Mast cell tutors Flashcards
How can mast cells degranute?
- IgE dependant
- IgE independant
-pressure, sunlight, heat, cold, excericse, stress, chemicals
-IgG and complement
+Mrgrprx2 (G protein coupled receptor)=ANAPHYLAXTOID REACTION /pseudo-allergic reactions
Is the p53 altered in MC tumors and correlated with survival time
-presence of mutant p53 protein in 13.75% to 44.6%
BUT mutant p53 immunoreactivity has NO CORRELATION with overall survival time and NOT an accurate predictor of biological behavior.
c- kit receptor mutations are confirmed in how many cases
in 40% of canine mast cell tumor lines
Why are c-kit mutations important
-result in constitutive (constant) activation -> unregulated intracellular signaling ->cell proliferation- >tumor formation
-RTKs (receptor tyrosine kinase) have implicated in angiogenesis and the process of metastasis
In wich breeds we have good prognosis with MCT
Boxer + Pug (hind limbs, multiple lesions )
What is different between well differentiated and poorly differentiated
Well differentiated: slow grow + hairless + solitary + for months
Poorly differentiated: rapid grow + ulcerated + pruritic + often satellite lesions +/- go to LFN
What are signs suggestive of agressive lesions
1) Rapid growth
2) Local irritation/inflammation
3) Local infiltration/poor demarcation from adjacent tissues
4) Ulceration
5) Satellite nodules
6) Paraneoplastic signs
Name special stains
- toluidine blue,
- pinacyanol,
- Wright’s or Wright-Giemsa stain (good to evaluated granules) whereas Diff-Quick best for nucleus
In wich species is histiocytic subtype seen and what is apperanace
-Siamese kitten
- often has a granulomatous appearance (many histio) -> confirm only by TEM
What does staging do
- defines nature (degree) and extent (LFN, liver, spleen, BM, satellite lesions)
- recommended if extensive or expensive tx is planned or a poorly differentiated or evidence of metastasis
- Most MCT are unlikely to metastasize
- Full staging = FNAs of draining LFN + Abd USG
Can we have mast cells in lymp nodes
- Up to 25% normal dogs have few normal masts in LFN ->up to 0,1% cells in healthy; up to 0,55% in CAD
- Plus, the cytologist may not tell if they are reactive or neoplastic.
How can we assume mast cells in LN are metastatic
->as a general rule, if mast cells appear in clusters or sheets -> suggestive of metastatic disease.
-> increased nº or abnormal morphology or effacement of normal LFN architecture on histology - all point to metastatic disease
Can we use buffy coat for diagnosis of MCT
- Buffy coat smears: probably poor value in dogs (questionable)
BUT appropriate in CAT with certain presentations of mast cell disease ->may incerase peripheral mast - bad PX!!
What is recommended if nodal metastais is seen
full staging w/ Abd US (w/ FNA of spleen and liver)
+ FNA of BM
+ Lung XRAY
Explain Grade I of Patnaik classification
well-differentiated- at dermis and interfollicular spaces
<10% metastasis
-slow grow, ↓death
Explain grade II Patnaik
intermediate-@ lower dermis + SC
-5-22% metastasis
-some can be cure with excisional surgery alone
-17–56% die of due to local treatment failure or metastatic disease
- Unpredictable behaviour
-subjective histopathological grading between pathologists -difficult to give Px
Grade III Patnaik
anaplastic- at SC + deeper tissues
>80% metastasis
-aggressive growth
-high recurrence
-↑ death
Kiupel 2 tier grading system HIGH vs LOW
High grade:
- 7 or > mitosis/10 hpf
- at least 3 multinucleate (3 or more nuclei) cells/10 hpf
- at least 3 bizarre nuclei/ 10 hpf
- Karyomegaly (i.e. nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold)
What are other bad prognostic criteria
- LFN metastasis (!! interpretation is challenging)
- Anatomic location
-mucocutaneous junctions + inguinal region: more malignant regardless of histological grade, but this is controversial
-viscera or BM - Clinical features and recurrence after treatment
How can c-kit mutation be confirmed and has it correlation with good or bad prognosis
- IHC or PCR
-increased metastasis risk increased local recurrence incerased tumor proliferation index
- RTK c-Kit is dysregulated in 15–40% of canine MCT
Name proliferation markers
- Mitotic index (no mitosis / 10hpf)
- Ki-67 protein
- AGNOR
- PCNA
What is AgNOR
Argyrophilic Nucleolar Organizing Region-associated proteins
- bind silver molecules, thus can be visualized using a silver-based histochemical stain
- the incresed nº of AgNOR dots/nucleus the more rapidly is cell division = more proliferative tumor
What is Ki-67
marker for proliferation, expressed during the cell cycle
- IHC
-increased Ki-67 = more proliferative tumor
What is PCNA
Proliferating Cell Nuclear Antigen = protein required for DNA synthesis.
- associated with cell proliferation
What are surgical recommendations for MCT removal
- 2cm/1 fascial plane recommended for tumors <4cm
- 3cm/deep fascial plane to grade III
- < or = 0.5 cm @ distal limbs -> 2-year recurrence-free rate of 93%.
What are 1st and 2nd line of chemoth
1st-line: vinblastine and prednisolone
2nd-line: lomustine
What is recommended supportive th
- medication to counter the effects of histamine
-H2 antagonists to treat gastric ulceration: cimetidine (4 mg/kg PO q8h), ranitidine (2 mg/kg PO q12h), famotidine (0.5–1mgkg−1 PO q12–24h)
-proton pump inhibitor omeprazole (0.5–1mgkg−1 PO q24h)
-H1 antagonists to decrease adverse effects of histamine release on peripheral vasculature and wound healing: diphenhydramine (2–4mg kg−1 PO q12h). - sucralfate is recommended in cases with GI signs.
Are COX-2 ihibitors indicated
- Cox 2 is overexpressed in high grade mastocytoma
Indication of toceranib phosphate
- approved for use in recurrent, nonresectable grade II/III -> no need to test for c-Kit mutation
- Side effects: GI, neutropenia, muscle cramping
Indications for masitinib
- approved for use in nonresectable grade II/III MCT with established c-Kit mutation
- Side effects: GI, neutropenia, muscle protein losing nephropathy
What are 2 clinical presentation of MCT in cats
- Mastocytic
a)nodule
b)plaque
c)multiple SC nodules - Histiocytic
Desribe mastocytic MCT disease in cats
-10 years»_space;> kittens can be affected
-Male and Siamese
++ head & neck
-3 types
+++ Nodule: solitary, firm, well-circumscribed, hairless or ulcerated, dermal
Plaque: flat, pruritic, resemles eosinophilic granuloma (may be multiple)
Multiple SC nodules
How is mastocytic MCT subdivided
-well-differentiated (formally compact form): 50–90% of cases, + benign
-pleomorphic (formally diffuse form): histologically + anaplastic; clinically + malignant, poor Px
What are prognostic factors in cats
-multiple cutaneous MCT carry a more guarded prognosis (contrary to dog)
-pleomorphic phenotype is worse
-KIT immunoreactivity score
-MI
-Ki67
High vs low grade in cats
Histiocytic MCT in cats
-From 2M-old to <4y Siamese
-kittens (2 litters, same mum) suggesting a genetic influence
-multiple firm, pink papules and nodules @ head and pinnae
-eventually spontaneously regress.
-Easy to confuse with histiocytoma or lymphoma!!!
MCT in ferrets
-44% of all cutaneous and subcutaneous neoplasms in ferrets
-typically benign and neither local recurrence after surgical excision nor metastatic disease has been reported
-Histologically, most ferret MCTs consist of well‐differentiated mast cells where mitotic figures are rare and, similar to cats, few eosinophils are present
- there was no relationship between Kit immunostaining and prognosis
MCT in horses
- 3.4% of all cutaneous equine tumours (2006)
-head as a single nodule;
-multiple lesions are not indicative of malignant disease and may occur in any anatomical area of the skin
-Arabian horses at risk, but no sex predilection
-follow a benign disease course and appear histologically well differentiated with a low mitotic rate
-Aberrant cytoplasmic Kit staining is detected by immunohistochemistry in 15% of cases but is not correlated to malignant disease or a worse prognosis,
-Surgery alone is curative
MCT in bovine
-less than 1% of all bovine neoplasms
-neoplastic mast cells appear well differentiated in cattle, even in cases with metastasis
MCT in pigs
-from well differentiated, benign lesions to malignant and metastatic cancer
Name 4 MC driven disorders in humans
1- Urticaria
2- type I allergy
3- Mastocytosis
4- MC activation syndrome (MCAS)
In a study by Daniel, 2019 how did the tumor collagen index influenced mortality and survival in MCT
-quantity of intratumoral collagen was LOWER in high-grade MCT
-dogs with low Colagen MCT had incerased risk of death and shorter survival
-ECM plays a protective role?
Locations of MCT in horse
Head (lip, nostril, jaw, periorbital area) neck, trunk and limbs (near joints)
Hard, immovable
Also, nasal cavity, trachea, conjunctiva, sclera, nictitans, globe.
