High Risk LesionsElizabeth Morris MD FACR

Chief, Breast Imaging Section

Professor of Radiology

Memorial Sloan Kettering, NY, NY

High Risk Lesions

• Lesions found on percutaneous biopsy that have a significant risk of demonstrating cancer on excision

• Lesions that indicate an increased risk of breast cancer over a woman’s lifetime

High Risk Lesions

• Lesions found on percutaneous biopsy that have a significant risk of demonstrating cancer on excision

• Lesions that indicate an increased risk of breast cancer over a woman’s lifetime

Old thinkingBloodgood on papillomas 1920

“Every surgeon hesitates to mutilate a woman, and particularly this

organ, but every surgeon with a conscience will attack that which

is or may become cancer

‘Benign’ means ‘born good,’ but all tumors of the breast which have

this title are apt to go bad, and are not to be trusted”

High Risk Lesions at needle biopsy aka historically “not to be trusted”

• ADH

• Lobular neoplasia: ALH and LCIS

• Papillary lesions

• Radial scar

• Flat epithelial atypia

• Mucinous lesions

• Phyllodes tumor

Radiological Findings of High Risk Lesions

Calcs Stellate

lesion

Discrete

opacity

Multiple

opacities

Architectural

distortion

Nonspecific

density

Total

51(54%) 18(19%) 19(20%) 1(1%) 4(4%) 1(1%) 94

Flegg et al WJSO 2010: 8:78

Lesions without suggestive imaging features ADH, LN

Lesions with suggestive imaging featuresPapillary lesion, Radial scar

How frequent are these lesions at percutaneous biopsy?

Pathology Frequency

ADH 5%

LCIS 2%

Papillary lesion 1-3%

ALH 0.6%

Radial scar 0.04%

PPV Malignancy of High Risk Lesions

Subcategory Number Benign CA PPV%

ADH 141 78 63 44%

LN 23 9 14 61%

Papillary lesion 44 34 10 23%

Radial Scar 42 35 7 17%

Phyllodes 24 21 3 13%

Not specified 5 4 1 20%

TOTAL 279 181 98 35%

Houssami et al BJC (2007) 96, 1253-1257

Rationale for surgical removal

• Incomplete removal/ inadequate sampling

– Portion of lesion removed

– Volume of tissue removed correlated to likelihood of cancer found at surgery

– 14G true cut more likely to have cancer at surgery c/w 11G vacuum biopsy device

• Clear miss

Larger Volume of Tissue with Vacuum

devices

• Vacuum-assisted biopsy (VAB)

– 1 insertion, suction, fast, multiple, “directional”

• Core weights:

– 95 mg (11G) vs. 18 mg (14G) (Burbank 96, Berg 97)

• VAB for Ca++, US 14G for masses

What is Incidental High risk lesion?

• Some pathology are clearly incidental:

– Ca++: benign breast tissue with Ca++, however ADH is found without associated ca++

– Mass: benign concordant path, however a microscopic focus of ADH is seen

• Others are less clear

– Ca++: Ca++ in benign and in ADH/LN (? Relative size /proportion)

Radiologic Pathologic concordance Old thinking

BIOPSY PATHASSESSMENT

CLINICAL INFO &

IMAGING FINDINGS

DIRECT COMMUNICATION

RADIOLOGIST PATHOLOGIST

SURGEON

SURGERY

ROUTINE FOLLOW UP

HIGH RISK CLINIC

Radiologic Pathologic concordance New thinking

BIOPSY PATHASSESSMENT

CLINICAL INFO &

IMAGING FINDINGS

DIRECT COMMUNICATION

RADIOLOGIST PATHOLOGIST

SURGEON

SURGERY

ROUTINE FOLLOW UP

HIGH RISK CLINIC

The upgrade rates are dependent on assessment of radiologic pathologic concordance

Atypical duct hyperplasia (ADH)

• Most common high risk lesion: 5% of all percutaneous biopsies

• Variable definitions:– Some but not all features of DCIS

– All features of DCIS involving 1 or 2 ducts

– All features of DCIS but < 2 mm

• 4-5x increased risk of breast CA – Nonobligatory precursor to DCIS or invasive CA

ADH: Imaging Features

• No specific features

• MG: calcifications

– Up to 20% of amorphous calcifications

• US: no US appearance

– May see underlying process from which it arose

– usually florid ductal hyperplasia (enlargement of ducts or lobules)

ADH

Bx = ADH

Surgery = DCIS

ADH Upgrade - Related to percentage of the lesion removed (calcification retrieval)

Reduced with vacuum-suction device

Study 14G ACBB 14G VAB 11G VAB

Jackman, 94 9/16 (56%) --- ---

Liberman, 95 11/21 (51%) --- ---

Liberman, 97 20/37 (54%) --- ---

Burbank, 97 8/18 (44%) 0/8 (0%) ---

Liberman, 98 --- --- 1/10 (10%)

Brem, 99 --- --- 4/16 (25%)

Philpotts,99 6/30 (20%) --- 4/15 (27%)

Jackman, 97 26/54 (48%) 13/74 (18%) 4/31 (13%)

Meyer, 99 10/18 (56%) 9/24 (38%) 1/9 (11%)

Darlin, 00 11/25 (44%) 11/28 (39%) 16/86 (19%)

Liberman et al, Radiol Clin N Am 2002; 483-500

ADH on any imaging test requires surgery

Can Some ADH Be Defined as Probably Benign?

• 104 ADH lesions at stereo 11G VAB

– 21% (22/104) cancer at surgery

– DCIS in 86% (19/22), invasive in 14% (3/22)

• Lowest cancer rate (p<0.02)

– 16% (15/92) no family history

– 13% (9/67) lesion <1cm

– 8% (3/36) when mammo target removed

• No subgroup of ADH with <2% cancer risk

Jackman, Radiology 2002; 224: 548-554

Results MSK Audit confirm need for

surgery

Biopsy Upgrade

ALL ADH (N=536) 26%(IDC 28, ILC 2, DCIS 108)

ADH BORDERING DCIS (N=68) 50% (IDC 5, DCIS 29)

ADH (W/O BORDERING) (N=468) 22% (IDC 23, ILC 2, DCIS 79)

CCCWA/FEA (N=99) 10%(IDC 2, DCIS 8)

ATYPIA NOS (N=13) 15%(IDC 1, DCIS 1)

Lobular Neoplasia (LN): ALH + LCIS

• No specific imaging appearance

• Associated with increased risk of CA in either breast

– ALH: 4-5x

– LCIS: 8-10x ; 1% per year

• Spectrum of disease:

– ALH: cells do not fill or distend >50% of lobular acini

– LCIS: cells fill and expand lobules and terminal ducts

Cancer at surgery for LN has decreased over the years when careful criteria are applied

Caveat: pleomorphic LCIS

Pleomorphic LCIS on bxILC at excision

Pleomorphic LCIS must always be excised Regardless of detection modality

Papillary Lesions

• Comprise many entities from benign intraductal papilloma to malignant invasive papillary carcinoma

• Can be heterogeneous

• Can be difficult to remove entire lesion percutaneously

PAPILLOMA

• Intracystic or intraductal mass on US suggestive

• May appear as small circumscribed mass on MR +/- washout kinetics

INTRADUCTAL PAPILLOMA

• Central: 80%– Usually solitary

– Presents with nipple discharge

– 1.5-2x RR of invasive breast CA

• Peripheral: 20%– Often multiple

– Increased association with DCIS or ADH

– ~7x RR of breast CA

Large number of studies - wide range of upstage rate

– Studies reporting a very low rate or no upstage cases; recommend observation as appropriate management

– Philpotts, Radiology 2000 (6%) - Rosen, Am J Roentg 2002 (7%)

– Agoff, Am J Clin Pathol 2004 (0%) - Renshaw, Am J Clin Path 2004 (0%)

– Carder, Hostopathlogy, 2005 (0%) - Sydnor, Radiology 2007 (3%)

– Sohn, Ann Surg Oncol 2007 (7%)

– Studies with high upstage rate (up to 44 %) all recommend excision– Puglisi, Oncology 2003 (39%) - Gendler, Am J Surg 2004 (17%)

– Mercado, Radiology 2006 (23%) - Plantade. J Radiol 2006 (14%)

– Liberman, AJR, 2006 (14%) - Ashkenazi, Am J Surg 2007 (44%)

– Rizzo, Ann Surg Oncol 2008 (25%) - Bernik, Am J Surg 2009 (38%)

– Jaffer, Cancer 2009 (9%)

– Some more nuanced studies, recommend decision based on imaging and/or pathologic characteristics

– Ivan, Mod Pathol 2004 - Carder, Histopathology 2005

– Kil, Breast 2008 - Ahmadiyeh, Ann Surg Onc 2009

– Jung, World J Surg 2010 - Chang Eur Radiol 2010

– Bennett Acad Radiol 2010 - Youk, Radiology 2011

– Holley, Radiology, 2012 - Nakhlis, Ann surg Onc 2014 30

Why so much conflicting information about papillomas?

– Differences in biopsy techniques and expertise

– Differences in reporting

– Small numbers

– Papillary lesions are

• relatively rare

• varied appearance at imaging

• can be seen incidentally at biopsy

• are difficult to diagnose pathologically Holley, Radiology, 2012

Individual institutions may need to evaluate their internal data to

develop guidelines regarding excision and observation

Bennett Acad Radiol 2010

31

INTRADUCTAL PAPILLOMA

• Higher risk of Atypia or Cancer:

– Calcifications

– > 2 cm

– indistinct margins & angulated

– expands duct more than fluid & involves branches or TDLU

• Lower risk:

– <2 cm

– Nonexpansile, nonbranching & does not involve TDLU

Multiple papillomas

aka

“The saga case”

US

US biopsy

both sites

papillomas

MRI performed for potential follow up

Additional masses throughout left LIQProbably papillomas (papillomatosis)

2 site seed loc

Lx 8:00: papillomaLx 9:00: papilloma

…pt comes back in 1 year:

current 1 yr prior prior postbx

removed

removed

1.0 cm 0.7 cm

…pt comes back in 1 year:

Usbx: papilloma

benign

papilloma

Study n Upgrade benignpapilloma to cancer

Upgrade atypical papilloma to cancer

Valdes et al, 2006Ann Surg Oncol

80 23% 25%

Liberman et al, 2006AJR

35 14% n/a

Mercado et al, 2006Radiology

43 n/a n/a

Sydnor et al 2007Radiology

63 3% 67%

Youk et al, 2010Radiology

30 n/a 23%

Chang et al, 2011Ann Surg Oncol

60 0% 18%

Youk et al, 2011Radiology

160 5% n/a

Sohn et al, 2013J Ultrasound Med

39 0% n/a

• No studies compare upgrade rate of solitary vs multiple

• Path review of specimens show increased association of multiple papillomas with cancer

• Several studies show multiple has higher risk of developing cancer

Ali-Fehmi et al (Hum Path 2003): review of surgical specimens containing papillomas

-61 patients with multiple papillomas (at least 5 in one segment)

-no atypia: n=17-with atypia: n=11-with DCIS: n=20-with invasive carcinoma: n=13

Ohuchi et al (Cancer 1984)-6 of 16 with multiple papillomas had associated cancer-0 of 9 with central papillomas

Multiple Papillomas: associated malignancy

54% of specimens had cancer

38% of specimens had cancer

0% of specimens had cancer

increased risk c/w general population and solitary papillomas

Lewis et al Am J Surg Path 2006-372 patients with papillomas-followed for 16 years

- solitary papilloma- solitary papilloma w/ atypia- multiple papillomas- multiple papillomas w/ atypia

Multiple Papillomas: future cancer risk

Future cancer risk2x risk5.1x risk3x risk7x risk

• 1487 MRI VABs from January 2004-March 2011

• Papilloma found at MRI VAB in 75/1487 (5%)

• 25/75 (33%) had atypia, 50/75 (67%) no atypia

• Surgical bx 67/75 (89%)– DCIS 4 (6%;95% CI 2-15%)

– DCIS 2/23 (9%;95% CI 1-28%) with atypia

– DCIS 2/44 (5%;95% CI 0.4-16%) without atypia

Brennan et al 2012 AJR

MSKCC experience with papillomas• MRI upgrade lower without atypia (5% versus 9%)

• If pathologist can say lesion completely included in biopsy specimen (& no atypia or other risk factors) then PERHAPS these cases can be followed

• Currently reviewing all papillomas on stereo and US hoping that the upgrade will be lower than MRI

• Currently consensus group thinks we have to recommend excision

MSKCC Spreadsheet – work in progressDx by US CNB Dx by US VAB Dx by Stereo VAB

Extravasted mucin w/o Atypia 1/28 no upgrade 0 9/28 no upgrade

Extravasted mucin w/ Atypia 1/28; 1/1, 100% upgrade 0 16/28; 3/16, 19% upgrade

FEA in progress in progress in progressRadial Scar without atypia (N: 53; target (T): 35; incidental (I): 18)

27/53 (T: 22; I: 5); no upgrade 0/53

18/53 (T: 8; I: 10); 1/8 T-RS upgraded to DCIS

Radial Scar without atypia N: 17/39 (with Manuela/Sandra/Elizabeth) (eliminated ipsi ca and lost FU) 0 0 0Radial Scar with atypia and other high risk lesions N: 10/39 (with Manuela/Sandra/Elizabeth) 0 0 0

Papillary lesion without atypia in progress in progress in progress

Papillary lesion with atypia in progress in progress in progress

Phyllodes tumor

LN Classical Type (N= 72) 9 cases no upgrade

46 cases; 2 upgrades: 2mm low grade IDC&DCIS; 2mm

low grade DCIS

LN Classical Type - MRI study (N=44) NA NA NA

ADH in progress in progress in progress

RADIAL SCLEROSING LESION

• Size criteria:

– Radial scar: < 1.5 cm

– Complex sclerosing lesion: >1.5 cm

• Significance as high risk lesion controversial

– Some evidence for associated atypia or CA in periphery

– Other data suggests generalized risk marker

• 2x risk of breast CA

RADIAL SCAR

• Commonly occult:– 1-2% of biopsies, 28% in autopsy series

• MG:– Spiculated density with radiolucent center

– Architectural distortion without central mass

• US:– Irregular and angular mass

• Shadowing, taller than wide

– Indistinguishable from CA

ARCHITECTURAL DISTORTION FOUND AT SCREENING

Ultrasound Vacuum biopsy

POST-BIOPSY MAMMOGRAM

ML

Path: Benign breast tissue with biopsy site changes

Radial Scar at Image-guided Needle Biopsy: Is Excision Necessary?

• MSKCC 53 patients over 17 years• 48 patients had surgical excision • 1 “upgrade” to malignancy (2%)• Meta-analysis of 20 RS excision studies

– Overall upgrade rate of 10.4%– Higher rate in patients with a diagnosis of RS with atypia

(26%)– Upgrade rate for RS without atypia was 7.5% overall.

• lower rate of upgrade to malignancy in this study (2%) likely related to the thorough radiologic-pathologic review

• If multidisciplinary agreement & careful radiologic-pathologic correlation– may be appropriate for RS without atypia to undergo imaging

follow-upConlon N et al. American J Surg Path 2015 in press

Variations in radiologic & pathologic practice

Means that a universally applicable nomogram for management of breast atypia is extremely

challenging

Multidisciplinary assessment of the risk/benefit ratio of further surgery for each patient should be

assessed

General trend to do less rather than more

In general the following should be excised

• Atypical duct hyperplasia ADH

• Flat epithelial atypia

• Papillary lesions with atypia

• Radial scar with atypia

Observation may be considered

• Lobular neoplasia LN– Atypical lobular hyperplasia (ALH)– Lobular carcinoma in situ (LCIS)

• Papillary lesions without atypia• Radial scar without atypia

• Only if:– Rad- path concordance– Favorable features– Clinical & imaging stability – high risk clinic– No other high risk lesion with atypia– Not in a breast with a known cancer

• Surgical excision is a safe choice with low morbidity

Evolving Practice at MSKCC

• Radiological Pathological concordance KEY

• Anything with atypia excised

• Any high risk lesion in the same breast as a known cancer excised

• Papillomas/radial scars still excised unless complete excision can be confirmed by imaging and path

• Multiple papillomas followed by imaging

• LN not excised

Take home for Radiologists

• Collaborate with pathologists

• Consider clinical context

• Track your outcomes

• Women with ADH, ALH and LCIS are at sufficient increased risk of development of breast cancer that they should be counseled on the benefits & risks of

1. Enhanced screening

2. Risk reduction strategies

Question 1

High risk lesions include the following EXCEPT:

a. ADH

b. LCIS

c. ALH

d. all of the above

Question 1

High risk lesions include the following EXCEPT:

a. ADH

b. LCIS

c. ALH

d. all of the above

Question 2

Observation of high risk lesions can be considered IF there is/are:

a. Radiological pathological concordance

b. Favorable features

c. No cancer present

d. Careful clinical & imaging follow up available

e. All of the above

Question 2

Observation of high risk lesions can be considered IF there is/are:

a. Radiological pathological concordance

b. Favorable features

c. No cancer present

d. Careful clinical & imaging follow up available

e. All of the above

Question 3

True or False: LCIS should always be excised

a. True

b. False

c. I don’t know

Question 3

True or False: LCIS should always be excised

a. True

b. False

c. I don’t know

Question 4

What high risk lesion do we most see at persutaneous biopsy?

a. ADH

b. Radial scar

c. LCIS

d. Papilloma

Question 4

What high risk lesion do we most see at persutaneous biopsy?

a. ADH

b. Radial scar

c. LCIS

d. Papilloma

Thank you!

Thank You

PPV for Malignancy of High Risk Lesions

Subcategory Number Benign CA

ADH 36 19 (53%) 17 (47%)

ALH 4 4 (100%)

LCIS 5 3 (60%) 2 (40%)

Radial Scar 18 18 (100%)

FEA 5 3 (60%) 2 (40%)

MLL 3 3 (100%)

Papillary lesion 23 21 (91%) 2 (8%)

TOTAL 94 71 (76%) 23 (24%)

Flegg et al WJSO 2010: 8:78

ADH

ADH