Alimentary lymphoma in cats

Question 1

What can increase the risk of developing lymphoma

Answer 1

 Siamese and oriental breeds ( mediastinic LSA , FeLV neg)
 Retroviral infections (FeLV, FIV)
 Diet
 Chronic inflammations
 Environment: - Pollution?
- Passive smoking: x2.4,
>5 years exposure: x3.2

Question 2

What are the variables when considering the area of lymphoma

Answer 2

Age of presentation, FeLV status, T or B Cell

Question 3

What are the main methods of diagnosis of lymphoma in cats

Answer 3

• Cytology – Often insufficient in cats !
• Lymph node or tissue histology – morphological diagnosis
• Immunohistochemistry – Immunophenotype
• Clonality tests (PARR)

Question 4

What information can histology provide for lymphoma dx?

Answer 4

Morphological diagnosis
88.5-90% intermediate to high-grade LSA
Other variants: Hodgkin’s like lymphoma, T-cell-rich large B-cell lymphoma and small cell lymphoma
DD Low versus intermediate/high-grade lymphoma

Question 5

What information does immunohistochemistry provide?

Answer 5

CD3 (T cells) vs CD79a (B cells)
Immunophenotype not prognostic
DD with other tumours (mast cell tumours,
undifferentiated carcinomas/sarcomas, etc)
Does not test clonality

Question 6

What is PARR?

Answer 6

PCR for Antigen Receptor Rearrangement
DNA amplification to evaluate if cells developed from a common original clone
Distinction between neoplastic lymphoid cells (monoclonal expansions) or inflammatory (polyclonal expansions)
PARR for T-cells – Target: T-cell receptor
PARR for B-cells – Target: Immunoglobulin heavy-chains
PCR primers target preserved regions found by hypervariable regions.

Question 7

What are the indications for PARR?

Answer 7

Inconclusive diagnosis with histopathology and IHC
Distinction between alimentary lymphoma vs IBD
Distinction between atypical hyperplasia vs follicular
lymphoma
NEVER without morphologic diagnosis!
Negative result does not rule out lymphoma because:
65% feline lymphoma (sensitivity)
75% canine lymphoma (sensitivity)
Specificity 95% canine lymphoma >90% feline lymphoma

Question 8

Outline the use of clinical staging

Answer 8

Goal: prognostic staging, general health state
obtain baseline to monitor therapy and side effects

 Minimal staging: haematology including blood smear,
biochemistry, urine analysis, FeLV & FIV tests, serum T4,
blood pressure measurement
 Complete staging:
Thoracic radiographs
Abdominal ultrasonography
Bone marrow evaluation (cytology/histology/PCR FeLV)
>50% in CNS LSA

Question 9

When should you sample bone marrow for staging?

Answer 9

circulating neoplastic leukocytes
if bicytopaenia or tricytopaenia
non regenerative anaemia
 persistent haematologic anomalies

Question 10

What are the stages of feline lymphoma

Answer 10

1. 1 node involvement/ tumour
2. single tumour with regional LN involvement, 2 or more nodes on same side of diaphragm, 2 single tumours without LN involvement on same side of diaphragm, resectable GI tumour, with or without mesenteric LN involvement
3. Nodes or tumours on both sides of diaphragm, extensive non resectable abdo dz, spinal dz,
4. 1,2,3 with liver or spleen involvement
5. 1,2,3, or 4 with bone/ BM or brain involvement

substage a - well, b - unwell

Question 11

What are prognostic factors

Answer 11

 Anatomic localization
Nasal LSA and Siamese with mediastinic
CNS LSA
 Low vs High grade
 Immunophenotype – NOT PROGNOSTIC IN THE CAT
 Sub-stage b – NEGATIVE
 FeLV - NEGATIVE
 Response to therapy
 BCS <5/9
 BWT loss  Early nutritional support!
 Treatment with doxorubicin
 Clinical stage by Mooney

Question 12

Where are most GI lymphomas?

Answer 12

 Small intestine (50-80%), stomach (25%), ileocaecocolic junction, colon

Question 13

How is helicobacter related to GI lymphoma?

Answer 13

Gastric Helicobacter spp associated to chronic inflammation and neoplastic transformation in man and lab animals.
Man: 50% of infections by H. pylori, 0.1% gastric lymphoma responsive to antimicrobial therapy, cause or contributing factor 35-60% gastric cancer.
THEORY: a clone inflammatory lymphocyte stimulated by the infection populates and destroys MALT lymphoid follicles (mucosal associated lymphoid tissue)
Low grade MALT lymphoma remission with antimicrobial therapy
Experimental lymphoma by H. pylori induces fullicular gastritis in the cat.
Possibly a relation to FeLV infection too - makes cats then more susceptible to lymphoma d/t other infections

Question 14

What may you see on abdo u/s with GI lymphoma?

Answer 14

 Gastric wall thickness and/or intestinal
 Muscolaris thickening
 Presence of a mass
 Decreased motility and normal wall layers
Parietal thickening,
Hypoechogenicity,
Layers loss
 Ascites
 Mesenteric lymphadenopathy of variable severity

Question 15

How may the spleen appear on u/s if affected?

Answer 15

mottled/ spotted often

enlarged

Question 16

How may the liver appear on u/s

Answer 16

may see hypoechoic nodules

Question 17

How may the kidney appear on u/s

Answer 17

enlarged, hyperechoic cortex, decreased corticomedullary definition, subcapsular thickening
Prominent lobulated medullary sections, hyperechoic halo at the periphery of the cortex
May see several hypoechoic poorly defined masses/nodules and loss of normal parenchymal architecture

Question 18

How do you sample GI lymphoma

Answer 18

 Mesenteric lymph nodes cytology for morphologic
diagnosis, ICC
 Histopathology:
-endoscopic pinch biopsies
-exploratory laparotomy & full thickness biopsies

Question 19

What information can you get from bloods in a lymphoma patient?

Answer 19

 Full haematology:
cytopenias, mycrocytic hypochromic anaemia, macrocytic anaemia without reticulocytosis, lymphocytosis, anaemia or thrombocytopenia, eosinophilia or basophilia
 Blood smear examination:
confirmation of automated cell count, assessment of cell morphology (lymphocytes), detection of a leukemic state
 Serum biochemistry & Urine analysis:
organ dysfunction or endocrinopathy
neoplastic infiltration of organs (eg kidney, liver) or concurrent disease. `

Question 20

What may you see on a blood smear?

Answer 20

Neoplastic lymphocytosis
Microcytic hypochromic anaemia (±urea)
-iron deficiency anaemia
-gi bleeding, chronic bleeding
Macrocytic anaemia without reticulocytosis
-FeLV infection
Neutropaenia, thrombocytopaenia
-myelophthisis
-Immune-mediated
-sepsis, toxic neutrophils
-coagulopathy, DIC
Paraneoplastic syndromes
Eosinophilia, basophilia
-careful with automated in-house counts

Question 21

Why may you see hyper or hypo protein levels?

Answer 21

-Hypergammaglobulinemia – monoclonal gammopathy
-excessive production of immunoglobulins from plasma cells or malignant lymphocytes
Hypoalbuminemia ± hypoglobulinemia
-PLE (protein loosing enteropathy):
Permeability x erosion, ulceration, lymphatic obstruction
-PLN (protein losing nephropathy):
autoimmune glomerulonephritis, NDI, tubular precipitation with hypercalcaemia, ATLS (acute tumour lysis syndrome)
-EPI (exocrine pancreatic insufficiency)
DD hepatic insufficiency, malnutrition/cachexia, blood/ plasma loss (vasculitis, pleuritis, peritonitis),
haemodilution (oedema, fluids, SIADH)

Question 22

What may you see if the pancreas is affected?

Answer 22

Pancreatitis
low serum fPLI
(pancreatic lipase immune-reactivity test)
Proximal malassorbtion - fasting
low serum folate
Distal malabsorption
low serum cobalamin
Maldigestion – EPI
low serum TLI
(tripsin-like immunoreactivity)

Question 23

What should you always consider when staging an animal

Answer 23

Investigate other concomitant clinical signs
Possible systemic/multicentric involvement
Respiratory/cardiac signs
Neurologic signs
Cutaneous signs
Ocular signs
Peripheral lymphadenopathy

Question 24

What GI supportive treatment may need to be given

Answer 24

 Nutritional support – especially if anorexic
 Appetite stimulants:
mirtazapine (15 mg, ¼ tablet every 3 days PO) cyproheptadine (0.2 mg/kg PO q12h)
 Stomach protectors: omeprazole/ famotidine etc
- Pancreatic enzymes
- Vitamina B12 (cyanocobalamyn) 20 ug/kg SC q7days
for 6 weeks, then q14gg for 6 weeks, then q30days
- Folic acid 0.5-2 mg/cat q24h for 1 month or continue if
EPI

Question 25

When is surgery helpful?

Answer 25

 Diagnosis, obstructive disease or peritonitis

Question 26

Why is a fast response to chemo important?

Answer 26

Good initial response - better prognosis

No response within 3-4 doses - change protocol

Question 27

What is the chemo treatment of choice for low grade lymphoma?

Answer 27

Anticancer Therapy
 Induction therapy:
Chlorambucil and prednisolone
 Rescue therapy:
Cyclophosphamide – single agent
Lomustine – single agent
COP protocol

Question 28

What is the prognosis for low grade GI lymphoma?

Answer 28

Good to excellent prognosis
Median survival 18-24 months
19.3 months (Complete Remission - CR) versus 4.1 months (no CR)

Question 29

What is the chemo treatment of choice for high grade lymphoma?

Answer 29

Anticancer Therapy
 Induction therapy: COP (cyclophosphamide, vincristine, prednisolone)
CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)
 Rescue therapy: No studies
NO doxorubicin – single agent
L-asparaginase, lomustine, prednisolone response 38%
Mitoxantrone – single agent
MOPP (mechloretamine, vincristine, procarbazine, prednisolone)
TKIs in T cell LSA or chemo-radiosensitizer?

Question 30

What is the prognosis for medium/ high grade lymphoma?

Answer 30

Median survival 4-9 months –longer if good initial
response
Response 60-70% with 11-54% CR depending on
protocol, individual sensibility and clinical stage/substage
Large granular cell lymphoma or globule leukocyte
tumours poor response to chemotherapy but no large
clinical studies

Question 31

how may radiotherapy be used

Answer 31

Some good experimental results for use as a rescue therapy