oncology 3 Flashcards

1
Q

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?

A
  • 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
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2
Q

what stain for MCT?

A

wright-giemsa is good
- diff-quick not great

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3
Q

MCT incidence and signalment

A

– 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…

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4
Q

MCT - canine, location

A
  • Cutaneous and subcutaneous most common
  • 50% trunk
  • 40% extremity
  • 10% head and neck
  • visceral - metastatic
    > spleen, liver, kidney
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5
Q

MCT clinical signs

A

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**

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6
Q

contents of mast cells

A
  • Histamine
  • Heparin
  • Eosinophilic chemotactic factor
  • Proteolytic enzymes
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7
Q

MCT Location, Appearance, Clinical Signs

A
  • 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
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8
Q

clinical staging of MCT - how do we do it?

A
  • diagnosis: FNA ± biopsy (for histology grading)
    ()
    Staging:
    – CBC & biochemical profile
    – Cytology of draining LN
    – Abdominal ultrasound + cytology
    ()
    – ± Bone marrow
    – ± Coagulogram (PT, PTT, FDP)
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9
Q

cancer stage vs grade

A
  • 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.
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10
Q

what does it mean if we find mast cells in the liver, spleen, or lymph nodes when trying to stage the MCT?

A
  • 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
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11
Q

use of CT for MCT staging, etc.

A
  • useful for staging abdomen on large dog
  • useful to evaluate lymph node
  • useful to plan surgery
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12
Q

what are the stages for a mast cell tumor and what do they mean?

A
  • 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
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13
Q

are multiple MCT common? related to one another? how should we approach the 2nd tumour?

A
  • 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
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14
Q

MCT diagnostic / staging steps - how do we decide what to do next?

A
  1. Anatomic site amenable to wide surgical excision?
    > if yes…
  2. negative prognostic factors present?
    > if no…
  3. excise with wide surgical margins. submit for grade and margin
    > if complete margins, intermediate or low grade, and no negative prognostic indicators
  4. 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:
  5. biopsy for histologic grade (+/- KIT analysis)
  6. lymph node aspirate
  7. abdominal US +/- spleen/liver aspirate
  8. CBC, biochem
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15
Q

how do we answer: how bad is it? for MCT

A
  • diagnosis: FNA
  • biopsy for histo grading
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16
Q

MCT prognosis requires:

A
  • histologic grade
  • stage
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17
Q

Patniak groups for MCT grade: what are they and what criteria is considered? what are most of them?

A

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

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18
Q

Kiupel 2 tier system: high grade vs low grade MCT prognisis

A
  • High Grade associated with a significantly shorter time to metastasis and survival time
    > low grade > 2 years
    > high grade < 4 months
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19
Q

markers of proliferation other than mitotic index? what is a negative prognostic factor for MCT?

A
  • the higher the marker the worse the tumor
    > AgNORs
    > Ki-67
    > PCNA
    > Doubling time
    ()
    -rapid tumor growth and sudden appearance negative prognostic facotr
20
Q

mutation in what gene affects MCT prognosis? what does it do?

A

c-kit
> encondes KIT, a tyrosine kinase receptor that binds stem cell factor, promoting the development/ function of mast cells

21
Q

canine MCT prognosis overall depends on:

A
  • 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
22
Q

prognostic factors for canine dermal MCT

A
  • systemic signs
  • growth rate
  • grade
  • mitotic index
  • proliferation markers
  • c-kit mutation
  • surgical margin
  • extent (stage)
  • breed
  • tumor location
23
Q

prognostic factors for canine subcutaneous MCT

A
  • grading system for cutaneous not valid for these
  • aggressiveness based on mitotic index
    > many act benign
24
Q

can you grade a MCT form cytology?

A

Bottom line with cytology:
If it looks bad, it probably is‐‐‐
If it doesn’t look bad, it still might be

25
what is considered a 'biologically high grade MCT'?
* High grade * low grade but with a positive lymph node * Muco‐cutaneous localisation
26
are all MCT similar?
Not one of them is like the other don’t ask me why, please ask your mother.
27
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
28
mainstay of treatment for MCT?
- surgery
29
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
30
MCT surgery indications / reasons to perform
1. curative excision 2. cytoreduction ("debulking") 3. palliation
31
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
32
MCT surgical challenges
* poorly defined masses * Poor local healing > histamine release * Determination of deep margin
33
MCT excision - dirty margins? now what?
reexcision or radiation therapy
34
MCT indications for radiation therapy - why we do it
- loco-regional control – alone or in combination with surgery and/or chemotherapy - curative vs palliative
35
types of radioation therapy for MCT
1. local vs systemic 2. palliative vs curative
36
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
37
MCT treatments, ranked:
1. wide surgical excision 2. radiation (50-75% CR) 3. chemotherapy > poor 3rd choice compared to local therapy
38
chemotherapy (systemic) MCT indications
* metastasis * high grade * non-surgical * microscopic without access to radiation therapy * muco‐cutaneous location
39
MCT chemotherapy treatment drugs
* glucocorticoids * vinblastine * lomustine (CCNU) * toceranib (Palladia®)
40
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
41
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
42
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
43
treatment approach for stage 0 or 1, grade I or II canine MCT
1. surgical excision if poss (wide margins, complete) > follow up () 2. 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 () 3. if surgical margins not complete: - Options: 1. reexcise with wider margins 2. adjuvant radiation therapy 3. adjuvant medical therapy > then follow up
44
treatment approach for high grade biologically aggressive canine MCT
1. wide surgical excision if possible > assess margins and confirm grade > if complete margins... > adjuvant medical therapy +/- regional node irradiation > follow up () 2. if wide excision not possible - Options: Ideal: 1. cytoreductive surgery 2. adjuvant radiation therapy +/- regional lymph node 3. adjuvant medical therapy Alternatives: 1. cytoreduction followed by medical therapy 2. medical therapy alone 3. radiation therapy and medical therapy () - if surgical excision attempted but margins not complete, options: 1. reexcision with wider margins 2. adjuvant radiation therapy to primary site +/- regional node > then adjuvant medical therapy +/- regional node irradiation
45
what type of masses make us suspicious of MCT?
all dermal/subcutaneous masses
46
are feline and canine MCT similar?
they are different