Breast Pathology

Approach to a breast mass

Triple assessment. A palpable breast mass is evaluated by clinical exam, imaging (mammography, with ultrasound in younger women) and biopsy. Most lesions, benign and malignant, arise in the terminal duct lobular unit, where luminal cells are surrounded by a myoepithelial layer and basement membrane.

Age sorts the odds. Under 30, a mass is usually benign (fibroadenoma, fibrocystic change); a new mass after 40 raises concern for carcinoma. A firm, marble-like mass that slides under the fingers in a 25-year-old is the classic fibroadenoma, whereas a fixed, rock-hard, irregular mass with skin dimpling or nipple retraction in a 60-year-old is a red flag for carcinoma.

Benign lesions

Fibroadenoma. The most common benign breast tumor in women under 35: a small, well-circumscribed, firm, rubbery and mobile "breast mouse" made of proliferating stroma around compressed glands. It is estrogen-sensitive, enlarging in pregnancy and before menses and regressing after menopause, and it carries no meaningful increase in cancer risk.

Fibrocystic change. The most common breast disorder in premenopausal women, causing lumpy, bumpy, cyclically tender breasts, often bilaterally. Nonproliferative changes (cysts, fibrosis) do not raise cancer risk. Proliferative changes such as sclerosing adenosis, which forms calcifications that can mimic carcinoma, and epithelial hyperplasia raise it, especially atypical hyperplasia.

Intraductal papilloma. A small papillary growth in a lactiferous duct beneath the areola and the most common cause of bloody (serosanguinous) nipple discharge in a premenopausal woman. It confers a slight increase in cancer risk.

Phyllodes tumor. A large fibroepithelial tumor with leaf-like architecture and stromal overgrowth, typically in women in their 40s–50s. Unlike fibroadenoma, it can be malignant and tends to recur locally.

Fat necrosis. It follows breast trauma or surgery, although many patients recall no injury. It can form a firm, irregular mass with skin retraction and calcifications on mammography, mimicking carcinoma; biopsy shows necrotic fat, saponification and foamy macrophages. It is benign.

Mastitis. Acute mastitis, usually Staphylococcus aureus entering through cracked nipples during breastfeeding, produces a red, tender breast that responds to antibiotics and continued nursing, the key contrast with inflammatory carcinoma.

In situ and invasive carcinoma

Ductal carcinoma in situ. DCIS is a malignant ductal proliferation that has not breached the basement membrane. It usually appears as clustered, often branching microcalcifications on screening mammography. The comedo subtype has central necrosis, which calcifies. DCIS is a direct precursor of invasive carcinoma.

Lobular carcinoma in situ. LCIS is an incidental finding without a mass or calcifications; its cells lack E-cadherin, and it marks increased risk of invasive carcinoma in either breast.

Invasive ductal carcinoma. The most common invasive breast cancer, about 80%. Desmoplasia makes a firm, fibrous, rock-hard mass with a stellate (spiculated) outline that can tether and dimple the overlying skin.

Invasive lobular carcinoma. Loss of E-cadherin, the adhesion molecule that binds cells together, lets tumor cells infiltrate in single file (Indian file). Lobular carcinoma is more often bilateral and multifocal, forms a vague thickening rather than a discrete hard mass, and characteristically metastasizes to unusual sites such as the peritoneum, GI tract and ovaries.

Prognosis. For invasive cancer, axillary lymph node involvement is the most important prognostic factor in early disease, followed by tumor size, grade and receptor status.

Skin and nipple presentations

Inflammatory carcinoma. Tumor emboli plug the dermal lymphatics, producing a swollen, erythematous, warm breast with peau d'orange (orange-peel) skin, often without a discrete mass. It mimics mastitis but does not respond to antibiotics, and it carries a poor prognosis.

A "mastitis" that fails antibiotics, especially in a woman who is not breastfeeding, needs a biopsy to exclude inflammatory carcinoma.

Paget disease of the breast. An eczematous, ulcerated, crusting nipple lesion caused by malignant Paget cells migrating into the nipple epidermis from an underlying DCIS or invasive carcinoma. Any persistent nipple eczema warrants biopsy.

Receptors, therapy and risk

Receptor status picks the drug. ER/PR-positive tumors respond to hormonal therapy: tamoxifen before menopause or aromatase inhibitors after it, when estrogen comes mainly from peripheral aromatization. HER2 (ERBB2)-positive tumors respond to the monoclonal antibody trastuzumab. Triple-negative tumors (ER, PR and HER2 all negative) lack targeted options, are treated with chemotherapy, are linked to BRCA1 and carry a worse prognosis.

Estrogen-related risk. Risk tracks lifetime estrogen exposure: early menarche, late menopause, nulliparity, late first pregnancy, obesity and postmenopausal hormone therapy, plus age and family history.

Inherited risk. BRCA1 (chromosome 17) is associated with triple-negative breast cancer and ovarian cancer. BRCA2 (chromosome 13) also raises male breast cancer risk. Li-Fraumeni syndrome (TP53) and Cowden syndrome (PTEN) are rarer causes of hereditary breast cancer.

BRCA1 (chromosome 17): triple-negative breast plus ovarian cancer. BRCA2 (chromosome 13): also male breast cancer.