Benign Breast Disease

Breast disease can arise from any of the following: the large ducts, the terminal ducts and lobules, the intralobular stroma, the interlobular stroma or the adipose tissue.

Click on the ‘hotspots’ to see the anatomy labelled:

It should be noted that breast tissue is under hormonal control during the reproductive years with rising post-ovulation progesterone levels leading to cell proliferation, increased numbers of acini and also oedema of the interlobular stroma.  These changes reverse as the hormone levels drop at menstruation.  These normal cyclical changes and can be experienced as increased lumpiness and also sometimes pain prior to menstruation.

During pregnancy, the number and size of the lobules increase where colostrum then milk is produced after birth.  Upon cessation of breastfeeding the lobules partially involute.

Post-menopausal women have an increase in fat and reduction in glandular tissue of their breasts.

Breast lesions are understandably a source of great anxiety to women and can present with a variety of symptoms.  We must always exclude malignancy, however, it is useful to remember that 90% of breast lumps in those <40years are benign and 40% of breast masses in >50years are benign.  There is, therefore, a large proportion of presentations which represent benign breast conditions so it is important to have a good understanding of these.

Women may present with a breast lump, nipple discharge, pain, nipple retraction or skin changes.  They may also have weight loss.

Most of these symptoms could represent either benign or malignant disease and a combination of history, examination, diagnostic testing and consideration of the patient’s age and family history are needed to reach a diagnosis.

It is important to remember that some causes of benign breast disease, like malignant disease, will be asymptomatic and will be picked up via participation in breast screening.  In Scotland, women between the ages of 50 and 70 are offered breast screening every 3 years.

Fibroadenomas are well-defined hypoechoic lesions on ultrasound:

 

The most reliable way to confirm a diagnosis of fibroadenoma is by doing a core biopsy.  This is performed by using local anaesthetic to numb the skin, inserting a wide bore hollow needle through the skin and, when it is within the breast lump, cutting out and removing a piece of tissue, sometimes using radiological guidance, for example, ultrasound.

The tissue is then sent to the lab for a pathologist to examine.  It is preserved in formalin fixative, embedded in wax, sliced very thinly with a microtome, then the cells are stained with Haematoxylin and Eosin, to give a pink and blue appearance.  Under the microscope this is what we can see:

Fibroadenoma is confirmed.  The epithelium is characteristically bi-layered.  The stroma is composed of spindle cells which are elongated cells with cigar-shaped bland nuclei.  Bland means the nuclei do not show the suspicious features which would be worrying for malignancy so they are not hyperchromatic (darker than usual) and are roughly the same size with no abnormal mitoses.

The pathologist reports all core biopsy specimens with a ‘B score’ which helps guide the next clinical steps:

Fibroadenomas are benign breast lesions so a B2 designation can be given.  Our patient can be reassured that this is a benign condition. In Edinburgh, all fibroadenomas >3 cm are excised.

Here is a picture of a fibroadenoma which has been removed.  Note it is rounded and well-circumscribed (has a well-defined edge) and has a smooth surface.

A 39 year old woman presents to her GP as she has noticed lumps in her breasts and has been experiencing pain for past 6 months.  The lumps are more prominent at certain times during her menstrual cycle and this is associated with tenderness, particularly in the week preceding her period.   There is no nipple discharge or skin changes.  She has no family history of breast cancer.

On examination there is a generalised lumpiness of both breasts and a more discrete area of  ‘thickening’ of the right breast at 10 o’clock.  The Scottish Cancer Referral guidelines, available online, provide helpful information about when a GP should refer to the One Stop Breast Clinic.  In this case the patient is referred as carcinoma must be excluded.

These changes in the breast are benign.  The commonest age group affected is women aged between 30 and 50 years old.  This affects pre-menopausal women and the cyclical symptoms are due to fluctuating hormone levels, particularly increased oestrogen to progesterone ratio, that occur during the menstrual cycle.

Our patient attends the one-stop breast clinic and undergoes ultrasound to determine the composition of the right breast lump revealing a cyst.

A biopsy of what fibrocystic change looks like under the microscope is shown below.  Changes tend to affect the terminal duct lobular unit:

With fibrocystic changes confirmed, our patient can be reassured.  These changes do not increase her risk of breast cancer.  She can be advised to continue to be breast aware and to seek help if she notices any new symptoms, unusual for her.  There is no specific treatment but sometimes GPs will prescribe hormonal regulation for symptom relief.

A 31-year-old smoker presents with a left-sided breast lump to her GP.  She is very anxious as her maternal aunt has recently undergone treatment for breast cancer.  The lump is not painful and she has not had any nipple discharge.

On examination, the lump is firm, ill-defined and poorly mobile.  There is no nipple retraction but there is slight retraction of the overlying skin just below a scar on her left breast.  She mentions that she had breast reduction surgery 9 months ago because she was having back pain.

The GP refers her to the one-stop breast clinic.

Following history and examination, she is sent for investigations.  She has an ultrasound which shows an ill-defined hypo-echoic mass with central acoustic shadowing.  She also has a mammogram which shows a poorly defined irregular mass with branching microcalcifications, overall resembling carcinoma.  She needs to have a tissue biopsy to confirm the diagnosis.  She has a core biopsy followed by a wide local excision (WLE) of the lump and the tissue is sent to pathology.

The histological examination under the microscope shows:

This diagnosis, which affects the interlobular stroma and surrounding adipose tissue, usually follows a history of surgery or trauma. It can present early following surgery, in which histology would show haemorrhage and central areas of liquefactive fat necrosis with neutrophils (acute inflammatory cells) or can have a delayed presentation, months later once the post-surgical swelling has resolved.  This can cause great anxiety for patients who have had reconstructive surgery post-mastectomy for breast malignancy due to the possibility of the lump representing recurrence of the carcinoma.

Our patient had breast reduction surgery, during which the pedicle of adipose tissue was supplied by one main arterial perforator branching into smaller capillaries.  If the blood supply is disrupted during this process, fat necrosis can occur in the more distal parts of the pedicle and overlying skin.  The main blood supply comes from the internal mammary artery perforators.  Smoking is an independent risk factor for fat necrosis after breast reduction.

She can be reassured that she does not have breast cancer and that there is no known risk of malignant transformation of fat necrosis.  Given her family history she should be given advice about breast awareness and to re-present should she discover new changes.  This is a prime opportunity for smoking cessation advice as smoking increases breast cancer risk as well as risk of other malignancies!

 

Remember that the other lesions, non-specific to the breast may also produce a lump. These include epidermoid cysts (benign skin cyst) and lipomas (benign tumour of adipose tissue) which can occur anywhere on the body.

A pregnant or lactating woman may notice palpable masses in her breasts which consist of normal-appearing breast tissue with lactational changes.  This represents an exaggerated local response to prolactin and is benign.  These are lactational adenomas.

A 26 year old woman who is 1 month post-partum presents to the GP with a left sided wedge shaped breast lump with overlying erythema and swelling.  She says if feels hot to touch and that she experiences a constant burning pain which is exacerbated during breastfeeding.  She has felt feverish and exhausted.  As for nipple discharge, she states she is obviously lactating but was worried that she may have seen a streak of blood coming out too.

On examination she has a temperature of 38.5 Celsius, and her heart rate is 110.  Her oxygen sats and respiratory rate are normal.  Her BP is 105/70.  On examination her left breast appears as below and the inflamed area is hot to touch and the woman winces with pain:

The bacteria enters the cracks and fissure that form in the nipple when a woman starts to breastfeed.  It affects one duct system at first but can spread throughout the breast if untreated.

This patient is systemically unwell and the GP suspects sepsis.  She sends the patient to hospital as she will require IV antibiotics and fluids to get better.  She may require surgical drainage of an abscess but this is rare.  Scarring and distortion of the breast shape can follow healing and scar formation.  In milder cases, mastitis can be managed in the community with a course of oral antibiotics however if the woman does not improve after one course, she should be referred to the breast team to exclude an inflammatory breast carcinoma.  Be aware that without this history, this appearance could look the same as breast carcinoma.

She has right-sided nipple discharge and a mildly painful palpable periareolar mass and is experiencing thick white/pale green nipple secretions.  There is no family history of breast cancer.  She is a non-smoker.

On examination, there is slight retraction of the right nipple, a poorly defined periareolar mass and there is a discharge.  The GP refers her to the one-stop breast clinic.

The breast surgeon examines her and organises for her to have a mammogram.  The mammogram shows nodular appearing retroareolar dilated ducts.  A core biopsy is performed.

As you can see at this medium power image, the ducts are ectatic (dilated) and filled with foamy macrophages and secretions.  Between ducts, a chronic inflammatory infiltrate of lymphocytes, macrophages and plasma cells can be seen.

This condition tends to occur in women in their 40s and 50s who have had children.  It occurs when one or more of the large ducts behind the nipple dilates and its walls thicken.  It then fills with a thick white/green substance consisting of breast secretions and inflammatory cells and debris.  Should this become blocked, then the duct can leak into the surrounding tissue causing inflammation and healing with fibrosis and scarring, hence the nipple retraction.  If the patient is symptomatic, the surgeon can excise the affected duct(s).

A 48-year-old woman presented to her GP as she has noticed some clear nipple discharge over the past couple of weeks which became bloodstained yesterday.  She is referred to the One-Stop Breast Clinic where an examination reveals a small lump palpable behind the nipple and the surgeon is able to express some blood-stained fluid from the nipple.  She organises mammography which reveals a 5mm subareolar mass.  This mass is sampled by core biopsy.

Histological examination reveals a lesion (green arrows) which has grown into the lumen of a dilated duct, consisting of multiple finger-like branching projections with fibrovascular cores lined by epithelial and myoepithelial cells.  They frequently include foci of epithelial hyperplasia and apocrine metaplasia.  The surgeon may offer to excise the affected duct (microdochectomy).  They must be carefully examined to exclude cytologic atypia, as a larger excision will be required if atypia is found.  This may entail total duct excision where all the ducts are removed, following which breastfeeding is not possible.

These benign lesions tend to form in women aged 35 – 55 years old.  They can form in the large ducts behind the nipple or further along the branches in the smaller ducts closer to the terminal duct lobular unit.  They produce a serous (clear) discharge when there is intermittent clogging then release of normal breast secretions.

 

A 64-year-old man presents to his GP having noticed rounded lumps in the subareolar region of both breasts.  He has no skin changes and no nipple discharge.  He has no family history of breast cancer.

The GP must consider possible causes of gynaecomastia which are linked to an imbalance between oestrogens and androgens.  Oestrogens stimulate breast tissue and androgens do the opposite.  Can you explain why the following circumstances may lead to gynaecomastia?

To show you what gynaecomastia looks like microscopically:

This is a low power view of the histology of gynaecomastia with increased dense collagen (the pink connective tissue) and moderate epithelial hyperplasia seen with tapering micropapillae protruding into the lumen of the ducts.

So, in summary, we have learned about:

• fibroadenomas which originate in the intralobular stroma
• fibrocystic change which affects the terminal duct lobular units
• fat necrosis which forms in the interlobular stroma after trauma
• duct ectasia which affects the large ducts
• Intraductal papilloma which can be in the large or small ducts
• Mastitis which enters via nipple fissures and can spread throughout the breast or cause an abscess
• Gynaecomastia – hormone-driven expansion of male glandular breast tissue
• Lipomas- benign tumours of adipose tissue non-specific to breast
• Epidermoid cyst – affects the skin, non-specific to breast

Well done for reaching the end of this module!  We have covered a lot of material and hopefully you now have an appreciation of presentations and underlying pathology of benign breast conditions.