Breast Pathology

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Paget disease of nipple

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Paget disease of nipple (malignant cells circled)

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Invasive ductal carcinoma (DS = desmoplastic stroma); tubular carcinoma

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Invasive ductal carcinoma; Mucinous carcinoma

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Invasive ductal carcinoma; inflammatory carcinoma

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Invasive ductal carcinoma; inflammatory carcinoma; cancer (circled) within dermal lymphatics

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Invasive lobular carcinoma (note single file structure)

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What is the functional unit of the breast?

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The terminal duct lobular unit

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Acute mastitis

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• Bacterial infection of breast (usually Staph. aureus)
• Associated with breast-feeding; fissures develop in nipple providing a route of entry for microbes
• Presents as an erythematous breast with purulent nipple discharge; may progress to abscess formation
• Treatment involves continued draining (e.g. feeding) and antibiotics (e.g. dicloxacillin)

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Periductal mastitis

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• Inflammation of subareolar ducts
• Usually seen in smokers (relative vitamin A deficiency results in squamous metaplasia of lactiferous ducts, producing duct blockage and inflammation)
• Clinically presents as a subareolar mass with nipple retraction

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Mammary duct ectasia

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• Inflammation with dilatation (ectasia) of subareolar ducts
• Rare; clinically arises in multiparous postmenopausal women
• Presents as periareolar mass with green-brown nipple discharge
• Chronic inflammation with plasma cells is seen on biopsy

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How does fat necrosis of breast present?

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• Mass on physical exam
• Abnormal calcification on mammography (due to saponification)
• Biopsy shows necrotic fat with associated calcifications and giant cells

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Fibrocystic change

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• Development of fibrosis and cysts in breast
• Most common change in premenopausal breast; thought to be hormone mediated
• Presents as vague irregularity of breast tissue, usually in upper outer quadrant
• Cysts have blue-dome appearance on gross exam

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Fibrocystic changes associated with increased risk for invasive carcinoma

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• Fibrosis, cysts, and apocrine metaplasia - NO RISK
• Ductal hyperplasia and sclerosing adenosis - 2X increased risk
• Atypical hyperplasia - 5X increased risk

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Intraductal papilloma

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• Benign papillary growth, usually into large duct
• Characterized by fibrovascular projections lined by epithelial (luminal) and myoepithelial cells
• Classically presents as bloody nipple discharge in premenopausal women

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How is intraductal papilloma distinguished from papillary carcinoma?

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• Papillary carcinoma is characterized by fibrovascular projections lined by epithelial cells without underlying myoepithelial cells
• Risk of papillary carcinoma increases with age; thus, it is more commonly seen in postmenopausal women

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Fibroadenoma

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• Tumor of fibrous tissue and glands
• Most common benign neoplasm of the breast; usually seen in premenopausal women
• Presents as well-circumscribed, mobile marble-like mass
• Estrogen sensitive--grows during pregnancy and may be painful during menstrual cycle
• Benign, with no increased risk of carcinoma

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Phyllodes tumor

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• Fibroadenoma-like tumor with overgrowth of fibrous component; characteristic 'leaf-like' projections are seen on biopsy
• Most commonly seen in postmenopausal women
• Can be malignant

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Ductal carcinoma in situ (DCIS)

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• Malignant proliferation of cells in dust with no invasion of basement membrane
• Often detected as calcification on mammography; doesn't usually produce mass
• Histologic subtypes are based on architecture

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Histological appearance of Comedo type DCIS

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comedo type is characterized by high-grade cells with necrosis and dystrophic calcification in the center of ducts

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Paget disease of breast

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DCIS that extends up the ducts to involve skin of nipple

• presents as nipple ulceration and erythema
• almost always associated with an underlying carcinoma

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Most common type of invasive carcinoma in breast

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Invasive ductal carcinoma

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How does invasive ductal carcinoma present?

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• As a mass that is usually 2 cm or greater
• Mammographically detected masses are usually 1 cm or greater
• Advanced tumors may show dimpling of skin or retraction of nipple
• Biopsy shows duct-like structures in desmoplastic stroma

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Special subtypes of invasive ductal carcinoma

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• Tubular carcinoma
• Mucinous carcinoma
• Medullary carcinoma
• Inflammatory carcinoma

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Tubular carcinoma

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Characterized by well-differentiated tubules that lack myoepithelial cells; good prognosis

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Mucinous carcinoma

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• Characterized by carcinoma with abundant extracellular mucin
• Tends to occur in older women (average age is 70)
• Relatively good prognosis

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Medullary carcinoma

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• Characterized by large, high-grade cells growing in sheets with associated lymphocytes and plasma cells
• Grows as well-circumscribed mass that can mimic fibroadenoma on mammography
• Relatively good prognosis
• Increased incidence in BRCA1 carriers

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Inflammatory carcinoma

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• Characterized by carcinoma in dermal lymphatics
• Presents classically as an inflamed, swollen breast (tumor cells block drainage of lymphatics) with no discrete mass; can be mistaken for acute mastitis
• Poor prognosis

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Lobular carcinoma in situ (LCIS)

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• Malignant proliferation of cells in lobules with no invasion of the basement membrane
• Does not produce a mass or calcifications and is usually discovered incidentally on biopsy
• Characterized by dyscohesive cells lacking E-cadherin adhesion protein
• Often multifocal and bilateral
• Treatment is tamoxifen + follow up (low risk of progression to invasive carcinoma)

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Invasive lobular carcinoma

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• Characteristically grows in single-file pattern
• Cells may exhibit signet-ring morphology
• No duct formation due to lack of E-cadherin

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Most important vs. most useful prognostic factors in breast cancer

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• Most important: metastasis
• Most useful: spread to axillarly lymph notes

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HER2/neu

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This gene is associated with response to transtuzumab (Herceptin), a designer antibody directed against the HER2 receptor; HER2/neu is a growth factor receptor present on the cell surface

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Which mutation is associated with breast and ovarian cancers?

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BRCA1

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Which mutation is associated with male breast cancer?

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BRCA2

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Male breast cancer

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• Usually presents as subareolar mass in older males
• Most common histological subtype is invasive ductal carcinoma
• Associated with Klinefelter syndrome