Lymphoma Flashcards

1
Q

Compare the px for high grade B and T cell lymphomas

A

When treated with CHOP‐based protocols, dogs with high‐grade T cell lymphoma (TCL) have a lower remission rate, and those that do achieve a remission are reported to relapse more quickly and survive a shorter time than dogs with comparable stage high‐grade, B cell lymphoma (BCL)

However, the prognosis for dogs with a separate entity of indolent TCL is mostly considerably better than for dogs with any other type of lymphoma

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2
Q

How can you identify T cell lineage

A

CD3
PARR
Some neoplastic T cells lose the CD3 antigen but retain the TCR, hence some TCL may be negative for CD3 but positive on PARR

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3
Q

Are most lymphomas B or T cell in dogs?

A

Mostly B cell, although certain breeds are more commonly T cell (e.g. Sharpei, CKCS)

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4
Q

Which type of lymphoma in dogs is more likely to cause hypercalcaemia

A

Dogs with TCL appear more likely to present with hypercalcaemia, which appears to be mediated primarily by upregulation of parathyroid hormone related protein (PTHrP

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5
Q

What are the major types of t cell lymphoma?

A

T zone lymphoma (TZL) and high‐grade TCL

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6
Q

What is T zone lymphoma?

A

characterised by an expanding paracortical population of T cells that compress the germinal centres causing atrophy throughout the medulla. Morphology of the neoplastic cells is small to intermediate with absent to rare mitoses
difficult diagnosis to make on cytology, as the histological characteristics are more important than cell size

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7
Q

When do you treat T zone lymphoma?

A

Often don’t need to start straight away
There is no consensus as to criteria to use to institute therapy in dogs with TZL. The presence of the following are suggested as reasons to start therapy:

▪ Clinical signs (substage b);

▪ Rapid progression (doubling time of <6 months);

▪ Circulating lymphocyte count >9.2;

▪ Bulky multiple sites >3 cm or one site >7 cm;

▪ Development of myelosuppression due to myelophthisis; or

▪ Organ dysfunction due to infiltration

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8
Q

What are some suggested aetiologies of lymphoma?

A

 Genetic and epigenetic changes and congenital
aberrations
 Possible infectious causes unproven as yet in dogs
 Environmental factors
 Chemical exposure, polluted sites, incinerators and
radioactive waste
 Immune system alterations
 Many cases have recent inflammatory event
 Prior immune mediated disease associated with a
higher risk of subsequent lymphoma

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9
Q

What are the main presentations of lymphoma?

A
 Multicentric 80%
 Increasingly being subclassified
 Craniomediastinal 5%
 Gastro-intestinal 5 – 7%
 Cutaneous
 Extra-nodal forms
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10
Q

How does multicentric lymphoma present?

A
 Usually aggressive disease
 Occasional indolent cases
 Typical presentation
 Well dog to mild lethargy, weight loss, inappetance,
pyrexia
 Rapid progression
 Ocular changes common
 Big lymph nodes
 Around 20% pu/pd due to hypercalcaemia
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11
Q

How does cranio-mediastinal lymphoma present?

A

 Can occur as solitary lesion or part of multicentric form
 Malaise
 Often pu/pd due to hypercalcaemia
 Possibly tachypnoea, dyspnoea
 Occasionally pre-caval syndrome
 Altered position of PMI for cardiac auscultation

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12
Q

How does the gastrointestinal form present?

A

 Tends to be aggressive in dogs
 Diagnosis often delayed due to investigation in to GI signs
 There may be progression from other GI disease
 Clinical signs
 Weight loss, anorexia, pan-hypoproteinaemia, evidence of malabsorption
 Abdominal masses
 Occasionally multicentric lymphadenopathy

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13
Q

How does cutaneous lymphoma present?

A

 Epitheliotrophic and non-epitheliotrophic forms

 Epitheliotrophic
 T cell
 solitary or generalised
 may have lesions elsewhere
 GI tract and local lymph nodes

 Non-epitheliotrophic
 More frequently B cell
 More likely to have lesions elsewhere

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14
Q

What extranodal forms are there?

A
 Hepatosplenic -  Aggressive, no peripheral lymphadenopathy
 T cell
 Intravascular
 Ocular signs
 CNS
 Bone marrow
 Renal
 Rectal lymphoma
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15
Q

What paraneoplastic forms are common with lymphoma?

A
 Hypercalcaemia
 T cell
 Immune mediated diseases
 IMHA IMTP and Pemphigus IMHA, IMTP and Pemphigus foliaceous
 Monoclonal gammopathies
 Neuropathies
 Cachexia
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16
Q

What are the ddx for multicentric lymphoma

A
 Neoplasia
- Multicentric lymphoma
- Other haematopoetic disease
 Reactive
- Viral, bacteria, fungi, parasites
- Check travel history - Leishmania, Ehrlichia sp. Etc.
- Immune mediated diseases
17
Q

What may you see on blood work with lymphoma?

A
Haematology
 IMTP: 30 – 50%
 Neutrophilia: 25 – 40 %
 Lymphocytosis: 20%
 Flow cytometry helpful
 Important to differentiate between leukaemia and stage V lymphoma
Biochemistry
 Hypercalcaemia
 Check for signs of organ dysfunction
18
Q

What diagnostic tests are available for testing for lymphoma?

A
 Cytology - Not from areas where reactive changes are likely
 Immunocytochemistry
 Histopathology
 Immunophenotyping
 Special techniques
 Immunohistochemistry
 Flow cytometry
 PARR
19
Q

What staging can be done for lymphoma?

A

 Always
 CBC and biochemistry and urinalysis
 Thoracic radiograph

 Often
 Abd l l d Abdominal ultrasound
 (Immunophenotyping)

 Occasionally
 Bone marrow aspirate (if Cytopaenias)
 Flow cytometry (if Lymphocytosis and/or atypia)

20
Q

What are the main prognostic factors for lymphoma?

A

 Strong
 Substage, immunophenotype, steroid pretreatment, craniomediastinal lymphadenopathy, anatomic location, ongoing response to treatment
 Modest
 Stage, histopathologic grading, hypercalcaemia, gender, proliferation indices, history of chronic inflammatory disease, low cobalamin
 Debatable
 circulating enzymes (TK, LDH)
 New / Experimental
 Ability to detect minimal residual disease after starting treatment

21
Q

What are extra considerations for treating GI lymphoma?

A

Significance of intestinal masses
 Pre-chemotherapy surgery ?
 Possibility of wound healing issues after surgery
 Perforation after successful initial treatment

If more diffuse involvement
 Translocation also a risk
 Perforation still possible

22
Q

What is the ox when chemotherapy is not initiated?

A

 No treatment
 MST 4 – 6 weeks
 Prednisolone alone
 OOR 30% Median response duration 1 – 2 months

23
Q

Outline high dose COP

A

Vincristine, pred, cyclophosphamide
 Preferred to low dose COP
 Well tolerated protocol
 Easily and safely administered in general practice setting
 Haematology performed prior to each treatment
 Urine sample prior to and post each cyclophosphamide
 Consider dose reductions at the start of treatment
 Overall response rate 60 % – 80 %
 Median survival around 6 – 9 months.

24
Q

Outline discontinuous CHOP

A

COP + doxorubicin
 Response rate 90 – 95%
 Median survival time 10 – 12 months
 No advantage to continuous treatment

25
Q

Outline local treatments with lymphoma

A

 Rarely indicated especially as sole treatments
 Radiation might be useful for:
 Stage I disease
 Palliation of local disease
 Half body radiation after inducing remission with
chemotherapy
 Lurie et al 2009, JVIM
 Surgery
 Could be considered for rare Hodgkin’s lymphoma and possibly extranodal and early stage I disease

26
Q

What are the considerations with CNS lymphoma

A
 Many drugs don’t penetrate the blood brain barrier
 Cytarabine
 CCNU
 Steroids
 l’asparaginase
27
Q

Why is complete remission so important?

A

 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.
 If CR is not achieved this suggests a resistant
population of tumour cells. These will rapidly
become the dominant population.

28
Q

What may cause resistance?

A

 Genetic resistance
 Increase in MDR-1 pGp activity
 P-Glycoprotein pumps include steroids, vinka alkaloids and anthracyclines amongst their substrates
 Other mutations
 Tumour cells in a protected site
 Inadequate dose intensity
 If relapse occurs in the low intensity part of the protocol then going back to induction phase might help

29
Q

Outline rescue protocols

A

 Law of diminishing returns with each rescue

 DMAC
 72% ORR, 44% CR, 28% PR
 Median remission duration 2 mths, 3.5 mths if CR achieved

 CCNU, l’asparaginase and prednisolone
 87% ORR, 52% CR
 Median time to tumour progression 63 days

 Single agent anthracyclines if not already used
 BUT unlikely to be beneficial if MDR-1 actvity is high.

30
Q

Outline tx follow up

A

 Restaging
 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
 Follow up for CR patients not on treatment
 Monthly
 Almost all canine lymphoma patients relapse eventually

31
Q

Outline treatment for epitheliotropic lymphoma

A

 Typical protocols are COP or CCNU + P
 No proven extension of life span
 May improve QoL
 Response to treatment can be hard to gauge due to natural behaviour of disease
 Retinoids have also been used with moderate success for controlling clinical signs
 Radiation therapy is very useful for localised mucocutaneous disease