Mast Cell Tumor and Transitional Cell Carcinoma

What is the most commonly diagnosed skin tumour in the dog?

Mast cell tumour

At what sites can mast cell tumours be found?

Skin, subcutaneous tissue, conjunctiva, oral mucosa, GIT

(Very variable behaviour)

What breeds are predisp to MCT?

Boxer, Boston terrier (no age/sex predis)

Where do MCT commonly metastasis to?

local LNs

spleen, liver

How do mast cells tumours present clinically?

• Cutaneoius mass of variable external appearance

• Anywhere in body

• Most solitary mass (can be mutliple in 11-14% esp in certain breeds —> pug, GR)

  • commonly reoccur post-tx

• Intracystoplasmic granules containing histamine, heparin and proteases cause degranulation

  • Local effects eg erythema, oedema, pruritus, haemorrhage (Darier’s sign)

• Systemic signs (rare): V+, meleana, rarely collapse

visceral form —> rare, v. aggressive

How is MCT diagnosed?

• FNA (usually diagnostic)-> round cells, characteristic purple granules

  

• Diff quick usually fine but occ need specialist stains (e.g.- toluidine blue)

  • sometimes poorly stain granules —> esp in higher stage as less differentiated

• (For some poorly differentiated biopsy +/- IHC)

What tests can be done to stage a MCT?

• Haematology/ Biochemistry/Urine analysis

• FNA or biopsy of local LN:

• Abdominal ultrasound

  • FNA spleen and liver

• Thoracic Rx

  • Lung metastasis uncommon

  • evaluate sternal LNs

• Buffy coat

• Bone marrow aspirates

• Biopsy

What are the prognostic factors of a MCT?

Clinical

• Location eg Nail bed, oral, muzzle, prepuce, perineum, mucocutaneous junction

• Breed (Sharpei vs boxer)

• Appearance

• Systemic illness

• Recurrence

• ?Clinical staging (i.e. presence of metastatic disease)

Lab:

• Tumour histological grade (Most important)

• Other:

  • Ki67

  • AGNORs

  • C-kit mutation

  • Kit staining pattern

What are the two histological grading systems for MCTs?

• Patnaik grading system

  • grades I - III

• Kiupel grading system

  • low grade / high grade

n.b. most labs report both grading systems together (higher agreement between pathologists with Kiupel system)

Describe a grade I Patnaik MCT.

• Well differentiated

  • Benign behaviour (<10% metastasise)

  • Low recurrence rates

  • Unlikely to cause death (up to 7-12%)

Describe a grade II Patnaik MCT.

• Intermediate

  • Variably metastatic (5-22% metastasise)

  • Cause of death in 17-56% of patients

  • Nodal metastases associated with poorer prognosis

  • n.b. most tumours are in this category which can be problematic for decision-making

Describe a grade III Patnaik MCT.

• Poorly differentiated

  • Highly metastatic (>80%)

  • Likely to be cause of death

What is the median survival time based on the Kiupel grading system of MCT in dogs?

• Low-grade MCTs: > 2 yrs

• High-grade MCT: < 4mths

What are the treatment options for MCT?

• Surgery

  • MCT is considered a surgical disease

• Chemotherapy

• Radiotherapy

Often a multi-modal approach is required. Tailor treatment to individual cases.

What are the usual surgical margins for MCT?

• 3cm margins & 1 fascial plane

  • 1-2cm lateral margins may be adequate for grade I and II tumours

• n.b. always send excised mass for Histopathology to check margins

Is surgery curative in MCT?

• Grade I and II: potentially curative (if adequate margins)

• Grade III: rarely curative (requires adjuvant therapy e.g. radiotherapy / chemotherapy)

What are the indications for radiotherapy in MCT?

• Post-op following incomplete incision

• Local node metastasis

• Gross disease if surgery is not an option

  • however can cause degranulation and is not advised unless completed necessary

What are the indications for chemotherapy in MCT?

• High grade and/or confirmed metastasis

• Neoadjunctively prior to surgery to shrink tumour to make surgery easier

  • Ensure you document where tumour is clearly prior to treatment (it may shrink so much its difficult to find)

• Residual microscopic disease (more controversial)

What are the commonly used chemotherapeutic drugs in MCT?

• Vinblastine with prednisolone

• Lomustine as a single agent or alternating with vinblastine

• What are TKIs?

• What are the indications of TKIs?

• = Tyrosine kinase inhibitors (non-cytotoxic)

• Indications:

  • unresectable, metastatic or high grade MCT

  • (shouldn't be used instead of surgery)

• n.b. can assess kit mutation status to determine response to treatment (but can take a while to get results)

What are the disadvantages with tyrosine kinase inhibitors?

• Can have effect on other receptors (e.g. VGFR, PDFR)

• Varied range of toxicities

  • GI, renal, hepatic, myelosuppression, lameness

• Expensive

(should not be used as a substitute for surgery)

Describe cutaneous MCT in cats.

• Second most common cutaneous tumour in cats (20%)

• Usually causes a raised hairless mass, often in head region, that is easily diagnosed by cytology

• Rarely metastatic and not very aggressive

• Surgical excision usually curative (even marginally)

Visceral MCTs are more common in cats than dogs. What are the two most common locations in cats?

• Spleen

  • most common ddx for splenic disease

• Intestines

  • third most common intestinal tumour

• What clinical signs are seen with splenic MCT in cats?

• How are the treated?

• Non-specific clinical signs of systemic disease (e.g. lethargy, weight loss, anorexia, vomiting)

• Treat with splenectomy - even if other organs are affected.

• MST 12-19 months

• What are the clinical signs associated with intestinal MCT in cats?

• What is the prognosis?

• Clinical signs:

  • GI signs

  • Systemic - anorexia, weight loss, lethargy

  • palpable abdominal mass

• Poor prognosis

  • Metastasis common

  • Often euthanised at / just after time of diagnosis

What is the most common bladder tumour in dogs?

Transitional cell carcinoma

• but bladder tumours only account for 2% all tumours

What is the most common location of TCC in dogs?

Bladder trigone

• also urethra and prostate in males

• What is the likelihood of metastasis with TCC in dogs?

• Where are common locations of metastasis?

• High metastatic rate

  • 14-16% to LN and distant but up to 50% at necropsy

• Metastasis sites:

  • Medial iliac LNs

  • Liver

  • Spleen

  • Bones (especially lumbar vertebrae)

What are the breed predispositions for TCC?

• Small terriers

  • WHWT

  • Scottish terriers

Describe the clinical presentation of TCC

• Low urinary tract signs:

  • haematuria

  • stranguria

  • pollakyuria

  • often concurrent UTI

• Occasionally signs related with bone metastasis (lameness) or renal dysfunction.

• Signs can be present for months as dog gets treated for “complicated UTIs”

  • Signs may improve with courses of antibiotics.

How can you diagnose TCC?

• Histopath although sometimes cytology very suggestive.

  • NOT FNA - Risk of seeding

  • Traumatic catheterization

    • rub tip of catheter against lesion under US guidance

  • Prostatic wash

  • Cystoscopy (mainly females)

  • Surgical biopsy - risk of seeding with suture material; change your instruments & suture material

(round to polygonal cells - anisocytosis & anisokaryosis)

What techniques can be used to stage a TCC?

• Haematology/ Biochemistry/Urine analysis (including culture):

  • May show neutrophilia, renal dysfunction, presence of UTI

  • Rule out any other problems and suitability for subsequent therapies

• Abdominal ultrasound

  • Assess bladder wall, urethra, prostate and kidneys +/-metastasis in other organs.

  • FNA.

    

• T&A radiography

  • Lung metastasis uncommon

  • Bone metastasis (especially lumbar vertebrae)

What are the treatment options for TCC?

• Cystectomy (rarely poss but best survival)

• External beam radiotherapy -(complications++)

• Brachytherapy

  • Suitable for prostatic and urethral tumours with improved survival.

• Medical treatment - commonly the only feasible option

  • NSAIDs and Mitoxantrone

  • Other chemotherapy drugs (Vinblastine, chlorambucil, carboplatin etc.)

• Palliative care

  • Regular urine cultures and AB courses as appropriate

  • Cystotomy tubes/ Urethral stents (not good QoL)

What is the general prognosis of TCC?

• Poor long term prognosis but quality of life can be maintained for several months.

• Local disease most likely cause of death/euthanasia (MST 6-8 months).

• Rapid deterioration due to renal failure or clinical signs associated with bone metastasis (pain) also possible.

• Owner counselling and regular monitoring of quality of life.