Apocrine gland adenocarcinoma of the anal sac: Catch it early to improve prognosis

Although anal-sac tumors make up only 2 percent of all cutaneous neoplasms in dogs, they comprise a significant portion of the referrals to veterinary surgeons and oncologists.

Because of the large size of these tumors at the time of diagnosis and the early development of metastasis, the majority are found in more advanced stages, making successful treatment difficult. Treatment often is a multi-step process involving surgery, radiation therapy and chemotherapy. With aggressive treatment, even patients with advanced disease can experience prolonged control of these tumors with a good quality of life.

Biologic behavior

Initially, it was believed that these tumors were more commonly found in older, female dogs, but recent studies found there is no gender predilection (Moore, 2006). Breed predilections include German Shorthair Pointers, English Cocker Spaniels, Dachshunds and Alaskan Malamutes. In breeds that are predisposed to anal-sac tumors, bilateral tumors can be seen. In our clinic, English Cocker Spaniels frequently present with bilateral anal-sac tumors.

Photo 1: Pulmonary metastasis in a dog with an anal-sac tumor. (Photographs courtesy of Dr. Kim L. Cronin)

Anal-sac tumors are considered highly malignant. Not only do they infiltrate the surrounding tissues, they metastasize early to the regional lymph nodes. Metastasis to the regional lymph nodes has been reported in 46 percent to 96 percent of patients (Withrow, 2007). Other sites of metastasis include the lungs, spleen, liver, kidneys and lumbar vertebrae (Photos 1 and 2).

Photo 2: Metastasis to the sublumbar lymph nodes on CT scan.

Mapping the clinical course

Metastasis to distant sites typically occurs in later stages of the disease.

The clinical course of anal-sac tumors can be insidious. The tumors can be an incidental finding during a routine examination. It is not uncommon for dogs referred to our clinic for another malignancy to be found with a previously undetected anal-sac mass. This underscores the importance of a rectal examination as part of a routine physical. Early detection will provide the best chance of achieving long-term control.

The slow progression of these tumors allows patients to adapt to enlarging tumors with few clinical signs. It is not until these tumors reach a critical volume that clinical signs develop.

The two most significant clinical symptoms are tenesmus and hypercalcemia. Tenesmus is associated with large primary tumor size and/or the presence of metastasis to the sublumbar lymph nodes.

Fast fact

Anal-sac tumors are the second most frequent malignant cause of hypercalcemia in dogs, next to lymphoma. The most effective method of controlling the hypercalcemia is by treatment of the primary tumor and/or metastatic disease. Dogs that present with hypercalcemia of an unknown origin, particularly older dogs, should have a thorough evaluation of the anal sacs, because even small tumors can cause significant hypercalcemia.

Hypercalemia can be found in up to 25 percent of dogs with anal-sac tumors (Moore, 2006). Not all dogs that are hypercalcemic will have clinical signs associated with hypercalcemia. Anal-sac tumors can produce a protein called PTH-rp (parathyroid hormone-related protein) that is capable of binding to PTH receptors, leading to alterations in calcium homeostasis and subsequent hypercalcemia and hypophosphotemia. PTH levels are low in these patients due to negative feedback.

Staging and diagnosis

Aspirates of an anal-sac mass can confirm the presence of a tumor. The cells typically are polyhedral and have uniform round nuclei (Photo 3). Given that these tumors are epithelial in origin, the cells are found in clusters. The cytologic features of anal-sac tumors can be relatively benign because they lack many of the typical features of malignancy. However, this appearance is misleading, given the potential for invasion and early metastasis.

Photo 3: Cytology of an anal-sac tumor at 1000x. (Photographs courtesy of Dr. Kim L. Cronin)

Routine staging for anal-sac tumors should include a CBC, chemistry profile, abdominal ultrasound, abdominal radiographs and thoracic radiographs. Abdominal ultrasound is more sensitive in identifying the presence of regional lymph-node metastasis as well as evaluating the liver and spleen for metastatic disease. Abdominal radiographs can detect metastasis to the sublumbar lymph nodes in some patients and can be used to identify bone lysis in the lumbar region. Bone lysis can be secondary to local osteolysis from metastatic disease in the sublumbar lymph nodes or from metastatic disease to the bone (Photo 4).

Photo 4: Cytology on an anal-sac tumor at 500X. Note that the cells are well differentiated and have few features of malignancy. (Photographs courtesy of Dr. Kim L. Cronin)

Prognostic factors

Treatment outcome can be influenced by several factors, including tumor size, presence of hypercalcemia and the presence of distant metastasis. For dogs with tumors <10 cm, the survival time was 584 days, while for dogs with tumors >10 cm the survival time was only 292 days (Williams, 2003).

In the same study, it was found that dogs that were normocalcemic had survival times of 19 months while those with hypercalcemia lived only 9.6 months. As would be expected, the presence of pulmonary metastasis reduced the survival time from 18 months to seven months.

Interestingly, the presence of iliac lymph-node metastasis did not affect the overall survival time in this study. This supports the recommendation to treat dogs with regional lymph-node metastasis aggressively.

Treatment options

The treatment of anal-sac tumors typically involves multi-modal therapy and includes surgery, radiation therapy and chemotherapy.

The first step in treating these tumors is to assess the potential for surgical excision.

Given their location and size, it can be difficult to obtain a wide margin without risk of significant surgical complications (Photo 5). Complications include wound dehiscence, incontinence and infection.

Photo 5: Anal-sac tumor post-excision. Note the narrow margin.

In hypercalcemia patients, reduction in the tumor burden can reduce or normalize the calcium levels. Dogs treated with surgery alone have been reported to have survival times of six to 12 months.

Even for those dogs that have sublumbar lymph-node metastasis, surgery still may be an option. For those owners who wish to be aggressive, removal of both the primary tumor and the sublumbar lymph nodes should be considered. Successful excision of the lymph nodes is possible in some dogs, although in others removal is prevented by the tumor vascularity. The most common complication associated with lymph-node removal is hemorrhage. It is not always possible to determine which patients are good surgical candidates through non-invasive means such as ultrasound.

Radiation therapy can be used either as an adjunct to surgery or the primary means of tumor control. As with any tumor, radiation therapy is most effective when the tumor volume has been reduced to a microscopic level. Full-course radiation therapy or curative intent radiation therapy would be recommended as an adjuvant to surgery. This type of radiation therapy involves the use of 15-19 treatments of radiation therapy given over a three-week to six-week period. Radiation therapy can be started once patients have reached two weeks post-op.

Given the high rate of regional metastasis to the regional lymph nodes, it is recommended that the sublumbar lymph node bed be irradiated as well, regardless of whether there is measurable disease present. Potential acute side effects from radiation therapy include colitis, moist desquamation and alopecia, although these are self-limiting and will resolve two to four weeks after the completion of radiation therapy (Photo 6).

Photo6: Patient treated with full-course radiotherapy, two weeks post-treatment. (Photographs courtesy of Dr. Kim. L. Cronin)

Late radiation side effects, which occur months to years after the completion of radiation therapy, have been reported and include rectal stricture and chronic colitis. These side effects would not be expected to resolve, but in many cases are manageable with supportive care (i.e., stool softeners).

Radiation therapy has been used to treat patients that are not surgical candidates. Full-course radiation therapy has been used in these patients, although due to the larger tumor volume control rates often are reduced.

An alternative course of radiation therapy is palliative radiation therapy, intended to provide symptomatic relief from the tumor. The treatment schedule for palliative radiation may differ among clinics, but typically involves three to five large doses of radiation over one to four weeks.

Unmasking signs of anal-sac tumors

Patients can experience symptomatic relief with this type of radiation therapy with reduced side effects. Resolution of hypercalcemia and/or tenesmus can be seen after palliative radiation therapy. However, it should be kept in mind that this type of radiation therapy is designed for symptom relief and not tumor control.

Therapeutic approaches

Given the high metastatic rate, chemotherapy is recommended as part of the treatment plan. The most commonly used drugs include cisplatin, carboplatin and mitoxantrone. In most studies, chemotherapy has been combined with surgery and/or radiation therapy, so the true benefit of chemotherapy is not fully known. In one study, dogs that received chemotherapy alone had significantly shorter survival times (212 days) compared to those treated with a combination of surgery and/or radiation therapy as well as chemotherapy (589 days) (Williams, 2003).

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In a second study, cisplatin resulted in a 31 percent response rate for the treatment of measurable disease (Bennett, 2002). Dogs treated with both surgery and chemotherapy had significantly longer survival times than either surgery or chemotherapy alone.

It was once believed these tumors had a guarded to poor prognosis and that the survival times were short. The most recent studies suggest that with multi-modal therapy the prognosis is fair. The reported survival time for 104 dogs treated with surgery, radiation therapy, chemotherapy or a combination of these modalities was 544 days (Williams, 2003). In a second study, it was found that dogs treated with a combination of surgery, radiation therapy and mitoxantrone chemotherapy had control of their tumors for a median of 287 days and had survival times of almost 2.5 years (Turek, 2003).