Mammary gland: neoplasia in Cats (Felis) | Vetlexicon
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Mammary gland: neoplasia

ISSN 2398-2950


Introduction

  • Third most common tumor in cats after hematopoietic and skin tumors; incidence of 25 per 100,000 females and 12% of feline tumors regardless of sex. 85-95% are malignant.
  • Benign tumors, carcinomas, sarcomas of interstitial connective tissue, myoepithelial cells peripheral to ducts or alveoli, and ductar epithelium. >80% are adenocarcinomas.
  • Signs: mammary mass(es), sometimes with associated discharge. Weight loss.
  • Incidence highest in middle aged or older cats. Occasionally seen in males.
  • Treatment: surgery if no evidence of pulmonary metastasis. +/- Chemotherapy depending on histopathology results.
  • Prognosis: good with benign tumors; guarded to poor with malignancies.
  • Prevention: ovariohysterectomy Ovariohysterectomy before puberty.
    Print off the owner factsheet Breast cancer in cats Breast cancer in cats to give to your client.

Presenting signs

  • Palpable mass(es) in mammary gland.
  • Abnormal mammary secretion.
  • Weight loss.
  • Ulceration of overlying skin  Mammary adenocarcinoma in right thoracic gland .

Acute presentation

  • Rapidly spreading, ulcerating mass(es) invading the surrounding skin would be typical of malignant masses.
  • 'Blue dome' appearance - blue raised area in mass.

Age predisposition

  • Middle to old aged.
  • 10-12 years mean age occurrence. May occur at younger age in Siamese Siamese.
  • Risk increases with age but becomes significant after 7-9 years.

Breed/Species predisposition

  • ?Siamese Siamese at increased risk - although no proven breed predilection. May occur at younger age in Siamese.

Pathogenesis

Predisposing factors

General

  • Hormonal - estrous cycle.
  • Cats spayed prior to 6 months of age have 91% less risk of developing a mammary tumor.
  • Cats spayed between 7 and 12 months of age have 86% less risk of developing a mammary tumor.
  • Cats spayed between 13 and 24 months of age have 11% less risk of developing a mammary tumor. No benefit is seen after 24 months.

Specific

  • Progestins increase the incidence of mammary hypertrophy, which may result in the development of benign tumors or carcinomas.
  • A-type and C-type retrovirus have been isolated from feline mammary tumors. Significance unknown.

Pathophysiology

  • Small clones of preneoplastic epithelial cells established during first few estrous cycles   →   true neoplasms after many years.
  • Approximately 20-40% of mammary tumors are thought to have estrogen receptors and some exhibit marked estrus-related growth. 40% of feline malignant tumors express progesterone receptors.
  • HER-2/neu (epidermal growth factor receptor) expression is reported in 5.5-90% feline mammary tumors.
  • Benign tumors include adenomas, fibroadenomas, lipomas and duct papillomas. 
  • Malignant tumors are mostly epithelial in origin, mainly adenocarcinomas (divided between tubular and papillary). Sarcomas are rare.

Timecourse

  • Weeks to months.

Diagnosis

Presenting problems

  • Mammary mass(es).

Client history

  • Mammary gland enlargement.
  • Abnormal mammary secretion.
  • Ulceration of overlying skin (~25% of cases)  Mammary adenocarcinoma in right thoracic gland .

Clinical signs

  • Masses vary from solitary, firm, mobile nodules to multiple neoplasms in several glands.
  • Less common in cranial glands.
    Clinical staging (TNM system Neoplasia: TNM staging) at time of presentation assists in tumor description and prognosis.
  • Abnormal discharges.
  • Skin ulceration.
  • Lymph node enlargement.
  • Infiltration of lymphatics may be apparent as subcutaneous linear, beaded chains.
  • >50% of cats have >1 gland involved.

Diagnostic investigation

General investigation

Histopathology

  • For accurate prognosis following surgery.
  • NB. Even behaviorally benign tumors may show areas of marked cellular aplasia.
    Edge of lesion most useful but avoid necrotic tissue.
  • Lymph node status (if submitted), grade and lymphovascular invasion of the primary tumor should be reported.

Biopsy

  • Confirmation of diagnosis in inoperable lesions.
  • Only indicated when results are likely to influence the subsequent surgical approach.

Radiography

  • Thoracic radiographs (3 views) or CT scan for lung metastases Lung: metastases - radiograph lateral  Lung: classic cannonball metastases - radiograph lateral advisable.
  • Sentinel lymph node mapping reported with intramammary injection of iopamidol or ethiodized oil injection followed by radiographic evaluation.

Cytopathology

  • Fine needle aspiration Fine-needle aspirate to rule out other subcutaneous masses.
  • Examination of milk smears and fine-needle biopsy/aspiration.
  • Evaluation of regional lymph nodes by fine-needle aspirate or biopsy (may need to be performed ultrasound-guided Fine needle aspirate: ultrasound-guided).

TNM staging system

  • Used for mammary carcinomas (not sarcomas).
  • Depends on size of the tumor, lymph node status, and distant metastasis.

Confirmation of diagnosis

Discriminatory diagnostic features

  • History.
  • Clinical signs.

Definitive diagnostic features

  • Histopathology.

Histopathology findings

  • Cell origin: interstitial connective tissue, myoepithelial cells peripheral to ducts/alveoli, ductar epithelium.

Carcinoma

  • Adenocarcinoma Adenoma / adenocarcinoma (most common) divided into papillary or tubular and subclassified as simple or complex.
  • Solid and anaplastic carcinomas.

Sarcoma

Benign

  • Duct papilloma, adenoma, fibroadenoma, ductal adenoma.

Differential diagnosis

  • Fibroepithelial hyperplasia in young cycling intact females (Hayden et al, 1981). Hormonally induced.

Treatment

Standard treatment

  • Radical unilateral mastectomy Mastectomy is most likely to be successful in preventing local recurrence.Local excision ('lumpectomy') not advisable.
  • Radical 2-staged bilateral mastectomy may be considered in view of venous drainage. Lymph nodes may also be removed if affected. Only advisable if tumors are bilateral. Must stage the surgeries (do one side, wait a few weeks, then do the other side).
    The two cranial glands have lymphatic drainage into the axillary lymph nodes. The two caudal ones are drained by the superficial inguinal nodes. Venous drainage is both ipsi and contralateral.Ovariohysterectomy at time of mastectomy is known to have no effect on subsequent tumor behavior, future malignant mammary tumors, or on incidence of metastatic spread.
  • Bilateral mastectomy needs to be staged. The second side is excised about 3 weeks after the first. Wound closure is otherwise very difficult.

Subsequent management

Treatment

  • Chemotherapy Chemotherapy; general principles has a controversial efficacy. A combination of doxorubicin Doxorubicin and cyclophosphamide Cyclophosphamide showed a response rate of 40-50% for gross disease.
  • Chemotherapy post-operatively extends disease-free interval but not overall survival.
  • Doxorubicin (single agent) is currently recommended at 1 mg/kg IV every 3 weeks for 6 treatments and can be combined with NSAIDs Analgesia: NSAID and cyclophosphamide.
  • Poor response to chemotherapy is probably due to advanced nature of disease when diagnosed.
  • Chemotherapy is recommended for cat with large tumors (>3 cm) and/or nodal or distant metastasis. Its benefit is more controversial for smaller tumor and should be elected depending on the grade of the tumor and if lymphovascular invasiveness is observed on histopathology.

Monitoring

  • Regular physical examinations.
  • Follow up thoracic radiography for malignant tumors.

Prevention

Prophylaxis

Ovariectomy

  • Early ovariohysterectomy prior to first estrus is probably responsible for very low incidence of mammary neoplasia in spayed cats.

Outcomes

Prognosis

  • Good with benign tumors.
  • Guarded to poor, even if complete surgical excision, for primary malignant tumor(s).
  • Tumor volume - most important prognostic factor.
    • <2cm diameter = 3 years median survival post-surgery.
    • 2-3cm = 2 years.
    • >3cm = 6 months.
  • Most relevant indicator for carcinomas is mode of growth at edge of mass (histopathology).
  • Other indicator is tumor stage at surgical excision.
  • Unfavorable prognostic markers:
    • Large tumor volume.
    • High grade tumor.
    • Histopathological type.
    • Infiltration (skin, muscle).
    • Ulceration.
    • Lymph node or distant metastasis. Cats with metastasis to the lymph nodes die within the first 9 months of diagnosis.
  • Equivocal prognostic markers:
    • Location of affected gland.
    • Breed (Siamese)?
    • Age (older cats).

Expected response to treatment

  • Recurrence.
  • Metastasis.

Reasons for treatment failure

  • Local recurrence and metastases.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Mills S W, Musil K M, Davies J L et al (2015) Prognostic value of histologic grading for feline mammary carcinoma: a retrospective survival analysis. Vet Pathol 52 (2), 238-249 PubMed.
  • Zappulli V, Rasotto R, Caliari D et al (2015) Prognostic evaluation of feline mammary carcinomas: a review of the literature. Vet Pathol 52 (1), 46-60 PubMed.
  • Matos A  J, Baptisa C S, Gärtner M F et al (2012) Prognostic studies of canine and feline mammary tumours: The need for standardized procedures. Vet J 193 (1), 24-31 PubMed.
  • Seixas F, Palmeira C, Pires M A et al (2011) Grade is an independent prognostic factor for feline mammary carcinomas: A clinicopathological and survival analysis. Vet J 187 (1), 65-71 PubMed.
  • Dias Pereira P & Gärtner F (2003) Expression of E-cadherin in normal, hyperplastic and neoplastic feline mammary tissue. Vet Rec 153 (10), 297-302 PubMed.
  • Hahn, K A & Adams W H (1997) Feline mammary neoplasia: biological behaviour, diagnosis and treatment alternatives. Feline Pract 25 (2), 5-11 VetMedResource.

Other sources of information

  • Sorenmo K U, Worley D R, Goldschmidt M H (2013) Tumors of the mammary gland. In: Small Animal Clinical Oncology. Eds S J Withrow, D M Vail, R L Page. 5th edn. Chapter 27, pp 547-552. Philadelphia: W B Saunders.
  • Oglivie, K & Moore, A S (1995) Managing the Cancer Patient. Veterinary Learning Systems pp 434-440.