Breast

• Benign epithelial lesions are classified into three groups

  • Nonproliferative breast changes
  • Proliferative breast disease
  • Atypical hyperplasia
• Nonproliferative breast changes (Fibrocystic changes)


  Common morphologic alterations often grouped under the term fibrocystic changes
• Cysts


  Form by the dilation of lobules and may coalesce to form larger cysts
• Cysts


  • Turbid, semitranslucent brown- or blue-colored fluid (blue-dome cysts)
  • Lined by flattened atrophic epithelium or by metaplastic apocrine cells
• Calcifications are common in cysts
• Fibrosis


  Cysts frequently rupture, releasing secretory material into the adjacent stroma, contributing to palpable nodularity of the breast
• Adenosis


  Increase in the number of acini per lobule
• Adenosis is a normal feature of pregnancy
• Lactational adenomas


  Palpable masses in pregnant or lactating women that regress after cessation of breastfeeding, consisting of normal-appearing breast tissue with lactational changes
• Flat epithelial atypia


  Clonal process characterized by the presence of dilated acini and cysts lined by epithelial cells that display mild cytologic atypia, associated with deletions of chromosome 16q and the earliest morphologically recognizable clonal lesion of the breast
• Flat epithelial atypia is often associated with lesions that increase the risk of cancer (e.g., atypical hyperplasia) but has not been shown to increase risk in isolation
• Atypical ductal hyperplasia


  A duct is filled with a mixed population of cells consisting of highly atypical, but fall short of a diagnosis of ductal carcinoma in situ
• Atypical lobular hyperplasia


  A population of monomorphic small, round, loosely cohesive cells partially fills a lobule, morphologically identical to the cells of lobular carcinoma in situ, but the extent of involvement is not sufficient for this diagnosis
• Atypical ductal hyperplasia and atypical lobular hyperplasia express high levels of estrogen receptor (ER), have a low rate of proliferation, and may have acquired chromosomal aberrations such as losses of 16q and 17p or gains of 1q, features also found in low-grade carcinoma in situ and ER-positive invasive breast cancer
• Atypical lobular hyperplasia also shows loss of E-cadherin expression, a feature it shares with LCIS
• Proliferative changes


  Associated with a 1.5- to 2-fold increased risk compared to nonproliferative changes
• Proliferative disease with atypia

  Confers a 4- to 5-fold increased risk
• Both breasts are at increased risk for women with benign epithelial changes
• Risk reduction can be achieved by bilateral prophylactic mastectomy or treatment with estrogen antagonists, such as tamoxifen
• Fewer than 20% of women with atypical hyperplasia develop breast cancer, and therefore many choose close clinical and radiologic surveillance over intervention
• Benign epithelial lesions


  • Usually do not cause symptoms but are frequently detected as mammographic calcifications or densities
  • The majority are not precursors of cancer
  • These lesions are classified according to the subsequent risk of cancer in either breast
  • Although risk reduction can be achieved by surgery or chemoprevention, the majority of women will not develop cancer, and many women choose surveillance instead of intervention
• Gynecomastia


  Enlargement of the male breast, the only benign lesion seen with any frequency in the male breast
• Gynecomastia


  • Presents as a button-like subareolar enlargement, may be unilateral or bilateral
  • Microscopically, there is an increase in dense collagenous connective tissue associated with epithelial hyperplasia of the duct lining, but lobule formation is almost never observed
• Causes of gynecomastia


  Imbalance between estrogens, which stimulate breast tissue, and androgens, which counteract these effects<|>Most important cause is cirrhosis of the liver, since this organ is responsible for metabolizing estrogen<|>In older males, gynecomastia may stem from a relative increase in estrogens as testicular androgen production falls<|>Drugs such as alcohol, marijuana, heroin, antiretroviral therapy, and anabolic steroids have been associated with gynecomastia<|>Rarely, gynecomastia occurs as part of Klinefelter syndrome (XXY karyotype) or in association with functioning testicular neoplasms
• Atypical hyperplasia


  A clonal proliferation having some, but not all, of the histologic features of carcinoma in situ, associated with a moderately increased risk of carcinoma
• Atypical ductal hyperplasia


  Present in 5% to 17% of specimens from biopsies performed for calcifications, recognized by its histologic resemblance to DCIS but only partially filling involved ducts
• Atypical lobular hyperplasia


  An incidental finding in fewer than 5% of biopsies, consisting of cells identical to those of lobular carcinoma in situ (LCIS) but not filling or distending more than 50% of the acini within a lobule
• Complex sclerosing lesion


  Has components of sclerosing adenosis, papilloma, and epithelial hyperplasia, including the radial sclerosing lesion ("radial scar") which closely mimics invasive carcinoma
• Radial sclerosing lesion


  Has a central nidus of entrapped glands in a hyalinized stroma surrounded by long radiating projections into stroma, an irregular shape that closely mimics invasive carcinoma
• Papilloma


  Grows within a dilated duct and is composed of multiple branching fibrovascular cores, with frequent epithelial hyperplasia and apocrine metaplasia
• Large duct papillomas


  Situated in the lactiferous sinuses of the nipple, usually solitary
• Small duct papillomas


  Commonly multiple and located deeper within the ductal system
• More than 80% of large duct papillomas produce a nipple discharge, which may be bloody due to torsion of the stalk, leading to infarction
• Proliferative breast disease without atypia


  Lesions characterized by proliferation of epithelial cells, without atypia, associated with a small increase in the risk of subsequent carcinoma in either breast
• Epithelial hyperplasia


  Increased numbers of both luminal and myoepithelial cell types fill and distend ducts and lobules, with irregular lumens often discernible at the periphery of the cellular masses
• Sclerosing adenosis


  An increased number of acini that are compressed and distorted in the central portion of the lesion, with stromal fibrosis completely compressing the lumens to create the appearance of solid cords or double strands of cells lying within dense stroma
• Epithelial hyperplasia


  The lumen is filled with a heterogeneous, mixed population of luminal and myoepithelial cell types. Irregular slit-like fenestrations are prominent at the periphery.
• Sclerosing adenosis


  There are an increased number of acini that are compressed and distorted in the central portion of the lesion. On occasion, stromal fibrosis completely compresses the lumens to create the appearance of solid cords or double strands of cells lying within dense stroma, a pattern that superficially resembles invasive carcinoma.
• Sclerosing adenosis

  • May come to attention as a palpable mass, a radiologic density, or calcifications
• Sclerosing adenosis. The involved terminal duct lobular unit is enlarged, and the acini are compressed and distorted by dense stroma. Calcifications are present within some of the lumens. Unlike carcinomas, the acini are arranged in a swirling pattern, and the outer border is well circumscribed.