Malignant anal sac melanoma in dogs: eleven cases (2000 to 2015).

OBJECTIVES: To report the signalment, clinical presentation, treatments pursued and outcomes of dogs with malignant anal sac melanoma. METHODS: Medical records from five institutions from January 2000 through December 2015 were reviewed and dogs with cytologically- or histologically-confirmed malignant anal sac melanoma were identified. Signalment, clinical signs, staging, cytology, histopathologic analysis, surgical and non-surgical treatments were extracted from the medical records. The referring veterinarians and owners were contacted for follow-up data. RESULTS: Eleven dogs were included and survival data was available for all. The most common clinical signs were bloody anal sac discharge and perianal licking. Initial treatments pursued included surgery (n=8), chemotherapy (n=1), and palliative treatment with pain medications and stool softeners (n=2). In an adjuvant setting, melanoma vaccine was pursued following surgery in three dogs and chemotherapy in one dog. Regardless of treatment, progression-free survival (mean 92 · 5 days) and overall survival times (median 107 days) were short. CLINICAL SIGNIFICANCE: Dogs in this case series had a guarded to poor prognosis regardless of treatment. Ten of 11 dogs were euthanased due to local or distant disease progression. Only 1 of 11 dogs was alive one year after diagnosis. An understanding of tumour behaviour in this location could lead to improved survival times with earlier diagnosis and treatment.

Humoral hypercalcemia of malignancy in nude mouse model of a canine adenocarcinoma derived from apocrine glands of the anal sac. Biochemical, histomorphometric, and ultrastructural studies.

A serially transplantable tumor line, designated CAC-8, has been developed in nude mice from a spontaneously occurring adenocarcinoma of the anal sac from a hypercalcemic dog. Nude mice with transplanted CAC-8 developed hypercalcemia (mean 16.3 +/- 0.6 mg/dl) and moderate hypophosphatemia without bone metastasis. Urinary excretion of calcium and hydroxyproline were increased 6- and 2.3-fold, respectively. Urinary excretion of cAMP was moderately increased but phosphorus excretion was not significantly altered. Serum 1,25-dihydroxycholecalciferol was increased significantly in tumor-bearing nude mice in proportion to the magnitude of tumor-induced hypercalcemia. Histomorphometric evaluation of lumbar vertebrae from nude mice with CAC-8 revealed decreased total and cortical bone volume, a 3.3-fold increase in bone resorption rate and a 2.5-fold increase in bone formation rate at the tissue level. The transplanted CAC-8 has maintained the histologic pattern of the original carcinoma up to the present sixth passage. Ultrastructural evaluation of transplanted tumor cells revealed 150-250-nm secretory-like granules. The granules did not stain by using an ultrastructural cytochemical (uranaffin) stain specific for neuroendocrine secretory granules. Ultrastructurally, the parathyroid glands of nude mice with CAC-8 appeared inactive with large intracytoplasmic whorl of agranular membranes. These data suggest the transplanted carcinoma secreted a humoral factor which resulted in hypercalcemia. The tumor line (CAC-8) propagated in nude mice represents an animal model of humoral hypercalcemia of malignancy that shares many features with the syndrome described in human patients. Unique features of this transplanted carcinoma associated with hypercalcemia include increased serum dihydroxycholecalciferol, increased rate of bone formation as well as bone resorption, an absence of bone metastases, and evidence of parathyroid gland suppression.