Hodgkins & Non-Hodgkins Lymphomas

1. HODGKINS & NON-HODGKINS LYMPHOMAS
MINISTRY OF EDUCATION REPUBLIC OF BELARUS
VITEBSK ORDER OF PEOPLES’ FRIENDSHIP MEDICAL UNIVERSITY
DEPARTMENT OF INTERNAL MEDICINE NO:2
Presented by:
Dinoosh De Livera
5th Course
Group 49
International Students’ Faculty
VSMU

2. What is a Lymphoma? Definition.
 Clonal proliferation of lymphoid cells of various degree of maturity, within a
single organ.
 Cancer of the lymphatic system.
 They maybe:
o Nodal – 2/3 of lymphomas which arise from lymph nodes
o Extranodal – Spleen, skin, stomach, intestine, mediastinum, brain

3. Classification of Lymphomas
 Main types:
1. Hodgkin lymphoma
2. Non Hodgkin lymphoma
 B-cell lymphoma
 T-cell lymphoma
3. Other

4. Hodgkin’s Lymphoma (HL)
Definition: lymphoid malignant tumor characterized by the presence of
multinucleated giant cells (Reed- Sternberg) and their mononuclear analogues
(Hodgkin's cells).
 Malignant process of lymphoreticular system
 6% of pediatric cancer
 5% of cancer in < 14 yr
 15% in person 15-19 yr
 Rare < 10 yr
 Accounts for ~ 30% of all malignant lymphomas
 Composed of two different disease entities:
1) Lymphocyte-predominant Hodgkin’s (LPHL)~ 5% of cases
2) Classical HL ~ 95% of all HLs

5. Definition of HL
Definition:
A neoplastic transformation of lymphocytes particularly in
lymph nodes.
Characterized by:
1) the presence of Reed-Sternberg cells on histology
2) spreading in an orderly fashion to contagious lymph nodes
( For example, Hodgkin lymphoma that starts in the cervical lymph nodes
may spread first to the supraclavicular nodes then to the axillary nodes )

6. Reed-Sternberg cells
Hallmark of disease
Cells with mirror image nuclei
and prominent,
eosinophilic,
inclusion-like nuclei. Reed –Sternberg cell
Large (15-45 m) multiple / multi-lobulated nuclei
Colonal in origin
Arises from germinal center B cells

7. Histological / Rye Classification of HL
1) Nodular lymphocyte predominance Hodgkin's
lymphoma
2) Classical Hodgkin's lymphoma
 Nodular sclerosis Hodgkin's lymphoma
 Lymphocyte-rich classical Hodgkin's lymphoma
 Mixed cellularity Hodgkin's lymphoma
 Lymphocyte depletion Hodgkin's lymphoma

8. Histology
 Lymphocyte-predominant has the Best
prognosis.
 Lymphocyte-depleted has the Worst
prognosis.

9. Ann-Arbor Staging of HL / Clinical Classification
I - Lymph nodes in one region or a single organ or site.
II - Lymph nodes of two or more regions on one side of the diaphragm (above or below).
III – Involvement groups of lymph nodes on both sides of the diaphragm, including the spleen.
IV - Multiple and disseminated involvement of extralymphatic organs and tissues, such as liver or
bone marrow.

10. Epidemiology
 Bimodal incidence
 Early peak middle to late 20s
 Second peak after 50 yr
 Sex Male : Female
4: 1 for 3-7 yr
3: 1 for 7-9 yr
1-3: 1 for > 10 yr
 100 folds risk for unaffected monozygotic twin of affected twin
 Associated with specific HLA antigen
 Infectious agents
-Human herpes virus 6
-CMV
-Epstein – Barr virus
 Immunodeficiency

11. Etiological Factors
1) Certain viruses:
 Epstein-Barr virus (EBV)
 Human immunodeficiency virus (HIV)
2) Weakened immune system:
 inherited condition
 certain drugs used after an organ transplant
3) Age:
 Hodgkin lymphoma is most common among teens and adults aged 15 to 35 years and adults
aged 55 years and older.
4) Family history:
 Family members, especially brothers and sisters, of a person with Hodgkin lymphoma or
other lymphomas may have an increased chance of developing this disease.

12. Clinical Presentation
General Symptoms Local Symptoms
Observed almost every third
patient LH.
These include: fever, sweating,
especially at night, weakness,
fatigue, weight loss, itchy skin,
headaches, pain in the bones
and joints.
Due to location and size of the
affected lymph nodes and
other lesions in various organs
and tissues.

13. Clinical Presentation
 Enlarged, painless, rubbery, non- erythematous, nontender lymph nodes are the
hallmark of the disease.
 May become painful after drinking alcohol
 Patients may develop ‘’B’’ symptoms (Systemic symptoms) which are:
# Drenching night sweats (Diaphoresis)
# 10% weight loss
# Fever
 25% have ''B'' symptoms
 Although pruritus is common in the disease it is not one of the ‘’B’’ symptoms.
 Cervical, supraclavicular and axillary lymphadenopathy are the most common
initial signs of the disease.

14. Clinical Presentation
 Lymphadenopathy cervical / supraclavicular
 Painless, non tender, firm and rubbery
 Hepatosplenomegaly
 Cough, dyspnea, hypoxia
 Pleural or pericardial effusion
 Heptocellular dysfunction
 B.M infiltration
(Anemia, neutropenia, thrombocytopenia)
 Disease below diaphragm is rare (only3%)’
Emergency presentation:
 Infections
 SVC obstruction ( facial edema, increased JVP and Dyspnea)
Mediastinal Mass in Hodgkins Disease

15. Systemic Symptoms (B Symptoms)
 Important in staging
 Unexplained fever > 390C
 Weight loss > 10% in 3m
 Drenching night sweats
Immune System abnormalities
 Anergy to delayed-hypersensitivity skin test
 Abnormal cellular immune response
 Decreased CD4:CD8 ratio
 Reduce natural killer cell cytotoxicity

16. Clinical Presentation
 Extralymphatic sites may be involved such as:
# Spleen
# Liver
# Bone marrow
# Lung
# CNS
 Extralymphatic involvement is more common with non-hodgkin lymphoma.
 Lymph nodes above the diaphragm is found in nearly 90% of cases and only 10% of patients the
changes observed in the lymph podtsiafragmalnyh collectors.
 The disease often begins with increasing the nodes in the neck - in 50-75% of all cases.
 Affected lymph nodes have elastic consistency, not fused with each other and with the underlying
tissues, their palpation painless. The skin over the tumor conglomerate is not changed, not
hyperemic and infiltrated

17. Cervical
Lymph node
Involvement

18. Diagnostic Procedures
 Excisional Biopsy
 Light Microscopy
 Immunocytochemistry
 Molecular Studies
 Chest X – Ray
 Mediastinal Mass
 CT Scan
 Chest
 Abdomen
 Pelvis
 Blood CP & ESR
 LFT’s
 Bone Marrow Aspiration
 Serum Copper & Ferritin
 Bone Scan
 Gallium 67 Scan / FDG/PET Mediastinal Mass in Hodgkins Disease

19. Diagnosis
 An excisional lymph node biopsy is the essential first step
in diagnosis.
 A biopsy is the only sure way to diagnose Hodgkin lymphoma. The
biopsy can be:
1) Excisional biopsy
2) Incisional biopsy
3) Fine needle aspiration usually cannot remove a large enough
sample for the pathologist to diagnose Hodgkin lymphoma.
 After that the most important step is to determine the
extent of the disease because the stage will determine the
nature of the therapy, that is, radiation vs. chemotherapy

20. Investigations used for staging
 Chest x-ray : X-ray pictures may show swollen lymph nodes or other
signs of disease in the chest .
 CT: Chest, abdomen and pelvis ( CT is sensitive enough to detect
any abnormal nodes)
 MRI
 PET scan
 LP for CSF cytology if any CNS signs
 Lymphangiography and laparotomy are no longer used for
staging.
 A bone marrow biopsy is used when :
1) B symptoms
2) Stage3 or 4

21. Abnormal lab tests ( don’t alter the stage of the disease)
 CBC: anemia and high WBC ( Eosinophilia is common)
 LDH: high ( poor prognostic factor)
 ESR: high ( poor prognostic factor)
 LFTs: help determine the need for liver biopsy

22.  After lymphoma is diagnosed, a variety of tests may be
carried out to look for specific features characteristic of
different types of lymphoma. These include:
1) Immunophenotyping
2) Flow cytometry
3) FISH testing.
 The classification of lymphoma can affect treatment and prognosis.
 Classification systems generally classify lymphoma
according to:
1) Whether or not it is a Hodgkin lymphoma.
2) Whether the cell that is replicating is a T cell or B cell.
3) The site that the cell arises from.

23. Treatment
 Treatment depends on :
 Stage of the disease
 Age at diagnosis
 Presence / absence of B symptoms
 Presence of hilar lymphadenopathy
 Presence of bulky nodal disease
 Current Treatment Regimen
 Combined chemotherapy with or without low dose involved field radiation therapy

24. Chemotherapy Regimens
 MOPP
(Mechlorethamine , Vincristine , Procarbazine , Prednisolone)
 COPP
(Cyclophosphamide , Vincristine , Procarbazine , Prednisolone)
 ABVD
(Adriamycin , Bleomycin , Vinblastine , Dacarbazine)
 BEACOPP ( For advanced stage disease )
(Bleomycin , Etoposide , Doxorubicin , Cyclophosphamide , Vincristine ,
Procarbazine , Prednisolone)

25. For patients with favorable and intermediate prognosis standard chemotherapy scheme is ABVD,
and for the treatment of patients with poor prognosis - BEACOPP scheme.
The interval between courses - 2 weeks.
Start following cycle - on the 15th day after the last administration of chemotherapy.
ABVD Scheme ВЕАСОРР Scheme
1) Doxorubicin -
25 mg / m2 intravenously 1st and 14th days.
2) Bleomycin -
10 mg / m2 intravenously 1st and 14th days.
3) Vinblastine -
6 mg / intravenous 1st and 14th days.
4) Dacarbazine
- 375 mg / m2 intravenously 1st and 14th days
1) Cyclophosphamide -
650 mg / m2 / in 1 day.
2) Doxorubicin -
25 mg / m2 / in 1 day.
3) Etoposide -
100 mg / m2 / in the 1st and 2nd, 3rd days.
4) Procarbazine
- 100 mg / m2 inwardly on days 1-7.
5) Prednisolone
- 40 mg / m2 inwardly 1-14 days.
6) Vincristine
- 1.4 mg / m2 / in the 8th day.
7) Bleomycin -
10 mg / m2 / in the 8th day.

26. Treatment
 Therapy is entirely based on the stage.
 Localized disease ( stage IA and IIA ) is managed predominantly with radiation.
 All patients with evidence of ‘’B’’ symptoms as well as stage III and IV are managed with
chemotherapy.
 The most effective combination chemotherapeutic regimen for Hodgkin lymphoma is ABVD
(adriamycin, bleomycin, vinblastin and dacarbazine).
 ABVD is superior to MOP (meclorethamine, vincristin, prednisolone and procarbazine)
because ABVD has fewer side effects such as:
1) Permanent sterility
2) Secondary cancer formation
3) Aplastic anemia
4) Peripheral neuropathy

27. Hodgkin’s Lymphoma – Management Algorithm
BIOPSY
Tissue
STAGING
CT/PET
PROGNOSTIC
FACTORS
EARLY STAGE
(Favourable)
ABVD (3) +
IFRT
EARLY STAGE
(Unfavourable)
ABVD (6) +
IFRT
ADVANCED
STAGE
(Favourable)
ABVD (6 – 8)
ADVANCED
STAGE
(Unfavourable)
BEACOPP (6-8)

28. Longterm Complications
 Secondary malignancy
 Acute Myelogenous Leukemia
 Non Hodgkin lymphoma
 Carcinomas of breast , lungs & thyroid
 Short stature
 Hypothyroidism
 Sterility
 Dental caries
 Sub clinical pulmonary dysfunction
 Ischemic heart disease

29. International Prognostic Index
 The International Prognostic Index (IPI) was first developed to help doctors determine
the prognosis for people with fast-growing lymphomas. The index depends on 5 factors:
1) The patient’s age
2) The stage of the lymphoma
3) Whether or not the lymphoma is in organs outside the lymph system
4) Performance status (PS) – how well a person can complete normal daily activities
5) The blood (serum) level of (LDH)

31. Prognostic Score for Advanced HD
Hasenclever et al, NEJM 1998
7 independent prognostic factors
 Albumin < 40g/l
 Hb < 10.5g/dl
 Male
 > 45 y.o.
 Ann Arbor stage IV
 WCC > 15 x 10 /l
 Lymphopaenia <0.6 x10 /l or < 8 % total WCC
9

32. Prognosis
 Early Stage Disease
 5 year survival ….95%
 Advanced Stage Disease
 5 year survival ….90%
 Relapses common within first 3 years from diagnosis
 Relapses treated with Autologous Stem Cell Transplantation

33. Non-Hodgkins Lymphoma (NHL)
Definition:
Neoplastic transformation of either B or T cell lineages of lymphatic cells, in which
the histogenic source of which are the cells of lymphoid germ hematopoiesis.
 NHL causes the accumulation of neoplastic cells in both the lymph nodes as well
as more often diffusely in extralymphatic organs and the bloodstream.
 Absent reed-Sternberg cells.

34. Classification of Cellular Neoplasias
I. B-cell tumors:
B-lymphoblastic lymphoma (Leukemia) from precursor cells (B-cell acute lymphoblastic leukemia
cells from precursor).
II. B-cell tumor of the peripheral (mature) cells:
1) B-cell chronic lymphocytic leukemia (lymphoma), small lymphocytic
2) plasma cell myeloma (plasmacytoma)
3) extranodal B-cell lymphoma, marginal zone of MALT-type
4) follicular lymphoma
5) lymphoma, mantle cell
6) diffuse large cell lymphoma
7) lymphoma (leukemia) Burkitt

35. III. T and NK-cell tumors:
1) from T-cell precursors
2) T-cell lymphoma from peripheral (mature) cells
3) Mycosis fungoides (Sezary syndrome)
4) Peripheral T-cell lymphoma, unspecified

36. Pathological Sub-types of NHL
 Burkitt Lymphoma
40% of NHL
B Cell Origin
 Lymphoblastic Lymphoma
30% of NHL
80% T Cell Origin & 20% B Cell Origin
 Diffuse Large B Cell Lymphoma
20% of NHL
B Cell Origin
 Anaplastic Large Cell Lymphoma
10% of NHL
70% T Cell Origin

37. Burkitt Lymphoma

38. Epidemeology
• 60% of all lymphomas in children
• 8-10% of all malignancies in children between 5-19 yrs of age
• Secondary causes of NHL include;
• Inherited / acquired immune deficiencies
• Viruses
• HIV
• EBV
• Genetic Syndromes
• Ataxia Telangiectasia
• Bloom syndrome

39. Risk factors
INFECTIONS:
 Human immunodeficiency virus (HIV)
 Epstein-Barr virus (EBV): linked to Burkitt lymphoma.
 Helicobacter pylori: Extranodal tissues generating lymphoma
include MALT ( Mucosa associated lymphoid tissue)
 Human T-cell leukemia/lymphoma virus( HTLV-1)
 Hepatitis C virus
Age:
Most people with non-Hodgkin lymphoma are older than 60.

40. Clinical Presentation
Clinical presentation is the same as for Hodgkin lymphoma.
 The difference is that Hodgkin is localized to cervical and
supraclavicular nodes 80%-90% of the time. Whereas NHL
is localized 10-20% of the time.
 CNS involvement is more common with NHL.
 HIV positive patients often have CNS involvement.

41. Clinical Presentation
 Burkitt Lymphoma
 Abdominal Tumor
 Head & Neck Disease
 Involvement of bone marrow & CNS
 Lymphoblastic Lymphoma
 Intrathoracic / mediastinal supradiaphragmatic mass
 Involvement of bone marrow & CNS
 Diffuse Large B Cell Lymphoma
 Abdominal Mass
 Mediastinal Mass
 Anaplastic Large Cell Lymphoma
 Primary cutaneous manifestation
 Systemic disease ( fever , weight loss)
 Dissemination to liver , spleen , lung , mediastinum & skin

42. Clinical Presentation
 Other clinical features include;
 Lymphadenopathy
 Superior vena cava syndrome
 Dyspnea
 Abdominal Mass
 Intestinal obstruction / intussusception
 Ascites
 Nasal Stuffiness
 Earache
 Tonsil enlargement
 Localised bone involvement
 Acute paraplegia secondary to CNS / spinal cord compression
 Tumor Lysis Syndrome

43. Staging and diagnosis
Staging and Diagnosis are the same as for Hodgkin lymphoma.
Differences:
 Bone marrow biopsy is more central in the initial staging of NHL
 Because the presence of bone marrow involvement means the patient
has stage IV disaese and therefore needs combination chemotherapy,
further invasive testing such as laparotomy is not required.

44. Staging system for childhood NHL
Stage Description
I A single tumor (extranodal) or single anatomic area (nodal) with the exclusion of
mediastinum or abdomen
II A single tumor (extranodal) with regional node involvement
two or more nodes areas on the same side of diaphragm
Two single (extranodal) tumors with or without the regional node involvement on
same side of diaphragm
A primary gastrointestinal tract tumor usually in the ileocecal area, with or without
involvement of associated mesenteric nodes, must be grossly ( > 90%) resected
III Two single tumors (extranodal) on opposite side of the diaphragm
Two more nodal areas above and below the diaphragm
Any primary intarthoracic tumor (mediastinal, pleural, or thymic)
Any extensive primary intra – abdominal disease
IV Any of the above, with initial involvement of central nervous system or bone marrow at time of diagnosis

45. Grades
 NHL divided into Low or high grade
 A high grade lymphoma has cells which look quite different from
normal cells.
They tend to grow fast (aggressive).usually look follicular. Incurable.
Wider dissemination at presentation.
 Low grade lymphomas have cells which look much like normal cells
and multiply slowly(indolent).usually look diffuse. Long term
treatment maybe achievable.

46. Low-grade lymphomas
 Many low-grade lymphomas remain indolent for many years.
 Treatment of the non-symptomatic patient is often Avoided.
 In this case watchful waiting is often the initial course of action.
This is carried out because the harms and risks of treatment
outweigh the benefits.
 If a low-grade lymphoma is becoming symptomatic, radiotherapy
or chemotherapy are the treatments of choice.
 They don’t cure the lymphoma, they can alleviate the symptoms.
 Patients with these types of lymphoma can live near-normal
lifespans, but the disease is Incurable.

47. High-grade lymphomas
 Treatment of the aggressive, forms of lymphoma can result in a
cure in the majority of cases.
 However, the prognosis for patients with a poor response to
therapy is worse.
 Treatment for these types of lymphoma typically consists of
aggressive chemotherapy, including the CHOP or R-CHOP
regimen.

48. Differential Diagnosis
 Hodgkin Disease
 Leukemia
 Germ Cell Tumor
 Wilms Tumor
 Neuroblastoma
 Rhabdomyosarcoma
 Reactive lymphadenitis

49. Laboratory Findings
• Tissue biopsy for;
• Flow cytometry
• Karyotyping
• Complete Blood Count
• Serum Electrolytes, Calcium , Phosphorus , Uric acid
• LFT’s & RFT’s
• Bone Marrow Aspiration & Biopsy
• CSF Examination
• Chest X Ray
• CT Scan
• Head & Neck
• Chest
• Abdomen & Pelvis
• PET Scan & Bone Scan

50. Treatment
 Systemic Chemotherapy
 Intrathecal chemotherapy
 Radiotherapy indicated in ;
 CNS Disease
 SVC Syndrome
 Paraplegia

51. Chemotherapy Regimens
 COPAD
(Cyclophosphamide , Vincristinr , Prednisolone , Doxorubicin)
 COMP
(Cyclophosphamide , Vincristine , Methotrexate , 6 Mercaptopurine ,
Prednisolone)
Duration:
 Burkitt Lymphoma & Diffuse Large B Cell Lymphoma 6 weeks to 6 months
 Lymphoblastic Lymphoma 24 months

52. Supportive Treatment
 G-CSF prophylaxis for fever & neutropenia
 Antibiotic prophylaxis
 Blood & platelet transfusions
 Allopurinol
 Parenteral nutrition

53. Complications
 Infections
 Mucositis
 Pancytopenia
 Electrolyte imbalance
 Poor nutrition
 Growth retardation
 Cardiac Toxicity
 Gonadal Toxicity with Infertility
 Secondary malignancies

59. Thank you for your attention!
Questions?