Mammary Gland Disorders of the Dog and Cat

Mammary Gland Anatomy

The mammary glands are highly modified and enlarged sweat glands. The gland itself consists of epithelial glandular tissue, and the supporting connective tissue.

Although the number and location of mammary glands is variable, most dogs will have 5 bilaterally symmetric pairs. The glands are named based on their location as: cranial thoracic, caudal thoracic, cranial abdominal, caudal abdominal, and inguinal. Most cats will have 4 bilaterally symmetric pairs of glands (cranial and caudal thoracic, abdominal, and inguinal) [1,2].

Blood supply to the individual mammary glands is based on location. The thoracic glands receive their primary arterial supply from the perforating sternal branches of the internal thoracic artery. Abdominal and inguinal glands are supplied by mammary branches of the epigastric arteries. The cranial superficial epigastric artery is located at the level of the costal arch. It supplies the cranial abdominal gland and joins the caudal superficial epigastric artery. The caudal superficial epigastric artery is a branch of the pudendal artery. It runs cranially under the inguinal mammary gland to supply the inguinal gland and the caudal abdominal gland. Cranial to this, it joins the terminal branches of the cranial superficial epigastric artery [1].

Lymphatic drainage of the mammary glands is bilaterally symmetric and is variable. The cranial thoracic glands drain directly to the axillary node. The inguinal gland drains directly into the inguinal lymph node. Drainage of the caudal thoracic and abdominal mammary glands can be to either or both the inguinal or axillary lymph nodes. Communication between left and right sides has also been documented [3].

Disorders of the Mammary Gland

Pseudopregnancy

Pseudopregnancy is a normal physiologic syndrome seen during diestrus in nonpregnant bitches; usually occurring 6 to 8 weeks after estrus. Clinical signs associated with pseudopregnancy include behavioral changes (nesting and maternal behavior) as well as physical changes (weight gain, mammary enlargement, lactation, and contractions). The cause of pseudopregnancy is thought to be the rapid decrease in serum progesterone that stimulates synthesis and secretion of prolactin. Some nonpregnant bitches may be more sensitive to prolactin, causing an exaggerated response and leading to marked mammary gland enlargement and lactation [4].

Bitches that present with exaggerated pseudopregnancy may be treated conservatively if the signs are mild. Pseudopregnancy is self-limiting and signs will usually subside within 3 weeks. An Elizabethan collar can be used to decrease mammary gland stimulation.

If a more aggressive therapy is necessary, treatment with prolactin inhibitors has been reported [5,6]. Cabergoline was used at a dose of 5 μg/kg orally once daily for 5 to 7 days or as a subcutaneous injection at a dose of 1.5 to 5 μg/kg every 48 hours for 2 to 3 treatments. The outcome of treatment was successful, with 95% to 100% of cases having resolution of mammary swelling and lactation within 5 to 7 days of the start of administration [5,6]. The most common side effects were vomiting, lethargy, and anorexia. Other prolactin inhibitors that have been used to treat pseudopregnancy include bromocriptine 10 to 100 mg/kg/day for 10 to 14 days and metergoline 0.2 mg/kg/day for 8 to 10 days [4].

While ovariohysterectomy is the treatment of choice for the long-term prevention of pseudopregnancy in bitches that are not intended for breeding, its use as a primary treatment for pseudopregnancy is not advocated [4]. Ovariohysterectomy will lead to a sudden and severe decrease in progesterone levels and can exacerbate the rapid increase in serum prolactin concentration. For this reason, many surgeons will delay ovariohysterectomy for several months after estrus.

Mastitis

Mastitis is uncommon in lactating bitches. Patients will present to the veterinarian with systemic clinical signs such as lethargy, anorexia, and mammary gland pain of variable intensity. Diagnosis is based on history and physical examination findings of a large, swollen, hot, and painful mammary gland. Culture and sensitivity tests are helpful in identification of specific pathogens. Escherichia coli, beta-hemolytic streptococci, and staphylococci are most common [4]. Although antibiotic therapy (ampicillin or oxacillin [4]) are usually effective treatments, occasionally, severely infected glands may become necrotic and require surgical debridement.

In some cases, swollen, enlarged, and painful mammary glands can arise from nonseptic inflammation and milk stasis. Often, this will follow acute weaning of puppies from an actively lactating bitch. Treatment may be either to reintroduce the puppies to nursing or to try to stop lactation [4]. Surgery is not necessary for these patients because there is no progression to abscessation and necrosis of the glands.

Mammary Gland Neoplasia

Canine Mammary Gland Tumors

Mammary gland tumors are among the most common tumors in female dogs. The average age for the development of mammary gland neoplasia is 8 to 10 years, with young dogs having a higher incidence of benign tumors [7]. Several factors have been shown to increase the risk of mammary gland tumor formation. These factors include obesity at 1 year of age, obesity 1 year prior to the diagnosis of the mammary gland tumors, intake of homemade versus commercial diets [8] and ovariohysterectomy [9].

The influence of female hormones has been well established. Ovariohysterectomy at a young age reduces the risk of development of mammary gland tumors. Compared with an intact female dog, the risk of developing mammary gland tumors in a dog that has an ovariohysterectomy before the first heat cycle is 0.05%. That risk increases to 8% if the ovariohysterectomy is performed after the first heat cycle and 26% if the ovariohysterectomy is performed after the second heat cycle. There is no protective benefit if ovariohysterectomy is performed after the third heat cycle [9].

The presence of estrogen and progesterone receptors in canine mammary tumors has been established. Almost 100% of normal canine mammary tissue contains receptors for progesterone and estrogen. These receptors are found on 70% of benign mammary tumors and 50% of malignant mammary tumors [10].

Tumor Types and Behavior

Approximately 50% of mammary tumors in dogs are benign. Benign tumor types include fibroadenomas, benign mixed tumors, simple adenomas, and benign mesenchymal tumors [11].

The most common malignancies (the other 50% of tumors) are carcinomas (solid carcinoma, tubular adenocarcinoma, papillary adenocarcinoma, and anaplastic carcinoma).

Sarcomas comprise approximately 10% of malignancies. Reported sarcomas include osteosarcoma, fibrosarcoma, and osteochondrosarcoma. Extraskeletal osteosarcoma commonly occurs in the mammary gland. These osteosarcoma are typically seen in older female dogs. The reported metastatic rate for mammary gland osteosarcoma is 63% with a median survival of 90 days [12].

Mixed malignant mammary gland tumors have histologic characteristics of mesenchymal and epithelial cell origin. They comprise approximately 8% of malignancies and behave similarly to carcinomas.

Inflammatory mammary gland tumors are rare in dogs. Inflammatory mammary gland tumors are characterized by rapid growth, edema, erythema, and firmness and warmth of the tissue. Inflammatory mammary gland tumors must be differentiated from inflammatory and infectious diseases of the mammary gland. Fine-needle aspirate of inflammatory mammary gland tumors is usually suggestive of carcinoma. Prognosis for patients with inflammatory mammary gland tumors is poor. Distant metastasis is often present at the time of diagnosis and hemostatic abnormalities consistent with disseminated intravascular coagulation are present in 30% of patients [13].

Diagnosis and Clinical Staging

Patients with mammary tumors may present to the veterinarian with clinical signs referable to the mass(es) in the mammary chain or signs related to lymphatic obstruction or metastasis.

Biopsy with histopathologic evaluation is the most accurate method of diagnosis of canine mammary tumors. Fine-needle aspiration is discouraged owing to the insensitivity of cytology to differentiate malignant from benign tumors [14].

Staging of patients with mammary tumors should always include thoracic radiographs and a minimum database of information including complete blood count, serum chemistry profile, and urinalysis. Nuclear bone scans may be helpful in the identification of dogs with osseous metastasis. Pulmonary metastasis may be present in up to 50% of patients with malignant mammary tumors. When present, pulmonary metastasis may appear as well define nodules (64%), as poorly differentiated interstitial nodules (18%), or as pleural effusion with no evidence of pulmonary lesions (18%) [15,16].

Treatment

Treatment can ensue once a histologic diagnosis has been obtained and staging has been performed. Surgery is the first line of treatment for mammary tumors. Effective surgical planning requires knowledge of anatomy, vascular and lymphatic supply, and the behavior of the tumor being treated.

In canine patients, surgical dose has not been associated with improved survival [17], but has theoretical implications based on lymphatic drainage for invasive tumors. Options for surgical treatment include simple lumpectomy, mammectomy, regional mastectomy and radical mastectomy.

Performing ovariohysterectomy concurrent with the removal of mammary gland tumors in intact females is controversial. In two studies, concurrent ovariohysterectomy improved survival 45% [11,18] however, other studies indicate no difference in survival [17,19].

Prognosis

Several prognostic indicators have been identified in canine mammary gland malignancy (Table 77-1). Among these are tumor size, tumor fixation to underlying tissue, skin ulceration, tumor type, tumor grade, evidence of vascular or lymphatic invasion, lymphoid infiltration into the tumor, lymph node involvement, and the presence of estrogen or progesterone receptors [20].

Feline Mammary Gland Tumors

Mammary gland tumors are the third most common cancer in cats [21]. Of mammary gland tumors in cats, 80% are malignant (adenocarcinoma), 25% of cats have ulcerated masses, and more than 50% have more than one gland involved. More than 80% of cats with mammary cancer will develop metastasis; 49% of cats have lymph node metastasis [22].

Prognosis for cats with mammary gland carcinoma is dependent on tumor size. Overall median survival is approximately 12 months. Cats with tumors less than 2 centimeters in diameter have a median survival of 2 years. Cats with tumors between 2 and 3 centimeters have a median survival of 2 years. Cats with tumors larger than 3 centimeters have a median survival of 6 months. Cats with histologically well-differentiated tumors with no evidence of lymphatic invasion have a better prognosis than those with higher grade tumors [22].

Surgery is the most effective means of treatment of feline mammary tumors. Radical mastectomy is recommended to decrease the chances of local recurrence. Local recurrence with conservative surgery is 66% [22].

Feline Mammary Fibroadenomatous Hyperplasia

Fibroadenomatous hyperplasia is an important differential diagnosis for mammary gland neoplasia in cats. Fibroadenomatous hyperplasia is a progestogen-dependent ductal hyperplasia. While the most common occurrence is in intact young female cats within 2 weeks of estrus, it has been reported in male and spayed female cats after treatment with megesterol acetate [23]. Clinically, cats present with large, red, and swollen mammary glands. Although most cases will respond to ovariohysterectomy or resolve spontaneously within 4 to 6 weeks, there have been reports of the use of the progesterone antagonist aglepristone for the treatment of cats with fibroadenomatous hyperplasia that does not respond to ovariohysterectomy. Aglepristone was used at a dose of 10 to 20 mg/kg in variable frequency (1 to 2 times weekly). With this treatment, tumor regression was rapid in all cats within 1 to 2 weeks. Pregnant cats had a high tendency to abort and develop endometritis [24,25].