Pathoma: Breast Pathology Flashcards
General
Breast
Mammary Gland
- Modified sweat gland embryologically derived from skin
- Breast tissue (and pathology) can develop anywhere along the milk line
- Milk line runs from axilla to vulva
- Functional unit of breast: terminal duct lobular unit (TDLU)
- Lobules make milk that drains via ducts to nipple
- Lobules & ducts are lined by 2 layers of epiehlium
- Luminal layer: inner layer; responsible for milk production
- Myoepithelial layer: outer layer; contractilons propel milk towards nipple
Breast
Terminal duct lobular unit (TDLU)
General
Breast
Hormone Sensitivity
Breast tissue is hormone sensitive
* Before puberty, male & female breast tissue primarily consists of large ducts under nipple
* Development after menarche is primarily driven by estrogen & progesterone
* Lobules & small ducts form and are present in highest density in the upper outer quadrant
* Breast tenderness during menstrual cycle is a common complaint, especially prior to menstruation
* During pregnancy, breast lobules undergo hyperplasia
* Hyperplasia is driven by estrogen & progesterone produced by the corpus luteum (early 1st trimester), fetus, and placenta (later in pregnancy
* After menopause, breast tissue undergoes atrophy
General
Galactorrhea
Milk production outside of lactation
* Not a symptom of breast cancer
* Causes include:
* Nipple stimulation
* Normal, physiologic cause
* Prolactinoma of anterior pituitary
* Common pathologic cause
* Drugs
Inflammatory Conditions
Bacterial infection associated with breast-feeding
* Fissures develop in nipple providing route of entry for microbes
Pathophysiology
Acute mastitis
Inflammatory Conditions
Usually due to S. aureus
Etiology
Acute mastitis
Inflammatory Conditions
Presents as a warm, erythematous breast with purulent nipple discharge
* May progress to abscess formatiom
Clinical Presentation
Acute mastitis
Inflammatory Conditions
Treatement of acute mastitis
Approach to Therapy
- Continued drainage
- e.g., feeding
- Antibiotics
- e.g., dicloxacillin
Inflammatory Conditions
Inflammation of subareolar ducts
Pathophysiology
Periductal mastitis
Inflammatory Conditions
Usually seen in smokers
* Relative Vit A deficiency results in squamous metaplasia of laciferous ducts producing duct blockage & inflammation
Epidemiology
Periductal mastitis
Inflammatory Conditions
Presents as a subareolar mass with nipple retraction
Clinical Presentation
Periductal mastitis
Inflammatory Conditions
Inflammation with dilation (ectasia) of subareolar ducts
Pathophysiology
Mammary duct ectasia
Inflammatory Conditions
Rare; classically arises in multiparous post-menopausal women
Epidemiology
Mammary duct ectasia
Inflammatory Conditions
- Presents as a periareolar mass with green-brown nipple discharge (inflammatory debris)
- Chronic inflammation with plasma cells seen on biopsy
Clinical Presentation
Mammary duct ectasia
Green-brown nipple discharge = hallmark symptom
Inflammatory Conditions
Necrosis of breast fat
Pathophysiology
Fat necrosis
Inflammatory Conditions
Usually related to trauma
Etiology
Fat necrosis
Inflammatory Conditions
- Presents as a mass on physical exam or abnormal calcification on mammography
- Calcification due to saponification
- Biopsy shows necrotic fat associated with calcificatins & giant cells
Clinical Presentation
Fat necrosis
Inflammatory Conditions
Usually related to trauma
Etiology
Fat necrosis
Benign Tumors & Fibrocystic Changes
Development of fibrosis & cysts in breast
Pathophysiology
Fibrocystic change
Benign Tumors & Fibrocystic Changes
Most common change in premenopausal breast
* Thought to be hormone driven
Pathophysiology
Fibrocystic change
Benign Tumors & Fibrocystic Changes
Presents as vague irregularity of breast tissue (“lumpy breast”), usually in upper outer quadrant
Clinical Presentation
Fibrocystic change
Benign Tumors & Fibrocystic Changes
Cysts have blue-done appearance on gross exam
Gross Appearance
Fibrocystic change
Benign Tumors & Fibrocystic Changes
Benign, but some fibrocystic-related changes are a/w increased risk for invasive carcinoma
* Fibrosis, cysts, apocrine metaplasia: 0
* Ductal hyperplasia; sclerosing adenosis: 2x
* Atypical hyperplasia: 5x
Potential Complications
Fibrocystic change
Benign Tumors & Fibrocystic Changes
Fibrocystic change
Apocrine metaplasia, abundant pink cytoplasm; no increased cancer risk
Benign Tumors & Fibrocystic Changes
Papillary growth, usually into large duct
* Characterized by FV projections lined by epithelial (luminal) & myoepithelial cells
Histopathology
Intraductal papilloma
Papilloma = benign
Benign Tumors & Fibrocystic Changes
Classically presents as bloody nipple discharge in premenopausal woman
Clinical Presentation
Intraductal papilloma
Benign Tumors & Fibrocystic Changes
Intraductal papilloma
Approach to Diagnosis
- Must be distinguished from papillary carcinoma
- Papillary carcinoma also presents as bloody nipple discharge
- Histology: no underlying myoepithelial cells
- Epidemiology: more common in postmenopausal women
Benign Tumors & Fibrocystic Changes
Tumor of fibrous tissue & glands
* Estrogen sensitive: grows during pregnancy; may be painful during menstrual cycle
Histopathology
Fibroadenoma
Benign Tumors & Fibrocystic Changes
- Most common benign neoplasm of the breast
- Usually seen in premenopausal women
Epidemiology
Fibroadenoma
Benign Tumors & Fibrocystic Changes
Presents as a well-circumscribed, mobile marble-like mass
Clinical Presentation
Fibroadenoma
Benign Tumors & Fibrocystic Changes
Benign, with no increased risk of carcinoma
Potential Complications
Fibroadenoma
Benign Tumors & Fibrocystic Changes
Fibroadenoma
Fibrous tissue, glands; sharply demarcated from adjacent tissue
Benign Tumors & Fibrocystic Changes
Fibroadenoma-like tumor with overgrowth of fibrous componenet
* Characteristic “leaf-like” projections seen on biopsy
Histopathology
Phyllodes tumor
“Leaf-like” projections = histological hallmark
Benign Tumors & Fibrocystic Changes
Most commonly seen in postmenopausal women
Epidemiology
Phyllodes tumor
Benign Tumors & Fibrocystic Changes
Can be malignant in some cases
Potential Complications
Phyllodes tumor
Cancer is more common in post-menopausal women
Benign Tumors & Fibrocystic Changes
Phyllodes tumor
“Leaf-like” projection = hallmark; overgrowth of fibrous component
General
Breast Cancer
Epidemiology
- Most common carcinoma in women by incidence (excluding skin cancer)
- 2nd most common cause of cancer mortality in women
- Risk factors related to estrogen exposure
General
Breast Cancer
Risk Factors
- Female gender
- Age: cancer usually arises in postmenopausal women, except hereditary breast cancer
- Early menarche / late menopause
- Obesity
- Atypical hyperplasia
- First-degree relative with breast cancer
Breast Cancer
Malignant proliferation of cells in ducts with no invasion of basement membrane
Histopathology
Ductal carcinoma in situ (DCIS)
Malignant cells are bound by basement membrane
Breast Cancer
- Calcifications detected on mammogram
- Usually does not produce mass
- Biopsy of calcifications required for Dx
Approach to Diagnosis
DCIS
Note: calcifications can also be a/w benign conditions & fat necrosis
Breast Cancer
Characterized by high-grade cells with necrosis & dystrophic calcification in center of ducts
Histology
DCIS, comedo type
Breast Cancer
DCIS, comedo type
Duct full of cells with central necrosis & calcification
Breast Cancer
DCIS that migrates along duct to involve nipple epidermis
Pathology
Paget’s disease of the breast
Breast Cancer
Presents as nipple ulceration & erythema
Clinical Presentation
Paget’s disease of the breast
Breast Cancer
Almost always associated with underlying carcinoma
Complications
Paget’s disease of the breast
Unlike Extramammary Paget’s disease
Breast Cancer
Paget disease of the breast
Breast Cancer
Paget disease of the breast
Breast Cancer
Invasive carcinoma that forms duct-like structures
Histopathology
Invasive ductal carcinoma (IDC)
Breast Cancer
Most common type of invasive carcinoma in the breast
Epidemiology
IDC
Accounts for >80% of cases
Clinical Presentation
- Presents as a mass detected by physical exam or mammography
- Clinically: masses >2 cm
- Mammography: masses >1 cm
- Advanced tumors may result in dimpling of skin or retraction of nipple
Clinical Presentation
IDC
Breast Cancer
Biopsy shows duct-like structures in desmoplastic stroma
Histology
IDC
Breast Cancer
Subtypes of IDC
Histology
- Tubular carcinoma
- Mucinous carcinoma
- Medullary carcinoma
- Inflammatory carcinoma
Breast Cancer
Characterized by well-differentiated tubules that lack myoepithelial cells
Histology
Tubular carcinoma
IDC; very good prognosis
Breast Cancer
Tubular carcinoma
Well-differentiated tubules, no myoepithelial cells; desmoplastic stroma
Breast Cancer
Characterized by carcinoma with abundant extracellular mucin
Histology
Mucinous carcinoma
IDC; older women (age > 70); very good prognosis
Breast Cancer
Mucinous carcinoma
“Tumor cells floating in pool of mucus”
Breast Cancer
Characterized by large, high-grade cells growing in sheets containing lymphocytes & plasma cells
Histology
Medullary carcinoma
IDC; relatively good prognosis
Breast Cancer
Increased incidence in BRCA1 carriers
Epidemiology
Medullary carcinoma
IDC
Breast Cancer
Well-circumscribed mass that can mimic fibroadenoma on mammography
Morphology
Medullary carcinoma
IDC; relatively good prognosis
Breast Cancer
Characterized by carcinoma in dermal lymphatics
Histology
Inflammatory carcinoma
IDC; poor prognosis
Breast Cancer
Presents as an inflamed, swollen breast with no discrete mass
Inflammatory carcinoma
Tumor cells block drainage of lymphatics; can be mistaken for mastitis
Breast Cancer
Inflammatory carcinoma
IDC; inflamed, swollen breast; can be mistaken for acute mastitis
Breast Cancer
Inflammatory carcinoma
Tumor cells in dermal lymphatics
Breast Cancer
Malignant proliferation of cells in lobules with no invasion of basement membrane
* Often multifocal & bilateral
* Low risk of progression to invasive carcinoma
Histopathology
Lobular carcinoma in situ (LCIS)
Breast Cancer
Discovered incidentally on biopsy
* No mass or calcifications
Approach to Diagnosis
LCIS
Breast Cancer
Characterized by dyscohesive cells lacking E-cadherin adhesion protein
Histopathology
LCIS
E-cadherin = protein that holds adjacent celsl together
Breast Cancer
Treatment of LCIS
Approach to Therapy
- Tamoxifen: reduces risk of subsequent carcinoma
- Close follow-up
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Breast Cancer
Invasive carcinoma that characteristically grows in single-file pattern
* May exhibit signet-ring morphology
Histopathology
Invasive lobular carcinoma (ILC)
No duct formation due to lack of E-cadherin
Breast Cancer
ILC
Tumor cells growing in single-file pattern = histological hallmark
Prognostic & Predictive Factors
Breast Cancer: Prognostic Factors
Prognosis is based on TNM staging
* Metastasis is most important factor, but most patients present before metastasis occur
* Spread to axillary lymph nodes is most useful prognostic factor
* Sentinel lymph node biopsy is used to assess axillary lymph nodes
Prognostic & Predictive Factors
Breast Cancer: Predictive Factors
Predictive factors predict response to treatment
* Most important factors: estrogen receptor (ER), progesterone receptor (PR), and HER2/neu gene amplification (overexpression) status
* Presence of ER & PR: responsive to anti-estrogenic agents (e.g., tamoxifen)
* HER2/neu amplification: responsive to trastuzumab (designer Ab against HER2 receptor)
* “Triple negative tumors”: ER-neg, PR-neg, HER2/neu-neg; poor progrnosis
* African-American women have increased risk of triple-negative carcinoma
Breast Cancer
IHC: estrogen receptor (ER)
ER & PR are located in nuclei; ER/PR-pos = resposive to tamoxifen
Breast Cancer
IHC: HER2/neu amplification
GF receptor on cell surface; HER2-pos = responsive to trastuzumab
Breast Cancer
Prevalence of hereditary breast cancer
Epidemiology
- 10% of breast cancer cases
Breast Cancer
Features suggesting HBC
Epidemiology
- Multiple first-degree relatives with breast cancer
- Tumor at early age (premenopausal)
- Multiple tumors in a single patient
Breast Cancer
BRCA1 & BRCA2 mutations
Etiology
Most important single-gene mutations associated with HBC
Breast Cancer
BRCA1 mutation
Etiology
Associated with breast & ovarian carcinoma
* Increased propensity for medullary carcinoma
* Ovary: classically serous carcinoma
Breast Cancer
BRCA2 mutation
A/w breast carcinoma in males
Breast Cancer
Male Breast Cancer
Epidemiology
- Rare: 1% of all breast cancers
- Presents as subareolar mass in older males
- Highest density of breast tissue in males is underneath nipple
- May produce nipple discharge
- Most common histological subtype = IDC
- Lobular carcinoma is rare; male breast develops very few lobules
- Associated with BRCA2 mutations & Klinefelter syndrome
Breast Cancer
Male Breast Cancer
Epidemiology
- Rare: 1% of all breast cancers
Breast Cancer
Male Breast Cancer
Presentation
- Presents as subareolar mass in older males
- Highest density of breast tissue in males is underneath nipple
- May produce nipple discharge
Breast Cancer
Male Breast Cancer
Most common type of carcinoma
- Most common histological subtype = IDC
- Lobular carcinoma is rare
- Male breast develops very few lobules
Breast Cancer
Male Breast Cancer
Most common type of carcinoma
- Most common histological subtype = IDC
- Lobular carcinoma is rare
- Male breast develops very few lobules