BREAST PATHOLOGYBREAST PATHOLOGYbyby

Dr. Richard RaymondDr. Richard Raymond

MASTITISMASTITIS Acute MastitsAcute Mastits

a)a) Common during lactationCommon during lactationb)b) Organism:Organism: Staphylococcus Staphylococcus

aureusaureus (most common) (most common)

Fat necrosisFat necrosisa)a) Often related to trauma or prior Often related to trauma or prior

surgerysurgeryb)b) May produce a palpable mass or May produce a palpable mass or

lesion on mammographylesion on mammography

                                            

There are two types of Mastitis: 1. Cellulitis - which involves an infection of the connective tissue. 2. Adenitis - which is an infection in the milk duct. In either case, mastitis usually affects only one breast.

A patient with inflammatory breast cancer generally presents with a tender, firm and enlarged breast, rather than a discernable mass. This patient was diagnosed with acute mastitis carcinomatosa involving the entire breast.

FIBROCYSTIC CHANGESFIBROCYSTIC CHANGES

Old name: fibrocystic diseaseOld name: fibrocystic disease Age 20 – 50 (i.e., < 50 yrs)Age 20 – 50 (i.e., < 50 yrs) Extremely common and benignExtremely common and benign May produce a palpable mass or May produce a palpable mass or

nodularitynodularity Most often involves the upper outer Most often involves the upper outer

quadrantquadrant ““lumpy – bumpy” and painfullumpy – bumpy” and painful Bloody dischargeBloody discharge

Fibrocystic breast disease is a common and benign change within the breast characterized by a dense irregular and bumpy consistency in the breast tissue. Mammography or biopsy may be needed to rule out other disorders.

Nonproliferative Verus Nonproliferative Verus Proliferative Fibrocystic Proliferative Fibrocystic

ChangesChanges

NonproliferativeNonproliferative Proliferative Proliferative ChangesChanges

FibrosisFibrosis Cysts (blue- Cysts (blue- domed)domed) Apocrine Apocrine metaplasiametaplasia MicrocalcificationsMicrocalcifications

Ductal Ductal hyperplasiahyperplasia

+/- Atypia+/- Atypia Sclerosing Sclerosing adenosisadenosis Small duct Small duct papillomaspapillomas

Relative Risk of Developing Relative Risk of Developing Breast Breast Cancer with Cancer with

Fibrocystic ChangesFibrocystic Changes

RelativeRelative RiskRisk

Fibrocystic ChangesFibrocystic Changes

No increaseNo increase Fibrosis, cysts, apocrine Fibrosis, cysts, apocrine metaplasia, adenosismetaplasia, adenosis

1.5 – 2x1.5 – 2x Sclerosing adenosis, Sclerosing adenosis, ductal hyperplasia, ductal hyperplasia, papillomaspapillomas

4 – 5x4 – 5x Atypical ductal or lobular Atypical ductal or lobular hyperplasiahyperplasia

Features That Features That Distinguish Fibrocystic Distinguish Fibrocystic

Change from Breast CancerChange from Breast Cancer

Fibrocystic Fibrocystic ChangeChange

Breast CancerBreast Cancer

Often bilateral Often bilateral Often UnilateralOften Unilateral

May have multiple May have multiple nodulesnodules

Usually singleUsually single

Menstrual variationMenstrual variation No menstrual variationNo menstrual variation

Cyclic pain & Cyclic pain & engorgementengorgement

No cyclic pain or No cyclic pain or engorgementengorgement

May regress during May regress during pregnancypregnancy

Does not regress Does not regress during pregnancyduring pregnancy

BENIGN NEOPLASMSBENIGN NEOPLASMS FibroadenomaFibroadenoma

a)a) Most common benign breast Most common benign breast tumor in women <35tumor in women <35

b)b) Presentation:Presentation: palpable, round, palpable, round, movable, rubbery massmovable, rubbery mass

c)c) Gross:Gross: well circumscribed, tan, well circumscribed, tan, rubbery mass with small, cleft-rubbery mass with small, cleft-like spaceslike spaces

d)d) Micro:Micro: proliferation of benign proliferation of benign stroma, ducts, & lobulesstroma, ducts, & lobules

Mammogram Gross; cross section

Ultrasound

HU2400 Imaging

Mammography

Phyllodes tumor Phyllodes tumor (cystosarcoma phyllodes)(cystosarcoma phyllodes)

a)a) Fibroadenoma variant usually Fibroadenoma variant usually involves an older patient involves an older patient population population

b)b) Micro:Micro: increased cellularity, increased cellularity, stromal overgrowth, & irregular stromal overgrowth, & irregular marginsmargins

c)c) May locally recur or rarely May locally recur or rarely metastasizemetastasize

Intraductal papillomaIntraductal papilloma

a)a) Commonly presents as a Commonly presents as a bloody nipple dischargebloody nipple discharge

b)b) Micro:Micro: benign papillary growth benign papillary growth within lactiferous ducts or within lactiferous ducts or sinusessinuses

Intraductal papilloma is a benign tumor inside a milk duct. Removal of the duct for biopsy may be recommended to rule out cancer.

                                              

                             

MALIGNANTMALIGNANT NEOPLASMSNEOPLASMS

Carcinoma of the breastCarcinoma of the breasta)a) EpidemiologyEpidemiology

i.i. Most common cancer in Most common cancer in females (1 in 9 women in the females (1 in 9 women in the U.S.)U.S.)

1.1. > 50 yrs.> 50 yrs.

ii.ii. Second most common cause Second most common cause of cancer deathof cancer death

iii.iii. United States > JapanUnited States > Japaniv.iv. Incidence is increasingIncidence is increasing

b)b) Risk FactorsRisk Factors

i.i. Incidence increases with ageIncidence increases with age

ii.ii. First-degree relative with breast First-degree relative with breast cancercancer

iii.iii. Hereditary (5-10% of breast Hereditary (5-10% of breast cancers)cancers) BRCA1 chromosome 17q21BRCA1 chromosome 17q21 BRCA2 chromosome 13q12-13BRCA2 chromosome 13q12-13 P53 germ-line mutation: Li P53 germ-line mutation: Li

Fraumeni syndromeFraumeni syndrome

The TP53 gene is a tumor suppressor gene. When an individual inherits a mutation in this type of gene from one of his or her parents, there is an increased risk for developing certain kinds of cancer. Females with LFS have an increased risk for developing breast cancer.

Pedigree of family with Li-Fraumeni syndrome. (Redrawn from Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990;250:1233-1238.)

iv.iv. Prior breast cancerPrior breast cancer

v.v. Long length of reproductive Long length of reproductive lifelife

vi.vi. NulliparityNulliparity

vii.vii. ObesityObesity

viii.viii. Exogenous estrogensExogenous estrogens

ix.ix. Proliferative fibrocystic Proliferative fibrocystic changes, especially atypical changes, especially atypical hyperplasiahyperplasia

c)c) Clinical PresentationClinical Presentationi.i. Mammographic calcifications or Mammographic calcifications or

architectural distortionarchitectural distortionii.ii. Physical exam: solitary painless Physical exam: solitary painless

massmassiii.iii. Nipple retraction or skin Nipple retraction or skin

dimplingdimplingiv.iv. Fixation to the chest wallFixation to the chest wallv.v. Most common in upper outer Most common in upper outer

quadrantquadrantd)d) Gross:Gross: stellate, white-tan, gritty stellate, white-tan, gritty

massmass

e)e) Histologic variantsHistologic variants

i.i. PreinvasivePreinvasive1.1.Ductal carcimona Ductal carcimona in situin situ

(DCIS)(DCIS)

2.2. Lobular carcinoma in situ Lobular carcinoma in situ (LCIS)(LCIS)

Range of Ductal Carcinoma in situ (DCIS)

Image - Lobular Carcinoma in situ (LCIS)

Normal breast with lobular carcinoma in situ (LCIS) in an enlarged cross–section of the lobule.Breast profile:A ductsB lobulesC dilated section of duct to hold milkD nippleE fatF pectoralis major muscleG chest wall/rib cage

Enlargement:A normal lobular cellsB lobular cancer cellsC basement membrane

Lobular Carcinoma in situ (LCIS)

b)b) Invasive (infiltrating) ductal Invasive (infiltrating) ductal carcinomacarcinoma

i.i. Most common (>80%)Most common (>80%)ii.ii. Micro:Micro: tumor cells form ducts tumor cells form ducts

within a desmoplastic stromawithin a desmoplastic stromac)c) Invasive (infiltrating) lobular Invasive (infiltrating) lobular

carcinomacarcinomai.i. Some 5-10% of casesSome 5-10% of casesii.ii. Micro:Micro: small, bland tumor cells small, bland tumor cells

form a single-file patternform a single-file patterniii.iii. High incidence of multifocal & High incidence of multifocal &

bilateral diseasebilateral disease

Range of Ductal Carcinoma in situ (DCIS)

Normal breast with invasive lobular carcinoma (ILC) in an enlarged cross–section of the lobule.Breast profile:A ductsB lobulesC dilated section of duct to hold milkD nippleE fatF pectoralis major muscleG chest wall/rib cage

Enlargement:A normal cellsB lobular cancer cells breaking through the basement membraneC basement membrane

Invasive Lobular Carcinoma (ILC)

d)d) Mucinous (colloid) carcinomaMucinous (colloid) carcinomai.i. Micro:Micro: clusters of bland tumors clusters of bland tumors

float within pools of mucinfloat within pools of mucinii.ii. Better prognosisBetter prognosis

e)e) Tubular carcinoma: rarely Tubular carcinoma: rarely metastasizesmetastasizes

f)f) Medullary carcinomaMedullary carcinomai.i. Micro:Micro: Pleomorphic tumor cells Pleomorphic tumor cells

from syncytial group, from syncytial group, surrounded by a dense surrounded by a dense lymphocytic host responselymphocytic host response

ii.ii. Better prognosisBetter prognosis

g)g) Inflammatory carcinomaInflammatory carcinoma

i.i. Red, warm, edematous skinRed, warm, edematous skin

ii.ii. Peau d’ orange: thickened Peau d’ orange: thickened skin resembles an orange skin resembles an orange peelpeel

iii.iii. Extensive dermal lymphatic Extensive dermal lymphatic invasion by tumorinvasion by tumor

The image is an example of peau d'orange, the orange-peel texture often associated with inflammatory breast cancer.

Inflammatory breast cancer of the left breast showing peau d’orange and inverted nipple.

Normal breast with cancer cells invading the lymph channels and blood vessels in the breast tissue.A blood vesselsB lymphatic channels

Enlargement:A normal duct cellsB cancer cellsC basement membraneD lymphatic channelE blood vesselF breast tissue

PrognosisPrognosisa)a) Axillary lymph node statusAxillary lymph node statusb)b) Size of tumorSize of tumorc)c) Histological type & grade of Histological type & grade of

tumortumord)d) ER/ PR receptor statusER/ PR receptor status

i.i. ERER1.1. due to due to plasma estrogen (e.g.,post menopausal) plasma estrogen (e.g.,post menopausal)

e)e) Overexpression of c-erbB2 Overexpression of c-erbB2 (HER2/neu)(HER2/neu)

f)f) Flow cytometry S-phase & DNA Flow cytometry S-phase & DNA ploidyploidy

TreatmentTreatment

a)a) Local diseaseLocal disease

i.i. Mastectomy or lumpectomy Mastectomy or lumpectomy with radiationwith radiation

ii.ii. Axillary dissectionAxillary dissection

b)b) Metastatic diseaseMetastatic disease

i.i. TamoxifenTamoxifen

ii.ii. ChemotherapyChemotherapy

OTHEROTHER MALIGNANCIESMALIGNANCIES

Paget disease of the nipplePaget disease of the nipple

a)a) Ulceration, oozing, crusting, & Ulceration, oozing, crusting, & fissuring of the nipple & areolafissuring of the nipple & areola

b)b) MicroMicro

i.i. Intraepidermal spread of tumor Intraepidermal spread of tumor cells (Paget cells)cells (Paget cells)

ii.ii. Tumor cells occur singly or in Tumor cells occur singly or in groupsgroups

iii.iii. Often have a clear halo Often have a clear halo surrounding the nucleussurrounding the nucleus

c)c) Commonly associated with an Commonly associated with an underlying invasive or underlying invasive or in situin situ ductal carcinomaductal carcinoma