Benign Conditions of the Breast

Lesson 6 of 18

While in low- and middle-income countries, patients are more likely to present with malignancy,
overall, the majority of breast conditions for which patients seek care will be benign. Patients may
present with a breast lump, breast pain, or nipple discharge, or they may have an imaging finding
that warrants further work up. It is important for the surgeon to have a solid understanding of
benign breast disease, even those conditions that do not require surgical intervention.

When we think about how to approach the discussion of benign breast diseases, it is important to
understand that some benign breast conditions specifically affect the epithelial tissue of the breast,
that is, the ductal and lobular tissue. We can classify these conditions by the time during which they
occur in the phases of change of the breast tissue, in which we think about them as aberrations of
normal breast development and involution (ANDI). Each ANDI disorder can also be thought of by
its histology. By this, we mean whether the cells are growing and proliferating and whether they are
atypical in their appearance. These features contribute to the malignant potential of each condition. 

Non-ANDI conditions, or those that are not specific to the epithelial tissues, include such
pathologies as infectious and inflammatory conditions and trauma.
Aberrations of Normal Breast Development and Involution
As discussed in the previous section, female breast tissue goes through three phases of change:
development and maturation, cyclical and lactational, and postmenopausal involution. Because of
the hormonal changes that occur, at each phase, the breast tissue may develop benign abnormalities,
or aberrations, related to the hormonal environment. These are collectively known as aberrations
of normal breast development and involution (ANDI), and this classification helps to associate
various conditions with the time in which they commonly occur. While most are managed
nonoperatively, some necessitate operation.
Normal Effects Abnormal Effects
1. Fibroadenoma or
giant fibroadenoma
1. Lobular growth and 2. Adolescent
hypertrophy hypertrophy or
2. Stromal growth and gigantomastia
Development and
hypertrophy 3. Nipple inversion,
Maturation
3. Nipple enlargement which if severe, may
and eversion lead to subareolar
abscesses and
fistulae

1. Cyclical mastalgia,
1. Cyclical menstrual which may become
changes severe, and breast
2. Lobular and ductal nodularity or cysts
Cyclical and Lactational
hyperplasia of and macrocysts
pregnancy 2. Bloody nipple
discharge

Postmenopausal Involution 1. Lobular and ductal 1. Sclerosing lesions,

involution and ductal ectasia
2. Epithelial turnover 2. Epithelial
hyperplasia with or
 Normal Effects Abnormal Effects
without atypia

While each of the above conditions is benign, some may have a higher risk of cancer development
than others. Thus, it is helpful to look at benign breast conditions based on their histological, or
pathological, characteristics, which helps us better understand which ones carry a higher risk of
malignant development. In this classification, each of the above conditions is grouped based on the
degree of proliferation, or growth and division, of the cells and the degree of atypia, or irregularity,
of the cells. These categories include: nonproliferative, proliferative without atypia, and atypical
hyperplasia.

A. Nonproliferative breast disease

Nonproliferative breast disease (NPBD) are a group of benign breast lesions in which there is no
excessive growth of cells and the cells are normal in their structure and appearance. While this
encompasses several lesions, here we will focus on cysts. When palpable, cysts are defined
as macrocysts. Microcysts are non-palpable and are part of the entity of cyclic nodularity, a
change in nodularity of the breast tissue that occurs with cyclic hormonal changes. Previously, this
spectrum of conditions, as well as some others, was known as fibrocystic disease. However, this is a
non-specific and unhelpful grouping and so has fallen out of favor as a term. It is best to be specific
about the condition or lesion being diagnosed.

Simple cysts of the breast

Breast cysts are the most common NPBD. They typically occur after the age of 35, are the most
common cause of breast lumps of women in their 40s, and are unusual after menopause. They
originate from the lobule and are well-circumscribed lesions that carry almost no risk of malignancy
(0.1%). These typically present as breast lumps, and Cysts can cause pain due to their size or
enlargement with fluid. 

Cysts are typically identifiable on ultrasound, and when symptomatic, can be aspirated to dryness.
Fluid does not need to be sent for cytology. If following aspiration, there is a persistent mass, this
should be biopsied. If the cyst recurs more than twice, it should also be biopsied. 

B. Proliferative lesions without atypia

Benign proliferative conditions without atypia are those in which there is an abnormal growth of
some particular cell type, but there is no cytological irregularity to the cells. While these conditions
are benign, the presence of some may increase the risk of developing breast cancer. Proliferative
lesions without atypia include:
a. fibroadenomas,
b. ductal hyperplasia without atypia,
c. intraductal papillomas,
d. radial scars, and
e. sclerosing adenosis.

Fibroadenomas and phyllodes tumors

+Fibroadenomas are benign solid tumors, composed mainly of the stroma and less of lobular or
ductal epithelium. They are the most common benign breast tumor, and account for about half of all
breast biopsies. They most commonly occur in women under age 25, and are typically 1-2 cm in in
diameter.
Fibroadenomas were historically considered nonproliferative lesions, but are now considered
proliferative. Because these tumors involve mostly stroma and not epithelial cells, for most women
there is no increased risk of breast cancer and the lesions themselves are benign. However, when
there is adjacent proliferative change, complexity to the fibroadenoma, or a family history of breast
cancer, they may indicate an increased cancer risk.

Similar to cysts, fibroadenomas are well-circumscribed, mobile masses, which appear on ultrasound
as solid ovoid, encapsulated masses. In a young patient (< 25) with a  mass that appears typical of a
fibroadenoma on ultrasound and is less than 2 cm, reassurance is appropriate without biopsy or
repeat imaging. However, the lesion require excision if it is symptomatic or creating anxiety, is
greater than 2 cm in size, or is enlarging.

Fibroadenomas are a type of fibroepithelial lesion. Fibroepithelial lesions occur on a spectrum

based on the degree of cellularity of the tissue involved. Whereas fibroadenomas involve mostly
stromal tissue with little cellularity, when tumors have increased cellularity of the stroma, we
classify them as phyllodes tumors. Phyllodes tumors may be benign, borderline, or malignant, and
tend to occur in older women. Highly cellular phyllodes tumors can even begin to resemble
sarcomas, hence their historic name of cystosarcoma phyllodes. If a biopsy shows a phyllodes
tumor, the mass should be excised. Benign or borderline lesions require only negative margins.
Malignant lesions should be excised with a 1-cm margin, which helps to prevent local recurrence.
However, mastectomy does not need to be performed unless the size of the tumor necessitates it,
and lymph nodes do not need to be removed.

The images below show a 2-cm fibroadenoma on ultrasound and post-excision. Note the well-
circumscribed, ovoid appearance of the solid mass.

Ductal hyperplasia without atypia

Ductal hyperplasia without atypia is typically an incidental pathologic finding in which there is an
increase in the cellular layers lining the lactiferous ducts. The cells are benign, and no further
treatment is necessary for this pathologic finding. Pathologist will sometimes call ductal hyperplasia
"usual ductal hyperplasia" when there is no atypia.

Intraductal papilloma
+Intraductal papillomas are polyps of the epithelial lining of the ducts and grow into the lumen.
They may be identified as a mass on imaging or they may present with bloody nipple discharge, due
to the friability of the proliferative tissue. They are the most common cause of unilateral bloody
nipple discharge. They may occur as a solitary lesion or multiple. While papillomas themselves are
benign, they may harbor atypia or ductal carcinoma in situ (DCIS), which will be discussed later.

When identified on core needle biopsy, especially if there is atypia, or when there is persistent
bloody nipple discharge, ductal excision is recommended.
Sclerosing adenosis
+Adenosis is a proliferation of the glandular tissue of the lobules. Sclerosing refers to a hardening
or fibrosis of the tissues. There is often a deposition of calcium within these cells, which creates the
appearance of microcalcifications. The proliferative nature of this lesion can create a mass on
imaging, and the appearance of microcalcifications, which is characteristic of DCIS or malignancy,
can make it appear suspicious for a malignancy on imaging. Once confirmed on biopsy, however,
no further treatment or intervention is necessary as it is a benign condition.

Radial scar

+A radial scar, another type of sclerosing lesion, is typically an incidental pathological finding in a
biopsy specimen. As with intraductal papillomas, radial scars are not malignant but may harbor
malignancy. As this may occur in 10-15% of specimens, it is recommended that, when identified on
core needle biopsy, a radial scar undergo excisional biopsy.

C. Atypical hyperplasia

Atypical hyperplasia can include either component of the epithelial tissue of the breast, meaning
there can be atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH). Recall that
atypia means the cells are irregular or abnormal in their appearance. These atypical cells share
some, though not all of the features of carcinomas in situ, and are commonly found in biopsy
specimens following an abnormal mammogram or for workup of a breast mass. Each of these
findings increase the risk of breast cancer, however, they are interpreted differently. 

Some women with atypical hyperplasia may be candidates for hormonal therapy with selective
estrogen receptor modulators, such as tamoxifen, or an aromatase inhibitor. While these
medications are used to treat breast cancers that express estrogen or progesterone receptors, they
may also be used to reduce the risk of breast cancer development in women with elevated risk. This
is known as primary prevention.

a. Atypical ductal hyperplasia

ADH seems to be a precursor lesion or represent a lower-grade form of low-grade DCIS. Further,
when ADH is identified on core needle biopsy, once the lesion is excised, there is a > 20%
likelihood of identifying DCIS within the pathologic specimen. For these reasons, it is
recommended to perform an excisional biopsy when ADH is identified on core biopsy.

b. Atypical lobular hyperplasia

Contrary to ADH, ALH does not seem to be a precursor to LCIS or breast cancer. Unless there are
other concerning imaging findings or a mass or a second pathologic finding that requires excision,
ALH does not need to be routinely excised. This is because the likelihood of finding a malignancy
within an excised pathologic specimen is low. Instead, ALH or LCIS indicate an elevated risk of
breast cancer in either breast in any location.

Infectious and Inflammatory Conditions

Mastitis and abscesses
Mastitis, cellulitis of the breast, and breast abscesses may occur in the peripartum timeframe,
known as a lactational infection, or may be non-lactational.

Lactational infections occur due to the trauma to the breast and introduction of skin bacteria, most
commonly Staphylococcus aureus. Breast milk provides an excellent culture medium for bacterial
growth.
Mastitis in a lactating woman.

Mastitis presents as any cellulitis, with warmth, erythema, pain and edema. Underlying abscess
should be ruled out by ultrasound. It is treated with antibiotics, and the mother should be
encouraged to continue breastfeeding during treatment.

For abscesses, aspiration, either by physical exam or by ultrasound, with culture and tailored
antibiotics, is the preferred approach to treatment.

In lactating women, surgical drainage is avoided due to the risk of creating milk fistula, a
potentially devastating complication that results in uncontrolled drainage of milk through the
wound. It is preferable to perform repeat aspirations in order to avoid surgical drainage. Incision
and drainage is reserved for large, loculated abscesses that are not amenable or do not respond to
aspiration.

Wound complications due to a milk fistula following drainage of an abscess in a lactating woman
can be devastating as shown here.

Non-lactational infections are often related to underlying conditions, most commonly heavy
smoking or diabetes. Infections are typically peri- or retroareolar. These can be difficult to manage,
as they often recur and require multiple courses of antibiotics. The patient should be strongly
advised to stop smoking, and good glucose control is important.

Any infection that fails to resolve, whether lactational or non-lactational, should raise suspicion for
underlying malignancy. A core needle biopsy should be performed to rule out malignancy or a
different diagnosis, such as mammary tuberculosis or idiopathic granulomatous mastitis.

Mammary tuberculosis
Mammary tuberculosis may mimic bacterial mastitis or malignancy, and should be considered in
the differential diagnosis in sub-Saharan Africa. Caseating granulomas may be seen on
histopathology following biopsy. Core biopsy with polymerase chain reaction (PCR) testing and
culture are the recommended method of diagnosis but may lack sensitivity. Treatment requires a
full course of medical therapy for tuberculosis, and subsequent surgical intervention is rarely
required.
Mammary tuberculosis may mimic malignancy. Note the multifocal granulomas in this case.

Idiopathic granulomatous mastitis

While similar in presentation to mammary tuberculosis, idiopathic granulomatous mastitis is an
inflammatory mastitis, not an infectious mastitis. Biopsy is necessary for diagnosis, and
histopathology shows histiocytes and relative paucity of necrosis. Treatment is with steroids.
Because steroids would worsen an infectious mastitis, including tuberculosis, it is important to
avoid misdiagnosis!

Mondor's disease
Mondor's disease is thrombophlebitis of a superficial vein of breast and anterior chest wall. The
diagnosis is based on the clinical presentation of a tender, cord-like structure or structures. Biopsy is
appropriate if there is an associated mass or if the diagnosis is unclear. Treatment consists of non-
steroidal anti-inflammatory drugs (NSAIDS) and warm compresses. Strongly consider a biopsy if
the condition fails to resolve in 4-6 weeks. If pathology is benign, excision of affected vein may be
considered.

Mondor's disease. Note the cord-like structure of the breast and anterior chest wall.

Fat necrosis
Fat necrosis is a breakdown of the fatty tissue of the breast that can result following trauma or
surgery. While not a risk factor for malignancy, it may cause a palpable mass or a density with
microcalcifications on imaging. Once the pathology is confirmed on biopsy, reassurance without
further intervention is all that is necessary.
Gynecomastia
As previously mentioned, gynecomastia is abnormal breast enlargement or development. Most
commonly, this term is used to indicate enlarged breast(s) in a male, though it can occur in infants
of either sex, where it is the result of maternal hormones crossing the placenta. Beyond infancy, in
men, it can occur in adolescence, where it is typically unilateral, or in senescence, or older age,
where it is typically bilateral. Gynecomastia is differentiated from pseudogynecomastia, which
is fat deposition in the breasts commonly seen in overweight or obese men. Gynecomastia will have
characteristic imaging findings, such as "flame-shaped" subareolar density on mammogram. 
Breast tissue in men has no lobular component but does have ductal tissue as well as adipose tissue.
Because the ductal tissue is most affected by estrogen, gynecomastia beyond infancy is the result of
elevated estrogen relative to testosterone, which can occur for a variety of reasons. In adolescence,
the issue is typically an elevation of estrogen, and it is most frequently unilateral. In senescence, it
is usually caused by decreased testosterone and is more commonly bilateral.

Gynecomastia in an adolescent male.

Gynecomastia is a normal but transient part of male puberty, and is normal for about 1-2 years.
However, its failure to resolve is pathologic. Common causes of gynecomastia include:

Medications/drugs - Medications and some recreational drugs are associate with gynecomastia,
including spironolactone, hormonal therapies for prostate disease, proton pump inhibitors, tricyclic
antidepressants, ketoconazole, phenytoin, marijuana, and anabolic steroids. These work by
increasing the synthesis or effect of estrogens or by decreasing the synthesis or effect of androgens.
Tumors - Testicular tumors such as Leydig cell or Sertoli cell tumors, adrenal tumors, pituitary
tumors, and lung cancers can all cause gynecomastia.
Systemic conditions - Gynecomastia is associate with liver cirrhosis, chronic renal failure,
malnutrition, hyper- and hypothyroidism, Klinefelter's syndrome (XXY genetic condition leading to
decreased testosterone) and testicular atrophy.
While many causes of gynecomastia can be reversed or should be treated medically, surgery should
be considered for patients without a reversible cause whose gynecomastia is symptomatic, when it
persists longer than 18 to 24 months in the adolescent male, when there are fibrotic changes to the
breast tissue, and when it occurs in the setting of Klinefelter's syndrome, because the low androgens
that cause of gynecomastia in Klinefelter's also put these patients at higher risk for breast cancer.
While gynecomastia is not a risk factor for breast cancer, a mass should be ruled out in the workup
of gynecomastia.
Algorithms for Common Breast Complaints
Patients do not present with a diagnosis; they present with a complaint. Most commonly for a
surgeon, that complaint will be a breast lump, nipple discharge, or abnormal imaging. When a
patient presents with an abnormal finding on imaging, it most frequently requires biopsy, with
further decision making based on the pathology identified. For a patient who presents with a breast
lump or nipple discharge, it is helpful to have a suggested algorithm to guide the workup.
Algorithm for workup of a palpable breast lump.

Algorithm for workup of nipple discharge.

Knowledge Check
Check your recall and understanding of the information presented above by answering the
following questions.
Fibroadenoma is an ANDI associated with which phase of change of the breast tissue?

Development and maturation

Cyclical and lactational
Postmenopausal involution
It is associated with all phases of breast tissue change

Which of the following categories of epithelial breast conditions has the highest malignant

potential?

Nonproliferative lesions
Proliferative lesions without atypia
Atypical hyperplasia
None of the above has malignant potential as they are all benign.
Which of the following bacteria is the most likely cause of lactational mastitis or abscess?

Strep epidermidis
Staph aureus
E. coli
It is most likely to be multibacterial.