Neoplasias in the perianal area of the dog are frequent, and there are two main groups of glands from which tumors can originate:
1. Apocrine anal sac glands
2. Perianal or circumanal glands, also known as hepatoid glands
From these glands, both benign (adenoma) as well as malignant (adenocarcinoma) tumors can develop. Additionally, other skin tumour types, such as mast cell tumor, melanoma or lymphoma can also be found in this anatomic location.
Anal Sac Gland Neoplasia
Tumors of the anal sacs originate from the apocrine glands of the anal sac wall. Adenocarcinoma of the anal sac is quite common and represents about 2% of all canine skin tumours. The average age of affected dogs is 11 years and breeds such as Spaniels, Dachshunds, and Shepherd dogs are predisposed. Genetic factors in English Cocker Spaniels have recently been extensively studied (Polton 2009). Earlier studies reported a higher incidence in female dogs, but a more recent report shows a more equal distribution between both sexes (f:m = 56:44%). In this study, approximately 2/3 of the animals were castrated, confirming the assumption that anal sac tumours occur independently of hormonal status (Polton et al. 2006). Anal sac adenomas are extremely rare.
Adenocarcinomas present as circumscribed or infiltrative masses of 0.2–10 cm diameter. Small tumors are usually discovered by careful rectal palpation; in cases of larger tumors, a perianal bulging mass or swelling can often be seen externally. The tumor is most often unilateral; however, in 10% of the cases, bilateral tumors are present. Sometimes the neoplasia reaches enormous proportions (up to 10 cm in diameter), which in combination with metastatic enlarged sublumbar lymph nodes can cause compression of the rectum resulting in constipation and tenesmus. The biological behavior of adenocarcinoma is characterized by invasive growth, a typical metastatic pattern and the occurrence of paraneoplastic hypercalcemia. Metastases to the regional lymph nodes (Lnn. lumbales aortici - "sublumbar lymph nodes") occur quite rapidly and are present in up to 75% of the cases at time of diagnosis. The metastases can reach sizes that exceed that of the primary tumor by far. Systemic metastasis occurs in later stages of the disease, mostly to the lungs and abdominal organs. The rate of systemic metastasis varies from study to study and ranges between 50% and 90%. Sometimes metastasis can be found in the lumbar vertebrae. Hypercalcemia is the most common paraneoplastic syndrome and is encountered in 30–50% of the cases. Hypercalcemia is caused by a parathyroid hormone-like substance (parathyroid hormone related polypeptide - PTHrp) released by the tumor, which leads to a rise in blood calcium levels and clinical symptoms such as polyuria/polydipsia, lethargy, anorexia, weight loss, weakness, bradycardia, vomiting and constipation. The high blood level of calcium is responsible for these symptoms, as it affects the kidneys, causes a reduced excitability of both smooth and striated muscles and leads to a general dampening of the central nervous system. Some animals with hypercalcemia also develop hypophosphatemia. About 1/3 of the patients are presented with difficulty defecating, which is the result of a combination of hypercalcemia-associated constipation, dehydration, and compression of the rectum from sublumbar or intrapelvic metastases.
Cytology is usually sufficient to establish a definite diagnosis. As in all tumors with endocrine activity, the cellular features of anal sac carcinoma look quite "benign." Careful staging, including digital rectal exam, hematologic and serologic (calcium!) examinations, thoracic radiographs as well as abdominal sonography is mandatory to formulate a treatment plan. If available, computed tomography is superior to ultrasound in detecting sublumbar and intrapelvic metastases and is highly preferable for surgical treatment planning. Staging using the modified scheme by Polton and Brearley (2007) is diagnostic.
The first therapeutic choice for anal sac adenocarcinoma is surgical removal followed by irradiation and/or chemotherapy. In all cases of anal sac tumors, a segmental resection of the anal sphincter is required. Radical resections involving more than 180° of the sphincter circumference may be associated with partial or complete fecal incontinence. Whenever possible, metastatic sublumbar or intrapelvic lymph nodes should be removed. The author recommends beginning the tumor surgery with a caudal laparotomy for removal of the lymph nodes followed by the resection of the primary tumor. Surgical planning using computed tomography greatly improves detection of smaller metastatic lymph nodes. Following successful therapy, blood calcium levels usually promptly return to normal, but in the case of tumor recurrence or in the presence of metastasis, they can rise rapidly. For this reason, monitoring of calcium as a tumor marker is recommended in cases initially presenting with hypercalcemia. After the surgical wound has healed, radiation therapy including the site of the primary tumor and the area of the sublumbar lymph nodes and/or chemotherapy is started. If lymph nodes or primary tumor are not surgically removable, primary irradiation therapy followed by chemotherapy is recommended.
Radiation therapy is usually administered hypofractionated (3–5 x 6 Gy, weekly or twice weekly). Carboplatin chemotherapy (300 mg/m2 BSA over 20 min IV; 5 applications 3–4 weeks apart) can be given concurrently or after finishing radiation. Cisplatin and Carboplatin led to a partial remission in 1/3 of cases studied (Bennet et al. 2002). In a study with 104 dogs, multimodality therapy had the best prognosis and surgical therapy had the biggest impact on prognosis. Patients that were treated by surgery followed by chemotherapy had a significantly better survival time compared to patients treated with chemotherapy alone (median ST of 584 vs. 212 days). Median survival time of all dogs in this study was 544 days (range, 0 to 1873 days; Williams et al. 2003). The most important prognostic factors are type of therapy, size of the tumor, presence of hypercalcemia and metastasis. In a large study with 104 cases, hypercalcemic dogs (n= 29; 27%) had a significantly shorter survival time (median 256 days) compared to normocalcemic patients (median 584 days; Williams et al. 2003). In the same study, patients with tumors >10 cm2 had a significantly shorter ST (median 292 days) compared to those with smaller tumors (median 584 days). Dogs with and without pulmonary metastasis survived a median of 219 and 548 days, respectively. The presence of lymph node metastasis appeared not to affect the prognosis.
Tumors of the Circumanal Glands ("Hepatoid Glands")
When the canine perianal glands were first described they were named "hepatoid glands" due to their morphologic resemblance with liver cells. Hepatoid glands are present primarily in the perianal area, but to a lesser degree they can also be found in other body regions; e.g., base of the tail, vulva, prepuce, hind legs and caudal dorsum. On the tail, they can be found in the "violet gland" or "supracaudal gland" ("organum caudae") on the dorsal aspect of the tail base. The exact function of the hepatoid glands is unknown. Their cells contain receptors for androgens and estrogens as well as growth hormone (GH), and it is known that growth and function of these glands are regulated by sexual hormones. Both carcinomas and adenomas of hepatoid glands contain androgen receptors.
Tumors of the perianal glands are among the most common neoplasias in the dog. Benign adenomas make up 81–96%, while perianal gland carcinomas play only a minor role. Sexually intact male dogs are predisposed to perianal adenoma development with a five- to six-fold increased risk. In the bitch, adenomas are more common in castrated animals, which points to a protective effect of female sexual hormones. Usually older dogs are affected, and the Cocker Spaniel and Fox Terrier are predisposed. Many dogs have concurrent testicular tumors. Carcinomas affect predominately male uncastrated or late castrated males. All breeds are affected, but there seems to be a predisposition for larger breeds.
Histologically perianal adenomas usually display a lobular architecture, but focal regions with distinct cellular pleomorphism may exist which can lead to overinterpretation as a carcinoma. Next to the well-differentiated adenomas and the perianal carcinomas, some pathologists will recognize a category of an intermediately differentiated group of adenomas. This intermediate form can also be recognized clinically as a more invasive subtype of adenoma.
Adenomas of the hepatoid glands present as solitary or multiple, sometimes ulcerative masses in the perianal or preputial area, which can be secondarily altered by infection and automutilation. Since signalment and clinical appearance of perianal adenomas are very characteristic, the tumors can usually be easily recognized. Malignant forms can look similar to adenomas, but usually they are more infiltrative and have a more aggressive clinical appearance. A protracted course of disease, lasting up to one year, is not uncommon. Carcinomas are difficult to differentiate from adenomas by cytology, since even adenomas may have fairly pleomorphic cellular characteristics.
A digital rectal exam is indicated in all perianal tumors and includes the assessment of the degree of invasion, palpation of the prostate and the sublumbar lymph nodes (Lnn. lumbales aortici). The testicles should also be examined by palpation or sonography. If a carcinoma is suspected, sonography of the caudal abdomen and thoracic radiographs to search for metastasis are indicated. Taking all published cases together, 20 of 165 (12%) carcinomas had metastasis at time of diagnosis, with the lymph nodes and lungs most commonly affected.
The therapy of choice for small and nonulcerated tumors in sexually intact males is castration. Surgical resection is indicated in ulcerated or bleeding tumors, in cases with recurrence and in bitches. Without castration, tumor recurrence or de novo development is common. Small tumors frequently regress after surgery or do not progress. Radiation therapy for adenomas is effective (remission duration > 1 year in almost 70% of dogs) but is primarily used for stud dogs. With castration ± tumor removal, the prognosis for perianal adenomas is good and recurrence rates are < 10%. In recurrences despite castration, a second biopsy to rule out a carcinoma is strongly recommended.
Carcinomas of the perianal glands do not respond to castration alone, and a wide surgical resection is indicated. Prognosis depends on the stage of disease and is good for dogs with low invasive tumors of < 5 cm diameter without metastasis, as long as wide surgical resection is feasible. In inoperable or only marginally resectable cases, primary or adjuvant radiation of the tumor site and the sublumbar lymph nodes is recommended. 47% of 70 dogs with carcinomas that were treated with 30–40 Gy in 5 fractions survived longer than 1 year. However, dogs with advanced disease frequently seem to respond poorly to radiation (Vail et al. 1990). The author recommends a treatment schedule as for anal sac carcinomas (see above).
Tumors of the Anal Sacs in Cats
In the cat, anal sac carcinomas are extremely rare and only few single cases and one case series have been reported (Shoieb et al. 2009). In this case series, female cats (61%) were predisposed and Siamese cats were significantly overrepresented. The age of affected cats was between 6 and 17 years (average 12 years).
The most common clinical symptoms are dyschezia, constipation, and changes in fecal diameter. The perianal mass is frequently ulcerated and is often initially mistaken for a perianal abscess. Most tumors have a diameter of < 2 cm. Metastasis to the sublumbar lymph nodes, lungs, and other organs has been described, but metastatic frequency has not been systematically studied. Hypercalcemia seems to be rare.
If possible, surgical resection is recommended. There is no information on the success of chemotherapy. Only in one case report, a partial remission of the tumor following Carboplatin chemotherapy was described. One-year survival rate in 39 cats was 19%, and the median survival time was 3 months (range, 0–23 months; Shoieb et al. 2009).
References
1. Bennett PF, DeNicola DB, Bonney P, et al. Canine anal sac adenocarcinomas: clinical presentation and response to therapy. J Vet Intern Med. 2002;16:100–104.
2. Polton G. Examining the heritability of anal sac gland carcinoma in cocker spaniels. J Small Anim Pract. 2009;50:57.
3. Polton GA, Brearley MJ. Clinical stage, therapy, and prognosis in canine anal sac gland carcinoma. J Vet Intern Med. 2007;21:274–280.
4. Polton GA, Mowat V, Lee HC, et al. Breed, gender and neutering status of British dogs with anal sac gland carcinoma. Vet Comp Oncol. 2006;4:125–131.
5. Shoieb AM, Hanshaw DM. Anal sac gland carcinoma in 64 cats in the United Kingdom (1995–2007). Vet Pathol. 2009;46:677–683.
6. Williams LE, Gliatto JM, Dodge RK, et al. Carcinoma of the apocrine glands of the anal sac in dogs: 113 cases (1985–1995). J Am Vet Med Assoc. 2003;223:825–831.
7. Wright ZM, Fryer JS, Calise DV, et al. Carboplatin chemotherapy in a cat with a recurrent anal sac apocrine gland adenocarcinoma. J Am Anim Hosp Assoc. 2010;46:66–69.
8. Vail DM, Withrow SJ, Schwarz PD, et al. Perianal adenocarcinoma in the canine male: a retrospective study of 41 cases. J Am Anim Hosp Assoc. 1990;26:329–334.