2. INTRODUCTION
• The term lymphoma identifies a heterogeneous groupof biologicallyand clinically
distinct neoplasms thatoriginate from cells in the lymphoid tissue.
•They have been historicallydivided into 2 distinctcategories : Hodgkin’s and Non-
Hodgkin’s Lymphoma.
• 85% of lymphomas originate from mature Bcells
• 10% to 15% derive from the T-celllineage.
3. ANATOMY OF THE LYMPHOID
SYSTEM
Lymphoid Tissuescan bedivided into 2 majorcategories :
1) CENTRAL or PRIMARY LYMPHOID TISSUES:
• Theseare tissues in which the lymphoid precursorcells mature toa stageatwhich
theyarecapableof performing their function in responsetoan antigen
• Includes Bone Marrow andThymus
2) PERIPHERAL or SECONDARY LYMPHOIDTISSUE
• Theseare tissues in whichantigen specific reactionsoccur
• Includes Lymph Nodes, Spleen and Mucosa Associated LymphoidTissue
4. A) CENTRAL LYMPHOID ORGANS
a) BONE MARROW
• It is the siteof generation of all circulating blood cells in an adult.
• Gives rise toall cellsof the immune system bya processcalled
haematopoiesis.
• It is of 2 types :
a) Red marrow
1. Contains haematopoietic tissue
2. Found in flatbones like skull, scapula, pelvic bone, vertebrae,ribs
3. Also found in epiphyseal and metaphyseal ends of longbones.
5. b) YellowMarrow
• Contains mainly fatty tissue
• Present in diaphysis of long bones
•Asa person’s age advances, red marrow is
converted into yellow marrow.
•Processcan be reversed if there isa need for
haematopoiesis.
6. b) THYMUS
• Bi-lobed gland situated in thethorax
above the heart.
• It increases progressively in size upto
adolescence following which itatrophies.
• Divided into a cortex andmedulla
FUNCTION:
•Site at which immature T cells , which
migrate from the bone marrow undergo
maturation and selection to naive Tcells
7. 2) PERIPHERAL LYMPHOIDTISSUES
a) Lymph Nodes
• Bean shaped structures strategicallypositioned
at various sites throughout thebody
• They have afferent vessels entering at the
peripheryand efferentvesselsemerging at the
hilus.
• Arranged in groups, along the blood vesselsor
the flexural side of ajoint
FUNCTION
• Toprocess antigens present in lymphfluid
drained from tissues and organs via the
afferent lymphatics.
8. HISTOLOGY
• Divided into a capsule, cortex, medullaand
sinuses.
•Sinuses are present at three sites :
Subcapsular, cortical and medullary.
• Sinuses contain numerous macrophages
which filter the lymph fluid, identify and
process antigens and present them to
lymphocytes.
• Cortex contains B cellfollicles
• Paracortex contains highendothelial
venules and T cellzones.
• Medulla contains medullary cordsand
sinuses.
9. B) SPLEEN
• Location
• Left epigastricregion
• between 9th-11th rib
• in line of 10th rib
• Largest lymphatic organ in thebody.
• Can varyconsiderably in sizeand weight
HISTOLOGY
• Spleen has 2 majorcompartments
a) Red Pulp
b) White Pulp
• Red pulp is a complex web of sinuses
lined by phagocytic cells andfunctions
as a filter for particulate antigens and
formed elements of blood.
• White pulp is identical tolymphoid
tissue of the lymphnode
10. FUNCTIONS OF SPLEEN
• Important role in haematopoiesis during fetaldevelopment.
•Mechanical filtration of pathogens located within cells or circulating inthe
plasma.
• Recognizes and removes old, damaged or malformedRBCs.
11. HODGKINS LYMPHOMA
• Hodgkin lymphomaencompassesadistinctive groupof neoplasms that are
characterized by the presence of a Reed-Sternberg cell.
•Arise in a single lymph node orchainof lymph nodes and typicallyspread in a
stepwise fashion to anatomically contiguousnodes.
• Twomajor sub-types are now recognized:
a) Classic Hodgkins Lymphoma
b) Nodular Lymphocyte predominant Hodgkins lymphoma
12. CLINICAL FEATURES
• Hodgkins Lymphoma patients present with peripherallymphadenopathy.
•Involved nodesare non tenderwith nooverlying skin changes,discreteand freely
movable.
• Characteristic clinical presentation is enlarged superficial lymph nodes inyoung
adults.
• Commonly involved lymph nodes are cervical and supraclavicular(60-80%),
followed byaxillary lymph nodes. Inguinal and femoral lymph node groupsare less
commonly involved.
• Central lymphadenopathy is seen in somesub-types.
13. B SYMPTOMS :
A) FEVER (25-50%)
B) DRENCHING NIGHT SWEATS
C) WEIGHT LOSS
D) OTHER NON-SPECIFIC SYMPTOMS (pruritus, fatigue and pain after
drinking alcohol)
SYMPTOMS OF EXTRA NODAL MANIFESTATION
a) Involvement of Liver
1) Abdominal swelling secondary to hepatomegaly orhepatosplenomegaly
2) Jaundice and ascites
14. b) Signs of mediastinal involvement
1) Retrosternal Chestpain
2) Cough and shortness of breath
3) Pleural and pericardialeffusion
15. INVESTIGATIONS
A. DETAILED HISTORY WITH ATTENTION TO PRESENCE OR ABSENCEOF
CLINICAL SYMPTOMS
B. CAREFUL PHYSICAL EXAMINATION EMPHASIZING NODE CHAINS ,
WALDEYERS RING AND SIZE OF LIVER AND SPLEEN
C. ROUTINE LABORATORYTESTS
• Complete Blood Cell Count
• Erythrocyte Sedimentation Rate
• Liver Function Test
16. D. CHEST RADIOGRAPH
• Low cost method fordiagnosis and surveillance in Hodgkins Lymphoma
• Useful for detecting mediastinaldisease
17. E. CT SCAN
• Standard thoracic examination for patients withHL
• Useful fordetermination of siteson initial involvement as well asextentof
disease
• Helps in classification of earlystage patients into favourable orunfavourable
prognosis.
18. F. ADEQUATE SURGICAL BIOPSY OF AFFECTED LYMPH NODES
E. STAGING LAPAROTOMY( to determine involvement of abdominal lymph
nodes)
( Staging laparotomy was extensively used when radiation therapy was preferred
treatment for early stage Hodgkins lymphoma. It was mandatory to define the
extentof abdominal involvement todetermine whethertherewasan indication
for chemotherapy. Nowadays, with availability of better imaging techniquesand
with with routine use of chemotherapy for early stage disease, staging
laparotomy is not indicated as a routine procedure)
19. REED STERNBERG CELL
• Thesine qua non of Hodgkin lymphoma is the Reed Sternberg (RS) cell
• Thesearedifferent kinds of giantcells.
• Usually derived from B lymphocytes.
• Enormous bilobed or multilobatenucleus,
exceptionally prominent nucleoli and
abundant, usually slightly eosinophilic
cytoplasm.
•Particularly characteristic are cells with
two mirror-image nuclei , each containinga
large acidophilic nucleolus surrounded by a
clear zone, features that impart an “owl-
eye” Appearance.
24. NON HODGKINS LYMPHOMA
INTRODUCTION
•Non-Hodgkin’s lymphomas (NHL) are neoplastic transformations of mature B,T,
and natural killer (NK) cells.
• In children diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma (BL),and
lymphoblastic lymphoma are mostcommon.
• DLBCL is also the mostcommon histologicsubtype in adults.
• Poorerprognosis ascompared to Hodgkins Lymphomaas complete cureachieved
in less than 50% of patients(compared toover 80% in Hodgkins).
25. CLINICAL FEATURES
NHLs have been divided into groups based onclinical behaviour
A) LOW-GRADE LYMPHOMAS
• Peripheral adenopathy that is painlessand slowlyprogressive.
• Spontaneous regressionof enlarged nodes mayoccur (waxing and waning
LN’s)
• Primary extra-nodal involvement and B symptoms are notcommon in patients
with low gradedisease.
B) INTERMEDIATE OR HIGH GRADE
• Peripheral lymphadenopathy
• Morethan one third of patients presentwith extranodal involvement; the most
common sites are the gastrointestinal tract , skin, bone marrow, sinuses,
genitourinary tract, thyroid, and central nervous system.
26. •Involvement of retroperitoneal, mesenteric, and pelvic nodes is commonin
most histologic subtypes of NHL.
•Primary lymphomas of bone are very rare(5%)Most common sites arefemur,
pelvis and vertebrae.
• Primary GI lymphomas often present with hemorrhage, pain, or obstruction
•Mostcommon site is the stomach. Common histological subtypes presenting
are Diffuse Large B Cell Lymphoma, Mantle Cell Lymphoma and MALT
Lymphoms.
• B-symptoms are more common( 30-40% ofpatients)
27. INVESTIGATIONS
A) BIOPSY
• INDICATION : lymph node larger than 1.5 × 1.5 cm that is not associated with a
documented infection and that persists longer than 4 weeks should be
considered for a biopsy.
•A biopsy should be performed immediately for patients with other findings
suggesting malignancy
B) LABORATORYINVESTIGATIONS
• Complete Blood Count
• Liver Function tests
• Serum Protein Electrophoresis
• LDH and b-2 microglobulin
28. C) IMAGING
a) CTSCAN
• Chest, abdominal and pelvic CT scansaredone routinely.
• Essential for accurate staging of thedisease.
b) PET SCAN
• 18F-Fluorodeoxyglucose PET scan is highlysensitive fordetecting both nodal
and extra-nodal disease.
• Particularly useful for histologically aggressivelymphomas
• PET scanning detects an actively metabolizing tumor in residual masses
following or during chemotherapy, and persistent abnormal uptake predicts for
early relapse and/or reducedsurvival.
c) MRI SCAN is useful in detecting bone, bone marrow, and CNS diseases in the
brain and spinalcord.
29. • Concept of staging has less impact in NHL than in HL
• Prognosis is more dependent on histology and clinical parameters than thestage
at presentation.
•Staging in NHLs, therefore, is done to identify the minority of patients who can
be treated with local therapy or combined modality treatment.
30. CLINICAL FEATURES
• Long standing lymphadenopathy whichwaxesand wanesover theyears
• Bone marrow involvement is present in 70% ofpatients
• Mean ageat presentation is around 60 yearswith a female predominance.
• Involvement of other non-lymphoid organs isuncommon.
• Less than 20% of patients presentwith B symptoms
32. TREATMENT
TREATMENT OF EARLY STAGE DISEASE
• Early Stage Disease Includes Stage I,II andIIIA
• Less than 10% of patients with FL present with early stagedisease.
• Radiotherapy is the treatmentof choice( forearlystagedisease)
• A doseof 24 to 30 Gy is highlyeffective, with noevidence of benefit for higherdoses
• Chemoradiotherapy improves Progression Free Survival as ComparedTo
Radiotherapy Alone, but has no impact on OverallSurvival.
33. TREATMENT OF ADVANCED STAGE DISEASE
• The majorityof patients presentwith advanced diseaseat diagnosis.
• Indications for treatment include symptomatic nodal and extranodaldisease,
compromised end organ function, B symptoms, orcytopenias.
• CHEMOTHERAPY REGIMENS
a) CHOP-R :
b) CVP-R
c) R-FM
d) BR
:
:
:
Cyclophosphamide, hydroxydaunorubicin, Oncovin ,
Prednisolone Rituximab
cyclophosphamide, vincristine, prednisone, and rituximab
Rituximab, fludarabine, and mitoxantrone
Bendamustine, Rituximab
34. • The BR regimen is commonly in use todaydue to lower toxicityand
favourable results.
• Radioimmunotherapy has also been used as consolidation following
conventional chemotherapy in patients with advanced stagedisease.
35. DIFFUSE LARGE B CELL LYMPHOMA
• DLBCL constitutes 31% of all NHLs, and is the mostcommon histologicsubtype
• DLBCLsconsist of adiffuse proliferation of largecells that have a high mitotic rate.
• Cell of origin is usually Germinal Centerand Postgerminal centeractivated B cells.
• Can prove to be rapidly fatal if leftuntreated.
36. CLINICAL FEATURES
• Mean age at presentation is 64years.
• Patients presentwith rapidly enlarging masses, either nodal enlargement or
extranodal disease.
•Extranodal sitesarecommon, occurring in 40% of cases, including the GI tract, the
testis, the bone, the thyroid, the skin andCNS.
•DLBCL is highly invasive, with local compression of blood vessels,airways,
involvement of peripheral nerves, and destruction of bone.
37. • Thediseasepresentsas Stage I or Stage II in approximately 40 % of thecases.
• Stage IV disease is seen in another 40% of cases.
• B symptomsare present in around 40 % of patients.
38. TREATMENT
A) EARLY STAGE
• This includes patients whopresentwith localised disease.
• Therapyof earlystage Diffuse Large Cell Disease is controversial.
• Recommended treatment is combination chemo-immunotherapywith
additional IF-RT.
• CHOP-R regimen : Cyclophosphamide, Hydroxydaunorubicin, Oncovin,
Prednisoloneand Rituximab ( usuallygiven as first line therapy)
• Addition of IF-RT also increases 5 year Progression Free Survival as well as
overall Survival( Total dose of 30-40 Gy)
39. B) ADVANCED STAGE DISEASE
• Current recommendation for the treatmentof advanced stage DLBCL is
combination chemotherapy withCHOP-R.
C) RELAPSED OR REFRACTIVE DISEASE
• The majorityof relapses from CHOP-R therapyare seen within the first 2 years
after the completion of treatment.
•For patients with poor performance status, particularlyelderlypatients, thegoal
is often palliation.
•The majorityof patients with relapsed and refractory DLBCL receive highdose
combination chemotherapy, often withrituximab.
40. MARGINAL ZONE LYMPHOMAS
MZLsare indolent NHLs that include threediseasesarising from
post-GC marginal zone Bcells:
A) Nodal Marginal Zone Lymphomas
B) Splenic Marginal Zone Lymphoma
C) Extranodal Marginal Zone Lymphoma
41. A) NODAL MARGINAL ZONE LYMPHOMA(MZL)
• Constitute less than 1% of alllymphomas
• Disease process restricted to LymphNodes
PATHOLOGY
• Within lymph nodes, therearecollections of B cells in a parafollicular,
perivascular, and perisinusoidaldistribution.
• Thesecells maysurround reactive-appearing GCs and mantle zones
42. CLINICAL FEATURES
• Majorityof patients presentwith Stage III/IVdisease
• Asymptomatic
• The 5-yearsurvival for patients with nodal MZL is 55% to 79%.
TREATMENT
• Patients are frequently treated withchemoimmunotherapy
• Regimens include eitheralkylating agents or purine analogs plus rituximab.
43. B) SPLENIC MARGINAL ZONE LYMPHOMA
• Median age at presentation is 65-70years
• No genderpredominance
• Associated with viral infections like hepatitisC
PATHOLOGY
• Expansion of marginal zones in the
spleen
•Replacement of the lymphoid follicles
of the white pulp with neoplastic cells.
•Small darker lymphocytes in thecenter
merging with pale staining cells in the
periphery.
44. CLINICAL FEATURES
• Patients typically present with splenomegaly and cytopenias
• Lymphadenopathy is uncommon.
• B symptoms and elevated LDH areuncommon.
• More than 90% of cases have Stage IV diseaseatdiagnosis.
• Survival of patients is in excess of 70% at 10years
45. TREATMENT
• Asymptomatic patients withoutsplenomegalyorcytopeniascan beobserved.
• Splenectomy results in relief of symptoms and reversal ofcytopenias.
•For those patients with Hepatitis C, treatmentof the infection results in
regression of disease.
• Radiation therapy is indicated in patients not fit forsurgery
• Total doseof 150cGygiven to theentirespleen threetimes aweek.
46. EXTRANODAL MARGINAL ZONE
LYMPHOMA
• Also known as MALT Lymphomaor Mucosa Associated Lymphoid Tissue
Lymphoma
• The mostcommon site is the stomach.
• Associated with various chronic inflammatory and infectious conditionsinfections
like H. Pylori, Borrelia, Chlamydia, and Hepatitis CVirus
• MALT lymphoma behaves indolently.
•Associated with auto-immune conditions like Sjogren’s syndrome andautoimmune
thyroiditis.
47. PATHOLOGY
• MALT lymphomas are malignancies of antigen- stimulated B cells,which
normally reside in lymph nodes within the marginal zone
•characterized bya monoclonal infiltrateof small- to medium-sized cellswith
abundant cytoplasm and irregular nuclearcontours.
•presence of lymphoepithelial lesions
created by the invasion of mucosal
glands and crypts by aggregates of
lymphomacells
48. CLINICAL FEATURES
• Clinical presentation depends upon thesite of disease.
a) Gastric and intestinal MALTlymphomas
1. Dyspepsia and vague abdominalpain
2. Bowel Obstruction
3. Rarely bleeding
b) OcularAdnexa
1. Photophobia
2. Painless Conjunctival Injection
49. c) Bronchus associated Lymphoid Tissue( BALT)
1. Usually seen in oldermen
2. Presentwith cough, feverand weight loss
TREATMENT
•Depends on stageand siteof disease
EARLY STAGE DISEASE
• For H.Pylori positive Lymphomas, eradication of H.Pylori withantibiotics
• Radiotherapy is indicated in patients with H.Pylori negative lymphomas ,those
unresponsive to anti- H. Pyloritreatment
• RT is also indicated in lymphoma of ocularadnexa
50. ADVANCED STAGE DISEASE
• If patient is asymptomatic, then observation till symptomsappear.
• Chemoimmunotherapy with alkylating agents like chlorambuciland
cyclophosphamide, purine analogs like cladribine andbortezomib.
51. MANTLE CELL LYMPHOMA
• MCL is a malignancy of small- to medium-sized B cells in the mantle zone
PATHOLOGY
• Mantlecell lymphomas are neoplasticcounterparts of naive Mantlezonecells.
• Neoplasticcellsaresmall- to medium-sized and have irregular nuclei and scant
cytoplasm.
52. CLINICAL FEATURES
• Constitutes 7% of all NHLs
• Male predominance (75 % aremales)
• Mean age at presentation of 63years
•Typical sites of involvement are the lymph nodes, spleen, liver,Waldeyer’s
ring.
• Can occasionally involve the GI tract, presenting aspolyposis.
53. TREATMENT
•The majorityof patients with MCL have adisseminated disease requiring
treatment.
• Chemotherapy is the primary treatmentmodality.
•The treatmentof MCL involves singlealkylating agents as well as combination
chemotherapy (CVP, CHOP).
• The median survival of patientswith MCL is 4 to 5 years.
