Feline Lymphoma

How was the FeLV vaccine impacted the more common types of lymphoma seen?

Pre FeLV: mediastinal/ multicentric lymphoma in young/adult cats

Post FeLV: GI lymphoma in geriatric cats

What is the most common intestinal tumour in cats?

GI lymphoma (followed by adenocarcinoma and MCT)

What viruses are factors that can increase risk of developing lymphoma?

• FeLV>

• FIV- more likely B cell lymphoma, and GI tract more affected

  • oncogenesis through immune suppression

What are some aetological factors of feline lymphoma?

• Genetic predisposition

• Altered expression of oncogenes, tumour suppressor genes (c-myc, N-ras)

• Epigenetic modifications

• Tobacco smoke

• Chronic inflammatory conditions (i.e. IBD)

List the types of lymphoma in cats

• Nodal lymphoma (multicentric)

• Alimentary lymphoma

• Mediastinal lymphoma

• Extranodal lymphoma

  • Nasal/retrobulbar lymphoma (nasal discharge, epistaxis, obstruction, exopthalmos)

  • Laryngeal lymphoma (pharynx and trachea)

  • Renal lymphoma (malaise, anorexia, renomegaly (bilat.), azotaemia)

  • CNS lymphoma (signs depend on site)

  • Ocular lymphoma

  • Cutaneous lymphoma

How does nodal multicentric lymphoma present in cats?

• True multicentric (symmetrical, generalised distribution)= rare

  • Regional lymphadenopathy more common (submandibular LN, medial iliac LN)

• Middle aged

• Non-painful lymph node enlargement

• Anorexia

• Depression

• Non-specific malaise

• Pyrexia

• (PU/PD)

What may mimic lymphoma in cats?

Generalised lymphadenopathies

• Young cats

• histopathological phenomenon

• generally resolve without treatment

• poss retrovirus involvement

What are the differentials for nodal multicentric lymphoma?

• Retroviral, viral, bacterial, fungal, mycobacterial and (protozoal), infections

• (Other haemopoietic malignancies)

• Immune mediated disease

• Idiopathic forms

• Metastatic disease (regional)

What are the clinical signs of mediastinal lymphoma?

• Respiratory distress

• Regurgitation/dysphagia

• Weight loss

• Lethargy, exercise intolerance

• Cough (rare)

• Palpable reduction in compressibility of cranial thorax

• Decreased lung sounds

Younger cats?

What breed is predisposed to mediastinal lymphoma?

Siamese

What are the differentials for mediastinal lymphoma?

• Thymoma (double pos CD4/CD8)

• Other cranial mediastinal lymphadenopathy

• Other causes of pleural effusion

  • Congestive cardiac failure

  • Pyothorax

  • FIP

  • (Haemothorax)

How does alimentary lymphoma usually present?

• Older cats

• Insidious weight loss

• Anorexia

  • more common and severe in cats than dogs

• Diarrhoea poss

• Malabsorption/PLE (protein losing enetropathy)

• Occasionally vomiting

  • gastric involvement, secondary gastritis

  • more common in cats than dogs

What are the ddxs for alimentary lymphom?

• Many and various

  • Other causes of GI signs

• All other causes of mesenteric lymphadenopathy

  • FIP

    • Peritonitis of other aetiologies

  • IBD

  • Metastatic neoplasia

  • Pancreatitis

  • Mycobacterial infection

What two forms of lymphoma are interrelated in cats?

High incidence of CNS involvement in cats with renal lymphoma

(add cytosine arabinoside in induction to cross BBB when tx)

What is the most common form of cutaenous lymphoma in cats?

Non-epitheliotropic

How do you treat cutaneous lymphoma in cats?

• Generally don't respond well to chemo

• Retinoids can ammelioriate C/S

How do you diagnose lymphoma in cats?

• FNA (less likely diagnostic in cats)

• flow cytometry (measure physical + chemical characteristics of pop of cells)

• Biopsy

• PARR

How does the diagnosis of lymphoma by FNA/ flow cytometry differ in cats cf to dogs?

• Often low grade small cell or mixed so more difficult in cats- less likely to be diagnostic than dogs

  • esp multicentric/peripheral lymphomas

  • hard differentiate from reactive hyperplasia

• Cranial mediastinal and extranodal may be higher grade so easier to diagnose on FNA

  • renal lymphoma often need biopsy

• GI lymphoma - often high grade but FNA rarely diagnostic

What methods can be used to perform a biopsy for a lymphoma diagnosis?

• Excision biopsy of node

• Avoid trucut (except for renal) —> check coag

• Wedge biopsy from extranodal lesion or enormous lode (impression smear)

If chance of mycobacterial disease (or fungal) keep some fresh tissue

What are the pros and cons of diagnosing with PARR? (PCR for antigen receptor rearrangements)

Pro

• Clonality is a feature of neoplasia

• Identify a clonal population in a background of normal lymphocytes

• high specificity, a positive results support the diagnosis of lymphoma

Cons

• Clonality is not only a feature of neoplasia (just suggestive)

• Oligoclonality and monoclonality in inflammation

• Negative result if no enough cells

• Primers

• Identify only 65-70% of lymphomas in cats

• A negative result does not exclude lymphoma

What are the positive prognostic indicators for lymphoma in cats?

• Achieving CR

• Small volume extranodal disease (?)

  • Nasal lymphoma

What are the negative prognostic indicators for lymphoma in cats?

• Failure to achieve CR

• FeLV +ve status

  • ?impact on chance or remission, but overall remissions shorter

How is lymphoma treated in cats?

• Euthanasia (median survival without therapy = 4 wks)

• Corticosteroids

• Multi drug regimens

  • COP (high dose = best tx for cats)

  • CHOP (best tx for dogs)

  • COAP

• Non continuous regimes

What drugs are involved in high dose COP regime?

• Vincristine

• Cyclophosphamide

• Prednisolone

What are the side effects of chemo in cast?

• Myelosuppressive agents

  • check haem prior to every bolus dose

    • tolerate neutropenia well

  • on low dose COP, check at appropriate intervals

• Probably a good idea to intermittently check urine

  • ?UTI

• Hair loss (whiskers)

• GI signs

How can alimentary lymphoma be treated?

• Surgical excision of solitary mass (must biopsy nodes)

  • lymphoma is systemic dz so not curative

• Follow up chemotherapy

• Adequate supportive therapy (appetite stimulants, O tube, vit B12)

• Staggered induction for case with extensive infiltration (reduced risk of perforation)

• Gastric lymphoma very difficult to treat

large granular lymphocytes lymphoma has poor response to chemo

How can epitheliotropic lymphoma be tx?

Low grade “ epitheliotropic” tend to respond to chlorambucil and prednisolone only

What rescue therapy can be used in cats?

Single agent doxorubicin or lomustine

What is the prognosis in feline lymphoma?

• Goal is to induce complete remission

• Most cats will develop drug resistance and will relapse

  • consider radiation if local disease (e.g. nasal)

• A small percentage of cases will be cured

How are leukaemia classified?

• Acute vs chronic

  • Acute= rapidly progressive, fatal diseases

• Lymphoid vs myeloid

What is recognised as a precursor to acute leukaemia in FeLV positive cats?

Myelodysplastic syndrome

How do acute leukaemias present?

• Rapidly progressive, fatal diseases

• High WBC counts

• Concurrent pancytopenias

• Poor prognosis (weeks-months) even with chemotherapy

What are Myelodysplastic syndromes characterised by?

cytopenias (RBCs, platelets, neutrophils) without circulating neoplastic cells

How is acute leukaemia treated?

• Supportive therapy – very sick patients

  • Blood transfusion

  • Antibiotics

  • Barrier nursing

  • CSF?

• Multi-agent chemotherapy protocols

  • COP vs CHOP

  • Addition of cytarabine infusions may improve response

What are chronic leukaemias?

Neoplastic proliferation of well differentiated cells

What are the features of chronic lymphoid leukaemia?

Proliferation of mature lymphocytes in bone marrow.

• Rare (T cell > B cell > T-ve, B-ve)

• Lymphocyte counts >30×10⁹/L

• Decision to treat based on the individual (presence of CS, degree of lymphocytosis)

How is chronic lymphoid leukaemia treated?

Prednisolone/chlorambucil

survival times of 1-3 yrs

What are the features of chronic myeloid leukaemia?

Proliferation of mature myeloid cells (normally neutophils) in bone marrow

• Very rare

• Have to exclude other causes of extreme neutrophilia; infection, immune mediated disease; paraneoplastic syndrome

• May undergo blast crisis??

How is leukaemia diagnosed?

• Haematology with manual differential and smear evaluation

• Flow cytometry of peripheral blood

• Staging to evaluate extent of disease

  • Thoracic radiographs

  • Abdominal ultrasound

  • Cytology of liver/spleen

• Bone marrow biopsy (cytology + histology)

What are the features of multiple myeloma?

Myeloma related disorders

• Systemic neoplastic proliferation of plasma cells results in overproduction of antibody (IgA, IgG)

• Can start as extramedullary plasmacytoma which can progress to multiple myeloma

What can mutliple myeloma lead to?

• Hyperproteinaemia can lead to hyperviscosity syndrome

  • Neurological symptoms, retinal detachment, congestive heart failure (cats > dogs), hypertension, coagulopathy

• Cytopenia - due to bone marrow involvement

• Renal disease present in a lot of these (multifactorial due to proteinuria, hypercalcaemia, renal infiltration, urinary infection).

How is multiple myeloma diagnosed?

Haematology, biochemistry, urinalysis

• Non-specific, may see circulating plasma cells

• Proteinuria (Bence-Jones proteins)

• Hypercalcemia

• Hyperglobulinemia

Serum protein electrophoresis

• Monoclonal gammopathy

Diagnostic imaging

• Hepatosplenomegaly

• Osteolytic bone lesions

Cytology: Liver, spleen + bone marrow

Need to assess extent of disease to determine therapy

What criteria do dogs have to fulfill to be diagnosed with multiple myeloma?

2 of the following:

1. Monoclonal gammopathy

2. Radiographic evidence of osteolytic bone lesions

3. >5% neoplastic plasma cells or >10-20% plasmacytosis in the bone marrow

4. Bence-Jones proteinuria

feline myeloma related disorder rarely bone marrow involvement so should demonstrate plasma cell infiltration of visceral organs.

How is multiple myeloma treated?

Supportive care

• Blood transfusions

• Plasmaphoeresis

• Antibiotics if secondary infection

• Therapy for hypercalcaemia

Systemic disease

• Prednisolone (~ 40 days)

• Chemotherapy: Prednisolone and Melphanan

  • Cumulative myelosuppression is seen —> perform haematology

Local extramedullary plasma cell disease may be treated surgically if no systemic involvement