Benign Epithelial Lesions

• Benign epithelial lesions are often detected incidentally via mammography or in surgical specimens.
• These lesions are divided into non-proliferative disease, proliferative disease without atypia, and proliferative disease with atypia.

Non-Proliferative Breast Changes

• These changes are not associated with an increased risk of breast cancer.
• Fibrocystic changes are an example.

Proliferative Disease Without Atypia

• This encompasses polyclonal hyperplasia and has a slightly increased breast cancer risk.
• Epithelial hyperplasia is an example.

Proliferative Disease With Atypia

• Includes monoclonal precancers that are modestly associated with increased breast cancer risk.
• Atypical ductal and nodular hyperplasia are examples.

Proliferative breast changes (Fibrotic changes)

• Characterized by increased proliferation associated with clonal genetic aberrations.
• Clinicians refer to it as "lumpy bumpy" breast
• Pathologists consider it a benign breast tissue.
• Majority of palpable breast masses will have a fibrocystic change or fibroadenoma

Principal Morphologic Changes

• Cystic change often involves apocrine metaplasia.
• Fibrosis occurs when cysts rupture, leading to inflammation and nodularity.
• Adenosis involves an increased number of acini per lobule.
• Calcifications can be seen in imaging.
• Gross examination may show cysts filled with dark turbid fluid ("blue domed" cyst).

Lactational Adenoma

• This presents as palpable masses in pregnant or lactating individuals.
• It is due to local exaggerated response to gestational hormones (prolactin).

Galactocele

• This is a lesion associated with lactational adenoma.
• Cystically dilated ducts are seen with flattened cuboidal cells.
• It will regress after the cessation of breastfeeding.
• Scant Stroma.

Flat Epithelial Atypia

• Considered non-proliferative if seen in isolation.
• Associated with lesions that increase malignancy risk if seen adjacent to atypical ductal or nodular hyperplasia.
• It involves dilated acini and cysts with mildly atypical epithelial cells.
• Normally, ducts are lined by 2 layers of epithelial cells, myoepithelial and luminal cells.

Epithelial Hyperplasia

• Increased numbers of both luminal and myoepithelial cells.
• Ducts and lobules become filled and distended.
• Presence of irregular lumens/slit-like fenestrations usually located in the periphery.

Sclerosing Adenosis

• It is a proliferative lesion.
• Can be a palpable mass.
• Increased number of compressed and distorted acini in the central portion.
• Solid cords or double strands of cells lie within the dense stroma.
• Acini are arranged in a swirling pattern.
• Outer border is well-circumscribed and non-infiltrative.

Complex Sclerosing Adenosis

• Contains sclerosing adenosis + papilloma + epithelial hyperplasia.

Papilloma

• Grows within a dilated duct.
• Multiple branching fibrovascular cores are present with an arborizing pattern.
• Epithelial hyperplasia and apocrine metaplasia can be associated.
• Large duct papillomas are more superficial and can cause nipple discharge.
• Small duct papillomas are located deeper in the breast tissues.

Gynecomastia

• Enlargement of the male breast
• Button-like subareolar enlargement unilaterally or bilaterally
• Secondary to hormonal imbalance (higher estrogen vs testosterone)

Proliferative Breast Disease with Atypia

• Features similar to flat epithelial atypia.
• Has some but not of the histologic features needed to diagnose carcinoma in situ
• Moderately increased risk of carcinoma
• Two forms exist: atypical ductal hyperplasia and atypical lobular hyperplasia

Atypical Ductal Hyperplasia

• Important to differentiate from epithelial hyperplasia.
• Presence of monomorphic cells.
• Basement membrane is intact.
• Formation of micropapillae, tufts, fronds, bridges, solid and/or cribriform patterns within the involved space.

Atypical Lobular Hyperplasia

• Identical to lobular carcinoma in situ (LCIS).
• Does not fill or distend more than 50% of the acini within a lobule.
• Atypical cells exist between the ductal basement membrane and overlying normal luminal cells.

Clinical significance of benign epithelial changes

• Risks by carcinoma based on changes
  • Nonproliferative - 1.0x risk
  • Proliferative without atypia - 1.5 - 2x risk
  • Proliferative with atypia - 4-5x risk
  • Carcinoma in situ - 8-10x risk
• Risk reduction via:
  • Bilateral prophylactic mastectomy
  • Chemoprevention treatment with estrogen antagonists(tamoxifen)
  • Close surveillance