Mast cell tumours Flashcards
Outline the make up of mast cell tumours
Start as CD34+ progenitor’s in bone marrow
Mature in peripheral tissue
Barrier’s – GIT, skin, lungs
Granules contain
▪ Histamine and heparin amongst others
▪ Released due to trauma, heat, IgE binding
MCT granules can be stained after released into periphery, not before
Can use Touridine blue stain for histo.
Where do you get MCTs?
Most commonly cutaneous
Occasionally mucocutaneous
Rarely visceral,GI or bone marrow
What are the common breeds for MCT
Brachycephalics,GRT and Labs predisposed.
▪ Boxers and Pugs mostly low grade
▪ Sharpei’s more aggressive disease
What is darier’s sign?
A wheal around the tumour
How common is it to get more than one tumour?
10-20% dogs will have more than 1 at dx
40% will get more than one in life
Compare FNAs and biopsies
FNA Round cell (fried egg) with variable numbers of granules Some correlation with grade but biopsy better Biopsy – incisional Grading information MI Can measure proliferation indices
What are the main grading systems?
Patnaik currently currently most used
Good differentiation between high and low
Grade 2 problematic
Kiupel
Two grade system
Some improvement in performance
What is the use of proliferation indices?
MI ▪ >5 is bad ▪ No additional cost ▪ Good link with prognosis prognosis Ki67 ▪ Independent risk factor for recurrence, metastasis and death
How does grade reflect metastatic rate?
Metastatic rates Grade 1 – 10 % or less Grade 2 – 22% or less Grade 3 ~ 80% Therefore I discuss staging for all MCTs and recommend staging for: all G2 and G3 tumours all tumours with aggressive appearance or behaviour all recurrences – upstaging?
Assume all grade 3s have spread
What staging should be done?
Aspiration of local lymph nodes
Thoracic radiographs
Tumours located in areas that drain to thoracic lymph
nodes
Abdominal ultrasound
Aspiration of spleen and liver
There can be metastatic disease in the liver without
ultrasonographic structural abnormalities
What factors affect prognosis?
Possibly breed Appearance Location
Controversial but possibly scrotal or inguinal worse
Recurrence after surgery
LN and distant metastasis
Grade High proliferation markers Kit mutation
Poor response to medical therapy
What is the order of preference for local treatment of MCTs?
Surgery
Neoadjuvant medical therapy then surgery
▪ Surgery and RT
▪ rTKI
Other medical therapy
rTKI inhibitors are not a substitute for surgical excision
Outline the use of Sx in MCT tx
Treatment of choice for localised non‐metastasised
MCTs
Loco‐regional control improves outcome even in higher grade disease
Combination of surgery and radiation therapy effective forG1 and 2 tumours with nodal metastasis
Manipulation carries a risk of degranulation
Gentle handling
Consider pre and perioperative anti‐histamines
How radical does surgery need to be?
Grade is known
‘Concerning’ grade 2 and grade 3
▪ 3 cm laterally and 1 fascial plane/muscle layer deep to the deepest tumour tissue
Grade 2 or 1
▪ 2 cm laterally and at least 1 fascial plane
Grade unknown
3 cm laterally and 1 fascial plane/ muscle layer deep to the deepest tumour tissue
What are the options if you are not confident in getting a good margin?
Refer to a soft tissue surgeon Surgery alone ▪ Surgery followed by radiation therapy Neoadjuvant treatment Prednisolone VBL + Prednisolone Tyrosine kinase inhibitor (licenced) ▪ Masitinib /Toceranib
Outline the use of neoadjuvant therapy
Aim – to shrink a non‐resectable tumour sufficiently to allow resection Prednisolone ▪ 2.2 mg/kg for 10 days OOR of 70% ▪ mean 50% reduction in size Vinblastine and prednisolone ▪ no more than 2 cycles ▪ Also thought to reduce size indicated in high risk tumours as adjuvant therapy
Outline the use of tyrosine kinase inhibitors in gross disease
Mastinib
50% have ~ 50% reduction in tumour size within 6
months
Toceranib
~ 40% response rate in ‘non‐resectable disease’
BUT HOW LONGUNTIL MAXIMUM EFFECT?
BUTWHEN DOYOU STOP?
What are the indications for adjunctive therapy?
Confirmed metastasis High k ris tumours Grade 3 Other grade with high MI ▪ Other grade with high KI 67
Outline the use of prednisolone and vinblastine
8 cycle protocol Staging before first and after last treatment. Haematology before each treatment Adjuvant treatment All tumours MST > 570 days Grade III – MST 330 days
How often should follow up/ staging be performed?
Regular follow up is indicated for all tumours
Re‐staging based upon risk
At the end of treatment
One month after the end of treatment
Then every 3 months for at least a year
Then every 6 months to a year
If the patient is unwell
Outline oral/ perioral MCTs
Comparatively rare presentation
Cutaneous grading scheme does not apply
MST prolonged prolonged – 52 mths
But shorter with nodal metastasis – 14 mths
Outline subcutaneous MCTs
Cutaneous grading systems unproven Combination of following predictive of outcome ▪ MI ▪ Ki‐67 ▪ KIT cellular localisation
Outline multiple cutaneous MCTs
Not clear whether these are metastatic or not
Prognosis for multiple MCTs treated with surgery
is not necessarily worse than single MCTs
However
High rate of de novo appearance of new tumours
▪ Often low grade
Treatment
Repeat surgeries
Short course of chemotherapy
Outline BM/ visceral/ GI MCTs
Rare in dogs GI disease poorly reported
Prognosis seems to be variable
Visceral disease
Reported MST of 90 days
Newer / more aggressive adjuvant therapy may improve
this
Bone Marrow
Poor survival ~ 45 days
Poor response to conventionaltreatments