ONCOLOGY - Lymphoma, Leukaemia, Multiple Myeloma Flashcards
What is lymphoma?
Lymphoma is the malignant proliferation of peripheral lymphoid tissue which can cause secondary infiltration of other tissues, including the bone marrow
What are the anatomical classifications of lymphoma?
Multicentric lymphoma
Alimentary lymphoma
Mediastinal lymphoma
Cutaneous lymphoma
Extranodal lymphoma
List the anatomical classifications of lymphoma in order of frequency in dogs
Multicentric lymphoma
Gastrointestinal lymphoma
Medistinal lymphoma
Cutaenous lymphoma
List the anatomical classifications of lymphoma in order of frequency in cats
Gastrointestinal lymphoma
Extranodal lymphoma
Multicentric lymphoma
Mediastinal lymphoma
What are the risk factors for lymphoma?
Genetics
Age
Neutered females
Environment
FeLV in cats
Which dog breed is predisposed to B cell lymphoma?
Cocker Spaniel
Which dog breed is predisposed to T cell lymphoma?
Boxer
Which environmental factors can increase the risk of lymphoma?
Passive smoking (inhaling second-hand smoke) can increase the risk of lymphoma
What is the clinical approach to lymphoma?
- Assess history and clinical signs
- Confirm diagnosis
- Clinical staging
- Identify any concurrent disease
- Treatment
What are the general clinical signs of lymphomaa?
Asymptomatic with lymphadenomegaly
Lymphadenomegaly
Lethargy
Inappetence
Weight loss
Pyrexia
Paraneoplastic syndrome
Which paraneoplastic syndromes can be seen with lymphoma?
Hypercalcaemia
Hyperviscosity syndrome
Which cell lineage for lymphoma is most likely to cause hypercalcaemia?
T cell lymphoma
Which cell lineage for lymphoma is most likely to cause hyperviscosity syndrome?
B cell lymphoma
What is the key clinical sign of multicentric lymphoma?
Non-painful lymphadenomegaly of the peripheral lymph nodes
What are the peripheral lymph nodes?
Submandibular lymph nodes
Prescapular lymph nodes
Axillary lymph nodes
Popliteal lymph nodes
Inguinal lymph nodes
Which cell lineage is most commonly associated with multicentric lymphoma?
B cell lymphoma
What is the typical signalement for alimentary lymphoma?
Older, FeLV negative cats
What are the clinical signs of alimentary lymphoma?
Vomiting
Diarrhoea
Anorexia
Weight loss
Palpable abdominal mass or thickened loops of intestine
Which diagnostic test should be done if you suspect alimentary lymphoma?
Ultrasound
What are some of the key features of alimentary lymphoma on ultrasound?
Gastrointestinal mass
Loss of layering of the gastrointestinal wall
Gastrointestinal lymphadenomegaly
Gastrointestinal hypomotility
What are the features high grade alimentary lymphoma?
High grade alimentary lymphoma tends to form a gastrointestinal mass and is composed of large, immature, undifferentiated lymphoblasts
What are the features low grade alimentary lymphoma?
Low grade alimentary lymphoma tends to have diffuse infiltrationn of the gastrointestinal tract and is composed of small, more differentiated lymphocytes
What is the typical signalement for mediastinal lymphoma?
Young, FeLV positive cats
What are the clinical signs of mediastinal lymphoma?
Cough
Dyspnoea
Muffled heart and lung sounds on auscultation
Mediastinal lymphoma can cause compression and effusion of thoracic structures
What are the key features of mediastinal lymphoma on radiography?
Soft tissue/fluid opacity mass in the mediastinum
Dorsal displacement of the trachea
Lymphadenomegaly of the tracheobronchial lymph nodes
What are the clinical signs of mediastinal lymphoma?
Pruritis
Erythema
Ulceration
Nodules
Plaques
What is primary cutaneous lymphoma?
Primary cutaneous lymphoma is when the lymphoma originates in the skin and is always T cell mediated
What is secondary cutaneous lymphoma?
Secondary cutaenous lymphoma is where the lymphoma has metastasised to the skin and can be B or T cell mediated
What is extranodal lymphoma?
Extranodal lymphoma is lymphoma which originates outside of the lymphoid tissue
Which form of extranodal lymphoma has the best prognosis?
Nasal extranodal lymphoma
How do you diagnose lymphoma?
History and clinical signs
Fine needle aspirate (FNA)
Biopsy
When is biopsy indicated in the diagnosis of lymphoma?
A biopsy is indicated if fine needle aspirate cannot confirm lymphoma or to provide a more precise classification of the lymphoma
How should you carry out a biopsy for lymphoma?
If you suspect lymphoma, remove the whole lymph node to examine the architecture
How do you approach histological diagnosis of lymphoma from a lymph node?
- Determine if the lymphocyte infiltration is diffuse or nodular
- Determine if the lymphocyte size is large, intermediate or small
- Determine if the lymphoma is high or low grade
- Determine if the lymphocytes are B cell or T cell in lineage
What are the features of high grade lymphoma on histology?
Large, immature, undifferentiated lymphoblasts
What are the features of low grade lymphoma on histology?
Small, mature, differentiated lymphocytes
How can you determine if a lymphoma has a B cell or T cell lineage?
Immunohistochemistry
Flow cytometry
PCR for antigen receptors rearrangement (PARR)
What is immunohistochemistry?
Immunohistochemistry is a technique which used antigen-antiobody interactions to detect specific markers present on B cells and T cells
Which marker is used to identify B cell lymphoma?
CD79a
Which marker is used to identify T cell lymphoma?
CD3
What is flow cytometry?
In flow cytometry, cells are suspended in a liquid with flueorescent markers added to label specific markers. The sample will flow through the flow cytometer and as the cells flow through, they will pass lasers which will cause the marked cells to emit fluorescence
What is PCR for antigen receptors rearrangement (PARR)?
PCR for antigen receptors rearrangement (PARR) is a clonality assay which helps to distinguish clonal lymphocytes from polyclonal lymphocytes. Neoplastic lymphocyte antibodies are all the same and thus detect the same antigens, however inflammatory lymphocytes are polyclonal and each antibody differs and detects a different antigen. Markers on B cells and T cells have gene segments which have a unique rearrangement and PCR primers can be used to amplify these gene segments and determine whether it is B or T cell lymphoma
What is one of the main benefits of PCR for antigen receptors rearrangement (PARR)?
PCR for antigen receptors rearrangement (PARR) can be used to confirm a diagnosis of lymphoma and determine cell lineage with a very small sample
Which serum biomarkers can be indicative of lymphoma?
Thymidine kinase
Lactate dehydrogenase
Remember these are not specific or diagnostic
What is thymidine kinase?
Thymidine kinase is a DNA salvage pathyway enzyme involved in regenerating thymidine for DNA synthesis and DNA damage, that increases in response to lymphoma and decreases in response to lymphoma treatment
What can serum thymidine kinase levels be used for?
Serum thymidine kinase levels can be used to monitor treatment progression for lymphoma and the pretreatment values of thymidine kinase are prognostic, with increased levels associated with a worse prognosis
What is lactate dehydrogenase?
Lactate dehydrogenase is an enzyme which catalyses the conversion of pyruvate to lactate and increases in response to lymphoma and decreases in response to lymphoma treatment
What can lactate dehydrogenase kinase levels be used for?
Lactate dehydrogenase can be used for monitor treatment progression for lymphoma
What are the clinical stages of lymphoma?
Clinical stage I: Single lymph node or lymphoid tissue in a single organ
Clinical stage II: Several lymph nodes in a regional area
Clinical stage III: Generalised lymph node involvement
Clinical stage IV: Liver and spleen involvement
Clinical stage V: Bone marrow and/or extranodal tissue
Each stage can be subclassified as a) if there are clinical signs and b) if there are no clinical signs
How do you determine the clinical stage of lymphoma?
History and clinical signs
Haematology and biochemistry
Urinalysis
Diagnostic imaging
Bone marrow biopsy
What can haematology be used to determine when clinically staging lymphoma?
Haematology assesses the level of haematopoietic cells in the blood which can be indicative of bone marrow involvement and provide baseline data prior to chemotharpy
What can biochemistry be used to determine when clinically staging lymphoma?
Biochemistry assesses organ function and thus can indicate the degree of other organ involvement and paraneoplastic syndromes
What can urinalysis be used to determine when clinically staging lymphoma?
Urinalysis can be used to provide baseline data prior to chemotherapy
What can diagnostic imaging be used to determine when clinically staging lymphoma?
Diagnostic imaging can be used to determine if there has been any metastasis
What can a bone marrow biopsy be used to determine when clinically staging lymphoma?
A bone marrow biopsy can be used to determine if the lymphoma has infiltrated the bone marrow
Why is it so important to identify any concurrent disease when clinically staging lymphoma?
Affects prognosis
Affects treatment decisions
Affects choices of chemotherapy drugs
What are the potential responses to lymphoma treatment?
Complete remission (CR)
Partial remission (PR)
Progressive disease (PD)
Stable disease (SD)
What is complete remission (CR)?
Complete remission (CR) is where there is no gross disease visible
What is partial remission (PR)?
Partial remission (PR) is where there has been over a 30% decrease in the size of gross disease
What is progressive disease (PD)?
Progressive disease (PD) is where there has been over a 20% increase in the size of gross disease
What is stable disease (SD)?
Stable disease (SD) is where there has been either no change in gross disease, or less change than ib partial remission or progressive disease
How do you approach lymphoma treatment?
- Stabilise the paraneoplastic syndromes
- Treat the lymphoma
Why is it so important to stabilise paraneoplastic hypercalcaemia?
It is so important to stabilise paraneoplastic hypercalcaemia as hypercalcaemia can cause progressive, irreversible renal damage
What are the treatment options for lymphoma?
Palliative steroids
Chemotherapy
What is the prognosis for lymphoma with no treatment?
1 to 2 months
What is the prognosis for lymphoma with palliative steroids?
2 to 3 months
What is the prognosis for lymphoma in dogs with chemotherapy?
In dogs, lymphoma has an 80 - 90% rate of complete or partial remission, with 6 to 9 months to live with the COP protocol and 10 to 12 months to liver with the CHOP protocol
What is the prognosis for lymphoma in cats with chemotherapy?
In cats, lymphoma has a 50 - 70% rate of complete or partial remission, with 6 to 8 months to liver with high grade lymphoma and 17 to 23 months to live with low grade lymphoma
Which factors contribute to a good prognosis for lymphoma?
Low clinical stage
Clinical substage a (no clinical signs)
B cell mediated (in dogs)
Use of doxorubicin in cat chemotherapy protocol
Which factors contribute to a poor prognosis for lymphoma?
High clinical stage
Clinical substage b (clinical signs)
T cell mediated (in dogs)
Central anatomical locations
FeLV positive (in cats)
Prior steroid use
Why does prior steroid use contribute to a poor prognosis for lymphoma?
Prior steroid use can contribute to the development of multidrug resistance of lymphoma to steroids
What is leukaemia?
Leukaemia is the malignant poliferation of haematopoietic tissue originating in the bone marrow, which can cause secondary infiltation of the blood and other tissues
What are the classifications of leukaemia?
Lymphoid leukaemia
Myeloid leukaemia
Lymphoid leukaemia is more common
Describe the pathogenesis of leukaemia
Leukaemia is the proliferation of haematopoietic neoplastic cells within the bone marrow resulting in myelophthisis, cytopenias, neoplastic cells in the bloodstream and secondary infiltration of other organs and tissues such as the lymph nodes, spleen and liver resulting in lymphadenomegaly, splenomegaly and hepatomegaly. Leukaemia can also result in extramedullary haematopoiesis
What is myelophthisis?
Myelophthisis is the displacement of other haematopoietic cell lines in the bone marrow due to leukaemia, resulting in cytopenias
What can be a key sign of neoplastic cells within the bloodstream?
A large ‘buffy coat’ on PCV can be a key sign of neoplastic cells within the bloodstream and leukaemia
What is acute leukaemia?
Acute leukaemia is where there is neoplastic transformation of the haematopoietic cells early in the cell lineage (i.e. the -blast cells)
What are the features of chronic leukaemia?
Generally systemically well
May have mild lymphadenomegaly
May have splenomegaly
May have hepatomegaly
Leukocytosis and cytopenias on haematology
Paraneoplastic syndromes
Increased mature, well differentiated cells on bone marrow biopsy
What is chronic leukaemia?
Chronic leukaemia is where there is neoplastic transformation of the haematopoietic cells later in the cell lineage (i.e. mature, differentiated cells)
What are the features of acute leukaemia?
Generally systemically unwell
Mild lymphadenomegaly
Splenomegaly
Hepatomegaly
Clinical signs of cytopenias
Leukocytosis and cytopenias on haematology
Unlikely to have paraneoplastic syndromes
Increased immature blast cells on bone marrow biopsy
How do you diagnose leukaemia?
History and clinical signs
Haematology
Bone marrow biopsy
Flow cytometry
How do you treat leukaemia?
Chemotherapy
What is the prognosis for acute leukaemia?
Very poor prognosis, often not treated and euthanised
What is the prognosis for chronic leukaemia?
Good prognosis
What is multiple myeloma?
Multiple myeloma is the neoplastic proliferation of plasma cells originating in the bone marrow, which can cause secondary infiltration of the blood and other tissues
Describe the pathogenesis of multiple myeloma
Multiple myeloma is the proliferation of neoplastic plasma cells within the bone marrow resulting in myelophthisis, cytopenias, neoplastic cells in the bloodstream and secondary infiltration of the bones resulting in osteolytic lesions Multiple myeloma also results in increased/abnormal production of immunoglobulins resulting in hyperproteinamia, hyperviscosity syndrome and immune dysfunction as the immunoglobulins are not fully functional
How do you diagnose multiple myeloma?
Haematology
Radiography
Bence Jones proteinuria
Bone marrow biopsy (more than 10% plasma cells)
What is a key sign of multiple myeloma on haematology?
Hyperproteinaemia
What should you do if there is a hyperproteinaemia on haematology?
Serum protein electrophoresis to seperate albumin and immunoglobulins by charge and determine if the immunoglobulins are clonal or polyclonal
What is a key sign of multiple myeloma on radiography?
‘Punched out’ lesions of the spinous processes and pelvis due to multiple myeloma metastasis
How do you treat multiple myeloma?
Stabilise paraneoplastic syndromes
Treat any secondary infections
Chemotherapy
Describe the pathogenesis of hyperviscosity syndrome
When there is excessive immunoglobulin production due to multiple myeloma, this causes the blood to become more viscous and results in reduced blood flow and tissue perfusion
What are the clinical consequences of hyperviscosity sydrome?
Cardiomyopathies
Retinal lesions, detachment and blindness
Seizures
Azotaemia
Coagulopathy
How do you treat hyperviscosity syndrome?
Plasmapheresis
What is plasmapheresis?
Plasmapheresis is where you removing blood plasma from the body by withdrawing blood, separate it into plasma and cells, and transfuse the cells back into the bloodstream
