Carboplatin Chemotherapy in a Cat With a Recurrent Anal Sac Apocrine Gland Adenocarcinoma

Introduction

The most common tumors of the perianal region in dogs include sebaceous gland adenoma, adenocarcinoma, and anal sac apocrine gland adenocarcinoma.¹ Cats lack the classic sebaceous glands of the anus that are found in dogs. Consequently, tumors of these glands (perianal adenomas and adenocarcinomas) are highly uncommon in cats.¹ Furthermore, while cats do have anal sac glands, they do not have the same prevalence of anal sac apocrine gland carcinomas as seen in dogs. To the authors’ knowledge, only three cases of anal sac apocrine gland carcinoma have been reported in cats, and responses to chemotherapy have not been reported.^2–4 The purpose of this case report is to describe the fourth documented case of feline anal sac apocrine gland carcinoma, as well as the cat’s clinical response to surgery and chemotherapy.

Case Report

An 8-year-old, castrated male, domestic shorthaired cat was presented to the Texas A&M University Veterinary Medical Teaching Hospital for evaluation of a mass of the left perianal region. The owner first noticed the cat excessively grooming the anal region over the previous 4 months. No changes were reported in appetite, attitude, urination, or defecation during that time, and no other significant clinical signs were reported. One month previously, the cat began scooting his anus on the carpet and was presented to the referring veterinarian for evaluation. A left-sided anal mass was noted, and 3 weeks prior to his referral, the cat had an incisional biopsy of the mass. The histopathology report described a high-grade, invasive carcinoma with moderate levels of necrosis.

When first examined, the cat was bright and alert; body weight was 6.39 kg; and all vital signs were within normal limits. A large, left-sided perianal mass was at the region of the left anal sac. The lesion was nonulcerative, fixed, and very firm on palpation. The mass did not appear to cause complete obstruction of the rectum on rectal examination. No blood was noted on the examination glove after the rectal examination. The remainder of the physical examination was unremarkable.

Routine diagnostic staging was performed. A complete blood count revealed no abnormalities except for a lymphopenia of 792/μL (reference range 1500 to 7000/μL). A serum biochemical panel revealed a creatinine value of 2.1 mg/dL (reference range 0.8 to 1.8 mg/dL), with the remainder of the biochemical serum values (including ionized calcium) within reference ranges. Urinalysis was not performed, and a coagulation panel was unremarkable. No evidence of metastasis or any cardiopulmonary pathology was seen on three-view thoracic radiographs. Likewise, abdominal radiographs and ultrasound revealed no abnormalities, and sublumbar lymph nodes were normal in size.

A unilateral anal sacculectomy was performed, which included removal of approximately 40% of the cat’s external anal sphincter. The surgery was uneventful, and complete fecal continence was maintained postoperatively. The excised mass measured 4.0 × 3.0 × 2.5 cm for a total cubic volume of 30.0 cm³. The mass was placed in buffered formalin and processed routinely for histopathology.

Histologically, the mass was composed of a highly invasive, poorly demarcated, and partially encapsulated neoplasm that was compressing the adjacent internal and external anal sphincters. The mass was formed by neoplastic nests of tubules with necrotic centers separated by desmoplastic connective tissue. Cells were cuboidal, with a moderate amount of wispy, lightly eosinophilic cytoplasm and irregularly rounded nuclei with finely stippled chromatin and a single prominent nucleolus. Mitotic index was reported as 24/10 high-power field. Moderate anisocytosis and anisokaryosis were seen. Vascular or lymphatic invasion was not observed in biopsy specimens, but the neoplasm extended to surgical borders, indicating residual microscopic disease. The cell of origin could not be confirmed because of the lack of normal anal sac epithelium within several sections; however, a diagnosis of apocrine gland carcinoma of the anal sac was made based on location, morphological changes characteristic of malignancy, and invasive profile [Figures 1, 2].

As the biology of such a tumor is unknown in cats, adjuvant chemotherapy was recommended postoperatively but declined by the owners at that time. The cat was prescribed 0.3 mg/kg of piroxicam^a for a total of 2 mg q 48 hours. Five months after surgical excision, the cat was presented for evaluation of tumor regrowth. At presentation, the mass measured 2.5 × 2.25 × 2.75 cm for a total of 15.46 cm³. Cytology collected by the referring veterinarian was consistent with regrowth of the original anal sac apocrine adenocarcinoma. Routine staging involving imaging was again performed; no changes were noted from the previous staging results, with the exception of a reduced creatinine of 1.4 mg/dL (reference range 0.8 to 1.8 mg/dL) and the persistent lymphopenia of 1064/μL (reference range 1500 to 7000/μL). Urinalysis was normal. Surgical re-excision was recommended but declined by the owners; they instead elected to pursue chemotherapy. Piroxicam therapy was discontinued at the time of tumor recurrence.

The cat was initially treated with carboplatin^b at 150 mg/m² for a total dose of 50 mg given intravenously (IV) every 4 weeks for four treatments. No side effects to the treatment protocol were reported. Four weeks after the first dose of chemotherapy, the total cubic volume of the mass was 7.75 cm³. After two doses, the mass had a total cubic volume of 6.68 cm³, indicating a continued partial response. The third treatment of carboplatin resulted in stable disease. After four treatments of chemotherapy (16 weeks after initiating treatment), the mass had grown and had a total cubic volume of 17.05 cm³, indicating progressive disease. Because of disease progression, routine staging was again performed; this included three-view thoracic radiographs and abdominal ultrasound, complete blood count, and serum biochemical analysis. The only abnormalities noted were a mild leukopenia of 5.2/μL (reference range 5.5 to 19.5/μL) and persistent lymphopenia of 780/μL (reference range 1500 to 7000/μL). Imaging was again unremarkable. Doxorubicin^c was administered at a dose of 1 mg/kg for a total dose of 6.5 mg IV. The owners elected to discontinue all therapy after the initial dose of doxorubicin, and they failed to return the cat for follow-up visits.

Approximately 5 months after the final chemotherapy treatment and a total of 15 months after initial diagnosis, the cat was presented for euthanasia and necropsy. The owners elected euthanasia because of the cat’s obviously progressing tumor, the need for weekly enemas subsequent to the development of megacolon, and a general decline in the cat’s attitude and appetite. No further staging was done prior to euthanasia. Grossly, two irregularly shaped, firm, discretely nodular, and white anal masses (2.0 × 1.8 cm right and 4.0 × 2.0 × 1.5 cm left) were compressing the most distal and ventrolateral aspects of the rectum [Figure 3]. On cut section, both masses were white and firm with multifocal areas of hemorrhage and necrosis. Similar nodular masses ranging from 2 to 5 mm in diameter were also seen within the lung parenchyma [Figure 4]. Likewise, the sacral and hypogastric lymph nodes were enlarged with the same nodular lesions as seen in the anal mass and lungs. Histopathology of both anal masses was consistent with a diagnosis of anal sac adenocarcinoma. Histological examination of the masses in the lymph nodes and lungs revealed metastases to these organs.

Discussion

While rare, anal sac adenocarcinomas are the most common malignant perianal tumor of the dog.¹ This tumor appears to affect older dogs with a median reported age of 9 to 11 years and no clear sex predilection.^5–7 Labrador retrievers, golden retrievers, and cocker spaniels appear to be overrepresented.^5–7 These tumors display a high metastatic potential most commonly to the sublumbar lymph nodes.^5,6 In fact, a recent retrospective study found 59% of dogs had evidence of sublumbar metastasis at the time of diagnosis.⁷ Distant metastasis to the lungs and hematopoietic organs has also been reported.^5,6 A distinct feature of canine anal sac apocrine adenocarcinoma is the association with hypercalcemia of malignancy. As many as 27% to 51% of dogs with apocrine gland adenocarcinoma experience hypercalcemia as a result of neoplastic-derived parathyroid hormone-related protein (PTH-rp).^5,6

Surgical removal of the primary tumor continues to be the standard of care even though the incidence of regrowth is high.^5,6 Furthermore, evidence suggests removal of lymph nodes with metastases is effective at prolonging survival time and controlling clinical signs secondary to hypercalcemia.⁸ Chemotherapy protocols with platinum drugs or melphalan as an adjuvant to surgery have been shown to elicit partial responses and improve survival times in a subset of animals with metastatic disease.^5–7,9 Finally, postoperative radiation and adjuvant mitoxantrone therapy appear to improve survival when compared to surgical excision as a single therapy.¹⁰

Perianal tumors of any type are exceptionally rare in cats.¹ To the authors’ knowledge, this is the fourth reported case of feline anal sac adenocarcinoma but the first that describes response to adjuvant chemotherapy and detailed follow-up with a necropsy report.^2–4 Histopathologically, three of the four documented cases had similar findings, including levels of necrosis, desmoplasia, and high mitotic activity. Interestingly, the mass originated in the left anal sac in all four reported cases. None of the cats reported in the literature had hypercalcemia, a common finding in the canine counterpart.^2–4 This is significant, as a considerable amount of dogs are initially presented with signs of hypercalcemia (e.g., polyuria, polydypsia, and lethargy) as opposed to lower gastrointestinal symptoms (e.g., tenesmus).⁶ Overall survival for these tumors is relatively unknown, but a series of 10 cases were reported via personal communication in a feline oncology textbook. The median survival for these 10 cats was 5 months compared to the 15-month survival for the cat in this report.¹¹

The cat in this report was placed on the nonsteroidal anti-inflammatory drug piroxicam after the first surgical excision. It appears unlikely that the piroxicam played any role in inhibiting tumor progression in this case, because significant tumor regrowth was noted 5 months after surgical excision. The antitumor properties of piroxicam are well documented in veterinary medicine.¹² However, to the authors’ knowledge, cyclooxygenase-2 (COX-2) expression has not been noted in canine anal sac adenocarcinomas. Furthermore, most feline tumors, including various types of carcinoma, have been shown to have very little COX-2 expression.¹³ Consequently, little evidence supports the role of piroxicam in future cases of feline anal sac adenocarcinoma.

The response of this cat to carboplatin chemotherapy was encouraging. In future cases, it is reasonable to offer adjuvant carboplatin postoperatively or perhaps perioperatively for suggestively inoperable tumors that compromise >50% of the external anal sphincter. Future studies are needed to evaluate the biology of feline anal sac adenocarcinomas with regard to metastatic potential, local recurrence, and response to adjuvant therapies that include chemotherapy (i.e., carboplatin, melphalan, or mitoxantrone) and/or radiation treatment.

Conclusion

An 8-year-old, castrated male, domestic shorthaired cat was presented for evaluation of a perianal carcinoma. Marginal excision supported a diagnosis of anal sac adenocarcinoma. Regrowth of the tumor was treated with four doses of carboplatin, and a partial response lasted approximately 16 weeks. Follow-up was insufficient to determine the tumor response to a single course of doxorubicin therapy. The cat was euthanized 15 months after the initial diagnosis because of general decline and tumor progression. A necropsy confirmed metastasis to the regional lymph nodes and pulmonary parenchyma.