Leukaemia and lymphadenopathy 2 Flashcards
What are the 2 forms of plasmacytomas?
Cutaneous and extramedullary
Describe cutaneous plasmacytomas
- Solid masses which may be single or multiple
- Usually benign, best prognosis
- Well demarcated, excision with good margins generally curative
Describe extramedullar plasmacytomas
- Solid tissue tumour
- Malignant
- Produce monoclonal immunoclobulins
- Solitary masses
- Cause amyloidosis
- Take over tissues
Which organs are commonly affected by extramedullary plasmacytomas?
- Arises most frequently in GIT
- Also trachea, spleen, kidney, uterus, CNS, elsewhere
How are extramedullary plasmacytomas diagnosed?
On serum/plasma
What are the effects of amyloidosis?
Deposition of abnormal proteins that cannot be broken down in the liver/kidney, leading to loss of function and atrophy of normal tissue
what are multiple myelomas?
Malignant tumour of plasma cells arising in the bone marrow
Describe the pathogenesis of multiple myelomas
- Secrete large amounts of Ig (hyperglobulinaemia, monoclonal gammopathy) and cytokines that activate osteoclasts
- Osteolysis leads to hypercalcaemia
- Highly proliferative
Describe the appearance of multiple myelomas
- Shotgun appearance lesions in bone
- Light chain proteinuria
- Possible anaemia
- Possible amyloidosis
- haemorrhages due to secondary platelet dysfunction
- Hyperviscosity syndrome
- Cytopaenias
What are the clinical signs of myeloid tumours generally caused by?
Loss of other cell lines
Outline myeloid dysplasias
- Rare
- Tumours starting in bone
Name histiocytic neoplasias
- Cutaneous histiocytoma
- Histiocytic sarcoma
Describe the typical presentation of a cutaneous histiocytoma
- Young dog
- Circular raised, alopecic nodule
- No damage to surrounding tissues
Outline the treatment for a cutaneous histiocytoma
- Often spontaneously regress
- Can be left, but excise if needed
Describe histiocytic sarcomas
Uncommon, malignant tumours of dendritic cells or macrophages
How may histiocytic sarcomas cause anaemia?
Sometimes cause haemophagocytic syndrome
Which breeds are predisposed to histiocytic sarcomas?
Rottweilers, Bernese Mountain dogs
Which form of histiocytic sarcomas is rapid and aggressive?
Disseminated form
Describe the cytological appearance of a histiocytic sarcoma
- Neoplastic cells are round cells with abundant grey-blue cytoplasm
- Multinucleation, prominent nucleoli, mitotic figures visible
- Hyperchromatic nuclei
Describe the gross appearance of a spleen with a haemophagocytic histiocytic sarcoma of macrophage origin
Diffuse splenomegaly with ill-defined mass formation
Where do mast cell proliferations typically develop?
Mostly cutaneous or subcutaneous, can occasionally develop in the spleen, liver, intestine or elsewhere
Outline the importance of KIT in the development of mast cell proliferations
- Mutations of the c-kit protooncogene that codes for KIT protein stem cell factor receptor may be responsible for the development or progression of mast cell tumours
- KIT expression is inversely related to the degree of differentiation of canine mast cell tumours
- Increased KIT = less differentiated tumour
Describe the appearance of mast cell proliferations
- Solitary or multicentric, dermal or subcutaneous, nodular or pedunculated
- May be erythematous and oedematous
Describe the behaviour of mast cell proliferations
Some benign, others malignant. Some may appear benign but behave malignantly
Describe canine cutaneous mast cell tumours (prevalence, behaviour)
- Common
- Biological behaviour varies from benign to fatal malignancy
- Histological grading used to try and assess potential biological behaviour
Explain why eosinophils are often seen in mast cell tumours
IL-5 produced by mast cells attract them
What grading methods are used for canine cutaneous mast cell tumours?
Bostock, Patnaik, Kiupel
What is the Patnaik grading system for canine cutaneous mast cell tumours based on?
- Histologic criteria
- Cellular morphology (nuceli, size, granularity), degree of differentiation
- Mitotic index
- Cellularity
- Invasiveness
- Stromal reaction
Describe the criteria for a grade 1MCT based on the Patnaik system
- No mitotic figures
- Minimal stromal reaction or necrosis
Describe the criteria for a grade 2MCT based on the Patnaik system
- Moderate to high cellularity
- Moderately pleomorphic cells with round to indented nuclei
- Mostly finely granular cytoplasm
- Extend to lower dermis, subcutis and occasionally deeper tissues
- 0-2 mitotic figures per high power field
- Some contain areas of oedema, necrosis and hyalinised collaged
Describe the criteria for a grade 3MCT based on the Patnaik system
- Highly cellular
- Composed of pleomorphic mast cells
- Indented to round vesicular nuclei and 1 to multiple prominent nucleoli arranged in sheets that replace the subcutis and underlying tissues
- 3-6 mitotic figures per hpf
- Contain areas of haemorrhage, oedema, necrosis, hyalinised collagen
Describe the prognosis for a dog with a grade 1 MCT (Patnaik)
- 93% of dogs survive longer than 1500
- Good
Describe the prognosis for a dog with a grade 2 MCT (Patnaik)
Low to moderate metastatic potential and ~47% survive 1500 days (cannot tell which have good and which have poor prognosis)
Describe the prognosis for a dog with a grade 3 MCT (Patnaik)
High metastatic rate and ~6^ survival rate of 1500 days
Palliative care only
Describe the Kiupel grading system for MCTs
2-teir histologic grading system, giving diagnosis of either high or low
Describe the criteria for a high grade MCT based on the Kiupel system
Based on any one of the following
- at least 7 mitotic figures in 10 HPFs
- At least 3 multinucleated in 10HPFs
- At least 3 bizarre (marked indentation, segmentation, irregular shape) nuclei in 10 HPFs
- Karyomegaly
- 10% of neoplastic cells vary by at least two-fold
Compare the prognosis for a high grade vs a low grade MCT based on the Kiupel system
- High: <4month survival, shorter time to metastases
- Low: more favourable prognosis, >2yr survival time
Which of the grading systems for MCTs has a higher prognostic value?
Kiupel, also able to correctly predict the negative outcomes of some grade II MCTs on the Patnaik scale
Which dog and cat breeds are predisposed to lymphoma?
- Boxer/mastiff
- Siamese
What are the anatomical classifications of lymphoma?
- Multicentric
- Alimentary
- Cutaneous
- Mediastinal
- Extra-nodal
What are the histological classifications of lymphoma?
- Low, intermediate or high grade
- Small or large cell
What are the immunophenotypic classifications of lymphoma?
- B cell
- T cell
- Null cell
Which immunophenotypic classification of lymphoma carries the worst prognosis?
T cell
Discuss the monitoring of lymphoma
- Multicentric: palpate and measure nodes when come for chemo
- Extranodal: harder to monitor, use imaging, clinical signs, pleural fluid in mediastinal disease
- Hard to be sure of remission
- Best guess using blood tests looking for acute phase proteins, PCR etc. but not well validated or commercially available
Compare the median survival times in lymphoma when treated with either prednisolone only, COP or doxorubicin based protocols
- Pred: ~3 months
- COP: ~6 months
- CHOP: ~9 months
What are the main factors that influence how well an animal will respond to treatment for lymphoma?
- Clinical stage, substage, immunophenotype, pre-treatment with steroids
- Cats also FeLV status
- Major influence on outcome is initial response to treatment
Describe the breed predispositions for canine mast cell tumours
- Boxers, golden retrievers, pugs
- Pugs: multiple independent MCTs developing simultaneously, generally low grade
- Young Shar Peis and Labradors often higher grade
- Gold retrievers: multiple, recurrent primary mast cell tumours
Where do canine mast cell tumours generally metastasise to?
- Readily to the local lymph nodes, liver, spleen, bone marrow
- Not commonly the lungs
What are features of a mast cell tumour can act as grade predictors?
The site and mass type
Describe the typical gross appearance of well differentiated and poorly differentiated mast cell tumours
- Well: slow growing, hairless, solitary
- Poorly: rapid growing, ulcerated, pruritic
Which sites carry poorer prognosis for mast cell tumours?
- Visceral, intestinal, marrow involvement
- Mucocutaneous, muzzle, inguinal lesions may carry poorer prognosis, but controversia
What is required for the diagnosis of a canine mast cell tumour?
- FNA of mass
- FNA of local lymph node
- Cytological grading based on histopathology
Describe the use of mass FNAs in the diagnosis of a canine mast cell tumour
- Tol blue/Giemsa stain to reliably see granules
- Does not give grade, but provides strong suspicion of mass being MCT
Describe the use of local lymph node FNAs in the diagnosis of canine mast cell tumours
- Positive node: high suspicion for metastasis
- Metastasis requires different treatment
Describe the staging required for canine mast cell tumours
- Crucial to assess regional lymph node
- Scan liver and spleen with FNA of each to be complete
- Unlikely to metastasis to lungs so thoracic radiographs not important
Explain the assessment of regional lymph nodes for the staging of canine mast cell tumours
- Many dogs have local mets at time of presentation
- Rare to develop distant mets if local LN not involved
Explain the examination of the liver and spleen for the staging of canine mast cell tumours
- Unclear value if local LN is clear
- Some evidence that affected LN not always obvious regional node, and MCTs commonly metastasise to the liver and spleen
What are the 2 histological subtypes of feline mast cell tumours?
- Mastocytic
- Atypical form
Describe the cutaneous form of feline mast cell tumours (appearance, behaviour, treatment)
- Solitary dermal nodule 0.5-3cm diameter or multiple massess and ulceration common
- Can see plaque-like form which is siimilar to EGC
- Head and neck commonest site, esp/ ear base
- Typically behaviourally benign, single better prognosis than multiple or organ involvement
- Surgical treatment can be enough
Describe the visceral form of feline mast cell tumours (appearance, signs)
- Can be solitary masses but still poor prognosis
- Spleen, LN and liver; may be incidental finding but poor prognosis in general
- Intestinal forms exit but less common, generally solitary mass but may be diffuse and may cause diarrhoea
Describe the clinical presentation of mediastinal lymphoma in dogs
- Tachypnoea
- Hyperapnoea
- Mass compromising lung expansion
Describe the clinical presentation of CNS lymphoma in the dog
Seizures
Describe the clinical presentation of cutaneous lymphoma in the dog
Pruritus, scaling
Describe the clinical presentation of multicentric lymphoma in the dog
- Lymphadenopathy
- Often well despite this
Describe the paraneoplastic syndromes that may occur with lymphoma in the dog
- Hypercalcaemia leading to PUPD (most common with T cell lymphoma, or mediastinal lymphoma)
- Thrombocytopaenia
Describe the clinical presentation of lymphoma in cats
- Multicentric form rare
- Major association with FeLV: young cats typically with mediastinal involvement
- Extranodol more common than in dogs: hepatic, nasal CNS, mediastinal, renal
- Alimentary most common
- Lymphoma on any differentias list for a sick cat
Describe a common clinical presentation of lymphoma in calves and the treatment
- Thymic lymphoma will cause chronic bloat as this prevents eructation, diagnosis on percusion
- No treatment
Describe a common clinical presentation of lymphoma in horses and the treatment
- Can get splenic lymphoma
- Colic
- Splenectomy feasible but rare
Describe a common clinical presentation of lymphoma in camelids and the treatment
- Extranodal lymphoma
- Treat as dog if owner keen
What methods can be used to identify lymphoma as T or B cell?
- Flow cytometry
- Clonality testing (PARR)
- Immunohisochemistry
What are some oddities regarding lymphoma in dogs?
- Indolent lymphoma
- GI lymphoma
- Primary cutaneous lymphoma
Briefly describe indolent lymphomas in dogs
- Single node presentation, tend not to do so well
- Surgical excision not curative
Briefly describe GI lymphomas in dogs
- Thought to do badly
- Dogs with diarrhoea worse prognosis
- standard drugs ok, most treated with CHOP protocol
Briefly describe primary cutaneous lymphomas in dogs
- Several forms
- generalised scale
- Foci of erythroderma, crusting, ulceration
- Multiple dermal nodules/erythematous plaques
- Mucocutaneous lesions (may depigment)
- Lymph nodes may be involve
Describe feline alimentary lymphoma (presentation, forms, treatment, prognosis)
- Most common form in cats
- Lymphocytic: long remission, 17mo
- Lymphoblastic: short remission, 3mo
- Presentation: diarrhoea, weight loss, palpable mass, thickened bowel loops
- Small and large cell forms
- Small often T cell and low grade, respond well to pred and chlorambucil
- Large tend to do much worse
- Can be surgical if small area then chemo
Describe feline nasal lymphoma (presentation, diagnosis, progression, treatment)
- Often present as chronic rhinitis
- Can be associated with good long term survival
- Need advanced imaging/rhinoscopy
- May later develop renal lymphoma
- May just irradiate nose then chemo
What methods can be used to inform decisions on appropriate therapy and prognosis of a grade II MCT?
- Ki-67
- AgNOR
- c-KIT
Outline the use of Ki-67 as a prognostic marker for MCTs
- Antigen expressed during cell cycle
- Detect with immunohistochemistry
- Non-subjective, quantitative prognostic marker to predict MCT behaviour
How would you interpret an MCT with low Ki-6 and AgNOR?
May not need additional therapy
Outline the surgical approach to a MCT
- Send sample for histo to grade and assess surgical margins
- Pre-med with H1 blockers and H2 blockers to reduce risk of central and peripheral histaminic side effects
- Re-evaluate after histo report: further staging/surgery, radiation, chemo
Outline the follow up to surgical resection of an MCT
- Check scar, drainage, LNs
- Palpate abdomen
- FNA new lesions
Outline the staging of lymphoma
- Carried out once diagnosis made or during initial diagnostic investigations
- Stages I-V (only applies to nodal form)
Explain the requirement for staging for a lymphoma
- Most important prognostic factor is bone marrow involvement as it influences treatment and prognosis
- Pragmatic: save money for chemo
- Bone marrow is a significant site of chemo induced side effects
- Stage V carries very poor prognosis
- Need to know this in order to decide on treatment plan and give prognosis to owner
Describe the criteria for a stage I lymphoma
Single LN affected
Describe the criteria for a stage II lymphoma
Multiple LN affected in single area/region
Describe the criteria for a stage III lymphoma
Generalised lymphadenopathy
Describe the criteria for a stage IV lymphoma
Liver and/or splenic involvement (with or without stage I-III)
Describe the criteria for a stage V lymphoma
Bone marrow or blood involvement and/or any non-lymphoid organ (with or without stages I-IV)
Describe the criteria for substage a and substage b lymphoma and importance of this
- a: without clinical signs of disease
- b: with clinical signs of disease, poorer prognosis regardless of immunophenotype
What stage is given to ocular lymphoma without involvement of other LNs?
Stage V
What are the treatment options for lymphoma?
- Chemotherapy
- Radiotherpy
- Euthanasia
Why are steroids included in the chemotherapeutic protocols for lymphoma?
Lymphocytotoxic as well as anti-inflammatory effects
Outline the prognosis for lymphoma following chemotherapy
- 80% of dogs go into remission
- 50-70% of cats go into remission
Outline the phases of lymphoma chemotherapeutic treatment
- Diagnosis and decision to treat
- Induction therapy
- Remission
- Around 6 months, start maintenance
- Withdraw drugs
- Relapse
- Rescue treatmetn around 9 months usually
- Remission
- Relapse
Describe the rescue phase of lymphoma chemotherapeutic treatment
Initially try induction drugs again then use different drug protocol
Describe the second period of remission with chemotherapy for lymphoma
Will be less than 50% of the first period
List the chemotherapeutic protocols that can be used for lymphoma treatment
- COP
- CHOP (aka Madison Wisconsin)
- Doxorubicine alone
- Prednisolone alone
List the side effects caused by cyclophosphamide during chemotherapy for lymphoma
- Neutropaenia
- Haemorrhagic cystitis
List the side effects caused by doxorubicin during chemotherapy for lymphoma
- Neutropaenia
- Anaphylaxis
- Arrhythmia and cardiotocicity
- Severe skin sloughing in contact with skin
List the side effects caused by vincristine during chemotherapy for lymphoma
Severe skin sloughing in contact with skin
