Perianal tumors Flashcards
Perianal tumors represent what % of tumors in dogs and cats?
17% of all perianal malignancies in dogs; 2% and 0.5% (rare) of all skin and SQ tumors in dogs and cats
List 5 dogs breeds and risk and cat breed at risk
English cocker spaniels, other spaniels, dachshunds, GSD and Alaskan malamutes; Siamese cats.
Sex predilection
No sex predilection, neutering may be associated with increased risk in males
Mean age in dogs? cats?
9-11 years in dogs (as young as 5 yo, so always check the anal sacs on PE) and 13 in cats
List the 3 histological patterns of AGASACA?
95% are either classified as solid (closely packed cancer cells w/o much stroma)
tubules/rosettes (cancer cells arranged radially around a central tubule or vessel)
less commonly papillary
What is the biological behaivour of AGASACA?
locally invasive disease with moderate to high risk of local recurrence after surgery and a moderate to high metastatic rate in dogs and cats
Are AGASACA unilateral or bilateral tumor?
Bilateral incidence in dogs? cats?
Usually unilateral tumors
bilateral incidence is 14% for dogs and 0% for cats, includes temporarily separated
What are the 2 reported paraneoplastic syndromes associated with AGASACA?
hypercalcemia (caused by tumor secretion of PTHrP) seen in 16%-53% of dogs and 11% of cats
hypertrophic osteopathy (2 dogs with pulmonary mets)
Is metastasis common at diagnsosis? How common?
Regional LN metastasis?
Distant site metastasis and sites?
List risk factors for metastasis?
Common at diagnosis (26-96% in dogs, variable in cats), even when primary is small (<1cm).
Regional LN: (26-89% in dogs, 20% in cats) most commonly to the sacral and sublumbar nodes (medial and internal iliacs) and can show variable metastatic patterns (as evidenced by CT lymphography) not always following lymphatic drainage linearly from the perineum and sometimes skipping LNs.
Distant sites: (0-42%) lungs, liver, spleen and bone and less commonly “anywhere else” (including BM in 4 dogs)
Risk factors for metastasis: presence of clinical signs (vs tumor as incidental finding), marked peripheral infiltration, lymphovascular invasion (vs mitotic index and necrosis).
Some important genes and proteins in AGASACA
TSG: E-cadherin (overexpression associated with increased survival), p53 (expression detected w/o clinical implications)
o COX-2: detected in all tumor samples (expression was high in 12% and moderate in 36%), but also in normal anal sacs. Neuroendocrine differentiation proteins: synaptophysin, chromogranin A, neuro-specific enolase (30% expression).
o TKR: Urie et al (BMC Vet Res, 2012) detected VEGFR-2, PDGFR-a and 13, KIT and RET mRNA in all 25 tumor samples; but IHC detection was less consistent (most expressed VEGFR2, PDGFR-a and PDGFR-13, but only 1/3 KIT).
Two other possible anal sac tumors?
o Melanomas: 1 case series (n=11 dogs) by Vinayak et al (JSAP, 2017) documented moderate to aggressive unilateral tumors, with a mean size >3cm, a median mitotic index of 50/10 HPF, with metastasis to the LN (4/11) and lungs (1/11) at diagnosis, all presenting clinical signs (bleeding) and 10/11dying due to PD in only 107 days (MST).
o SCC: reports document unilateral tumors with no evidence of metastasis but do mention local recurrence.
IHC markers for AGASACA?
Cytokeratin+ (CK7+/CK14-), but usually not needed for diagnosis.
Mainstay therapy for AGASACA?
Surgical resection which is marginal
Complications with anal sacculectomy?
rate of 5-24% (related to tumor size and % of anal circumference resected), most common are dehiscence +/- infection, rectal perforation, fistulae formation and different degrees of fecal incontinence (especially if > 50% of the sphincter muscle is resected, old/very aggressive study reports a 19% rate out of which 60% was permanent).
What are the advantages and disadvantages for metastatic lymphadenectomy which is recommended for sublumbar and sacral LN?
Advantages: improve quality of life (by relieving pelvic canal obstruction and helping with hypercalcemia) and survival in some studies (Polton et al, JVIM 2007), but the opposite effect is reported in other studies (Potanas, JAVMA 2015).
Disadvantages: requires a second surgical approach (abdominal +/- pelvic osteotomy), has a complication rate of 012% which include severe infra-op hemorrhage which may require transfusion (LNs closely associated with aorta and caudal vena cava). Palliative RT has been proven more effective/tolerated in advanced cases.
Role of chemotherapy in AGASACA?
Cytotoxic chemotherapy drugs?
Recommended due to metastasis
Cytotoxic chemotherapy: drugs with documented anti-tumor activity are carboplatin, cisplatin, actinomycin D (gross disease), mitoxantrone and melphalan (residual disease post-op).
Williams et al JAVMA, 2003: n=113 dogs, MST=500 days with surgery alone vs MST=540 days with surgery + chemotherapy (cisplatin, carbo, mito and doxo). No significant difference.
Wouda et al, VCO, 2016: n=75 dogs, OS=581 and TTP=402 days with surgery alone vs OS=723 and TTP=384 days with surgery + carbo chemotherapy. No statistical difference.
Potanas et al, JAVMA, 2015: n=42 dogs, DF1=470 days with surgery alone vs surgery + DP7=226 days with chemotherapy (mostly carboplatin), similar MST. More advanced disease on chemo group
Role of RTKi?
RTKi (Palladia): modest tumors responses have been reported.
London et al, VCO, 2012: n=32 AGASACAs, clinical benefit=88%, with 25% PRs (8) and 63% SD (20), lasting 10-47 weeks, resolution of hypercalcemia was also reported.
Elliot, JAVMA, 2019: n=15 dogs with advanced stage AGASACA; noted CRs=0, PRs=0, SD=13 and PD=2, but also improvement of clinical signs (tenesmus, cough) in 5/10 dogs, PFI=354, ST=356 days.
Side effects associated with curative intent radiation therapy for AGASACA
late side effects, such as rectal stricture or perforation or chronic colitis; but also transient acute side effects such as severe moist desquamation and colitis.
<3Gy fractions and IMRT have been shown to decrease the chances of these adverse events observed in older studies.
What is the DFI after surgery with or without adjuvant therapy for AGASACA?
DFI after surgery with or w/o adjuvant therapy is 262-443 days (9-15 mo).
What is the overall MST for AGASACA and the 1- and 2- year survival rate?
Tumor related death?
Overall MST=386-960 days (1.0-2.6 yr)
1- and 2-year survival rates of 65% and 29%, with 41-81% tumor-related death rate
List the 8 prognostic factors for AGASACA?
Clinical stage
Metastasis
Primary tumor size
Clinical signs
Treatment modality
Histology
E-cadherin expression
Hypercalcemia
How is clinical stage a prognostic factor for AGASACA?
Dogs with no metastasis and small tumors (<2.5cm) treated with surgery have a good outcome. e.g., Polton et al, MST—-not reached, tumor-related death rate=only 9%.
How is metastasis a prognostic factor for AGASACA?
MST for dogs with LN mets, distant mets, no mets?
Presence of regional LN or distant metastasis is associated with a worse prognosis and 2.3x higher risk of tumor-related death. e.g., MST-293-448 days (10-15 mo) with LN mets and 71-356 days (2.4-12 mo) with distant mets treated with different modalities vs MST-529-1205 (1.4-3.3 yr) w/o metastasis.
How is primary tumor size a prognostic factor for AGASACA?
Prognostic for survival, nut the threshold varies across studies. e.g., Williams et al, MST-584 days for <10cm vs 292 days for >10cm; Polton et al, MST=1205 days for <2.5cm vs 722 days for >2.5cm; Turek et al, DFI=518 and MST=773 days for <4cm vs DFI=251 and M ST=433 days for >4cm.
