Urogenital & Mammary Tumors Flashcards
What is the most common urothelial tumor of dogs
transitional cell carcinoma (TCC)
malignant proliferation of the transitional epithelium
may affect renal pelvis, ureters, bladder, prostatic urethra, or distal urethra
transitional cell carcinoma (TCC)
transitional cell carcinomas can affect what anatomical structures
Renal Pelvis
Ureters
Bladder
Prostatic Urethra
Distal Urethra
What is the biologic behavior of transitional cell carcinomas
1) Locally aggressive at the primary site (urinary tract) with long invasive roots
2) Moderate risk for metastasis to regional lymph node, liver, spleen, lung and bone
3) Field carcinogenesis (field effect): microscopic cells with carcinogenic alterations that are distant to the primary tumor and within the same organ
What causes transitional cell carcinomas
1) Old topical flea and tick dip
2) Lawn herbicides
3) Obesity
4) Breed: esp scottish terrier
likely multifactorial
What breeds have an increased risk of transitional cell carcinomas **
1) Scottish terrier (18x risk)
2) Shetland sheepland (4x)
3) Beagle (4x)
4) Wirehaired fox terriers (3x)
5) West Highland white terrier (3x)
What is the most common location of transitional cell carcinomas
Trigone of the bladder
29% of males have prostatic involvement
56% of dogs have urethral involvement
What are the clinical signs of transitional cell carcinomas
Lower Urinary Tract signs
1) Dysuria
2) Hematura
3) Pollakiuria
these signs may be present for weeks to months
May resolve temporarily with antibiotic therapy
What might be some exam findings in dogs with transitional cell carcinomas
Rectal: thickening of urethra and enlarged iliac lymph nodes
Abdominal palpation: palpable mass or distended bladder
40% of dogs have normal physical exam
What are the different grades of TCC in dogs
Tis: pre-neoplastic lesion
T1: tumor invades into transitional epith and connective tissue
T2: tumor invade into muscle belly
T3: tumor invades through body wall
What is the grade breakdown of dogs presenting with TCC
80% T2 meaning its invaded into the muscle layer
20% T3 meaning its invaded into the neighboring organs
Where can TCC metasize to?
intermediate metastatic potential
1) Lymphatic spread
2) Hematogenous spread
to the spleen, liver, lungs, bone (lumbar vertebrae, pelvis), and skin
Why is bladder cancer a clinical challenge
Not common (2% of malignant tumors in dogs)
Lower urinary tract infections are much more common
Clinical signs of bladder cancer mimic clinical signs of LUT infection
Treatment with antibiotics may help mitigate signs initially (due to secondary infections)
some dogs may have delayed diagnosis due to multiple rounds of antibiotics and client hesitancy to proceed with more expensive / invasive diagnostics
this can lead to delay in diagnosis, resulting in many dogs being diagnosed at advanced stage disease (tumor invasive into bladder wall, metastasis)
How can we work towards early detection of TCC
1) encourage early work-up if clinical signs recur (after 1st round antibiotics or NSAIDs)
2) Recognize breeds: Scottish terriers, Shetland sheepdog, Beagle, Wirehaired fox terrier, West Highland white terrier
3) Consider CADET BRAF testing early
Neoplastic cells are presnet in the urine sediment of _______ % of dogs with TCC
30%
can be difficult for pathologist to differentiate malignant from reactive
What is the risk of cystocentesis with TCC
low risk (<0.009% risk, unknown risk)
discuss risks with client prior to proceeding
consider if other options for diagnosis not feasible
considered a <4% risk
For TCC, what would you see on rads
bone metastasis to LS/pelvic region (difficult to detect mass effect within bladder)
Positive contrast cystography
Excretory urogram
3 view thoracic radiographs to evaluate for sternal lymphadenopathy and pulmonary metastasis
What is a great first wave screening diagnostic
ultrasound - sensitive for detection and localization of bladder masses
evaluate for intra-abdominal metastasis
allows evaluation of the prostate
*pelvic urethra is hard to image (surrounded by bone)
CT imaging of TSS in dogs
improved detection of metastasis
possibly less inter-observer variability
*difficult to evaluate the pelvic urethra *
requires anesthesia which is more expensive for clients
Cystoscopy for TSS in dogs
*excellent for imaging the pelvic urethra *
evaluate for other lesions (field carcinogenesis) not detectable on US or CT in cases with solitary lesions at apex
assessment for cases with urethral involvement only
What is excellent for imaging for pelvic urethra
Cystoscopy
also good for cases with urethral involvement only
How do you obtain a definitive TSS diagnosis
1) Histopathology- cystoscopy or cystotomy
2) Cytology - cytospin, traumatic catherization, percutaneous FNA via ultrasound guidance
3) CADET BRAF urine testing
What is the risk of cystotomy for TSS diagnosis in dogs
1) Seeding
2) Invasive
3) Anesthesia
4) Expense
How can you do cytology for diagnosis of TSS
1) Cytospin- 30% will be diagnostic, inflammatory cells may confound ability to make diagnosis
2) Traumatic catherization- inflammatory cells may confound diagnosis, invasive, risk of trauma, heavy sedation
3) Percutaneous FNA via ultrasound guidance - risk of cutaneous seeding (low risk)
CADET BRAF and Vet Bladder Antigen urine testing should be paired with
imaging and ideally histo/cyto
What is the vet bladder tumor antigen test
Urine dipstick that measures glycoprotein complex
false positive results common - glucosuria, proteinuria, hematuria, and pyuria
old test
What is the major downside to the Vet Bladder Tumor Antigen Test
false positive results common - glucosuria, proteinuria, hematuria, and pyuria
which many of these dogs have these infection (LUTS)
What is BRAF
proto-oncogene that plays a role in the MAP-kinase cellular signaling pathway
mutated and upregulated in TSS
BRAF mutation is detected in urine of ____% of confirmed canine TSS
85%
What urine collection method is preferred for BRAF testing
free catch
How does BRAF work
free catch sample
uses special form of PCR- digital droplet PCR (ddPCR)
this improves detection level of rare forms of mutated DNA amongst the pool of wildtype (normal) DNA in the sample
can detect down to <0.03% of mutated alleles
What is the BRAF-plus test
the 15% of false negative BRAF tests can be done again to assess for a different mutation and detect an additional 10% of cases
If you get a positive BRAF test you should still follow up with a
abdominal ultrasound to look for evidence of a bladder mass
What are the advantages of BRAF
1) Convenient: free-catch, non-invasive, collected at home or in clinic
2) Sensitive
3) Robust: not affected by the presence of blood, protein, sugars, bacteria in urine
4) Rapid: results generally available in just 5-7 business days
What are TSS treatment options
Most intesive: Intensity Modulated Radiation Therapy (IMRT) + chemotherapy (vinblastine or mitoxantrone) + NSAIDs
Conservative: chemotherapy +NSAIDs +/- palliative radiation
Most conservative: NSAIDs +/- palliative radiation
Surgery: localized tumors at apex, dulking tumors at trigone, cystotomy tube, transurethral resection, urinary diversion
Laser ablation
What should you be cautious about when doing BRAF testing
false positives and negatives may result - recommend confirming presence of urothelial tumor using imaging (+/- cytology/histopathology) prior to treatment when positive BRAF results occur
-Do not base chemotherapy decision on euthanasia decision on b-raf positive alone **
What chemotherapy agents are used in TSS
(vinblastine or mitoxantrone) + NSAIDs
What is the prognosis of TSS
NSAIDs alone: MST 6-8 months
NSAIDs w chemotherapy: MST 9-11 months
NSAIDs w chemotherapy and IMRT: MST 15-24 months
What are the prognostic factors of TSS
lymph node and/or distant metastasis (poorer)
urethral disease - poorer
treatment pursued
clinical signs management
For TSS, why is using NSAiDs beneficial
1) Reduce inflammation and pain
2) COX-2 inhibition cancer effect
T/F: Positive BRAF test is sufficient to diagnose TSS
False- it is a screening test and this alone should not be used to make treatment decisions
What is the clinical presentation of most mammary tumors
Middle aged to older
Dogs: poodles, yorkies, springer spaniels, german shepherd, pointer, Dobe
Cats: Siamese
Late spayed or intact females > males
How do hormone influence the risk of mammary tumor development in Dogs **
Risk if OHE before 1st heat = 0.05% heat
Risk if OHE after 1st heat = 8%
Risk if OHE anytime after 2nd heat = 26%
How do hormones influence the risk of mammary tumor development in cats*
91% reduced risk if OHE before 6 months
86% reduced risk if OHE is between 7-12 months of age
11% reduced risk if OHE is between 13-24 months of age
In dogs, what percent of mammary tumors are benign vs malignant **
50% benign
-Adenoma
-Fibroadenoma
-Benign mixed tumor
-Duct papilloma
50% malignant
-Carcinoma
-Sarcoma
-Carcinosarcoma
In cats, what percent of mammary tumors are benign vs malignant **
10-15% benign
-Hyperplasia
-Adenoma
-Fibroadenoma
85-90% malignant
-Majority carcinoma
-Sarcoma and carcinosarcoma rare
In cats, 85-90% of mammary tumors are malignant, what type is this typically *
majority carcinoma
What should you do for first wave diagnostic when you suspect a mammary mass
Cytology of the mammary mass
-Rule out abscess, cyst, or other tumor type (mast cell tumor, soft tissue sarcoma, etc)
Difficult to differentiate adenocarcinoma vs adenoma on cytology due to small sample size. However, this is more straightforward in cats given the higher risk of malignant mammary masses
What is a downside of doing cytology of mammary masses
Difficult to differentiate adenocarcinoma vs adenoma on cytology due to small sample size. However, this is more straightforward in cats given the higher risk of malignant mammary masses
For dogs: educate client that cytology is not enough to distinguish adenoma vs adenocarcinoma but cytology can rule out abscess, cysts, other tumors
What should you do diagnostically to work up a mammary mass
1) CBC/ CHEM/ UA
2) Regional lymph node aspirate / cytology: lymph node metastasis imparts poorer prognosis /more advanced disease
3) Three view thoracic rads: look for pulmonary metastasis, intra-thoracic lymphadenopathy
4) Abdominal ultrasound +/- cytology - look for liver/ spleen mets, intra-abdominal lymphadenopathy
5) Histopathology: required to confirm malignancy, evaluate margins, determine tumor grade and histotype
How do you treat dogs with mammary masses **
Lumpectomy or mammectomy is sufficient
-if the caudal gland is affected, then dissect out inguinal lymph node and submit separately
If Grade 1 (low) or Grade 2 (intermediate) mammary carcinoma with complete margins then prognosis is excellent and no further treatment other than diligent monitoring
IF Grade 3 (high) or metastatic lymph node then recommend adjuvant chemotherapy (Doxorubicin based or 5-fluorouracil/cyclophosphamide) MST= 12-18 months
What should you do for dogs with mammary masses that are grade 3 (high) or metastatic lymph node *
then recommend adjuvant chemotherapy (Doxorubicin based or 5-fluorouracil/cyclophosphamide) MST= 12-18 months
What is the prognosis for mammary carcinoma in a dog that was removed with complete margins and came back to be Grade 1 (low) or Grade 2 (intermediate) **
If Grade 1 (low) or Grade 2 (intermediate) mammary carcinoma with complete margins then prognosis is excellent and no further treatment other than diligent monitoring
What factors make mammary tumors a poorer prognosis in dogs *
1) Larger tumor
2) Metastasis
3) Lymph/Vascular invasion
4) High grade (Grade 3)
How do you surgically treat cat with mammary tumors **
Chain Mammectomy
-Bilateral (right and left)
recommended due to cross connection of lymphatic vessels
some surgeons will stage the approach
What is the prognosis of mammary tumors in cats
Early detection of small tumors <2cm diameter and aggressive surgery (chain mammectomy) canresult in long term survival
Large tumors, metastatic disease, lymph/vascular invasion, high grade lend to a poorer prognosis
Benefit of chemotherapy is not well studied, but may help in theory
Various studies range from MST 450-1998 days with surgery and doxorubicin based chemotherapy
Does spaying at time of mammary tumor removal in dogs help
newer studies show that spay at MGT = 50% decrease in new (benign) MGT’s
improved outcome in intermediate grade (Grade 2) carcinomas
What is inflammatory mammary carcinoma associated with
recent estrus
inflammatory mammary carcinoma
Dermal lymphatic invasion is histopath hallmark
associated with recent estrus
coagulopathy (21%)
100% lymphnode metastasis in necropsy study
85% distant mets
Median survival time is 7-60 days
Avoid surgery
Palliative therapy only -Piroxicam (MST=180 days)
How do you treat inflammatory mammary carcinoma
Palliative: Piroxicam (MST = 180 days)
palliative RT may help alleviate discomfort
AVOID SURGERY
What is the difference in mammary tumor treatment in dogs vs cats
Dogs: Lumpectomy or mammectomy is sufficient
Cats: Bilateral chain mammectomy
