Canine Lymphoma Flashcards
What is lymphoma?
- Lymphoma is a diverse group of neoplasms that arise from the lymphoreticular cells (T or B cells).
- Normally arise from lymphoid tissue but it can arise from virtually any tissue.
- Comprises 7-24% of canine neoplasms and up to 83% of canine hematopoietic malignancies
What is aetiology of lymphoma?
- Genetic and molecular factors.
- Infectious diseases. Retrovirus/ Epstain-Barr virus/Helicobacter spp
- Toxins.
- Immunologic factors. Disease or treatment
How does lymphoma clinically present?
- IT CAN AFFECT VIRTUALLY EVERY DOG!!!
- Middle age to old dogs.
- Gender - males
- Breed predispositions and familiar traits - boxers, mastiff
- Different anatomic forms.
- Clinical signs depend on the affected location
What are the different lymphomas?
- Multicentric 80%
- Craniomediastinal 5%
- Gastro-intestinal 5 – 7%
- Cutaneous
- Extra-nodal forms (CNS, renal, heart, bladder)
What is multicentric lymphoma? Signs?
- Most common form in the dog
- Generalized peripheral lymphadenopathy +/- other clinical signs
- Moderate to marked lymph node enlargement
- Some dogs clinically well
- Rapid deterioration
- Non-specific signs (weight loss, inappetence/anorexia, lethargy, pyrexia)
- More specific signs (diarrhoea, vomiting, cough, ocular signs)
- Regional oedema if lymph drainage impaired
What is cranial mediastinal lymphoma? Signs?
- Can occur as solitary lesion or part of multicentric form
- Tachypnoea, dyspnoea
- Signs of hypercalcaemia (PU/PD, vomiting/diarrhoea, muscle tremors, anorexia, weight loss)
- Occasionally pre-caval syndrome
- Altered position of PMI for cardiac auscultation, displacement of apex beat
What is GI (alimentary) Lymphoma? Signs?
- Clinical signs =
- Vomiting, diarrhoea, weight loss, anorexia, pan-hypoproteinaemia (hypoalbuminemia), evidence of malabsorption.
- Abdominal masses or diffuse.
- Lymphadenopathy (abdominal and less commonly peripheral).
- Tends to be aggressive in dogs =
- Diagnosis often delayed.
- There may be progression from other GI disease
What is cutaneous lymphoma? Signs?
- Epitheliotrophic and non-epitheliotrophic forms.
- Epitheliotrophic = T cell, solitary or generalized
- Non-epitheliotrophic = More frequently B cell, More likely to have lesions elsewhere
- Different appearances. Progression to raised, erythematous plaques/nodules - Variable pruritus.
- In general poorly responsive to chemotherapy
What is extranodal lymphoma? Signs?
- Hepatosplenic = Aggressive, no peripheral lymphadenopathy, T cell
- CNS = Mass lesion or diffuse. Variable neurological deficits but commonly signs of multicentric or diffuse lesions. Commonly ocular involvement, Generally T cell
- Renal, urinary bladder, heart, muscle
What is a paraneoplastic syndrome?
- It is a syndrome (set of signs and symptoms) that it is a consequence of the tumour but it is not due to the presence of tumour cells in that location.
- Hypercalcaemia (PTHrp) = T cell (35%), Mediastinal and GI forms
- Immune mediated diseases = IMHA, IMTP and Pemphigus foliaceous
- Monoclonal gammopathies = B-cell
- Neuropathies
- Cachexia
How is lymphoma diagnosed?
- Cytology
- Histopath
- Ancillary tests - immunohistochemistry
- Biomarker tests
What are features with clinical or prognostic implications? (cytology)
- Grade (low, intermediate or high).
- Immunophenotype (B-cell, T-cell or null phenotype)
What are different stages of lymphoma?
I = involvement limited to a single lymph node / lymphoid tissue in a single organ
II = Involvement of lymph nodes in a regional area +/- tonsilitis
III = Generalised lymph node involvement
IV = Hepatic +/or splenic involvement
V = Manifestations in the blood + involvement of bone marrow +/or other organ systems (extranodal form)
What can be used to stage lymphoma?
- Haematology - Thrombocytopenia: 30 – 50%, Neutrophilia: 25 – 40 %, Lymphocytosis: 20%, Abnormal cells on smear
- Biochemistry - Hypercalcaemia, Check for signs of organ dysfunction
- Aspirate or biopsy of other lymph nodes/ organ
- Thoracic radiographs, abdominal ultrasound
- Bone marrow biopsy
What is Tx of lymphoma?
No treatment
* Median Survival Time = 4 – 6 weeks for asymptomatic dogs.
* Consider euthanasia on symptomatic dogs.
Prednisolone alone
* ORR~ 30% Median response duration 1 – 2 months.
* Resistance to chemotherapy.
Gold standard is multidrug chemotherapy
* Survival time varies depending on protocol and individual response.
* Lower doses of drugs and prolonger interval between doses compared to humans = Less side effects.
* Rarely curative and very prolonged survivals in ~20% of cases
= COP (Cyclophosphamide, oncovin (vincristine), Prednisolone)
= CHOP ( Cyclophosphamide, hydroxydaunomycin (doxorubicin) oncovin (vincristine), Prednisolone)
What are side effects of chemotherapy?
- GI toxicity = Vomiting diarrhoea, nausea.
- Myelosupression = Neutropenia, thrombocytopenia and anaemia.
- Drug specific toxicities =
- Sterile haemorrhagic cystitis = Cyclophosphamide = Furosemide, encourage urination.
- Cardiotoxocity = Doxorubicin and Epirubicin = Echocardiographic monitoring.
- Lomustine = Hepatotoxicity = Monitoring of ALT and liver protectors.
When would you use local treatment for lymphoma?
- Radiation - for stage 1 disease / if mass lesion on CNS
- Surgery - considered for rare Hodgkin’s lymphoma + extranodal + early stage 1 disease
What must be considered with CNS lymphoma?
- Many drugs can’t cross the blood brain barrier
(vincristine) - All these can cross the BBB
- Cytarabine
- Lomustine
- Steroids
- L-asparaginase
What is Tx of cutaneous lymphoma?
- COP - no proven extension of lifespan, may improve QoL
- Radiation therapy useful for localized mucocutaneous disease
How would you assess response to lymphoma treatment?
- Palpation of lymph nodes/other lesions prior to every treatment.
- Resolution of clinical signs.
- Repeating imaging (restaging) for internal lesions.
- Monitoring blood parameters (Ca, ALT etc.).
*Achieving a complete response (CR) is vital =
- Increases time to relapse
- Increases survival time
- Being in CR at the end of a discontinuous protocol leads to a very high chance of regaining remission later using the same protocol.
What is suggested if Complete response isn’t achieved?
- If CR is not achieved this suggests a resistant population of tumour cells
- These will rapidly become the dominant population
= BAD
What is usual follow up for complete response patients not on treatment?
- Monthly checks at least for the first 6 months and every 2-3 months thereafter
- Average time to relapse 4 months but very variable (1-18 months)
When would you restage a lymphoma?
- When there are no sentinel lymph nodes to follow.
- When patient not doing as well as expected or all clinical signs do not resolve.
- At the end of the induction phase.
- At the end of a discontinuous protocol
