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RADIOLOGICAL APPROACH FOR MALIGNANT BREAST LESIONSDR. ANJUM MEHDI MBBS, DMRD, FCPS (Radiology)Associate Professor RadiologyPunjab Medical College, Faisalabad.

Breast CancerIncidence = 90 / 100 000.

10 % of women will have a Breast Cancer

Treatment efficient for local disease

5 % of Women will die

Risk Factors Before Menopause

>>>Tall & SlimBorder Line Lesions> 1 AbortionLong StudyContraceptive Pill > 5 years very earlyShort Menstrual Cycles (>>>>????>>>>>>Nulliparous < 25 yearsFirst menstruation >>Menopause > 52 years>>>First menstrual cycle < 13 years>>>Obesity>>>Alcoholism>High social class>Urban Habitat>Family History>History of pulmonary TB?Celibate?

Predisposing Genes of Breast and Ovary cancer

Breast CancerOvarian CancerBRCA19 q 34 (Japan)BRCA 2BRCA 3 (8p)Androgen-R

FNAMagnificationCore BiopsySurgeryFallow-upSpotUltrasound

Decision

Micro calcificationsStellate LesionsMassScreening Mammography Diagnostic Stratgie

Breast Cancers

TNM ClassificationTumor T0 : No Clinical SignT is : Carcinoma in situ T1 < 2 cmT1a < 0,5 cmT1b > 0,5 cm &< 1 cmT1c > 0,5 cm &< 2 cm T2 :2 to 5 cm T3> 5 cm T4 : Skin or Pectoral AdherenceT4a : extension to the WallT4b : Edema, ulcerationT4c : Inflammatory CarcinomaNodesNon palpable : N0Mobiles :N1Fixed :N2Ipsilateral or Susclavian : N3MetastasisAbsent : M0Present : M1pNodes pN0 : No invasionpN1 : Axillary extent mobile pN1b: Metastasis >2 mm pN1a: Micro metastasispN2 : Axillary extent fixedpN3 : Internal Mammary ExtentPathologic Classification p TNM

STAGES

0IIIIIIIV

T is N0 M0T1 N0 M0Tn Nn M1T0 N1 M0T1 N1 M0T2 N0 M0T2 N1 M0T3 N0 M0

ABABT0 N2 M0T1 N2 M0T2 N2 M0T3N1&2M0T4 Nn M0

Mortality of Breast Cancer

0

20

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Death for 100000BreastUterusLung Ovaries

197519952015Women 35 - 64 years

BREAST ANATOMY

Breast tissue is composed of 3 layers. Premammary.Mammary.Retromammory. Breast contains 15-18 lobes, Each lobe contain 20-40 lobules.Coopers ligament are fibrous bands that course between the superficial fascia and the deep fascia.

BREAST ANATOMY

Basic functional unit of breast is a TDLU/lobule.TDLU consist of 10 -100 acini that drain into the terminal duct.The terminal duct drains into larger ducts main duct of the lobe nipple.The terminal ductal lobular unit is an important structure because most invasive cancers arise from the TDLU.It also is the site of origin of ductal carcinoma in situ (DCIS), lobular carcinoma in situ, fibroadenoma and fibrocystic disease.

BENIGN VS MALIGNANTFeatureBenignMalignantShapeRound, wider than tallTaller than wideMarginsSmoothIrregular, angular, spicularLobulationsNone or up to 3MultipleCapsuleEncapsulatedNo capsuleHaloAbsentEchogenic haloFixityNoneFixed to surrounding issue and/or underlying musclesShadowing or enhancementEnhancement, edge shadowingShadowing behind lesionSubstance echogenicityAnechoic (cystic), HyperechoicHypoechoic, calcification

FEATURE BENIGN MALIGNANTShapeRound, wider than tallTaller than wideMarginsSmoothIrregular, angular, spicularLobulationsNone or up to 3MultipleCapsuleEncapsulatedNo capsuleHaloAbsentEchogenic haloFixityNoneFixed to surrounding issue and/or underlying musclesShadowing or enhancementEnhancement, edge shadowingShadowing behind lesionSubstance echogenicityAnechoic (cystic), HyperechoicHypoechoic, calcification

ANGULAR MARGINS

Indicative of invasion.The angles of lesion margins can be acute, right angle or obtuse.A single angle of any type on the surface should be considered suspicious.Angles on the surface of the lesion occur in regions of low resistance to invasion(fatty tissue).

MARKEDLY HYPOECHOIC

Marked hypoechogenicity of a solid nodule (compared with fat) is a suspicious sonographic finding for malignancy.

AXILLARY LYMPHADENOPATHYNormal lymph nodes have a hypoechoic cortex with a thickness up to 2 mm, and a fatty hyperechoic central hilum. Normal nodes can be very large but almost entirely made up of fat with a thin rim of hypoechoic cortex. Measurement of nodal length is therefore useless in predicting nodal infiltration by tumour. Normal nodes are typically oval in shape. Metastatic nodes are frequently round rather than oval (l:s axis ratio < 2),they show either concentric or eccentric cortical thickening of >2 mm with concomitant narrowing of the hilum. Some of the proposed criteria for malignant lymph nodes have included size greater than 2 cm, round or irregular shape and absence of a fatty hilum.

AXILLARY LYMPHADENOPATHYNormal lymph node. On sonography, features include an ovoid shape and thin cortex (arrowhead), well-defined margins, and a preserved fatty hilum (arrow).

AXILLARY LYMPHADENOPATHYSuspicious sonographic characteristics of lymph nodes. Nodes A and B show cortical thickening with compression and displacement of the central fatty hilum. Nodes C and D demonstrate focal eccentric cortical thickening. Nodes E and F are completely replaced with loss of hilum. Note the rounded configuration of nodes B and F. The ratio of the long-to-short axis is less than 2. Node G is hypervascular with a nonhilar blood flow pattern.

BREAST IMAGING REPORTING AND DATA SYSTEM (BIRADS) classification of breast lesionsis an attempt to standardize the reading and reporting of mammograms

0 Category additional evaluation (e.g., magnification or spot compression view, old films for comparison, or ultrasound ) needed

1 Categorybreasts are symmetric and normal, annual screening is recommended

2 Category benign lesions (stable mass, simple cyst, calcified fibroadenoma, scattered benign calcifications, normal lymph node) annual screening is recommended

67 Year old women with left cephalocaudal mammogram

Simple Cyst

3 Categoryprobably benign lesion (multiple rounded densities, round calcifications, circumscribed mass on a first mammogram) short interval follow up suggested (6 months)

Fibroadenomas

4 Categorysuspicious lesion(10-30% chance of malignancy) biopsy recommended

38 year-old woman with a palpable mass; Right MLO view (a) demonstrates a high density irregular mass with indistinct margins in the upper aspect of the right breast. Also present is adenopathy in the axilla. Ultrasound (b) demonstrates the palpable mass to be hypoechoic with irregular margins. Pathology: Invasive ductal carcinoma.

5 Category malignant lesion (spiculated lesion- 90% chance of malignancy) appropriate action (e.g.,biopsy, excision)should be taken.

43 year-old woman for screening mammography. Right craniocaudal views show a classical appearing carcinoma, which is a high density mass with spiculated margins, and microcalcifications. Pathology: Invasive ductal and lobular carcinoma.

Infiltrating ductal carcinoma71 year old women had a firm mass in the left breastCephalocaudal view of the left breast

Calcifications on mammographyMicrocalcifications less than 0.5mmNot specific to carcinomaIs seen in 30-40% of carcinoma on mammographyMacrocalcifications more than 0.5mmMay be found in carcinoma

PROBABLY BENIGNWidespread all one/both breasts.Macrocalcification of one size.Symmetrical distribution.Widely separated opacities.Superficial distribution.Normal parenchyma.

POSSIBLY MALIGNANT Biopsy indicatedMicrocalcification particularly segmental, cluster distribution (> 5 particles in 1.0 cm3 space; of these 30% will be malignant).Mixture of sizes and shapes linear, branching, punctate.Associated suspicious soft-tissue opacity.Microcalcification eccentrically located in soft-tissue mass.Deterioration on serial mammography.

PLEOMORPHIC CALCIFICATIONS

DUCTOGRAPHYGalactography, or ductography, is a mammographic technique that involves injection of a contrast agent (dye) into a milk duct. This study may be useful in the evaluation of unilateral spontaneous nipple discharge that is bloody. (Nipple discharge that is milky, yellow, or green is rarely associated with breast cancers.)

Ninety-degree mediolateral ductogram shows a filling defect (arrows) within dilated ducts, which represents a papilloma.

Carcinoma. Craniocaudal ductogram shows large filling defects near the nipple (arrow). Sanguineous spontaneous nipple discharge prompted acquisition of a diagnostic ductogram. The standard central duct excision would have resulted in excision of tissue within a cone limited by the white lines and the nipple. Note the filling defects outside the margin of the standard excision (arrowheads). Histologic analysis demonstrated extensive ductal carcinoma in situ (DCIS) involving much of the area opacified with ductography.

Where do we stand today in breast imaging?

41Lets take a quick snapshot of where breast imaging stands today in USA

Lymphoscintigraphy Pre-surgical marking of sentinal lymph nodePerformed for invasive cancers

Tc-99 SC injected at tumor site or peri-areolar

Static planner images or CT-SPECT to identify the sentinal lymph nodeLN marked on skinSurgeons explore with Gamma probe during surgery

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RadioGraphics 2004; 24:121145

RadioGraphics 2004; 24:121145

Ultrasound ElastographyUses assessing inherent tissue elasticity to find cancersCancers that are harder than breast tissues / benign lesions show different valuesCancers usually measures larger on elastograms compared to grey-scaleStandardization is currently a real problem

46Some new US machines come with elastography software

Elasticity Scores

Figure 1: Images present general appearance of lesions for elasticity scores of (a) 1, (b) 2, (c) 3, (d) 4, and (e) 5. Black circle indicates outline of hypoechoic lesion (ie, border between lesion and surrounding breast tissue) on B-mode images.

Elastography

RADIOLOGY: VOLUME 239: NUMBER 2 2006

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Breast specific gamma Imaging (BSGI)High sensitivity (>90%), specificity (>45%)Intravenous Tc-99 Sestamibi scintigraphyComparable images to mammographyNot affected by breast density

High dose of radiation (20-30 X mammography)Limitations with biopsy capabilities

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BSGI

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Positron Emission Mammography (PEM) F-18 FDGSensitivity and specificity similar to MRI> 90% sensitivity for DCISIs not affected by the breast density or hormonal statusNewer agents more specific to DNA synthesis

High dose of radiationCurrent limitation for biopsy

51METABOLIC ACTIVITY OF CELLSMONITER CANCERPLAN TREATMENTNOT FOR SCREENING AS TOOO EXPENSIVE AND COMBINED DOSE IS TOO HIGH FOR ANNUAL SCREENING

Positron Emission Mammography

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Positron Emission Mammography (PEM)

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Digital Tomosynthesis(3D-Mammography)Digital mammography and computed tomography3-D image slices through the breastInitial research suggest lesser recall and finding more cancerHybrid units with Tomo + functional imaging

Time consuming (scanning and reading)Not significantly better for calcifications

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Digital Tomosynthesis(3D-Mammography)

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Low dose breast CT scanStill in early stages of researchContrast enhanced CT improves detection of benign and malignant breast massesPrionas et al. Radiology Sept. 2010

57DEDICATED BREAST CT SAME RADIATION DOSE NO PAIN 17 SEC/ BREAST BETTER FOR MASS DETECTION RATHER THAN MICROCALCIFICATIONS

CT SPECT

Low dose breast CT scan

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Low dose breast CT scan

Calcifications Enhancing mass

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Contrast enhanced ultrasoundCEUSNot FDA approved in USA for clinical useAssesses enhancement suggesting neovascularity in cancerAnalysis of time-intensity curves or enhancement pattern (peak%, Time to peak, Mean transit time)Significant overlap between benign and malignantPeripheral enhancement seen with malignancy but low sensitivity (39.5%) and high specificity (98%)

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Homogeneous and peripheral enhancementInvasive cancers

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Breast MRI

INDICATIONSHigh risk for breast cancer: personal or strong family history (especially premenopausal cancer in first degree relative - mother, sister or daughter)

Breast cancer gene present

Prior to breast cancer conservation surgery to look for occult breast cancer in either breast

Problem-solving for breast diagnosis

Breast implants with a question of leakTechnique of choice in the differentiation between postoperative scarring and local recurrenceDifferentiation of axillary recurrence and brachial plexopathy post radiotherapy

A: Fibroadenoma

B: Invasive Lobular Carcinoma

Five minutes after contrast injection:

Subtracted images (only the cancer is visible):

Controlled Movement means that Subtraction can be used.

MRI SpectroscopyInformation on intracellular metabolites

Increased Choline peak between the water and lipid peaks in cancers

Has shown high sensitivity (83%) and specificity (85%)

Utility may improve with 3T MRRADIOGRAPHICS;27:1213-1229 2007

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MRI SpectroscopyImage-localized magnetic resonance spectroscopy (MRS) of a breast tumor. Left panel is an MRI image with tumor voxel (square) selected. Right panel is the corresponding 1H MRS spectrum with the tCho resonance at 3.2 ppm

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Breast MRI enhancement curves Following administration of Gadolinium there can be three possibleenhancement kinetic curvesfor a lesion onbreast MRI.

type I curve:progressive enhancement patterntypically shows a continuous increase in signal intensity throughout timeusually considered benign with only a small proportion of (~9%) of malignant lesions having this patterntype II curve:plateau patterninitial uptake followed by the plateau phase towards the latter part of the studyconsidered concerning for malignancytype III curve:washout patternhas a relatively rapid uptake shows reduction in enhancement towards the latter part of the studyconsidered strongly suggestive of malignancy

Breast MRI enhancement curves

RECOMMENDATIONS FOR SCREENINGAMERICAN CANCER SOCIETYAMERICAN COLLEGE OF RADIOLOGY

WOMEN AT NORMAL RISK SHOULD BEGIN ANNUAL BREAST CANCER SCREENING AT STARTING AT AGE 40

Team-work

70Breast care is a team work. There is a lot of collaborative effort by members of the team in pre-op planning and post op care

Survival of Invasive Ductal Carcinoma / Grade

Survival of Invasive Ductal Carcinoma Related to the Size

Survival of Invasive Ductal Carcinoma / Grade & Size

30-49 mm15-19 mm

BRCA-1 (chromosome 17), BRCA-2 (chromosome 13), BRCA3 (chromosome 11), and BRCA4 (chromosome 13) are tumor suppressor genes. Mutations in these genes are associated with an increased risk of hereditary (familial), early onset (pre-menopausal) bilateral breast or ovarian cancer. Hereditary breast cancer accounts for 5% of all breast cancer. The BRCA mutation confers a 50% - 85% lifetime risk of developing breast cancer, as compared to 10% for the general population. The mutation confers a 15% - 40% lifetime risk for ovarian cancer, as compared to 1.5% in the general population.