Breast Pathology Flashcards
Polythelia, supernumerary nipples
accessory nipples along the milk line
polymastia-
accessory true mammary gland
Amastia
abscence of breast
congenital inversion of nipple
may be confused with carcinoma
macromastia
treated by reduction mammoplasty
micromastia
treated by augmentation- implants, TRAM-transverse rectus abdominis, mycocutaneius flap.
needle core biopsy
needle for localized breast lesions, but some have been replaced by FNAC, excision biopsies-
masectomies
simple skin sparing
radical including pectoralis major muscles,
modified radical includes the axillary LN’s
subctaneous without skin, performed on men
Prophylactic and therapeutic masectomies
Galactocele
Pathogenesis- cystic dilatation of obstructed duct during lactation
-clinical- painful lump
complications- infected persistent induration.
Fibrocystic (disease of the breasechange(FCC)
Morphology- chronic cystic mastitis, mammary dysplasia, fibrocystic disease- stroma- fibrosis, duct epithelium- prolifferation -mild simple and severe atypical. could have bluedomed cysts (micro,macro),
- Mammography may show microcalcification in concretions of secretions or necrosed epithelial cell heaps0 mistaken for carcinoma.
- non proliferative is simple FCC, no epithelial hyperplasia RR-1
- proliferative disease without atypia- FCC RR 1.5-2 times-
- -sclerosing adenosis
- -florid benign hyperplasia
- -radial scar
- -papilloma
- Proliferative disease with atypia- RR4-5 times
- ADH
- -ALH- atypical lobular hyperplasia
Pathogneesis- exaggerated, distoreted cyclical changes associated with hormonal changes of menstrual cycle(even normal breast have some irregularity)
clinical: lumpiness, pain, tenderness, continuous or cyclicla- usually after 35-40, may persist after menopause, can be detected in autopsy
Therapy- Oral contraceptives somehow
complications- non-proliferative to proliferative atypical hyperplasia and can develop into malinancy
Simple FCC(non proliferative
Morphology- cysts and fibrosis, multifocal bilatera
- 1-5 cm blue domed cyts, serous or turbid fluid, apocrine metaplsia
- fibrosis and stroma
- lyphomononuclear infiltration
- duct extasia
- adenosis
- mild hyperplasia.
Proliferative FCC
Morphology:
epithelial hyperplasia- ducts and ducturles mild to severe, atypical, typical
-cribriforme pattern
-duct papillomatosis- mild, moderate, severe, may produce nipple discharge
-risk of carcinoma correlates with decree of atypical hyperplasia
- like simple FCC but with nippe discharge and microcalcification on mammography
Clinical- vague nodularity, bilateral tendency to increase before menses, skin normal no axiallary LN
Sclerosing Adenosis
Clincal: hard irregular lump, (suggests malignancy), borders not well defined(sugests infiltration) NOT MALIGNANT
Morphology
- histologically mimics carcinoma
- hard rubbery mass, dense fibrous stoma, mammography may be positive for calcification,
- masses of proliferated ducts and ductules with a back to back arrangement.
- look for double layer of cells- myoepithelial cells
Complications:very low risk of carcinoma.
Inflammation of the breast
Etiology
- acute mastitis- usually in lactating state inspisated secretions, fissure in nipples attract bactera
- Staph- small localized under nipple may leave residual indurated scar
- strep- whole breast, marked swelling and tenderness, heals without scar.
Clinical- usually female, nursing baby, has enlargement and painin her left breast, becomes reddish and nipple is cracked.
Duct ectasia, Plasma cell mastitis, granulomatous mastitis
morpohlogy- inspissated secretion, dilatation, rupture, inflammation, granular debris, leukocytes, foamy histocytes, lymphomononuclear cells, plsama cells, granulomas
Pathogenesis- dilated duct ruptre causing inflammation - will see plasma cells, histiocytes, giantcells, granulomas.
complications- induration, nipple retraction, mimics carcinoma clinically, bloody discharge, sudden painful enlargement.
Traumatic fat necrosis
Etiology uncommon- history of trauma, large pendulous breasts
Morphology- fat necroiss cholesterol clefts, neutrophils, lipid laden macrophages. later will see lympohcytes, fibrosis, cysts and calcification.
mimic carcinoma clinically-
Implants
complications: abscess, foreign body granuloma, fistulae
Fibroadenoma
Morphology- Loose edematous myxoid fibroblastic stroma+ ductlike lined cells
- pericanalicular- oval ducts surrounded by stroma
- intracanalicular- elongated compressed, distoreted ducts
- mixed pattern, no clinical significance of patterns,
- MOBILE lump, not fixed
Etiology: tumor of the stromal cells
Course- Benign tumor, no malignant potential. very low there is an assocaitin with cysts larger than .3 cm and papillary apocrine change
large lobulated popcorn calcifcation small clustered calcification on mammogram- require BX to exlude CA
Phylloides Tumor-cystosarcoma phylloides
- Morphology-Giant, lobulated, cut surface slits and clefts, leaf like
- Benign- zonal hypercellularity, mild atypia stromal cells , no stromal overgrowth, mitosis is less than 5/HPF pushing borders
- borderline- zonal hypercellularity, moderate stromal cells, no stromal overgrowth, mitosis 5-10/HPF, pushing borders
- if malignant - stroma,- mitosis, anaplasia(sarcoma- may recur, zonal hyperceullarity, mod-marked atypia stromal cells, stromal overgrowth, mitosis more than 10 /HPF infiltrative borders
Course: usually benign 1% of benign and 27% of malignant recur, 10% metastatisze,
Metastasis is through hematgenous route not LN, infiltrate surrounding breast
Treatment- wide local excision without LN dissection.
intraductal papilloma
Clinical: serous nipple discharge(nipple inthe lumen of major ducts, can be bloody.) retracted nipple, no inflammation, firm subareolar lump small palpable masses, desnity or calcification on mammogram for both papillomas.
diferential- duct extasia, carcinoma.
Morphology- delicate branching papillae in lumen, fibrovascular core, double layer of epithelial cells, no atypia or mitosis, if multpile,
- large duct papilloma- solitary, situated in lactiferous sinuses of nipple, bloody discharge
- small duct papillomas: multiple and located deeper within the ductal systems.
Pathogenesis- arise in the lumen of a large duct, singel less than 1 cm
Course: recurrence causes risk of cancer
Treatment-excise the whole duct system involved.
Carcinoma of breast
Epidemiology- Second most common malignancy in females, lung is commonest- accounts for 20% of cancer deaths in females, over 40 years, 25% postmenopausal, curable, rare in males.
Morphology- upper outer quadrant 50% central 20%, other 3 qudrants- 10% each, bilateral 4-10%, LN at time of diagnosis, axillary, internal mammary, l after supraclavicular.
Risk factors- US moe than japan or taiwan, familial, some autosomal dominant, ovarian carcinoma at early age, early menarche, late menopause, more nulliparous, if first child after 30 years of age, obesity, high fat diet,
Types:
- noninfiltrating (in situ) intraduct carcinoma (comedo, pappilalry, paget’s) lobular carcinoma in situ(LCIS)
- infiltrating carcinoma- duct(scirrhous, medullary, colloid, lobular.
Etiology- BRCA-1 gene Chr. 17q21, Brca 2 chr 13,q12, FCC with atypical epithelial hyperplasia.
Clinical- lump in breast 2.5 cm located in upper outer quadrant,firm, ill defined borders, overlying skin dimpled and adherent to the mass, axillary LN enarged., induration, nipple retraction
-lymphedema- skin thick around hairfollicles peaud’orange
prevention- self exam, clinical palpation, mammography in high risk routine. -1-2 years after 40 years of age
investigations- FNAC, needle biopsy, lumpectomy, nipple aspiration, ductal lavage, randome periareolar FNA, Core needle biopsy, vaccum assisted sterotactic, advanced breast biopsy instrument ( ABBI)
Metastais- lungs, bone, liver, adrenals, any site in the body, may appear 15 years after treatment of primary lesion.
Ductal carcinoma in situ (DCIS)
Bilateral 10-20%, develop carcinoma rate of 1% per year, (Low grade, undtread, small) death in less than 2%, Breast conservation surgery: what we look at to determine this. Recurrence- grade size margin status, ideal is less than 1 cm.
types- comedo- central area has a large necrotic focus, solid, crobriform, papillary, micropapillary
Comedo carcinoma
5% intraduct tumor (high grade DCIS)
- Necrotic center- Cells ispissated material(squeeze out like toothpaste)
- less often ER, PR positive, Her2Neu positive
- high recurrence rate
- up to 60% invasive
Infiltrating ductal carcinoma not otherwise stated
commmonest- 75%, scirrhous- hard, dense, desmoplasia,
cords and nest cells 3.4 cm.
- infiltrative edges
-necrosis, calcification.
Colloid carcinoma
Mucinous- (greater than 90% special type, rare( 1-6%
-intracellular and extracellular mucin,
assoicated with solid non-invasive paipplary carcinoma,
-very good prognosis.
Medullary carcinoma
2% fleshy, soft, large sheets of large oval cells, little stroma, lymphocytic immune response,
- better prognosis,
- structure similar to dysgerminoma ovary, seminoma testis
Lobular carcinoma
Etiology- arise from terminal ductules
- Multicentric 20% bilateral
- tyep types in situ and infiltrating,
- insitue no mass, detected incidentally in FCC or mammography
- micro entire lobule distended- oval noncohesive cells
- no pleomorphism or mitosis
- 30% cases exhibit invasive lobular or duct carcinoma, same side or opposite side.
Infiltrating lobular carcinoma
poorly outlined, induration, no distinct masses
- indian file- footprints of Indians on the sand in a linear fashion- single file of tumor cells, round, uniform
- Bull’s eye pattern- tumor cells around normal acini and ducts
- with or without carcinoma.
Inflammatory carcinoma
occasionally a carcinoma in pregnancy behaves very aggressively and clinically mimics an abscess- hot tender, called inflammatory carcinoma- bad prognosis.
Paget’s disease of breast
intraduct carcinoma in large duct with spread to skin, areola, nipple
excema even without a palpable masss
-hyperemia, edema, fissuring, ulcer, oozing
-can have infection
-biopsy paget’s cells, large hyperchromatic nucleus with halo
-look aggressively for underlying intraduct carcinoma.
assocation, neet to make sure that there sin’t invasive or underlying ductacl carcinoma.
Paget’s disease of nipple
1-4% cases, palpable mass- 50-60% underlying invasive carcinoma- poorly differentiated, ER negative, overexpress HER2Neu- prognosis of paget’s disease depends on features of underlying carcinoma.
- extend from DCIS via ductal system via lactiferous sinuses into nipple skin.
grading of ductal insitu and invasive
Grade1-3 - tubule formation, nuclear atypia, mitosis (score 1-3 for each feacture
Grade 1- well differentatied (3-5
Grade 2 (score 6-7)
Grade 3 (score above 7
Staging of ductal carcinoma insitu and invasive
1- up to 2 m no LN- 5 year survival-80%
2-2-5 cm plus regional LN- 65%
3- greater than 5 cm and other LN- 40%
IV- any size and distant metastasis- 10%
Biological behavoir of carcinoma in situ
Non-metastasizing- intraduct, insitu, lobular
- uncommonly metastaszing- colloid, medullary, infiltratting
- all others metastasizing.
ER/PR testing
at least one percent of tumor in the sample is a positive test, helps predict whether a patient is likely to benefit with endocrine treatment.
- 60% of breast carcinomas express ER,
- ER+, PR + tumors respond to tamoxifen in 60-70% of cases less to chemo
ER- PR+ up to 50%
ER+ PR- 40%
ER-PR- - less than 10 % more response to chemo.
Her 2 status
has a worse clinical outcome, lack of response to chemo, hormonal therapy, response to herceptin, but herceptin cannot cross blood brain barrie so not usefl against metastatic disease
Ductal Carcinoma, NOS
Luminal A 40-55%: ER + Her2neu -ve, post menopausal, slow growing, well to mod diff. respond well to hormonal treatment, decreased response to standard chemotherapy
Luminal B 15-20%: ER+, Higher grade, triple positive tumour, express Her2 neu, LN metastasis, may respond to chemo
Normal breast like 6-10%: well differentiated ER+, Her2Neu-ve, Basal like 13-25%: Triple negative, BRCA +, younger females, medulllary calcium, metaplastic calcium, spindle cell calcium. high grade, aggressive, mets to brain, 15-20% complete reponse to chemo, cure possible in chemo responsive group.
Prognosis for breast cancer
TMN staging and grading are most important,
- ER which respond to oopherectomy or tamoxifen,
- PR usually with estrogen receptors, if a lone, may indicate bad prognosis
- Her2neu (C-erbB2) high grade malignancy therapy with antibody- herceptin.
- proliferative rate, aneuploid- bad prognosis.
- oncogene amplification- activated myc, neu, loss of RB suppresor gene,
- angeiogenesis, high cathepsin D in tumor- degrades baement membrane and connective tissue- indicator of metastatic potential
Best Prognosis
tumor less then 2 cm
- without axillary LN involvement
- intraductal and LCIS
- with ER positivity
- which lack aneuploidy
- lack cathepsin D
- lack her 2neu
Mammography positive
60-80% of carcinomas
intraduct carcinoma
FCC proliferative, sclerosing adenosis.
Male Breast
gynecomastia+ male analog of FCC- relative or absolute increase in estrogens, reduced androgens, testicular angdrogen loss
Etiology
-cirrhosis klienfelter syndrome, estrogen therapy retroviral therapy t/t, anabolic steroids.
Morphology
button like nodule beneat areola,
-intraduct hyperplasia.
breast carcinoma in males
Rare
Etiology- reduced testicular funtion, XXY karyotype, 1st degree relatives with breast cancer, exogenous ER, increasing age, infertility, obesity, prior breast disease, ionizing radiation exposure
-4-14 % germline BRCA2 mutation
rapid infiltration because less amount of breast substance in male
-large ducts in nipple, 2-3 cm in size, nipple discharge, LN metastasis, distance metastasis, to lung, brain bone, liver
-Mastectomy with axillary clearance
