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Haematopoetic neoplasia Flashcards

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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
What are the differential diagnoses for cutaneous lymphoma?
Infectious dermatitis, immune-mediated dermatitis, histiocytic skin disease, other cutaneous neoplasia
26
What are the characteristics of mediastinal lymphoma?
Often T cell phenotype | Occurs in younger cats
27
What are the characteristics of renal lymphoma?
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
28
What are the characteristics of CNS lymphoma?
>80% have mixed site involvement One of the most common CNS tumours in cats Can be intra/extra dural
29
What are the characteristics of nasal lymphoma?
Tends to be older cats (9-10 years) 75% B cell often localised but can spread Intermediate to high grade
30
What are the different paraneoplastic syndromes that can be seen with lymphoma?
Hypercalcaemia Hypergammaglobulinaemia Haematological abnormalities Rarely immune-mediated disease, polyneuropathy, hypoglycaemia
31
Why do dogs with lymphoma become hypercalcaemic?
PTHrP acts on kidneys and bone to increase levels of calcium in the blood and increase vitamin D3 to increase gut absorption
32
How many dogs get hypercalcaemia secondary to lymphoma?
10-40%
33
What are the signs of hypercalcaemia?
PU/PD due to nephrogenic diabetes insipidus, dehydration, depression, lethargy, weakness, vomiting, constipation, bradycardia/bradydysrhythmias, muscle tremors
34
What can happen if hypercalcaemia is left untreated?
Renal failure may occur due to decreased renal blood flow and or nephrocalcinosis
35
How do animals develop hypergammaglobulinaemia with lymphoma and what effect does it have?
Monoclonal gammopathy due to aberrant antibody production and it can cause hyperviscosity
36
What haematological abnormalities can occur with lymphoma?
Anaemia often mild non-regenerative due to chronic disease or myelophthisis Thromboctyopaenia due to myelophthisis
37
What structures should be looked at closely if lymphoma is suspected on clinical exam?
Lymph nodes, mucous membranes, abdominal palpation, thoracic auscultations, percussion and compression
38
How are lymph node aspirates carried out?
23G needle only technique at multiple sites with ultrasound guidance of internal lymph nodes
39
Why is it best to chose lymph nodes other that the submandibulars?
Often have concurrent infection as mouth has lots of bacteria in it which can confuse cytology results
40
What should be done if cytology is inconclusive?
Lymph node, mass or organ biopsy for histopathology | Cytology of abdominal/pleural fluid and CSF analysis can also be useful
41
How are lymphomas subtyped?
Cytological/histological morphology, grade and immunophenotype can be important in deciding the specific subtype of classification
42
What impact can subtype have on treatment?
Different subtypes respond better to different treatments and have different prognoses
43
How are lymphomas graded and why is it important?
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
44
What kind of sample is needed for immunophenotyping?
FNA into cytocheck medium for flow cytometry or biopsy for immunohistochemistry/immunocytochemistry
45
How can lymphomas be classified?
Using cell surface markers as B cell (CD79a+, CD21+) or T cell (CD3+, CD4+, CD8+)
46
What impact does immunophenotyping have on diagnosis?
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
47
How are clonal assays or PARR used to clarify diagnosis in lymphoma?
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
What information does haematology results give in lymphoma?
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
How does biochemistry aid lymphoma diagnosis?
Assess which organs are involved and look for paraneoplastic effects Look for raised liver enzymes/bilirubin, azotaemia, hypoproteinaemia, hypercalcaemia, hyperglobulinaemia
50
How does urinalysis contribute to lymphoma diagnosis?
Essential for interpretation of azotaemia and good for baseline information prior to starting chemo
51
How is lymphoma staged?
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
What are the two substages used in staging of lymphoma?
Substage a = no clinical signs | Substage b = systemic signs (worse prognosis)
53
What do you look for in thoracic/abdominal radiography of lymphoma patient?
``` Thoracic = sternal/tracheobronchial lymphadenopathy, mediastinal mass, lung patterns, pleural effusion Abdominal = hepatomegaly, splenomegaly, renomegaly, abdominal lymphadenopathy, masses ```
54
What do you look for on ultrasound of abdomen?
Changes in echogenicity of organs, enlargement of organs, abdominal lymphadenopathy, abdominal masses, GI lymphoma
55
When would a bone marrow aspirate or biopsy be indicated?
For full staging in clinical studies
56
What is the minimum database of tests prior to starting lymphoma treatment?
Haematology, biochemistry and urinalysis
57
What are the options for treatment of lymphoma?
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
What is important to remember when using corticosteroids as a treatment for lymphoma?
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
What needs to be discussed with clients prior to chemotherapy treatment starting?
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
What two chemotherapy protocols are commonly use to treat lymphoma?
COP-based (cyclophosphamide, vincristine, prednisolone) | CHOP-based (COP plus doxorubicin)
61
How do COP and CHOP protocols differ other than drugs used?
COP has induction phase then oral maintenance phase | CHOP has more intensive induction phase with no maintenance
62
What is the structure of a CHOP protocol?
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
What is the structure of a COP protocol in dogs?
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
How does the COP protocol differ in cats?
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
What is the treatment for low grade GI lymphoma in cats?
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
What is the modified LOPP protocol for high grade T cell lymphomas in dogs structure?
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
What low cost protocols can be used to treat lymphoma?
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
What tests should be used to monitor patients on chemotherapy?
Regular physical examination, Haematology to check for myelosuppression, Biochemistry to monitor abnormal parameters, Urinalysis for haemorrhagic cystitis, Echocardiography if using doxorubicin
69
How do you manage GI disturbances in chemotherapy patients?
Frequently self-limiting and mild | If bright, alert and afebrile starve for 24 hours followed by bland diet and may require IVFT
70
What anti-emetics and gut protectants can be useful in a vomiting/diarrhoeic chemotherapy patient?
Maripotant, metaclopramide, ondansetron, probiotics, metronidazole
71
What can be used to manage anorexia in a chemotherapy patient?
Anti-emetics and gut protectants and consider appetite stimulants or feeding tubes
72
What should be done if a chemotherapy patient has myelosuppression?
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
How is haemorrhagic cystitis managed in chemotherapy patients?
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
How do animals with hypersensitivity to L-asparaginase/doxorubicin present?
``` Dogs = urticaria, oedema, hyperaemia, vomiting, diarrhoea Cats = respiratory distress, vomiting ```
75
How do you treat animals with hypersensitivity to chemotherapy drugs?
Stop treatment and give antihistamine and dexamethasone
76
How can extravasation of chemotherapy drugs IV be avoided?
Use first stick IV catheter
77
What should be done if extravasation occurs?
Leave catheter in place and attempt to withdraw as much drug as possible Ice doxorubicin and heat vincristine and seek specialist advice
78
What is the prognosis for dogs and cats with no treatment for lymphoma?
Up to 4-6 weeks median survival time
79
What is the prognosis for prednisolone treatment in dogs for lymphoma?
Remission rate of 33%, median remission time of 1 month and median survival time of 2-3 months
80
What is the prognosis for COP protocol in dogs to treat lymphoma?
Remission rate of 70-80%, median remission time of 3-6 months, median survival time of 7-9 months
81
What is the prognosis for COP protocol in cats to treat lymphoma?
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
What is the prognosis for CHOP protocol in dogs to treat lymphoma?
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
What is the prognosis for CHOP protocol in cats to treat lymphoma?
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
What is the prognosis for GI lymphoma in cats?
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
What is the prognosis for GI lymphoma in dogs?
Often poor with MST of 77 days but wide range from 6-700 days
86
What are the negative prognostic indicators for lymphoma in dogs?
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
What are the negative prognostic indicators for cats with lymphoma?
Failure to achieve complete remission, FeLV +ve status, high grade vs low grade, LGL lymphoma has very poor prognosis
88
What should be done if an animal relapses?
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
How is hypercalcaemia managed?
Saline diuresis at 6mls/kg/hr and once rehydrated introduce furosemide at 1-2mg/kg to promote calciuresis Treat the underlying cause
90
What are leukaemias?
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
What two broad categories can leukaemias be put into?
Lymphoid or myeloid depending on the cell line they originate from
92
What are the characteristics of an acute leukaemia?
``` 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
What are the characteristics of a chronic leukaemia?
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
How do you differentiate between lymphoid leukaemia and stage V lymphoma?
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
What are myeloproliferative disorders?
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
What are examples of acute myeloid leukaemias?
Undifferentiated leukaemia, myeloblastic leukaemia, myelomonocytic leukaemia, monoblastic leukaemia, megakaryoblastic leukaemia, erythroleukaemia and subtypes of all of the above
97
What are examples of myeloproliferative neoplasms or chronic myeloproliferative disorders?
Chronic nyelogenous leukaemia, eosinophilic and basophilic leukaemia, primary thrombocytosis, polycythaemia vera
98
What are the clinical signs of leukaemia?
Lethargy, weakness, malaise, anorexia, GI signs, mild generalised lymphadenopathy, hepatosplenomegaly Signs related to myelophthisis - fever, petechial haemorrhages, pallor Sometimes signs of hypercalcaemia
99
How is leukaemia diagnosed?
If abnormal cells are circulating then flow cytometry | May require a bone aspirate/core biopsy
100
What is the treatment for acute leukaemia?
For ALL can potentially use same drugs as leukaemia but maybe start with L-asparaginase and pred For AML can try cytosine arabinoside
101
What is the prognosis for acute leukaemia?
For a dog that responds to therapy (30%) MST 120 days with cats response rate is similar but remission slightly longer
102
What needs to be considered prior to treatment of acute leukaemia?
Pre-existing cytopenias are a problem as chemo drugs are myelosuppressive and significant risk of sepsis/bleeding
103
How is chronic lymphoid leukaemia (CLL) treated?
Chlorambucil and prednisolone
104
What is the prognosis for CLL?
Survivals of 1-3 years reported and median 1 year in dogs
105
What is the prognosis for chronic myeloid leukaemia (CML)?
4-15 months reported when treated with hydroxycarbamide in dogs
106
What is a myeloma?
Plasma cell tumour affecting the bone marrow in older animals
107
What are the clinical signs of a myeloma?
Mild pyrexia, lethargy, pallor, mild generalised lymphadenopathy, hepatosplenomegaly, signs of hyperviscosity
108
What does haematology and biochemistry show with an animal with myeloma?
Mild non-regenerative anaemia, cytopenias, hyperglobulinaemia, +/- hypercalcaemia
109
What do radiographs of myeloma show?
Punched out osteolytic lesions of diffuse osteopenia
110
What does urinalysis show in an animal with myeloma?
Immunoglobulin light chain sin urine (Bence-Jones proteinuria)
111
How is myeloma diagnosed?
Bone marrow aspirate/biopsy showing increased numbers of plasma cells
112
What is the treatment for myeloma?
Melphalan and prednisolone in dogs MST 12-18 months | Chlorambucil and predisolone in cats
113
What is polycythemia vera/primary erythrocytosis?
Proliferation of the erythroid cell series in the marrow
114
What are the clinical signs of polycythemia vera/primary erythrocytosis?
Bright red MM, neurological signs due to hyperviscosity of the blood, persistently high PCV with low or normal erythropoietin activity
115
What does polycythemia vera/primary erythrocytosis need to be differentiated from?
Dehydratioin and appropriate causes of increased RBC such as hypoxia EPO producing tumours
116
What is the treatment for polycythemia vera/primary erythrocytosis?
Phlebotomies and replacement of blood with colloids/electrolytes to alleviate hyperviscosity Hydroxycarbamide

Lymphoreticular and haematopoetic (12 decks)

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