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Clinical case challenge: Diagnosis and Treatment of Molly’s Anal Sac

Michele Keyerleber, DVM, DACVR (Radiation Oncology) and John Berg, DVM, DACVS

Case Description

Molly, an 11.5 -year -old spayed female Golden Retriever was referred for treatment of a 1 cm anal sac mass that was discovered incidentally on a routine physical examination.  The referring veterinarian had aspirated the mass, and cytology was consistent with anal sac adenocarcinoma (Figure 1).

figure 1

Figure 1 – Cytologic examination revealed sheets of closely adherent epithelial cells with uniform large nuclei.

The CBC and chemistry profile were normal on presentation. Hypercalcemia is not noted although it can be a common paraneoplastic finding with anal sac carcinoma.

Question 1:

What proportion of dogs with anal sac carcinoma present with hypercalcemia?

Answer:

Approximately 27%1

Question 2:

Does the presence of hypercalcemia have prognostic significance?

Answer:

Two of the largest available studies have shown shorter median survival times among hypercalcemic dogs: 1,2,however, other studies have failed to demonstrate a relationship.

Clinical Assessment and Diagnostic Approach

A diagnostic workup for this cancer includes obtaining a sample of cells, either through biopsy or fine needle aspirate to establish a definitive diagnosis.  Staging tests then help to determine the extent of disease throughout the body, as well as a dog’s general health.  These tests include bloodwork (including a complete blood count and chemistry profile), urinalysis, chest x-rays, abdominal ultrasound and aspirates of the regional lymph nodes (if enlarged). This information is used to develop the best treatment plan for an individual patient.

To complete her staging, Molly underwent a complete ultrasonographic examination of the abdomen and three view thoracic radiographs, both of which were normal.

Question 3:

What is the most common metastatic site for anal sac carcinoma, and what is the approximate metastatic rate?

Answer:

Reported metastatic rates range from 46% to 96%.  The medial iliac lymph nodes (“sublumbar” nodes) and intrapelvic nodes are by far the most common metastatic sites on presentation.

Question 4:

Of the various ultrasonographic features of abdominal lymph nodes (shape, cavitation, echogenicity, parenchymal uniformity and size), which is most closely correlated with whether the nodes are malignant vs. non-malignant?

Answer:

Size – malignant nodes are significantly more likely to be increased in size.3

Treatment

Once a diagnosis has been obtained, initial therapy is determined based upon the size of the tumor and ability of a surgeon to remove the tumor without complications.  It is recommended that the anal sac and the regional lymph nodes, if affected, be removed

Molly’s owners elected surgical removal of the anal sac mass.  A 5 French Foley catheter with a 3ml bulb was passed through the anal sac duct, and the bulb was inflated to facilitate identification of the wall of the anal sac.  A 4cm curvilinear incision was made directly over the anal sac, parallel to the anus.  The sac was removed with a 1 cm margin of surrounding fat (Figure 2).figure 2

Figure 2:  The anal sac duct was ligated near its opening at the mucocutaneous junction prior to dividing the duct.  Most small anal sac carcinomas involve the anal sac but do not extend into the duct.  Surgical margins are most likely to be incomplete at the periphery of the tumor, particularly adjacent to the rectal wall where wide margins cannot be obtained.

Histopathology confirmed the diagnosis of apocrine gland adenocarcinoma of the anal sac.  Cells exhibited moderate anisocytosis and anisokaryosis with 16 mitotic figures per 5 HPF.  Neoplastic cells extended to the surgical margins.

Question 5:

What is the reported survival time for surgery alone in the management of anal sac adenocarcinoma? What additional therapy can be pursued to increase survival?

Answer:

Reported survival time for surgery alone is approximately eight months.2, 4 Definitive radiation therapy and/or chemotherapy are recommended in the event of incomplete surgical excision.  The Average survival of dogs treated with surgery followed by definitive radiation therapy and/or chemotherapy has been reported on the order of 1.5 to 2.5 years.1, 5,6

Given the presence of neoplastic cells at the surgical margins, Molly subsequently underwent a course of definitive radiation therapy. Her treatment plan involved 20 daily treatments (M-F) of 2.5 Gy/fraction for a total dose of 50 Gy (Figure 3). Each treatment was delivered under a light plane of general anesthesia.

Figure 3: Graphical representation of Molly’s 3-D conformal radiation therapy plan. The target volume (consisting of the surgical bed, pelvic canal, and medial iliac lymph nodes) is represented by the red shaded region. The concentric colored lines represent the dose level as a percentage of the prescription dose.

chart

The radiation therapy course Molly underwent is associated with both short- term (acute) side effects and long -term (late) side effects. Acute side effects tend to develop during the second week of treatment and then progress throughout the remainder of the treatment and up to one week following the end of radiation therapy. Acute side effects include: erythema, hair loss, dry or moist desquamation of the skin in the perineal region, and mild to moderate colitis. We typically manage these acute side effects via the use of antibiotics, anti-inflammatory medications, pain medications, and topical ointments, as needed. Molly’s short-term side effects were fully resolved within two weeks following the end of her radiation therapy course.  Late side effects impact slower dividing cells, such as muscle and bone and connective tissues. These side effects are less common but can be more serious. Potential late side effects include fibrosis leading to rectal stricture, chronic colitis, and rarely osteonecrosis (bone death) or secondary cancers of bone (<3-5% incidence at 3-5 years post radiation).

Following completion of her radiation therapy course and resolution of acute side effects, Molly began mitoxantrone chemotherapy. To date, the longest reported survival time for anal sac adenocarcinoma reported is 31.4 months with a combined therapy of surgery, definitive radiation and mitoxantrone chemotherapy.5 Alternative chemotherapy options reported to be effective against this tumor include melphalan and Palladia (toceranib phosphate).

In the event that an anal sac tumor is very advanced at initial diagnosis and not amenable to surgical excision, a less aggressive course of radiation, known as palliative radiation therapy, can be considered. This treatment protocol typically involves either six once weekly treatments or ten daily radiation treatments (M-F), but other protocols are also available. Acute side effects are less common and less severe with palliative treatment. Average survival after palliative radiation therapy for anal sac adenocarcinoma in dogs is typically about 6-12 months.

References

  1. 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 223:  825-831, 2003.
  2. Ross JT, Scavelli TD, Matthiesen DT, et al.  Adenocarcinoma of the apocrine glands of the anal sac in dogs: a review of 32 cases.  J Am Anim Hosp Assoc 27: 349-355, 1991.
  3. DeSwarte M, Alexander K, Rannou B, et al.  Comparison of sonographic features of benign and neoplastic deep lymph nodes in dogs.  Vet Rad Ultrasound 52: 451-456, 2011.
  4. 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.
  5. 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: 94-104, 2003.
  6. Polton GA, Brearley MJ. Clinical stage, therapy, and prognosis in canine anal sad gland carcinomas. J Vet Intern Med 21: 274-280, 2007.