Breast Nodules and Carcinoma

Part 1: Benign Breast Nodules

Fibroadenoma

• Size ranges from <1 cm to tumors replacing most of the breast
• Mammographic density in younger women; clustered calcifications in older women
• Gross: well-circumscribed, rubbery, gray-white nodule that bulges above surrounding tissue
• Histology: delicate myxoid stroma resembling normal intralobular stroma, with:
  • Pericanalicular pattern - stroma surrounds patent ducts
  • Intracanalicular pattern - stroma compresses ducts into cleft-like spaces
• In older women: densely hyalinized stroma, atrophic epithelium

• Peak age: 20s and 30s
• Frequently multiple and bilateral
• Hormonally responsive - grow during pregnancy (can infarct, mimicking carcinoma), regress post-menopause
• A notable association: ~50% of females on cyclosporin A after renal transplantation develop multiple bilateral fibroadenomas
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 984

Phyllodes Tumor

• Varies from a few cm to massive lesions replacing the entire breast
• Larger lesions have bulbous, leaf-like protrusions (phyllodes = Greek for "leaf-like")
• Graded as benign, borderline, or malignant based on stromal atypia, cellularity, and mitotic activity
• Malignant phyllodes tumors can resemble sarcoma when there is marked stromal overgrowth

• Peak age: sixth decade (10-20 years later than fibroadenoma)
• Up to 75% are benign - may recur locally but do not metastasize
• Borderline and malignant tumors have higher recurrence rates; margin status is the most important predictor
• Lymphatic spread is rare; axillary lymph node dissection is contraindicated
• Malignant lesions: ~1/3 develop hematogenous distant metastases (only stromal component metastasizes)
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 984

Other Benign Stromal Lesions

Part 2: Breast Carcinoma - Epidemiology and Risk Factors

Risk Factors

• Increasing age (75% of cancers diagnosed after age 50)
• Hormonal factors: early menarche, late menopause (prolonged estrogen exposure)
• Genetic mutations: ~12% of all breast cancers are caused by germline mutations
  • BRCA1 (17q21): 50-85% lifetime risk of breast cancer + up to 40% risk of ovarian cancer; cancers are mostly TNBC
  • BRCA2 (13q12.3): up to 50-60% lifetime breast cancer risk + 20% ovarian cancer risk; also associated with prostate, colon, pancreatic cancers
  • Other high-penetrance genes: PALB2, TP53, Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome
• Bailey and Love's Short Practice of Surgery 28th Edition, p. 952

Part 3: Carcinoma in Situ

Ductal Carcinoma In Situ (DCIS)

• A precursor to invasive ductal carcinoma
• Most often found on mammographic screening as microcalcifications
• If untreated and carcinoma develops, it is usually an invasive ductal carcinoma in the same breast

Lobular Carcinoma In Situ (LCIS)

• A marker of increased risk AND a precursor lesion
• When carcinoma later develops: two-thirds in the same breast, one-third in the contralateral breast
• Histology: small, rounded, loosely cohesive cells filling and expanding lobular acini
• Immunohistochemistry: E-cadherin negative (distinguishes from ductal carcinoma)
• Pleomorphic LCIS variant: large pleomorphic cells with abundant cytoplasm mixed with small rounded cells
• Robbins & Kumar Basic Pathology, p. 719

Part 4: Invasive Breast Carcinoma - Classification

Histological Classification (Foote & Stewart)

Fig. Invasive breast carcinoma of no special type. (A) Mammographic radiodense mass. (B) Gross specimen. (C) Exuberant desmoplastic stromal reaction on histology. - Robbins, Cotran & Kumar Pathologic Basis of Disease

• Presents as a chronic, eczematous eruption of the nipple that may progress to an ulcerated, weeping lesion
• Usually associated with extensive DCIS; may have an underlying invasive cancer
• Pathognomonic: Paget cells - large, pale, vacuolated cells in the rete pegs
• Differentiation from melanoma: Paget's disease is CEA-positive; melanoma is S-100 positive

Histologic Grading (Nottingham Score)

Part 5: Molecular Classification

• Robbins, Cotran & Kumar Pathologic Basis of Disease

Part 6: Staging (AJCC 8th Edition)

• T - Tumor size (T1: ≤2 cm, T2: 2-5 cm, T3: >5 cm, T4: skin/chest wall involvement)
• N - Nodal status (N0: no nodes, N1-N3: increasing nodal involvement)
• M - Distant metastasis

Part 7: Management

Surgery

Adjuvant Radiotherapy

• All patients after BCS (breast-only if node-negative: 40-42.5 Gy in 15-16 fractions hypofractionation, or 45-50.4 Gy in 25 fractions)
• After mastectomy if: tumor ≥5 cm, skin/chest wall involvement, lymphovascular invasion (grade 3), or lymph node-positive disease
• Locally advanced cancers (T3, T4, N1-N3): locoregional radiotherapy covering chest wall + supraclavicular region

Systemic Therapy

Metastatic Disease (Stage IV)

• Hormone receptor-positive with bony/limited visceral metastasis: endocrine therapy preferred
• Hormone receptor-negative or visceral crisis: systemic chemotherapy
• Bone metastases: palliative radiotherapy to weight-bearing areas + bisphosphonates
• Pleural effusions: intercostal drainage + pleurodesis
• Solitary visceral metastasis in good performance status: surgical resection may be considered
• Bailey and Love's Short Practice of Surgery 28th Edition

Part 8: Hereditary and Familial Breast Cancer

• Hereditary breast cancer (HBC): 5-10% of all breast cancers; identifiable genetic mutation, more aggressive, earlier onset, more often multicentric and bilateral
• Familial breast cancer (FBC): 20-30%; affects family members but no known single mutation
• High-penetrance mutations: BRCA1, BRCA2, TP53 (Li-Fraumeni), PTEN (Cowden), STK11 (Peutz-Jeghers), CDH1 (hereditary gastric cancer)
• Genetic risk evaluation is recommended for high-risk individuals (strong family history, early onset, bilateral or male breast cancer)

Summary Table: Key Breast Nodules at a Glance