Lymphoma Flashcards
What is the function of the lymphatic system?
- Fluid balance
- Immune system
- Absorption of fats & fat soluble vitamins
Remind yourself of the structure of the lymphatic system
- Made of lymphatic vessels, lymph nodes & lymph organs
- Lymph organs contain lymphatic tissue and are involved in blood filtering and maturation of lymphocytes (spleen, thymus, red bone marrow, tonsils, peyers patch, appendix)
- Superficial vessels and deep vessels
- Superficial vessels drain to deep vessels
- Deep vessels drain internal organs
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Drainage:
- Lymph channels
- Lymph vessels
- Lymph vessels drain through several lymph nodes
- Lymph vessels empty into lymphatic trunks
- Lymphatic trunks converge to form the right lymphatic duct and thoracic duct
- Right lymphatic duct drains lymph from RUQ of body
- Thoracic duct drains lymph from rest of body
- Both ducts then drain into venous circulation at the subclavian veins
State what organs in the lymphatic system
State some causes of lymphadenopathy
Broadly speaking, what is lymphoma?
State the two main categories of lymphoma and any subcategories within each
- Group of cancers caused by malignant proliferation of lymphocytes resulting in solid tumours(these lymphocytes proliferate within lymph nodes causing lymphadenopathy). Usually originate from B cell lineage
- Categories:
- Hodgkin’s lymphoma
-
Non-Hodgkin’s lymphoma
-
B cell lymphomas
- High grade
- Burkitt lymphoma
- Diffuse large B cell lymphoma
- Mantle-cell lymphoma
- Low grade
- Follicular lymphoma
- MALT-omas
- High grade
- T Cell lymphomas
-
B cell lymphomas
Is lymphoma common?
Yes, in top 10
Which is more common Hodgkin’s or non-Hodgkins lymphoma?
Non-Hodgkins
For Hodgkin’s lymphoma, discuss:
- Age of presentation
- Male to female ratio
- Risk factors
- Bimodal: 20-30yrs and >75yrs
- Male:female is 2:1 (except in nodular sclerosis)
- Risk factors:
- EBV
- Immunosuppression
- HIV
- Autoimmune conditions e.g. RA, sarcoidosis
- FH
State the 4 different histological classifications of Classical Hodgkin’s lymphoma
*also have nodular lymphocyte predominant Hodgkin’s lymphoma
State the B symptoms
B symptoms are features of lymphoma:
- Fever >38degrees with typical remittent pattern (Pel-Ebstein fever)
- Weight loss (more than 10% of body mass in previous 6 months)
- Night sweats
State some signs & symptoms of lymphoma; highlight the key, common presenting symptom
- B symptoms
- Weight loss (>10% in 6 months)
- Night sweats
- Fevers
- Lymphadenopathy (asymmetrical, non-tender, rubbery, some pts may have pain in nodes when drink alcohol)
- Fatigue
- Recurrent infections
- Generalised pruritis
- Cough
- SOB
- Abdo pain (left sided may be due to splenic enlargement)
- Back ache from para-aortic lymph nodes
- Hepatomegaly
- Splenomegaly
- Abdominal mass (due to para-aortic or mesenteric lymph nodes)
- SVCO (if mediastinal lymphadenopathy)
What investigations would you do if you suspect Hodgkin’s lymphoma (for each state why)
- FBC with differential: frequently normal but may see lymphocytosis. Also checking for bone marrow involvement (may see anaemia, neutropenia, thrombocytopenia)
- ESR: may be raised (NOTE CRP may also be raised) but ESR useful for monitoring & prognosis. Poor prognostic factor if raised)
- LDH: often raised but is non-specific (can be raised in other malignant and non-malignant diseases. Poor prognostic factor if raised)
- Blood film: Reed-Sternberg cells
- U&E’s
- LFTs
- HIV (risk factor)
- Immunohistochemical studies: Hodgkin’s is classically CD30 +ve and sometimes CD15 +ve
- CT TAP: may see enlarged lymph nodes
- PET scan: staging
- CXR: may show mediastinal shadowing due to enlarged lymph nodes
- Excisional lymph node biopsy: key diagnostic test- Reed Sternberg cells
*NOTE: bone marrow biopsy not routinely done for those with stage I-III nodal disease. Becoming less commonly done for those with extranodal disease as PET scan can show bone marrow involvement
What cell, found on lymph node biopsy, indicates Hodgkin’s lymphoma?
Reed Sternberg cell (abnormally large B cells with multiple nuclei that have nucleoli inside of them). Looks like an owl with large eyes.
Where (what organs) is lymphoma commonly found in?
- Lymph nodes
- Spleen (multiple nodules)
- Liver (multiple nodules)
Less commonly may get infiltration of bone marrow, lungs, skin or CNS
What staging is used for Hodgkin’s lymphoma? Describe this staging
Ann-Arbor Classification
Staging
- The most common staging system used for non-Hodgkin’s lymphoma is the Ann Arbor system.
- Stage 1 - One node affected
- Stage 2 - More than one node affected on the same side of the diaphragm
- Stage 3 - Nodes affected on both sides of the diaphragm
- Stage 4 - Extra-nodal involvement e.g. Spleen, bone marrow or CNS
- The stage is combined with the letter A or B to indicate the presence of ‘B’ symptoms. With the letter A indicating no B symptoms present and B indicating any of the beta symptoms present. For example, a patient with a single node affected and no ‘B’ symptoms would be stage 1A.
What is meant by bulky disease in lymphoma
Tumours in the chest that are at least ⅓ as wide as the chest, or tumours in other areas that are at least 10 centimetres across.
Discuss the management of Hodgkin’s lymphoma
- Key treatments are chemotherapy (AVBD), radiotherapy and steroids
- Immunotherapy (e.g. with rituximab) can be used for some subtypes (e.g. rituximab for lymphocyte pre-dominant) or targeted therapy for recurrence (e.g Brentuximab).
- In relapsed disease, high dose chemotherapy and autologous stem cell transplantation
- Vaccinations (as immunocompromised)
- (usually successful but there is risk of relapse, other haem cancers and side effects of medications)
What is meant by bulky disease
Tumours in the chest that are at least ⅓ as wide as the chest, or tumours in other areas that are at least 10 centimetres across.
Discuss the prognosis of Hodgkin’s lymphoma
State some factors associated with poor prognosis (7)
Treatment is usually successful but there is a risk of relapse, other haematological cancers and side effects of medications. 5yr survival is 87%.
Poor prognostic factors:
- Age >45yrs
- Male
- Stage IV disease
- Low haemoglobin
- Low albumin
- Leucocytosis
- Lymphopenia
Hodgkin’s lymphoma can relapse; briefly outline management of relapse
- Chemotherapy, radiotherapy or both
- Consider for autologous stem cell transplantation
- Targeted therapies e.g.
State some potential complications of Hodgkin’s lyphoma, split into:
- Tumour related
- Treatment related
Tumour Related
- Local pressure effects leading to:
- Dysphagia,
- SVCO
- Renal failure (from ureteric obstruction)
- Lower limb oedema (pelvic node involvement)
Treatment Related
- Acute complications chemo: N&V, alopecia, immunosuppression
- Radiotherapy depends on site but examples include: hypothyroidism, pneumonitis, lung fibrosis (bleomycin), pericarditis (Adriamycin is cardiotoxic), sterility
- Increased risk of second malignancies e.g. AML, solid tumours
There are many types of non-Hodgkin’s lymphoma; state a few key ones to know
What is most common lymphoma?
- Burkitts lymphoma
- MALT lymphoma
- Diffuse large B cell lymphoma
Diffuse large B cell lymphoma is most common according to BMJ best practice.
For non-Hodgkins lymphoma, discuss:
- Typical age of presentation
- Risk factors
- What % are have B-cell origins and what % have T cell origins
- Majority >50yrs
- Risk factors depend on type of non-Hodgkin’s lymphoma:
- HIV
- EBV (associated with Burkitt’s)
- H.pylori (MALT lymphoma)
- Hepatitis B or C
- FH
- Autoimmune disorders e.g. coeliac disease (intestinal T-cell lymphoma), RA, SLE
- Immunosuppressive drugs
- B cell origin=70-80%, T cell origin=20-30%
Presentation of non-Hodgkin’s lymphoma is similar to Hodgkin’s lymphoma; true or false?
True
However, extranodal disease is more common in NHL hence may experience symptoms related to that e.g.
- GI (dyspepsia, dysphagia, abdo pain)
- Bone marrow (bone pain, pancytopenia)
- Skin (lumps)
- CNS (weakness, altered sensations, raised ICP)
Extra-nodal disease is more common in non-Hodgkin’s than in Hodgkin’s; true or false?
True
Often involves GI tract, liver, CNS, skin, lung, thyroid and other organs
Compare high grade NHL and low grade NHL in terms of:
- Onset
- B symptoms
- Extra-nodal involvement
- BM infiltration
What investigations would you do for suspected non-Hodgkin’s lymphoma?
Similar to HL (as only way to distinguish between the two is via lymph node biopsy):
- FBC with differential: frequently normal but may see lymphocytosis. Also checking for bone marrow involvement (may see anaemia, neutropenia, thrombocytopenia)
- Blood film: help rule out other haematological malignancies
- ESR: may be raised- poor prognostic factor
- LDH: often raised but is non-specific (can be raised in other malignant and non-malignant diseases). Poor prognostic factor.
- Immunohistology: identify subtype
- CT (Imaging of choice): may see enlarged lymph nodes
- PET scan: staging
- CXR: may show mediastinal shadowing due to enlarged lymph node
- Lymph node biopsy: key diagnostic test
- ?Bone marrow aspirate/biopsy dependent on type: to see if BM infiltration
Other investigations also useful e.g. LFTs, LP if neurological symptoms)
Does everyone with lymphoma need a bone marrow biopsy?
No, nowadays PET/CT scans are often used to stage lymphoma however may be needed to help stage lymphoma in some cases where lymphoma in bone marrow can be difficult to see on PET/CT scans e.g. low grade Hodgkin’s lymphomas such as follicular lymphoma
What staging is used for NHL?
Ann-Arbor Classification
- I: involvement of a single lymph node region or lymphoid structure (e.g., spleen, Waldeyer ring)
- II: involvement of 2 or more lymph node regions on the same side of the diaphragm or a single lymph node region plus single extranodal organ on same side of diaphragm
- III: involvement of lymph node regions or structures on both sides of the diaphragm which may also be accompanied by extralymphatic extension in association with adjacent lymph node involvement (IIIE) or by involvement of spleen (S)
- IV: involvement of extra-nodal site(s) beyond that designated E (D-skin, H-liver, S-spleen, may also involve liver, lungs, CSF).
Following annotations/suffixes may be seen:
A: no B symptoms
B: B symptoms present (fever, drenching night sweats, weight loss)
X: bulky disease (>one third widening of mediastinum at T5 and T6, or >10-cm nodal mass)
Definitive differentiation between HL and NHL is via lymph node biopsy; however, there are some elements of clinical presentation that can help differentiate- state 3
- In HL pts may experience alcohol-induced pain in the node
- B symptoms typically occur earlier in HL and later in NHL
- Extra-nodal disease is much more common in NHL than in HL
Discuss the management of NHL
Management depends on specific subtype and staging but may include:
- Watchful waiting in those who are asymptomatic with low grade NHL
- Radiotherapy (localised disease can be treated with curative intent)
- Monoclonal antibodies e.g. rituximab
- Chemotherapy (may be used in indolent disease or in high grade. In high grade use R-CHOP regime)
- Stem cell transplantation (in those with high grade)
Other aspects of management: flu & pneumococcal vaccination, abx prophylaxis if neutropenic
State some potential complications of NHL
- Bone marrow infiltration leading to anaemia, neutropenia, thrombocytopenia
- SVCO
- Metastatic/malignant spinal cord compression
- Metastasis
- Treatment related complications
Discuss the prognosis of NHL
Depends on subtype and staging.
- Low grade have better prognosis
- High grader have worse prognosis but higher cure rate
Poor prognostic factors include according to IPI: age, performance status, stage, serum LDH
What is the difference between low grade and high grade lymphomas
- Low grade: very slow growing, may need little or no treatment for some time and some people will never require treatment. Most common low grade= follicular lymphoma
- High grade: more quickly growing/aggressive lymphomas requiring immediate treatment. Most common high grade= diffuse large B cell lymphoma
In most cases lymphoma is treatable & curable; true
True
What is typical microscopy appearance for Burkitt’s lymphoma?
Starry sky appearance
Discuss the 2WW referral criteria for lymphadenopathy
For Waldenstrom macroglobulinemia (also known as lymphoplasmacytoid lymphoma) discuss:
- What it is
- Age of presentation
- Signs & symptoms
- Management
- Haematological malignancy in which there is a raised number of lymphoplasmacytic cells (a type of B cell) that produce large amount IgM/paraprotein; causes blood to become more viscous
- Median age of onset is 70yrs
- Patients can present with hyperviscosity symptoms e.g. headaches, epistaxis, visual disturbance) but may also present with weight loss, lethargy, anaemia symptoms, lymphadenopathy, Raynaud’s, parasthesia in extremities, balance problems (protein can cause nerve damage)
- It develops slowly so many pts don’t need treatment for months or years and are just monitored; may need treatment when symptoms start to cause problems, IgM is increasing, decrease in blood counts etc… Treatment is often combination of immunotherapy (with rituximab) and chemotherapy and steroids. May also have stem cell transplants, blood transfusions and plasmapheresis/plasma exchange to thin the blood.
