Diagnosis and Management of Lymphoid Diseases Flashcards
(96 cards)
1
Q
What is lymphoma?
A
Tumour of WBC
2
Q
Name breed predilection to lymphoma
A
–Boxer/Mastiff
–Siamese
3
Q
What are the 3 types of lymphoma classification?
A
•Classification based on anatomy
–Multicentric
–Alimentary
–Cutaneous
–Mediastinal
–Extra-nodal
•Classification based on histology
–Low, intermediate or high grade
–Cell size – small vs. large cell
•Classification based on immunophenotype
–B cell (most common canine variety)
–T cell
–Null cell
4
Q
What is the clinical presentation of lymphoma?
A
–Depends on type (anatomic)
- Mediastinal – tachypnoea/hyperpnoea
- CNS – seizures
- Cutaneous – pruritus/scaling
–Multicentric is easier to identify due to lymphadenopathy
•Dogs often very well despite this
–Paraneoplastic syndromes e.g.
•hypercalcaemia – PU/PD
–Commonest with T-cell
–Due to parathyroid hormone related protein (PTHrp) and other cytokines
•thrombocytopaenia
5
Q
What is the clinical presentation of lymphoma in cats?
A
- Multicentric form rare, seen in Australia
- Historically major association with FeLV
–Young cats with typically with mediastinal involvement
–Following introduction of vaccination this has fallen dramatically
•Extranodal more common than in dogs
–hepatic, nasal, CNS, mediastinal, renal
–Alimentary form now more common than rest in older cats but can be difficult to diagnose
•Association with helicobacter in gastric lymphoma?
6
Q
What lymphoma is common in calves? What is it a cause of?
Diagnosis?
Treatment?
A
Thymic lymphoma as a cause of chronic bloat
–Diagnose on percussion, no treatment
7
Q
Wt lymphoma is common in horses?
A
Splenic lymphoma
8
Q
What type of lymphoma is seen in camelids?
A
Extranodal lymphoma
9
Q
How can you diagnose lymphoma?
A
–FNA often good enough to get initial Y/N
•FNA cannot tell the B vs. T type well
–Biopsy by tru-cut often adequate for histo
–Can remove a node but can get seromas…….
- Immunohistochemistry for further characterisation
- Enables clarification of B vs. T – influence on prognosis?
–Flow cytometry - immunophenotyping
•Becoming a more widely available test
–Clonality tests – PCR test for antigen receptor gene rearrangement (PARR test)
- FNA, histo
- Can also use for phenotyping
10
Q
What iis staging? How is it done? Is it essential?
A
–This refers to the extent of the disease
–Carried out once diagnosis has been made
•Or during initial diagnostic investigations
–Stages I-V
- Thoracic and abdominal imaging
- Bone marrow evaluation
–Single site should be sufficient no need for multiple
–BUT is staging essential?
•Most important prognostic factor is bone marrow involvement
–Influences treatment
–Prognostication?
•Pragmatic – save money for chemo??
11
Q
What is the criteria of lymphoma stafes 1-4?
A
Stage
Criteria
I
Single LN affected
II
Multiple LN affected in single area/region
III
Generalised lymphadenopathy
IV
Liver AND/OR splenic involvement (with or without stages I-III)
V
Bone marrow OR blood involvement AND/OR any non-lymphoid organ (with or without stages I-IV)
Substage – (applicable to any stage I-V)
a – without clinical signs of disease
b – with clinical signs of disease
12
Q
Which form do 1-4 lymphoma refer to?
A
Nodal form
13
Q
Which neoplasia starts in the marrow and which works its way in?
A
- Lymphoma (probably) starts outside the marrow and works its way there
- Leukaemia starts in the marrow
14
Q
Is lymphoma a surgical disease?
A
Only if very localised
15
Q
How do you treat lymphoma?
A
- Ensure you have a definite diagnosis first!
- Chemotherapy as the mainstay NOT surgery
- Lymphoma is also radiosensitive
–Local disease or as part of complex protocols
–Nasal lymphoma…..
- Some choose to euthanase at diagnosis
- Median survival time depends on treatment?
- Many different protocols with many drugs
–Most protocols will use corticosteroids
–B versus T therapies?
16
Q
What % of lymphoma cases go into remission after treatment?
A
80%
17
Q
What is the common lymphoma protocol?
A
•COP and CHOP
–C = Cyclophosphamide (capsule)
–H = Doxorubicin (injection, care on handling)
–O = Vincristine (injection)
–P = prednisolone (tablet or injection)
18
Q
How do you monitor multicentric lymphoma?
A
Palpate and measure nodes
19
Q
How do you monitor extranodal lymphoma?
A
Image and clinical signs
20
Q
Name 6 side effects of chemotherapy for lymphoma (8)
A
–Neutropenia (cyclophosphamide and dox)
–Nausea, vomiting and diarrhoea (infrequent but many)
–Haemorrhagic cystitis (cyclophosphamide)
–Hair loss (all drugs, continual hair coat dogs)
–Anaphylaxis (doxorubicin)
–Arrhythmia and cardiotoxicity (doxorubicin)
–Severe skin slough if goes round catheter (doxorubicin>vincristine)
–PUPD, hunger, muscle wastage - glucocorticoids
21
Q
How do we dose for chemotherapy?
A
•mg/m2, NOT mg/kg
22
Q
What must we do for giant breeds undergoing chemo?
A
Reduce steroids?
23
Q
Discuss the prognosis for lymphoma
A
- Depends on the site, stage, treatment, owners……
- May not treat aggressive dogs/cats?
- Median survivals:
–Prednisolone only ~3 mths
–COP ~ 6 months
–Doxorubicin based protocols (CHOP) ~9 months
•Hard to predict how a dog will respond
–Factors that influence
- Clinical stage (III vs. V), substage a vs. b, mediastinal, immunophenotype, pre-treatment with steroids
- Cats would also need to include FeLV status, and immunophenotype has not been clearly associated with outcome
–Major influence on outcome is initial response to treatment
24
Q
What is an indolent lymphoma and how is it treated?
A
–Single node presentation
–Surgically excise?
25
Which type of lymphoma is thought to do very badly in dogs?
GI lymphoma
26
What are the different forms of primary cutaenous lymphoma?
–Generalised scale, pruritus
–Foci of erythroderma, crusting, ulceration
–Multiple dermal nodules/erythematous plaques
–Mucocutaneous lesions (may depigment)
27
What is the difference between non-epitheliotropic lymphoma and epitheliotropic lymphoma?
Non-epitheliotropic lymphoma= Rapid metastasis, grave prognosis
Epitheliotropic lymphoma= Chronic, may wax/wane initially
28
How do we treat cutaenous lymphoma and what is the prognosis?
Median survival time in terms of months
## Footnote
Chemotherapy for cutaneous lymphoma is lomustine and prednisolone can also use CHOP or in some cases Retinoids
Surgery if solitary/localised?
Surgery or radiotherapy if localised EL of lips/mouth?
29
What is the most common form of lymphoma in cats?
Feline alimentary lymphoma
30
Feline alimentary lymphoma:
A) How do cats present?
B) What are the forms?
C) How can we treat?
D) Which form doesnt do as well?
A) Diarrhoea, weight loss, palpable masses, thickened bowel loops
B) Small and large
C) Can be surgical if small area, then chemo- Small cell can respond well to prednisolone and chlorambucil with good MST
D) Large
31
Which lymphoma tends to present in cats as chronic rhinitis?
Feline nasla lymphoma
32
Feline nasal lymphoma:
A) What do we need to do to test?
B) What may develop later?
C) How can we treat?
A) Image/rhinocscopy
B) Renal lymphoma
C) Irradiate the nose and chemo
33
What is the general signalment for canine mast cell tumours?
* Usually older dogs (mean 9yo)
* A number of predisposed breeds
–Boxer, G Retrievers and pugs
–Pugs can suffer with multiple MCTs but are low-grade
–Young Shar-Peis (+ Labradors): often higher grade
–Golden Retrievers: multiple (recurrent) primary mast cell tumours
34
Where do mast cell tumours readily metastasise? (4)
Lymph node, liver, spleen and bone marrow
35
What are Basophilic intracytoplasmic granules (‘spotty fried egg’) on cytology often accompanied by?
Eosinophils
36
What is the difference between well and poor differentiaed MCT masses?
–Well differentiated mass – slow growing, hairless, solitary
–Poorly differentiated – rapid growth, ulcerated, pruritic
37
How can we go about diagnosing mast cell tumours?
* FNA
38
What do we do about staging MCT?
–Crucial to assess regional lymph node
* Many dogs (~1/3 or more) have local mets at time of presentation
* Rare to develop distant mets if local LN not involved
–Scan liver and spleen with FNA of each to be complete
* However this is of unclear value if the local LN is clear
* Some evidence that affected lymph nodes not always obvious regional node (sentinel lymph node mapping)
–Unlikely to metastasise to lungs therefore thoracic radiographs not important however these may aid with staging if find evidence for metastasis elsewhere
39
How do we use hhistopathology with a MCT?
–Definitive approach for grading tumour
* Essential step for prognostication
* Patnaik system grade I-III (reflects well to poorly diff)
* New system
–Incisional is best in order to plan surgery in advance
–Excisional acceptable if know MCT present and treat as poorly diff
–Can only GRADE on a biopsy – incisional or excisional biopsies
–Recent evidence would suggest Ki-67 and mitotic index can help differentiate tumours with poorer prognosis and survival
40
What shall we do about a grade II MCT?
–These show variable clinical behaviour
–Additional methods help with deciding on appropriate therapy and prognosis
•Ki-67, AgNOR, c-KIT
–Helps with conventional classification
–Ki-67
* Antigen expressed during cell cycle
* Detect with immunohistochemistry
* Non-subjective , quantitative prognostic marker to predict MCT behaviour
–Low Ki-67 and AgNOR grade II MCT may not require additional therapy
–Review of aggressively treated grade II MCT recently suggested
* Excellent MST with surgery plus chemotherapy of \>40 months
* No surgery alone group….
* LN removal may improve prognosis in grade II MCT with LN involvement
41
How can we treat MCT with the following presentations:
1. Grade I, resectable
2. Grade I, too big to resect
3. Grade II resectable
4. Grade II, too big to resect
5. Grade III
1. Surgery
2. Cytoreductive steroids, surgery
3. Surgery
4. Cytoreductive steroids, surgery
OR refer for surgery
OR debulk then irradiate
OR debulk then monitor
OR debulk then chemotherapy
OR tyrosine kinase drugs
5. Refer/talk to an oncologist for:
Chemotherapy
Prednisolone plus one of vinblastine/chlorambucil/lomustine
OR Tyrosine kinase drugs
42
For a Grade I (low grade) mast cell tumour what are the::
A) Required margins?
B) Depth of resection?
A) 1cm (wide local)
B) Down to and including muscle or fascial plane below tumour
43
For a Grade II (intermediate grade mast cell tumour):
A) Required margins?
B) Depth of resection?
A) 2cm (wide llocal)
B) Down to and including muscle or fascial plane below tumour
44
For a Grade III (high grade) mast cell tumours):
A) Required margins?
B) Depth of resection?
A) 3cm (radical)
B) Down to and including two muscle or fascial planes below tumour
45
Discuss when tyrosine kinase inhibitors can be used
–Proliferation/survival of mast cells controlled by c-Kit (a receptor tyrosine kinase)
–Mutation in c-Kit in 30% and 70% of canine and feline MCT (respectively)
–Mastinib and toceranib = Tyrosine kinase inhibitors
=Inhibits c-kit dependent mast cell proliferation
–For non-resectable MCTs Grades II, III (surgery remains treatment of choice where possible)
46
What are tyrosine kinase inhibitors?
* Tyrosine kinases are receptors on cell surface, nucleus or cytoplasm
* Act to transmit signals from outside to inside
* Lots of functions other than oncology
* New drug target – human and animal
47
What are the side effects of Masive and Palladia?
–Both: anorexia, vomiting, bleeding
–Masivet: Protein losing nephropathy
–Palladia: neutropenia, muscle cramps
48
Name 3 situations we refer a MCT to a specialist (4)
•If advanced skin reconstruction required
–Best to refer in the first instance, cf after conservative surgery
•For radiotherapy
–Best to contact oncologist before surgery – may advise preferred surgery to optimise efficacy of radiotherapy
•For chemotherapy
–if unsure re use of chemotherapeutic drugs, including control of side effects and protection of people
•For incompletely excised tumours
–evidence would suggest repeat surgery and local therapy improves survival time
49
What are the 2 histological subtypes of feline MCT?
50
Feline MCT:
A) Where are they predominantely seen?
B) Which breed might be predisposed?
A) Older cats
B) Siamese
51
Discuss the prescence of cutaenous forms of feline MCT
–Solitary dermal nodule of 0.5-3cm diam
–Multiple masses and ulceration common
–Can see a plaque-like form which is similar to EGC
–Head and neck commonest site, esp. ear base
–Typically behaviourally benign (single better Px than multiple or with involvement of other organs)
52
Discuss the prescence of feline mast cell tumours of the visceral form.
–Spleen, LN and liver – may be incidental finding but poor Px in general
–Intestinal forms:
* Exist but are less common
* More commonly solitary mass but may be diffuse
* Diarrhoea is frequently seen
53
Discuss treatment options for feline MCT
•Excise cutaneous ones and splenic
–Intestinal usually diffuse therefore surgery usually not helpful
* RTx possible but often diffuse or benign so questionable value in such cases
* Little published data on chemotherapy in cats with MCT
* Corticosteroids though well established in dogs are of unclear benefit in cats
* Chemotherapy is generally reserved for cats with histologically pleomorphic (diffuse), locally invasive and/or metastatic tumours.
–Vinblastine, chlorambucil and lomustine have been used
–one study reports an overall response rate of 50% in cats with measurable disease treated with lomustine, and a median duration of response of 168 days
–TK inhibitors have had preliminary investigations in cats
54
What is the ideal treatment for lymphoma?
Chemotherapy
55
What is the ideal treatment for MCT?
surgery
56
What are the primary lymphoid organs of birds ?
•Bursa of Fabricius
–B Lymphocytes
•Thymus
–T Lymphocytes
57
Name secondary lymphoid organs of birds?
* Spleen
* Gut Associated Lymphoid Tissue
* Bronchial Associated Lymphoid Tissue
* Harderian Gland & Conjunctiva
* Bone Marrow
* Blood
* Disease of the lymphoid organs or lymphocytes will spread in a lot of places – wide spread, they are in different places
58
Name a bird disease of the thymus
–Chicken Infectious Anaemia (Chick Anaemia Virus, circovirus)
59
Name diseases of the bursa?
–Infectious Bursal Disease (birnavirus)
–Tumours
60
Name diseass of the spleen of importance
–Tumours
* Mareks Disease (Herpesvirus)\*\*\*
* Avian Leukosis (retrovirus)
* Reticuloendotheliosis (retrovirus)
–Marble Spleen Disease of Pheasants (adenovirus)
–Haemorrhagic Enteritis of Turkeys (adenovirus)
61
Infectious bursal disease:
A) What is the aetiology?
B) What clinical signs are present?
C) What are the lesions?
A) Birnavirus trophic for B lymphocytes
–Very resistant virus that persists in environment
B)
–Depression, ataxia, ruffled feathers (head and neck)
–Diarrhoea – stained around vent (lots of urates)
–Anorexia
–Acute mortality
–Variable long term immunosuppression +/- secondary infections
C) Gross Lesions – often sufficient for diagnosis
–Bursa – enlarged, oedematous, congested +/- haemorrhagic
–Muscular haemorrhages
–+/- swollen kidneys
62
What is this?
Infectious bursal disease
63
How can you control infectious bursal disease?
* Cleaning and disinfection of housing
* Vaccination (complicated…)
–Broiler breeders
* 1 live vaccine around 4 weeks
* 1 inactivated around 16 weeks to protect progeny
–Broilers
* Most UK producers give live vaccine (maternal immunity variable, around 3 weeks)
* Gold standard is to obtain blood samples from day old chicks for serology to decide age and vaccine (different levels of attenuation)
–Egg layers
•1 live vaccine around 4 weeks
64
Marek's Disease:
A) What is the aetiology?
B) What is the pathogenensis?
A) Herpesvirus (gallid herpesvirus 2)
## Footnote
B)
–Initial viral replication in lungs
–Cytolytic phase in lymphocytes – immunosuppression
–Latent phase – transformation and lymphomas
–Virus shed from feather follicle epithelium – dander protects virus.
–Incubation period – 4 week minimum, usually longer.
–Asymptomatic shedding possible…..
–Infected birds remain viraemic for life
65
Mareks Disease:
A) What are the clinial signs?
B) What are the gross lesions?
C) What are the histopath lesions?
A)
–Depression/Cachexia/presented dead most common
–Paralysis
–Blindness
–Secondary infection/ill thrift
B)
–Tumours – all parenchymatous organs common
–Swollen nerves
–Swollen feather follicles
–Iris infiltration (less common)
C)
–T cell lymphosarcoma
–Lymphocytic neuritis
–Perivascular cuffing in brain
66
What is this?
Marek’s tumours
67
What is the treatment and control for Marek's disease?
No specifc treatment
## Footnote
–Hygiene and disinfection (virus protected in dander)
–Backyard - ensure vaccination of new stock – must be done in ovo or as day old chicks.
•In ovo vaccination – vaccinating eggs prior to hatch
–Commercial – long lived birds all vaccinated. Most broilers in UK not vaccinated.
–Several serotypes of vaccine available, all require injection. Good technique important for protection.
68
Canine thymoma:
A) What do they present with?
B) What is seen on radiology?
C) What do we do to distinguish from lymphoma?
D) What do you do to treat?
A) Respiratory distress, may see cranial caval syndrome, myasthenia gravis
B) Large thoracic mass
C) Biopsy
D) Surgery
69
Where are most cow spleen diseases seen?
PM
70
What is a differential for splenomegaly in cows?
Anthrax
71
What pig disease causes splenic infarcts?
Swine fever
72
What causes splenomegaly in pigs?
PMWS\* (circovirus 2) and Glasser’s disease (Haemophillus parasuis)
73
What causes moderate to marked splenomegaly in pigs?
Erysipelas
74
Horses:
A) What is good about the spleen?
B) What is the relation with PCV?
C) How can it ben involved with colics?
D) Can you remove?
A) Protect
B) Increase PCV
C) Nephrosplenic entrapment
D) Yes
75
What is seen in alpaca spleens?
–Splenic haematomas and torsions seen
76
Are splenic haemangiosarcoms or MCT more common?
MCT
77
Discuss the prevelance, diagnositcs and treatment of MCT in cats?
–50% of all feline MCTs splenic in some studies
–Mean age of about 10 years
–Present with splenomegally +/- effusion
–Widespread mets very common
–FNA cytology often diagnostic
–Even with mets, splenectomy IS indicated as many go into remission for 12-18 months
–Chemotherapy doesn’t improve prognosis
78
Name 3 diseases of the canine spleen (5)
* Splenic masses moderately common
* Haematoma\>neoplasia?
–Problem that most surveillance from PM
* Common site for secondary masses
* Age not a discriminant for malignant vs. not (ACVIM abstract 2013)
* Present as mass or haemoabdomen….
79
What is the presentation of splenic mass presentation?
* Mid abdominal mass, usually ventral, non-painful
* May already have widespread mets if HAS so may present with cough etc
* Ruptured mass common presentation:
–Pallor, tachypnoea, tachycardia (anaemia)
–Ascitic/distended abdomen
–May have palpable fluid thrill
–Sudden death feasible if huge bleed
–Can see waxing and waning signs over months with repeated bleeding and recovery
•Can see splenic torsion as part of GDV
80
How can we diagnose canine splenic masses?
•Haematology to check PCV
–Remember this may not be low if bleed is very recent
* Palpation – often mid-ventral firm mass
* Imaging – radiography/ultrasound
* Abdominocentesis if free fluid seen
–Should not clot if free blood
–May clot however if very very recent
•FNA/biopsy mass/splenectomy?
–Need histo for definitive dx
81
Discuss the surgery options of splenic
* Very hard to get good diagnosis pre-op
* Met check thorax (min 2 inflated views)
* Care - may have coagulopathy
* If bled, need to volume replace pre-op
* Splenectomy probably better than hemi
* Care with post op arrhythmias – monitor for 24-48h post op, V Tach\>others
* Risk factors for perioperative death in dogs undergoing surgery for bleeding splenic masses
82
Discuss the prevelance, common sites and treat haemangiosarcoma?
* GSD\>Labrador and retriever, less common in cats
* Extremely malignant tumour
* Other common site right atrium
–About 15-25% have spleen plus atrial masses
–Some studies suggest common to have RA mass therefore cardiac US in all cases??
* High metastatic rate of \>90% to lungs, liver, nodes, brain and potentially skin/SC tissues
* Surgery as primary treatment
–Thoroughly check abdomen for mets
•Post operative chemotherapy indicated in pretty much all cases
83
How do you treat haemangiosarcoma?
* Splenectomy alone – survival ~ 3 months
* Splenectomy plus chemotherapy ~ 6 months
–Survival of \> 1 year even with drugs \<10%
–Die of diffuse metastatic disease
–Prognosis better if spleen not ruptured?
–Chemo of choice doxorubicin every 3 weeks
–Prognosis from atrial masses similar
–Also true for cats
84
Splenic torsion in dogs:
When is it common?
What is usually underlyinh?
How do they present?
What is seen on radiograph?
How do you treat?
* Commonest as part of GDV
* Usually underlying splenic disease
* May present with abdominal pain, collapse, pallor, tachydysrhythmia
* May be chronic problem
* Reverse C shaped spleen on radiograph
* Treat with splenectomy – risks as with other splenic surgery
85
How can leukaemia be characterised?
–Myeloid, lymphoid, megakaryocyte, erythrocyte
–Can be characterised according to degree of differentiation
* Acute – usually poorly differentiated
* Chronic – usually well differentiated
* Response to treatment usually poor for acute and reasonable for chronic
86
What is leukaemia?
•ny bone marrow derived haematopoetic neoplasm
–Lymphoid (L) vs myeloid (M; anything NOT a lymphocyte)
–Acute (AML/ ALL) vs chronic leukaemia (CLL/CML)
– Chronic \> acute chemosensitivity
87
What is multiple myeloma?
•= plasma cells
–Secrete excess Igs of one clonal class
–Usually present due to paraneoplastic signs
–Chemosensitive
88
What is the clinical presentation of lymphoid leukaemia in cats and dogs?
* Cats – usually FeLV positive if acute – see other lectures
* Dogs – usually middle aged to older
–Usually non specific clinical signs
•Including lethargy, wt loss, PU/PD, anorexia
–Acute lymphoblastic form very acute
•More common than chronic forms
–Typically anaemic and thrombocytopenic
•Myelophthesis – crowding out of marrow
–Usually huge numbers white cells on smear
•Can see aleukaemic presentation
89
How do you diagnose lymphoid leukaemia?
On blood smears and bone marrow
–Blasts in acute, mature lymphocytes if chronic
–NB some acute are aleukaemic (~10%) and disease is localised to marrow
–May have Bence Jones proteinuria (see next)
–Cell markers may be prognostic – flow cytometry worth doing?
90
What is the prognosis of lymphoid leukaemia:
A) Acute?
B) Chronic? How do we treat?
A) Die very fast, poor response to treatment
B) Chronic – treat only if clinically ill
–Prednisolone and chlorambucil
91
What is Polycythemia vera?
Chronic red blood cell leukaemia = commonest, dogs\>\>\>cats
–Present with bone marrow derived polycythemia – very high PCV
–Treat with repeat phlebotomy/leaches/drugs
•Hydroxyurea commonest drug
92
What is Multiple myeloma (MM)?
* Clonal proliferation of plasma cells (Ab producing B cells) in marrow
* Produce excessive immunoglobulin
–M compoment
–May be light chain only (Bence Jones protein)
93
What is the presentation of mutiple myeloma?
–Hyperviscosity – bleeding, renal disease
–Hypercalcaemia of malignancy
–Cytopaenias – anaemia, thrombocytopaenia, neutropaenia
–Severe bone pain – multiple lucencies and fractures (25-30%)
94
Multiple myeloma:
A) How do you diagnose?
B) How do you treat?
C) What is the prognosis?
A)
–Bone marrow aspirate, urinary B-J proteins (not detected on normal urine stix)
–Serum protein electrophoresis
B) –Prednisolone and melphalan, plasmapheresis
C) May do well with treatment
–MST in dogs up to 18 months
95
Where are the locaions for Extramedullary plasmacytomas? and the behaviour?
–Oral cavity and cutaneous - usually benign
–Intestinal - usually malignant
•NB colonic seems to have more favourable Px
96
How do you manage Extramedullary plasmacytomas?
•For solitary disease – surgery and monitoring
–Oral and cutaneous can be curative
•For alimentary forms – surgery with follow-up chemo when spread has been documented
–Recurrence common and MST ~1y or more can be seen
