1/24/2014

1
BreastPathology
MarkFons,DO
Email:mfons@iuhealth.org
Normalbreast
anatomy
Modifiedskinappendage
terminalductlobularunit
(TDLU)
2celltypeslineTDLU
Breaststroma 2types
Terminal Duct Lobular Unit(TDLU)
Post-pubertal female breast TDLU >>male or pre-pubertal female
Siteanddiseaseassociation
Young women
Radiodense,
Predominance fibrous interlobular
stroma
Pregnancy
Branched ducts
Larger lobules
Postpartum/Lactation
Colostrum (high protein) Milk (higher
fat and calories) over 10 days.
Maternal antibodies (IgA)
Senescence:
Lobular atrophy and Fatty replacement
Increased radiolucency
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DisordersofDevelopment
MilkLineRemnants
Axillaryfoldto perineum
Supranumerynipples
AccessoryAxillaryBreastTissue
CongenitalNippleInversion
(distinguishfromacquiredinversion cancer)
Clinical
presentationof
Breastdisease
CommonCausesofMass Lesionsby
AgeGroup
Age Group Most Common Lesion
15-35 Fibroadenoma
35-50 Fibrocystic change > cancer
>50 Cancer till proven otherwise
Pregnant/Lactating Lactating adenoma > cyst> mastitis > cancer
DiagnosticModalities:
EvaluationofBreastMasses
Selfexamination
RadiologicImaging
Mammography
Ultrasound
MRI
Tissuediagnosis
Coreneedlebiopsy
Excision
Mammogram
SuspiciousFindings: Density orMicrocalcifications
Screening
4050y:
annual/biannual
>50y:annual
1stdegree
relative:10y
prior
Ultrasound
Youngerwomenusuallyclinicallybenignlesion
http://radiologyspirit.blogspot.com/
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MRI
Preoperativeevaluationofmalignantdisease.
Eval tumorresponsetoradiationtherapyorchemotherapy
CoreNeedleBiopsy
Coreneedlebiopsy Excision Lumpectomy
BenignBreast Inflammatory
Acutemastitis
Periductal Mastitis
Mammaryductectasia
Fatnecrosis
AcuteMastitis
Incidence:
Lactation
Clinical:
Erythema,Pain,Fever
Causes:
Staph.aureus>
Streptococci
Therapy:
Antibiotics,
expressionofmilk
DDx Inflam carcinoma
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AcuteMastitis
Periductal Mastitis(Subareolar abcess)
Clinical:Pain,erythema,subareolar mass
Cause:90%smokers
Mammaryductectasia (plasmacellmastitis)
Incidence:
50 60y,
multiparous
Clinical:
Masslike
Thicksecretions,
Lymphadenopathy
Mammaryductectasia (plasmacellmastitis)
Fatnecrosis
Definition:
Nodulardead
adipose
Incidence:
Priortrauma/
surgery
Clinical:
Painless
palpablemass
FatNecrosis
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Haematoxylum
campechianum (Logwood)
"Benign"Breast
Stromallesions/tumors
Fibroadenoma
Phylloidestumor
Lowgrade
Highgrade
Epitheliallesions
NonproliferativeBreastChanges(Fibrocystic)
ProliferativeBreastdiseasewithoutatypia
ProliferativeBreastdiseasewithatypia
RisksforBreastcancer
Disease Risk Ratio
Nonproliferat
ive
Fibroadenoma
Fibrosis
Cysts
Apocrine metaplasia
No increased risk
Proliferative
No atypia
Papilloma
Sclerosing adenosis
Usual ductal hyperplasia
1.5-2x
Proliferative
with atypia
Atypical Ductal Hyperplasia
(ADH)
Atypical Lobular Hyperplasia
(ALH)
4-5x
Ductal Carcinoma In-Situ (DCIS)
Lobular Carcinoma In-Situ (LCIS)
8-10x
Fibroadenoma
Incidence:
3rddecade
Mostcommontumor
youngadults
Clinical:
Wellcircumscribed
Mobile
Mostlypainless
Fibroadenoma
Phylloidestumor
Incidence
5060y,
Latin3 4x
incidence
Clinical
Rapidgrowth
Otherinfo
<1%ofbreast
tumors
15%
malignant
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Phylloides
tumor
Pseudoangiomatous stromalhyperplasia
(PASH)
Clinical:
Benign,incidental,nodulelike
Pseudoangiomatous stromal hyperplasia (PASH)
http://webpathology.com
PASH
Inset:Angiosarcoma
Non-proliferative Breast
Changes (Fibrocystic Changes)
Mostcommonbreast lesion
Premenopausal
Painfromswellingtiedto
menstrualcycle
Nippledischarge
Lumpybumpy
Nocancerrisk
Radiology
multiple ill-defined densities usually bilaterally, no calcifications
Non-proliferative Breast Changes
(Fibrocystic Changes)
Apocrine Metaplasia with microcalcifications
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RisksforBreastcancer
Disease Risk Ratio
Nonproliferat
ive
Fibroadenoma
Fibrosis
Cysts
Apocrine metaplasia
No increased risk
Proliferative
No atypia
Papilloma
Sclerosing adenosis
Usual ductal hyperplasia
1.5-2x
Proliferative
with atypia
Atypical Ductal Hyperplasia
(ADH)
Atypical Lobular Hyperplasia
(ALH)
4-5x
Ductal Carcinoma In-Situ (DCIS)
Lobular Carcinoma In-Situ (LCIS)
8-10x
Prolif BreastDiseaseW/OAtypia
Intraductal papilloma
Radiology:densities,calcifications
Clinical:
Bloody,nipple
discharge
Intraductal Papilloma
PBDWithoutAtypia:Sclerosing Adenosis
PBDWithoutAtypia:Usualductalhyperplasia
RisksforBreastcancer
Disease Risk Ratio
Nonproliferat
ive
Fibroadenoma
Fibrosis
Cysts
Apocrine metaplasia
No increased risk
Proliferative
No atypia
Papilloma
Sclerosing adenosis
Usual ductal hyperplasia
1.5-2x
Proliferative
with atypia
Atypical Ductal Hyperplasia
(ADH)
Atypical Lobular Hyperplasia
(ALH)
4-5x
Ductal Carcinoma In-Situ (DCIS)
Lobular Carcinoma In-Situ (LCIS)
8-10x
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Proliferative
BreastDisease
with Atypia
ADH:Oftenassociated
withductalcarcinoma
insitu
Atypical ductal hyperplasia - ADH ALH
MalignantBreastTumors
Carcinoma(95%)
Insitu
Invasive
75%,ductaladenocarcinomas
Geneticsubclassifications
Otherhistologicsubtypes
DiagnosisofNeoplasms
Benign/Malignant?
Histologic
Classification
Prognostic
markers
Genetics
subtype
Grading
Staging
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Familialcancer
syndromes
Tumorsuppressors
HereditaryBreastCarcinoma
Gene Locus Assoc
cancers
Function Comment
BRCA1 17q21
Breast
Ovarian
Male breast
Tumor
suppressor,
dsDNA repair
50% hereditary cancers.
2% of breast cancers
Usually basal-like (Triple neg).
More common: medullary and
poorly differentiated carcinoma
Majority have both breast and
ovarian carcinoma
BRCA2 13q12 Same as above Same
32% hereditary breast cancers
1% of breast cancers
14% both breast and ovarian
carcinoma
Male breast cancer
p53 17p13
Li-Fraumeni
syndrome
As above and
+ cell cycle
+ apoptosis
Most common mutation in sporadic
cancer
Carcinomaprogression
RisksforBreastcancer
Disease Risk Ratio
Nonproliferat
ive
Fibroadenoma
Fibrosis
Cysts
Apocrine metaplasia
No increased risk
Proliferative
No atypia
Papilloma
Sclerosing adenosis
Usual ductal hyperplasia
1.5-2x
Proliferative
with atypia
Atypical Ductal Hyperplasia
(ADH)
Atypical Lobular Hyperplasia
(ALH)
4-5x
Ductal Carcinoma In-Situ (DCIS)
Lobular Carcinoma In-Situ (LCIS)
8-10x
Ductal
Carcinoma
inSitu(DCIS)
Radiology:
Linear/branching
calcifications
Screening,increased
dx<5%toupto30%
Therapy:
Hormone,
Radiation,Surgery
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DCIS DCIS
Comedotype
P63 IHC
Cribriform
DCIS
SolidDCIS
(Noncomedo)
PapillaryandMicropapillary
DCIS(Noncomedo)
Pagetsdiseaseofthebreast/nipple
(DCIS)
DCISPagetsDisease
MicroscopicFindings
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LobularCarcinomaInSitu(LCIS)
LCIS
InvasiveductalcarcinomaNOS,NST
(NototherwisespecifiedorNoSpecialType)
Incidence:
75%>50y
Lifetimeriskis1in8
Clinical:
Palpablemass
Retractionofthenipple
Prognosis
85%,5yearsurvival
Radiology:
Masswithirregular
borders,calcifications
InvasiveductalcarcinomaNOS
InvasiveductalcarcinomaNOS
MicroscopicFindings:
Grade1 Grade2 Grade3
PrognosticFactorsinBreast
Cancer
Stage(TNM)
GradeMakingducts?,uglynuclei?,mitosesnotgood
Histologicaltype Hormonereceptors(Therapeutic
markers)
Lymphovascular invasion
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Theraputic markers:Hormones
Estrogenreceptor(ER)
Progesteronereceptor(PR)
Predictresponsetotamoxifine
Triple negative = ER-, PR-, Her2
unamplified.
Her2/
neu
Chromosome17q21;synonym:hEGFR,ERbB2
SignalingpathwaysactivatedbyHER2receptor
30%breastcancer,Her2amplified
Herceptin (Trastuzumab)antibodyinactivatesHER2protein
Her2/neu methods
cDNA microarray
eachrow =gene
eachcolumn=cell
line.
Greensquares,
transcript levels
belowthe median
Redsquares,
transcript levels
greaterthanthe
median.
Molecular/geneticsubtype(NST)
Type ER Her2 Cells Other
Luminal A
+ -
Genes similar to lumen
cells
50% in this group, ductal/lobular
Tamoxifen responsive
Luminal B
+ +(Most)
Genes similar to lumen
cells
20%
Triple positive
Standard chemotx
Basal-like
- -
Genes similar to
ovarian serous
carcinoma.
20%
Triple negative
Many BRCA1
Medullary and Metaplastic
Her-2
- +
Poorly differentiated 10%
Herceptin responsive, aggressive,
poor differentiated, brain mets
Molecular cancer groups correlate prognosis and therapy response.
InvasiveLobularCarcinoma
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Medullary
Carcinoma
OftenBRCA1gene+
Alltriplenegative Basaltype
Betterprognosisthanductal
Mucinous
(Colloid)
Carcinoma
Excellentprognosis
Tubular
Carcinoma
Excellentprognosis
Metaplastic
Carcinoma
Moreaggressivethaninvasive
ductalNOS
AlltriplenegativeBasaltype
Papillarycarcinoma
ofbreast
InflammatoryCarcinoma
Clinicaldiagnosis:Nothistological
subtype,skinwithunderlyingcarcinoma
Badprognosis
DDx:acutemastitis
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Angiosarcoma
3settings
Spontaneous
Postradiation:<0.5%riskpost
radiationtreatment
Stewart Trevessyndrome:
Chroniclymphedemafromlymph
nodedissection
Badprognosis
MaleBreast Gynecomastia
Clinical
Breastenlargement
Palpablesubareolar mass
Syndromes
Klinefelter XXY
Systemicdisease(Highestrogen)
Cirrhosis
Drugs
Anabolicsteroids
Carcinoma
Rare:0.1%(compareto1in8
women)
AssociatedwithBRCA2mutations
Present@latestage
Treatment
Surgery
Lumpectomy(conservative)
Mastectomy
Lymphnodedissection,SentinelLymphnodes
Radiation
Systemictreatment
Chemotherapy
Hormonaltherapy
Neoadjuvant :Presurgical Radiationand
Chemotherapy
Treatmentofhighriskpatient(BRCApositive)
Bilateralprophylacticmastectomy(5090%risk)
Oopherectomy isoptional(40%riskOvarian
cancer)
Chemoprevention(Tamoxifen)
Sideeffects
Venousthromboembolism
Increasedriskendometrialcancer
Cataracts
Axillarynodedissection
Axillarylymphnodestatus:important
prognosticfactor
Axillarylymphnodedissection
Stagebreastcancer
Preventregionalrecurrenceofthe
disease.
RiskofLymphedema,riskofStewart
Trevessyndrome(angiosarcoma)
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Sentinelnodebiopsy(SLNB)
1Radioactivesubstance+/
bluedyeisinjectednearthe
tumor.
2Injectedmaterialislocated
visuallyand/orwithGeiger
3Thesentinelnode(s)(the
firstlymphnode(s)totakeup
thematerial)is(are)removed
andcheckedforcancercells.
http://www.cancer.gov
Sentinelnodebiopsy:mightbesufficientforstagingbreastcancerinwomen
withoutsignsofaxillarymetastasis.
?