Breast masses Notes

NOTES NOTES BREAST MASSES GENERALLY, WHAT ARE THEY? TREATMENT PATHOLOGY & CAUSES ▪ Diverse breast tissue disorders; often in biologically-female individuals, often benign ▫ Young: ↑ benign masses ▫ Elderly: ↑ breast cancer CAUSES ▪ Hormonal stimulation ▪ Genetic predisposition COMPLICATIONS ▪ Possibility that benign mass → breast cancer SIGNS & SYMPTOMS ▪ Possibly asymptomatic ▪ Breast size/appearance change DIAGNOSIS ▪ Suggestive physical findings, medical/ family history DIAGNOSTIC IMAGING Mammogram MRI Ultrasound LAB RESULTS ▪ Biopsy, histological analysis 720 OSMOSIS.ORG ▪ Benign disorders may regress spontaneously SURGERY ▪ Lumpectomy ▪ Mastectomy OTHER INTERVENTIONS ▪ Alternatives (e.g. cryoablation, radiation therapy)

Chapter 122 Breast Masses BREAST CANCER osms.it/breast-cancer PATHOLOGY & CAUSES ▪ Diverse malignant breast lesions with different microscopic features, biologic behavior ▫ ↑ common non-skin malignancy in biologically-female individuals ▫ Rare in biologically-male individuals TYPES Molecular subtypes ▪ Molecular subtypes classified by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) expression; protein Ki67 levels (controls cancer cell growth) ▫ Luminal A: ER, PR positive, HER2 negative, ↓ protein Ki67 levels ▫ Luminal B: ER, PR positive, HER2 negative or positive, ↑ protein Ki67 levels ▫ Triple-negative: ER, HER2, PR negative ▫ HER2 enriched: ER, PR negative, HER2 positive ▫ Normal-like: ER, PR positive, HER2 negative, ↓ protein Ki67 levels Most common types ▪ Ductal carcinoma in situ (DCIS) ▫ In ducts → possible invasive ductal carcinoma (usually in same breast) ▪ Lobular carcinoma in situ (LCIS) ▫ In lobules → ↑ cancer risk in either breast ▪ Invasive ductal carcinoma ▫ 70% of all invasive cancers ▫ Subtypes: tubular, medullary, mucinous, papillary, cribriform ▪ Invasive lobular carcinoma ▪ Inflammatory breast cancer ▫ Rare aggressive form ▫ Poor prognosis Figure 122.1 The gross pathological appearance of breast cancer in a wide local excision specimen. CAUSES ▪ Genetic aberrations ▪ Hormonal exposure ▪ Inherited susceptibility genes (familial, 10% of cases) ▫ Breast cancer 1 (BRCA1), breast cancer 2 (BRCA2) (80–90% of singlegene familial breast cancers, 3% of all cancers) RISK FACTORS Breast cancer prior history ↑ age → ↑ risk Breast cancer in first-degree relatives Individuals who are biologically female Race/ethnicity ▫ Highest incidence in white people of Ashkenazi Jewish descent ▪ Hormonal influence ▫ Estrogen exposure (e.g., menopausal hormone therapy) ▫ Early menarche (< 11 years old) ▫ Late menopause ▪ ▪ ▪ ▪ ▪ OSMOSIS.ORG 721

▫ Nulliparity/ > 35 years old at first birth ▫ ↓ breastfeeding duration ▫ Obesity ▪ Toxin exposure ▫ Ionizing radiation ▫ Smoking ▫ ↑ alcohol consumption Ultrasound ▪ Differentiate cystic/solid masses ▪ Provide procedure guidance ▪ Hypoechoic lesion ▫ Calcifications, shadowing, irregular margins COMPLICATIONS ▪ Metastasis (bone, lung, liver, brain common) ▪ Treatment complications ▫ Lymph node resection → lymphedema ▫ Cytotoxic chemotherapy → infertility ▫ Chemotherapy, radiation therapy → cardiac disorders (e.g. cardiomyopathy) and/or myeloid neoplasms SIGNS & SYMPTOMS ▪ Possibly asymptomatic (especially premalignant breast masses) ▪ Palpable mass (hard, nontender, irregular borders, immobile) ▪ Palpable lymph nodes ▫ Axillary, supraclavicular ▪ Skin dimpling (orange peel skin) ▪ Nipple retraction, discharge (usually bloody), eczema-like rash (Paget’s disease of breast) ▪ Inflammatory breast cancer ▫ Presentation mimics inflammation (tenderness, warmth, swelling, erythema) ▫ Orange peel skin over mass Figure 122.2 An inverted nipple caused by a sub-areolar breast tumor. DIAGNOSIS DIAGNOSTIC IMAGING Breast MRI ▪ High-risk individuals (with mammography) Mammogram ▪ Ill-defined, spiculated mass ▫ Clustered microcalcifications 722 OSMOSIS.ORG Figure 122.3 A mammogram of the breast demonstrating a well circumscribed tumor.

Chapter 122 Breast Masses LAB RESULTS ▪ Core biopsy ▫ Histological analysis, tumor grading ▪ Immunohistochemistry analysis ▫ Detect estrogen/progesterone receptor expression; HER2 overexpression ▪ Sentinel lymph node biopsy OTHER DIAGNOSTICS ▪ Suggestive physical findings, medical/ family history Figure 122.4 The histological appearance of breast carcinoma, no special type. This subtype can take many forms but in this instance there are cords of pleomorphic, atypical cells with open chromatin and prominent nucleoli. TREATMENT SURGERY ▪ Lumpectomy/mastectomy ▫ Individual’s choice OTHER INTERVENTIONS ▪ Radiation therapy ▪ Chemotherapy ▪ Adjuvant hormone therapy/ chemoprevention (some cancers) Figure 122.5 A fungating tumor of the left breast. The tumor involves almost the entire organ and extends into the axilla where the overlying skin has ulcerated. OSMOSIS.ORG 723

FIBROADENOMA osms.it/fibroadenoma PATHOLOGY & CAUSES ▪ Benign, estrogen-sensitive proliferative breast lesion (from stromal, epithelial components) ▫ ↑ occurence young people (< 35 years old) ▫ Most common benign breast neoplasm ▪ Cause unknown; possibly hormone presence ▫ Pregnancy, pre-menstruation → ↑ proliferation ▫ Regresses with age TYPES ▪ Giant fibroadenomas ▫ >10cm/3.9in (phylloid tumors appear similar) ▪ Juvenile ▫ Young individuals (10–18 years of age), grow rapidly, ↑ glandularity, ↑ stromal cellularity ▪ Complex fibroadenomas ▫ Proliferative changes (e.g. sclerosing adenosis, calcifications/hyperplasia) DIAGNOSIS DIAGNOSTIC IMAGING Breast ultrasound ▪ Well-defined, solid, hypoechoic lesion Mammogram ▪ Circumscribed, dense lesion, possible clustered calcifications LAB RESULTS Biopsy ▪ Definitive diagnostic test ▫ Glandular, fibrous tissue ▪ Excludes breast cancer OTHER DIAGNOSTICS ▪ Suggestive physical findings COMPLICATIONS ▪ Size increases → possible infarction/ inflammation ▪ Mildly ↑ breast cancer risk (especially complex fibroadenomas) SIGNS & SYMPTOMS ▪ Typical presentation: 2–3cm/0.79–1.2in average size, firm, well-circumscribed, round, palpable, mobile, painless (possibly painful during menstrual cycle) ▪ Often multiple, bilateral 724 OSMOSIS.ORG Figure 122.6 The histological appearance of a fibroadenoma. There is overgrowth of both the stroma and the glandular epithelium.

Chapter 122 Breast Masses TREATMENT ▪ Therapy seldom required; often regress post-menopause SURGERY ▪ Surgical excision OTHER INTERVENTIONS ▪ Cryoablation Figure 122.7 A fine needle aspirate of a fibroadenoma of the breast. Sheets of epithelial cells are arranged in a staghorn pattern. FIBROCYSTIC BREAST CHANGES osms.it/fibrocystic-breast-changes PATHOLOGY & CAUSES ▪ Common benign breast disease ▪ Bilateral tenderness, multiple lumps related to cyclic ovarian hormonal stimulation ▫ AKA fibrocystic disease, mammary dysplasia, cystic mastitis ▫ Premenopausal individuals (< 35 years old) → ↑ common; 50% of reproductiveage biologically-female individuals ▫ Increased breast cancer risk not associated (non-proliferative breast lesions) ▪ Characteristic changes ▫ Cysts ▫ Adenosis ▫ Stromal fibrosis TYPES ▪ Epithelial hyperplasia ▫ Cells in terminal ductal/lobular epithelium, atypical cells → ↑ carcinoma risk COMPLICATIONS ▪ Some subtypes (sclerosing adenosis, atypical hyperplasia) → ↑ increased invasive carcinoma risk (both breasts) SIGNS & SYMPTOMS ▪ Menstrual cycle-related clinical manifestations ▫ Bilateral breast pain, tenderness ▫ Multiple, smooth, well-defined, mobile lumps (“lumpy bumpy” breasts); usually upper outer quadrant ▪ Sclerosing adenosis ▫ Acini, stromal fibrosis, calcifications associated, slight ↑ cancer risk OSMOSIS.ORG 725

TREATMENT DIAGNOSIS DIAGNOSTIC IMAGING Mammogram ▪ Dense breasts with cysts Ultrasound ▪ Fluid-filled cysts LAB RESULTS Aspiration ▪ If mass persistent ▪ Excludes tumor ▪ If clear fluid obtained, mass disappears → fibrocystic breast changes Biopsy ▪ Cysts ▫ Blue serous fluid (“blue dome” appearance), various sizes, calcifications common ▪ Fibrosis ▫ Due to chronic inflammation from cyst rupture, material release to stroma ▪ Adenosis ▫ ↑ acini per lobule OTHER DIAGNOSTICS ▪ Suggestive physical findings Figure 122.8 The histological appearance of fibricystic change of the breast. There are numerous small cysts surrounded by fibrous tissue. The cysts are lined with ductal epithelium. 726 OSMOSIS.ORG MEDICATIONS ▪ Conservative measures ▫ Oral contraceptives; analgesics (e.g., nonsteroidal anti-inflammatory agents (NSAIDs)) SURGERY ▪ Surgical intervention often unnecessary; resolves with menopause ▪ Surgical treatment ▫ Complex cysts, if biopsy results atypical/ malignancy revealed OTHER INTERVENTIONS ▪ Conservative measure ▫ Caffeine elimination ▪ Conservative measures fail → therapeutic aspiration

Chapter 122 Breast Masses INTRADUCTAL PAPILLOMA osms.it/intraductal-papilloma PATHOLOGY & CAUSES ▪ Rare benign fibroepithelial breast tumor arising from lactiferous duct epithelium TYPES ▪ Central ▫ Develops near nipple, usually solitary, often arise near menopause ▪ Peripheral ▫ Often multiple, usually in younger individuals RISK FACTORS ▪ Biologically female, 20–30 years old COMPLICATIONS Mammogram ▪ Excludes breast cancer ▪ Intraductal papilloma usually too small to detect Ultrasound ▪ Projections extending from duct wall within lumen; used to diagnose/guide surgical resection LAB RESULTS Biopsy ▪ Fibrovascular intraductal projections lined by myoepithelial, epithelial cells OTHER DIAGNOSTICS ▪ Suggestive physical findings ▪ Slightly ↑ breast cancer risk ▪ Peripheral ▫ ↑ risk ▪ ↑ age → ↑ risk SIGNS & SYMPTOMS ▪ Intermittent bloody/serous nipple discharge (especially premenopausal) ▪ Breast feels full (relieved by discharge passage) DIAGNOSIS DIAGNOSTIC IMAGING Galactography ▪ Contrast-enhanced mammogram; definitive test but invasive ▪ Filling lactiferous duct defect Figure 122.9 Breast ductography demonstrating a solitary intraductal papilloma. TREATMENT ▪ Small, incidental papillomas: treatment may be unnecessary SURGERY ▪ Breast duct removal OSMOSIS.ORG 727

Figure 122.10 The histological appearance of a papilloma of the breast. There are multiple infolded papillae giving a cribriform pattern. The papillae are lined by benign ductal epithelium. PAGET'S DISEASE OF THE BREAST osms.it/pagets-disease-of-the-breast PATHOLOGY & CAUSES ▪ Rare cutaneous breast cancer manifestation ▫ Eczema-like skin changes in nipple, areola ▪ Pathogenesis ▫ Epidermotropic theory: underlying mammary carcinoma present (85–88% of cases) → malignant cells migrate through ductal system → nipple epidermis ▫ In situ transformation theory: nipple keratinocyte transformation → malignant cells (independent of other breast pathology) SIGNS & SYMPTOMS ▪ Typical presentation: unilateral; nipple + adjacent areolar skin; scaly; itching, burning; erythematous 728 OSMOSIS.ORG ▪ Less common: bloody nipple discharge, nipple inversion, pain ▪ Palpable mass in 50–60% of cases → worse prognosis Figure 122.11 The clinical appearance of Paget’s disease of the breast.

Chapter 122 Breast Masses DIAGNOSIS DIAGNOSTIC IMAGING Mammogram ▪ Identify associated mass, microcalcifications, tissue distortion LAB RESULTS ▪ Ultrasound-guided mass core biopsy, histopathological analysis ▪ Nipple scrape cytology/full-thickness wedge/punch biopsy ▫ Malignant, intraepithelial adenocarcinoma cells (Paget cells) present Figure 122.12 The histological appearance of Paget’s disease. There are tumor cells migrating upward toward the skin surface individually and in small groups. OTHER DIAGNOSTICS ▪ Suggestive physical findings TREATMENT SURGERY ▪ Mastectomy, breast-conserving surgery OTHER INTERVENTIONS ▪ Whole breast radiotherapy PHYLLODES TUMOR osms.it/phyllodes-tumor PATHOLOGY & CAUSES ▪ Rare fibroepithelial breast tumor ▫ Typical phyllodes (leaf-like) projections on pathologic examination ▫ AKA cystosarcoma phyllodes ▪ Generally benign, can become malignant sarcoma ▪ Arises from periductal breast stroma ▪ Associated with acquired chromosomal mutations; most commonly gains in chromosome 1q COMPLICATIONS ▪ Local recurrence after excision ▪ Local hemorrhage, necrosis ▪ High-grade tumors can give distant hematogenous metastasis; lymphatic spread rare RISK FACTORS ▪ Biologically female, 30–50 years old OSMOSIS.ORG 729

SIGNS & SYMPTOMS ▪ Mass ▫ Large, palpable, firm, multinodular, wellcircumscribed, mobile, painless ▪ Slow-growing or develops rapidly over entire breast ▪ Overlying skin possibly shiny, stretched ▪ Possible bloody discharge DIAGNOSIS DIAGNOSTIC IMAGING Breast MRI ▪ Well-circumscribed lesion, ↑ signal intensity on T1-weighted, ↓ signal intensity on T2weighted Mammogram ▪ Smooth, polylobulated mass, resembles fibroadenoma Ultrasound ▪ Solid, hypoechoic, well-circumscribed lesion; possible cystic areas within mass, microcalcifications absent LAB RESULTS Core needle biopsy ▪ Histologic grading: ↑ cellularity, ↑ mitotic rate, nuclear polymorphism, fibrous stroma overgrowth, leaf-like lobulations, cysts ▫ Cellular pleomorphism indicates malignancy OTHER DIAGNOSTICS ▪ Suggestive physical findings TREATMENT SURGERY ▪ Treatment of choice: surgical removal (wide local excision) OTHER INTERVENTIONS ▪ Large, high-risk/recurrent tumors: adjuvant radiotherapy/chemotherapy 730 OSMOSIS.ORG Figure 122.13 The histological appearance of a Phyllodes’ tumor. Whilst similar in appearance to a fibroadenoma, the stroma is more cellular and constitutes a larger component of the tumor

Chapter 122 Breast Masses OSMOSIS.ORG 731