Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow characterized by increased proliferation of immature blast cells. It results from mutations that affect the common myeloid progenitor cell. Symptoms include fatigue, fever, bleeding, and infections. Diagnosis involves blood and bone marrow tests showing elevated white blood cell counts with immature blasts. Standard treatment is 7-day continuous cytarabine with 3-day daunorubicin induction chemotherapy, with hematopoietic stem cell transplant for high risk cases. Prognosis depends on risk factors like age and genetic abnormalities.

1. ACUTE MYELOID LEUKAEMIA
DR CHETAN

2. INTRODUCTION
 Acute leukaemia's are stem cell disorders characterized by malignant neoplastic proliferation
and accumulation of immature and non functional hematopoietic cells in the bone marrow.
 The neoplastic cells show increased proliferation and/or decreased apoptosis.
 If the defect primarily affects the common myeloid progenitor (CMP) then it is called Acute
myeloid leukaemia.

3.  Acute myeloid leukaemia (AML) is a neoplastic disease characterized by infiltration of the
blood, bone marrow, and other tissues by proliferative, clonal undifferentiated cells of the
hematopoietic system.
 AML is the result of a sequence of somatic mutations in a multipotential primitive
hematopoietic cell or, in some cases, a more differentiated progenitor cell.
 It can be slow growing or rapidly fatal.
 AML is the predominant form of leukaemia during the neonatal period

5.  Incidence : 1.5/100,000/year in infants decreases to approximately 0.4 per
100,000 children ages 5 to 9 years, increases gradually to 1.0 persons per
100,000 until age 25 years, and thereafter increases exponentially until the
rate reaches approximately 25/100,000 persons.
 AML accounts for 15 to 20 percent of the acute leukemias in children and 80
percent of the acute leukemias in adults.
 Men > Women (4.5 : 3)

6. ETIOLOGY
 HEREDITY
 1) Chromosomal aneuploidy like Trisomy 21 noted in Down syndrome
 2) Defective DNA repair, e.g., Fanconi anemia, Bloom syndrome, and Ataxia
telangiectasia
 3) Congenital neutropenia ie Kostmann syndrome
 4) Germline mutations of CCAAT/enhancer-binding protein α (CEBPA), runt-related
transcription factor 1 (RUNX1), and tumor protein p53 (TP53) have also been associated with
a higher predisposition to AML

7.  RADIATION
 Peaks after 5 to 7 yrs of exposure.
 Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people
also exposed to alkylating agents.
 CHEMICAL AND OTHER EXPOSURES
 Exposure to benzene, plastic, rubber, petroleum products, paint, ethylene oxide, herbicides
and pesticides can increase the risk.
 Smoking can also increase the risk

8.  DRUGS
 Anticancer drugs are the leading cause of therapy-associated AML.
 Alkylating agent–associated leukaemia occur on average 4–6 years after exposure, and
affected individuals have aberrations in chromosomes 5 and 7.
 Topoisomerase II inhibitor–associated leukaemia occur 1–3 years after exposure, and affected
individuals often have aberrations involving chromosome 11q23.
 Other agents like Chloramphenicol, phenylbutazone, and, less commonly, chloroquine and
methoxy psoralen.

9. CLINICAL FEATURES
 SYMPTOMS :
 Present with nonspecific symptoms initially.
 Fatigue is the first symptom
 Fever with or without infection will be present in approximately 10% patients
 Bleeding, easy bruising
 occasionally, bone pain, lymphadenopathy, nonspecific cough, headache, or diaphoresis
 Rarely patients may present with symptoms from a myeloid sarcoma, a tumour mass

10.  PHYSICAL FINDINGS :
 Splenomegaly, Hepatomegaly, Lymphadenopathy, Sternal tenderness
 Evidence of infection and haemorrhage
 Severe gastrointestinal bleeding, intrapulmonary haemorrhage, or intracranial haemorrhage
occurs mostly in APL
 Infiltration of the gingivae, skin, soft tissues, or meninges with leukemic blasts is characteristic
of the monocytic subtypes.

11. LABORATORY FINDINGS
 PERIPHERAL BLOOD
 LEUCOCYTES
 - Elevated count,
 - 50% cases will have decreased or within reference interval.
 - Counts ranges from <1000 to >100000/ml.
 - Presence of blasts > 20% suggests AL diagnosis.
 Typically the myeloblasts seen in AML is 20mcM in diameter with nucleus composed primarily
of dispersed chromatin and variable prominent nucleoli.
 Golgi apparatus is present but its not easily visible.
 Granules may be present but not visible by bright field microscopy.

12.  ERYTHROCYTES
 - Typically decreased and macrocytic,
 - RDW is increased,
 - Erythrocyte inclusions such as Howell-Jolly bodies, Pappenheimer bodies and
basophilic stippling is seen.
 -Nucleated RBCs can be present in proportion to anaemia or marrow damage.
 PLATELETS
 - Typically decreased
 - Hypo granular forms and sometimes giant platelets.
 - Qualitative platelet defect .

13.  The presence of AUER RODS in blasts excludes ALL. Presence of azurophilic granules is helpful
in identifying myeloid nature of the leukaemia.
 Other abnormal findings in blood smear include monocytosis and neutropenia.
 Neutrophils shows dysplasia including hypo segmentation , hypo granulation and small
nuclei with hyper condensed chromatin.
 Eosinophils and Basophils are mild to markedly elevated.

14.  BONE MARROW
 - Hypercellular with decreased fat content.
 - predominance of blasts and sometimes with fibrosis.
 - Auer rods are present in BM blasts in half of AML cases
 OTHER LABORATORY FINDINGS
 - Hyperuricemia and increased lactate dehydrogenase due to increased cell turn over
 - Hypercalcemia due to increased bone resorption
 - Increased serum and urine muramidase with monocytic component

15. CELL LINEAGE IDENTIFICATION
 CYTOGENETICS
 Common stains used are Myeloperoxidase (MPO), Sudan Black B (SBB), Naphthol AS-D
Chloroacetate (specific esterase) and alpha naphthyl esterase (non specific esterase).
 Granulocytic cells stain positive with MPO & SBB, whereas lymphoblasts are negative. So
differentiates AML & ALL.
 Granulocytic cell stains positive with specific esterase where as monocytic cell lineage stain
positive with non specific esterase. So esterase helps to differentiate these two.

16. IMMUNOPHENOTYPING BY FLOW CYTOMETRY
 Its done when morphological appearance and cytochemical reactions do not clearly define
cell lineage or when presence of more than one neoplastic cell population is suspected.
 First panel should differentiate AML from B cell ALL and T cell ALL., then second panel should
be used to subtype the AML into granulocytic, monocytic, erythrocytic, and megakaryocytic
lineages.

17. CYTOGENETIC OR MOLECULAR ANALYSIS
 2/3 rd of patients with AML have detectable cytogenetic abnormalities which includes
aneuploidies and translocations.
 Commonly observed aneuploidies include trisomy 8 & 21 , monosomy 7 & 21, and loss of x
& y chromosomes.
 Random cytogenetic abnormalities are observed in AML with recurrent genetic abnormalities
and therapy related myeloid neoplasms which are characteristic.

22.  Complete remission (CR) is traditionally defined by < 5 % blasts, absolute
neutrophil count (ANC) < 1000/µL and platelets (plt) > 100000/µL in adult and
> 80000/µL in paediatric AML.

23. STANDARD INDUCTION THERAPY
 Includes a regimen based on a 7-day continuous infusion of cytarabine (100–200 mg/m2 /d)
and a 3-day course of daunorubicin (60–90 mg/m2 /d).
 IDAC : cytarabine 1.0–1.5 g/m2, 2 times per day
 TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA: Tretinoin (all-trans-retinoic acid [ATRA]),
an oral drug that induces the differentiation of leukemic cells bearing the t(15;17).
 with or without anthracycline-based chemotherapy and possibly maintenance with tretinoin.
 HSCT

24. ACUTE LYMPHOBLASTIC LEUKEMIA.

25.  Acute Lymphoblastic Leukaemia is defined as Malignant disease of marrow in which early
lymphoid precursors proliferate and replace the normal Hematopoietic cells.
 It is the most common Malignancy in children of 2-10 years of age, with peak incidence at 4-5
years of age.
 Has Bimodal distribution with 2nd peak at 65 years of age.
 Acute onset with short duration of history.
 85% are B cell (Pre B ALL- Good prognosis)
 15% are T cell

28. TREATMENT OF ALL
 Induction therapy -
 If Philadelphia Chromosome present -
Steroid + Tyrosine Kinase Inhibitor
 If other mutations -
VADD regimen if Age <40 ( Vincristine, Asparaginase, Doxorubicin, Dexamethasone)
Hyper CVAD regimen if Age > 40 ( Hyperfractionated Cyclophosphamide, Vincristine,
Anthracycline/Doxorubicin, Dexamethasone)

29. CNS Prophylaxsis -
 Intrathecal Methotrexate + Cytarabine
 With or without WBRT (Whole Brain Radiotherapy) - in those with high risk features :
1. WBC count >50000 at the time of presentation
2. T Cell phenotype
3. Ph Chromosome positive
4. t(4;11)

30.  Remission is defined as <5% blasts in bone marrow.
 Post Remission treatment is based on whether the patient belongs to Standard risk or High
risk group.
 For standard Risk, Consolidation therapy for 7 months , which is followed by Maintenance
phase for 2-3 years.
 For High risk, Re Induction with High Dose Chemotherapy, followed by Allogenic Stem Cell
Transplantation.

31. LYMPHOMAS

32. HODGKINS LYMPHOMA
• Hodgkin lymphoma encompasses adistinctive group of neoplasms thatare
characterized by the presenceof a Reed-Sternberg cell.
•Arise in a single lymph node orchain of lymph nodes and typically spread in a
stepwise fashion toanatomically contiguous nodes.
• Two majorsub-typesare now recognized :
a) Classic Hodgkins Lymphoma
b) NodularLymphocyte predominant Hodgkins lymphoma

33. CLINICAL FEATURES
• Hodgkins Lymphoma patients presentwith peripheral lymphadenopathy.
•Involved nodes are non tenderwith nooverlying skin changes,discreteand 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 somesub-types.

34. 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 and spleen
Abdominal swelling secondary to hepatomegaly
or hepatosplenomegaly
Jaundice and ascites
b) Signs of mediastinal involvement
Retrosternal Chest pain
Cough and shortnessof breath
Pleural and pericardial effusion

35. 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

36. D. CHEST RADIOGRAPH
• Lowcost method fordiagnosis and surveillance in Hodgkins Lymphoma
• Useful fordetecting mediastinal disease

37. E. CT SCAN
• Standard thoracicexamination for patients with HL
• Useful fordetermination of sites on initial involvement as well as extent of
disease
• Helps in classification of earlystage patients into favourable orunfavourable
prognosis.

38. F. FDG-PET SCAN
• Whole body PET using 18F-
fluorodeoxyglucose is asensitive indicator for
disease.
• It is used in initial evaluation aswell as in
staging procedures after treatment to assess
response to therapy.
• Recommended whenotherdiagnostic
modalities are inconclusive
• FDG-PET moreaccurately identifies the
correctpretreatment stage in HL compared
with CECT (which tends to understage or
overstage thedisease)
• FDG-PET is able todistinguish viable/active
tumorcells from fibrosisor necrosis in a
residual massafter treatment

39. REED STERNBERG CELL
• Thesinequa 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 , eachcontaining a
large acidophilic nucleolus surrounded by
aclearzone, features that impart an “owl-
eye” Appearance.

40. 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 , neutrophils and histiocytes.
• Subtypesof Classic Hodgkins Lymphoma( cHL):
a) Nodular Sclerosis type
b) Mixed cellularity
c) Lymphocyte Rich
d) Lymphocyte Depleted

41. NODULAR SCLEROSIS TYPE
• It is the mostcommon subtype (of cHL)
• Mostcommon in adolescents and young adults
• Mediastinum and othersupra-diaphragmatic sites arecommonly involved
PATHOLOGY :
• Characterised by Collagen bands that
surround at leastone nodule
• “ Lacunar” type Reed Sternberg cells
• Background consists of lymphocytes,
histiocytes, plasmacells, eosinophils
and neutrophils.

42. MIXED CELLULARITY TYPE
• Thissubtypecomprises 15-30 % of Hodgkins Lymphoma cases.
• Can occurat any age.
• Abdominal Lymph nodes and spleen arecommonly involved.
PATHOLOGY :
•Infiltrate is usuallydiffuse orvaguely nodular
• Consists of lymphocytes, eosinophils, cellsand
histiocytes.
• Reed Sternberg cellsareof theclassic, diagnostic type
with bi-lobed, double or multiple nuclei.

43. LYMPHOCYTE RICH TYPE
• Comprises of 5 % cases of Hodgkins Lymphoma
• Predominant in males.
• Isolated cervical oraxillary lymphadenopathy
• Betterprognosis than othersub-typesof cHL
PATHOLOGY
• Background infiltrate consisting
predominantly of lymphocytes with almost
no eosinophils
• presence of lymphohistiocytic variant RS
cells that have a delicate multilobed, puffy
Nucleus (“ Popcorn cells”)

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

45. COTSWOLDS MODIFICATION OF ANN ARBOR CLASSIFICATION

46. STAGING OF HODGKINS LYMPHOMA

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

48. RADIOTHERAPY
• Radiation therapy is the mosteffective single therapeuticagent for treating early
stage Hodgkins lymphoma.

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

50. CHEMOTHERAPY

51. EARLY FAVORABLE STAGES :
• Treatment consists of a brief chemotherapy ( 2-3 cycles) plus IF-RT
EARLY UNFAVORABLE STAGES :
• Moderate amount of chemotherapy( around 4 cycles) plus IF-RT
ADVANCED STAGES :
• Extensive chemotherapy ( typically 8 cycles ) with orwithout radiotherapy

52. NODULAR LYMPHOCYTE PREDOMINANT HODGKINS LYMPHOMA
• Rare sub-typeaccounting for 5 % of all thecases
• Differ from cHL in termsof clinical features as well as immunophenotype
•The RS cell variants( alsocalled Lymphocyte Predominant RS cellsor LP RS cells)
express full program of B cell antigens.
• More indolent clinical course.
• Mostoften diagnosed in earlystages

53. CLINICAL FEATURES
• Male patient presenting with a single siteof lymphadenopathy that has been
enlarging for months toyears.
• Commonly presents in middle age
• Mostcommonly presents with peripheral lymphadenopathy , cervical, axillary
and inguinal
• Mediastinal and retroperitoneal lymph node involvement is rare
• Relative absenceof B symptoms

54. PATHOLOGY
• Monoclonal B cell neoplasm characterised bya nodularand diffuse proliferation of
scattered large neoplasticcells known as LP RS cell variants.
• LP cells have vesicular, poly-lobated nuclei
and distinct but small, usually peripheral ,
nucleoli without perinuclear halos.
• Absenceof classic RS cells
•Background consists of predominantly
lymphocytes, clustersof epithelioid
histiocytes may bepresent.

55. TREATMENT
A) EARLY FAVOURABLE STAGE
• Radiotherapy is defined as the mainstay of treatment
• Most largestudygroups recommend IF-RTas the standard of care forpatients
with early favourable disease.
B) EARLY UNFAVOURABLE AND ADVANCED STAGES
• Treatment plan is identical to thatof cHL
• Relapserate is higher in NLPHL ascompared tocHL

56. 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 lymphomaare mostcommon.
• DLBCL is also the most common histologic subtype in adults.
• Poorerprognosis as compared to Hodgkins Lymphoma as complete cureachieved
in less than 50% of patients(compared toover 80% in Hodgkins).

57. CELL OF ORIGIN OF DIFFERENT NHL’S

58. ETIOLOGY

59. 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)
• Primaryextra-nodal involvement and B symptoms are not common in patients
with lowgrade disease.
B) INTERMEDIATE OR HIGH GRADE
• Peripheral lymphadenopathy
• Morethan one third of patients presentwith extranodal involvement; the most common sites
are thegastrointestinal tract , skin, bone marrow, sinuses, genitourinary tract, thyroid, and
central nervous system .

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

61. • 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 lymphomas are high-grade neoplasms of B-cell origin. Most
lymphomasoriginating in the CNS are largecell lymphomas or
immunoblastomas, and theyaccount for 1% of all intracranial neoplasms.
• Symptoms of primary NHL of the CNS include headache, lethargy, focal
neurologic symptoms, seizures, and paralysis.

62. CLASSIFICATION

63. 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

64. C) IMAGING
a) CT SCAN
• Chest, abdominal and pelvic CT scansaredone routinely.
• Essential foraccurate staging of the disease.
b) PET SCAN
• 18F-Fluorodeoxyglucose PET scan is highlysensitive fordetecting both nodal
and extra-nodal disease.
• Particularly useful for histologically aggressive lymphomas
• PET scanning detectsan actively metabolizing tumor in residual masses
following or during chemotherapy, and persistentabnormal uptake predicts for
earlyrelapse and/orreduced survival.
c) MRI SCAN is useful in detecting bone, bone marrow, and CNS diseases in the
brain and spinal cord.

65. STAGING

66. • 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 therapyorcombined modality treatment.

67. PROGNOSIS

68. FOLLICULAR LYMPHOMA
• Second mostcommon lymphoma
• Comprises of 20 % of all NHL’s
PATHOLOGY
•Follicular Lymphomas are malignant counterparts of normal germinal center
B cells.
• Neoplastic cellsconsist of a mixture of centrocytes and centroblasts.
•Theclinical aggressiveness of the tumorcorrelateswith the numberof
centroblasts thatare present.

69. PATHOLOGY CONTD..
• WHO GRADING OF FOLLICULAR LYMPHOMAS
Grade 1 : 0-5 centroblasts per high powered field
Grade 2 : 6-15 centroblasts per high powered field
Grade 3 : >15 centroblasts per high powered field
3A : Predominantly centrocytes
3B : Sheets of centroblasts

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

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

72. PROGNOSIS

73. 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 treatment of choice( forearlystage disease)
• A doseof 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.

74. TREATMENT OF ADVANCED STAGE DISEASE
• The majority of patients presentwith advanced disease at diagnosis.
• Indications for treatment include symptomatic nodal and extranodal disease,
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

75. DIFFUSE LARGE B CELL LYMPHOMA
• DLBCL constitutes 31% of all NHLs, and is the most common histologic subtype
• 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.

76. CLINICAL FEATURES
• Meanageat 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, theskin and CNS.
• DLBCL is highly invasive, with local compression of blood vessels, airways,
involvement of peripheral nerves, and destruction of bone.

77. • Thediseasepresentsas Stage I or Stage II in approximately 40 % of thecases.
• Stage IV disease is seen in another 40% of cases.
• B symptoms are present in around 40 % of patients.

78. TREATMENT
A) EARLY STAGE
• This includes patients whopresentwith localised disease.
• Therapyof earlystage Diffuse Large Cell Disease is controversial.
• Recommended treatment is combination chemo-immunotherapy with
additional IF-RT.
• CHOP-R regimen : Cyclophosphamide, Hydroxydaunorubicin, Oncovin,
Prednisolone and Rituximab ( usuallygiven as first line therapy)
• Addition of IF-RTalso increases 5 year Progression Free Survival aswell as
overall Survival( Total doseof 30-40 Gy)

79. B) ADVANCED STAGE DISEASE
• Currentrecommendation for the treatmentof advanced stage DLBCL is
combination chemotherapy with CHOP-R.
C) RELAPSED OR REFRACTIVE DISEASE
• The majorityof relapses from CHOP-R therapyareseen within the first 2 years
after thecompletion of treatment.
• Forpatients with poor performance status, particularlyelderly patients, thegoal
is often palliation.
•The majorityof patients with relapsed and refractory DLBCL receive high dose
combination chemotherapy, often with rituximab.

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

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

82. 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 or purine analogs plus rituximab.

83. B) SPLENIC MARGINAL ZONE LYMPHOMA
• Median ageat presentation is 65-70 years
• Nogender predominance
• Associated withviral infections like hepatitis C
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.

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

85. TREATMENT
• Asymptomatic patients without splenomegaly or cytopenias can be observed.
• Splenectomy results in relief of symptoms and reversal of cytopenias.
• 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 theentire spleen three times aweek.

86. EXTRANODAL MARGINAL ZONE
LYMPHOMA
• Also known as MALT Lymphoma or Mucosa Associated 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 withauto-immune conditions like Sjogren’ssyndromeand autoimmune
thyroiditis.

87. 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 cellswith
abundant cytoplasm and irregular nuclearcontours.
• presenceof lymphoepithelial lesions
created by the invasion of mucosal
glands and crypts byaggregates of
lymphoma cells

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

89. c) Bronchusassociated Lymphoid Tissue( BALT)
1. Usuallyseen in older men
2. Presentwith cough, feverand weight loss
TREATMENT
• Depends on stage and siteof 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

90. ADVANCED STAGE DISEASE
• If patient is asymptomatic, then observation till symptoms appear.
• Chemoimmunotherapy with alkylating agents like chlorambucil and
cyclophosphamide, purine analogs like cladribine and bortezomib.

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

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

93. TREATMENT
• The majority of patients with MCL have a disseminated disease requiring treatment.
• Chemotherapy is the primary treatment modality.
• The treatment of MCL involves single alkylating agents as well as combination chemotherapy (CVP,
CHOP).
• The median survival of patients with MCL is 4 to 5 years.

94. THANK YOU