oncology 3 Flashcards
Describe & discuss the different methods of diagnosis for mast cell tumours (MCT)
- which is usually best? how can we tell what we are looking at? what possible negative effect?
- FNA
> cytology usually diagnostic
>characteristic appearance - mononuclear, granules
=> graulation varies (often with grade)
=> stain can affect ability to see granules
>may produce inflammatory reaction, bleeding after aspiration
=> “Darier’s sign” due to degranulation, release of contents such as heparin, histamine
=> Premedication with diphenhydramine (Benadryl) if concerned
() - incisional biopsy
- excisional biopsy
what stain for MCT?
wright-giemsa is good
- diff-quick not great
MCT incidence and signalment
– 7‐21% of all skin tumours
– 11‐27% of all malignant tumours
()
mean age = 9 years
– BUT there is a WIDE AGE RANGE
()
- many breeds predisposed: Boxer, Boston, Lab, pug, golden…
MCT - canine, location
- Cutaneous and subcutaneous most common
- 50% trunk
- 40% extremity
- 10% head and neck
- visceral - metastatic
> spleen, liver, kidney
MCT clinical signs
Mass
* solid skin mass
> may ulcerate, swell, or be pruritic
* Lipoma‐like
* Subcutaneous
* Mucosal (oral)
()
Paraneoplastic effects
- edema, shock
- GI signs
- bleeding tendencies
- ulceration, wound dehiscence
- pruritis
** systemic illness common with metastatis disease**
contents of mast cells
- Histamine
- Heparin
- Eosinophilic chemotactic factor
- Proteolytic enzymes
MCT Location, Appearance, Clinical Signs
- most frequently dermal or subcutaneous
- most solitary
- usually raised, may be ulcerated
- may be solid, soft (like lipoma), mucosal (e.g. oral)
- may have been present for long period of time
- no specific signs, but pruritis, GI ulceration possible, bleeds
> Systemic illness common with metastatic disease - CAN LOOK LIKE ANYTHING
clinical staging of MCT - how do we do it?
- diagnosis: FNA ± biopsy (for histology grading)
()
Staging:
– CBC & biochemical profile
– Cytology of draining LN
– Abdominal ultrasound + cytology
()
– ± Bone marrow
– ± Coagulogram (PT, PTT, FDP)
cancer stage vs grade
- a grade describes the appearance of cancer cells and tissue
- a stage explains how large the primary tumor is and how far the cancer has spread in the patient’s body.
what does it mean if we find mast cells in the liver, spleen, or lymph nodes when trying to stage the MCT?
- presence of mast cells in the liver or spleen does NOT equal metastatic mast cell tumour
- LN shouldn’t have large numbers of mast
cells in a normal population
use of CT for MCT staging, etc.
- useful for staging abdomen on large dog
- useful to evaluate lymph node
- useful to plan surgery
what are the stages for a mast cell tumor and what do they mean?
- Staging (modified from WHO)
> Stage I: single skin tumour
> Stage II: single skin tumour + regional lymph node (LN)
> stage III: multiple skin tumours or single large deep tumour ± regional LNs
>Stage IV: distant spread (blood or bone marrow)
()
> a: without systemic signs
> b: with systemic signs - Prognosis worse with increasing stage
- Multiple tumours may not have a worse prognosis
are multiple MCT common? related to one another? how should we approach the 2nd tumour?
- 20-25% of dogs with a MCT will get a 2nd MCT during their lifetime
- unrelated to 1st MCT
- likely predisposition
- needs to be treated like a new primary and not as a metastatic site
MCT diagnostic / staging steps - how do we decide what to do next?
- Anatomic site amenable to wide surgical excision?
> if yes… - negative prognostic factors present?
> if no… - excise with wide surgical margins. submit for grade and margin
> if complete margins, intermediate or low grade, and no negative prognostic indicators - routine follow-up
()()()
- if not amenable to wide surgical excision
OR
- if negative prognostic factors present
OR
- if poorly differentiated, highly proliferative, or surgical margins incomplete…
> Expand diagnostics prior to definitive therapy: - biopsy for histologic grade (+/- KIT analysis)
- lymph node aspirate
- abdominal US +/- spleen/liver aspirate
- CBC, biochem
how do we answer: how bad is it? for MCT
- diagnosis: FNA
- biopsy for histo grading
MCT prognosis requires:
- histologic grade
- stage
Patniak groups for MCT grade: what are they and what criteria is considered? what are most of them?
3 groups:
> low (I): well differentiated
> intermediate (II)
> high (III): poorly differentiated
()()
Based on:
* Mitotic figures
* Differentiation
* nuclear pleomorphism
> multinucleated cells, bizare nucleu, karyomegaly
* depth?
()()
vast majority will get a grade II
> ‘high vs low’ grade II
Kiupel 2 tier system: high grade vs low grade MCT prognisis
- High Grade associated with a significantly shorter time to metastasis and survival time
> low grade > 2 years
> high grade < 4 months
markers of proliferation other than mitotic index? what is a negative prognostic factor for MCT?
- the higher the marker the worse the tumor
> AgNORs
> Ki-67
> PCNA
> Doubling time
()
-rapid tumor growth and sudden appearance negative prognostic facotr
mutation in what gene affects MCT prognosis? what does it do?
c-kit
> encondes KIT, a tyrosine kinase receptor that binds stem cell factor, promoting the development/ function of mast cells
canine MCT prognosis overall depends on:
- grade
- extent (clinical stage)
- tumour location
> subungual, oral, mucous membranes mucocutaneous jct worse
> preputial, scotal worse
> SC better prognosis - breed
> boxer less aggressive disease - growth rate
- proliferation indices
> MI, AGNORs, PCNA, Ki-67 - recurrence
- systemic signs
- c-kit mutation
prognostic factors for canine dermal MCT
- systemic signs
- growth rate
- grade
- mitotic index
- proliferation markers
- c-kit mutation
- surgical margin
- extent (stage)
- breed
- tumor location
prognostic factors for canine subcutaneous MCT
- grading system for cutaneous not valid for these
- aggressiveness based on mitotic index
> many act benign
can you grade a MCT form cytology?
Bottom line with cytology:
If it looks bad, it probably is‐‐‐
If it doesn’t look bad, it still might be
what is considered a ‘biologically high grade MCT’?
- High grade
- low grade but with a positive lymph node
- Muco‐cutaneous localisation
are all MCT similar?
Not one of them
is like the other
don’t ask me why,
please ask your mother.
MCT treatment modality chosen depends on?
- Based on clinical stage & histo grade
– this doesn’t mean we necessary do a biopsy
every time!
– often treat based on a presumptive grade
> behaviour and cytology
mainstay of treatment for MCT?
- surgery
surgery for MCT - recommendations are based on what type of MCT?
- what type of excision? how do we do it?
- recommendations & grading based on cutaneous MCT
- mainstay of treatment for MCT
- well differentiated & intermediate
> wide surgical excision
> early better
=> “proportional margins” (> 5 mm & < 3 cm) + clean fascial plane deep
=> clean margins
=> surgical cure
MCT surgery indications / reasons to perform
- curative excision
- cytoreduction (“debulking”)
- palliation
guidelines for MCT surgery
- margins? considerations?
- always know your local anatomy and fascial planes
> If you are unsure of either of these, mass is likely in a location that needs advanced imaging - for masses < 1cm, often 1 cm margin enough … but need to consider the behaviour and anticipated grade
- for masses >1cm, often 2 cm enough but need to consider behaviour
- we don’t know for sure the most appropraite margin for grade 3
() - biopsy if it will be challenging to get 2 cm margins and close primarily > important to know if grade 3 in these cases
- clip wide
- be prepared for a big hole - have a plan!
- remember 3cm margins + 1 cm mass = ~10cm scar
- consider the consequences if dirty margins
MCT surgical challenges
- poorly defined masses
- Poor local healing
> histamine release - Determination of deep margin
MCT excision - dirty margins? now what?
reexcision or radiation therapy
MCT indications for radiation therapy - why we do it
- loco-regional control
– alone or in combination with surgery and/or chemotherapy - curative vs palliative
types of radioation therapy for MCT
- local vs systemic
- palliative vs curative
how does radiation for MCT work?
- In principle:
– radiation destroys cells
– primary target is DNA
– indirect effect by destruction of tumour vasculature
– usually, cells have to divide in order to die
MCT treatments, ranked:
- wide surgical excision
- radiation (50-75% CR)
- chemotherapy
> poor 3rd choice compared to local therapy
chemotherapy (systemic) MCT indications
- metastasis
- high grade
- non-surgical
- microscopic without access to radiation therapy
- muco‐cutaneous location
MCT chemotherapy treatment drugs
- glucocorticoids
- vinblastine
- lomustine (CCNU)
- toceranib (Palladia®)
MCT targetted therapy
tyrosine kinase inhibiitor (TKI)
- we want to stop:
> KIT is a tyrsine kinase receptor that binds stem cell factor, promotes development and function of mast cells
ancilliary therapies for MCT? types and their purpose
- used in MCT to combat the effects of histamine
- H2 antagonsits
> famotidine, ranitidine - omeprazole
- sucralfate
- +/- misoprostol
- H1 antagonists
> diphenhydramine
how does stelfonta (tigilanol tiglate) work? what is it for?
– injection for non‐metastatic MCT in dogs
– Licensed in USA not yet in Canada
- destroys tumours inducing rapid hemorrhagic necrosis
treatment approach for stage 0 or 1, grade I or II canine MCT
- surgical excision if poss (wide margins, complete)
> follow up
() - If wide surgical excision not possible:
Ideal: cytoreductive surgery and adjuvant radiation therapy
Alternate:
- cytoreduction followed by medical therapy
- radiation therapy alone (ossible surgery to follow)
- medical therapy alone (possible surgery to follow)
- amputation
() - if surgical margins not complete:
- Options: - reexcise with wider margins
- adjuvant radiation therapy
- adjuvant medical therapy
> then follow up
treatment approach for high grade biologically aggressive canine MCT
- wide surgical excision if possible
> assess margins and confirm grade
> if complete margins…
> adjuvant medical therapy +/- regional node irradiation
> follow up
() - if wide excision not possible
- Options:
Ideal: - cytoreductive surgery
- adjuvant radiation therapy +/- regional lymph node
- adjuvant medical therapy
Alternatives: - cytoreduction followed by medical therapy
- medical therapy alone
- radiation therapy and medical therapy
()
- if surgical excision attempted but margins not complete, options: - reexcision with wider margins
- adjuvant radiation therapy to primary site +/- regional node
> then adjuvant medical therapy +/- regional node irradiation
what type of masses make us suspicious of MCT?
all dermal/subcutaneous masses
are feline and canine MCT similar?
they are different
