By J. Lee Talbott, DVM, DACVO (Medical Oncology)
The perianal region of the dog contains several glands, specifically apocrine sweat glands, which are normally responsible for emptying their secretions into the lumen of the anal sacs. One of the most frequently observed cancers in this region is an apocrine gland adenocarcinoma of the anal sac, representing approximately 17% of all perianal malignancies.1,2 The average age of dogs diagnosed with this disease is between 9-11 years with an even sex distribution.3,4 The most commonly reported breeds affected are German Shepherds, Cocker Spaniels, and Golden Retrievers.3
Anal sac apocrine gland adenocarcinoma is locally invasive and typically affects one anal sac; however, bilateral tumors can occur.4 The metastatic potential is reported to be between 50-80% at initial presentation, most commonly to the regional sublumbar and pelvic lymph nodes.5,6 Sites of the distant metastatic disease include the liver, lungs, spleen, bone and less commonly, heart, adrenal glands, pancreas, and kidneys. The incidence of paraneoplastic hypercalcemia of malignancy is approximately 30% and is mediated by tumor secretion of the parathyroid hormone-related peptide.6,7 The degree of plasma-ionized calcium concentrations is higher with anal sac apocrine gland adenocarcinoma and lymphoma, as compared to other types of neoplasia and other causes of hypercalcemia.8
Figure 1: Apocrine gland adenocarcinoma of the left anal sac
The most common presenting complaint often relates to the presence of the primary mass (including perianal discomfort, swelling, bleeding, and scooting) approximately 50% of the time (Figure 1). Patients with hypercalcemia of malignancy often present with polydipsia, secondary polyuria, anorexia, lethargy, or vomiting. Occasionally tenesmus secondary to obstruction of the pelvic canal by regional lymph node metastasis may occur. In approximately 30-50% of cases the primary tumor is incidentally diagnosed on physical examination.5,6 Diagnosis is often made by fine needle aspirate of the primary tumor or enlarged metastatic lymph nodes.
Currently, there is no accepted standard of care for anal sac apocrine gland adenocarcinoma and the optimal combination of therapies is unknown. This is a result of a large number of reports with heterogeneous patient populations and treatments applied. Treatment options include surgery and/or radiation therapy for the primary tumor and regional lymph nodes, and chemotherapy for control of the distant metastatic disease. Surgical removal of the primary tumor is recommended however complete resection of larger tumors is difficult due to the anatomic location in close proximity to the rectum and poor definition of perineal tissue to define an adequate margin. For this reason, surgical margins are interpreted as dirty or incomplete.
The role of post-operative radiation therapy to the primary tumor isn’t clear based on the literature available, however in one study, patients treated with surgery and definitive radiation therapy to the primary tumor site, and adjuvant chemotherapy with mitoxantrone, the median survival time was approximately 2.5 years. The impact of chemotherapy versus radiation therapy wasn’t clear from this study.9 Definitive radiation therapy to the perineal region is generally well tolerated with self-limiting, acute side effects including mild to severe moist desquamation, colitis, and perineal discomfort that may last for 2-4 weeks after the conclusion of radiation therapy. Chronic complications may include tenesmus, rectal stricture, and narrow stool. Radiation therapy protocols using less than 3 Gy per fraction have been shown to reduce the risk of chronic complications.10 While generally well tolerated, the author doesn’t routinely recommend treatment with post-operative radiation due to a lack of available evidence to support a survival benefit.
Treatment with chemotherapy is indicated in all patients with apocrine gland adenocarcinoma of the anal sac due to the high rate of metastatic disease. Several chemotherapy agents have demonstrated activity in both the gross disease and adjuvant treatment setting, including carboplatin, mitoxantrone, and melphalan to name a few.9,11,12 More recently, toceranib phosphate (palladia®) has been associated with tumor response in patients with multiple prior failed therapies and the antitumor effect is thought to be mediated through inhibition of platelet-derived growth factor receptor β (PDGF-β).13 The author’s chemotherapy of choice in the adjuvant setting is mitoxantrone, whereas carboplatin or palladia® are considered in the gross disease setting.
Previously identified negative prognostic factors include large primary tumor size, the presence of lymph node metastasis, the presence of distant metastasis, hypercalcemia, and the treatment pursued.3,5,6 That being said, the presence of multiple negative prognostic factors shouldn’t preclude treatment. Specifically related to hypercalcemia, treatment of the primary tumor and metastatic disease results in resolution of hypercalcemia.3,5,9 The return of hypercalcemia after therapy usually signals local recurrence or metastasis, and therefore clients should be educated on the clinical signs associated with hypercalcemia and what to monitor for at home. At the time of recurrence or metastasis, repeated treatment involving any combination of surgery, radiation therapy (palliative or definitive), and/or chemotherapy should be considered due to the additional survival benefit in these cases.12,14,15
It is difficult to accurately predict the prognosis of individual dogs with anal sac apocrine gland adenocarcinoma as a result of significant variability within the literature regarding the stage of disease and treatments used. Identification of reliable prognostic criteria is necessary to assist in predicting outcome and treatment response. Based on the available literature, we know that prolonged survival is possible, despite varying tumor stage and treatments performed. When considering all data, the estimated median survival time for patients with anal sac apocrine gland adenocarcinoma is between 1.5 – 2.5 years.3,9,12 Whenever possible surgery to remove the primary tumor is recommended followed by adjuvant chemotherapy. If surgery isn’t possible, radiation therapy should be considered for the primary tumor and metastatic lymph nodes if present, followed by adjuvant chemotherapy.
- Nielsen SW, Aftosmis J: Canine perianal gland tumors, J Am Vet Med Assoc 144:127-135, 1964.
- Berrocal A, VosJH, van den Ingh TS, et al: Canine perineal tumours, J Vet Med Ser A 36:739-749, 1989.
- Polton GA, Mowat V, Lee HC, et al: Breed, gender and neutering status of British dogs with anal sac gland carcinoma, Vet Comp Oncol 4(3):125-131, 2006.
- Goldschmidt MH, Zoltowski C: Anal sac gland adenocarcinoma in the dog: 14 cases, J Small Anim Pract 22:119-128, 1981.
- Bennett PF, DeNicola DB, Bonney P, et al: Canine anal sac adenocarcinomas: clinical presentation and response to therapy, J Vet Intern Med 16: 100-104, 2002.
- Williams LE, Gliatto JM, Dodge RK, et al: Carcinoma of the aprocrine glands of the anal sac in dogs: 113 cases (1985-1995), J Am Vet Med Assoc 223:825-831, 2003.
- Rosol TJ, Capen CC, Danks JA, et al: Identification of parathyroid hormone-related protein in canine apocrine adenocarcinoma of the anal sac, Vet Pathol 27:89-95, 1990.
- Messinger JS, Windham WR, Ward CR: Ionized hypercalcemia in dogs: a retrospective study of 109 cases (1998-2003), J Vet Intern Med 23:514-519, 2009.
- Turek MM, Forrest LJ, Adams WM, et al: Postoperative radiotherapy and mitoxantrone for anal sac adenocarcinoma in the dog: 15 cases (1991-2001), Vet Comp Oncol 1(2):94-104, 2003.
- Anderson CR, McNiel EW, Gillette EL, et al: Late complications of pelvic irradiation in 16 dogs, Vet Radiol Ultrasound 43(2):187-192, 2002.
- Emms SG: Anal sac tumours of the dog and their response to cytoreductive surgery and chemotherapy, Aust Vet J 83(6):340-343, 2005.
- Wouda RM, Borrego J, Keuler NS, Stein T: Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs, Vet Comp Oncol 14(1):67-80, 2016.
- London C, Mathie T, Stingle N, et al: Preliminary evidence for biologic activity of toceranib phosphate (Palladia) in solid tumours, Vet Comp Oncol Epub ahead of print, 2011.
- Hobson HP, Brown MR, Rogers KS: Surgery of metastatic anal sac adenocarcinoma in five dogs, Vet Surg 35:267-270, 2006.
- Hoelzler MG, Bellah JR, Donofro MC: Omentalization of cystic sublumbar lymph node metastases for long-term palliation of tenesmus and dysuria in a dog with anal sac adenocarcinoma, J Am Vet Med Assoc 219(12):1729-1731, 2001.