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Overview of benign breast disease

Author
Michael S Sabel, MD Section Editor
Anees B Chagpar, MD, MSc, MPH Deputy Editor
Susan E Pories, MD, FACS

Last literature review version 17.1: January 2009 | This topic last updated: November 14,
2008 (More)

INTRODUCTION Benign breast disease represents a spectrum of disorders. Following


establishment of a benign diagnosis, treatment in general is aimed at symptomatic relief
and patient education. Some benign breast disease such as atypical hyperplasia, does
confer a moderate increase in the patient's future risk of developing breast cancer, and
should lead to counseling about screening recommendations and risk reduction strategies.
This topic will review the pathologic classification and treatment of benign breast disorders.
Evaluation of women presenting with symptoms related to the breast and diagnosis of
breast disorders are discussed separately. (See "Initial approach to the woman with breast
complaints" and see "Primary care evaluation of breast lumps" and see "Breast pain" and
see "Nipple discharge").

CLASSIFICATION OF BENIGN BREAST LESIONS Benign epithelial breast lesions


can be classified histologically into three categories: non-proliferative, proliferative without
atypia, and atypical hyperplasias. The categorization is based upon the degree of cellular
proliferation and atypia [1-10] . Non-proliferative lesions - Non-proliferative lesions, such as
simple cysts, do not increase a woman's risk of developing breast cancer [1] . Proliferative
lesions - Proliferative lesions of the breast without atypia, such as usual ductal hyperplasia,
or intraductal papillomas confer a small increase in the risk of developing breast cancer
(relative risk 1.6 to 1.9). This risk may be even smaller or not present in women with no or a
weak family history of breast cancer [4] . Fibroadenomas are now included in this category,
but it is important to note that the histologic features of the fibroadenoma influence the risk
of breast cancer. The risk of subsequent breast cancer is slightly elevated only if the
fibroadenoma is complex, there is adjacent proliferative disease or a family history of breast
cancer. For the majority of women with simple fibroadenomas, there is no increased risk of
developing breast cancer [2-5,11] . Atypical hyperplasias - Atypical hyperplasias, including
atypical ductal hyperplasia and atypical lobular hyperplasia, confer a moderate increase in
the risk of subsequent breast cancer (relative risk 3.7 to 5.3) [3,4,7,12] .

NONPROLIFERATIVE BREAST LESIONS Nonproliferative epithelial lesions are


generally not associated with an increased risk of breast cancer [1] . It should be noted that

terms such as fibrocystic changes, fibrocystic disease, chronic cystic mastitis, and
mammary dysplasia refer to nonproliferative lesions and are less useful clinically, as they
encompass a heterogeneous group of diagnoses [5,13] . The most common
nonproliferative breast lesions are breast cysts.

Breast cysts Cysts are fluid filled, round or ovoid masses derived from the terminal duct
lobular unit. Cysts are found in as many as one third of women between 35 and 50 years
old. Acute enlargement of cysts may cause severe, localized pain of sudden onset. Simple
cysts and complicated cysts are discussed here. Complex masses have a cystic
component, but are considered more suspicious for malignancy and are discussed
separately [14] . (See "Complex masses" below).

Simple cysts On ultrasound evaluation, simple cysts are circumscribed, anechoic, with
posterior acoustic enhancement, lack of Doppler signal, and absence of solid components.
Simple cysts are benign by definition and no intervention is necessary, although aspiration
is often performed to relieve pain; simple non-painful cysts identified on ultrasonography
need not be aspirated. The cyst should disappear with removal of the fluid and the patient
can be reassured. If the cyst does recur, a second attempt at aspiration is reasonable. If a
breast cyst recurs a third time, the patient should be evaluated by a surgeon for
consideration of excision [7] . If clear fluid is obtained on aspiration of a cyst, this can be
discarded, however if the fluid is bloody it should be sent for cytologic analysis. (See
"Primary care evaluation of breast lumps", section on Fine needle aspiration biopsy).

Complicated cysts Complicated cysts are defined as those meeting most, but not all,
criteria for simple cysts on ultrasound examination. This includes lesions with internal
echoes, fluid or debris levels, thin septations, a perceptible wall, or lack of posterior
acoustic enhancement. These lesions are rarely malignant (0.4 percent) but should be
aspirated to confirm diagnosis or followed with imaging [15] .

Complex cysts Complex cysts, also referred to as complex masses, contain mixed
cystic and solid components or an intracystic solid mass. Complex masses do require
biopsy. Core needle biopsy is utilized, if possible, and a clip must be placed to ensure that
the lesion can be localized to allow excision if the core biopsy is positive. These lesions
have a relatively high rate of cancer, ranging from 20 to 43 percent [14] .

PROLIFERATIVE BREAST LESIONS WITHOUT ATYPIA Proliferative lesions without


atypia are associated with a slightly increased risk of developing breast cancer,
approximately 1 to 2 times that of the general population [2,5,8,11,16-21] . As the risk of
subsequent breast cancer in this population is small, chemoprevention is not indicated.

Fibroadenomas Simple fibroadenomas - Simple fibroadenomas are benign solid tumors


containing glandular as well as fibrous tissue. They usually present as a well-defined,
mobile mass. In 20 percent of cases, multiple fibroadenomas occur in the same breast or
bilaterally. The etiology is not known; a hormonal relationship is likely since they persist
during the reproductive years, can increase in size during pregnancy or with estrogen
therapy, and regress after the menopause. They are most commonly found in women
between the ages of 15 and 35 years [22] . Although originally classified as nonproliferative lesions, fibroadenomas are now considered proliferative breast lesions [11] .
However, it is important to note that the histologic features of the fibroadenoma influence
the risk of breast cancer. The risk of subsequent breast cancer is slightly elevated only if
the fibroadenoma is complex, there is adjacent proliferative disease or a family history of
breast cancer. For the majority of women with simple fibroadenomas, there is no increased
risk of developing breast cancer [2-5,11] .
The diagnosis of fibroadenoma is best confirmed with a core biopsy or excisional biopsy.
Most surgeons recommend a core biopsy to make the diagnosis. Ultrasound alone or fine
needle aspiration (FNA) cannot differentiate between a fibroadenoma and a phyllodes
tumor. While phyllodes tumors may appear similar to fibroadenoma on ultrasound, they are
unusual fibroepithelial tumors characterized by rapid growth. Phyllodes tumors will require
more extensive surgical resection and in some cases will require radiation treatment as
well. Phyllodes tumors are discussed elsewhere in detail. (See "Primary nonepithelial
breast malignancies").
It is not necessary to excise all fibroadenomas. If the biopsy proven fibroadenoma is
asymptomatic, then it can be left in place, although some women wish to have the lump
excised so that they will not worry further. After confirming the pathologic diagnosis, shortterm follow-up (six months) with ultrasound is recommended to assure stability. Most
fibroadenomas will get smaller over time and can be left in place unless they increase in
size, are symptomatic, or the patient desires excision [23-25] . Disadvantages of excisional
surgery include scarring at the incision site, dimpling of the breast from the removal of the
tumor, damage to the breast's duct system, and mammographic changes (eg, architectural
distortion, skin thickening, increased focal density).
The technique of cryoablation has been utilized as an alternative to surgical excision of
fibroadenomas, after a core biopsy diagnosis has been made [23,24,26] . A multicenter trial
of 50 patients who underwent office-based cryoablation under ultrasound guidance
reported the lesions tended to disappear progressively [24] and 75 percent were not
palpable at 12 months follow-up [26] . Transient side effects included ecchymosis, local
swelling, and discomfort that lasted as long as a few weeks after treatment. Percutaneous
vacuum-assisted ultrasound-guided excision is another alternative to open excision
technique for removal of fibroadenomas, but may be less effective for lesions >2 cm [27] .
Giant fibroadenomas - Giant fibroadenomas refer to fibroadenomas over 10 cm in size.
Excision is recommended. The primary challenge for the pathologist is to exclude these
from phyllodes tumors. (See "Primary nonepithelial breast malignancies"). Juvenile
fibroadenomas - Juvenile fibroadenomas are a variant of fibroadenoma found in young
women between the ages of 10 and 18. They vary in size from 5 to 20 cm in diameter.
These are usually painless, solitary, unilateral masses that grow rapidly. Juvenile
fibroadenomas are distinguished from adult fibroadenomas by exhibiting more glandularity
and greater stromal cellularity. Excision is recommended as these tumors can cause
discomfort, anxiety, and breast asymmetry [28] . Complex fibroadenomas - Complex
fibroadenomas contain other proliferative changes, such as sclerosing adenosis, duct

epithelial hyperplasia, epithelial calcification, or papillary apocrine changes [29] . They are
associated with a slightly increased risk of cancer when multicentric proliferative changes
are present in the surrounding glandular tissue.
Appropriate management of complex fibroadenomas is controversial. While some believe
that complex fibroadenomas warrant complete removal for histological examination, others
suggest that they can be managed conservatively following core biopsy [29] . In one series
of 401 fibroadenomas, 63 (15.7 percent) were considered complex. At a mean follow-up of
two years, invasive carcinoma was found in only one of the 63 patients with complex
fibroadenomas; her initial core biopsy had shown atypical lobular hyperplasia.

Usual ductal hyperplasia Ductal hyperplasia without atypia is characterized by an


increased number of cells within the ductal space; although the cells vary in size and
shape, they retain the cytological features of benign cells [5,6] . No additional treatment is
needed for ductal hyperplasia. The risk of subsequent breast cancer in women with usual
ductal hyperplasia is modest and chemoprevention is not indicated.

Papilloma Solitary intraductal papillomas may present as a breast lump, a nodule on


ultrasound, or may be the cause of nipple discharge and can be seen on ductography [30] .
(See "Nipple discharge"). Solitary papillomas consist of a monotonous array of papillary
cells that grow from the wall of a cyst into its lumen.
Solitary papillomas can harbor areas of atypia or ductal carcinoma in situ (DCIS). Although
there is some debate in the literature, the standard recommendation for management of
papillomas is that they be excised whenever they are diagnosed by core needle biopsy [3135] .
Once the diagnosis of solitary papilloma is confirmed by excisional biopsy, no additional
treatment is needed. Unless there is associated atypia, there is no increased risk of
subsequent breast cancer.

Multiple papillomas Diffuse papillomatosis


minimum of five papillomas within a localized
excision, additional treatment is not needed
subsequent breast cancer in women with
chemoprevention is not indicated.

(multiple papillomas) is defined as a


segment of breast tissue [36,37] . After
for diffuse papillomatosis. The risk of
diffuse papillomatosis is modest and

Sclerosing adenosis Sclerosing adenosis is a lobular lesion with increased fibrous


tissue and interspersed glandular cells. It can present as a mass or a suspicious finding on
mammogram [38,39] . No additional treatment is needed for sclerosing adenosis. The risk
of subsequent breast cancer in this population is modest and chemoprevention is not
indicated.

Radial scars Radial scars are usually discovered incidentally when a breast mass is
removed for other reasons; occasionally they are large enough to be detected by
mammography, which cannot reliably differentiate between these lesions and spiculated
carcinoma [40-43] . Radial scars are characterized microscopically by a fibroelastic core
with radiating ducts and lobules.
When radial scars are found on core biopsy, the entire lesion must be excised. In addition
to the possibility of finding an unrecognized in situ or invasive component, there is some
evidence that radial scars are premalignant lesions that can slowly progress from scar to
hyperplasia to carcinoma over time [44] . No additional treatment is needed for radial scars.
The risk of subsequent breast cancer in this population is modest and chemoprevention is
not indicated.

ATYPICAL HYPERPLASIAS Proliferative lesions with atypia include atypical ductal


hyperplasia (ADH) and atypical lobular hyperplasia (ALH). ADH and ALH are often referred
to as atypical hyperplasia (AH). Patients with this diagnosis on core biopsy need excisional
biopsy to confirm the diagnosis. They are counseled about risk reduction strategies,
including close screening, avoidance of adjuvant hormone use, avoidance of heavy alcohol
use, and consideration of chemoprevention of breast cancer with tamoxifen or raloxifene.
Flat epithelial atypia is a separate entity. (See "Flat epithelial atypia" below).

Atypical hyperplasia AH is a specific lesion of either ductal or lobular elements with


uniform cells and loss of apical-basal cellular orientation. The relative risk of invasive breast
cancer associated with AH ranges from three to six-fold [3,45-47] . Multifocal lesions,
especially those associated with calcification, increase risk 10-fold [47] .
AH is associated with an increased risk of contralateral breast cancer and thus provides
evidence of underlying breast abnormalities that predispose to breast cancer [4] . In a
report from the Nurses' Health Study, only 56 percent of cancers that developed in women
with AH occurred in the ipsilateral breast [46] . The cumulative incidence of breast cancer
over 30 years approached 35 percent. Data on the effect of family history of breast cancer
in women with atypical hyperplasia are conflicting [48] .
Women who have atypical hyperplasia on core biopsy always require surgical excision.
Analysis of more extensive tissue removed at the time of surgery results in an upgrade in
diagnosis to ductal carcinoma in situ (DCIS) in up to 50 percent of cases [49,50] . Most
revisions in pathologic diagnosis are due to the presence of DCIS or invasive carcinoma
[50,51] . (See "Breast ductal carcinoma in situ and microinvasive carcinoma").

Risk reduction strategies Women with AH are counseled regarding risk reduction
strategies. Ongoing surveillance with yearly mammography and twice yearly breast exams
is appropriate [2,8,11,16-19] . Women with AH should stop taking birth control pills and
avoid hormone replacement therapy. Tamoxifen or raloxifene may be considered in women
with AH for breast cancer risk reduction, although the risks and side effects must be
discussed thoroughly [52-54] . The Gail breast model incorporates atypical proliferative
disease into a risk calculation that can be used to identify women who are appropriate
candidates for breast chemoprevention. (See "Selective estrogen receptor modulators for

the prevention of breast cancer" and see "Epidemiology and risk factors for breast cancer"
and see "Patient information: Tamoxifen and raloxifene for the prevention of breast
cancer").

Flat epithelial atypia Flat epithelial atypia, also referred to as columnar cell change with
atypia, columnar cell hyperplasia with atypia, or clinging carcinoma, is usually diagnosed on
breast biopsies done for calcifications. When diagnosed on a core needle biopsy specimen,
excision should be performed as about one-third of cases will show a more advanced
lesion. The relationship between flat epithelial atypia and cancer is still being defined, but
the available data suggest that the risk of local recurrence or progression to invasive
cancer is low [55] .

Lobular carcinoma in situ Women with lobular carcinoma in situ (LCIS) have a
significantly increased risk of breast cancer and require referral to a specialist for a full
discussion of treatment options. This topic is discussed separately. (See "Lobular
carcinoma in situ").

MISCELLANEOUS BENIGN LESIONS OF THE BREAST


Lipoma Breast lipomas are benign, usually solitary tumors composed of mature fat
cells. These present as soft, non tender, well circumscribed masses. Clinically, it is
sometimes difficult to distinguish lipomas from other conditions; the diagnosis can be
confirmed with a core or excisional biopsy. Core biopsies are somewhat problematic for
lipomas as it is difficult to be certain that the diagnosis is concordant and lipomas should be
surgically excised if they cause diagnostic confusion, continue to enlarge or grow rapidly [6]
. For smaller lesions, excisional biopsy is often preferable.There is no increased risk of
subsequent breast cancer associated with lipomas.

Fat necrosis Fat necrosis of the breast is a benign condition that most commonly
occurs as the result of breast trauma or surgical intervention. Fat necrosis can be confused
with a malignancy on physical exam and may also mimic malignancy on radiologic studies.
It is sometimes necessary to biopsy these lesions to confirm the diagnosis, although
experienced radiologists can usually determine that a lesion represents fat necrosis on the
basis of mammographic and ultrasound findings such as oil cysts [6,56] . Once diagnosis is
established, excision is not necessary and there is no increased risk of subsequent breast
cancer.

Diabetic mastopathy Diabetic mastopathy is most commonly seen in premenopausal


women who have longstanding type 1 diabetes mellitus. The typical presentation is a
suspicious breast lump with a dense mammographic pattern. Core biopsy is recommended
for diagnostic confirmation. Pathology shows dense keloid-like fibrosis and periductal,
lobular, or perivascular lymphocytic infiltration [57-59] . Once the diagnosis is established,
excision is not necessary and there is no increased risk of subsequent breast cancer.

Galactocele Galactoceles (milk retention cysts) are cystic collections of fluid, usually
caused by an obstructed milk duct. At mammography, galactoceles may appear as an
indeterminate mass, unless the classic fat-fluid level is seen. Ultrasound may show a
complex mass. Diagnosis can be made on the basis of the clinical history and aspiration,
which yields a milky substance [60] . Once diagnosis is established, excision is not
necessary and there is no increased risk of subsequent breast cancer. (See "Common
problems of breastfeeding in the postpartum period").

Hamartoma Hamartomas are benign lesions, also known as fibroadenolipoma,


lipofibroadenoma, or adenolipoma. Hamartomas have varying amounts of glandular,
adipose, and fibrous tissue. They present as discreet, encapsulated, painless masses or
are found incidentally on screening mammography. The diagnosis can be difficult to make
with limited tissue as hamartomas do not have specific diagnostic features. Coincidental
malignancy can occur; excision is recommended for this reason [6] .

Adenoma Adenomas are pure epithelial neoplasms of the breast. They are
distinguished from fibroadenomas by their sparse stromal elements. Adenomas are divided
into two main groups; tubular and lactating adenomas. Lactating adenomas occur
commonly in pregnancy. They are well circumscribed and lobulated. Although they may
require excision because of their size, they do not have malignant potential [5,6] .

Idiopathic granulomatous mastitis Idiopathic granulomatous mastitis (IGM) is an


inflammatory mass in the breast. Patients typically present with a firm breast mass, often
associated with inflammation of the overlying skin. Nipple retraction, peau d'orange like
changes, and axillary adenopathy may be present [57,61-63] . The symptoms may be
mistaken for non-puerperal mastitis, a breast abscess, or most often, carcinoma. The
radiologic findings of IGM, like the physical findings, are worrisome for malignancy [58,6468] . Biopsy is necessary to make a diagnosis. IGM is a diagnoses of exclusion, as there
are several processes, such as sarcoidosis or tuberculosis of the breast, that may also
induce a granulomatous mastitis. When IGM is suspected, the biopsy specimen should be
sent for acid fast bacilli and fungal stains in addition to pathology.
While antibiotics are often initiated during the work-up, they will have little impact on true
cases of IGM. For the asymptomatic patient, excision is not necessary and observation
alone is a reasonable option. For symptomatic patients with localized disease, excision is a
reasonable option if the entire area can be excised with minimal cosmetic impact [69] .
Steroid therapy is sometimes considered for symptomatic patients, based on the idea that
this is an autoimmune disease [65] . There is no increased risk of subsequent breast
cancer associated with IGM.

Pseudoangiomatous stromal hyperplasia Pseudoangiomatous stromal hyperplasia


(PASH) may present as a mass on physical exam or radiologic studies. PASH is a benign
stromal proliferation which is found as an incidental microscopic finding in as many of 25
percent of breast biopsy specimens. The histologic appearance is characterized by
anastomosing slit-like empty spaces lined by spindle cells.

PASH is benign, but should be distinguished from a malignancy and is often confused with
mammary angiosarcoma [6,70] . If there are any suspicious features on imaging, the
diagnosis of PASH on a core biopsy should not be accepted as a final diagnosis and
excisional biopsy should be performed. However, in the absence of suspicious imaging
characteristics, a diagnosis of PASH at core biopsy is considered sufficient, and surgical
excision is not always necessary [71] . There is no increased risk of subsequent breast
cancer associated with PASH.

Sarcoidosis Breast symptomatology in sarcoidosis is rare and seen primarily in patients


with systemic involvement. Sarcoidosis of the breast presents as firm hard masses,
mimicking carcinoma. The mammographic appearance is also suspicious with irregular ill
defined, spiculated masses that are solid on ultrasound. Biopsy is needed for confirmation
of diagnosis [67,72] . There is no increased risk of subsequent breast cancer associated
with sarcoidosis of the breast.

COMPLEX MASSES Complex masses with mixed cystic and solid components or an
intracystic solid mass require biopsy. Core needle biopsy is utilized, if possible, and a clip is
placed to ensure that the lesion can be localized to allow excision if the core biopsy is
positive. These lesions have a relatively high rate of cancer, ranging from 20 to 43 percent
[15] .

NIPPLE DISCHARGE Discharge is considered pathologic if it is spontaneous,


persistent, or arises from a single duct. It is also pathologic if the discharge contains gross
or occult blood. This topic is discussed in detail separately. (See "Nipple discharge").

BREAST PAIN Breast pain is classified as cyclical (ie, related to the menstrual cycle),
noncyclical, or extramammary. Breast cancer may present as breast pain, thus a breast
examination is indicated. Younger women (< 30 years of age) with complaints of cyclical
diffuse breast pain who are at no increased risk for breast cancer and have a normal breast
examination should have a follow up examination scheduled in two to three months to
confirm the initial impression of normalcy. For women who have localized breast pain, an
increased risk of breast cancer or an abnormal breast exam, further evaluation with a
targeted breast ultrasound and mammography is indicated. In general however,
mammography is not effective or useful for women under the age of 30 as breast tissue in
this age group is normally very dense. This topic is discussed in detail separately. (See
"Breast pain").
Cyclical breast pain occurs in about 60 percent of premenopausal women, and historically
had been attributed to "fibrocystic breast changes," a term that is no longer considered
helpful as it encompasses normal and benign breast conditions (see "Classification of
benign breast lesions" above). Symptomatic relief may be achieved with the use of a soft
brassiere with good support, acetaminophen, and/or a nonsteroidal antiinflammatory drug.

The role of diet and lifestyle in relieving cyclical breast pain is unclear, with a strong
likelihood of a placebo response for many interventions. A low fat (15 percent of calories),
high complex carbohydrate diet has been effective in some observational studies [73,74] .
Elimination of caffeine has not been effective in controlleld trials [75-78] , although it seems
to be helpful in some women. Inconclusive evidence exists for the role of vitamin E [79] and
evening primrose oil [80] in reducing pain. Hormone replacement therapy can cause breast
pain and this should be discontinued if at all possible [81] .
For patients with more severe mastalgia, tamoxifen 10 mg can provide breast pain relief
[82] , although this medication is associated with side effects including include menopauselike symptoms such as hot flashes, vaginal dryness, joint pain, and leg cramps. Tamoxifen
also increases the risk of blood clots, strokes, uterine cancer, and cataracts. (see "Use of
selective estrogen receptor modulators in postmenopausal women"). Tamoxifen has not
been approved by the US Food and Drug Administration for treatment of breast pain and is
infrequently used for this indication. Several other drugs that affect estrogen or prolactin
secretion (including danazol, bromocriptine, and GNRH agonists) have been studied [8385] , but are not advocated for use in patients with severe mastalgia because of significant
side effect profiles.

SUMMARY AND RECOMMENDATIONS Benign breast lesions can be classified into three
categories on the basis of histologic findings: non-proliferative, proliferative without atypia,
and atypical hyperplasias. (See "Classification of benign breast lesions" above).
Nonproliferative lesions are not generally associated with an increased risk of breast
cancer. Management is directed at making a definitive diagnosis and providing relief of
symptoms. (See "Nonproliferative breast lesions" above). Proliferative disease without
atypia is associated with a slightly increased risk of subsequent breast cancer. Once the
diagnosis is established, no additional treatment is indicated. (See "Proliferative breast
lesions without atypia" above). Atypical hyperplasia is associated with a moderate increase
in risk of subsequent breast cancer. These women should be monitored closely and
counseled regarding risk reduction strategies. (See "Atypical hyperplasia" above).
Papillomas, radial scars, atypical hyperplasia or flat epithelial atypia when diagnosed on
core biopsy should be excised to ensure accuracy of diagnosis. (See "Papilloma" above
and see "Radial scars" above and see "Atypical hyperplasia" above and see "Flat epithelial
atypia" above). Core biopsy, rather than fine needle aspiration, should be performed on
complex cystic masses to ensure accurate diagnosis. We recommend clip placement to
mark the biopsy site. (See "Complex masses" above).

ACKNOWLEDGEMENT The authors and editorial staff at UpToDate, Inc. would like to
acknowledge Richard J Santen, MD for his contributions to previous versions of this topic.

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES


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