b cell lymphoma
TRANSCRIPT
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B Cell Lymphoma
Dr. Istikhar Ali Sajjad
PGR Medical Unit II,Punjab Medical College
Faisalabad.
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LymphomaClonal malignant disorders that are derived Clonal malignant disorders that are derived
from lymphoid cells: either precursor or from 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%)
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Classification of B cell Classification of B cell Lymphoma Lymphoma
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
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Hodgkin’s Disease
Histologically & clinically a distinct Histologically & clinically a distinct malignant diseasemalignant disease
Predominantly, B-cell diseasePredominantly, B-cell diseaseCourse of the disease is variable, Course of the disease is variable,
but the prognosis has improved but the prognosis has improved with modern treatmentwith modern treatment
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Etiology
? Infection – ? Infection – EBVEBV
? Environmental factors? Environmental factors
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REAL* ClassificationClassic:
Nodular SclerosisNodular SclerosisLymhocyte richLymhocyte richMixed CellularityMixed CellularityLymhocyte depletedLymhocyte depleted
Non-ClassicNodular Lymphocyte predominant Nodular Lymphocyte predominant
*REAL – Revised European,American,lymphoma
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Clinical featuresBimodal age distribution :distribution :
young adults young adults ( 20-30 yrs)( 20-30 yrs) & elderly & elderly (> 50yrs) (> 50yrs) MMay occur at any ageay occur at any age
M > FM > FLymphadenopathyLymphadenopathy::
most often cervical region most often cervical region asymmetrical, discreteasymmetrical, discretepainless, non-tenderpainless, non-tenderelastic character on palpation ( rubbery)elastic character on palpation ( rubbery)not adherent to skinnot adherent to skin fluctuate in sizefluctuate in size
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Contiguous spread via the lymphatic chain Contiguous spread via the lymphatic chain eg.eg.involvement of abdominal & thoracic involvement of abdominal & thoracic LNs LNs
Extra nodal disease - rareExtra nodal disease - rareHepatospleenomegalyHepatospleenomegaly
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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 cyclical Fever sometimes cyclical (‘Pel-Ebstein fever’)Pain at the site of disease after drinking Pain at the site of disease after drinking
alcoholalcoholPallorPallorPruritis Pruritis Symptoms of Bulky (>10 cm) diseaseSymptoms of Bulky (>10 cm) disease
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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 mass CXR- mediastinal mass CT thorax / abdomen / pelvis-for stagingCT thorax / abdomen / pelvis-for staging Other: Gallium scan, PET, Other: Gallium scan, PET, Lymphangiography , Lymphangiography ,
LaporotomyLaporotomy
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LN FNAC / biopsyLN FNAC / biopsy : :
Malignant Malignant REED-STERNBERG ( RS) Cell: Bi-: Bi-nucleate cell with a prominent nucleolus. Derived nucleate 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 cells lymphocytes, plasma cells
Fibrous tissueFibrous tissue
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REED-STERNBERG ( RS ) CellREED-STERNBERG ( RS ) Cell
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RS cell and variantsRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
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>10 cm
Bulky disease
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LymphangiographyLymphangiography
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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 an Two or more LN regions involved (II) or an
extra lymphatic site and lymph node regions on the extra lymphatic site and lymph node regions on the same side of diaphragmsame side of diaphragm
Stage III : Involvement of lymph node regions on both Involvement 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 the extra lymphatic involvement or involvement of the spleen (IIspleen (IISS) or both (IIS) or both (IISEE) )
Stage IV : Involvement outside LN areas (Liver, bone Involvement outside LN areas (Liver, bone marrow)marrow)
AA : Absence of ‘B’ symptoms : Absence of ‘B’ symptoms BB : B symptoms present : B symptoms present
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Treatment
Radiotherapy (RT)Radiotherapy (RT)ChemotherapyChemotherapyBone marow transplantBone marow transplantAntibody treatment: Rituximab target CD-20Antibody treatment: Rituximab target CD-20SupportiveSupportive
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Treatment - Guidelines Indications for RT:
Stage I diseaseStage I diseaseStage II disease with 3 or lesser areas involvedStage II disease with 3 or lesser areas involvedFor Bulky diseaseFor Bulky diseaseFor pressure problemsFor pressure problems
Indications for CTAll with B symptomsAll with B symptomsStage II disease with >3 areas involvedStage II disease with >3 areas involvedStage III and IV diseaseStage III and IV disease
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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 with either 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)
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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 ofsecondary malignancy: (secondary malignancy: (leukemia , NHL), Solid ), Solid
tumors- Lung, breast InfectionsInfectionsCardiac, pulmonary, endocrinal abnormalitiesCardiac, pulmonary, endocrinal abnormalities
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International Prognostic Index (IPI)
AgeAgeAdvanced stage diseaseAdvanced stage diseasePerformance statusPerformance statusElevated LDHElevated LDHPresence of Extra nodal diseasePresence of Extra nodal disease
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Non Hodgkin’s lymphoma Incidence is increasingIncidence is increasingNHL>HDNHL>HDMedian age of presentation is Median age of presentation is 65-70 yrs65-70 yrsM>FM>FMore often clinically disseminated at More often clinically disseminated at
diagnosisdiagnosisB-cell-70% ; T-cell-30%B-cell-70% ; T-cell-30%
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Clinical features Widely disseminated at presentation Widely disseminated at presentation Nodal involvementNodal involvement: :
Painless lymphadenopathyPainless lymphadenopathy, often cervical region is , often cervical region is the most common presentationthe most common presentation
HepatospleenomegalyHepatospleenomegaly ExtranodalExtranodal : : Intestinal
lymphoma ( abdominal pain, anemia, dysphagia); ( abdominal pain, anemia, dysphagia); CNSCNS ( headache, cranial nerve palsies, spinal cord ( headache, cranial nerve palsies, spinal cord compression) ;compression) ;
Skin, Testis; Thyroid; Lung Bone marrow (low grade): (low grade): PancytopeniaPancytopenia
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Systemic symptomsSystemic symptomsSweating, weight loss, itchingSweating, weight loss, itchingMetabolic complications:Metabolic complications:
hyperuricemia, hyperuricemia, hypercalcemia, hypercalcemia, renal failurerenal failure
Compression syndrome:Compression syndrome:Gut obstructionGut obstructionAscitesAscitesSVC obstructionSVC obstructionS/C CompressionS/C Compression
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Diagnosis and staging
Similar to HD Similar to HD plus, Bone marrow aspirate & trephineBone marrow aspirate & trephine Immunophenotyping : Monoclonal antibodies Immunophenotyping : Monoclonal antibodies
directed against specific lymphocyte associated directed against specific lymphocyte associated antigens antigens B B cell antigens ( CD 19, 20, 22); cell antigens ( CD 19, 20, 22); T cell antigens ( CD 2, 3, 5 & 7)T cell antigens ( CD 2, 3, 5 & 7)
Immunoglobulin determination: Ig G / IgM Immunoglobulin determination: Ig G / IgM praprotein markerpraprotein marker
HIVHIV
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ClassificationREALREALClinical / Working FormulationClinical / Working Formulation
Low gradeLow grade Inermediate gradeInermediate grade High gradeHigh grade
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Classification
Low grade
Proliferation: LowProliferation: LowCourse:Course: Indolent IndolentSymptoms: -veSymptoms: -veTreatment: Not curable Treatment: Not curable
High grade
HighHighRapid, fatal(un-Rx)Rapid, fatal(un-Rx)+ve+vePotentially CurablePotentially Curable
StagingSimilar to HD
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Etiology Cannot be attributed a single causeCannot be attributed a single cause Chromosomal translocationsChromosomal translocations: t (14, : t (14,
18)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, organ transplantationHIV, organ transplantation
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Management Low grade: Asymptomatic : No treatment ; Asymptomatic : No treatment ;
RadiotherapyRadiotherapy for localised disease (Stage 1); for localised disease (Stage 1); Chemotheraphy: mainstay is Chemotheraphy: 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/BMTSCT/BMT
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Aggressive ( high / intermediate grade):
ChemotherapyChemotherapy: mainstay : mainstay CHOP -every 3 weeks, at least -every 3 weeks, at least 6 cycles 6 cycles Cyclophosphamide, yclophosphamide, Doxorubicin oxorubicin HHydrochloride, ydrochloride, Vincristine, incristine, Prednisolononerednisolonone
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High risk cases with poor prognostic High risk cases with poor prognostic factors or relapse : factors or relapse : High dose chemotherapy High 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
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PrognosisLow grade : Median survival –10 yrsLow grade : Median survival –10 yrsHigh Grade:High Grade:
Increasing age, advanced stage, concomitant Increasing age, advanced stage, concomitant disease, raised LDHdisease, raised LDH,,T- cell phenotypeT- cell phenotype : Poor : Poor prognosisprognosis
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