This document provides information about lymphomas, specifically Hodgkin's lymphoma. It begins with an introduction to lymphomas and the lymphatic system. It then discusses the anatomy of the lymphatic system including central and peripheral lymphoid tissues. The document outlines Hodgkin's lymphoma including clinical features, investigations, Reed-Sternberg cells, sub-types, staging, and treatment methods such as radiotherapy and chemotherapy. It concludes by discussing treatment related side effects.

1. LYMPHOMAS
PRESENTER : RAHUL BOSE
GUIDE: DR. SHARATH CHANDRA B.J.
JSS MEDICAL COLLEGE,
MYSURU

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 distinct categories : Hodgkin’sand Non-
Hodgkin’s Lymphoma.
• 85% of lymphomasoriginate from mature B cells
• 10% to 15% derive from the T-cell lineage.

3. ANATOMY OF THE LYMPHOID
SYSTEM
Lymphoid Tissues can bedivided into 2 majorcategories :
1) CENTRAL or PRIMARY LYMPHOID TISSUES :
• Theseare tissues in which the lymphoid precursorcells mature toa stageat which
theyarecapableof performing their function in response toan antigen
• Includes Bone Marrowand Thymus
2) PERIPHERAL or SECONDARY LYMPHOID TISSUE
• Theseare tissues in whichantigen specific reactionsoccur
• Includes Lymph Nodes, Spleen and MucosaAssociated Lymphoid Tissue

4. A) CENTRAL LYMPHOID ORGANS
a) BONE MARROW
• It is the site of generation of all circulating blood cells in an adult.
• Gives rise toall cells of the immune system bya process called
haematopoiesis.
• It is of 2 types :
a) Red marrow
1. Contains haematopoietic tissue
2. Found in flat bones like skull, scapula, pelvic bone, vertebrae,ribs
3. Also found in epiphyseal and metaphyseal ends of long bones.

5. b) Yellow Marrow
• Contains mainly fatty tissue
• Present in diaphysisof long bones
• As a person’sageadvances, red marrow is
converted into yellow marrow.
•Process can be reversed if there is a need for
haematopoiesis.

6. b) THYMUS
• Bi-lobed gland situated in the thorax
above the heart.
• It increasesprogressively in size upto
adolescence following which it atrophies.
• Divided into a cortexand medulla
FUNCTION:
• Site at which immature T cells , which
migrate from the bone marrow undergo
maturation and selection to naive T cells

7. 2) PERIPHERAL LYMPHOID TISSUES
a) Lymph Nodes
• Bean shaped structuresstrategically positioned
atvarious sites throughout the body
• They haveafferentvessels entering at the
peripheryand efferentvessels emerging at the
hilus.
• Arranged in groups, along the blood vessels or
the flexural side of a joint
FUNCTION
• Toprocess antigens present in lymph fluid
drained from tissues and organsvia the
afferent lymphatics.

8. HISTOLOGY
• Divided into a capsule, cortex, medullaand
sinuses.
• Sinuses are presentat threesites :
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 cell follicles
• Paracortex contains high endothelial
venules and T cell zones.
• Medulla contains medullary cordsand
sinuses.

9. th th
th
B) SPLEEN
• Location
• Left epigastric region
• between 9 -11 rib
• in line of 10 rib
• Largest lymphaticorgan in the body.
• Can vary considerably in sizeand weight
HISTOLOGY
• Spleen has 2 majorcompartments
a) Red Pulp
b) White Pulp
• Red pulp is acomplexwebof sinuses
lined byphagocyticcellsand functions
as a filter for particulateantigens and
formed elements of blood.
• White pulp is identical to lymphoid
tissueof the lymph node

10. FUNCTIONS OF SPLEEN
• Important role in haematopoiesis during fetal development.
• Mechanical filtration of pathogens located within cellsorcirculating in the
plasma.
• Recognizes and removesold, damaged or malformed RBCs.

11. MUCOSA ASSOCIATED LYMPHOID
TISSUE(MALT)
• Specialised lymphoid tissue , found in association with certainepithelia, in
particular:
a) Nasoand Oro-Pharynx : Adenoids, palatine tonsils
b) Gastro-Intestinal tract : Gut associated Lymphoid tissue, Peyer’s patchesof
distal ileum, mucosal lymphoid aggregates in colon and rectum.
c) Lung : Bronchusassociated lymphoid tissue
HISTOLOGY
• Prominent B cell follicleswith germinal centers, mantle zones,broad marginal
zones and discrete T cell zones(similiar to paracortex of LN)
FUNCTION
• Response to intra-luminal antigens
• Generation of mucosal immunity

12. SCHEMATIC REPRESENTATION OF A LYMPHOID FOLLICLE

13. HODGKINS LYMPHOMA
• Hodgkin lymphomaencompassesadistinctive groupof neoplasms thatare
characterized by the presence of a Reed-Sternberg cell.
• Arise in a single lymph node orchain of lymph nodes and typicallyspread in a
stepwise fashion toanatomicallycontiguous nodes.
• Two majorsub-types are now recognized :
a) Classic Hodgkins Lymphoma
b) Nodular Lymphocyte predominant Hodgkins lymphoma

14. CLINICAL FEATURES
• Hodgkins Lymphoma patients presentwith peripheral lymphadenopathy.
• Involved nodes are non tenderwith no overlying skin changes,discrete and freely
movable.
• Characteristicclinical presentation is enlarged superficial lymph nodes in young
adults.
• Commonly involved lymph nodes arecervical and supraclavicular(60-80%),
followed byaxillary lymph nodes. Inguinal and femoral lymph node groupsare less
commonly involved.
• Central lymphadenopathy is seen in some sub-types.

15. 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 hepatomegalyor hepatosplenomegaly
2) Jaundice and ascites

16. b) Signs of mediastinal involvement
1) Retrosternal Chest pain
2) Cough and shortnessof breath
3) Pleural and pericardial effusion

17. INVESTIGATIONS
A. DETAILED HISTORYWITH ATTENTION TO PRESENCE OR ABSENCE OF
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

18. D. CHEST RADIOGRAPH
• Low cost method fordiagnosis and surveillance in Hodgkins Lymphoma
• Useful fordetecting mediastinal disease

19. E. CT SCAN
• Standard thoracicexamination for patients with HL
• Useful fordetermination of siteson initial involvement as well as extentof
disease
• Helps in classification of earlystage patients into favourable orunfavourable
prognosis.

20. F. ADEQUATE SURGICAL BIOPSY OF AFFECTED LYMPH NODES
E. STAGING LAPAROTOMY( todetermine involvement of abdominal lymph
nodes)
( Staging laparotomy wasextensively used when radiation therapywaspreferred
treatment forearlystage Hodgkins lymphoma. Itwas mandatory todefine the
extentof abdominal involvement todeterminewhethertherewasan indication
forchemotherapy. Nowadays, with availability of better imaging techniques and
with with routine useof chemotherapy forearlystagedisease, staging
laparotomy is not indicated as a routine procedure)

21. F. FDG-PET SCAN
• Whole body PET using 18F-
fluorodeoxyglucose is a sensitive indicator for
disease.
• It is used in initial evaluation as well as in
staging procedures after treatment to assess
response to therapy.
• Recommended whenotherdiagnostic
modalities are inconclusive
• FDG-PET moreaccurately identifies the
correct pretreatmentstage in HL compared
with CECT (which tends to understageor
overstage the disease)
• FDG-PET is able todistinguish viable/active
tumorcells from fibrosis or necrosis in a
residual mass after treatment

22. REED STERNBERG CELL
• Thesine qua non of Hodgkin lymphoma is the Reed Sternberg (RS) cell
• Thesearedifferent kinds of giant cells.
• Usuallyderived from B lymphocytes.
• Enormous bilobed or multilobate nucleus,
exceptionally prominent nucleoli and
abundant, usually slightlyeosinophilic
cytoplasm.
• Particularlycharacteristicarecells with
two mirror-image nuclei , each containing a
large acidophilic nucleolus surrounded by
aclearzone, features that impart an “owl-
eye” Appearance.

23. CLASSIC HODGKINS LYMPHOMA
• Monoclonal Lymphoid Neoplasm, composed of mononuclear Hodgkins cellsand
multi- nucleated Reed Sternberg cells in an infiltrate containing a mixtureof
eosinophils, small lymphocytes , neutrophilsand histiocytes.
• Subtypes of Classic Hodgkins Lymphoma( cHL):
a) Nodular Sclerosis type
b) Mixed cellularity
c) Lymphocyte Rich
d) Lymphocyte Depleted

24. NODULAR SCLEROSIS TYPE
• It is the most common subtype (of cHL)
• Mostcommon in adolescentsand young adults
• Mediastinum and othersupra-diaphragmaticsitesarecommonly involved
PATHOLOGY :
• Characterised by Collagen bands that
surround at leastone nodule
• “ Lacunar” type Reed Sternberg cells
• Background consistsof lymphocytes,
histiocytes, plasmacells, eosinophils
and neutrophils.

25. MIXED CELLULARITY TYPE
• This subtype comprises 15-30 % of Hodgkins Lymphoma cases.
• Can occurat anyage.
• Abdominal Lymph nodes and spleen arecommonly involved.
PATHOLOGY :
• Infiltrate is usuallydiffuse orvaguely
nodular
• Consists of lymphocytes, eosinophils,
cells and histiocytes.
• Reed Sternberg cellsareof theclassic,
diagnostic type with bi-lobed, doubleor
multiple nuclei.

26. LYMPHOCYTE RICH TYPE
• Comprises of 5 % casesof Hodgkins Lymphoma
• Predominant in males.
• Isolated cervical oraxillary lymphadenopathy
• Betterprognosis than othersub-types of cHL
PATHOLOGY
• Background infiltrate consisting
predominantlyof lymphocyteswith almost
no eosinophils
• presence of lymphohistiocytic variant RS
cells that haveadelicate multilobed, puffy
Nucleus (“ Popcorn cells”)

27. LYMPHOCYTE DEPLETED TYPE
• Least common variant ( less than 1%)
• Mostcommon in olderpatients, HIV positive individuals
• Abdominal lymphadenopathywith involvement of spleen and mesenteric nodes.
PATHOLOGY
• Diffuse and hypocellular infiltrate.
• Large numberof RS cellswith
“sarcomatous” variants.
• Paucityof other inflammatory cells

28. STAGING OF HODGKINS LYMPHOMA

29. COTSWOLDS MODIFICATION OF ANN ARBOR CLASSIFICATION

30. TREATMENT METHODS
1. RADIOTHERAPY
2. CHEMOTHERAPY
3. COMBINED TREATMENT MODALITY

31. RADIOTHERAPY
• Radiation therapy is the most effective single therapeuticagent for treating early
stage Hodgkins lymphoma.

32. EXTENDED FIELD RADIOTHERAPY
1)MANTLE FIELD•
The targetvolume for mantle field includes :
• Occipital
•Submental
•Submandibular
•Anteriorand Posteriorcervical
•Infraclavicular
•Axillary
•Medial pectoral
•Paratracheal
•Mediastinal and hilar nodes

33. Treatment Field FOR MANTLE:
Superiorly:
Inferior portion of mandible bisecting
the mastoid process
Laterally:
Both theaxillae
Inferiorly:
T10-11 interspace
2) MINI MANTLE FIELD
• Mantlewithout mediastinum and
hilar lymph nodes
3) MODIFIED MANTLE FIELD
• Mantlewithout axilla
MANTLE FIELD

34. SUB-DIAPHRAGMATIC FIELD
Classicsub-diaphragmatic field is the Inverted Y
Target Volume :
• Para-aortic node
• Pelvic nodes
• Spleen
• B/L Inguinal nodes

35. INVOLVED FIELD RADIOTHERAPY:
• Mostcommonly used technique
• The main objective is to treat the involved site and immediatelyadjacent
continuous sites.
• The involved field is limited to the site of clinically involved lymph node groups. •
Different involved fields include
a) Neck
b) Mediastinum
c) Axilla
d) Paraaortic
e) Inguinal

36. DOSE:
EARLY STAGE :
• IFRT 30Gy in daily 2Gy fractions over 2 to 3 weeks.
ADVANCED STAGE :
• Radiotherapy forresidual diseaseafterchemotherapy includes doses of 30-34 Gy in
15-20 fractions of 1.8-2.0 Gyover 3 to 4 weeks.

37. CHEMOTHERAPY

38. PROGNOSTIC GROUPS

39. EARLY FAVORABLE STAGES :
• Treatmentconsistsof a brief chemotherapy ( 2-3 cycles) plus IF-RT
EARLY UNFAVORABLE STAGES :
• Moderateamount of chemotherapy( around 4 cycles) plus IF-RT
ADVANCED STAGES :
• Extensive chemotherapy ( typically 8 cycles ) with orwithout radiotherapy

40. TREATMENT RELATED SIDE
EFFECTS
A) PULMONARY COMPLICATIONS
• Radiation pneumonitis typicallyoccurs 1-6 months after completion of
radiotherapy.
• 10-15% of patients with large mediastinal tumours whoreceive a combination of
chemotherapyand mantle field radiation therapydevelop radiation pneumonitis.
CLINICAL FEATURES
• Mild, non-productive cough
• Low grade fever
• Dyspnoeaon exertion
RADIOLOGIC FEATURES
• Formation of infiltrates confined to theoriginal radiation fields.

41. B) CARDIAC COMPLICATIONS
a) Chemotherapyassociated Cardiac Complications
• Caused byanthracyclines
• Presentsas ECG changes, arrythmias orcardiomyopathy leading tocongestive
heart failure
• Caused bydirectdamage to thecardiac myoepitheliem
• Cardiotoxicity caused bydoses greater than 500mg/m2 of bodysurface area
b) Radiotherapyassociated Cardiac Complications
• Wide spectrum of cardiacdiseases such as coronaryarterydisease, myocardial
dysfunction, valvular heartdisease.
• Radiation associated heartdiseases usuallypresent 10-15 yearsafter exposure.

42. C) SECONDARY NEOPLASIA
• Radiotherapy and certain chemotherapeutic agents such as nitrogen mustards,
procarbazine, cyclophosphamide and etoposide are known to induce secondary
malignancies.
• Acute leukaemias are thecommonestsecondary malignancies, usuallyoccuring
within the first 10 yearsof initial treatment.
• Secondary Non-Hodgkins Lymphomas after Hodgkins Lymphoma.

43. • Incidence of secondarysolid organ tumours increaseswith time.
• Solid organs most at risk of developing a secondary malignancy are lung and
breast.
• Othersecondarycancers thatoccurafter succesful completion of treatment
include sarcomas, melanomas and bone tumours.

44. GONADAL DYSFUNCTION
MALES
• Post treatmentgonadal damage is most often associated with chemotherapy
regimens that include alkylating agents such as cyclophosphamideand
procarbazine.
• Rateof azoospermia after MOPP and ABVD regimens is high, ranging between
80% to 100%.
• Cryoconservation of sperm should beoffered toeveryyoung male before
undergoing therapy for Hodgkins Lymphoma.

45. FEMALES
• Alkylating agents causegonadal damage in females also – prematureovarian
failure
• Prematureovarian failure is defined as amenorrhea for a period of at least 2 years
following treatmentwith elevated levels of FSH.
• Anti-Mullerian hormone is the most sensitive indicatorof gonadal function and
can be used for post- treatmentassessmentof ovarian reserve.

46. st
TREATMENT FAILURES
DIVIDED INTO 3 CATEGORIES:
A) PRIMARY PROGRESSIVE DISEASE : Patients who neverachieved a complete
remission or relapsewithin 3 months after
end of first line of treatment
B) EARLY RELAPSE : Relapseoccurs 3 to 12 months after theend
of 1 treatment
C) LATE RELAPSE : Relapseafter acomplete remission lasting at
least 12 months

47. NODULAR LYMPHOCYTE PREDOMINANT
HODGKINS LYMPHOMA
• Raresub-type accounting for 5 % of all thecases
• Differ from cHL in termsof clinical featuresas well as immunophenotype
• The RS cell variants( alsocalled Lymphocyte Predominant RS cells or LP RS cells)
express full program of B cell antigens.
• More indolent clinical course.
• Mostoften diagnosed in earlystages

48. CLINICAL FEATURES
• Malepatient presenting with a singlesite of lymphadenopathy that has been
enlarging for months toyears.
• Commonly presents in middle age
• Mostcommonly presentswith peripheral lymphadenopathy , cervical, axillary
and inguinal
• Mediastinal and retroperitoneal lymph node involvement is rare
• Relative absenceof B symptoms

49. PATHOLOGY
• Monoclonal B cell neoplasm characterised bya nodularand diffuse proliferation of
scattered large neoplastic cells known as LP RS cell variants.
• LP cells havevesicular, poly-lobated nuclei
and distinct but small, usuallyperipheral ,
nucleoli without perinuclear halos.
• Absenceof classic RS cells
• Background consistsof predominantly
lymphocytes, clustersof epithelioid
histiocytes may be present.

50. TREATMENT
A) EARLY FAVOURABLE STAGE
• Radiotherapy is defined as the mainstayof treatment
• Most largestudygroups recommend IF-RT as the standard of care for patients
with early favourabledisease.
B) EARLY UNFAVOURABLE AND ADVANCED STAGES
• Treatmentplan is identical to thatof cHL
• Relapserate is higher in NLPHL as compared tocHL

51. NON HODGKINS LYMPHOMA
INTRODUCTION
• Non-Hodgkin’s lymphomas (NHL) are neoplastic transformations of mature B, T,
and natural killer (NK) cells.
• In childrendiffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma (BL), and
lymphoblastic lymphomaare mostcommon.
• DLBCL is also the most common histologicsubtype in adults.
• Poorerprognosisas compared to Hodgkins Lymphoma as complete cureachieved
in less than 50% of patients(compared toover 80% in Hodgkins).

52. CELL OF ORIGIN OF DIFFERENT NHL’S

53. ETIOLOGY

54. CLINICAL FEATURES
NHLs have been divided into groups based on clinical behaviour
A) LOW-GRADE LYMPHOMAS
• Peripheral adenopathy that is painless and slowlyprogressive.
• Spontaneous regressionof enlarged nodes mayoccur (waxing and waning
LN’s)
• Primary extra-nodal involvement and B symptoms are not common in patients
with lowgrade disease.
B) INTERMEDIATE OR HIGH GRADE
• Peripheral lymphadenopathy
• More than one third of patients presentwith extranodal involvement; the most
common sitesare thegastrointestinal tract , skin, bone marrow, sinuses,
genitourinary tract, thyroid, and central nervous system .

55. • Involvement of retroperitoneal, mesenteric, and pelvic nodes is common in
most histologicsubtypes of NHL.
• Primary lymphomasof bone arevery rare(5%)Mostcommon sitesare femur,
pelvis and vertebrae.
• Primary GI lymphomas often presentwith hemorrhage, pain, orobstruction
• Mostcommon site is the stomach. Common histological subtypes presenting
are Diffuse Large B Cell Lymphoma, Mantle Cell Lymphoma and MALT
Lymphoms.
• B-symptomsare morecommon( 30-40% of patients)

56. • Lymphoblastic lymphoma, a high-grade lymphoma, often manifests with an
anterior superior mediastinal mass, superior vena cava (SVC) syndrome, and
leptomeningeal diseasewith cranial nerve palsies.
• Primary CNS lymphomasare high-grade neoplasms of B-cell origin. Most
lymphomasoriginating in the CNS are largecell lymphomasor
immunoblastomas, and theyaccount for 1% of all intracranial neoplasms.
• Symptoms of primary NHL of the CNS include headache, lethargy, focal
neurologicsymptoms, seizures, and paralysis.

57. CLASSIFICATION

58. INVESTIGATIONS
A) BIOPSY
• INDICATION : lymph node largerthan 1.5 × 1.5 cm that is not associated with a
documented infection and that persists longer than 4 weeks should
beconsidered for a biopsy.
• A biopsy should be performed immediately for patients with other findings
suggesting malignancy
B) LABORATORY INVESTIGATIONS
• Complete Blood Count
• Liver Function tests
• Serum Protein Electrophoresis
• LDH and b-2 microglobulin

59. C) IMAGING
a) CT SCAN
• Chest, abdominal and pelvic CT scans aredone routinely.
• Essential for accuratestaging of thedisease.
b) PET SCAN
• 18F-Fluorodeoxyglucose PET scan is highlysensitive fordetecting both nodal
and extra-nodal disease.
• Particularlyuseful for histologicallyaggressive lymphomas
• PET scanning detectsan actively metabolizing tumor in residual masses
following or during chemotherapy, and persistentabnormal uptake predicts for
earlyrelapse and/or reduced survival.
c) MRI SCAN is useful in detecting bone, bone marrow, and CNS diseases in the
brain and spinal cord.

60. STAGING

61. • Concept of staging has less impact in NHL than in HL
• Prognosis is more dependent on histologyand clinical parameters than the stage
at presentation.
• Staging in NHLs, therefore, is done to identify the minority of patients whocan
be treated with local therapy orcombined modality treatment.

62. PROGNOSIS

63. FOLLICULAR LYMPHOMA
• Second most common lymphoma
• Comprises of 20 % of all NHL’s
PATHOLOGY
• Follicular Lymphomas are malignantcounterpartsof normal germinal center
B cells.
• Neoplasticcellsconsist of a mixtureof centrocytes and centroblasts.
• Theclinical aggressiveness of the tumorcorrelates with the numberof
centroblasts thatare present.

64. PATHOLOGYCONTD..
• WHO GRADING OF FOLLICULAR LYMPHOMAS
Grade 1 : 0-5 centroblastsper high powered field
Grade 2 : 6-15 centroblastsper high powered field
Grade 3 : >15 centroblastsper high powered field
3A : Predominantlycentrocytes
3B : Sheets of centroblasts

65. • Small numberof T cellsand follicular
dendritic cells arealso present
• Involvement of the peripheral
blood with malignant cells is commonly
seen
• Morphologicallythesecells have notches
and hence referred toas buttock cells.

66. CLINICAL FEATURES
• Long standing lymphadenopathywhichwaxesand wanesover theyears
• Bone marrow involvement is present in 70% of patients
• Mean ageat presentation is around 60 yearswith a female predominance.
• Involvement of other non-lymphoid organs is uncommon.
• Less than 20% of patients presentwith B symptoms

67. PROGNOSIS

68. TREATMENT
TREATMENT OF EARLY STAGE DISEASE
• Early Stage Disease Includes Stage I,II and IIIA
• Less than 10% of patients with FL presentwith earlystage disease.
• Radiotherapy is the treatmentof choice( forearlystage disease)
• A dose of 24 to 30 Gy is highlyeffective, with no evidence of benefit for higherdoses
• Chemoradiotherapy improves Progression Free Survival as Compared To
Radiotherapy Alone, but has no impact on Overall Survival.

69. TREATMENT OF ADVANCED STAGE DISEASE
• The majorityof patients presentwith advanced disease atdiagnosis.
• Indications for treatment include symptomatic nodal and extranodal disease,
compromised end organ function, B symptoms, orcytopenias.
• CHEMOTHERAPY REGIMENS
a) CHOP-R : Cyclophosphamide, hydroxydaunorubicin, Oncovin ,
Prednisolone Rituximab
b) CVP-R : cyclophosphamide, vincristine, prednisone, and rituximab
c) R-FM : Rituximab, fludarabine, and mitoxantrone
d) BR : Bendamustine, Rituximab

70. • The BR regimen is commonly in use todaydue to lowertoxicity and
favourable results.
• Radioimmunotherapy hasalso been used as consolidation following
conventional chemotherapy in patients with advanced stagedisease.

71. DIFFUSE LARGE B CELL LYMPHOMA
• DLBCL constitutes 31% of all NHLs, and is the most common histologicsubtype
• DLBCLsconsist of adiffuse proliferation of largecells that havea high mitotic rate.
• Cell of origin is usually Germinal Centerand Postgerminal centeractivated B cells.
• Can prove to be rapidly fatal if left untreated.

72. CLINICAL FEATURES
• Mean ageat presentation is 64 years.
• 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 and CNS.
• DLBCL is highly invasive, with local compressionof blood vessels, airways,
involvement of peripheral nerves, and destruction of bone.

73. • Thedisease presentsas 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.

74. 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)

75. B) ADVANCED STAGE DISEASE
• Current recommendation for the treatmentof advanced stage DLBCL is
combination chemotherapy with CHOP-R.
C) RELAPSED OR REFRACTIVE DISEASE
• The majorityof relapses from CHOP-R therapy are seen within the first 2 years
after thecompletion of treatment.
• Forpatients with poor performancestatus, particularlyelderlypatients, thegoal
is often palliation.
• The majorityof patients with relapsed and refractory DLBCL receive high dose
combination chemotherapy, often with rituximab.

76. MARGINAL ZONE LYMPHOMAS
MZLsare indolent NHLs that include threediseases arising from
post-GC marginal zone B cells:
A) Nodal Marginal Zone Lymphomas
B) Splenic Marginal Zone Lymphoma
C) Extranodal Marginal Zone Lymphoma

77. A) NODAL MARGINAL ZONE LYMPHOMA(MZL)
• Constitute less than 1% of all lymphomas
• Disease process restricted to Lymph Nodes
PATHOLOGY
• Within lymph nodes, therearecollectionsof B cells in a parafollicular,
perivascular, and perisinusoidal distribution.
• Thesecells may surround reactive-appearing GCs and mantle zones

78. CLINICAL FEATURES
• Majorityof patients presentwith Stage III/IV disease
• Asymptomatic
• The 5-yearsurvival for patients with nodal MZL is 55% to 79%.
TREATMENT
• Patients are frequently treated with chemoimmunotherapy
• Regimens include eitheralkylating agents orpurine analogs plus rituximab.

79. B) SPLENIC MARGINAL ZONE LYMPHOMA
• Median ageat presentation is 65-70 years
• Nogender predominance
• Associated with viral infections like hepatitis C
PATHOLOGY
• Expansion of marginal zones in the
spleen
• Replacementof the lymphoid follicles
of the white pulp with neoplastic cells.
• Small darker lymphocytes in thecenter
merging with pale staining cells in the
periphery.

80. CLINICAL FEATURES
• Patients typically presentwith splenomegaly and cytopenias
• Lymphadenopathy is uncommon.
• B symptomsand elevated LDH are uncommon.
• More than 90% of cases have Stage IV diseaseat diagnosis.
• Survival of patients is in excessof 70% at 10 years

81. TREATMENT
• Asymptomatic patients without splenomegalyorcytopenias can beobserved.
• Splenectomyresults in relief of symptomsand reversal of cytopenias.
• For those patients with Hepatitis C, treatmentof the infection results in
regressionof disease.
• Radiation therapy is indicated in patients not fit forsurgery
• Total dose of 150cGy given to theentirespleen three times a week.

82. EXTRANODAL MARGINAL ZONE
LYMPHOMA
• Also known as MALT Lymphoma or MucosaAssociated Lymphoid Tissue
Lymphoma
• The most common site is the stomach.
• Associated with various chronic inflammatory and infectious conditions infections
like H. Pylori, Borrelia, Chlamydia, and Hepatitis C Virus
• MALT lymphoma behaves indolently.
• Associated with auto-immune conditions like Sjogren’ssyndromeand autoimmune
thyroiditis.

83. PATHOLOGY
• MALT lymphomasare malignancies of antigen- stimulated B cells, which
normallyreside in lymph nodes within the marginal zone
• characterized bya monoclonal infiltrate of small- to medium-sized cells with
abundant cytoplasm and irregular nuclearcontours.
• presenceof lymphoepithelial lesions
created by the invasion of mucosal
glandsand crypts byaggregatesof
lymphomacells

84. CLINICAL FEATURES
• Clinical presentation depends upon the site of disease.
a) Gastricand intestinal MALT lymphomas
1. Dyspepsiaand vagueabdominal pain
2. Bowel Obstruction
3. Rarely bleeding
b) OcularAdnexa
1. Photophobia
2. Painless Conjunctival Injection

85. c) Bronchusassociated Lymphoid Tissue( BALT)
1. Usuallyseen in older men
2. Presentwith cough, feverand weight loss
TREATMENT
• Depends on stage and site of disease
EARLY STAGE DISEASE
• For H.Pylori positive Lymphomas, eradication of H.Pylori with antibiotics
• Radiotherapy is indicated in patients with H.Pylori negative lymphomas , those
unresponsive toanti- H. Pylori treatment
• RT is also indicated in lymphomaof ocularadnexa

86. ADVANCED STAGE DISEASE
• If patient is asymptomatic, then observation till symptoms appear.
• Chemoimmunotherapywith alkylating agents likechlorambucil and
cyclophosphamide, purine analogs like cladribineand bortezomib.

87. MANTLE CELL LYMPHOMA
• MCL is a malignancy of small- to medium-sized B cells in the mantle zone
PATHOLOGY
• Mantlecell lymphomasare neoplastic counterpartsof naive Mantle zonecells.
• Neoplasticcellsaresmall- to medium-sized and have irregular nuclei and scant
cytoplasm.

88. CLINICAL FEATURES
• Constitutes 7% of all NHLs
• Malepredominance (75 % are males)
• Mean ageat presentation of 63 years
• Typical sitesof involvement are the lymph nodes, spleen, liver, Waldeyer’s
ring.
• Can occasionally involve the GI tract, presenting as polyposis.

89. TREATMENT
• The majorityof patients with MCL havea disseminated disease requiring
treatment.
• Chemotherapy is the primary treatment modality.
• The treatmentof MCL involves singlealkylating agents as well ascombination
chemotherapy (CVP, CHOP).
• The median survival of patients with MCL is 4 to 5 years.

90. REFERENCES
• Devita, Hellman’s Concepts and Principles of Oncology
• Robbins Basic Pathology
• Sabiston’s Textbook of Surgery

91. THANK YOU