Pathology Breast Lesions Flashcards
Thelarche
- Rapid growth of breasts at onset of puberty, usually age 10-11 in females
- Entry into Tanner stage II of development
- Growth is due to fat deposition, periductal connective tissue and elongation and thickening of ductal system
- Influenced by estrogens, growth hormone and prolactin, but not progesterone
Premature Thelarche
- Prior to 9 y/o
- Isolated or part of precocious puberty
- No lobules are present
Tanner Stage I
- Preadolescent; no breast buds
Tanner Stage II
- Breast budding (Thelarche) w/ small area of surrounding glandular tissue
- Areola begins to widen
Tanner Stage III
- Enlargement of areolar diameter
Tanner Stage IV
- Areola/papilla form secondary mound w/ separation of contours
Tanner Stage V
- Mature female breast
Nonproliferative Breast Change (Fibrocystic changes) Lesions
- Duct ectasia
- Cysts
- Apocrine change
- Mild hyperplasia
- Adenosis
- Fibroadenoma w/o complex features
Proliferative Disease W/O Atypia Lesions
- Moderate or florid hyperplasia
- Sclerosing adenosis
- Complex sclerosing lesion (radial scar)
- Fibroadenoma w/ complex features
Proliferative Disease W/ Atypia Lesions
- Atypical ductal hyperplasia (ADH)
- Atypical lobular hyperplasia (ALH)
Carcinoma In Situ Lesions
- Lobular carcinoma in situ (LCIS)
- Ductal carcinoma in situ
Pathologic Lesions Ductal Morphology Chart
Histologically where most breast pathology occurs
- Terminal duct-lobular unit
Breast Lobule Structure
- Breast composed of 15-25 lobes, emptying into separate major duct terminating in nipple
- Lobule is divided into 10-100 alveoli
- Pregnancy increases the lobuloacinar differentiation
Breast Lobules Immunohistochemical Histology
- Immunohistochemical stain for lactalbumin showing secretory product in lobules and secretory tissue
- Smooth muscle actin demonstrating myoepithelial cells
- Normally have the grape like cluster of smooth like ovals, usually ~1 cell layer thick, cells are fairly uniform in size and shape and pretty bland looking w/ no prominent nuclei or atypia
***NOTE: When looking at a immunohistochemical stain blue is usually the background stain just showing that the dye is working, brown is usually the targeted substance we are trying to highlight
*in the attached histology slide they are staining for lactablumin; a product found in breast milk
*the stained brown rim around the lumen is smooth muscle actin which is important to look at for carcinoma insitu b/c smooth muscle actin will highlight epithelial cells that are suppose to surround normal lobules and ducts and help squeeze the milk out; if we lose myoepithelial cells or breaking thru of this layer this is then a sign of either invasive cancer or indication of losing the myoepithelial structure thru some pathologic process
Macromastia
- Condition in females where breasts undergo rapid and massive enlargement at puberty
- Exuberant connective tissue w/ minimal lobular formation
Supernumerary Nipples/Breast
- Persistent epidermal thickenings along milk line
- Primordial breast cells that fail to involute
- Combinations of breast glandular tissue and nipple
- Occurs in 2-6% of females and 1-3% of males; may be more common on left side in males
- In women, may not be noticed until pregnacy
- Can get breast cancer in these regions if theres enough ductal tissue
Presentation of Breast Disease Pie Graph
- If the lumps are multiple in that not just one breast mass or lump where pt. describes “lumpy bumpy” feel and especially when it is B/L; this is usually a benign fibrocystic change
*only 1% w/ these presenting symptoms have cancer
- Breast pain; can also be due to just fibrocystic change and influence of caffeine or and type of trauma; breast discomfort is unusual for breast cancer
*5% of these presenting symptoms have cancer
- Nipple discharge is usually from a benign intraductal papilloma
*7% actually have cancer
- Palpable mass indice for cancer goes up w/ age; in younger women more likely to be a cyst or fibrocystic change or other things not cancer
*12% will actually have cancer
Age vs. Likelihood a Breast Mass is Cancer
- <40 more likely benign growth
- 40-50 chance of cancer is increased
- >50 more likely to be cancer
Benign vs. Malignant Lesions Mammography Apperance
- Benign lesions tend to be:
*well-circumscribed
*round
- Malignant lesions tend to be:
*stellate and circular w/o calcifications (64%)
*stellate and circular w/ calcifications (17%)
*calcifications only (19%)
Fine Needle Aspiration (FNA)
- Minimally invasive technique to examine if tissue might have a cyst and is a superficial lesion
Core Biopsy
- Minimally invasive technique
- Stereotactic needle guided biopsy
- Digital mammogram machine connected to computer
- Needle guidance system to sample lesion that is not palpable
- Enables to the testing of more deep non-palpable lesions
- Angle of procedure has to be just right for adequete diagnosis
Acute Mastitis
- Assoc. w/ lactation and cracks in nipple
- Will usually find this if a women is nursing on one side more than the other
- Mastitis occurs in 5-15% of post-partum primiparous women
- Usually unilateral
- Most often due to Staphylococcus, but bacteria may not be isolated from culture
- Can lead to abscesses
Acute Mastitis Histologically
- Keratinizing squamous epithelium extending into nipple ducts
- Trapped keratin debris can cause duct dilation and rupture
- Neutrophils
Periductal Mastitis
- More severe form of acute mastitis; in response to irritation the epithelial cells which instead of being on the surface of the areola, start tracking back which aren’t suppose to; thats the cuboidal epithelium; so we’re getting metaplasia of cells that are suppose to be on the outside, tracking in; this can result in the cells keratin breaking of and forming plugs in the ducts
*majority of pts are smokers
- AKA subareolar abscess, squamous metaplasia of lactiferous ducts
- Presents w/ painful, erythematous, subareolar mass; appears infectious
- Majority are smokersd
Duct Ectasia
- 50-60 y/o women
- Multiparous, related to stagnant colostrum
- May cause retraction or inversion of nipple and discharge, clinically looks like cancer
Duct Ectastia Histologically
- Microscopically- dilated large ducts w/ foamy macrophages in lumen
- Calcifications common
Breast Fat Necrosis
- Duct ectasia or fibrocystic disease—>rupture cysts extravasate luminal content causing reaction
- Trauma (ie steering wheel in car accident, sports injury) compressing tissue leading to necrosis
- Can cause dippling on the skin; can be scary looking as cancer can also pull skin inward
- On Mammography can form “egg-shell” oil cysts and display calcifications
Foreign Body Reaction Breast Lesion
Often biopsy related
- Not encapsulated
- Giant cells
- Other inflammatory cells
- Fat necrosis
- Calcification
- Cholesterol clefts
- Hemosiderin
- May see suture or polarizable material
Foreign Body Reaction Histologically
- Foamy clefts w/ foamy macrophages; fat tissue that got compressed leaving behind fat cholesterol crytals
Reactions to Silicone Breast Implants
- Silicone can leak allowing for droplets of silicone to initiate a foreign body reaction; foamy macrophages, giant cells, lymphocytes
Granulomatous Mastitis
- Rare
- Young women (avg 36 y/o) w/ inflammatory breast processes
- Corynebacterium (normal skin flora?)
- Not related to smoking
- Grossly can look like breast cancer
Granulomatous Mastitis Diagnosis
- Diagnosis of exclusion
- Must rule out:
*systemic granulomatous disease ie Wegener’s granulomatosis, sarcoidosis
*infections ie mycobacteria, fungi, cat scratch disease (Bartonella henselae)
*panniculitis
*foreign body reaction
*fat necrosis
Lymphocytic Mastitis
- AKA diabetic mastopathy, usually DM type I
- Uncommon
- Mainly women, but may occur in men w/ gynecomastia
- Often B/L
- Treated w/ excision, but often recurs, not serious but can cause clinically confusion w/ looking like cancer
- Lymphocytes are infiltrating around ductal and lobular tissue; not clear why
Benign Breast Diseases
- Fibrocystic “disease”
- Duct hyperplasia
- Adenoma
- Intraductal papilloma
- Nipple adenoma
- Adenosis
Benign nonproliferative Lesions
- Single nonproliferative lesions are not assoc. w/ increased risk for cancer
*fibrocystic change
*solitary papilloma
*fibroadenoma
- Unclear if multiple nonproliferative lesions increase the risk for breast cancer
Proliferative Lesions Risk of cancer
- Proliferative lesions, w/o cytologic atypia have slightly increased risk of cancer (relative risk 1.3 - 2)
*complex fibroadenoma
*florid hyperplasia
*sclerosing adenosis
*intraductal papillomas
- Proliferative lesions w/ atypia have a higher risk of cancer (relative risk 4 - 6)
*atypical lobular hyperplasia
*atypical ductal hyperplasia
- Risk is higher (10-fold) when the atypia is multifocal
Fibrocystic Changes
- Freq. seen in 25-45 y/o women
- More common in Caucasians
- Hormonal influence? exact pathogenesis unknown
- Usually B/L
- Mainly affects TDLU
- Aberration of normal development
- Blue-dome cysts contain turbid fluid
- “Lumpy-bumpy” described as
- Oral contraceptives decrease fibrocystic changes b/c of balanced estrogen and progesterone effect
- If “non-proliferative” = no significant increase in risk of breat cancer
Fibrocystic Disease Features
- Fibrosis; background stroma may be thicker and denser than it normally would
- Cysts (apocrine metaplasia)
*cysts line by apocrine epithelium (abundant, granular eosinophilic cytoplasm)
- Other:
*calcification
*chronic inflammation
*epithelial hyperplasia
Fine Needle Aspiration of Fibrocystic Cells Histology
Florid Duct Hyperplasia
- Filling of duct w/ lining cells, slit-like fenestrations
- Cells are oval, streaming in pattern
- Normal ducts have 2 cell layers, if > 4 cell layers then 1.5 - 2x risk of breast cancer
How to deal w/ FCC discomfort
- Supportive bras
- OTC pain relievers such NSAIDs
- Reduced intake of caffeine and stimulants found in coffee, tea, chocalate, and soft drinks
- Oral contraceptives may help women w/ severe symptoms
Atypical Ductal Hyperplasia
- Increased risk of breast cancer (4 - 5x)
- Risk equal in both breasts
- Risk higher (10x) if 1st degree relative has breast cancer
- Usually small foci (<3mm)
- Excision recommended b/c assoc. w/ DCIS
Atypical Duct Hyperplasia Features
- Bland, monomorphic cell pop.
- Low-grade cytologic features- minimal nuclear pleomorphism
- Cells haphazardly arranged
- Size smaller than 3mm in greatest dimension
- Can resemble DCIS
Usual Hyperplasia vs. Atypical Ductal Hyperplasia Chart
Atypical Ductal Hyperplasia “Roman bridges” Histology
Atypical Lobular Hyperplasia
- 4 - 5x usual risk of breast cancer, higher in ipsilateral breast, higher if age <50
- 19% develop invasive cancer at mean 15yrs, 42% are special subtypes w/ good prognosis
- Excision is recommended b/c some cases assoc. w/ DCIS
Atypical Lobular Hyperplasia Histology
Intraductal Papilloma
- May present w/ bloody nipple discharge
- Gross: polypoid mass protruding into dilated duct
- Histology: arborizing architecture, nuclei generally bland, but may have minor pleomorphism
Nipple Adenoma
- Can have complex arborizing pattern—> must be careful not to overdiagnose as cancer
Lactating Adenoma
- Reproductive age women
- Presents as mass <5cm
- Gross: lobular, yellow mass, vascular (will blee unlike most lesions)
- Histology: hyperplastic lobules w/ cytoplasmic vacuolization
*will generally recede
Sclerosing Adenosis
- Relatively common, often B/L, usually assoc. w/ another form of proliferative fibrocystic change
- Can present as a palpable mass, well-circumscribed, <2cm
- Usually microscopic finding
- Approx. 1.7x risk of invasive carcinoma
- Retention of loulocentric architecture
Sclerosing Adenosis Histology
- Proliferation of small duct-like structures w/ distortion of lobules
- Retention of myoepithelial cells as evidenced by smooth muscle actin stain
Radial Scar
- Often multifocal or B/L
- Grossly and radiographically can mimic cancer- stellate lesion
- 1.8x cancer risk
Radial Scar Histology
- Histology: normal breast structures surrounding and entrapped by central scar tissue
- Elastin stain shows scar tissue
*black is scar tissue
*red is normal breast parenchyma
Stromal Tumors
- Fibroadenoma
- Phyllodes tumor
Fibroadenoma
- Most common, benign tumor of breast
- Women 25-35 y/o
- Incrases in size during pregnancy
- Tends to regress w/ age
- Sharply demarcated
- Usually <3cm
- White, tan, bulging surface
- Whirling pattern of slit-like spaces
- Can be drug-related; 1/2 of women receiving cyclosporin A after renal transplant develop FA
Fibroadenoma Fine Needle Aspiration (FNA)
- Cohesive, bland nuclei
- Staghorn configuration
Fribroadenoma Histology
- Cellular, fibroblastic stroma encasing glandular and cystic spaces, often cleft-like spaces
Juvenile Fibroadenoma
- Also called giant fibroadenoma
- Adolescents, often African-American
- B/L, w/ rapid growth to >10cm
- May have ductal hyperplasia but not atypical ductal hyperplacia or ductal carcinoma insitu
- Low overall risk of carcinoma
- Follow-up recommended
- Differential includes phyllodes tumor, but rare in adolescents
Juvenile Fibroadenoma Histology
- Stroma may be more cellular than typical FA
- Ducts may show epithelial hyperplasia
Benign Phyllodes Tumor
- Polypoid tumor w/ a leaflike pattern
- Stroma is similar to a fibroadenoma, but more cellular
- 75% are benign, trated by local excision
Galactorrhea
- Lactation in men or in women who are not breastfeeding
- Pituitary adenomas can secrete prolactin (classified by the hormone they secrete)
*Dx: measure prolactin lvls and imaging test
*Treatment: tumor inhibition w/ dopamine agonist drugs or resection of adenoma
Pituitary Adenoma
- Most are microadenomas (<10mm)
- Most grow slowly and are considered benign
- Can invade the cavernous sinus, sphenoid sinus and base of brain
- Classified by hormone production (growth hormone, prolactin, TSH, ACTH, or FSH)
Galactorrhea Causes
- Assoc. w/ certain drugs, including phenothiazines, certain anti-hypertensives ie alpha-methyldopa, opioids
- Assoc. w/ primary hypothyroidism
*increased lvls of thyroid-releasing hormone increases secretion of prolactin as well as thyroid-stimulating hormone (TSH)
Gynecomastia
- Enlargement of the male breast
- Imbalance b/w estrogens and androgens
- Puberty or aged
- Usually resolves spontaneously
Gynecomastia Causes
- Klinefelter syndrome
- Drugs; marijuana, heroin, anabolic steroids, psychoactive drugs
- Hormone-secreting adrenal or testicular tumors
- Paraneoplastic production of gonadotropins by cancers
- Liver disease and hyperthyroidism (increased conversion of androstenedione into estrogens)
Gynecomastia Histology
- Proliferation of ducts w/o lobules
- Dense, periductal stromal fibrosis
- Can have edema w/ micropapillary hyperplasia and mild lymphocytic infiltrate
- Myoepithelial cells preserved
