AGASACA + Perianal Tumors Flashcards
True or false - cats can develop perianal adenoma/perianal adenocarcinoma
False - don’t have perianal sebaceous glands
Development and progression of perianal adenomas is _____ with growth stimulated by ______ and suppressed by _____
Sex hormone-dependent androgens estrogens
Perianal adenomas in female dogs occur almost exclusively in ______
spayed animals - have low estrogen = no tumor suppression
T/F: Perianal adenocarcinomas are hormonally dependent?
False
Rate of metastasis for perianal adenocarcinomas
Low, <15%
Most frequent sites of mets from perianal adenocarcinomas? Less frequent?
Regional LN and lungs; liver, kidney, bone
What five things are increased histologically/molecularly in perianal adenocarcinomas compared to adenomas?
Increased proliferating cell nuclear antigen (PNCA), apoptotic corpuscles, Ki67, VEGF, serum magnesium levels
What is needed to definitively tell perianal adenoma from adenocarcinoma?
Incisional bx
What IHC can help differentiate perianal adenoma from adenocarcinoma?
Monoclonal Ab against carcinoma-associated Ags 4A9, 1A10; PCNA, Ki67
What can help differentiate a perianal adenocarcinoma from AGASACA?
cytokeratin expression patterns
What margins can perianal adenomas be removed with?
Minimal margins, <1cm
Other than surgical removal of the primary tumor, what else is recommended for treatment in dogs with perianal adenomas?
Castration
What if a perianal adenoma is diffuse or too large to be removed? Treatment?
Surgical staging - castration first, may shrink tumor Cryosurgery CO2 laser ablation Hyperthermia RT ECT
What is the repoarted response rate for perianal adenomas treated with ECT
>90%, 65% CR
Do perianal adenocarcinomas respond to castration?
Nope
What has a significant influence of DFI and OSTs for dogs with perianal adenocarcinoma?
Stage of tumor - T2 tumors (<5cm) do better
2-year control rate for T2 perianal adenocarcinoma treated with surgery? Also, what is a T2 tumor?
<5cm >60%
MST for dogs with LN or distant mets from perianal adenocarcinoma
7mo (but aggressive therapy not pursed for most dogs)
What breeds have an increased risk of AGASACA?
Spaniels (particularly English cocker spaniels) German Shepherds Alaskan malamutes Dachshunds
Gender/neuter status assoc. with risk of AGASACA?
Neutering may be associated with increased risk for males
What are the three histologic patterns of AGASACA?
Solid Tubules/Rosettes/Pseudorosettes Papillary
Which are the most common histologic patterns of AGASACA
solid and tubules/rosettes/pseeudorosettes in 95%
What is the rate of bilateral AGASACA (simultaneously or temporally separated)
up to 14%
Rate of paraneoplastic hypercalcemia in dogs with AGASACA?
16-53%
Mediator of hypercalcemia in canine AGASACA?
PTHrp from neoplastic tissue
Overall rate of mets for dogs with AGASACA? LN? Distant?
Overall: 26-96% LN 26-89% Distant 0-42%
What are the less common sites of AGASACA mets?
heart, omentum, stomach, adrenal glands, panc, kindeys, Ubladder, mediastinum
What has been associated histologically with risk of metastasis at diagnosis for canine AGASACA?
Marked peripheral infiltration into surrounding tissue, LV invasion, solid pattern
Does high or low levels of E-cadherin expression in AGASACA correlate with a better survival time?
Higher
Rate of mets from AG melanoma in dogs?
4/8 sublumbar LN, 1/11 pulmonary
Rate of mets from regional LN for feline AGASACA?
20%
Have bilateral AGASACA been reported in cats?
Nope
What percentage of dogs have an AGASACA be an incidental finding?
up to 47%
What is the most common clinical sign for cats with AGASACA?
Perineal ulceration or discharge
What IHC staining can confirm AGASACA dx if needed?
Cytokeratin pattern CK7+/CK14-
What was shown to be the only consistently abnormal feature of abdominal malignant LNs?
Size
What three LN centers can be involved in AGASACA
medial and internal iliac, sacral
What is the complication rate after local surgery for AGASACA and what is the most common complication?
5-24% wound dehisence, rectal perforation, rectocutaneous fistulation, incisional infection, transient fecal incontinence
What can help limit the complications of surgical removal of AGASACA
Smaller anoplasty - previous studies showed 40-60% rate of fecal incontinence when 120-270 degree anoplasties performed
Complication rate of LN extirpation for dogs with AGASACA?
0-12% - hemorrhage, uncresectable LN, LN rupture and abdominal wall dehisence
T/F: treatment of recurrent AGASACA or progressive nodal mets is not recommended for dogs as it does not improved survival
False
When can you pursue splenectomy for AGASACA?
If confirmed mets to spleen + context of slowly progressive dz and no other mets
What drugs have demonstrated antitumor activity in gross disease setting for AGASACA in dogs
carbo, cisplat, actinomycin D
Measurable response rates for dogs with AGASACA with bulky disease treated with RT (hypofx or fx protocols)?
38-75%
Over what radiation dose per fraction to the colon are late radiation side effects more likely to occur?
3Gy
Palliative RT protocols result in an improvement in clinical signs in up to ______, including resolution of____
up to 63% Obstipation
Palliative RT protocols can resolve ____% of hypercalcemic dogs with AGASACA. What improves this %?
RT alone 31% RT + Pred + bisphosphonate = 46% additional
Reported PFIs and MSTs for dogs treated with palliative RT for AGASACA?
PFI 10-11 mo MST 8-15mo
Is rate of local recurrence for dogs treated with AGASACA related to the completeness of excision?
Nope
What is associated with a shorter median DFI for dogs with AGASACA treated with surgery (across multiple studies)
LN mets: 134-197d vs. 529-760d if not
Est. 1 and 2 yr survival rates for dogs with AGASACA
65%, 29%
Poor prognostic factors for AGASACA in dogs (10)
Primary tumor size, presence of clinical signs, presence of LN mets, size of LN mets, distant mets, no surgery, tx with chemo alone, E-cadherin expression, solid histo type; hypercal in some.
PFI and OST for dogs treated for AG melanoma with a variety of treatments?
3mo, 3.5mo
MST for cats with AGASACA treated with surgically +/- chemo and/or RT?
260d
Poor prognostic factors for survival in cats with AGASACA
local tumor recurrence Increased nuclear pleomorphic score (2 or 3)
What was the agreement for intra- and peri-mural Tc99 injected for sentinel LN mapping of AGs? (Linden VRU 2019)
50% agreement
Which method of Tc99 injection was uptake faster for, perimural or intramural? (Linden, VRU 2019)
Intramural
What was the MST for dogs treated with surgery, RT and mitoxantrone chemotherapy (Turek VCO 2003)? What was the RT protocol?
MST 956d.
RT 3.2Gy x 15 = 48 Gy
Late RT effects developed in what percent of dogs treated for AGASACA with RT, Mito and surgery? (Turek VCO 2003)
50% of dogs - nonconformal RT used
Protocol 3.2Gyx15=48 Gy
Curative-intent RT protocols should limit pelvic radiation to ____Gy/fraction
< 3Gy/fraction
Median OST/TTP for dogs treated with adjuvant carboplatin and surgery compared to treated with surgery alone? (Wouda VCO 2016)
Carbo group: OST 703d, TTP 384d
Surgery alone: OST 581d, TTP 402 (no significant difference)
n=74 dogs, 44 carbo, 30 surgery alone
What was found to significantly affect OST/TTP in dogs with AGASACA treated with surgery +/-chemo (Wouda VCO 2016)
Primary tumor size
LN mets
What significantly prolonged survival in dogs treated with surgery +/- carbo for AGASACA? (Wouda VCO 2016)
Treatment
In 130 dogs with AGASACA, what were found to be prognostic factors? (Polton JVIM 2007)
Lack of treatment
Presence of distant mets
LN mets
Primary tumor size (2.5cm)
What algorithm for treatment for dogs with AGASACA was developed in the 2007 Polton paper (130 dogs with AGASACA)
Treat with neoadjuvant chemotherapy if local LN >4.5cm or if primary >2.5cm
Prognostic factors for dogs with AGASACA based on Williams, JAVMA 2003
Tumors >10cm2
hypercalcemia
pulmonary metastasis
Response rate to Palladia for dogs with stage IV AGASACA? (Elliot JAVMA 2019)
13/15 (87%) SD, no CR or PR
What percentage of dogs with stage IV AGASACA treated with Palladia had improvement in clinical signs? (Elliot JAVMA 2019)
5/13 dogs with SD = 38% of dogs with SD or 5/15=33% for all dogs included
mPFI and MST for dogs treated with Palladia for stage IV AGASACA (Elliot JAVMA 2019)
mPFI 354d, MST 356d
Longer compared to historic data
PFI and MST for dogs with stage 3b AGASACA treated with surgery or hypofx RT? (Meier VCO 2017)
Surgery: PFI 159d, MST 182d
RT (8x3.8Gy = 30.4Gy): PFI 347d, MST 447d
Percent resolution for hypercalcemia in dogs with AGASACA treated with hypofractionated RT? (McQuown, VCO 2016)
31% resolution
PR rate to hypofractionated RT for dogs with advanced AGASACA? What about improvement in clincal signs? (McQuown, VCO 2016)
38% PR (n=77 dogs total)
63% improvement in signs
MST and PFS for dogs with advanced stage AGASACA treated with hypofractionated RT (McQuown VCO 2016)
MST 329d.
PFS 289d.
MST for dogs with early-stage AGASACA (no mets) treated with surgery alone? Size cutoff? Skorupski JAVMA 2018
MST 1,237d (<3.2cm)
Tumor recurrence and median time to recurrence for dogs with early-stage AGASACA treated with surgery alone? (Skorupski JAVMA 2018)
7/34 (20%) had recurrence
median time to recurrence = 354d
Rate of and time to metastasis for dogs with early stage AGASACA treated with surgery alone? (Skorupski JAVMA 2018)
9/34 (25%)
Time to mets = 589d
What was positively associated with development of metastasis in dogs with early stage AGASACA treated with surgery alone? (Skorupski JAVMA 2018)
Cellular pleiomorphism positively associated with developing mets
What was the rate of complications for dogs treated with surgery for AGASACA (Barnes JSAP 2017)
12% rate for perineal surgery
What was associated with decreased survival time in 42 dogs treated with surgical excision +/- chemo for AGASACA (Potanas JAVMA 2015)
Sublumbar LN mets, surgical LN extirpation (not consistent throughout rest of literature)
Was there a difference in survival or DFI for dogs treated with surgery +/- chemo for AGASACA (Potanas JAVMA 2015)
Nope, no difference for complete, marginal or incomplete
What histo features were not associated with nodal mets at presentation in dogs with AGASACA? (Pradel VCO 2018)
mitotic counts, necrosis
What histo features were associated with decreasd PFI and OST for AGASACA? (Pradel VCO 2018)
Solid tumor pattern
increased peripheral infiltration into surrounding tissue
presence of necrosis
lymphovascular invasion
What IHC markers do AGASACA express? (Suzuki Vet Path 2013)
Chromogranin A (40.6%)
Neuron-specific enolase (46.4%)
Synaptophysin (15.9%)
What molecular factors are expressed in canine AGASACA? (Urie and London BMC 2012)
PDGFRa/b
VEGFR2
KIT
Ret - posphorylated in 54%
What LNs were identified for dogs with AGASACA using CT lymphography (Majesk VRU 2017)
Sacral, internal iliac and medial iliac
Ipsilateral in 8/12, contralateral in 4/12
What LNs were identified for dogs with AGASACA using CT lymphography (Majesk VRU 2017)
Sacral, internal iliac and medial iliac
Ipsilateral in 8/12, contralateral in 4/12
What molecular factors are expressed in canine AGASACA? (Urie and London BMC 2012)
PDGFRa/b
VEGFR2
KIT
Ret - posphorylated in 54%
What IHC markers do AGASACA express? (Suzuki Vet Path 2013)
Chromogranin A (40.6%)
Neuron-specific enolase (46.4%)
Synaptophysin (15.9%)
What histo features were associated with decreasd PFI and OST for AGASACA? (Pradel VCO 2018)
Solid tumor pattern
increased peripheral infiltration into surrounding tissue
presence of necrosis
lymphovascular invasion
What histo features were not associated with nodal mets at presentation in dogs with AGASACA? (Pradel VCO 2018)
mitotic counts, necrosis
Was there a difference in survival or DFI for dogs treated with surgery +/- chemo for AGASACA (Potanas JAVMA 2015)
Nope, no difference for complete, marginal or incomplete
What was associated with decreased survival time in 42 dogs treated with surgical excision +/- chemo for AGASACA (Potanas JAVMA 2015)
Sublumbar LN mets, surgical LN extirpation (not consistent throughout rest of literature)
What was the rate of complications for dogs treated with surgery for AGASACA (Barnes JSAP 2017)
12% rate for perineal surgery
What was positively associated with development of metastasis in dogs with early stage AGASACA treated with surgery alone? (Skorupski JAVMA 2018)
Cellular pleiomorphism positively associated with developing mets
Rate of and time to metastasis for dogs with early stage AGASACA treated with surgery alone? (Skorupski JAVMA 2018)
9/34 (25%)
Time to mets = 589d
Tumor recurrence and median time to recurrence for dogs with early-stage AGASACA treated with surgery alone? (Skorupski JAVMA 2018)
7/34 (20%) had recurrence
median time to recurrence = 354d
MST for dogs with early-stage AGASACA (no mets) treated with surgery alone? Size cutoff? Skorupski JAVMA 2018
MST 1,237d (<3.2cm)
MST and PFS for dogs with advanced stage AGASACA treated with hypofractionated RT (McQuown VCO 2016)
MST 329d.
PFS 289d.
PR rate to hypofractionated RT for dogs with advanced AGASACA? What about improvement in clincal signs? (McQuown, VCO 2016)
38% PR (n=77 dogs total)
63% improvement in signs
Percent resolution for hypercalcemia in dogs with AGASACA treated with hypofractionated RT? (McQuown, VCO 2016)
31% resolution
PFI and MST for dogs with stage 3b AGASACA treated with surgery or hypofx RT? (Meier VCO 2017)
Surgery: PFI 159d, MST 182d
RT (8x3.8Gy = 30.4Gy): PFI 347d, MST 447d
mPFI and MST for dogs treated with Palladia for stage IV AGASACA (Elliot JAVMA 2019)
mPFI 354d, MST 356d
Longer compared to historic data
What percentage of dogs with stage IV AGASACA treated with Palladia had improvement in clinical signs? (Elliot JAVMA 2019)
5/13 dogs with SD = 38% of dogs with SD or 5/15=33% for all dogs included
Response rate to Palladia for dogs with stage IV AGASACA? (Elliot JAVMA 2019)
13/15 (87%) SD, no CR or PR
Prognostic factors for dogs with AGASACA based on Williams, JAVMA 2003
Tumors >10cm2
hypercalcemia
pulmonary metastasis
What algorithm for treatment for dogs with AGASACA was developed in the 2007 Polton paper (130 dogs with AGASACA)
Treat with neoadjuvant chemotherapy if local LN >4.5cm or if primary >2.5cm
In 130 dogs with AGASACA, what were found to be prognostic factors? (Polton JVIM 2007)
Lack of treatment
Presence of distant mets
LN mets
Primary tumor size (2.5cm)
What significantly prolonged survival in dogs treated with surgery +/- carbo for AGASACA? (Wouda VCO 2016)
Treatment
What was found to significantly affect OST/TTP in dogs with AGASACA treated with surgery +/-chemo (Wouda VCO 2016)
Primary tumor size
LN mets
Median OST/TTP for dogs treated with adjuvant carboplatin and surgery compared to treated with surgery alone? (Wouda VCO 2016)
Carbo group: OST 703d, TTP 384d
Surgery alone: OST 581d, TTP 402 (no significant difference)
n=74 dogs, 44 carbo, 30 surgery alone
Curative-intent RT protocols should limit pelvic radiation to ____Gy/fraction
< 3Gy/fraction
Late RT effects developed in what percent of dogs treated for AGASACA with RT, Mito and surgery? (Turek VCO 2003)
50% of dogs - nonconformal RT used
Protocol 3.2Gyx15=58 Gy
What was the MST for dogs treated with surgery, RT and mitoxantrone chemotherapy (Turek VCO 2003)? What was the RT protocol?
MST 956d.
RT 3.2Gy x 15 = 48 Gy
Which method of Tc99 injection was uptake faster for, perimural or intramural? (Linden, VRU 2019)
Intramural
What was the agreement for intra- and peri-mural Tc99 injected for sentinel LN mapping of AGs? (Linden VRU 2019)
50% agreement
What was the difference in AUS vs. CT for staging of dogs with AGASACA? (Palladino JVIM 2016)
AUS only detected correct number of enlarged LN in 30% but did identify at least 1 enlarged LN in 100% of affected dogs
Did AUS or CT identify more abnormal iliosacral LN for dogs with AGASACA? (Pollard VCO 2015)
Ultrasound
MST for cats treated with surgery for AGASACA, 1- and 2-yr survival rates? (Shoieb VetPath 2009)
MST 3mo, 1yr 19%, 2yr 0%
What is the MST for tumors expressing high vs. low E-cadherin in AGASACA? (Polton VCO 2017)
>75% of cells expressing e-cadherin: 1168d
<75% of cells: 448d
Response to stage 4 AGASACA dogs to palladia? (Elliot JAVMA 2019)
13/15 SD, no PR or CR 5/13 had improvement of clinical signs
mPFI and MST for dogs with stage 4 AGASACA treated with Palladia? (Elliot JAVMA 2019)
mPFI 354d, MST 356
Most common clinical sign for cats with AGASACA? (Amsellem JAVMA 2019)
perianal ulceration or discharge (85%)
Time to local recurrence in cats with AGASACA treated with surgery +/- chemo and/or RT; risk factors for local recurrence?(Amsellem JAVMA 2019)
96d; incomplete margins and higher nuclear pleomorphic score
DFI and MST for cats with AGASACA treated with surgery +/- chemo and/or RT; Anything associated with DFI or MST? (Amsellem JAVMA 2019)
DFI 234d, MST 260d. nuclear pleomorphic score associated with both