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Oncology AP > Mast cell tutors > Flashcards

Mast cell tutors Flashcards

1
Q

How can mast cells degranute?

A
  1. IgE dependant
  2. IgE independant
    -pressure, sunlight, heat, cold, excericse, stress, chemicals
    -IgG and complement

+Mrgrprx2 (G protein coupled receptor)=ANAPHYLAXTOID REACTION /pseudo-allergic reactions

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2
Q

Is the p53 altered in MC tumors and correlated with survival time

A

-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.

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3
Q

c- kit receptor mutations are confirmed in how many cases

A

in 40% of canine mast cell tumor lines

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4
Q

Why are c-kit mutations important

A

-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

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5
Q

In wich breeds we have good prognosis with MCT

A

Boxer + Pug (hind limbs, multiple lesions )

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6
Q

What is different between well differentiated and poorly differentiated

A

Well differentiated: slow grow + hairless + solitary + for months
Poorly differentiated: rapid grow + ulcerated + pruritic + often satellite lesions +/- go to LFN

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7
Q

What are signs suggestive of agressive lesions

A

1) Rapid growth
2) Local irritation/inflammation
3) Local infiltration/poor demarcation from adjacent tissues
4) Ulceration
5) Satellite nodules
6) Paraneoplastic signs

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8
Q

Name special stains

A
  1. toluidine blue,
  2. pinacyanol,
  3. Wright’s or Wright-Giemsa stain (good to evaluated granules) whereas Diff-Quick best for nucleus
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9
Q

In wich species is histiocytic subtype seen and what is apperanace

A

-Siamese kitten
- often has a granulomatous appearance (many histio) -> confirm only by TEM

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10
Q

What does staging do

A
  • 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
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11
Q

Can we have mast cells in lymp nodes

A
  • 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.
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12
Q

How can we assume mast cells in LN are metastatic

A

->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

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13
Q

Can we use buffy coat for diagnosis of MCT

A
  • 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!!

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14
Q

What is recommended if nodal metastais is seen

A

full staging w/ Abd US (w/ FNA of spleen and liver)
+ FNA of BM
+ Lung XRAY

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15
Q

Explain Grade I of Patnaik classification

A

well-differentiated- at dermis and interfollicular spaces
<10% metastasis
-slow grow, ↓death

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16
Q

Explain grade II Patnaik

A

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

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17
Q

Grade III Patnaik

A

anaplastic- at SC + deeper tissues
>80% metastasis
-aggressive growth
-high recurrence
-↑ death

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18
Q

Kiupel 2 tier grading system HIGH vs LOW

A

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)

19
Q

What are other bad prognostic criteria

A
  • 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
20
Q

How can c-kit mutation be confirmed and has it correlation with good or bad prognosis

A
  • IHC or PCR

-increased metastasis risk increased local recurrence incerased tumor proliferation index

  • RTK c-Kit is dysregulated in 15–40% of canine MCT
21
Q

Name proliferation markers

A
  1. Mitotic index (no mitosis / 10hpf)
  2. Ki-67 protein
  3. AGNOR
  4. PCNA
22
Q

What is AgNOR

A

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

23
Q

What is Ki-67

A

marker for proliferation, expressed during the cell cycle
- IHC
-increased Ki-67 = more proliferative tumor

24
Q

What is PCNA

A

Proliferating Cell Nuclear Antigen = protein required for DNA synthesis.
- associated with cell proliferation

25
Q

What are surgical recommendations for MCT removal

A
  • 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%.
26
Q

What are 1st and 2nd line of chemoth

A

1st-line: vinblastine and prednisolone
2nd-line: lomustine

27
Q

What is recommended supportive th

A
  • 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.
28
Q

Are COX-2 ihibitors indicated

A
  • Cox 2 is overexpressed in high grade mastocytoma
29
Q

Indication of toceranib phosphate

A
  • approved for use in recurrent, nonresectable grade II/III -> no need to test for c-Kit mutation
  • Side effects: GI, neutropenia, muscle cramping
30
Q

Indications for masitinib

A
  • approved for use in nonresectable grade II/III MCT with established c-Kit mutation
  • Side effects: GI, neutropenia, muscle protein losing nephropathy
31
Q

What are 2 clinical presentation of MCT in cats

A
  1. Mastocytic
    a)nodule
    b)plaque
    c)multiple SC nodules
  2. Histiocytic
32
Q

Desribe mastocytic MCT disease in cats

A

-10 years&raquo_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

33
Q

How is mastocytic MCT subdivided

A

-well-differentiated (formally compact form): 50–90% of cases, + benign

-pleomorphic (formally diffuse form): histologically + anaplastic; clinically + malignant, poor Px

34
Q

What are prognostic factors in cats

A

-multiple cutaneous MCT carry a more guarded prognosis (contrary to dog)
-pleomorphic phenotype is worse
-KIT immunoreactivity score
-MI
-Ki67

35
Q

High vs low grade in cats

A
36
Q

Histiocytic MCT in cats

A

-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!!!

37
Q

MCT in ferrets

A

-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

38
Q

MCT in horses

A
  • 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
39
Q

MCT in bovine

A

-less than 1% of all bovine neoplasms
-neoplastic mast cells appear well differentiated in cattle, even in cases with metastasis

40
Q

MCT in pigs

A

-from well differentiated, benign lesions to malignant and metastatic cancer

41
Q

Name 4 MC driven disorders in humans

A

1- Urticaria
2- type I allergy
3- Mastocytosis
4- MC activation syndrome (MCAS)

42
Q

In a study by Daniel, 2019 how did the tumor collagen index influenced mortality and survival in MCT

A

-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?

43
Q

Locations of MCT in horse

A

Head (lip, nostril, jaw, periorbital area) neck, trunk and limbs (near joints)
Hard, immovable
Also, nasal cavity, trachea, conjunctiva, sclera, nictitans, globe.

44
Q
A

Oncology AP (4 decks)

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