Non-Hodgkin's Lymphoma Flashcards
Is NHL common?
Relatively
How many cases of NHL are there per year in the UK?
7500
Which gender is NHL more common in?
Men
What is the median age of presentation for all subtypes of NHL?
50 years
What are the most common types of NHL seen in children and young adults?
- High-grade lymphoblastic
- Small non-cleaved cell
Are low grade NHL more common in the young or old?
Old (37% of cases in 35-64, but 16% of cases below 35)
What appears to influence the development of NHL in specific areas?
Certain geographical factors
What kind of NHLs are affected by certain endemic geographical factors?
- Human T-cell lymphotrophic virus-1 (HLTV-1)-associated lymphoma/leukaemia
- Burkitt’s lymphoma
- Follicular lymphoma
- Peripheral T-cell lymphoma
Where does HLTV-1-associated T cell lymphoma/leukaemia occur most frequently?
- Japan
- Caribbean
Where is Burkitt’s lymphoma more common?
Africa, particularly Nigeria and Tanzania
Describe the geographical distribution of follicular lymphoma?
More common in North America and Europe, but rare in Caribbean, Africa, China, Japan, and Middle East
Describe the geographical distribution of peripheral T-cell lymphoma?
More common in Europe and China
In whom is there a significantly higher incidence of primary CNS lymphoma?
Patients with HIV infection and immunosuppression
What is important in the pathogenesis of NHL?
Non-random chromosomal and molecular rearrangements
What does the chromosomal and molecular rearrangements in NGL correspond with?
The immunophenotype
What is the most common chromosomal finding in NHL?
t(14;18)(q32;q21) translocation
What does t(14;18)(q32;q21) translocation produce?
A juxtaposition of the BCL2 apoptoptic inhibitor oncogene to the heavy-chain region of the immunoglobulin locus
What NHL is t(14;18)(q32;q21) translocation most common in?
- Follicular lymphoma (85% of cases have this mutation)
- High grade tumours (28% have it)
What chromosomal abnormality is associated with mantle cell lymphoma?
t(11;14)(q13;q32)
What does the t(11;14)(q13;q32) translocation result in?
Over-expression of BCL1
What is BCL1?
A cell cycle control gene on chromosome 11q13
What chromosomal abnormality is frequently seen in high-grade small non-cleaved cell lymphomas?
Chromosomal translocations involving 8q24
What do chromosomal translocations involving 8q24 lead to?
c-myc deregulation
What viruses have been implicated in the pathogenesis of NHL?
- EBV
- HTLV-1
- HCV
What type of NHL is EBV associated with?
Burkitts lymphoma
What kind of NHL is HTLV-1 associated with?
Adult T-cell leukaemia/lymphoma
How does HCV increase the risk of NHL?
It predisposes B cells to malignant transformation by enhancing signal transduction in binding to CD81
What is the classic presentation of NHL?
- Systemic B symptoms
- Fatigue
- Weakness
What are systemic B symptoms?
- Fever
- Weight loss
- Night sweats
At what stage can the classical presentation of NHL occur?
More common in intermediate- and high grade tumours, but may be present in all stages and tumour subtypes
How can low-grade NHL present?
Painless, slowly progressive peripheral lymphadenopathy, which sometimes waxes and wanes
Can spontaneous regression of enlarged lymph nodes occur in low-grade NHL?
Yes
What is the problem with spontaneous regression of enlarged lymph nodes in low-grade NHL?
Can confuse low-grade NHL with infectious conditions
What features are uncommon at presentation in low-grade NHL?
- Primary extranodal involvement
- B symptoms
Is the bone marrow involved in low-grade NHL?
Frequently is
What might the bone marrow involvement be associated with in low-grade NHL?
Pancytopenia
What % of patients with low-grade NHL have splenomegaly?
About 40%
How does the presentation of intermediate and high grade NHL differ from low grade?
Presents in a more varied manner
What do the majority of patients with intermediate or high grade NHL present with?
Lymphadenopathy
What % of cases of intermediate or high grade NHL have extra-nodal involvement?
40%
What are the most common sites of extra-nodal involvement in intermediate or high grade NHL?
- GI tract (stomach and small intestine)
- Skin
- Bone marrow
- Sinuses
- Oral cavity
- GU tract
- Thyroid
- CNS
What % of patients with intermediate or high grade NHL have B symptoms?
40%
How does lymphoblastic lymphoma often present?
- Anterior superior mediastinal mas
- SVC obstruction
- Leptomeningeal disease with cranial nerve palsies
How do patients with Burkitt’s lymphoma present?
Large abdominal mass and symptoms of bowel obstruction
What investigations may be done in NHL?
- Careful history and examination
- Histological evaluation
- Imaging
- Bloods
- Cytogenetic and molecular analyses
- Examination of CSF
What is histologically evaluated in NHL?
- Affected lymph nodes
- Bone marrow
How is the affected lymph node tissue for histological evaluation acquired?
Excision biopsy of affected lymph node
How is bone marrow for histological evaluation acquired?
Aspiration and triphine
What imaging may be done in NHL?
- CXR
- CT of chest and abdomen
- Bone scan
- PET
What is looked for on CXR in NHL?
- Mediastinal or hilar lymphadenopathy
- Pleural effusions
- Parenchymal lesions
What is looked for on CT of chest and abdomen in NHL?
- Mediastinal, hilar, or parenchymal pulmonary disease
- Para-aortic or mesenteric lymph nodes
- Splenomegaly
- Filling defects in liver and spleen
When is bone scan indicated in NHL?
If there are MSK symptoms or an elevated alkaline phosphatase
What is PET imaging used for in NHL?
Determine stage and extent of disease involvement
What bloods should be done in NHL?
FBC with differential, serum biochemistry, LDH, and ß2 macroglobulin
When should HIV serology be considered in NHL?
In patients with diffuse large cell, immunoblastic, and small non-cleaved-cell histology
When should HTLV-1 serology be considered in NHL?
In patients with cutaneous T-cell lymphoma, particularly if they have hypercalcaemia
What tissues might cytogenetic and molecular analysis be performed on in NHL?
- Lymph node
- Bone marrow
- Peripheral blood
When is examination of the CSF required in NHL?
- Diffuse aggressive NHL with bone marrow, epidural, testicular, paranasal sinus, or nasopharyngeal involvement
- High-grade lymphoblastic lymphoma and small non-cleaved cell lymphomas
- HIV-related lymphoma
- Primary CNS lymphoma
What are the types of small non-cleaved cell lymphomas?
Burkitts and non-Burkitts types
What is stage I in NHL?
Disease confined to one lymph node or two contiguous lymph node groups
What is stage II in NHL?
Disease on one side of the diaphragm in two separate lymph node groups
What is stage III in NHL?
Disease on both sides of the diaphragm
What is stage IV in NHL?
Extranodal spread with diffuse or disseminated involvement of one or more extralymphatic organs, including any involvement of the liver, bone marrow, or nodular involvement of the lungs
What is the problem with treating low grade NHL?
They are frequently disseminated at diagosis
How is low grade NHL that are stage I with small volume disease managed?
Radiotherapy
How is low grade NHL that is stage 2-4 managed?
Systemic chemotherapy
What is the problem with systemic chemotherapy in stage 2-4 low grade NHL?
Associated with bone marrow suppression and can result in neutropenic sepsis
What is rituximab?
A monoclonal antibody
What does rituximab do?
Targets the CD20 antigen
Where is the CD20 antigen found?
On the surface of more than 90% of B-cell lymphomas
What is rituximab used for?
- Treatment of relapsed low-grade NGL
- Combination with chemotherapy for follicular, mantle cell, and diffuse aggressive NHL
How often is rituximab given in relapsed low grade NHL?
Weekly for 4-8 weeks
What is the response rate to rituximab in relapsed low grade NHL?
60%
How does the stage at presentation of high-grade and intermediate-grade lymphomas differ to low grade?
They are more likely to be confined to one lymph node group (stage 1)
What is the result of high and intermediate grade NHL being more likely to be confined to one lymph node group on its management?
Radiotherapy can be effectively used
What might improve the outcome over radiotherapy in high and intermediate grade NHL?
Combination chemotherapy with involved field radiotherapy
How are patients with high and intermediate grade large volume stage I NHL managed?
Chemotherapy
What can patients with poor prognosis lymphoma at presentation or relapse be considered for?
High-dose chemotherapy with autologous or allogenic stem cell transplantation
What is required for patients having allogenic stem cell transplantation?
Long-term immunosuppressio
What is the limitation of stem cell transplantation in the treatment of NHL?
There is treatment associated mortality of this approach, which may exceed 10%
What do lymphoblastic lymphoma have a propensity for?
CNS relapse
What is the result of the propensity of lymphoblastic lymphoma for CNS relapse?
Prophylaxis with intrathecal chemotherapy is incorporated into the chemotherapy regime
How long is maintenance therapy given for in lymphoblastic lymphoma?
2-3 years
Describe the prognosis of disseminated low-grade NHL?
They are not cured with treatment, and although 85% of patients achieve a complete remission, this is transient
What is the median time of relapse in disseminated low-grade NHL?
18 months
What is the median time until disseminated low-grade NHL transforms into high grade NGL?
7.5 years after diagnosis
What is the chance of cure in patients with low-volume stage I high grade tumours?
95%
What kind of high-grade lymphomas have a worse prognosis?
- Mantle cell
- Burkitt’s
