bcl-XL
Bax, Bad
Pro-survival oncogene

9. Over-expression of Bcl-2 may prevent the apoptosis
of germinal center B cells
activation
Germinal center Germinal center
apoptosis
IgH-Bcl2
activation
Germinal center Germinal center
Plasma cells
Memory cells
follicular lymphoma
Apoptosis inhibited
Most follicular lymphoma Ig V regions contain
somatic hypermutation.

11. • Bcl 2 translocation rearrangements,
• 1) mcr ---- 95% 3year failure
• 2)MBR ---- 76% free survival
• 3)Germ line mutation ---57% rate.

12. Investigation
• Diagnostic confirmation-tissue biopsy,BMA,
PS.
• Assessment of clonality
• Immunophenotype,cytogenetics,molecular
study.
• Viral testing
• Laboratory assessment of organ function
• CD4,LDH,serum beta2
microglobulin,se.AFP/BetaHCG
• CXR,CT scan, PET scan

13. IMMUNOPHENOTYPE
POSITVE
• Monoclonal surface Ig
• Bcl 2
• CD10
• CD 19
• CD 20
• CD 22
• CD 79a
NEGATIVE
• CD 5
• CD 11
• CD 23c
• CD 43

14. GRADING
• WHO Morphalogical grading,
• Grade I -- < 5 centroblasts /HPF
• Grade II -- 6-15 centroblasts /HPF
• Grade III -- >15 centroblasts /HPF.
• IIIa -- centrocyte still present
• IIIb --- fully contains centroblasts

15. Stage I Stage II Stage III Stage IV
Staging of lymphoma
A: absence of B symptoms
B: fever, night sweats, weight loss

16. ANN ARBOR STAGING
• Stage I Involvement of a single lymph-node region (I) or a
single extralymphatic organ or site (IE)
• Stage II Involvement of two or more lymph-node regions
on the same side of the diaphragm (II) or localized involvement
of an extra-lymphatic organ or site (IIE)
• Stage III Involvement of lymph-node regions on both sides
of the diaphragm (III) or localized involvement of an extra-
lymphatic organ or site (IIIE), spleen (IIIS), or both (IIISE)
• Stage IV Diffuse or disseminated involvement of one or
more extralymphatic organs, with or without associated lymph-
node involvement; the organ(s) involved should be identified
by a symbol: (P) pulmonary, (O) osseous, or (H) hepatic.
(A) indicates an asymptomatic patient;
(B) indicates the presence of fever, night sweats, or weight loss >
10% of body weight.

17. FOLLICULAR LYMPHOMA
INTERNATIONAL PROGNOSTIC INDEX
(FLIPI)
• Age 60 or more
• Ann Arbor stage III & IV
• LDH level above the upper limit at the
diagnosis.
• Hb < 12gms% at diagnosis.
• Presence of more than 4 nodal site
involement

18. Treatments
IFRT (30-35 Gy)
Stage I,II
22-33%
Watch and Wait
R-CHOP
Stage III,IV
67-78%
Follicular Lymphoma (grade I,II)
R-CHOP + IFRT
Stage I,II
Watch and Wait
R-CHOP
Stage III,IV
Follicular Lymphoma (grade III)
= curable
= incurable
Indolent Aggressive

19. Treatment
• Waxing n waning course- wait n watch
low grade (I, II)
Most radio sensitive
• Radiotherapy uesd for localised disease
• Involved field or extended field RT
ranging from 35 to 50Gy
• Achive remission in 50% patients

20. • Single agent chemotherapy
• chlorambucil
• fludarabine
• rituximab
• idelasilib –phophoinositide 3 kinase delta
inhibitor ( Pl3k)

22. • Multi agent chemotherapy
• R-CVP
• R – CHOP
• FCR
• RFCM
• FR

25. • HEMATOPOIETIC STEM TRANSPLANTATION
• Allogenic
• autologus

26. • Targeted radio immuno therapy
Radio sensitive tumor
• Iodine 131 labeled Tosutumomab.
• Yettrium 90 labeled Ibritumomab Tiuxetan.

27. • Interferan alpha
• Interleukin 2
• Anti idiotype therapy: murine monoclonal
antiidiotype antibody combined with INF aplha or
chlrambucil or antibody alone can be given.
• Vaccine therapy: Idiotypic protein coupled to
keyhole limpet hemocyanin (KLH) and combined
with an immunologic adjuvant
• Immuno toxin therapy:
Monoclonal antibody specific for tumor-associated
antigens conjugated toxins -- immunotoxins.
Ricin is a heterodimeric protein- inhibits protein
synthesis by the action of its cytotoxic A-chain.