24th May 2025

Benign Breast Disease

Breast Lumps

Breast masses are a common clinical finding, particularly in women of reproductive age. Although the vast majority of these masses are benign (over 90%), it is important to exclude breast cancer during the assessment of any patient presenting with a new breast lump.

Fibroadenoma

Fibroadenomas are the most common benign breast tumour, accounting for approximately 50% of all breast biopsies. They can affect women of any age, but are frequently seen in adolescent and young women between the ages of 15 and 35 years. Whilst they typically present as a solitary, unilateral breast lump, in 20% of cases, multiple fibroadenomas may manifest within the same breast or bilaterally.

The aetiology of these lesions remains unknown, however hormonal influences are thought to play a role due to their persistence during reproductive years and typical involution following menopause. Furthermore, changes in their size are often associated with pregnancy or in response to oestrogen therapy.  

Fibroadenomas classically present as a small (1-3cm in size), firm, painless and mobile mass with a smooth texture on clinical examination. Accompanying imaging is usually performed, with ultrasound being the preferred modality in younger women, due to dense breast tissue rendering mammography more challenging. Ultrasound and mammography usually reveal a well-defined, round to ovoid, hypoechoic lesion with smooth margins. Involutional change, typically seen in older, postmenopausal women, may also show characteristic ‘Popcorn calcifications’ on x-ray. 

In cases where there is diagnostic uncertainty, further investigation may be warranted by way of core biopsy or fine needle aspiration (FNA). This may include an enlarging lesion, atypical findings on imaging, a lesion >2.5cm in size or for ‘peace of mind’ for the patient. Histologically, fibroadenomas appear as a biphasic lesion comprising proliferation of both glandular and stromal tissue.

The majority of fibroadenomas do not carry an increased risk of breast cancer and therefore, most patients require no treatment or follow-up. However, surgical excision can be performed if the lesion is particularly large, or at the patient’s request.

Simple Breast Cyst

Breast cysts represent one quarter of all benign breast lesions. As with fibroadenomas, they can affect women of any age, but are more common in women between the ages of 35 and 50 years. The majority of cysts present as a unilateral, solitary mass and are usually found in conjunction with fibrocystic change.

It is believed that most breast cysts result from hormonal influences and their fluctuating levels, resulting in the blockage of the breast acini and a subsequent fluid-filled dilatation of the duct(s). In particular, cysts tend to become larger and painful around menstruation.

A large proportion of women will remain asymptomatic and may be unaware that they have a cyst. In those that do detect a breast lump, cysts typically present as a painful or painless, round to ovoid mass, ranging from a few millimetres to several centimetres in size. Acute enlargement frequently causes severe, localised pain of sudden onset and is usually associated with hormonal changes. However, cysts tend to stop forming in the postmenopausal period and may regress on their own accord.

Clinical examination usually reveals a smooth, firm, discrete, tender mass with a distinct border, said to resemble a ‘grape’ in texture. As with other benign breast disease, accompanying imaging is usually determined by the patient’s age. Features seen on ultrasound include a round to ovoid, anechoic mass, with circumscribed margins and posterior acoustic enhancement. Mammography typically reveals a round to ovoid mass with circumscribed margins only.

Breast cysts are not associated with an increased risk of malignancy and therefore, treatment is not usually indicated. Larger, more painful cysts may be aspirated to provide symptomatic relief. Cytological analysis of the aspirate is only warranted if there are any concerning features, such as blood-stained fluid. Otherwise, the material is typically discarded.

Fat Necrosis

Fat necrosis is a benign breast condition that commonly occurs after direct trauma or surgery to the breast. Whilst it can affect women of any age, middle-aged women seem to be most at risk. Due to its variable character on both examination and imaging, fat necrosis can often mimic malignancy and therefore, may warrant further investigation.

Fat necrosis is characterised by the saponification of fatty tissue, often in response to localised inflammation as a result of direct trauma. The most common causes include breast biopsy, surgery (lumpectomy, reduction, reconstruction, enlargement), lipomodelling and trauma related to seat belts. However, up to 50% of patients may have no history of prior surgery or trauma.

Clinical examination usually reveals a painful or painless, firm, round lump, with a predilection for the subareolar and periareolar regions. The lump may also be associated with changes to the overlying skin, such as erythema, bruising, dimpling or a retracted nipple. Given that the onset can be considerably delayed to the causative event (>10 years), fat necrosis can have a variable appearance on imaging and where possible, comparison with previous imaging is essential.

In the acute phase, ultrasound will show increased echogenicity around the lesion. In the days to months after, the lesion typically develops into an ill-defined complex cystic lesion surrounded by oedematous fat. After several years, fat necrosis may appear as a spiculated mass with calcified walls and posterior shadowing. Mammography, on the other hand, is usually characterised by an ill-defined, irregular, spiculated mass, with or without associated calcification. With time, the lesion will develop into an ‘oil cyst’, characterised by a curvilinear, calcified wall and homogenous centre. 

Due to the potential for diagnostic uncertainty, it may be necessary to biopsy these lesions in order to establish a definitive diagnosis. Histology reveals necrotic fat cells surrounded by macrophages, multi-nucleate giant cells and variable inflammatory cells. More established lesions may show varying degrees of fibrosis and calcifications, as part of a scar formation.

Fat necrosis does not carry an increased risk of breast cancer and therefore, the majority of patients do not require treatment. Surgery is usually avoided, due to the association with developing further fat necrosis. For that reason, intervention is limited to those with symptomatic fat necrosis, persistent/enlarging lesions or for aesthetic purposes.

Phyllodes Tumour

Phyllodes tumours are an uncommon breast neoplasm, accounting for around 1% of all breast tumours. Whilst they can affect women of any age, Phyllodes tumours are more commonly found in premenopausal women between the ages of 40 and 50 years. Akin to a fibroadenoma in their appearance, they are characterised by a fibroepithelial proliferation, with a potential to undergo malignant transformation.

Clinical examination usually reveals a smooth, multinodular, mobile, painless breast mass with rapid growth, averaging 3 to 5cm in size at presentation. Larger tumours can distort the overlying skin, resulting in a shiny, stretched appearance. Palpable axillary lymphadenopathy may also be present in as many as 20% of cases, though the underlying pathology is usually reactive in nature, as opposed to metastatic involvement.

Phyllodes tumours usually appear as a well circumscribed, round-to-oval or lobulated lesion with smooth margins on mammography. A radiolucent halo may also be seen. Ultrasound typically reveals an inhomogeneous, solid appearing mass, largely indistinguishable from a fibroadenoma. As such, imaging alone is insufficient for diagnosis and histological evaluation is necessitated.

Core biopsy is the preferred modality for histological assessment, as fine needle aspiration (FNA) is associated with a high false negative rate and low overall diagnostic accuracy. Histology shows a biphasic proliferation of both epithelial and stromal elements, with an overarching ‘leaf-like’ architecture. Due to the heterogeneity of the tumour, up to 30% of core biopsy specimens may also provide a false negative result and therefore, surgical excision may be required. This may involve breast conserving surgery in the form of a wide-local excision, or a full mastectomy. 

Phyllodes tumours are graded on their histological appearance, which incorporates the degree of cellular atypia, stromal overgrowth and number of mitoses, amongst other features. The vast majority of tumours will fall into the benign category, whilst more atypical tumours may be graded as borderline or malignant. Irrespective of the grading, Phyllodes tumours have a propensity to recur and therefore, follow-up is recommended. However, these tumours are not associated with an increased risk of invasive breast cancer.

Pseudoangiomatous Stromal Hyperplasia (PASH)

Pseuodangiomatous Stromal Hyperplasia (PASH) is a relatively uncommon benign breast condition, that usually affects women of reproductive age. PASH is characterised by a benign proliferation of stromal tissue that mimics a vascular lesion. Typically, it is asymptomatic and therefore, is usually an incidental finding during clinical examination and/or imaging. Whilst hormonal changes are thought to be responsible, the exact aetiology is unknown.

Clinical examination typically reveals a single, painless, well circumscribed mass of varying size, ranging from anywhere between 1cm and 12cm anecdotally. Imaging (both mammography and ultrasound) demonstrates a round, well circumscribed, non-calcified mass, features which are largely non-specific and therefore, histological confirmation is often warranted.

Histology reveals a pattern of slit-like spaces, set within a dense collagenous stroma and lined by spindle shaped myofibroblasts with bland nuclei. The slit-like spaces may resemble vascular channels and as such, PASH may be confused with low grade angiosarcoma.

PASH does not carry an increased risk of breast cancer and for the majority of patients, no treatment or follow-up is indicated. Further assessment is usually reserved for any patients that notice a change in size or character of the lump.

Nipple Discharge

After breast pain and breast lumps, nipple discharge represents the 3rd most common breast-related complaint. As many as 80% of women of reproductive age, will experience at least one episode of nipple discharge. It can be further classified into lactational (normal), physiological or pathological, the majority of which is of a benign origin.

Intraductal Papilloma

Intraductal papillomas are the most common cause of pathological nipple discharge, classically seen in women between the ages of 40 and 50 years. They are characterised by the development of a wart-like lump within the milk ducts and are usually found in the vicinity of the nipple, though they can occur anywhere in the breast. Central intraductal papillomas, located in the subareolar region, arise from large lactiferous ducts and are usually solitary in nature. Peripheral intraductal papillomas meanwhile, involve the terminal duct lobular unit (TDLU) and are usually several in number, termed papillomatosis.

As papillomas can be asymptomatic, they are often noted incidentally during routine imaging. However, clinical examination may reveal a painless retroareolar mass. In instances of nipple discharge, papillomas are typically associated with unilateral, spontaneous and persistent discharge of bloody or serosanguinous fluid, often less than 6 months in duration. 

Mammography is usually normal, though findings may include a solitary or multiple dilated ducts, with an associated subareolar mass that is benign in appearance, with or without calcification. On ultrasound, a papilloma can be seen as a well-defined mass, partially outlined by fluid, with colour doppler demonstrating a vascular stalk. Further investigation is usually warranted, usually by way of an excision biopsy, which reveals a dual population of both epithelial and myoepithelial cells lining a fibrovascular core and set within a duct.

Papillomas are not associated with an increased risk of breast cancer, unless they are noted to contain atypical cells during histological assessment. Follow-up is typically reserved for those in which atypical cells have been identified, or those with multiple papillomas.

Mammary Duct Ectasia/Periductal Mastitis

Mammary duct ectasia and periductal mastitis are terms that are often used interchangeably, though some literature has described them as being two distinct entities. They are another common cause of benign nipple discharge, accounting for up to 30% of cases. Duct ectasia is typically seen in perimenopausal women over 35 years of age and is thought to arise due to age-related shortening and widening of the ducts, with subsequent obstruction secondary to inspissated secretions. Periductal mastitis, however, is more common in younger women and occurs when the ducts become inflamed and/or infected. The latter has a strong association with smoking.

Duct ectasia may be asymptomatic, but can present with thick, “cheesy” nipple discharge, but can also be watery in consistency, as well as brown, green or blood-stained. Occasionally, a lump may be felt behind the nipple and the nipple itself may become red, tender and retracted. At this point, periductal mastitis may be more appropriate terminology and the surrounding breast tissue may become painful, hot and erythematous. If left untreated, a pus filled abscess or fistula may also develop.

Mammography and ultrasound imaging reveal similar features, characterised by dilated, branching tubular structures in the subareolar region. X-ray may also show rod like calcifications pointing towards the nipple. Biopsy of the area shows dilated duct lumens containing foamy macrophages, with surrounding periductal chronic and/or granulomatous inflammation, particularly if there has been rupture. In the latter stages, periductal fibrosis and obliteration of the lumen may also be seen.

Duct ectasia will often resolve spontaneously and may only require simple analgesia for pain relief. Periductal mastitis will usually be treated with a course of antibiotics, though some cases will resolve on their own accord. In the presence of complications, such as an abscess or the development of a fistula, specialist input may be required for further management. This can include aspiration of the pus, or incision and drainage. Surgical intervention may be warranted in recurrent disease or in cases that do not respond to the aforementioned measures. However, neither duct ectasia or periductal mastitis are associated with an increased risk of developing breast cancer.

Galactorrhoea

Galactorrhoea is characterised by milky nipple discharge unrelated to pregnancy or breastfeeding and can be physiological or pathological in nature. It can affect as many as 1 in 4 women and can occur at any age, including after menopause. Raised serum prolactin levels are responsible for the discharge, of which there are many underlying causes.

Physiological nipple discharge can be attributed to several factors, one of which is excessive nipple stimulation. This can be through sexual activity, frequent breast examinations (including imaging) or high-impact exercise. Stress is also known to increase serum prolactin levels, which can result in galactorrhoea.

Pathological nipple discharge can be secondary to a wide variety of endocrine and iatrogenic factors. Hyperprolactinaemia can be associated with disorders of the hypothalamic-pituitary axis, of which lactotroph adenomas are the most common. Accounting for up to 40% of all pituitary adenomas, lactotroph adenomas are usually benign sporadic prolactin secreting tumours, though occasionally they may form part of an underlying Multiple Endocrine Neoplasia Type 1 (MEN 1) Syndrome. Disorders affecting the hypothalamus may also lead to increased prolactin levels, usually by way of reduced dopaminergic inhibition of the pituitary gland. These can include benign tumours (such as craniopharyngioma), malignancy (such as metastatic breast carcinoma), infiltrates (such as sarcoidosis) or trauma.

Drug induced hyperprolactinaemia is also a common cause of pathological galactorrhoea. The most common cause of pharmacologically induced hyperprolactinaemia is antipsychotic medication, typically due to their antagonistic effect on dopamine receptors. Other medications that have been associated with raised prolactin levels include selective serotonin reuptake inhibitors (SSRIs), the gastric motility drugs Metoclopramide and Domperidone, Methyldopa and Verapamil.

Other less common causes of galactorrhoea include familial hyperprolactinaemia (characterised by a germline, loss of function mutation in the prolactin receptor gene PRLR), hypothyroidism, macroprolactinaemia (aggregates of prolactin and antibodies) and chronic kidney disease.

Investigations and treatments for galactorrhoea are dependent upon the underlying cause. Evaluation usually requires an extensive history, coupled with clinical examination, serum prolactin levels and imaging, such as an MRI scan of the pituitary gland. The presence of galactorrhoea alone does not always necessitate treatment, unless it is bothersome to the patient. When indicated, the pharmacological treatment for lactotroph adenomas and idiopathic hyperprolactinaemia usually involves the introduction of a dopamine agonist, such as Cabergoline or Bromocriptine. Larger tumours that are unresponsive to initial medical therapy may require more invasive measures, such as transsphenoidal surgery and postoperative radiotherapy. Drug induced hyperprolactinaemia can be managed through patient counselling and education surrounding medication side effects. In some circumstances, dose tapering or discontinuing the medication may be required.

Other Common Benign Breast Conditions

Although the majority of benign breast conditions are more prevalent amongst women, it is important to remember that men can present with the same underlying diagnoses. However, the most common benign breast condition associated with the male population, is gynaecomastia.

Gynaecomastia

Gynaecomastia is characterised by the benign proliferation of the glandular tissue of the breast and is frequently seen amongst the adolescent male population, with 2 in every 3 teenagers experiencing some degree of gynaecomastia. Whilst true gynaecomastia is reserved for enlargement of the breast tissue itself, gynaecomastia can also be used to describe breast enlargement secondary to an increase in fatty tissue, sometimes termed pseudo-gynaecomastia.

Clinical examination usually reveals a symmetrical enlargement of breast tissue that is centrally placed and tender upon palpation. Pain is typically associated with an adolescent population and many older men with gynaecomastia may remain asymptomatic. Some patients may only experience a unilateral enlargement of the breast tissue.

The main cause of gynaecomastia in adolescents is almost always puberty related and the majority of cases will resolve spontaneously. However, 1 in 4 will suffer with persistent pubertal gynaecomastia. Drug induced gynaecomastia accounts for around 20% of cases, with a plethora of medications having been implicated, most notably those that affect androgen and/or oestrogen levels. Those with the best evidence include Spironolactone, Cimetidine, Ketoconazole, Gonadotropin-releasing hormone (GnRH) agonists and 5-alpha-reductase inhibitors. Other, less common causes, include liver cirrhosis, hypogonadism, testicular tumours, hyperthyroidism and chronic kidney disease.

Investigating gynaecomastia mandates a thorough history and examination. Signs and symptoms related to the aforementioned disease processes should be evaluated, alongside a detailed medication review. Biochemical testing can be performed and may focus on androgen levels, glucose levels and thyroid function, as well as assessing baseline liver and renal function. Imaging is of little diagnostic use and should be reserved for suspicious cases or those with unilateral breast enlargement. Similarly, histological assessment may be indicated in those with suspicious clinical or radiological findings.

Management is dependent upon the underlying cause. As discussed, the majority of puberty-related gynaecomastia will resolve spontaneously and therefore, no treatment or follow-up is indicated. Drug induced gynaecomastia requires careful consideration of the benefits of the medication versus the unwanted side effect profile. Adapting the dosage, changing or discontinuing the causative medication are all viable options that could be explored. Occasionally, pharmacological management may be suggested, including Tamoxifen and Danazol, whilst surgical intervention is reserved for exceptional circumstances, where prior treatments have failed or quality of life is sufficiently affected. Importantly, gynaecomastia is not associated with an increased risk of breast cancer.

References

1. https://breastcancernow.org/about-breast-cancer/breast-lumps-and-benign-not-cancer-breast-conditions/
2. https://www.uptodate.com/contents/clinical-manifestations-differential-diagnosis-and-clinical-evaluation-of-a-palpable-breast-mass?source=history
3. https://www.uptodate.com/contents/overview-of-benign-breast-diseases?source=history
4. https://radiopaedia.org/articles/fibroadenoma-breast?lang=gb
5. https://www.uptodate.com/contents/breast-cysts-clinical-manifestations-diagnosis-and-management?source=history
6. https://radiopaedia.org/articles/simple-breast-cyst-1?lang=gb
7. https://radiopaedia.org/articles/fat-necrosis-breast-2?lang=gb
8. https://www.uptodate.com/contents/phyllodes-tumors-of-the-breast?source=history
9. https://radiopaedia.org/articles/phyllodes-tumour?lang=gb
10. https://www.pathologyoutlines.com/topic/breastpash.html
11. https://www.uptodate.com/contents/nipple-discharge?source=history
12. https://www.pathologyoutlines.com/topic/breastpapilloma.html
13. https://www.uptodate.com/contents/causes-of-hyperprolactinemia?source=history
14. https://www.uptodate.com/contents/epidemiology-pathophysiology-and-causes-of-gynecomastia?source=history