Benign Breast Conditions

Benign breast epithelial lesions are grouped histologically as nonproliferative, proliferative without atypia, and atypical hyperplasia. The classifications are based on subsequent cancer risk in either breast. The nonproliferative type carries no risk, while fibroadenoma, the most common benign tumor, is a proliferative breast lesion (i.e., has a slight increase in malignancy risk). Because atypical hyperplasia shares some features with breast carcinoma in situ, future cancer potential is increased. Management ranges from frequent monitoring to surgical excision, depending on certain factors, including the inherent risk of the pathologic diagnosis. Other breast disorders without malignant possibility are associated with underlying infection or systemic disease, so treatment differs. Benign breast diseases are common but present diversely. It is important to distinguish between them to determine the likelihood of cancer and the best course of treatment.

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Nonproliferative Epithelial Breast Lesions

Definition

Nonproliferative breast lesions are conditions generally not associated with an increased risk of breast cancer.

Simple breast cyst

  • Round or oval fluid-filled masses from the terminal duct lobular unit
  • Epidemiology:
    • Prevalence: estimated to be 50%90%
    • Up to ⅓ of women aged 3050 have breast cysts
  • Clinical presentation:
    • Felt as a palpable mass
    • Pain noted with acute enlargement of cyst
  • Diagnosis:
    • Ultrasonography (US): 
      • Differentiates masses (solid, fluid-filled, or with mixed elements)
      • Simple cyst: well-circumscribed, anechoic, with no solid components
    • Mammogram: oval or round shape with circumscribed margins
  • Management:
    • No further intervention most of the time
    • Fine needle aspiration
      • For signs of infection or inflammation 
      • Pain from increased size

Mild hyperplasia of the usual type

  • Pathology
    • Cells look very close to normal. 
    • An increase in the number of epithelial cells within a duct
    • Cell depth is more than 2 but not more than 4 cells.
  • Clinical presentation: found on biopsy or surgical excision
  • Management: no treatment needed

Papillary apocrine change

  • Pathology
    • Proliferation of ductal epithelial cells with apocrine features
    • May be simple, complex, or highly complex lesions 
  • Clinical presentation: found on histological examination (biopsy or surgical excision)
Breast USG

Breast US shows a simple cyst (A) presenting as an anechoic lesion with posterior enhancement and a cyst (B) with a septum (arrow). Breast US (C) in a 26-year-old woman with a painless palpable lump in her left breast shows a complex cyst with an eccentrically placed echogenic focus (arrow) representing the scolex of a cysticercus granuloma. The patient also had a similar swelling in the right upper arm, a US (D) of which revealed a cyst (arrow) with an echogenic scolex (arrowhead), within.

Image: “Breast USG” by Advanced Radiology Centre, Mumbai, India. License: CC BY 2.0

Proliferative Epithelial Lesions without Atypia

Definition

In proliferative breast lesions without atypia, the development of breast cancer is 1.5–2 times the risk of the general population.

Intraductal papilloma

  • Benign mass with a papillary configuration of breast stroma and epithelium within a breast duct
  • Epidemiology:
    • Peak incidence: 3050 years of age
    • < 10% of benign breast lesions
    • High-risk precursor lesion with the following predisposing factors:
      • Contraceptive use
      • Hormone replacement therapy
      • Family history of breast cancer
  • Clinical presentation: depends on the size and location
    • Central type:
      • Frequently a solitary mass, close to or behind the nipple within principal lactiferous ducts
      • Usually large enough to be palpated
      • Unilateral serous or bloody nipple discharge: a common presentation
      • Mostly benign
    • Peripheral type: (10% of cases)
      • Often appears as multiple papillomas and affects younger premenopausal women 
      • Found on the outer areas of the breast (growth in terminal ducts)
      • Usually non-palpable and less likely to have discharge
      • Appears as mammographic calcifications
      • Increased risk for breast cancer
  • Diagnosis:
    • Mammography: 
      • Can be occult
      • When seen, oval/round mass; margins can be ill-defined
      • May have calcifications
    • Core needle biopsy (CNB) (guided by ductogram or US):
      • Preferred over fine needle biopsy (risk of inadequate tissue sample)
      • Shows papillary cells with a central branching fibrovascular core
  • Management: 
    • Surgical excision/lumpectomy with complete removal: due to risk of atypical ductal hyperplasia or ductal carcinoma in situ (DCIS)
    • Annual breast exam and mammogram

Simple fibroadenoma

  • A benign solid breast mass composed of fibrous and glandular tissue
  • Epidemiology:
    • Most common benign tumor of the breast
    • Peak incidence: 1535 years of age
    • For majority, no potential for cancer
    • Risk factors of subsequent cancer:
      • Proliferative histology
      • Complex mass 
      • Family history of breast cancer
  • Clinical presentation:
    • Small, well-defined, spherical, mobile mass 
    • Rubbery or firm consistency, non-tender
    • Size: usually ≤ 3 cm in diameter, solitary
    • Location: often in the upper outer quadrant
    • Mass size and tenderness influenced by estrogen levels:
      • Increased size: pregnancy, lactation, pre-menstruation, and oral contraceptives
      • Regresses after menopause
  • Diagnosis:
    • US: well-defined solid mass, regular boundaries, and a weak echo signal
    • Mammogram: 
      • Well-circumscribed oval mass, may have lobulations
      • Popcorn-like calcifications in involuting fibroadenomas
    • Biopsy:
      • Indications: 
        • > 5 cm or increasing size
        • Irregular borders 
        • Considerable pain
      • Cytology: uniformly distributed epithelial cells (honeycomb or antler-like pattern)
      • Microscopy: stroma and epithelial cells either in pericanalicular or intracanalicular pattern
    • MRI: may have dark internal septations
      • T1: iso- or hypointense to normal parenchyma
      • T2: varies with amount of myxoid or fibrous elements
  • Management:
    • Fibroadenoma with benign features: observation, breast exam, and annual mammogram
    • Cryoablation: an option for small but symptomatic fibroadenomas 
      • CNB done first to confirm diagnosis
      • Criteria:
        • For fibroadenomas < 4 cm in size, < 3 in number
        • No bleeding tendency and no local skin infection 
    • Surgical excision for: 
      • Adolescent-onset fibroadenoma persisting through adulthood (risk of breast cancer increases)
      • Increase in size or with atypical features or symptoms

Related videos

Radial scars

  • Complex sclerosing lesions
  • Clinical presentation: 
    • Incidental finding in a biopsy done for other reason
    • If large, seen in mammogram as an architectural distortion
  • Pathology: fibroelastic core with radiating ducts and lobules
  • Management: surgical excision as lesions may be premalignant (up to 17% have malignancy)

Sclerosing adenosis

  • Enlarged and distorted lobules (milk-producing sacs) with stromal fibrosis and interspersed glandular cells
  • Clinical presentation: felt as a palpable mass
  • Diagnosis
    • Mammogram: calcifications, well-circumscribed to spiculated mass
    • CNB
  • Management
    • Small risk of subsequent malignancy
    • Observation with annual breast exam and mammogram

Usual ductal hyperplasia

  • Pathology: increased cells in ductal space or lobule (without atypia)
  • Clinical presentation: seen incidentally on biopsy or as calcifications on mammogram
  • Management:
    • Small risk of subsequent malignancy
    • Observation with annual breast exam and mammogram
Ductal hyperplasia

Usual ductal hyperplasia after review. Note the epithelial cells displaying a haphazard orientation and the presence of slit-like secondary lumina peripherally located.

Image: “Usual ductal hyperplasia” by Breast Pathology Laboratory, School of Medicine, Federal University of Minas Gerais (UFMG), Av, Professor Alfredo Balena, 190, Belo Horizonte, Minas Gerais 30130-100, Brazil. License: CC BY 2.0

Benign Epithelial Breast Lesions with Atypical Hyperplasia

Atypical ductal hyperplasia (ADH)

  • Found in 5%20% of breast biopsies
  • Moderate increase in breast cancer risk
  • Clinical presentation: too small for palpation, discovered incidentally on biopsy (for mammographic findings such as calcifications)
  • Diagnosis: 
    • CNB
    • Pathology: proliferation of monomorphic epithelial cells in the breast duct
    • Shares features of low-grade DCIS without meeting full criteria
  • Management: 
    • Surgical excision: standard of care (ADH is premalignant) 
    • Breast exam every 612 months and annual mammogram
    • Avoid hormone replacement therapy, oral contraceptives
    • Lifestyle and dietary changes
Atypical ductal hyperplasia

Atypical ductal hyperplasia (arrows)

Image: “Atypical ductal hyperplasia” by Breast Pathology Laboratory, School of Medicine, Federal University of Minas Gerais (UFMG), Av, Professor Alfredo Balena, 190, Belo Horizonte, Minas Gerais 30130-100, Brazil. License: CC BY 2.0

Atypical lobular hyperplasia (ALH)

  • Increased risk of developing breast cancer in either ipsilateral or contralateral breast
  • Clinical presentation: discovered incidentally on biopsy (for mammographic findings such as calcifications)
  • Diagnosis:
    • Pathology: Within the acini of terminal duct lobular unit, there is over-proliferation of dyshesive epithelial cells.
    • Shares features of lobular carcinoma in situ or invasive lobular carcinoma without meeting full criteria
  • Management:
    • Surgical excision is generally appropriate but not routine.
    • Excision for high-risk patients (family/personal history of breast cancer, BRCA1 or BRCA2 mutation)
    • In carefully selected lower-risk patients: 
      • Estrogen receptor modulators
      • Increased mammogram and follow-up frequency 
    • Risk-reduction measures: 
      • No hormone replacement therapy, oral contraceptives
      • Lifestyle and dietary changes
Atypical lobular hyperplasia

Photomicrograph of atypical lobular hyperplasia associated with columnar cell changes and incidental to targeted microcalcifications

Image: “Atypical lobular hyperplasia” by Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. License: CC BY 3.0

Flat Epithelial Atypia

  • A distinct lesion from ADH and ALH 
  • Flat growth pattern (does not meet architectural criteria of ADH)
  • High-risk or atypical breast lesion but risk remains undefined
  • Clinical presentation: discovered on biopsies done for mammographic calcifications
  • Diagnosis: pathology characterized by columnar changes with atypia
  • Management:
    • Surgical consultation with risk assessment
    • Observation is an option along with frequent exam and mammogram.
Flat epithelial atypia

Columnar cell lesions with atypia (flat epithelial atypia)

Image: “Flat epithelial atypia” by Department of Pathology, Wilford Hall Medical Center, Lackland AFB, TX, USA. License: CC BY 2.0

Breast Abscess

  • Epidemiology: usually associated with mastitis 
    • Known risk factors (in lactating women): 
      • Age > 30 years
      • Primiparous
      • Late delivery
      • Smoking
    • Known risk factors (in non-lactating women):
      • African American
      • Obesity 
      • Diabetes 
      • Smoking
  • Clinical presentation:
    • Unilateral and fluctuant mass
    • Painful, erythematous, and edematous breast 
    • Possible purulent discharge from the nipple
    • Fever
  • Diagnosis:
    • Clinical: history and findings of a fluctuant, tender, palpable mass 
    • Nipple discharge: Culture may help guide choice of antibiotic. 
    • Ultrasound: ill-defined hypoechoic collection with internal septations
    • Needle aspiration reveals purulent contents. 
  • Management:
    • Incision and drainage especially: 
      • If with skin ischemia or pressure necrosis
      • If needle aspiration and/or antibiotics fail
    • Needle aspiration:
      •  Can be an initial treatment if overlying skin is not ischemic or abscess(es) < 3 cm
      • Repeated every 23 days until there is no collection
    • Antibiotics that target most common causative agent, Staphylococcus aureus: cephalexin, dicloxacillin, or amoxicillin-clavulanate
Breast abscess

Sonogram of a 22-year-old woman showing a right breast abscess. Note the oval shape of the abscess, which measures 2.64 cm by 1.54 cm before aspiration under ultrasound guidance.

Image: “Breast abscess” by Department of Surgery, Weil Bugando University College of Health Sciences, Mwanza, Tanzania. License: CC BY 2.0

Miscellaneous Breast Lesions

Diabetic mastopathy

  • Lymphocytic mastopathy or lymphocytic mastitis
  • May be due to secondary autoimmune reaction from effects of hyperglycemia on connective tissue
  • Seen in up to 13% of patients with diabetes mellitus type 1
  • Clinical presentation: painless mass, seen in long-standing diabetes mellitus type 1
  • Diagnosis: 
    • Mammogram: solid mass with asymmetric density
    • Ultrasound: irregular hypoechoic mass
    • CNB
  • Management: 
    • Excision not needed as there is no increased risk for breast cancer
    • Known to recur after surgical removal
    • Annual mammogram

Sarcoidosis

  • Seen in patients with systemic sarcoidosis but mammary involvement can be the sole manifestation
  • Clinical presentation: firm breast masses
  • Diagnosis:
    • Mammogram: irregular, ill-defined masses
    • CNB: noncaseating granulomas
  • Management: 
    • Glucocorticoids
    • Surgical excision an option

Galactocele

  • A retention cyst within the mammary gland containing milk 
  • An obstruction of a lactiferous duct → accumulation of epithelial cells and milk → distention of the duct → cyst formation
  • Epidemiology: most common benign breast condition in lactating women
  • Clinical presentation:
    • Palpable, firm mass in the subareolar region
    • Presents with no fever or pain (pain suggests secondary bacterial infection)
    • Unilateral
  • Diagnosis:
    • Mainly clinical
    • Fine needle aspiration reveals milky contents
    • Mammogram:
      • Complex cystic masses
      • With fat/fluid levels (from the layering of portions of retained milk)
    • Ultrasound:
      • Depends on the fat and water cystic content
      • Typically, a homogeneous hypoechoic lesion with acoustic attenuation, well-defined margins, and thin walls
  • Management: 
    • Most cases resolve spontaneously.
    • Increased breastfeeding, warm compresses, and massage 
    • Repeated needle aspiration or surgical excision: for symptomatic cysts
Galactocele

Galactocele:
A: Lesion parallel to the skin with well-defined borders showing anechoic (cystic) and echogenic (solid) components, with discrete posterior acoustic enhancement and well-defined borders.
B: Predominantly hypoechoic lesion parallel to the skin with well-defined borders, peripheral areas of hyperechogenicity, and posterior acoustic enhancement.

Image: “ Galactocele” by US National Library of Medicine. License: CC BY 4.0

Phyllodes tumor

  • Cystosarcoma phyllodes
  • Fibroepithelial tumor similar to fibroadenomas, characterized by rapid growth
  • Epidemiology:
    • Most common in women between 40 and 50 years of age
    • Account for < 1% of all breast neoplasms
    • Although usually benign, some may become malignant (25% of cases)
  • Clinical presentation:
    • Painless, multinodular, firm, rapidly growing mass 
    • Usually 47 cm in diameter
    • About 20% nonpalpable, identified on mammography
  • Diagnosis:
    • Mammography: lobulated mass, resembles fibroadenoma
    • Ultrasonography: well-defined, hypoechoic mass (like fibroadenomas, without microcalcifications)
    • MRI: well-circumscribed with irregular walls, high signal intensity on T1, and low signal intensity on T2 
    • CNB: 
      • Papillary projection (phyllodes/“leaf-like”) of proliferating epithelium-lined stroma 
      • Varying degrees of atypia and hyperplasia (depends on benign or malignant nature)
  • Management: 
    • Surgical resection with wide margins (due to high recurrence rate)
    • Breast exam and mammogram every 6 months for 2 years, then annually
Phyllodes tumor

Phyllodes tumor of the breast

(a) Transverse US image shows a circumscribed heterogenous echo with a small cystic space (arrow) and a slight posterior acoustic enhancement.
(b) Photomicrograph shows leaf-like processes containing cellular stroma lined with benign ductal epithelial cells projecting into the cystic space (haematoxylin & eosin stain; x100).

Image: “Benign phyllodes tumour in a 35-year-old woman” by Department of Radiology, Chiang Mai University, Chiang Mai, Thailand. License: CC BY 2.5

Giant juvenile fibroadenoma

  • Approximately 0.5%2% of all fibroadenomas
  • Usually occurs in African American adolescents
  • Clinical presentation:
    • Rapid increase in size; unilateral tumors > 5 cm in diameter
    • May cause skin ulceration and venous engorgement
  • Management: surgical excision (as they are not easily distinguished from phyllodes tumors on examination or imaging studies)

Complex fibroadenoma

  • Fibroadenoma containing pathologic features: 
    • Sclerosing adenosis
    • Duct epithelial hyperplasia
    • Cysts > 3 mm  
    • Apocrine metaplasia
  • Slight increase in cancer risk
  • Clinical presentation: presents as a palpable lump or mass on breast imaging
  • Diagnosis: biopsy distinguishes it from simple fibroadenoma
  • Management: observation, risk assessment with annual exam and mammogram

Differential Diagnosis

  • Fibrocystic changes of the breast: refers to the changes that happen to breast tissue as a woman ages. The normal histologic appearance of predominant ducts, lobules, intralobular stroma, and interlobular stroma is replaced by fibrous tissue and cystic formation.
  • Fat necrosis of the breast: usually due to breast injury. As the damaged breast tissue is repaired, it is replaced by scar tissue. Some fat cells may have a different response, however, and form what are known as oily cysts (seen in mammogram and ultrasound).
  • Gynecomastia: unilateral or bilateral breast enlargement in males due to increased glandular proliferation. A very common and mostly physiologic condition that is seen in neonates, pubertal boys, and elderly patients. Some cases are pathologic and are secondary to drugs, hyperthyroidism, neoplasms, and chronic liver and kidney disease.
  • Mastitis: inflammation of the mammary gland tissue, which can be lactational or non-lactational. Mastitis is most common in women in the childbearing years.

References

  1. Ajmal, M., Van Fossen, K.(2020). Breast Fibroadenoma. https://www.ncbi.nlm.nih.gov/books/NBK535345/
  2. Dilaveri, C., MacBride, M., Sandhu, N., Lonzetta, N., Ghosh, K., Wahner-Roedler, D.(2012) Breast manifestations of systemic diseases. Int J Womens Health. 4: 35–43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282604/
  3. Guray, M, Sahin, A. (2006). Benign breast diseases: classification, diagnosis and management. Oncologist 11(5):435-49. https://pubmed.ncbi.nlm.nih.gov/16720843/
  4. Lee, M., Soltanian, H.(2015). Breast fibroadenomas in adolescents:current perspectives. Adolesc Health Med Ther. 6: 159–163. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562655/
  5. Li, A., Kirk, L.(2020). Intraductal papilloma. https://www.ncbi.nlm.nih.gov/books/NBK519539/
  6. Neal, L., Sandhu, N., Hieken, T., Glazebrook K., Mac Bride, M.B., Dilaveri, C., Wahner-Riedler, D.; Ghosh, K; Visscher, D.(2014) Diagnosis and Management of Benign, Atypical and Indeterminate Breast lesions detected on core needle biopsy. Mayo Clinic Proceedings. ;89(4):536-547. https://www.mayoclinicproceedings.org/article/S0025-6196(14)00146-3/pdf
  7. Sabel,M., Chagpar, A. & Chen, W. (Eds.). (2018). Overview of benign breast disease. Uptodate. Retrieved August 23, 2020, from https://www.uptodate.com/contents/overview-of-benign-breast-disease
  8. Santen, R. (2018). Benign breast disease in women. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK278994/
  9. Visccher, D. et al. (2014). Sclerosing adenosis and risk of breast cancer. Breast Cancer Res Treat. 144(1): 205–212. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924024/

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