a comprehensive review of pathophysiology and diagnosis of b cell lymphoma

1. B Cell
Lymphoma
Dr. Istikhar Ali Sajjad
PGR Medical Unit II,
Punjab Medical College
Faisalabad.

2. Lymphoma
 Clonal malignant disorders that are derivedClonal malignant disorders that are derived
from lymphoid cells: either precursor orfrom lymphoid cells: either precursor or
mature T-cell or B-cellmature T-cell or B-cell
 Majority are of B- cell origin (80%)Majority are of B- cell origin (80%)
 T cell Lymphoma (15%)T cell Lymphoma (15%)

3. Classification of B cellClassification of B cell
LymphomaLymphoma
 Divided into 2 main types :Divided into 2 main types :
1.1. Hodgkin’s lymphomaHodgkin’s lymphoma
2.2. Non - Hodgkin’s lymphomaNon - Hodgkin’s lymphoma

4. Hodgkin’s Disease
 Histologically & clinically a distinctHistologically & clinically a distinct
malignant diseasemalignant disease
 Predominantly, B-cell diseasePredominantly, B-cell disease
 Course of the disease is variable,Course of the disease is variable,
but the prognosis has improvedbut the prognosis has improved
with modern treatmentwith modern treatment

5. Etiology
 ? Infection –? Infection – EBVEBV
 ? Environmental factors? Environmental factors

6. REAL* Classification
Classic:
Nodular SclerosisNodular Sclerosis
Lymhocyte richLymhocyte rich
Mixed CellularityMixed Cellularity
Lymhocyte depletedLymhocyte depleted
Non-Classic
Nodular Lymphocyte predominantNodular Lymphocyte predominant
*REAL – Revised European,American,lymphoma

7. Clinical features
Bimodal age distribution :distribution :
 young adultsyoung adults ( 20-30 yrs)( 20-30 yrs) & elderly& elderly (> 50yrs)(> 50yrs)
MMay occur at any ageay occur at any age
 M > FM > F
 LymphadenopathyLymphadenopathy::
most often cervical regionmost often cervical region
asymmetrical, discreteasymmetrical, discrete
painless, non-tenderpainless, non-tender
elastic character on palpation ( rubbery)elastic character on palpation ( rubbery)
not adherent to skinnot adherent to skin
fluctuate in sizefluctuate in size

8.  Contiguous spread via the lymphatic chainContiguous spread via the lymphatic chain
eg.eg.involvement of abdominal & thoracicinvolvement of abdominal & thoracic
LNsLNs
 Extra nodal disease - rareExtra nodal disease - rare
 HepatospleenomegalyHepatospleenomegaly

10.  Constitutional symptoms (B symptoms)Constitutional symptoms (B symptoms)
Night sweats,Night sweats,
sustained fever > 38 degree celsius,sustained fever > 38 degree celsius,
loss of weight >10% of body weight in 6 moloss of weight >10% of body weight in 6 mo
 Fever sometimes cyclicalFever sometimes cyclical (‘Pel-Ebstein fever’)
 Pain at the site of disease after drinkingPain at the site of disease after drinking
alcoholalcohol
 PallorPallor
 PruritisPruritis
 Symptoms of Bulky (>10 cm) diseaseSymptoms of Bulky (>10 cm) disease

11. Investigations
 CBPCBP ::
Anemia ( normochromic / normocytic), eosinophilia,Anemia ( normochromic / normocytic), eosinophilia,
neutrophilia, lymphopenianeutrophilia, lymphopenia
 ESR -raisedESR -raised
 LFT- (liver infil / obs at porta hepatis)LFT- (liver infil / obs at porta hepatis)
 RFT- prior to treatmentRFT- prior to treatment
 Urate , Ca,Urate , Ca,
 LDH - adverse prognosisLDH - adverse prognosis
 CXR- mediastinal massCXR- mediastinal mass
 CT thorax / abdomen / pelvis-for stagingCT thorax / abdomen / pelvis-for staging
 Other: Gallium scan, PET,Other: Gallium scan, PET, Lymphangiography ,Lymphangiography ,
LaporotomyLaporotomy

12.  LN FNAC / biopsyLN FNAC / biopsy ::
MalignantMalignant REED-STERNBERG ( RS) Cell: Bi-: Bi-
nucleate cell with a prominent nucleolus. Derivednucleate cell with a prominent nucleolus. Derived
from B cell, at an early stage of differentiationfrom B cell, at an early stage of differentiation
Reactive background of eosinophils,Reactive background of eosinophils,
lymphocytes, plasma cellslymphocytes, plasma cells
Fibrous tissueFibrous tissue

14. REED-STERNBERG ( RS ) CellREED-STERNBERG ( RS ) Cell

15. RS cell and variantsRS cell and variants
popcorn celllacunar cellclassic RS cell
(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)

17. >10 cm
Bulky disease

19. LymphangiographyLymphangiography

20. Staging
 Stage I : Involvement of single LN region (I) or extra: Involvement of single LN region (I) or extra
lymphatic site (IAlymphatic site (IAEE ))
 Stage II : Two or more LN regions involved (II) or anTwo or more LN regions involved (II) or an
extra lymphatic site and lymph node regions on theextra lymphatic site and lymph node regions on the
same side of diaphragmsame side of diaphragm
 Stage III : Involvement of lymph node regions on bothInvolvement of lymph node regions on both
sides of diaphragm, with (IIIsides of diaphragm, with (IIIEE) or without (III) localized) or without (III) localized
extra lymphatic involvement or involvement of theextra lymphatic involvement or involvement of the
spleen (IIspleen (IISS) or both (IIS) or both (IISEE))
 Stage IV : Involvement outside LN areas (Liver, boneInvolvement outside LN areas (Liver, bone
marrow)marrow)
AA : Absence of ‘B’ symptoms: Absence of ‘B’ symptoms
BB : B symptoms present: B symptoms present

22. Treatment
 Radiotherapy (RT)Radiotherapy (RT)
 ChemotherapyChemotherapy
 Bone marow transplantBone marow transplant
 Antibody treatment: Rituximab target CD-20Antibody treatment: Rituximab target CD-20
 SupportiveSupportive

23. Treatment - Guidelines
 Indications for RT:
Stage I diseaseStage I disease
Stage II disease with 3 or lesser areas involvedStage II disease with 3 or lesser areas involved
For Bulky diseaseFor Bulky disease
For pressure problemsFor pressure problems
 Indications for CT
All with B symptomsAll with B symptoms
Stage II disease with >3 areas involvedStage II disease with >3 areas involved
Stage III and IV diseaseStage III and IV disease

24. Treatment
 Stage IA , Stage IIA with 3 or < 3 areas involved::
RadiotherapyRadiotherapy
 Stage IB, Stage II A with > 3 areas , Stage IIB::
ChemotherapyChemotherapy every 3-4 weeks, 6-8 cycles;every 3-4 weeks, 6-8 cycles;
either alone, or in combination witheither alone, or in combination with radiotherapyradiotherapy
 Stage III & IV :
ChemotherapyChemotherapy ++ RadiotherapyRadiotherapy ( for bulky( for bulky
disease or palliation of symptoms)disease or palliation of symptoms)

25. Prognosis
 Overall 10 yr survival – 80%Overall 10 yr survival – 80%
 In long term survivors there is a risk ofIn long term survivors there is a risk of
secondary malignancy: (secondary malignancy: (leukemia , NHL), Solid), Solid
tumors- Lung, breast
InfectionsInfections
Cardiac, pulmonary, endocrinal abnormalitiesCardiac, pulmonary, endocrinal abnormalities

26. International Prognostic Index (IPI)
 AgeAge
 Advanced stage diseaseAdvanced stage disease
 Performance statusPerformance status
 Elevated LDHElevated LDH
 Presence of Extra nodal diseasePresence of Extra nodal disease

27. Non Hodgkin’s lymphoma
 Incidence is increasingIncidence is increasing
 NHL>HDNHL>HD
 Median age of presentation isMedian age of presentation is 65-70 yrs65-70 yrs
 M>FM>F
 More often clinically disseminated atMore often clinically disseminated at
diagnosisdiagnosis
 B-cell-70% ; T-cell-30%B-cell-70% ; T-cell-30%

29. Clinical features
 Widely disseminated at presentationWidely disseminated at presentation
 Nodal involvementNodal involvement::
Painless lymphadenopathyPainless lymphadenopathy, often cervical, often cervical
region is the most common presentationregion is the most common presentation
 HepatospleenomegalyHepatospleenomegaly
 ExtranodalExtranodal ::
Intestinal lymphoma ( abdominal pain, anemia,( abdominal pain, anemia,
dysphagia);dysphagia);
CNSCNS ( headache, cranial nerve palsies,( headache, cranial nerve palsies,
spinal cord compression) ;spinal cord compression) ;
Skin, Testis; Thyroid; Lung
Bone marrow (low grade):(low grade):
PancytopeniaPancytopenia

30.  Systemic symptomsSystemic symptoms
Sweating, weight loss, itchingSweating, weight loss, itching
Metabolic complications:Metabolic complications:
hyperuricemia,hyperuricemia,
hypercalcemia,hypercalcemia,
renal failurerenal failure
 Compression syndrome:Compression syndrome:
Gut obstructionGut obstruction
AscitesAscites
SVC obstructionSVC obstruction
S/C CompressionS/C Compression

33. Diagnosis and staging
 Similar to HDSimilar to HD plus,
 Bone marrow aspirate & trephineBone marrow aspirate & trephine
 Immunophenotyping : Monoclonal antibodiesImmunophenotyping : Monoclonal antibodies
directed against specific lymphocytedirected against specific lymphocyte
associated antigensassociated antigens
B cell antigens ( CD 19, 20, 22);B cell antigens ( CD 19, 20, 22);
T cell antigens ( CD 2, 3, 5T cell antigens ( CD 2, 3, 5
& 7)& 7)
 Immunoglobulin determination: Ig G / IgMImmunoglobulin determination: Ig G / IgM
praprotein markerpraprotein marker
 HIVHIV

34. Classification
 REALREAL
 Clinical / Working FormulationClinical / Working Formulation
Low gradeLow grade
Inermediate gradeInermediate grade
High gradeHigh grade

35. Classification
Low grade
Proliferation: LowProliferation: Low
Course:Course: IndolentIndolent
Symptoms: -veSymptoms: -ve
Treatment: Not curableTreatment: Not curable
High grade
HighHigh
Rapid, fatal(un-Rx)Rapid, fatal(un-Rx)
+ve+ve
Potentially CurablePotentially Curable
Staging
Similar to HD

36. Etiology
 Cannot be attributed a single causeCannot be attributed a single cause
 Chromosomal translocationsChromosomal translocations: t: t
(14, 18)(14, 18)
 Infection:Infection:
 Virus:Virus:EBV, HTLV,HHV-8, HIVEBV, HTLV,HHV-8, HIV
 Bacteria: H.Pylori - Gastric lymphomaBacteria: H.Pylori - Gastric lymphoma
 Immunology:Immunology:
 Congenital immunodeficiency,Congenital immunodeficiency,
 Immunocompromised patients -Immunocompromised patients - HIV, organHIV, organ
transplantationtransplantation

37. Management
Low grade:
 Asymptomatic : No treatment ;Asymptomatic : No treatment ;
 RadiotherapyRadiotherapy for localised disease (Stage 1);for localised disease (Stage 1);
 Chemotheraphy: mainstay isChemotheraphy: mainstay is
ChlorambucilChlorambucil; Initial response good , but; Initial response good , but
repeated relapses, median survival 6-10 yrs;repeated relapses, median survival 6-10 yrs;
 Newer: Fludarabine, 2-CdA (Chlorodeoxyadenosine)Newer: Fludarabine, 2-CdA (Chlorodeoxyadenosine)
 Monoclonal antibody: RituximabMonoclonal antibody: Rituximab
 SCT/BMT

38. Aggressive ( high / intermediate grade):
 ChemotherapyChemotherapy: mainstay: mainstay
CHOP
-every 3 weeks, at least-every 3 weeks, at least
6 cycles6 cycles
Cyclophosphamide,yclophosphamide,
Doxorubicinoxorubicin HHydrochloride,ydrochloride,
Vincristine,incristine,
Prednisolononerednisolonone

39.  High risk cases with poor prognosticHigh risk cases with poor prognostic
factors or relapse :factors or relapse :
High dose chemotherapyHigh dose chemotherapy
combined with autologous BMT / SCTcombined with autologous BMT / SCT
 Monoclonal antibodyMonoclonal antibody
 With CNS involvement / leukemic relapse :With CNS involvement / leukemic relapse :
Similar to ALLSimilar to ALL

40. Prognosis
 Low grade : Median survival –10 yrsLow grade : Median survival –10 yrs
 High Grade:High Grade:
Increasing age, advanced stage, concomitantIncreasing age, advanced stage, concomitant
disease, raised LDHdisease, raised LDH,,T- cell phenotypeT- cell phenotype : Poor: Poor
prognosisprognosis