1. Lymphoma
Ismail M. Siala

2. Lymphomas
Neoplasms of lymphoid tissues that typically causes lymphadenopathy.
Classified pathologically into 2 types:
Hodgkin lymphoma
Non Hodgkin lymphoma

3. Epidemiology of lymphomas
A common cancer; 5th most frequently diagnosed cancer overall for both males and females
males > females

4. Epidemiology of Hodgkin Lymphoma
less frequent than non-Hodgkin lymphoma
A bimodal peaks at the 3rd and from the 6th decades.
20s
>50s
a bimodal age-incidence curve

5. Age distribution of new NHL cases

6. Etiology of HL

7. Etiology of NHL Infection: Immunodeficiency:
Viral Infections:
EBV  Burkitt
Chronic H.pylori infection  gastric lymphoma
Immunodeficiency:
AIDS
Organ transplant
Previous treatment for HL with chemo or radiotherapy

8. 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.

9. Sites of involvment in HL
Peripheral LN
Cervical and axillary LN (70%)
Generalized lymphadenopathy is not typical in HL
Thorax
Anterior mediastinum in NS HL
Lung
Pleural effusion
Pericardial effusion
SVC obstruction
Abdomen
Spleenomegaly
Hepatomegaly
Retroperitoneal LN

10. How a patient with lymphoma presents? Symptoms:
Painless swelling
Systemic symptoms;
Weight loss
Sweating
Itching
Fever
Pain;
Abdominal, bone, neurogenic or pain

11. Physical sings:
Enlarged Lymph nodes

12. Physical signs:
Splenomegaly
Hepatomegaly

13. Physical signs: Other physical findings
Effusions
Neurological deficits
Compression syndromes
SVC obstruction
Intestinal obstruction
Spinal cord compression
Skin infiltration

14. Differential Diagnosis of Lymphadenopathy
Infections
Autoimmune disorders
Malignant haematological diseases
Leukemias
Lymphoma
Metastasis from other primary.
AIDS
Benign
occiptial
Posterior auricular
Shotty inguinal nodes
Cervical nodes

15. Differential diagnosis of Splenomegaly:
Portal hypertension
Haematological Malignancies.
Leukemia
Lymphoma
Myeloma
Myeloproliferative disorders
Chronic Myeloid Leukemia.
Myelofibrosis.
Polycythemia Rubra Vera
Essential thrombocytosis
Autoimmune disorders
Systemic Lupus Erythematosus
Rheumatoid arthritis
Infections
Others
Normal
Splenic systs
Thyrotoxicosis
Sarcoidosis
Amyloidosis

16. What is next?

17. Get a tissue diagnosis

18. A biopsy could be obtained from:
Lymph node
Bone marrow biopsy
Imaging guided biposy for retroperitoneal and mesentric masses
Endocopic gastric biopsy

19. Send for pathological examination
Routine microscopic examination
Immunological examination
Hodgkin vs Non Hodgkin
CD20 positive or negative for some types of NHL

20. Reed-Sternberg Cells Large malignant lympoid cells Bi-nucleated
B-cell origin
Present in small numbers
Surrounded by reactive Tcells, plasma cells and eosinophils.

21. The pathology report Hodgkin Lymphoma Non-Hodgkin Lymphoma
Reed Sternberg Cell
The pathology report
Hodgkin Lymphoma
Non-Hodgkin Lymphoma

22. Which lymph node groups and organs are affected?
stage the disease
Which lymph node groups and organs are affected?
THE EXTENT OF DISEASE

23. Staging investigations Evaluation of the chest
1-Chest X-Ray

24. Staging investigations Evaluation of the abdomen and retroperitoneum
2-Abdominal ultrasonography
Lymphnodes
Liver, spleen, kidneys

25. Staging investigations
3-CT scan of the chest, abdomen and pelvis

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

27. Staging Investigations Hematological examination
Complete blood count
ESR
Liver function tests
Renal function tests
Serum LDH
Reflect level of tumour bulk and turnover
Particularly of relevance in aggressive NHL

28. Other staging investigations
Endoscopy for GIT lymophomas
Lumbar puncture
In some cases of Non Hodgkin Lymphoma
Burkitt lymphoma
Lymphoblastic lymphoma
Intermediate or high grade lymphoma involving;
Testes, paranasal sinuses, extensive bone marrow involvment.
MRI brain for AIDS related lymphoma
PET scan:
differentiate involved from non involved LN

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

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

31. 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

32. I A I B II A II B III A IV A IV B
Lymphoma Stages
I A
I B
II A
II B
III A
IV A
IV B

33. Hodgkin’s Lymphoma
Thomas Hodgkin
( )

34. Reed-Sternberg cell

35. Hodgkin lymphoma - Histological subtypes The WHO classification
Nodular lymphocyte predominant HL (5%)
Slow growing
localized
Classical Hodgkin lymphoma (95%)
nodular sclerosing
mixed cellularity
lymphocyte-rich
lymphocyte depleted

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

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

38. Treatment of HL Stage I-II Stage III-IV
Note:
For Stage IA-IIA of Nodular Lyphocyte Predominant HL  Radiotherapy alone is enough
Chemotherapy (ABVD) 2-6 courses
AND Radiotherapy
Stage III-IV
Chemotherapy (ABVD) 8 courses
Radiotherapy ONLY FOR:
1- Bulky disease
2- Residual disease

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

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

41. Non-Hodgkin Lymphoma

42. 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

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

44. Treatment of NHL
1- Grade of NHL ( Low or High)
2-STAGE OF NHL

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

46. Treatment of high Grade NHL
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

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

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

49. Related to H.pylori infection Surgery is not routinely performed.
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

50. Thank you all
for your attention

52. 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

53. 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%

54. 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)

55. 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