This document discusses lymphoma, including:
1. Lymphoma is a cancer of lymphocytes that develops in lymphatic tissue. There are two main types: Hodgkin's lymphoma and non-Hodgkin's lymphoma.
2. Hodgkin's lymphoma is characterized by Reed-Sternberg cells and has several subtypes. Non-Hodgkin's lymphoma is more common and includes over 60 subtypes.
3. The document covers epidemiology, risk factors, clinical presentation, diagnostic process, staging, treatment and prognosis for both Hodgkin's and non-Hodgkin's lymphomas. Treatment involves chemotherapy, radiation therapy, immunotherapy or stem cell transplantation depending on the lymphoma subtype and stage.
2. Learning Objectives
1. What is a Lymphoma?
2. Types of Lymphomas
3. Different subtypes of Lymphomas
4. Epidemiology of Lymphomas
5. Stages of Lymphomas
6. Signs and symptoms of Lymphomas
7. Diagnosis of Lymphomas
8. Treatment of Lymphomas
9. Prognosis of Lymphomas
3. Introduction
What is a Lymphoma?
Lymphoma is a group of blood cell tumors that develop from lymphocytes. These
are malignant tumors of lymphoid tissue origin, that result in proliferation of
lymphocytes.
Types of lymphoid tissue
1. Primary (central) lymphoid tissue: Where lymphoid precursor cells mature and
proliferate, this include bone marrow and thymus.
2. Secondary (peripheral) lymphoid tissue: Where antigen specific reactions take
place, this include the spleen, lymph nodes and mucosa associated lymphoid
tissues.
Types of Lymphomas
1. Hodgkin’s Lymphoma (85%)
2. Non-hodgkin‘s Lymphoma (15%)
4. Hodgkin’s Lymphoma
Named after Dr Thomas Hodgkin (1832). He noted a peculiar trend of tumors
in lymph nodes.
This is a localized or disseminated malignant proliferation of lymphoid cells in
the lymphoreticular system, affecting the liver, spleen, lymph nodes and the
bone marrow.
This is characterized by the presence of Reed Sternberg giant cells.
Hodgkin’s lymphoma usually arises from a single lymph node, or a chain of
nodes, and typically follows a contiguous spread.
There are two subtypes of Hodgkin’s Lymphoma:
1. Classical Hodgkin’s lymphoma
2. Lymphocyte predominant Hodgkin’s lymphoma
5. Epidemiology
Hodgkin’s lymphoma has male to female ratio of 1.4:1
It is bimodal, 1st peak incidence between 15-40 years, 2nd peak incidence
after 60 years of age. These tumors are rarely seen before 10 years of age.
According to the Global Cancer Observatory under WHO, Hodgkin’s Lymphoma
accounts to 1.3% of new cancer diagnosis, and 0.85% of cancer related deaths
as of 2018.
6. Etiology and Risk factors
Ebstein-Barr Virus infection
Age (between 15-40 years and after 60 years)
Gender (male to female ratio 1.4:1)
Family history (siblings are at increased risk)
Immunodeficiency (eg.HIV positive individuals and people on
immunosuppressive therapy)
Socioeconomic status (more common in individuals with a higher SES)
Geography (common in North America and northern Europe)
7. Classification of Hodgkin’s lymphoma
Based on morphology, immunophenotype, clinical features, genotype and
reactive cellular infiltrates as seen on lymph node dissection and biopsy:
1. Nodular sclerosis (most common, has good prognosis)
2. Mixed cellularity (2nd most common)
3. Lymphocyte rich (rare, but has good prognosis)
4. Lymphocyte depletion (associated with HIV positive individuals, has the worst
prognosis)
5. Lymphocyte predominant (common in young males, usually localized)
8. Clinical features
Asymptomatic
Painless lymphadenopathy (one or more nodes)
Pain associated with alcohol consumption
Splenomegaly
Hepatomegaly
Presence of B symptoms
- Significant fever
- Drenching night sweats
- Unexplained weight loss (>10% of body weight)
Other symptoms: Pruritus, fatigue, weakness, coughing, flushing of the face
9. Staging of Hodgkin’s Lymphoma
Ann Arbor Staging Classification
Stage I: Involvement of a single lymph node, or Involvement of a single extra
lymphatic organ or tissue.
Stage II: Involvement of two or more lymph nodes on the same side of the
diaphragm or involvement limited contiguous extra lymphatic tissue or organ.
Stage III: Involvement of lymph nodes on both sides of the diaphragm, which may
include the spleen, or limited contiguous extralymphatic tissue or organ or both.
Stage IV: Multiple or extralymphatic foci of involvement of one or more
extralymphatic organ or tissue or without lymphatic involvement.
Note:Each stage includes A (absence), and B (presence) of B symptoms.
10. Diagnosis
From history (B symptoms)
Examination (Lymphadenopathy)
Lymph node biopsy (microscopic examination)
Presence of Reed Sternberg cells (giant cells 15-45 um, multilobate nucleus,
prominent nucleoli, slightly eosinophilic cytoplasm) outnumbered by non-
neoplastic inflammatory cells (lymphocytes, eosinophils, and plasma cells).
Reed Sternberg cells are infected by EBV in 50% of the cases.
Imaging modalities: X-ray chest, CT scan of chest and abdomen (HL rarely
below diaphragm) and PET scan for staging.
11. Treatment
Based on the subtypes, the clinical stage of the tumor.
Early disease: Radiotherapy or chemotherapy.
Local therapy with radiotherapy following chemotherapy can control the
tumor and
provide a better outcome.
Large mass in the chest benefits from combination therapy of chemotherapy
and radiotherapy, as well as stem cell transplantation.
Chemotherapy combinations:
- ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine)
- MOPP (Mustin, Oncovin, Procarbazine, Prednisone)
• ABVD is the treatment of choice for both early and advanced disease.
These medications can cause neutropenias, acute leukemias, and
cardiovascular disorders.
12. Prognosis
Patients with stage I and stage II, 5 year survival rate is 95% .
Patients with stage III and stage IV,II year survival rate is 90%.
Relapse is common with the first 3 years from time of diagnosis. This can be
treated with autologous stem cell transplantation.
There are 4 prognostic groups
1. Early favorable disease (stage I and stage II)
2. Early unfavorable disease (stage I and stage II)
3. Advanced favorable disease
4. Advanced unfavorable disease
Bad prognostic indicators in early disease: large mediastinal mass, high ESR >
50, extranodal disease > 3 nodal sites, and presence of B symptoms.
Bad prognostic indicators in advanced disease: age >45 years of age, male,
stage IV, WBC >15000 cells/mm3, and lymphocytes <600 cells/mm3.
13. Non-hodgkin’s Lymphoma
This is a group of blood cancers that include all types of lymphomas except
Hodgkin’s Lymphoma.
There is a neoplastic transformation of either B or T cell lineages of the
lymphatic cells.
This causes the accumulation of neoplastic cells in both the lymph nodes as
well as often diffusely in the extralymphatic organs and the bloodstream.
Non-hodgkin’s lymphoma has absent Reed Sternberg cells.
These tumors are caused by chromosomal translocation, chronic
inflammation, infections, environmental factors and immunodeficiency.
14. Epidemiology
Common in males
Common after >60 years of age (median age of 65-75)
According to Global Cancer Observatory, it accounts for 5.5% of newly
diagnosed cancers, and 5.2% of cancer related deaths in Zambia.
85% are derived from B lymphocytes, with 15% from T lymphocytes.
15. Etiology and Risk factors
Infections with EBV, HIV, HHV8, Helicobacter pylori, Hepatitis C virus, HTLV.
Patients treated with radiotherapy for some other cancers
Immunodeficiency (HIV positive individuals)
Individuals on immunosuppressive therapies.
Age (risk increases with age, >60 years and older)
Autoimmune disorders (SLE)
Family history (first degree relatives)
16. Classification of Non-Hodgkin’s Lymphoma
B-cell NHL
1. Precursor B-cell neoplasms (neoplasms of immature B cells)
Precursor B lymphoblastic leukemia/Lymphoma
2. Peripheral B-cell neoplasms (neoplasms of mature B cells)
B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
Lymphoma of mucosa associated lymphoid tissue (MALT)
Follicular lymphoma
Mantle cell lymphoma
Diffuse large cell B cell lymphoma
Burkitt’s lymphoma
17. Classification continued
T cell NHL
1. Precursor T cell neoplasms (neoplasms of immature T cells)
Precursor T lymphoblastic lymphoma/Leukemia
2. Peripheral T cell and NK cell neoplasms (neoplasms of T cells and NK cells)
Adult T cell lymphoma/Leukemia
Mycosis fungiodes/Sezary’s syndrome
Peripheral T cell Lymphoma
Anaplastic large cell lymphoma, T/null cell, Primary systemic type
18. Grading of Non-Hodgkin’s Lymphoma
Low grade (indolent)
This is slow growing
Has waxing and weaning symptoms
Comprises 25-35% of NHL
Not curable, but has median survival of 10 years
Usually from B cells
Females more affected
Common among elderly people
This can transform into a more aggressive form
E.g of low grade include follicular lymphoma
19. Grading continued
High grade (aggressive)
This is fast growing
Comprises of 60-75% of NHL
30-60% of the cases are curable
Can arise from B cells or T cells
All ages affected, but common after >70 years of age
Usually with extranodal involvement
E.g include Diffuse large B cell lymphoma
20. Grading continued
Highly aggressive
This progresses very rapidly
Potentially curable
Usually metastases to the CNS
Usually seen in <45 years of age, 50% of the cases
Common in malaria prone regions
E.g Burkitt’s lymphoma, Lymphoblastic lymphoma
21. Clinical features
Similar to Hodgkin’s Lymphoma
10-20% of cases are localized
CNS involvement is common
Burkitt’s Lymphoma
Can affect the head and neck region, the abdomen, as well as the bone
marrow and CNS.
Lymphoblastic Lymphoma
Causes intrathoracic and mediastinal supradiaphragmatic mass, with
involvement of the bone marrow and CNS
Diffuse Large B cell Lymphoma
Presents as abdominal and mediastinal mass
Anaplastic Large Cell Lymphoma
This presents as cutaneous manifestations, with systemic disease causing
fever, weight loss and involvement of the liver, spleen, lungs.
22. Clinical features continued
Lymphadenopathy
Superior vena cava syndrome
Intestinal obstruction
Dyspnea
Ascites
Tonsilar enlargement
Nasal stuffiness
Tumor lysis syndrome
23. Staging of Non-Hodgkin’s Lymphoma
Ann Arbor Staging Classification
Stage I: Involvement of a single lymph node, or Involvement of a single extra
lymphatic organ or tissue.
Stage II: Involvement of two or more lymph nodes on the same side of the
diaphragm or involvement limited contiguous extra lymphatic tissue or organ.
Stage III: Involvement of lymph nodes on both sides of the diaphragm, which may
include the spleen, or limited contiguous extralymphatic tissue or organ or both.
Stage IV: Multiple or extralymphatic foci of involvement of one or more
extralymphatic organ or tissue or without lymphatic involvement.
Note:Each stage includes A (absence), and B (presence) of B symptoms.
24. Diagnosis
History (presence of B symptoms)
Physical examination (lympadenopathy)
Lymph node biopsy
Karyotyping
Serum electrolytes, urine tests, and blood tests (rule out infections)
LFTs, and RFTs
Bone marrow aspiration and biopsy
CSF analysis
Imaging modalities: X-ray chest, CT scan head and neck, chest and pelvis, as
well as PET scan for staging
26. Treatment of Non-Hodgkin’s Lymphoma
Based on grading of the tumor
Indolent;
If the patient is asymptomatic-
Watch and waitIf the patient is symptomatic-
- Stage 1 & Stage 2: treat with radiation therapy (chemotherapy may be useful
in high risk stage 2 disease e.g multiple site involvement).
-Stage 3 & 4:
i. oral therapy (akylating agent +/- Prednisolone)
ii. IV chemotherapy;
CVP regime: Cyclophosphamide + Vincristine + Prednisone
CHOP regime: CVP + Doxorubicine (if rapid response is necessary)
iii. Immunothearpy (Rituximab)
27. Treatment continued
Iv. Purine Analogs (Fludrabine)
Don’t cause nausea, vomiting or hairlossCan be used in refractory/relapse
advanced follicular lymphoma
V. Radiotherapy can also be used in relapse.
Aggressive Lymphoma
R-CHOP (6 cycles) +/- radiotherapy
If refractory or relapse
DHAP: dexamethasone, cytarabine, cisplatin
MINE: mesna, iflosamide, mitoxantrone, eptoposide
ICE: Ifosfomide, carboplatin, etoposide
Combined with Rituximab
28. Treatment continued
Highly aggressive Lymphoma;
Regimen should include CNS prophylaxis: such as intrathecal
methotrexate/cytarabine
R-CHOP may not be enough for intensive treatment
As such the best treatment;- Cyclophosphamide, vincristine, doxorubicin,
dexamethasone - or high dose Methotrexate & cytarabine
Complications of treatment
Infections
Mucositis
Pancytopenia
Electrolyte imbalance
Poor nutrition
Growth retardation
Cardiac toxicit
yGonodal toxicity with infertility
Secondary malignancies
29. Prognosis
Survival rates vary widely.
Overall 5-year survival rate is 63%
The 10-year survival rate is 51%
Survival rates have improved due to advances in treatment.
