Ruth Olson
Breast Pathology
2: Lobule/terminal duct: source
of 5-10% of Br Ca; Duct System:
source of 90% Br Ca
T3 basic elements: Skin / nipple,
Ducts / lobules, Fibroadipose
stroma
-Young breast: largely fibrous
stroma
- Older breast: largely adipose
stroma
1: The best predictor of developing carcinoma history in first degree maternal and
paternal relatives.
2: In the average patient it takes a long time (up to 30 years. But in some, it’s only a year.) 1: Lobular carcinoma invasive: 5-10%. The tumor starts with an in situ phase (LCIS).
Same biology of risk of developing invasivewe can’t predict. Can invade either
Patients can skip steps but we have no way to predict who. Ipsilateral invasion!
side!
1
Ruth Olson
Breast Pathology
Benign
Epidemiology
Fibroadenoma: benign
tumor derived from
stroma
Most common Br tumor in women < 35
Most commonly diagnosed Br tumor
Commonly develop in women taking cyclosporine.
Discrete movable, painless or painful mass
Stroma proliferates and compresses the ducts (duct epi isn’t neoplastic)
Increases in size during pregnancy (estrogen sensitive)
Does NOT progress to cancer.
General Facts
and Diagnosis
Circumscribed;
rubbery. Fine
needle or core
needle biopsy
Phyllodes tumor: Bulk
utmor derived from
stromal cells. (Usu
benign)
Intraductal papilloma:
Benign
Most common cause of bloody nipple discharge in women <50
Develop in lactiferous ducts or sinuses
No increased risk of Ca.
Type
Ductal carcinoma in situ (DCIS)
(non-invasive)
Lobular Carcinoma in situ (LCIS)
(non-invasive)
Infiltrating ductal carcinoma
Paget’s disease of the nipple
Medullary Carcinoma
Inflammatory carcinoma
Invasive lobular carcinoma
Tubular carcinoma
Colloid mucinous carcinoma
Gross: Histo
Treatment
Gross: Buldging grey/white surface
Surgical removal; cryoablation
Gross: Lobulated tumor with cystic
spaces containing leaf-life
extensions can be massive in
size.
Histo: hypercellular stroma w
mitoses malignancy
Wide excision
Big dilated duct.
If it’s bloody, it
represents
necrosis.
Comments
Nonpalpable; Patterns: cribirform (sieve-like) and coedo (necrotic center); commonly contain microcalicifications which allow it to be detected by mammogram;
1.3 eventually invade; treated with lumpectomy
Invasiveness:
Occurs almost always in region of prior biopsy of DCIS
-despite fact that up to 32% of patients will have multicentric (multiple quadrant) disease
-Lagios—mastectomy study—occult invasion found in 21% of patients with DCIS on biopsy
-DCIS with high nuclear grade and comedonecrosis—more likely to be multicentric, recur after local therapy, and be associated with invasive carcinoma
Nonpalbable; virtually always an incidental finding in a breast biopsy for other reasons; cannot be identified mammography; Lobules distended with BLAND
neoplastic cells; 1/3 invade; usus estrogen and progesterone receptor positive; Inc incidence of cancer in the opposite breast doesn’t have to be a lobular
cancer.
Stellate morphology; indurated(caused by reactive fibroplasiasdesmoplasia), grey-white tumor; Gritty on cut section
Extension of DCIS into lactiferous ducts and skin of nipple producing a rash with or without nipple retraction; Paget’s cells are present; palpable mass present in
50-60%
Associated with BRCA1 mutations; bulky soft tumor with large cells and lymphoid infiltrate; majority are estrogen and progesterone receptor NEGATIVE
Erythematous breast (looks like mastitis) with dimpling like an orange (peau d’orange) due to fixed opending of the sweat glands, which cannot expand with
lympedema; plugs of tumor blocking lumen of dermal lymphatics cause localize dlymphedema; very poor prognosis; combination chenmotherapy followed by
surgery and irradiation. Inflammatory carcinoma is already stage III/IV.
Neoplastic cells arranged in linear fashion or form concentric circles (bulls-eye appearance)
Develops in terminal ductules; inc incidence of cancer in opposive breast
Usu occurs in elderly women; neoplastic cells are surrounded by extracellular mucin. Less aggressive.
2
Ruth Olson
Breast Pathology
Breast Cancer
Epidemiology
Most common cancer in adult women. 2nd most common cancer killer (behind lung cancer.) Meanrisk age ~64 and risk inc. w/ age. Slightly dec. in incidence due to early detection
and treatment (thank you mammograms.)
Diagnosis
Clinical findings:
painless mass, usu
in upper outer
quadrant, skin or
nipple retraction,
painless axillary
lympadenopathy,
hepatomegaly and
bone pain if
metasticized
General facts
-Spread occurs locally (regional lymph nodes, breast skin, chest wall) and distantly lung/pleura, liver, bones, any organ)
-Distant (systemic) metastases may develop despite small primary tumors and initially negative axillary lymph nodes
-Some patients do not develop distant metastases despite larger tumors and positive axillary lymph nodes
-Early detection of breast carcinoma by means of mammography has reduced breast cancer mortality.
-Most patients with breast carcinoma have a long, indolent course  requiring long (years) follow-up to accurately evaluate different therapies
Biopsy (lumpectomy) alone
Lumpectomy + axillary node sampling : ± sentinel node identification and Radioactive dye hot spot locator. Positive: surgion complects resection. If neg, surgeon stops.
Lumpectomy followed by simple mastectomy
Lumpectomy followed by modifed radical mastectomy = mastectomy + axillary nodes
Rarely used: radical mastectomy = mastectomy, axillary nodes [extensive], and pectoralis muscles
Ductal carcinoma-in-situ: lumpectomy ± radiation; occasionally mastectomy
Additional staging information: Physical exam (general lymph nodes, organomegaly, any lumps), General chemistry and hematology screens, Radiologic imaging
Stage I (Early invasive)
Stage II(Early invasive) tumor size > 2 cm
Stage III (locally advanced)
Stage IV (Metastatic breast Ca)
Tumor less than 2 cm, axillary nodes
or positive but ipsilateral, mobile axillary
Extensive axillary nodal disease,
negative
nodes
supraclavicular node involvement, direct
tumor extension to chest wall or skin, or
inflammatory breast Ca
Family Hx in 1*relative (genetic basis in <10% of Br Ca  BRCA1 and BRC2 assoc.)
Age at menarche<12
Age at menopause> 55
Staging
Risk Factors
Palpation:
Fibrocystic disease
“Fibrous mastitis”
locally accentuated stroma
Lipomatous stroma
Fat necrosis
Fibroadenoma Cancer
Advantages:
Readily performed
Women can be instructed in
self-exam
Problems:
Cancers need to be relatively
sizeable & often advanced
before being palpable
Larger breasts are harder to
feel lumps in
Nonspecific:
90% of time a lump is found =
benign
Mammography: Advantages:
Utilizes conventional x-ray ± ultrasound
Tends to detect cancers much earlier than
palpation
can detect DCIS (calcification)
increased chance of cure
Can screen difficult to palpate, deeper
aspects of breast
MRI scanning—especially for sizing lobular
carcinoma
Disadvantages:
Relatively nonspecific: only ~25% of
"suspicious" mammograms show Ca on
biopsy
Most sensitive for Ca detection in older
breasts (more adipose tissue for
contrast) younger breasts are more
difficult to screen because of inc fibrous
stroma
Up to 10% of breast cancers maybe clinically
evident but mammographically occult
Open Surgical Biopsy = "gold
standard"
With/without prior
mammogram localization
Defines exact nature of palpable
and/or mammogram
abnormality
If positive for Ca, provides:
-Tumor type/subtype and
histologic grade (in situ vs.
invasive)
-Tumor size
-Status of biopsy margins
-Tumor tissue for special
studies: Hormone receptors
(ER/PR) and Other (her-2-neu,
DNA studies can indicate risk
of future occurance, etc.)
Stereotactic
Breast
Biopsy:
-Exact 3D
radiographic
localization
with
computer
needle
guidance
-Attemp to
reduce # of
“open”
surgical
biopsies
Fine Needle
Aspiration
Best use: confirming
clinically benign cyst
disease or clinically
obvious cancer
-If positive, may be
helpful in
planning/expediting
surgical therapy
-If negative with a
suspicious lump or
mammogram finding:
not helpful
need tissue biopsy for
more definitive
assessment
3
Ruth Olson
Breast Pathology
First child after age 35 Nulliparous
Fibrocystic change w/o epi hyperplasia
Fibroadenoma & sclerosing adenosis
Mod.-severe epil hyperplasia w/o atypia
Atypical ductal or lobular hyperplasia
Ductal or lobular carcinoma-in-situ
Invasive breast Ca: lifetime risk of contralateral Ca 20%
Obesity
High socioeconomic status
North American/Northern European
Intermediate Theory: Bloodstream important in tumor dissemination; operable Br Ca is a systemic disease in many but not all cases; variations in local-regional Rx are unlikely to
have a major influence on survival BUT are of significance in some patients; WE HAVE MOVED TOWARD MORE BREAST PRESERVATION
Treatment
Facts and
Paradoxes
Assays
Gynecomastia
and Br Ca in men
Radiation:
Chemotherapy: Two types:
In past—only used for more advanced Ca, recurrent Ca at
Hormone ablative: In past—oophorectomy, hypophysectomy, adrenalectomy . Now—estrogen antagonists (e.g.,
mastectomy site, or selected patients with distant
tamoxifen—for estrogen receptor positive tumors)
metastases producing focal symptoms
General cytotoxic: usually multiple drugs given in combination with nonspecific cytotoxic effects
Now—also used for in-situ or early invasive Ca in
conjunction with lumpectomy-only/nodes-only surgery
Newer, evolving therapies (e.g., oncogene targeting): Herceptin—attacking cells overexpressing her-2-neu receptors
May metastasize 10 to 15 years after treatment.
70% of patients with lymph node-negative disease will be cured by local (breast-only) therapy. Current challenge: how to identify the 30% with systemic micrometastases who might
benefit from adjuvant systemic chemo/other therapy. ? newer genetic analysis of tumor tissue to provide powerful prognostic predictors?
Oncotype assay:
21 gene assay of a patient’s tumor (RT-PCR method)
Currently being used for patients with lymph node-negative cancers
Has been shown to predict likelihood of recurrence at 10 years post-diagnosis into low (ave. 7%), medium (ave. 14%), and high (ave. 31%) risk groups
Low risk patients (about 50% of node-negative cancers) who are elderly or have other co-morbidities may choose not to receive adjuvant chemotherapy
Unilateral or bilateral breast enlargement in males caused by any state with relatively increased estrogen effect relative to androgen effect
General categories: Physiologic: neonatal, pubertal, involutional/aging (1/3-1/2 of older adult men) DOESN’T INC BR CA.
•
Pathologic:
–
tumors producing estrogen or HCG (testicular, adrenal)
–
primary (e.g., Klinefelter's) or secondary hypogonadism
–
liver disease, renal disease, hyperthyroidism
–
enzyme defects in androgen synthesis
–
miscellaneous, idiopathic drugs: estrogens and anti-androgens (prostate Ca Rx)
Male Br Ca
•
Rare compared to females (1 male breast Ca for every 100-150 female cases)
•
Typically older age, often advanced stage, almost always ductal type
•
Risk factorssimilar to women (family history, relative hyperestrogenism); Klinefelter's syndrome
Questions
5. What is the most common Br tumor in women < 35
1.
2.
3.
4.
T/F Gynecomastia increases risk of breast cancer in men
Name risk factors of developing breast cancer.
What are some of the advantages and disadvantages of palpation?
What are some of the advantages and disadvantages of mammography?
6.T/F Lobule/terminal duct is the source of 5-10% of Br Ca. Duct System is the source of 90% Br Ca.
7. Which tumor plugs lymphatic drainage causing an erythemetous “mastitis-like” breast?
8. T/F Tumors always metasticize to the ipsilateral breast.
4
Ruth Olson
Answers
1.
2.
3.
False
Family Hx o in primary relative
Age at menarche<12
Age at menopause> 55
First child after age 35 Nulliparous
Fibrocystic change w/o epi hyperplasia
Fibroadenoma & sclerosing adenosis
Mod.-severe epil hyperplasia w/o atypia
Atypical ductal or lobular hyperplasia
Ductal or lobular carcinoma-in-situ
Invasive breast
Obesity
High socioeconomic status
North American/Northern European
Palpation:
Breast Pathology
4. Mammography
: Advantages:
Utilizes conventional x-ray ± ultrasound
Tends to detect cancers much earlier than palpation
can detect DCIS (calcification)
increased chance of cure
Can screen difficult to palpate, deeper aspects of breast
MRI scanning—especially for sizing lobular carcinoma
Disadvantages:
Relatively nonspecific: only ~25% of "suspicious" mammograms show Ca on biopsy
Most sensitive for Ca detection in older breasts (more adipose tissue for
contrast) younger breasts are more difficult to screen because of inc fibrous stroma
Up to 10% of breast cancers maybe clinically evident but mammographically occult
5. Fibroadenoma
6. True
7. Inflammatory carcinoma
8. False
Fibrocystic disease
“Fibrous mastitis”
locally accentuated stroma
Lipomatous stroma
Fat necrosis
Fibroadenoma Cancer
Advantages:
Readily performed
Women can be instructed in self-exam
Problems:
Cancers need to be relatively sizeable & often advanced before being palpable
Larger breasts are harder to feel lumps in
Nonspecific:90% of time a lump is found = benign
5