ONCOLOGY - Mammary Tumours Flashcards
What are the risk factors for mammary tumours?
Genetics
Hormonal factors
Obesity (in dogs)
Previous mammary tumours (in dogs)
What are the two classifications of genetic factors which can contribute to the development of mammary tumours?
Sporadic genetics
Familial genetics
How can sporadic genetic changes contribute to the development of mammary tumours?
Sporadic genetic changes involve the upregulation and downregulation of genetic mutations acquired throughout life, i.e. the upregulation of oncogenes, and the downregulation of tumour suppressor genes sich as p53
How can familial genetics contribute to the development of mammary tumours?
Inheritence of the BRCA1 and BRCA2 genes has been associated with an increased risk of mammary tumour development in studies done on English Springer Spaniels. An increased risk of mammary tumours has been identified in other dog breeds who have inherited the BRCA1 gene, and inheritence of BRCA1 and BRCA2 has been associated with an increased risk of mammary tumours in cats
What circumstantial evidence suggests that hormonal factors influence the development of mammary tumours?
- There is a decreased prevalence of mammary tumours in countries in which ovariohysterectomies are performed routinely
- Patients treated with exogenous progestogens (as contraceptives) have an increased prevalance of mammary tumours
- Normal mammary tissue has been found to have a lot of oestrogen and progesterone receptors which supports the theory that hormones have an role in the development of mammary tumours (furthermore, low grade or benign mammary tumours tend to retain their oestrogen and progesterone receptors, however higher grade malignany mammary tumours don’t present with oestrogen and progesterone receptors)
Do ovariohysterectomies affect the risk of mammary tumour development in dogs?
Most studies suggest that an ovariohysterectomy before the third oestrus cycle in dogs will decrease the risk of mammary tumour development
Do ovariohysterectomies affect the risk of mammary tumour development in cats?
Most studies suggest that an ovariohysterectomy in cats before they reach 1 year old will decrease the risk of mammary tumour development. The risk is further decreased if you spay before 6 months of age
How does obesity increase the risk of mammary tumours in dogs?
Increased adipose tissue increases the expression of the aromatase enzyme which converts andorgens into oestrogens, thus increasing serum oestrogen levels and the hormonal influence on mammary tumour development
What evidence suggests that obesity increases the risk of mammary tumours in dogs?
Studies have found that there is a decreased risk of mammary tumours in spayed dogs that were thin at 9 - 12 months old, and that there is an increased risk of mammary tumours in dogs that were obese by one year of age
What are the differential diagnoses for a mammary mass in dogs?
Mammary tumour
Mastitis
Duct ectasia
Focal mammary gland fibrosis
Ductal hyperplasia
Lobular hyperplasia
Gynecomastia
What is duct ectasia?
Duct ectasia is the widening and thickening of the papillary duct with fluid accumulation forming a cystic lesion
What is indicated by gynecomastia in male dogs?
Hyperoestrogenism secondary to a sertoli cell tumour
What is indicated by gynecomastia in female dogs?
Hyperoestrogenism secondary to a granulosa cell tumour
What are the differential diagnoses for a mammary mass in cats?
Mammary tumour
Mastitis
Duct ectasia
Focal mammary gland fibrosis
Ductal hyperplasia
Lobular hyperplasia
What is the most significant differential diagnosis for a mammary mass in cats?
Lobular hyperplasia
What causes lobular hyperplasia in cats?
In cats, lobular hyperplasia is associated with increased progesterone levels so can be seen following metoestrus, during pregnancy or with exogenous progestogen treatment
What is the gross appearance of lobular hyperplasia in cats?
Lobular hyperplasia presents as one or more swollen, painful, oedematous mammary glands with no lactation (to differentiate from normal mammary gland changes seen in lactating cats)
What are the other clinical signs seen with lobular hyperplasia in cats?
Anorexia
Lethargy
Tachycardia
How do you treat lobular hyperplasia in cats?
Stop any exogenous progestogen treatment
Administer progesterone antagonists
Ovariohysterectomy
What is a key differentiating feature between lobular hyperplasia and mammary tumours in cats?
Lobular hyperplasia is typically seen in young cats whereas mammary tumours are typically seen in older cats
What is the typical signalement for mammary tumours?
Older, intact female dogs and cats
(T/F) Mammary tumours are typically benign in dogs
FALSE. In dogs, mammary tumours have an approximately 50:50 chance of being malignant or benign
(T/F) Mammary tumours are typically malignant in cats
TRUE. In cats 80 - 90% of mammary tumours are malignant
Which history questions are beneficial to ask when investigating a mammary mass?
Is the patient spayed?
When was the patient spayed?
Has there been any treatment with exogenous hormone therapies?
What the patient obese when they were young?
Has the patient had a previous mammary tumour?
When was the patients last season?
Has the patient been lactating recently?
Is the mass hot or painful?
Is there focal or diffuse mammary gland enlargement?
Has there been a rapid or slow growth of the mass?
Which differential diagnosis could be indicated if the patient has recently been lactating?
Recent lactation could be indicative of mastitis
Which differential diagnoses could be indicated if the mass is hot or painful?
If the mammary mass is hot or painful, this could indicate an inflammatory condition over neoplasia (unless an inflammatory carcinoma)
Which differential diagnoses could be indicated if the mass is diffuse?
If the mammary mass is diffuse, this could indicate an inflammatory condition over neoplasia
What are the benefits and limitations of fine needle aspirate (FNA) and cytology for mammary tumours?
Cytological evaluation of a fine-needle aspirate may help rule out certain nonmammary tumor types but may not differentiate benign from malignant tumors and may not be representative of the whole mass due to the heterogeneous nature of mammary tumors
What can be used for definitive diagnosis of mammary tumours?
Biopsy and histopathology allowed for definitive diagnosis, histopathological classification and grading of mammary tumours, and to assess surgical margins. However, be aware that for mammary tumours you typically send away your surgical excision for histopathology rather than doing a biospy first as the classification and grading of the tumour does not really change the surgical approach and thus this reduces the frequency of general anaesthetics required
Describe the normal anatomy of the mammary glands
The mammary glands consist of a series of ducts, lined with ductal epithelium, which drain from alveoli lined with lobular epithelium and surrounded by myoepithelium which contract to move the milk from the alveolar lumen into the lactiferous ducts. In between the alveoli, there is abundant adipose and connective tissue
What are the two non-epithelial mammary tumours?
Sarcomas (arise from the connective tissue surrounding the mammary glands)
Lipoma (arise from the adipose tissue surrounding the mammary glands)
(T/F) Mammary sarcomas are very common
FALSE. Mammary sarcomas are very rare however they are very malignant, aggressive and prone to metastasis
What are the histological classifications of benign epithelial mammary tumours?
Simple adenoma
Complex adenoma
Mixed adenoma
Fibroadenoma
What is a simple adenoma?
A simple adenoma is a benign tumour arising from a single type of mammary gland epithelium - usually the luminal epithelium
What is a complex adenoma?
A complex adenoma is a benign tumour arising from several types of mammary gland epithelium - usually the luminal epithelium and myoepithelium
What is a mixed adenoma?
A mixed adenoma is a benign tumour arising from mammary gland epithelium - usually the luminal epithelium ± myoepithelium - whilst also containing cartilage and bone
What is a mammary fibroadenoma?
A mammary fibroadenoma is a benign tumour arising from the mammary gland epithelium and the connective tissue surrounding the mammary glands
What is the most common benign mammary tumour seen in dogs?
Mixed adenoma
What is the typical gross presentation of a mixed mammary adenoma?
Mixed mammary adenomas typically present as circumscribed, non-fixed, hard and knobbly masses
What is the most common benign mammary tumours seen in cats?
Fibroadenoma
Remember benign mammary tumours are less common in cats
What are the histological classifications of malignant epithelial mammary tumours?
Simple carcinoma
Complex carcinoma
Mixed carcinoma
Carcinosarcoma
What is a simple carcinoma?
A simple carcinoma is a malignant tumour arising from a single type of mammary gland epithelium
What is a complex carcinoma?
A complex carcinoma is a malignant tumour arising from several types of mammary gland epithelium - usually the luminal epithelium and myoepithelium
What is a mixed carcinoma?
A mixed carcinoma is a malignant tumour arising from mammary gland epithelium - usually the luminal epithelium ± myoepithelium - whilst also containing cartilage and bone
What is a mammary carcinosarcoma?
A mammary carcinosarcoma is a malignant tumour arising from the mammary gland epithelium and the connective tissue surrounding the mammary glands
What is an inflammatory carcinoma?
Inflammatory carcinomas represent a uniquely aggressive subtype of carcinomas; histopathologically, these tumors are often anaplastic carcinomas but are characterised by extensive dermal lymphatic invasion, diffuse dissemination, inflammation, erythema, swelling, and pain
Inflammatory carcinomas can be clinically mistaken with mastitis
What is the typicaly gross appearance of a malignant mammary tumour?
Malignant mammary tumours tend to present as a solid, fixed, ulcerated mass with a rapid growth rate
What is the most common malignant mammary tumour seen in dogs?
Simple carcinoma
What is the most common malignant mammary tumour seen in cats?
Simple carcinoma
Which factors are assessed for histopathological grading of mammary tumours?
Tubule formation
Cellular pleomorphism
Mitotic index
What is the histological grading system for mammary tumours?
Low grade/grade I: Well differentiated
Intermediate grade/grade II: Moderately differentiated
High grade/grade III: Poorly differentiated
Higher grade mammary tumours have a worse prognosis
What are other histopathological features that are indicative of a poor prognosis for mammary tumours?
Surrounding connective tissue invasion
Vascular or lymphatic invasion
Lymph node involvement
How do you stage the primary mammary tumour?
Thorough clinical examination
Palpate both mammary chains and all mammary glands
Measure the primary tumours
Palpate the mammary tumours
Why is it so important to measure the primary mammary tumours?
It is important to measure the primary mammary tumours are the size directly correlates with prognosis. The larger the primary tumour, the worse the prognosis
Describe the WHO clinical staging system for mammary tumours in dogs
T1: Mammary tumour with a diameter less than 3cm
T2: Mammary tummour with a diameter between 3 - 5cm
T3: Mammary tumour with a diameter over 5cm
T4: Inflammatory neoplasm of any size
Increasing size is associated with a worse prognosis
What are the subclassifications of T1 for mammary tumours in dogs?
T1A: Mammary tumours less than 1cm in diameter
T1B: Mammary tumours between 1 - 3cm in diameter
What is the typical behaviour of a mammary tumour in dogs less than 1cm in diameter (T1A)?
A mammary tumour in dogs that is less than 1cm in diameter is almost always benign
Describe the WHO clinical staging system for mammary tumours in cats
T1: Mammary tumour less than 2cm in diameter
T2: Mammary tumour between 2 - 3cm in diameter
T3: Mammary tumour over 3cm in diameter
Which lymph nodes drain the mammary glands?
Axillary lymph nodes
Superficial inguinal lymph nodes
How do you stage mammary tumours for regional lymph node involvement?
Palpate the axillary and superficial inguinal lymph nodes
FNA and biopsy lymph nodes if enlarged
How do you stage mammary tumours for distant metastasis?
Thoracic radiography (pay attention to lungs as they are a common site of metastasis)
Abdominal radiography (pay attention to medial iliac and sternal lymph nodes as there are a common site of metastasis)
Abdominal ultrasound
CT
Scintigraphy
What are the benefits of CT for mammary tumour staging?
CT is more sensitive to lung and bone metastasis than radiography
Which diagnostic tests should you do to investigate for concurrent disease in patients with mammary tumours?
Haematology
Biochemistry
Coagulation panel
Why is it important to do a coagulation panel in patients with a mammary tumour?
Inflammatory carcinomas can cause coagulopathies (however it is rare)
What is the main treatment option for mammary tumours?
Surgical excision
What determines the surgical approach for excising mammary tumours?
The surgical approach for excising mammary tumours is dependent on the lymphatic drainage pattern of the mammary tumour
What is the normal lymphatic drainage of the mammary glands in dogs?
Dogs have two mammary chains each consisting of five mammary glands. For normal mammary glands, the first and second gland drain into the axillary lymph node, the third can drain into either the axillary or superficial inguinal lymph node, and the fourth and fifth glands drain into the superficial inguinal lymph node. It is important to know that lymph drainage from each gland passes through the other mammary glands in that chain to reach the lymph node
What is the lymphatic drainage of neoplastic mammary glands in dogs?
Lymphatic drainage of neoplastic mammary glands is much more unpredictable. The first and second gland can drain into the axillary and sternal lymph nodes, the third gland can drain into the axillary, superficial inguinal or medial iliac lymph node, the fourth gland can drain into the axillary or superficial inguinal lymph nodes and the fifth gland can drain into the superficial inguinal or popliteal lymph node
Which feature of normal lymphatic drainage of the mammary glands should you be aware of in the cat?
In the cat, there are vascular connections between the left and right mammary chains so neoplasia is much more likely to spread and become bilateral in the cat
What are the options for surgical excision of mammary tumours?
Lumpectomy
Simple mammectomy
Partial mastectomy
Radical mastectomy
When is a lumpectomy indicated?
A lumpectomy is a marginal excision indicated for unfixed lesions less than 0.5cm in diameter
What is a simple mammectomy?
A simple mammectomy is the excision of the affected mammary gland
When is a simple mammectomy indicated?
A simple mammectomy is indicated for centrally positioned lesions between 0.5 - 1cm in diameter
What is a partial mastectomy?
A partial mastectomy is the excision of the affected mammary gland as well as any other glands which drain from it via the lymphatics
When is a partial mastectomy indicated?
A partial mastectomy is indicated for any lesion beyond 1cm in diameter
What is a radical mastectomy?
A radical mastectomy is the excision of the entire mammary chain. This procedure can be uni- or bilateral
When is a radical mastectomy indicated?
A radical mastectomy is indicated when there is multiple lesions
What are the benefits and limitations of a radical mastectomy compared to a partial mastectomy in dogs?
Radical mastectomy decrease the risk of local recurrence compared to a partial mastectomy, however it does not increase the lifespan in dogs so you have to consider if it is worth the extra complications associated with a radical mastectomy
Which surgical procedure is indicated in all cats with mammary tumours?
Radical mastectomy (often bilateral) is indicated in almost all cats with mammary tumours due to the high degree of malignancy
What are the benefits of radical mastectomies in cats?
In cats, radical mastectomies have been shown to reduce the risk of local recurrence and increase survival time
When should lymph nodes be removed concurrently with mammary tumour excision?
The superficial inguinal lymph nodes are practically embedded into the 4th (in cats) and 5th (in dogs) mammary gland so will be removed with them. The axillary lymph nodes should be removed if they are enlarged
Should you do a concurrent ovariohysterectomy with mammary tumour excision?
Most studies have shown that a concurrent ovariohysterectomy has no effect on survival time, local recurrence, death and time to metastasis of malignant mammary tumours. However, an ovariohysterectomy will prevent pyometras which is often a concurrent disease seen in older female animals, prevent the need for treatment with exogenous progestogens and according to some studies could reduce the risk of growth of further benign mammary tumours
Be aware that there have been more recent studies which suggest that the oestrogen and progesterone receptor status and serum oestrogen levels at the time of mammary tumour excision could affect how beneficial concurrent spaying would be; studies found that dogs with high serum oestrogen that were oestrogen receptor positive had a decreased risk of recurrence following spaying. Studies have also found that dogs that were oestrogen receptor negative with high oestrogen levels ended up with increased recurrence following spaying
When is chemotherapy indicated in the treatment of mammary tumours?
Chemotherapy is indicated as adjunctive treatment for high grade mammary carcinomas however is not very effective
Which chemotherapy drug is typically used for high grade mammay carcinomas?
Sole agent doxorubicin chemotherapy
What are some of the other adjunctive treatment options for mammary tumours?
Anti-oestrogens
Anti-angiogenic drugs
What are the side effects of anti-oestrogens?
In dogs, anti-oestrogen drugs are metabolised into and oestrogenic metabolite which will result in oestrogenic side effects in dogs
Which anti-angiogenic drugs can be used in the treatment of mammary tumours?
NSAIDS
Thalidomide
Which factors should you consider when determining mammary tumour prognosis in dogs?
Histological type
Histological grade
Primary tumour size (less than 3cm is good, more than 5cm is poor)
Tumour clinical stage
Which factors should you consider when determining mammary tumour prognosis in cats?
Histological grade
Primary tumour size (less than 2cm is good, more than 3cm is poor)
Tumour clinical stage
Extent of surgery required (bilateral radical mastectomy provides best prognosis in cats)
