1. Lymphomas
Ismail M. Siala

2. Objectives: The types of lymphoma. Clinical Presentation of lymphomas
Diagnosis of lymphomas
Investigations of lymphomas.
Staging of lymphomas
Treatment options of Lymphomas.

3. Definition Lymphomas Neoplasms of lymphoid tissues
Typically causes lymphadenopathy.

4. Epidemiology of lymphomas
A common cancer
5th most frequently diagnosed cancer
Males > Females

5. Classification of Lymphomas

6. Lymph Node Bone Marrow Bx Other Tissue
Routine microscopic examination
Immunological examination

7. Reed-Sternberg Cell Large malignant lymphoid cell Bi-nucleated
B-cell origin
Present in small numbers
Surrounded by reactive T-cells, plasma cells and eosinophils.

8. Based on the pathological findings:
Reed Sternberg Cell
The pathology report
Based on the pathological findings:
Hodgkin lymphoma
Non Hodgkin lymphoma
Hodgkin Lymphoma
Non-Hodgkin Lymphoma

9. Hodgkin’s Lymphoma
Thomas Hodgkin
( )

10. Hodgkin Lymphoma
All are B-Cells

11. Hodgkin Lymphoma = Reed-Sternberg cell

12. Epidemiology Sex
> :
1.5 1

13. Epidemiology Age A bimodal peaks: the 3rd and the 6th decades.
a bimodal age-incidence curve

14. Epidemiology Aetiology
Unknown
Well-educated background
Small families.
Past history of infectious mononucleosis, no proven link to EB virus yet.

15. Clinical Features Symptoms

16. Clinical Features of Hodgkin Lymphoma Symptoms
Painless Neck Swelling

17. Large Mediastinal Mass Nodular Sclerosing disease
Dry Cough
Large Mediastinal Mass Nodular Sclerosing disease
Breathlessness

18. Clinical Features of Hodgkin Lymphoma Systemic Symptoms
Weight loss
Sweating
Itching
Fever

19. Clinical Features Physical Signs

20. Lymphadenopathy Painless, Rubbery
Usually at neck and supraclavicular areas
10% sub-diaphragmatic

21. Sites of LN involvment in HL
Peripheral LN
Cervical, supraclavicular and axillary LN (70%)
Generalized lymphadenopathy is not typical in HL
Thorax
Anterior mediastinum in NS HL
Others, Rare:
Lung
Pleural effusion
Pericardial effusion
SVC obstruction
Abdomen
Hepatosplenomegaly.
Retroperitoneal LN.

22. Differential Diagnosis of Lymph-adenopathy
Infections
Autoimmune disorders
Haematological
Lymphomas
Leukemias
AIDS
Metastases
Benign

23. Hepatosplenomegaly Could be because of: Disease infiltration.
Reactive ( no infiltration).

24. Spread to other LN groups
CONTIGUOUS SPREAD
From one LN to the next.

25. Extranodal Disease
Rare
Extranodal Disease:
Bone
Brain
Skin

26. Investigations of HL

27. Hodgkin lymphoma Treatment depends on: Histological Subtype
Clinical Stage

28. Investigations of HL Confirm the Diagnosis Histological Subtype
Staging
Hodgkin Lymphoma
Lymph Node Biopsy
Biopsy from other tissues
Blood Tests
Radiology
Other biopsies

29. Lymph Node Biopsy Taking the biopsy?
Surgical excision
Percutaneous needle biopsy under radiological guidance

30. Hodgkin lymphoma - Histological subtypes The WHO classification
Nodular lymphocyte predominant HL (5%)
Slow growing
Localized
Rarely Fatal
Classical Hodgkin lymphoma (95%)
nodular sclerosing young, F>M
mixed cellularity Elderly
lymphocyte-rich Men
lymphocyte depleted ?NHL

31. Investigations of HL Confirm the Diagnosis Histological Subtype
Staging
Hodgkin Lymphoma
Lymph Node Biopsy
Biopsy from other tissues
Blood Tests
Radiology
Other biopsies

32. Blood Investigations

33. Complete blood count ESR, may be raised May be Normal
Normochromic, normocytic anaemia
Lymphopenia ( A bad sign)
Eosinophilia
Neutrophilia
ESR, may be raised

34. Renal function tests, need to be normal before Rx.
Liver function tests
May be Normal
Abnormal
With infiltraion or without infiltraion
Obstructive pattern  enlarged LN at porta hepatis.
Renal function tests, need to be normal before Rx.
Serum LDH
Reflect level of tumor bulk and turnover
Not of great significance in HL

35. Radiological Investigations
Blood Investigations
Radiological Investigations

36. Chest X-Ray

37. Abdominal Ultrasound Evaluation of the abdomen and retroperitoneum Lymph Nodes Liver, Spleen, Kidneys

38. CT-Scan of Chest, Abdomen and Pelvis

39. Radiological Investigations
Blood Investigations
Radiological Investigations
Bone Marrow Biopsy

40. Bone Marrow biopsy Indications
1- Hodgkin Lymphoma when bone marrow involvement is suspected
abnormal full blood count
advanced stage of the disease.
2-ALL cases of Non Hodgkin Lymphoma.

41. Staging of lymphoma Ann Arbor classification
Stage I
Stage II
Stage III
Stage IV

42. Bulky Disease Mediastinal mass >⅓ of
the maximum transverse diameter of the chest
Presence of nodal mass with a maximal dimension > 10cm

43. LYMPHOMA STAGING “B” symptoms Stage A  No B symptoms
Unexplained Fever > 38oC
Unexplained Weight loss > 10% body weight within the preceding 6 months.
Drenching night sweets
Stage A  No B symptoms
Stage B  any one of the B symptoms

44. Stages of Lymphoma
I A
I B
II A
II B
III A
IV A
IV B

45. Management of Hodgkin Lymphoma

46. HODGKIN`S LYMPHOMA MANAGEMENT
INTENTION OF TREATMENT IS
CURE
With appropriate treatment:
90% of Stage IA are cured
70% of other stages are cured

47. Hodgkin lymphoma Treatment depends on: Histological Subtype
Clinical Stage

48. + Involved Field Radiotherapy (IFRT)
Treatment of HL
Stage I-II
Stage III-IV
Radiotherapy ONLY
Chemotherapy
(ABVD) 8 courses
Stage IA-IIA Nodular Lymphocyte Predominant HL
Radiotherapy ONLY FOR:
Chemotherapy
(ABVD) 2-6 courses
+ Involved Field Radiotherapy (IFRT)
1- Bulky disease
2- Residual disease

49. ADRIAMYCIN(DOXORUBICIN)
ABVD A
ADRIAMYCIN(DOXORUBICIN) B
BLEOMYCIN V
VINBLASTINE D
DACARBAZINE
Give day 1 & 15 every 4 weeks

50. Long term complications of treatment
Infertility
sperm banking should be discussed
premature menopause
secondary malignancy
skin, AML, lung, MDS, NHL, thyroid, breast...
cardiac disease

52. Non-Hodgkin Lymphoma

53. Epidemiology Sex
>

54. Age distribution of new NHL cases
Median Age: yrs

55. Etiology of NHL Infection: Immunodeficiency:
Viral Infections:
EBV  Burkitt
Human Herpes virus 8
HTLV
Chronic H.pylori infection  gastric lymphoma
Immunodeficiency:
AIDS
Organ transplant
Previous treatment for HL chemo or radiotherapy
Chromosomal, T(14:18) in follicular lymphoma

56. Intermediate/High grade NHL
Low grade NHL
Intermediate/High grade NHL
Small cell size
Round or cleaved nuclei
Low mitotic rate
Larger cell size
Prominent nucleoli
Higher mitotic rate
Indolent/ non aggressive NHL
Low proliferation rate
Late symptoms
Indolent course – uncurable with conventional therapy
Aggressive NHL
High proliferation rate
Rapidly produce symptoms
Fatal if untreated

57. Non-Hodgkin lymphoma Incidence
Diffuse large B-cell lymphoma
(High Grade)
Follicular Lymphoma
(Low Grade)
85% of NHL
Other NHL

58. Clinical Features Symptoms

59. Clinical Features of NHL Symptoms
Painless Swelling
Neck
Axilla
Groins

60. Clinical Features of NHL Systemic Symptoms
Weight loss
Sweating
Itching
Fever

61. Clinical Features Physical Signs

62. Lymphadenopathy

63. Hepatosplenomegaly
If present indicates;
Disease infiltration.

64. Spread to other LN groups
SKIPPY SPREAD

65. Specially in T-Cell Lymphoma
Extranodal Disease
Extranodal Disease:
Bone Marrow: Low Grade> High Grade
Gut
Thyroid
Lung
Testis
Brain
Skin
Bone , rare
More Common in nhl
Specially in T-Cell Lymphoma

66. Compression Syndromes
Intestinal Obstrucion
Ascites
SVC obstrucion
Spinal Cord Compression
More Common in NHL

67. NHL vs. HL Clinical Features
Extent at presentation
Localized
Disseminated
Spread to LN
Contingous
Skippy
Extra-nodal Disease
Rare
More common
Obstruction Syndromes
Less Common

68. Staging of lymphoma Cotswolds Staging classification
Stage I
Stage II
Stage III
Stage IV

69. LYMPHOMA STAGING “B” symptoms Stage A  No B symptoms
Unexplained Fever > 38oC
Unexplained Weight loss > 10% body weight within the preceding 6 months.
Drenching night sweets
Stage A  No B symptoms
Stage B  any one of the B symptoms

70. Investigations of NHL

71. As in Hodgkin Lymphoma Hematological examinatons:
Complete blood count
Liver function tests
Renal function tests
Serum LDH
Reflect level of tumor bulk and turnover
Particularly of relevance in aggressive NHL
Radiological examinatons

72. 3-Bone Marrow biopsy Indications of bone marrow biopsy:
1- Hodgkin Lymphoma when bone marrow involvement is suspected
abnormal full blood count
advanced stage of the disease.
2-ALL cases of Non Hodgkin Lymphoma.

73. As in Hodgkin Lymphoma PLUS
Immunophenotyping of surface antigens:
B-Cell or T-Cell
Immunoglobulin Levels, some NHL cause raised IgG or IgM levels.
Serum Uric Acid
Raised in high grade NHL  renal failure if not treated.
HIV testing, If relevant to clinical condition..

74. Non Hodgkin lymphoma Treatment depends on: Grade ( Low or High)
Clinical Stage

75. Treatment of Low Grade NHL
Indications for treatment
Systemic Symptoms
Rapid nodal growth
Bone Marrow involvment.
Compression Syndromes
Observation and Follow up
Active Treatment
Stage I-II
Radiotherapy
Palliative Radiotherapy for:
SVC obstruction
Spinal Cord Compression
Pain
Stage III-IV
Chemotherapy
Single agent (Chlarambucil, Fludarabine)
Or; Combination chemotherapy (CVP)
Rituximab (Monoclonal Antibody) for CD-20 positive follicular lymphoma

76. Treatment of high Grade NHL Chemotherapy (CHOP) 3 cycles
Stage I-II – Non Bulky
Chemotherapy (CHOP) 3 cycles
AND Radiotherapy
Stage I-II – Bulky
Stage III-IV
Chemotherapy (CHOP) 6-8 cycles
Chemotherapy (CHOP) + Rituximab
For CD20 + Diffuse large B Cell lymphoma
Radiotherapy to area of bulky disease
Relapsed Disease
Autologus Stem Cell Transplantation

77. Repeat cycle every 3 weeks
CHOP C
CYCLOPHOSPHAMIDE H
DOXORUBICIN O
VINCRISTINE (Oncovin) P
PREDNISOLONE
Repeat cycle every 3 weeks

78. Rituximab Monoclonal Antibody Against CD20 antigen.
Can be combined with other chemotherapy
Used for
Diffuse Large B cell Lymphoma
Follicular Lymphoma that is CD20 positive

79. Gastric MALToma Low grade histology Related to H.pylori infection
Surgery is not routinely performed.
Treatment:
Treat H.pylori infection
Chemotherapy if;
Large cell component
Deeply penetrating
Metastatic
Relapsing

80. Thank you all
for your attention

82. Classification of NHL The working formulation (1982)
Clinical behaviour + histopathological features
Not incorporated the origin of the cell ( B or T)
Missing a large variaty of new clinicopathological entities.
The WHO/REAL classification (1993)
Incorporates immunophenotypes
Differentiate between cells of T or B origin
Recognizes seversal less common entities

83. The International Prognostic Index (IPI) for NHL
Five independent prognostic factors
1- age older than 60 years
2- higher stage (III or IV)
3- More than one extranodal site involvement
4- lower performance status ( ECOG>1)
5- elevated serum LDH
0-1  5 yr survival is 73%
4-5  5 yr survival is 26%

84. A practical way to think of lymphomaHL
NHL
Incidence
4: /yr
12: /yr
Reed-Sternberg cells
Present
Absent
Cell Type
B-cell
B-cell(70%), T-cell(30%)
Sex
Males>Females
Medial Age
31 yrs
65-70 yrs
LN enlragement
Usually supradiaphragmatic
Any where
Spread pattern
Contiguous
Skipped
Extranodal involvement
Less common
More common
Determinants of treatment
Stage (I,II,III,IV)
B symptoms
Grade (Low/High)
Stage(I,II,III,IV)

85. A practical way to think of lymphoma
Category
Survival of untreated patients
Curability
To treat or not to treat
Non-Hodgkin lymphoma
Indolent
Low Grade
Years
Generally not curable
Generally defer Rx if asymptomatic
Aggressive
High Grade
Weeks Months
Curable in some
Treat
Hodgkin lymphoma
All types
Variable – months to years
Curable in most

86. Modes of Spread of Lymphoma
Hodgkin Lymphoma
Almost always originate in a LN
Contiguous spread
Extranodal disease to bone, brain or skin is rare.
Non Hodgkin Lymphoma
Usually widespread at presentation
Skippy spread
Extranodal involvement is more common than in HL
Bone marrow, GIT, Thyroid, Lung, Skin , testis, Brain and Bone.