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Benign breast conditions


Introduction

Over 90% of patients presenting to a breast clinic have normal breasts or benign breast disease. Knowledge of and an understanding of the benign conditions that can affect the breast, the symptoms they cause and their management will ensure correct treatment and patient satisfaction. Benign breast disease can cause considerable morbidity and anxiety, and with increasing patient awareness and expectations, the number of patients attending clinics is increasing. Accurate diagnosis and effective treatment followed by an adequate explanation of the condition with provision of relevant information are a rewarding part of a breast surgeon’s workload.

Benign breast disease can be divided into congenital abnormalities, aberrations of normal breast development and involution (ANDI) and a range of specific benign conditions.

Congenital abnormalities

Developmental abnormalities of the breast can cause considerable concern and are not uncommon reasons for referral to a breast clinic. They are discussed in Chapter 1 .

Aberrations of normal breast development and involution (ANDI)

The breast passes through phases related to breast development, cyclical change and involution. Defining what represents breast disease and what is normal is not a new problem. The ANDI classification was developed to provide a framework to help understanding of the pathogenesis and subsequent management of conditions that develop during the specific phases of breast development, cyclical change and involution. Some conditions are so common that they should not be considered as disease but rather as aberrations ( Table 3.1 ).

Table 3.1
Aberrations of normal breast development and involution
Age (years) Normal process Aberration
<25 Breast development
Stromal Juvenile hypertrophy
Lobular Fibroadenoma
25–40 Cyclical activity Cyclical mastalgia
Cyclical nodularity (diffuse or focal)
35–55 Involution
Lobular Macrocysts
Stromal Sclerosing lesions
Ductal Duct ectasia

Aberrations of breast development

Fibroadenomas

Fibroadenomas arise from the terminal duct lobular unit and are now considered as aberrations of normal breast development and are not neoplasms because they do not arise from a single cell, but contain a mixture of stromal/connective tissue and epithelial elements ( Fig 3.1a ). They are affected by hormones in a similar way to the normal breast, increasing in size during pregnancy. The stromal element of these tumours defines their classification and behaviour. A ‘simple’ fibroadenoma contains stroma of low cellularity and regular cytology. Phyllodes (leaf-like) tumours may or may not arise from fibroadenomas but contain stroma with increased cellularity and atypia. Benign phyllodes tumours can usually be differentiated from fibroadenomas on core biopsy. Fibroadenomas clinically are usually mobile, discrete, rubbery masses that present symptomatically in young women or are an incidental finding during breast imaging in older women. They account for about 13% of all palpable symptomatic breast masses, but in women aged 20 they account for almost 60% of such masses. They are usually solitary but some women do have multiple fibroadenomas in one or both breasts.

Figure 3.1, (a) Fibroadenoma and (b) juvenile fibroadenoma, right breast.

Ultrasound can usually differentiate fibroadenomas from cancers, and guidelines suggest that it is acceptable to omit biopsy in a patient under the age of 25 with unequivocal benign clinical and ultrasound findings. All lesions considered likely to be fibroadenomas clinically and on imaging in women aged 25 and over should be biopsied using a 14-gauge automated core biopsy – multiple passes with at least four samples from the lesion minimises misdiagnosis rates. With the use of shearwave elastography, the diagnostic accuracy of imaging has improved and some are questioning the need for core biopsy under the age of 40. Core biopsy is however a simple technique that can be performed under image guidance with little or no pain. It has an almost zero false-negative rate providing the lesion is sampled and a fibroadenoma is diagnosed on the core biopsy by a pathologist. In women presenting with multiple clinical and radiological fibroadenomas, core biopsy should be undertaken of the largest lesions – either one from both breasts or two from the same breast.

UK national guidelines recommend that for patients <25 years, a biopsy need not be performed if the following criteria are satisfied: ultrasound reveals a solid lesion which has benign ultrasound features (e.g. ellipsoid shape [wider than tall]), a well-defined outline with smooth edges or fewer than four gentle lobulations.

Natural history: Fibroadenomas were observed for 2 years in women under 40 years of age. The majority did not change in size (55%), some got smaller or resolved (37%) and only a small number increased in size (8%), the majority of which were in women under the age of 20.

Rapid growth of a fibroadenoma is rare but can occur in adolescence (juvenile fibroadenoma) ( Fig. 3.1b ). The term ‘giant fibroadenoma’ is used when the size exceeds 5 cm and these ‘giant fibroadenomas’ are seen more commonly in women of African origin. Macroscopically, fibroadenomas are discrete, bosselated, whitish tumours that appear to bulge when cut through. Only rarely does cancer develop within a fibroadenoma, but when it does it tends to be non-invasive and lobular in type.

Management

This depends on the patient’s age and preference as well as the results of triple assessment. In patients with lesions under 5 cm, where histology confirms the diagnosis, the patient can be reassured and if they do not wish their lump excised, they can be discharged without any follow-up.

Excision is indicated only if the fibroadenoma is symptomatic, for instance if it is large relative to the breast size or it is superficial or it causes significant distortion of the breast. Excision for pain rarely improves this symptom. Excision should be performed through a cosmetically placed incision. Another option is to remove smaller fibroadenomas with a vacuum-assisted large-volume core biopsy. A large fibroadenoma where histology has shown no suggestion that it could be a phyllodes tumour can be broken up to allow the lesion to be excised through a small incision.

Juvenile fibroadenomas occur in adolescent girls and sometimes undergo rapid growth, and almost always need excision as they can grow to be very large. An inframammary approach gives good results (although tunnelling to distant areas can leave numbness) and in such women removal of skin is rarely required. In some very large lesions, later revisional surgery is required but it is important to wait for up to a year after the initial excision as skin retracts and the breast reshapes over this period. Recurrence of a fibroadenoma can occur but is rare and may result from initial incomplete excision.

Tubular and lactating adenomas

A benign circumscribed lesion consisting of glandular breast tissue with very little intervening stroma is called a tubular adenoma. Lactating adenomas are similar to tubular adenomas, but occur during pregnancy or lactation and are often multiple. Tubular adenomas in non-pregnant women are managed in a similar way to fibroadenomas. Mammographically or on ultrasound, punctuate microcalcification within acini may be visible in both tubular and lactating adenomas. Lactating adenomas can be managed conservatively once a diagnosis has been established. They tend to regress following cessation of breastfeeding.

Macromastia, so-called virginal or juvenile hypertrophy

This is the excessive development of the breasts and tends to occur during puberty (juvenile hypertrophy) or with onset of lactation (gestational). Prepubertal breast enlargement may occur very rarely in conjunction with a hormone-secreting tumour. It results from excessive proliferation of ducts and stromal tissue but no lobule formation. Significant psychological and physical problems can be caused by macromastia and patients with significant breast enlargement benefit from breast reduction. Most centres have an assessment process for such women to determine who benefits most from surgery. This procedure is not without complications and should be performed by an appropriately trained surgeon. Care should be taken with timing of surgery as further growth may occur if the breast is still developing or can happen during a subsequent pregnancy.

Aberrations in the early reproductive period

Pain and nodularity

Cyclical pain or mastalgia and nodularity are so common that they can be regarded as physiological and not pathological. Severe or prolonged pain is regarded as an aberration of cyclical change. Nodularity that is usually tender is a common problem particularly in younger women and is the most common cause of an apparent breast lump in a woman referred to a breast clinic. Terms such as ‘fibroadenosis’, ‘fibrocystic disease’ and ‘mastitis’ should no longer be used by clinicians or pathologists for this change. Imaging reveals normal breast tissue. Focal asymmetric nodularity that persists after menstruation needs full triple assessment as cancer in young women can present as localised asymmetrical nodularity rather than a discrete mass.

Mastalgia

The aim for clinicians is to differentiate between true mastalgia (pain originating within the breast) and chest wall pain. Features suggesting that breast pain is originating in the chest wall rather than the breast include pain that:

  • is unilateral, and brought on by activity;

  • can be reproduced by direct pressure over a specific area of the chest wall.

Due to its hormonal aetiology, true breast pain is often worse before and relieved after menstruation. Exacerbating factors include the perimenopausal state (where hormone levels fluctuate) and the use of exogenous hormones (hormone replacement therapy or the oral contraceptive pill). The precise cause of cyclical mastalgia is unknown.

Assessment

Any patient complaining of breast pain should have a complete breast examination including palpation with the woman sitting up and then lying on each side allowing the breast to fall away from the chest wall. In women over 40 years of age, mammography should be performed to exclude an occult malignancy, as the positive predictive value (PPV) of breast pain increases with age (PPV 0.17 age 40–49 vs PPV 2.8 over 70 years age). If a dominant lump or lumpiness is palpable, then this should be investigated. Most breast pain that reaches the breast clinic arises from the chest wall.

Treatment

The mainstay of treating chest wall pain is reassurance that there is no serious underlying cause for the pain.

Wearing a soft supporting bra 24 hours a day improves chest wall pain. Non-steroidal anti-inflammatory drugs (NSAIDs), providing that there are no contraindications, are usually effective at controlling chest wall pain. There is some evidence that topical agents cause fewer gastrointestinal problems and are also effective. If the pain is localised to one specific area, then infiltrating the tender area in the chest wall with prednisolone 40 mg in depot form combined with long-acting local anaesthetic can produce long-lasting pain relief.

For true breast pain, a variety of agents have been tried but few are used now in clinical practice:

  • A meta-analysis of placebo-controlled trials of agents in mastalgia demonstrated significant improvements in pain scores with bromocriptine, danazol and tamoxifen, but not for evening primrose oil (EPO). Tamoxifen is associated with significantly fewer side effects although no direct comparison studies of these drugs are available. ,

  • Tamoxifen can be given at a dose of 10 mg in the luteal phase of the menstrual cycle and abolished pain in 85% of women in one study. Although tamoxifen does not have a product licence for breast pain, it is used widely and appears safe.

  • Selective serotonin reuptake inhibitors can improve mastalgia as part of premenstrual syndrome.

  • Phyto-oestrogens (e.g. soya milk) and Agnus castus (a fruit extract) produce some benefits but are not widely used.

  • Reducing fat intake to less than 15% of dietary calories improves symptoms of cyclical mastalgia but is difficult to maintain.

Breast pain overview

  • Breast pain alone or painful lumpiness is common and accounts for approximately 50% of all referrals of new patients to clinics.

  • Breast pain is rarely a symptom of breast cancer.

  • Pain in the breast can arise from the breast or from the underlying chest wall.

  • Careful examination can differentiate chest wall pain from true breast pain.

  • Few patients with breast pain need treatment with drugs.

Aberrations of involution

Palpable breast cysts

Palpable breast cysts are a common reason for presentation to a breast clinic and affect 7% of all women. They constitute 15% of all discrete breast masses. Cysts are distended and involuted lobules and are most common in perimenopausal women. They are less common after the menopause. Some women have multiple bilateral cysts. Most present as smooth discrete breast masses which can be firm.

Imaging

Mammographically, breast cysts have characteristic features. Ultrasound is essential to the management of cystic disease because not only does ultrasound distinguish between solid and cystic lesions, it also provides information on the cyst wall and fluid consistency. It is also an adjunct in ensuring accurate differentiation of simple from complex cysts, as well as allowing image-guided aspiration. A simple cyst has a smooth outline with no internal echoes and posterior enhancement. Complex (or complicated or atypical) cysts are characterised by internal echoes or thin septations, thickened and/or irregular wall and absent posterior enhancement. Complex cysts, although rarely malignant, require aspiration or review. If the cyst wall shows any projections, this may indicate the presence of an intracystic papilloma or carcinoma and guided core biopsy of the relevant area is indicated.

Management

Following imaging, simple, asymptomatic cysts should be left alone. Large, symptomatic or complex cysts should be aspirated to dryness. If the fluid is bloodstained, it should be sent for cytology; otherwise it should be discarded. If a palpable mass is still present after aspiration, further imaging and biopsy are indicated. If the cyst recurs, then repeat aspiration is performed. Only rapid and persistent refilling requires further investigation. Although women with cysts have a slightly increased risk of breast cancer, this risk is insufficient to warrant follow-up.

Sclerotic/fibrotic lesions

Stromal involution can result in areas of fibrosis within breast stroma. Three different stromal lesions are described: sclerosing adenosis, radial scars and complex sclerosing lesions (CSLs). Sclerosing adenosis can present with a palpable mass. Mammographically, it can be associated with microcalcification. It differs histologically from radial scars and CSLs in the degree of excessive myoepithelial proliferation seen together with fibrosis. Radial scars and CSLs are part of the same process but are differentiated on size (radial scar, ≤1 cm; CSL, >1 cm). They are usually asymptomatic and discovered as part of mammographic screening but can rarely present as a palpable mass or an area of breast distortion.

Radial scars and CSLs are themselves benign but clinically important because of the diagnostic problems they cause during breast screening and their association with ductal carcinoma in situ (DCIS) and cancer. , Diagnosis is by vacuum biopsy. Excision of radial scars and CSLs is usually recommended as up to 20% of these lesions are associated with DCIS or low-grade invasive cancers. Excision can often be performed by vacuum-assisted large-bore core biopsy and spares open surgery in the majority of patients.

Learning point: The mammographic appearance of sclerosing lesions mimics that of cancer, causing diagnostic problems during breast screening.

Duct ectasia

The major subareolar ducts dilate and shorten during involution and, by the age of 70, 40% of women have substantial duct dilatation or duct ectasia. Some women with excessive dilatation or shortening present with nipple discharge, nipple retraction or a palpable mass that may be hard or doughy. The discharge is usually cheesy and the nipple retraction is classically symmetrical and slit-like in contrast to the nipple indrawing and distortion seen in cancer. Bilateral multiduct green discharge is physiological and not related to duct ectasia. Surgery is indicated only if the discharge is troublesome. Surgery can evert the nipple but is not often performed. Duct ectasia should not be confused with periductal mastitis, which develops in younger women, mainly cigarette smokers, and is associated with recurrent subareolar infection.

Benign neoplasms and proliferations

Epithelial hyperplasia

Epithelial hyperplasia is an increase in the number of cells lining the terminal duct lobular unit. The degree of hyperplasia is graded as mild, moderate or florid (severe). If the hyperplastic cells also show cellular atypia, the condition is called atypical hyperplasia. Two types of atypical proliferation in the terminal duct lobular units are recognised. Lobular intraepithelial neoplasia (LIN) has loss of e-cadherin expression and incorporates both atypical lobular hyperplasia and lobular carcinoma in situ. Atypical ductal hyperplasia (ADH) or atypical intraductal epithelial hyperplasia (AIEDP) has expression of e-cadherin. The terminology does not indicate the site of origin as both lobular and ductal proliferations arise in the terminal duct lobular unit.

The absolute risk of breast cancer in a woman with AIEDP who does not have a first-degree relative with breast cancer is of the order of 8% at 10 years; for a woman with a first-degree relative with breast cancer, the risk is 20–25% at 15 years. Studies of chemoprevention with tamoxifen have shown that 5 years of tamoxifen at a dose of 20 mg per day can decrease the subsequent breast cancer risk of women with ADH by over 80%. A more recent study has demonstrated that tamoxifen is effective at a lower dose of 5 mg daily.

Learning point: Atypical intraductal epithelial proliferation in the terminal duct lobular unit is the only benign breast condition associated with a significantly increased risk of subsequent breast cancer, and appears to be a multipotent precursor.

Atypical epithelial proliferation on core needle biopsy

Atypical epithelial proliferations can produce indeterminate intraluminal calcifications that are visible on mammography and these calcifications can be the stimulus to perform a biopsy to determine their nature.

Rates of ‘upgrade’ from AIEDP cases diagnosed on core needle biopsy of indeterminate calcifications are up to 29% for DCIS and 9% for invasive carcinoma on subsequent excision. ,

For this reason, when AIEDP or LIN is diagnosed on core biopsy, consideration should be given to obtaining more tissue either by large-volume vacuum-assisted core biopsy as recommended by UK national guidelines or by excisional biopsy.

Ductal papillomas

These can be single or multiple. They are common and should be considered as aberrations rather than true benign neoplasms, as they show minimal malignant potential. They are characterised by epithelial fronds that have both the luminal epithelial and myoepithelial layers, supported by a fibrovascular stroma. The epithelial component can range from being completely benign to showing hyperplasia, metaplasia, atypical hyperplasia and in situ carcinoma.

Solitary intraductal papillomas are characteristically seen in subareolar ducts (within 5 cm of the nipple) in women aged 30–50 years and are the most common pathological cause of a bloody nipple discharge. Half of women with papillomas have bloody discharge while the others have a serous discharge. Microdochectomy or total duct excision in older women establishes the diagnosis and stops the discharge.

Papillomas are common abnormalities detected through breast screening. They are also sometimes visible on ultrasound performed in women with nipple discharge. As core biopsy cannot always differentiate reliably between benign and malignant papillomas, excision by a vacuum-assisted core device or with excision surgery is the current recommendation. Given the low malignant potential of these lesions and the accuracy of core biopsy, observation is a potential option for small papilloma lesions without atypia.

Multiple intraductal papilloma syndrome

This occurs with five or more clearly separate papillomas within a localised segment of breast tissue, usually in a peripheral location. These tend not to present with nipple discharge but as a palpable mass or are detected at screening. They are only associated with an increased risk of malignancy if there are areas of atypical hyperplasia. Repeated excision of papillomas in patients with multiple intraductal papillomas can result in significant breast asymmetry. One option in such patients is to excise these lesions with a vacuum-assisted core biopsy device. This provides sufficient material for the pathologist to assess that all excised lesions are benign. If surgery is required, excision of the affected duct system with an oncoplastic procedure to reshape the breast is preferable to mastectomy. Mastectomy should be considered as a last resort for multiple papilloma syndrome.

Juvenile papillomatosis is a rare condition seen in young women <30 years old and this condition usually causes a painless, mobile mass (similar to a fibroadenoma). Ultrasound findings are characteristic but somewhat non-specific, usually consisting of an ill-defined heterogeneous mass with multiple cystic areas most prominent at the periphery of the lesion. Pathologically there is a spectrum of benign proliferative changes in these lesions that vary in proportion from case to case. Treatment is by complete excision.

  • In juvenile papillomatosis long-term clinical follow-up is required only if there is:

  • a strong family history of breast cancer;

  • atypical change;

  • bilateral lesions;

  • multifocal lesions; or

  • recurrence.

Phyllodes tumours

The aetiology of phyllodes tumours is unknown. They are much less common than fibroadenomas (ratio of presentation 1:40 35 ). The age of onset is 15–20 years later than fibroadenomas. They can grow rapidly, sometimes producing marked distortion and cutaneous venous engorgement, which occasionally can lead to ulceration. The majority are benign in nature and feel like large fibroadenomas, and are diagnosed following core biopsy or excision. They are rarely fixed to skin or muscle. On cross-section they are more brownish in colour than fibroadenomas and can have areas of necrosis. Most diagnoses of phyllodes tumour are made on core biopsy before operation. The aim of surgery should be to remove benign phyllodes tumours with a clear but not wide microscopic margin. For benign phyllodes tumours re-excision is not recommended if the lesion has been removed intact but is close to one margin. Vacuum-assisted biopsy excision is also an option and has low rates of recurrence.

Current classification recognises benign, borderline and malignant phyllodes tumours. Differentiating these can be difficult and involves assessment of the size, ratio of stroma to epithelium, the border of the lesion, stromal cellularity, the number of stromal mitoses and the presence or absence of necrosis.

Overall, benign phyllodes tumours recur locally in less than 10% of patients. Most locally recurrent tumours are histologically similar to the original lesions, but occasionally benign phyllodes recur as borderline lesions. Malignant phyllodes tumours on average recur earlier than benign lesions. For borderline and malignant lesions, a microscopic margin of 1–2 cm is recommended. This may necessitate mastectomy in large lesions ( Fig. 3.2 ). Regional lymph node metastases are seen rarely in malignant phyllodes tumours, with nodes being affected in approximately 5%. Approximately 20% of those classified as malignant and 3% of those classified as borderline malignant phyllodes metastasise, depending on the exact criteria used for classification. , The most common site for metastasis is the lung, and patients who develop distant metastasis tend to have a poor clinical outlook, although the time that it takes for distant metastasis to develop can be very varied. Radiotherapy may have a role at reducing recurrence in malignant phyllodes tumours.

Figure 3.2, Ulcerated large borderline phyllodes tumour.

Lipomas

These soft, lobulated radiolucent lesions are common in the breast. Interest in these lesions lies in their confusion with pseudolipoma, a soft mass that can be felt around a breast cancer and that is caused by indrawing of the surrounding fat by a spiculated carcinoma.

Ultrasound is helpful in establishing whether a lesion is a lipoma. Biopsy or excision is indicated only if there has been rapid growth or if the lipoma is symptomatic.

Granular cell tumours

This is an uncommon, usually benign neoplasm that originates from Schwann cells of peripheral nerve sheath in the breast. About 6% of all granular cell tumours occur in the breast. The mean age at diagnosis is 40 years. Clinically and on imaging they are difficult to differentiate from a breast carcinoma due to their fibrous consistency, fixation to the pectoral fascia and skin retraction. Granular cell tumours are usually benign but malignant lesions have been described. Core biopsy can usually establish the diagnosis. Treatment is by local excision, ensuring a narrow clear margin to prevent recurrence.

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