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Lymphoreticular and haematopoetic > Haematopoetic neoplasia > Flashcards

Haematopoetic neoplasia Flashcards

1
Q

What is the aetiology of canine lymphoma?

A

Genetic factors may be involved as breed predispositions in Boxers, Scottish Terriers, Bassets, bulldogs, Labradors, Airedales and St Bernards have been reported as well as familial incidences
Environmental factors include herbicides, strong magnetic fields and residence in industrial areas

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2
Q

What is the aetiology of feline lymphoma?

A

FeLV +ve increases risk due to recombination of FeLV genetic material with host DNA and may still be implicated in some cats testing -ve on p27 ELISA
FIV +ve increases risk due to unknown mechanism
Young Siamese and oriental cats predisposed
Tobacco smoke, IBD and immunosuppression also linked

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3
Q

What are the lymphoma predilection sites in dogs?

A

85% multicentric, 7% GI, 3% mediastinal/thymic, others less common than in cats except skin

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4
Q

What are the lymphoma predilection sites in cats?

A

25% LN and other, 4-12% just LNs, 50% GI, 10-20% mediastinal/thymic, <5% CNS, 5-10% renal, 5-10% nasopharyngeal, hepatic/splenic 5-10%, 1% skin

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5
Q

How do dogs with multicentric lymphoma present?

A

Peripheral lymphadenomegaly, often asymptomatic but sometimes vague lethargy, malaise, weight loss, anorexia, pyrexia, PU/PD if hypercalcaemic, +/- liver/spleen enlargement

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6
Q

Which LNs should be assessed in dogs with suspected lymphoma?

A

Submandibular, Prescapular, Axillary, superficial inguinal, popliteal

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7
Q

What are the DDx for multicentric lymphoma in dogs?

A

Disseminated infection causing lymphadenitis, immune-mediated diseases, other haematopoietic tumours, metastatic/disseminated neoplasia of other types, generalised skin disease, sterile granulomatous lymphadenitis

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8
Q

How do cats with multicentric lymphoma present?

A

Unusual and mostly just single/regional LN enlargement

Uncommon distinct form exists which involves solitary or regional LNs of head and neck

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9
Q

What DDx should be considered for multicentric lymphoma in cats?

A

Disseminated infection causing lymphadenitis, immune-mediated diseases, other haematopoietic tumours, metastatic/disseminated neoplasia of other types, generalised skin disease, sterile granulomatous lymphadenitis, benign hyperplastic LN syndromes

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10
Q

What are the presenting signs of GI lymphoma?

A

Weight loss, anorexia, vomiting and/or diarrhoea
Occasionally jaundice if liver involvement
Localised mass or multifocal diffuse thickened loops of intestine +/- mesenteric lymph node enlargement

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11
Q

What are the two different grades of GI lymphoma in cats?

A

High grade = mass lesions with relatively short history of illness, signs of GI obstruction
Low grade = diffuse thickening of intestinal loops or mild lymphadenmegaly, may have more chronic history

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12
Q

What are the DDx for Gi lymphoma?

A

IBD, other GI tumours, foreign bodies, intussusception

For cats rule out hyperthyroidism/renal failure/diabetes mellitus

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13
Q

What clinical signs are seen with mediastinal lymphoma?

A

Increased RR, tachypnoea, dyspnoea, dysphagia, weight loss, regurgitation, caudally displaced heart sounds, lung sounds reduced ventrally, loss of compressibility, caval syndrome, Horner’s, hypercalcaemia in dogs

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14
Q

What are the DDx for mediastinal lymphoma?

A

Other tumours, non-neoplastic mass lesions, other causes of effusion

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15
Q

How do cases of renal lymphoma present?

A

Large irregular kidneys on palpation often bilaterally, signs of kidney disease (PU/PD, anorexia, weight loss)

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16
Q

What are the differential diagnoses for renal lymphoma?

A

Polycystic kidney disease, pyelonephritis, FIP, acute renal failure, hydronephrosis, perinephric pseudocyst, other renal tumours

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17
Q

How do animals with CNS lymphoma present?

A

Insidious or rapidly progressive neurological signs

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18
Q

What DDx should be considered to CNS lymphoma?

A

Other CNS tumours, trauma, infection, aortic thrombus/embolism, discospondylitis, FeLV associated non-neoplastic myelopathy

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19
Q

How do animals with nasal lymphoma present?

A

Chronic nasal discharge (serosanguinouse to mucopurulent), epistaxis, sneezing, stertor, anorexia, facial deformity, exophthalmus, epiphora

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20
Q

What are the DDx for nasal lymphoma?

A

Cat flu, other neoplasms, fungal infection

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21
Q

How do animals with laryngeal/tracheal lymphoma present?

A

Upper respiratory tract obstruction, dyspnoea often in older cats (median 9 years)

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22
Q

How does ocular lymphoma present?

A

Uveitis, blepharospasm, infiltration, haemorrhage, retinal detachment

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23
Q

Describe the epitheliotrophic form of cutaneous lymphoma

A

T-cell,
3 stages - scaling, alopecia, pruritis -> erythematous thickened, ulcerated, exudative -> proliferative plaques and nodules with progressive ulceration
May involve oral mucosa/mucocutaneous junctions

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24
Q

Describe the non-epitheliotrophic form of cutaneous lymphoma

A

Can be T or B cell

Affects mid to deep dermis sparing the epidermis

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25
Q

What are the differential diagnoses for cutaneous lymphoma?

A

Infectious dermatitis, immune-mediated dermatitis, histiocytic skin disease, other cutaneous neoplasia

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26
Q

What are the characteristics of mediastinal lymphoma?

A

Often T cell phenotype

Occurs in younger cats

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27
Q

What are the characteristics of renal lymphoma?

A

Median age at presentation is 9 years old
Can be concurrent lymphoma else where and 40-50% of treated cats develop CNS lymphoma
Often intermediate to high grade

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28
Q

What are the characteristics of CNS lymphoma?

A

> 80% have mixed site involvement
One of the most common CNS tumours in cats
Can be intra/extra dural

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29
Q

What are the characteristics of nasal lymphoma?

A

Tends to be older cats (9-10 years)
75% B cell often localised but can spread
Intermediate to high grade

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30
Q

What are the different paraneoplastic syndromes that can be seen with lymphoma?

A

Hypercalcaemia
Hypergammaglobulinaemia
Haematological abnormalities
Rarely immune-mediated disease, polyneuropathy, hypoglycaemia

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31
Q

Why do dogs with lymphoma become hypercalcaemic?

A

PTHrP acts on kidneys and bone to increase levels of calcium in the blood and increase vitamin D3 to increase gut absorption

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32
Q

How many dogs get hypercalcaemia secondary to lymphoma?

A

10-40%

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33
Q

What are the signs of hypercalcaemia?

A

PU/PD due to nephrogenic diabetes insipidus, dehydration, depression, lethargy, weakness, vomiting, constipation, bradycardia/bradydysrhythmias, muscle tremors

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34
Q

What can happen if hypercalcaemia is left untreated?

A

Renal failure may occur due to decreased renal blood flow and or nephrocalcinosis

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35
Q

How do animals develop hypergammaglobulinaemia with lymphoma and what effect does it have?

A

Monoclonal gammopathy due to aberrant antibody production and it can cause hyperviscosity

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36
Q

What haematological abnormalities can occur with lymphoma?

A

Anaemia often mild non-regenerative due to chronic disease or myelophthisis
Thromboctyopaenia due to myelophthisis

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37
Q

What structures should be looked at closely if lymphoma is suspected on clinical exam?

A

Lymph nodes, mucous membranes, abdominal palpation, thoracic auscultations, percussion and compression

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38
Q

How are lymph node aspirates carried out?

A

23G needle only technique at multiple sites with ultrasound guidance of internal lymph nodes

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39
Q

Why is it best to chose lymph nodes other that the submandibulars?

A

Often have concurrent infection as mouth has lots of bacteria in it which can confuse cytology results

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40
Q

What should be done if cytology is inconclusive?

A

Lymph node, mass or organ biopsy for histopathology

Cytology of abdominal/pleural fluid and CSF analysis can also be useful

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41
Q

How are lymphomas subtyped?

A

Cytological/histological morphology, grade and immunophenotype can be important in deciding the specific subtype of classification

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42
Q

What impact can subtype have on treatment?

A

Different subtypes respond better to different treatments and have different prognoses

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43
Q

How are lymphomas graded and why is it important?

A

In dogs nearly all high grade
In cats cell size and morphology is important with small cells = low grade, large cells/blasts = high grade
Affects treatment and prognosis

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44
Q

What kind of sample is needed for immunophenotyping?

A

FNA into cytocheck medium for flow cytometry or biopsy for immunohistochemistry/immunocytochemistry

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45
Q

How can lymphomas be classified?

A

Using cell surface markers as B cell (CD79a+, CD21+) or T cell (CD3+, CD4+, CD8+)

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46
Q

What impact does immunophenotyping have on diagnosis?

A

Affects prognosis in canine lymphoma with B cell = better prognosis
May affect treatment choice as in dogs high grade T cell lymphomas seem to respond well to alkyating agents

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47
Q

How are clonal assays or PARR used to clarify diagnosis in lymphoma?

A

Monoclonal population of cells, PCR used to amplify DNA of antigen receptor region from lymphoma cells a single band will be obtained following electrophoresis
If wasn’t lymphoma several bands would be present

48
Q

What information does haematology results give in lymphoma?

A

General health status - check for cytopenias or abnormal circulating cells, essential baseline prior to chemo
Anaemia - mild, normochromis, normocytic, non-regen
If multiple cytopenias = myelophthisis

49
Q

How does biochemistry aid lymphoma diagnosis?

A

Assess which organs are involved and look for paraneoplastic effects
Look for raised liver enzymes/bilirubin, azotaemia, hypoproteinaemia, hypercalcaemia, hyperglobulinaemia

50
Q

How does urinalysis contribute to lymphoma diagnosis?

A

Essential for interpretation of azotaemia and good for baseline information prior to starting chemo

51
Q

How is lymphoma staged?

A

Stage 1 = solitary node/lymphoid tissue of one organ
Stage 2 = multiple LNs in a single region
Stage 3 = generalised LN involvement
Stage 4 = liver and/or spleen involvement
Stage 5 = bone marrow involvement +/- other organs

52
Q

What are the two substages used in staging of lymphoma?

A

Substage a = no clinical signs

Substage b = systemic signs (worse prognosis)

53
Q

What do you look for in thoracic/abdominal radiography of lymphoma patient?

A 
Thoracic = sternal/tracheobronchial lymphadenopathy, mediastinal mass, lung patterns, pleural effusion
Abdominal = hepatomegaly, splenomegaly, renomegaly, abdominal lymphadenopathy, masses
54
Q

What do you look for on ultrasound of abdomen?

A

Changes in echogenicity of organs, enlargement of organs, abdominal lymphadenopathy, abdominal masses, GI lymphoma

55
Q

When would a bone marrow aspirate or biopsy be indicated?

A

For full staging in clinical studies

56
Q

What is the minimum database of tests prior to starting lymphoma treatment?

A

Haematology, biochemistry and urinalysis

57
Q

What are the options for treatment of lymphoma?

A

Combination chemotherapy is most effective
Radiation treatment good for nasal/localised lymphoma
Corticosteroids alone for palliative treatment
Surgery has few indications (Hodgkin’s like lymphoma in cats)

58
Q

What is important to remember when using corticosteroids as a treatment for lymphoma?

A

Effect lasts about 2-3 months
Promote multi-drug resistance so if planning on using chemotherapy wait and use steroids as part of protocol don’t pre-treat

59
Q

What needs to be discussed with clients prior to chemotherapy treatment starting?

A

Goals of treatment with owners (remission not cure), potential adverse effects not as bad as in people, owner’s commitment to costs, travel, frequent appointments and patient temperament

60
Q

What two chemotherapy protocols are commonly use to treat lymphoma?

A

COP-based (cyclophosphamide, vincristine, prednisolone)

CHOP-based (COP plus doxorubicin)

61
Q

How do COP and CHOP protocols differ other than drugs used?

A

COP has induction phase then oral maintenance phase

CHOP has more intensive induction phase with no maintenance

62
Q

What is the structure of a CHOP protocol?

A

Week 1 = vincristine and prednisolone
Week 2 = cyclophosphamide and prednisolone
Week 3 = vincristine and prednisolone
Week 4 = doxorubicin and prednisolone
Then 6 = V, 7 = C, 8 = V, 9 = D, 11 = V, 13 = C, 15= V, 17 = D, 19 = V, 21 = C, 23 = V, 25 = D
If patient in remission then treatment stopped at wk25

63
Q

What is the structure of a COP protocol in dogs?

A

Cyclophosphamide at 50mg/m^2 PO every 48 hours or on the 1st four days of each week
Vincristine 0.5-0.7mg/m^2 IV every 7 days
Prednisolone 40mg/m^2 PO daily wk1, then 20mg/m^2 every 48 hours
If in remission after 8 weeks go onto maintenance of 20mg/m^2 chlorambucil PO every 2 weeks, 20mg/m^2 pred PO every other day

64
Q

How does the COP protocol differ in cats?

A

50mg cyclophosphamide tablets can’t be split so usually give 200mg/m^2 cyclophosphamide in week 1 and 4
For renal/CNS incorporate sytosine arabinoside on day 1 an hour after vincristine at 250mg/m^2 IV infusion over 4-12 hours and repeat in week 4

65
Q

What is the treatment for low grade GI lymphoma in cats?

A

Chlorambucil 20mg/m^2 PO every 2 wks

Prednisolone 40mg/m^2 daily for one week then 20 mg/m^2 PO every other day

66
Q

What is the modified LOPP protocol for high grade T cell lymphomas in dogs structure?

A

Week 1 = Vincristine 0.5 mg/m^2 IV once, Prednisolone 40mg/m^2 PO daily, Procarbazine 50mg/m^2 PO
Week 2 = Lomustine 60-70 mg/m^2 PO once, Prednisolone 20mg/m^2 PO EOD
Week 3 = Prednisolone 20mg/m^2 PO EOD

67
Q

What low cost protocols can be used to treat lymphoma?

A

Prednisolone 40mg/m^2 daily for 7 days then 20mg/m^2 EOD
Prednisolone as above and chlorabucil 20mg/m^2 every 2 weeks
Lomustine 50-70 mg/m^2 every 21 days in dogs or 50mg/m^2 every 3-6 weeks in cats +/- prednisolone

68
Q

What tests should be used to monitor patients on chemotherapy?

A

Regular physical examination, Haematology to check for myelosuppression, Biochemistry to monitor abnormal parameters, Urinalysis for haemorrhagic cystitis, Echocardiography if using doxorubicin

69
Q

How do you manage GI disturbances in chemotherapy patients?

A

Frequently self-limiting and mild

If bright, alert and afebrile starve for 24 hours followed by bland diet and may require IVFT

70
Q

What anti-emetics and gut protectants can be useful in a vomiting/diarrhoeic chemotherapy patient?

A

Maripotant, metaclopramide, ondansetron, probiotics, metronidazole

71
Q

What can be used to manage anorexia in a chemotherapy patient?

A

Anti-emetics and gut protectants and consider appetite stimulants or feeding tubes

72
Q

What should be done if a chemotherapy patient has myelosuppression?

A

If marked neutropenia but asymptomatic consider prophylactic oral broad spectrum antibiotics
If febrile neutropenic crisis administer broad spectrum antibiotics IV, barrier nurse and consider gut protectants

73
Q

How is haemorrhagic cystitis managed in chemotherapy patients?

A

Stop cyclophosphamide, NSAIDs if preds stopped, oxybutinin, antispasmodica dn GAGs
Prevent by encouraging water uptake and give cyclophosphamide in morning giving plenty of opportunity to urinate, consider furosemide

74
Q

How do animals with hypersensitivity to L-asparaginase/doxorubicin present?

A 
Dogs = urticaria, oedema, hyperaemia, vomiting, diarrhoea
Cats = respiratory distress, vomiting
75
Q

How do you treat animals with hypersensitivity to chemotherapy drugs?

A

Stop treatment and give antihistamine and dexamethasone

76
Q

How can extravasation of chemotherapy drugs IV be avoided?

A

Use first stick IV catheter

77
Q

What should be done if extravasation occurs?

A

Leave catheter in place and attempt to withdraw as much drug as possible
Ice doxorubicin and heat vincristine and seek specialist advice

78
Q

What is the prognosis for dogs and cats with no treatment for lymphoma?

A

Up to 4-6 weeks median survival time

79
Q

What is the prognosis for prednisolone treatment in dogs for lymphoma?

A

Remission rate of 33%, median remission time of 1 month and median survival time of 2-3 months

80
Q

What is the prognosis for COP protocol in dogs to treat lymphoma?

A

Remission rate of 70-80%, median remission time of 3-6 months, median survival time of 7-9 months

81
Q

What is the prognosis for COP protocol in cats to treat lymphoma?

A

Remission rate of 50-80%, median remission time of 3-8 months (high grade) and median survival time of 3-10 months (high grade)

82
Q

What is the prognosis for CHOP protocol in dogs to treat lymphoma?

A

Remission rate of 80-94%, median remission time of 9 months, median survival time of 12-13 months, 20-25% survive over 2 years

83
Q

What is the prognosis for CHOP protocol in cats to treat lymphoma?

A

Remission rate of 50-70%, median remission time of 4 months (high grade), median survival time (3-10 months (high grade), 30% 1 year survival

84
Q

What is the prognosis for GI lymphoma in cats?

A

Low grade, small cell, lymphocytic T cell on clorambucil/pred = MST of 2 years
Feline high grade lymphobastic MST of 3-9 months
Feline large granular lymphocyte lymphoma = MST 1-2 months

85
Q

What is the prognosis for GI lymphoma in dogs?

A

Often poor with MST of 77 days but wide range from 6-700 days

86
Q

What are the negative prognostic indicators for lymphoma in dogs?

A

T cell immunophenotype, clinical substage b, hypercalcaemia, bone marrow involvement, prolonged pre-treatment with corticosteroids, failure to achieve complete remission, GI/renal/pure hepatic lymphoma

87
Q

What are the negative prognostic indicators for cats with lymphoma?

A

Failure to achieve complete remission, FeLV +ve status, high grade vs low grade, LGL lymphoma has very poor prognosis

88
Q

What should be done if an animal relapses?

A

If not currently receiving treatment restart original protocol, if on maintenance start induction again, if relapses during induction uses new drugs the tumour hasn’t been exposed to yet

89
Q

How is hypercalcaemia managed?

A

Saline diuresis at 6mls/kg/hr and once rehydrated introduce furosemide at 1-2mg/kg to promote calciuresis
Treat the underlying cause

90
Q

What are leukaemias?

A

Malignant neoplasms originating from haematopoietic precursor cells in the bone marrow or sometimes spleen
Malignant cells may be present in the circulation sometimes in large numbers and neoplastic cells sometimes proliferate in bone marrow causing cytopenias

91
Q

What two broad categories can leukaemias be put into?

A

Lymphoid or myeloid depending on the cell line they originate from

92
Q

What are the characteristics of an acute leukaemia?

A 
Aggressive biological behaviour with rapid disease progression and severe clinical signs
Immature cells (blasts) in the marrow or blood which are poorly differentiated with a high capacity for rapid cell division and have a poor prognosis
93
Q

What are the characteristics of a chronic leukaemia?

A

Slow disease course and mild clinical signs
Neoplastic cells are well-differentiated, late precursor cells with a lesser capacity for division and a reasonable prognosis

94
Q

How do you differentiate between lymphoid leukaemia and stage V lymphoma?

A

Dogs with acute lymphoid leukaemia (ALL) usually sicker and have more profound cytopenias and milkder lymphadenomegaly
Flow cytometry can be useful to differentiate as ALL have CD34 cell surface marker found on stem cells

95
Q

What are myeloproliferative disorders?

A

Neoplastic and possibly pre- or non-neoplastic conditions of all the non-lymphoid cells in the marrow and are uncommon and not well characterised in dogs and cats

96
Q

What are examples of acute myeloid leukaemias?

A

Undifferentiated leukaemia, myeloblastic leukaemia, myelomonocytic leukaemia, monoblastic leukaemia, megakaryoblastic leukaemia, erythroleukaemia and subtypes of all of the above

97
Q

What are examples of myeloproliferative neoplasms or chronic myeloproliferative disorders?

A

Chronic nyelogenous leukaemia, eosinophilic and basophilic leukaemia, primary thrombocytosis, polycythaemia vera

98
Q

What are the clinical signs of leukaemia?

A

Lethargy, weakness, malaise, anorexia, GI signs, mild generalised lymphadenopathy, hepatosplenomegaly
Signs related to myelophthisis - fever, petechial haemorrhages, pallor
Sometimes signs of hypercalcaemia

99
Q

How is leukaemia diagnosed?

A

If abnormal cells are circulating then flow cytometry

May require a bone aspirate/core biopsy

100
Q

What is the treatment for acute leukaemia?

A

For ALL can potentially use same drugs as leukaemia but maybe start with L-asparaginase and pred
For AML can try cytosine arabinoside

101
Q

What is the prognosis for acute leukaemia?

A

For a dog that responds to therapy (30%) MST 120 days with cats response rate is similar but remission slightly longer

102
Q

What needs to be considered prior to treatment of acute leukaemia?

A

Pre-existing cytopenias are a problem as chemo drugs are myelosuppressive and significant risk of sepsis/bleeding

103
Q

How is chronic lymphoid leukaemia (CLL) treated?

A

Chlorambucil and prednisolone

104
Q

What is the prognosis for CLL?

A

Survivals of 1-3 years reported and median 1 year in dogs

105
Q

What is the prognosis for chronic myeloid leukaemia (CML)?

A

4-15 months reported when treated with hydroxycarbamide in dogs

106
Q

What is a myeloma?

A

Plasma cell tumour affecting the bone marrow in older animals

107
Q

What are the clinical signs of a myeloma?

A

Mild pyrexia, lethargy, pallor, mild generalised lymphadenopathy, hepatosplenomegaly, signs of hyperviscosity

108
Q

What does haematology and biochemistry show with an animal with myeloma?

A

Mild non-regenerative anaemia, cytopenias, hyperglobulinaemia, +/- hypercalcaemia

109
Q

What do radiographs of myeloma show?

A

Punched out osteolytic lesions of diffuse osteopenia

110
Q

What does urinalysis show in an animal with myeloma?

A

Immunoglobulin light chain sin urine (Bence-Jones proteinuria)

111
Q

How is myeloma diagnosed?

A

Bone marrow aspirate/biopsy showing increased numbers of plasma cells

112
Q

What is the treatment for myeloma?

A

Melphalan and prednisolone in dogs MST 12-18 months

Chlorambucil and predisolone in cats

113
Q

What is polycythemia vera/primary erythrocytosis?

A

Proliferation of the erythroid cell series in the marrow

114
Q

What are the clinical signs of polycythemia vera/primary erythrocytosis?

A

Bright red MM, neurological signs due to hyperviscosity of the blood, persistently high PCV with low or normal erythropoietin activity

115
Q

What does polycythemia vera/primary erythrocytosis need to be differentiated from?

A

Dehydratioin and appropriate causes of increased RBC such as hypoxia
EPO producing tumours

116
Q

What is the treatment for polycythemia vera/primary erythrocytosis?

A

Phlebotomies and replacement of blood with colloids/electrolytes to alleviate hyperviscosity
Hydroxycarbamide

Lymphoreticular and haematopoetic (12 decks)

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