official journal of the american osteopathic college of radiology breast … · 2018-04-01 ·...

ISSN: 2165-3259

JJAAOOCCRR

Official Journal of the American Osteopathic College of Radiology

BREAST IMAGING

Guest Editor: Michelle C. Walters, D.O., FAOCR

Editor-in Chief: William T. O’Brien, Sr., D.O.

January 2013, Vol. 2, Issue 1

J Am Osteopath Coll Radiol 2013; Vol. 2, Issue 1 Page i

JAOCR About the Journal

Aims and Scope The Journal of the American Osteopathic College of Radiology (JAOCR) is designed to provide prac cal up‐to‐date reviews of cri cal topics in radiology for prac cing radiologists and radiology trainees. Each quarterly issue covers a par cular radiology subspecialty and is composed of high quality review ar cles and case reports that highlight differen al diagnoses and important teaching points. AccesstoArticlesAllarticlespublishedintheJAOCRareopenaccessonline.Subscriptionstothejournalarenotrequiredtoviewordownloadarticles.Reprintsarenotavailable.CopyrightsMaterialspublishedintheJAOCRareprotectedbycopyright.NopartofthispublicationmaybereproducedwithoutwrittenpermissionfromtheAOCR.GuideforAuthorsSubmissionsfortheJAOCRarebyinvitationonly.Ifyouwereinvitedtosubmitanarticleandhavequestionsregardingthecontentorformat,pleasecontacttheappropriateGuestEditorforthatparticularissue.Althoughcontributionsareinvited,theyaresubjecttopeerreviewand inalacceptance.Editor‐in‐ChiefWilliamT.O’Brien,Sr.,D.O.SanAntonio,TXDesignEditorJessicaRobertsCommunicationsDirector,AOCRManagingEditorTammamBeydoun,D.O.FarmingtonHills,MIEditorialBoardSusannSchetter,D.O.DanielJ.Abbis,D.O.LesR.Folio,D.O.MichaelW.Keleher,D.O.RockySaenz,D.O.KippA.VanCamp,D.O.JohnWherthey,D.O.

Page ii J Am Osteopath Coll Radiol 2013; Vol. 2, Issue 1

Table of Contents

Breast Imaging

Editor: Michelle C. Walters, D.O., FAOCR

Title/Author(s) Page No.

From the Guest Editor 1

Review Ar cles

MRI Breast Clinical Indica ons: A comprehensive Review 2

Michelle C. Walters, D.O., FAOCR, and Lennard Nadalo M.D., FACR

High‐Grade Ductal Carcinoma In Situ: An Overview for the Radiologist 18

Luke J. Ballard, M.D., and Geneva R. Ballard, M.D.

Case Reports

Peripherally Enhancing Breast Lesion With Central Fat 26

Sharon Kreuer, D.O., and Rocky C. Saenz, D.O.

Unilateral Axillary Lymphadenopathy 29

Shannon Gaffney, D.O.

JAOCR at the Viewbox

Mondor’s Disease 32

Amy Argus, M.D., and Arthur Ballard, M.D.

Ductal Carcinoma In Situ 33

Mary C. Mahoney, M.D., and Arthur Ballard, M.D.

J Am Osteopath Coll Radiol 2013; Vol. 2, Issue 1 Page 1

From the Guest Editor

In This Issue

Michelle C. Walters, D.O., FAOCR

Medical Director, Advanced Imaging, DeSoto, TX

The controversy surrounding breast imaging is astounding. We have heard that we are over‐diagnosing – and thus over‐trea ng – breast cancer in a recent New England Journal of Medicine ar cle. Then we are told that we are under‐diagnosing breast cancer in pa ents with dense breast ssue and now must inform pa ents about the density of their breast ssue and that addi onal screening tests,

such as US and MRI, may be useful. It would come as no surprise to me if breast imagers were as confused as our pa ents.

As breast imagers, we have to remember that early detec on of breast cancer does indeed save lives. It has been shown that screening mammography decreases breast cancer deaths in up to 25‐30% of women. These results have been reaffirmed in mul ple well designed, prospec ve, controlled studies. Nowadays, we must be cognizant of the issues surrounding breast imaging, as our pa ents o en read about these issues in the Wall Street Journal or in the local newspaper. We have to arm ourselves with the scien fic knowledge of proven research and technology. Breast imagers are direct pa ent advocates in the fight against breast cancer, and it takes special effort and for tude to maintain that fight and keep our pa ents in the fold of our screening efforts. However, I believe it is well worth the me and energy that this requires.

I hope that the ar cles in this sec on of the JAOCR will help you in your prac ce. I was honored to be asked by Dr. William O’Brien to be the guest editor for the breast imaging sec on of the JAOCR. It is exci ng to see this journal

grow and even more exci ng to be a part of this growth. You have to understand how much me Dr. O’Brien puts into each edi on of the JAOCR. His exper se is astounding. I thank him and the JAOCR staff for all that they do.

Thanks also to the contributors to this edi on of the JAOCR, to include Drs. Rocky Saenz, Luke and Geneva Ballard, Shannon Gaffney, and the breast imaging faculty at the University of Cincinna . Without their me and energy, this edi on would not have been possible. Special thanks to Dr. Lennard Nadalo for his help in edi ng my MRI breast ar cle. He made it actually readable. Finally, thanks to my staff for helping me si through almost 3,200 MRI breast cases and picking out the “great” ones (albeit slowly) for the ar cle.

For those who know me, breast MRI is (and has been for awhile) a passion of mine. I enjoyed pu ng pen to paper and looking over my cases for the past 5 years, and I am especially excited to share this informa on with you. I hope you find it useful.

I hope everyone has a wonderful 2013. There are a lot of changes coming to healthcare. I can only hope that there are some beneficial changes amidst all of the controversy and craziness that seems to be part of the process. I hope that radiology – and more specifically breast imaging – will flourish, that research will con nue to direct us, and that compassion will con nue to drive us. Don’t lose sight of the reason you became a physician and specifically a radiologist. Ours is truly one of the great special es.

J Am Osteopath Coll Radiol 2013; Vol. 2, Issue 1

Indica ons Breast MR, Walters et al.

Introduc on

Breast cancer is the second most common cancer in women, following skin cancer. It accounts for 1 in 3 cancers diagnosed in women and is one of the leading causes of mortality in the United States. The average rela ve life me risk of breast cancer in women is about 1 in 8 (12%).1

MRI of the breast has become an important imaging modality in the detec on, evalua on, staging, and management of breast cancer. MRI has proven value in numerous clinical se ngs, including screening for breast cancer in select high‐risk pa ents with the wider use of gene c tes ng; evalua on for mul centricity or bilaterality of a known cancer; determining the efficacy of neoadjuvant chemotherapy; differen a on of scar ssue versus recurrent tumor in pa ents who have undergone breast‐conserva on surgery; and evalua on of pa ents with metasta c axillary adenopathy with an unknown primary. MRI may also be very useful in problem solving for pa ents with dense breast ssue, a difficult physical exam, equivocal mammogram and ultrasound findings, or discordant pathology results. This review offers guidelines and indica ons for breast MRI as represented in the literature.

Technique

Although there is no standardized technique for breast MRI, the American College of Radiology (ACR) has established minimum standards for breast MRI accredita on. The standards include a T2‐weighted sequence, and most importantly, a mul ‐phase T1 weighted sequence. In accordance with the ACR standards, both breasts must be examined simultaneously. Acquisi on during pre and post‐contrast T1 weighted sequences must have a slice thickness ≤ 3.0 mm. There should be no gap, and the maximum in plane pixel dimension for phase and frequency should be ≤ 1.0 mm.2 T1 weighted GRE imaging should be performed quickly with dynamic

enhancement and delayed imaging performed. Computer aided detec on may be beneficial in interpreta on of the exam. Subtrac on images may prove useful as well. Diffusion weighted imaging (DWI) along with ADC evalua on has been shown to be useful for the differen a on of benign vs. malignant tumors.3 Figure 1 shows normal pre and post‐contrast T1 weighted images, along with a normal subtrac on image.

Evalua on of images and lesions should be based on several factors, most importantly enhancement characteris cs and morphology. Delayed imaging may be beneficial, especially with low grade DCIS (Figure 2). In our prac ce, we also include T1 and T2 weighted open field of view (FOV) sequences to evaluate the chest wall and other surrounding so ssues. We have discovered lung and liver metastases (Figure 3), as well as associated adenopathy (Figure 4), with open FOV sequences.

Repor ng

The most commonly accepted repor ng system for breast imaging is Bi‐Rads classifica on.

Bi‐Rads for MRI is iden cal to the Bi‐Rads classifica on in mammography.

For full lesion features and descrip ons for MRI, the ACR website has a MRI Lexicon Classifica on Form which may be used as a guideline.

MRI Breast Clinical Indica ons: A Comprehensive Review

Michelle C. Walters, D.O., FAOCR,1 and Lennard Nadalo M.D., FACR2

1Medical Director, Advanced Imaging, DeSoto, TX 2Department of Radiology, Methodist Health Systems, Dallas, TX

Category 0 – Incomplete: need for addi onal imaging

Category 1 – Nega ve

Category 2 – Benign findings

Category 3 – Probably benign findings

Category 4 – Suspicious abnormality

Category 5 – Highly sugges ve of malignancy

Category 6 – Known cancer


Indica ons Breast MR , Walters et al.

Breast Cancer Screening With MRI

Recommenda ons.

MRI of the breast is increasingly used to screen for breast cancer in the high‐risk pa ent. There are many factors used in the determina on of a pa ent’s overall rela ve life me risk of breast cancer. Breast cancer risk factors include a family history of breast and ovarian cancer, high risk pathology such as lobular

Figure 1. T1W pre‐contrast (A), post‐contrast (B), and subtrac on (C) images demonstrate a normal enhancement pa ern of the breast without focal or suspicious abnormality.

carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), radial scar, and women who have a history of radia on treatment for Hodgkin disease, etc.4‐6

Mammography remains the gold standard for breast cancer screening; however, for women with increased risk of breast cancer, other screening modali es, including US and MRI, have been shown to contribute to early the detec on of breast cancer. The American Cancer Society (ACS) issued recommenda ons for breast MRI screening in March 2007:

Recommend Annual MRI Screening

Pa ents with BRCA muta on; first‐degree rela ve of BRCA carrier, but untested; or life me risk ≥ 20‐25% as defined by BRCAPRO or other models that are largely dependent on family history.

(Based upon evidence from nonrandomized screening trials and observa onal studies)

A

C

B

Figure 2. Delayed MRI imaging can be cri cal at mes, especially in cases of DCIS. MLO view of the breast (A) shows an abnormality in the upper posterior breast which only demonstrates delayed enhancement on post‐contrast T1W MRI (B). Biopsy proven DCIS.

Figure 3. T2W axial image demonstrates a liver mass suspicious for metastases.

A B



Recommend Annual MRI Screening

Pa ents with radia on to the chest between the ages of 10 and 30 years or a personal history or first‐degree rela ve with Li‐Fraumeni, Cowden, and Bannayan‐Riley‐Ruvalcaba syndromes.

(Based upon expert consensus opinion/life me risk for breast cancer)

Insufficient Evidence to Recommend For or Against MRI Screening

Pa ents with a life me risk of 15‐20% as defined by BRCAPRO or other models that are largely dependent on family history; LCIS, ADH, or atypical lobular hyperplasia; heterogeneously or extremely dense breast on mammography; or a personal history of breast cancer, including DCIS. Screening decisions should be made on a case‐by‐case basis, as there may be par cular factors to support MRI. Payment should not be a barrier. More data on these groups is expected to be published soon.7

Recommend Against MRI Screening

Pa ents with <15% life me risk of breast cancer.

(Based upon expert consensus opinion)

BRCA1 and BRCA2 muta ons are responsible for 40‐50% of all familial cancers. The BRCA muta on increases the average life me risk of breast cancer to approximately 60‐80% and 40% for ovarian cancer (BRCA1).8 The ACS Guidelines recommend “intensified

surveillance” as an alterna ve to bilateral mastectomy. BRCA1 associated breast cancers tend to have benign morphological appearances (round shapes and minimal asymmetry) but an aggressive biological nature. Thus, screening should start at a younger age and occur more frequently in the case of BRCA muta ons. These women are younger at presenta on when average breast density is high. Earlier and more frequent screening in this popula on will result in a substan al cumula ve life me ionizing radia on dose.9,10 With the addi onal increased risk of breast cancer associated with mammographic screening (albeit minimal), poten ally dense breast

Figure 5. Dense breast ssue in a BRCA posi ve pa ent. Bilateral CC views (A) show dense breast ssue bilaterally, which limits the sensi vity of mammography. US (not shown) demonstrated several hypoechoic masses and patchy areas of shadowing. Axial T1W post‐contrast image with fat‐suppression (B) demonstrates benign bilateral fibrocys c changes, Bi‐Rads 2.

A B

Figure 4. T2W axial image reveals medias nal adenopathy.



ssue in the younger pa ent, and the need for increased sensi vity in the evalua on of these pa ents, MRI has become accepted as an integral part of surveillance in the high risk popula on (Figure 5).

For women with an average risk of breast cancer, there is no data that supports breast MRI for screening at this me. Although MRI does have increased sensi vity in the detec on of breast cancer, the posi ve predic ve value (PPV) is much lower than in the high risk popula on; therefore, the cost of rou ne MRI screening is not jus fied. Long‐term studies and further surveillance may change this perspec ve in the future.

Third Party Reimbursement

Insurance companies tend to follow the above guidelines for reimbursement. For the lower risk pa ent with dense breast ssue, a difficult physical exam, or significant fibrocys c changes, there are less objec ve recommenda ons and MRI of the breast may not be covered by insurance. Most insurance companies u lize a calcula on of risk factors using one of several methods: BRCAPRO ‐ Claus model ‐ Gail model – Tyrer‐Cuzick . The major carriers have policy guidelines for breast MRI.

Sensi vity and Specificity in MRI Breast

Screening

Sensi vity of mammography alone decreases in propor on to the increased density of the breast ssue. However, breast density does not affect the

sensi vity of MRI (Figure 6).11 There are numerous literature references for sensi vity and specificity of mammography, US, and MRI. The references vary but all clearly state that MRI is by far more sensi ve than mammography and US in the detec on of breast cancer for high‐risk pa ents, dense breast ssue,

A

C

B

Figure 6. Pa ent with personal and family history of breast cancer. Bilateral MLO views (A) demonstrate findings of prior lumpectomy on the le for invasive ductal carcinoma; right breast is very dense. US (not shown) demonstrated several hypoechoic masses bilaterally with patchy areas of shadowing. T1W pre (B), post‐contrast (C), and MIP (D) images reveal a cobblestone enhancement pa ern in the right breast at the 9‐10 o’clock posi on. Biopsy revealed high‐grade DCIS with central necrosis. D



pa ents on hormone replacement therapy (HRT), and in the younger popula on.12,13 According to the Na onal Cancer Ins tute (NCI) Breast Cancer Surveillance Consor um (BCSC), the sensi vity of screening mammography in the detec on of breast cancer (star ng at age 40) ranges from as low as 64% to as high as 100% based upon age and me from prior mammogram. Specificity was as low as 78% to as high as 94%.14

MRI breast does not replace screening mammography or diagnos c mammography with US evalua on. Rather, MRI is used in conjunc on with these modali es (Figure 7). Although breast MRI is more sensi ve in the detec on of breast cancer when compared to mammography and US, it has been reported as less specific overall.15 It should be noted, however, that in a recent ACRIN trial, the specificity of MRI breast was as high as 88%.16 MRI’s imperfect sensi vity comes from its inability to detect low grade DCIS due to the lack of enhancement. Mammography, on the other hand, may detect low grade DCIS as amorphous calcifica ons or small foci of architectural distor on, which may not be detected or be very subtle on breast MRI. Overall, however, MRI has been shown to be superior to mammography in detec ng cases of unsuspected DCIS.17 Contrast‐enhanced MRI of the breast has shown rela vely high sensi vi es, ranging from 94‐99% for invasive cancer and 50‐80% for in situ cancers.18

MRI Breast in the Newly Diagnosed Breast

Cancer Pa ent

Clinical Indica ons and Applica ons of Breast MRI.

The Na onal Comprehensive Cancer Network (NCCN) discussion of breast MRI recommends the use of MRI for the following clinical indica ons and applica ons:

Staging evalua on to define extent of cancer orpresence of mul focal or mul centric cancer in the ipsilateral breast.

Screening for contralateral breast cancer at meof ini al diagnosis.

Evalua on before and a er neoadjuvanttherapy to define extent of disease, response to treatment, and poten al for breast conserving therapy.

Figure 7. Complimentary role of mammography and MRI. Bilateral MLO views (A) demonstrate suspicious calcifica ons in the posterior le breast (biopsy proven DCIS), as well as faint, sca ered calcifica ons in the upper, posterior right breast; the calcifica ons on the right could not be seen well or biopsied on stereotac c technique. Pre (B) and post (C) contrast MR images reveal very minimal nodular enhancement in the far posterior, lateral right breast. Due to the faint calcifica on in this area, the pa ent underwent biopsy with the pathologic diagnosis of low‐grade DCIS. Pa ent also had lumpectomy changes on the le for intermediate grade DCIS. She subsequently opted for bilateral mastectomies.

A

C

B



staging of breast cancer is outlined in the 7th Edi on of the American Joint Commi ee on Cancer. Key staging components include tumor size; involvement of overlying skin or chest wall; involvement of local or regional lymph nodes, to include mobile or fixed, conglomerate, or extracapsular spread; and presence or absence of distant metastases.

MRI has been shown to increase the sensi vity in the evalua on of local‐regional disease involving the breast and axilla. When combined with mammography, US, and clinical exam, the sensi vity of MRI is as high as 99% in cases of newly diagnosed breast cancer (Figure 9).19 The reported low sensi vity of clinical exam (50%), mammography (60%), and US (83%) alone substan ate the use of MRI in the preopera ve staging of breast cancer pa ents. Breast MRI has been shown to detect both mul centric and bilateral breast cancers with increased sensi vity over clinical exams, mammography, and US (Figures 10 and 11).20,21 Ipsilateral mul centric disease detected with MRI has been reported in 10‐27% of pa ents. MRI detects occult contralateral breast cancer in about 3% of pa ents with invasive ductal carcinoma and in 6% of pa ents with invasive lobular carcinoma. Bilaterality has been reported in up to 10% in selected series.22,23

Overall tumor size is more accurately depicted on MRI compared to mammography when correlated with pathology specimens (Figure 9).24,25 Although it was thought that this may decrease the need for reexcision due to unclear margins, this has recently

Figure 8. Pa ent presented with signs and symptoms of Paget’s disease of the le nipple. CC and MLO views of the le breast (A) demonstrate skin thickening around the nipple region but no other findings. US (not shown) added no addi onal informa on. Post‐contrast color‐coded MR image (B) reveals the extent of the pa ent’s invasive disease.

A

B

Detect addi onal disease in women with mammographically dense breasts.

Iden fy primary cancer in women with axillary nodal adenocarcinoma or Paget’s disease of the nipple (Figure 8) with a breast primary not iden fied on mammography, ultrasound, or physical examina on.

The u lity of MRI in follow‐up screening of women with prior breast cancer is undefined. It should generally be considered only in those whose life me risk of a second primary breast cancer is greater than 20% based on models largely dependent on family history, such as in those with a risk associated with inherited suscep bility to breast cancer.

There is no data demonstra ng that the use of MRI to affect choice of local therapy improves outcomes (local recurrence or survival). Although breast MRI is more sensi ve than mammography or US, false posi ve findings on MRI are common. Therefore, surgical decisions should not be based solely on MRI findings. Tissue sampling of areas of concern iden fied by breast MRI is recommended prior to treatment planning.

Staging.

Treatment op ons for breast cancer are based upon staging. Breast cancer staging is determined by the extent of disease in the breast and axilla, as well as metasta c disease determina on. The current TNM



Figure 9. Pa ent presents with palpable mass on right. Bilateral MLO views of the breast (A) demonstrate a mass in this region with an US correlate (B). Biopsy revealed invasive ductal carcinoma. MRI breast (C and D) demonstrates more anterior and superior lateral extension than is perceived by mammogram or US.

Figure 10. Bilateral/contralateral breast cancer. MLO (A) and CC (B) views demonstrate a mass in the upper outer le breast, which was confirmed as suspicious on US (not shown). Post‐contrast (C), MIP (D), and color‐coded (E) images reveal the known breast cancer on the le , as well as an unsuspected enhancing mass in the right breast. Second look US was performed with subsequent biopsy; pathological diagnosis was invasive ductal carcinoma.

A

C B

D

A

B

C

D

E



been shown not to be true. The COMICE trial performed in the UK demonstrated similar need for reexcision in pa ents who had pre‐opera ve MRIs versus those who did not. However, further study with long‐term evalua on and follow‐up is needed.26

In the clinical se ng of DCIS, MRI is useful to rule out underlying invasive carcinoma. This can be accomplished with MRI due to its high nega ve predic ve value (NPV) in the diagnosis of invasive breast cancer. MRI and mammography compliment each other in the diagnosis of DCIS. Although MRI has greater overall sensi vity, it does not detect all DCIS cases, especially those which are non‐enhancing and are only seen as calcifica ons on mammography. Mammography is similarly limited in the detec on of DCIS, especially in the absence of calcifica ons where lesions are only detected as abnormal enhancement on MRI. Research has shown that the overall sensi vity of MRI for high‐grade DCIS is higher than that of mammography.27

Controversy.

Breast surgeons have concerns regarding MRI causing a delay in treatment and/or increasing mastectomy rates. In most cases, the delay in treatment is minimal, since an MRI can be performed quickly a er biopsy with the diagnosis of cancer. As for the increase in mastectomy rates related to breast MRI and the opinion that radia on therapy eradicates or delays progression of residual disease, these are not proven. While there have been reports of unnecessary mastectomies based upon false‐posi ve MRI exams, this emphasizes the point that surgical management of breast cancer should be based upon confirmed histology, i.e. MRI‐guided biopsy.28

With breast conserva on therapy, the rate of recurrence is low but not zero. The statement that outcomes in women who undergo breast conserva on

Figure 11. Bilateral/contralateral breast cancer in a pa ent with a palpable mass on the right. MLO (A) and CC (B) views reveal an asymmetry in the mid‐lower, inner right breast, similar to prior studies. US was performed (not shown), and biopsy demonstrated invasive ductal carcinoma. Color‐coded (C) and MIP (D) post‐contrast images be er delineate the breast cancer on the right and iden fy an addi onal suspicious mass in the le breast. Second look US of le breast was performed with biopsy; pathological diagnosis was invasive ductal carcinoma.

A

B

C

D



are equivalent to the outcomes in women who undergo mastectomy is debatable. The trials that have been performed to date have shown that women who undergo breast conserva on have a higher risk of local recurrence. Thus, disease free survival is not equivalent.29 It was previously thought that local recurrence did not affect overall survival. However, it is now well accepted that local relapse does affect overall survival. Therefore, preven ng local recurrence is considered as important as the early diagnosis of the primary breast cancer. The ability to prevent local recurrence requires more accurate staging and subsequent treatment; this is where MRI can play a cri cal role.30‐32

The threshold of radia on therapy to eradicate any residual disease has not been established. Each pa ent should be offered the best treatment for long‐term survival. In essence, a staging MRI examina on which demonstrates only one focal cancer site allows the pa ent, surgeon, and oncologist to explore the op on of conserva on therapy, since the likelihood of any residual disease will be low. It should also be clarified that mul centricity does not necessarily require mastectomy.

It must be stated clearly that there are no published

randomized, prospec ve trials that have assessed the impact of breast MRI on mastectomy rates, or the impact on the recurrence rates or mortality. The long‐term determina on of this controversy will only come from controlled studies with long‐term follow‐up. Un l that me, MRI should be used in the context of staging and improved pathologic confirma on of local regional disease. Treatment plans in tumor boards can be discussed and implemented with be er knowledge of the pa ent’s disease extent and the treatment needed.

Neoadjuvant Chemotherapy Follow‐Up

Neoadjuvant chemotherapy has been increasingly used over the past several years for pa ents with locally advanced breast cancer (LABC). LABC typically refers to breast cancer lesions that are larger than 5 cm with or without spread to lymph nodes. The primary advantage of neoadjuvant chemotherapy is to reduce the size of the overall tumor burden. This allows for a higher percentage of pa ents to undergo breast conserva on therapy, while s ll offering significant reduc on in local recurrence rates and improved overall survival.33,34

Figure 12. Good response to neoadjuvant chemotherapy. Color‐coded post‐contrast MR images pre (A) and post (B) treatment reveal markedly decreased enhancement of the mass within the inner, posterior right breast.

Figure 13. Good response to neoadjuvant chemotherapy. Color‐coded post‐contrast MR images pre (A) and post (B) treatment reveal markedly decreased rim‐enhancement of the mass within the mid, anterior right breast, as well as the mul centric masses in the le breast.

B B

A A



Diagnos c imaging is performed to monitor the tumor response to chemotherapy as early as possible and to iden fy any residual tumor. Informa on regarding tumor response during the early stages of neoadjuvant chemotherapy is useful for treatment op miza on. Tumor size may not necessarily decrease immediately in the early phase of treatment; therefore, evalua on of metabolic response becomes important. PET scanning and MRI have established roles in the early assessment of metabolic “func onal” response. MRI demonstrates a posi ve response to chemotherapy as a decrease in the enhancement characteris cs of the tumor (Figures 12 and 13). The enhancement curve changes and typically fla ens with a diminished wash‐out pa ern. Wash‐in changes occur as well; the wash‐in will be slower. A decrease in tumor size typically occurs later.35 MR Spectroscopy and diffusion‐weighted (DWI) MRI have been shown to help evaluate “responders” versus “non‐responders” as early as 24 hours a er the first cycle of chemotherapy. DWI detects cytotoxic effects of the chemotherapy by the change in the free inters al water diffusion rates. There are standard protocols for DWI and ADC mapping; the literature provides sugges ons for protocols and visual and numerical references. As protocols become standardized and controlled studies are performed, DWI and ADC may become standard in the evalua on for ini al response to chemotherapy.36

A er neoadjuvant chemotherapy, MRI is o en used to evaluate for any residual tumor. A recent ACRIN study (Protocol 6657) concluded that tumor response to chemotherapy as measured volumetrically by MRI was a much stronger and early predictor of pathologic response than clinical or tumor diameter. Several studies have demonstrated similar findings, indica ng that MRI is superior to conven onal mammography, US, and clinical exam.37,38 However, MRI correla on with tumor response is not 100%. It has been shown in some cases, par cularly with chemotherapeu c agents that demonstrate an vascular effects, that residual vital tumor may be iden fied in up to 30% of pa ents whose MRI showed no residual abnormal enhancement. The accuracy of MRI in post‐neoadjuvant chemotherapy evalua on also appears to vary with tumor subtype. It appears to be more accurate in ER‐/HER2+ and triple nega ve and less accurate in luminal tumors.39,40

Problem Solving

MRI can be used for problem solving in clinical scenarios such as discordant pathology results (Figures 14 and 15), markedly dense breast ssue with mul ple palpable lumps (Figure 16), or complex mammographic findings (Figure 17). MRI is also useful in cases with equivocal or inconclusive findings on mammograms or US. Pa ents who have undergone breast conserva on therapy may benefit from MRI if there is clinical concern of recurrent tumor versus developing scar ssue.

If there is a single abnormality on either US or mammogram, then US‐guided or stereotac c biopsy is more efficient. These two biopsy techniques are readily available, rela vely safe, easy to perform, and provide a histologic diagnosis.

In the pa ent with mul ple areas of asymmetry on a mammogram (without calcifica on) and no US abnormality; a mammographic abnormality seen only on one view; or for the pa ent with mul ple round, smooth masses that are equivocal on mammogram and US (i.e. breast cancer vs. mul ple sclero c fibroadenomas or mul ple complex cysts), MRI has a very high nega ve predic ve value (NPV). Some ins tu ons may put these pa ents in short‐term 6 month follow‐up, Bi‐Rads 3, diagnosis; however, rather than short‐term follow‐up or biopsy, MRI may also be considered. A 3‐year consecu ve study recently reported that breast MRI should be used in the diagnos c work‐up of non‐calcified Bi‐Rads 3 lesions. It was stated that malignancy is ruled out with a very high level of confidence in the majority of pa ents, thus avoiding invasive diagnos c procedures.41

Abnormal nipple discharge is most o en caused by benign e ologies, such as ductal ectasia or solitary or mul ple papillomas.42 Mammogram and US are performed ini ally to evaluate for the underlying cause and to rule out associated or causa ve breast cancer. Mammography and US are complimentary in evalua ng abnormal nipple discharge. However, in the majority of cases, both exams will o en be normal. Galactography may be performed and can be helpful; however, o en mes (up to 10% of cases) a galactogram cannot be performed due to technical reasons (i.e. intermi ent discharge, discharge from more than one orifice, etc). Also, the diagnos c informa on obtained with a galactogram is limited.



Figure 14. Problem solving with discordant results. Bilateral CC views (compressed and magnified on the le ) (A) demonstrate suspicious calcifica ons within the outer, posterior le breast, as well as a mass in the posterior right breast. Right breast US (B) reveals a suspicious, lobulated, hypoechoic mass with posterior shadowing. Le breast biopsy demonstrated invasive ductal carcinoma. Right breast US‐guided biopsy demonstrated sclerosing adenosis, which was felt to be discordant with the imaging findings. Post‐contrast color‐coded MR image (C) reveals extensive tumor in the le breast and findings highly sugges ve of malignancy (abnormal rapid enhancement as well as irregular margins) on the right. MRI‐guided right breast biopsy revealed infiltra ng carcinoma with apocrine features.

Figure 15. Problem solving with discordant results. Ini al bilateral MLO analog images from 6 months earlier (A) are normal. Follow‐up MLO (B) and CC (C) digital images of the le breast demonstrate an area of spicula on (best seen on the MLO view) underlying the palpable marker. Le breast US (D) reveals an ill‐defined area of low level echoes. Biopsy was performed with US guidance and the pathology results were fibrosis and chronic inflamma on, which was felt to be discordant. Post‐contrast MR images demonstrates two irregular suspicious enhancing masses in the le breast (E), as well as a very large enhancing mass in the inferior le lateral axilla (F). Biopsy under MR guidance revealed infiltra ng ductal carcinoma with axillary metastasis.

A

C B

A C B

E

F

D



Figure 16. Young woman with dense breast ssue and palpable mass on the right. MLO (A) and CC (B) views demonstrate a mass in the mid, posterior right breast. US (C) with biopsy revealed mucinous carcinoma. Post‐contrast MR image (D) is beneficial in determining size and extent of tumor, especially in the se ng of markedly dense breast ssue and difficult US and physical exams.

Figure 17. Problem solving with complex mammogram. Bilateral MLO views (A) reveal numerous silicone injec on granulomas, greatly reducing the sensi vity of mammography. Post‐contrast color‐coded MR image (B) demonstrates normal enhancement of underlying breast ssue. There may be normal rim enhancement of some of

the silicone granulomas.

A

A

C

B

D

B



Sensi vity for detec on of a malignant lesion has been reported as very low (0‐55%).43 MRI can help detect intraductal lesions not seen on mammogram and/or US and allows for localiza on of the lesion (Figure 18); subsequent image‐guided biopsy may be performed.44

Axillary Adenopathy With Unknown Primary

Few women diagnosed with breast cancer ini ally present with metasta c axillary adenopathy. Historically, mastectomy was the treatment of choice in a pa ent with adenocarcinoma metastasis to the axillary lymph nodes in which the clinical exam, conven onal mammogram, and/or US were unable to detect an abnormality, as it was usually thought to originate from a primary breast cancer in the ipsilateral breast. MRI can detect the primary tumor in up to 70% of these pa ents (Figure 19).45,46 This effec vely changes their staging from T0 (unknown primary) to a defined TNM classifica on. The pa ent can then undergo more appropriate and focused surgical and oncologic therapy.

Due to the nega ve predic ve value of MRI in the detec on of invasive breast cancer, a nega ve MRI can be used to suggest that a mastectomy is not needed. Some oncologists advocate the use of radia on

therapy alone in women with a nega ve MRI.47

Ongoing Screening Debate

Recent controversial opinions concerning the value of breast cancer screening have challenged the very basis of why we offer mammography and by extension, breast MRI.48 It is cri cal that breast imagers base their prac ce on the firm convic on that mammography ‐ and by extension MRI of the breast ‐ saves lives. Nearly 20% of cancers which are detected with screening mammograms are found in women 40‐50 years old. Recent nega ve opinions have been the products of retrospec ve analysis by physicians who do not directly treat or diagnose breast cancer. The mantra that “early detec on save lives” is s ll as true as ever before. Breast MRI allows very early detec on of cancers in women who are at high risk. Breast MRI also allows for a less invasive means of follow‐up for those women at moderate risk. It is important to support prospec ve studies related to breast cancer detec on while we con nue to offer the safest means possible to detect and manage breast cancer in our pa ents.

Figure 18. Le ‐sided nipple discharge. MLO and CC views of the le breast (A) are normal, as was ini al US (not shown). Post‐contrast subtrac on MR image (B) shows abnormal ductal enhancement within the le breast at the 4 o’clock posi on. Second look US (C) demonstrates low level echoes, sugges ng an intraductal mass. Biopsy demonstrated a papillary lesion, which was surgically excised.

A B

C

D



Summary

In summary, breast MRI has proven to be a valuable tool in the diagnosis, work‐up, and management of breast cancer. Common indica ons include screening for breast cancer in select high‐risk pa ents, problem solving in cases of dense breast ssue or equivocal or discordant findings on mammogram or US, evalua on for mul centricity or bilaterality of a known cancer, determining the efficacy of neoadjuvant chemotherapy, differen a on of scar ssue versus recurrent tumor, and evalua on of axillary adenopathy with an unknown primary. The clinical indica ons will likely con nue to expand as clinical trials demonstrate addi onal benefits of MRI in breast imaging. When used in conjunc on with mammogram and US, this useful tool will assist in decreasing morbidity and mortality associated with breast cancer.

Figure 19. Axillary adenopathy with unknown primary. Bilateral MLO views performed at an outside ins tu on (A) were read as benign and unchanged from an exam two years prior. Pa ent felt a mass in her right underarm one week a er the mammogram. A surgeon performed a biopsy in his office, and the pathology came back as cancer. Post‐contrast MR images demonstrate a mass far lateral posterior right breast at the 7 o’clock posi on with abnormal enhancement and abnormal morphology (B), as well as an enlarged right axillary lymph node (C) which was previously biopsied. MRI‐guided biopsy demonstrated invasive lobular carcinoma.



References

1. American Cancer Society. Detailed Guide: Breast Cancer What Are the Key Sta s cs for Breast Cancer?. AmericanCancer Society Cancer Resource Informa on. h p://www.cancer.org

2. ACR Breast Magne c Resonance Imaging Accredita onProgram Requirements.

3. Tsushima Y, Takahashi‐Taketomi A, Endo K. Magne cresonance (MR) differen al diagnosis of breast tumors usingapparent diffusion coefficient (ADC) on 1.5T. Journal ofMagne c Resonance Imaging: JMRI 2009;30(2):249‐255.

4. Bedeil, Falcini F, Sanna PA, et al. Atypical ductal hyperplasiaof the breast: The controversial management of a borderlinelesion: experience of 47 cases diagnosed at vacuum‐assistedbiopsy. Breast 2006; 15(2): 196‐202.

5. Chuba PJ, Hamre MR, Yap J, et al. Bilateral risk for subsequentbreast cancer a er lobular carcinoma‐in‐situ: analysis ofsurveillance, epidemiology, and end results data. J Clin Oncol2005;23:5534‐5541.

6. Ford D, Easton DF, Bishop DT, et al. Risks of cancer in BRCA 1‐muta on carriers. Breast Cancer Linkage Consor um. Lancet1994;343:692‐695.

7. Saslow D, Boetes, C, Burke W, et al. American Cancer SocietyGuidelines for Breast Screening with MRI as an Adjunct toMammography. CA Cancer J Clin 2007;57:75‐89.

8. Hoskins KF, Stopfer JE, Calzone KA, et al. Assessment andcounseling for women with a family history of breast cancer: aguide for clinicians. JAMA 1995 ;273:577 ‐585.

9. Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI andmammography for breast‐cancer screening in women with afamilial or gene c predisposi on. N Engl J Med 2004;351:427‐437.

10. Kuhl CK, Schrading S, Leutner CK, et al. Mammography,breast ultrasound, and magne c resonance imaging forsurveillance of women at high gene c risk for breast cancer.J Clin Oncol 2005;23:8469‐8876.

11. Berg WA, Gu erriz L, Ness Aiver MS, et al. Diagnos c accuracyof mammography, clinical examina on, US, and MR imagingin preopera ve assessment of breast cancer. Radiology.2004;233:830‐849.

12. Vachon CM, van Gils CH, Sellers TA, et al. Mammographicdensity, breast cancer risk and risk predic on. Breast Cancer Res 2007;9:217.

13. Carney PA, Migliore DL, Yankaskas B, et al. Individual andcombined effects of age, breast density, and hormonereplacement therapy use on the accuracy of screeningmammography. Ann Intern Med 2003;138:168‐175.

14. Na onal Cancer Ins tute, Breast Cancer SurveillanceConsor um. Performance measures for 1,960,150 ScreeningMammography Examina ons from 2002 to 2006 by Age &Time (Months) Since Prior Mammography – based on BCBSdata as of 2009. www.cancer.org

15. Lord SJ, Lei W, Cra P, et al.: A systema c review of theeffec veness of magne c resonance imaging (MRI) as anaddi on to mammography and ultrasound in screening youngwomen at high risk of breast cancer. Eur J Cancer 2007; 43(13): 1905‐17.

16. Lehman CD, Gatsonis C, Kuhl CK, et al. MRI Evalua on of theContralateral Breast in Women with Recently DiagnosedBreast Cancer. N Engl J Med 2007;356:1295‐1303.

17. Hwang ES, Kinkel K, Esserman LI, et al. Magne c resonanceimaging in pa ents diagnosed with ductal‐carcinoma‐in‐situ:Value in the diagnosis of residual disease, occult invasion andmul centricity. Ann Surg Oncol. 2003;10:381‐388.

18. Sardanelli F, Giusseppe GM, Panizza P, et al. Sensi vity ofMRI Versus Mammography for Detec ng Foci of Mul focal,Mul centric Breast Cancer in Fa y and Dense Breasts Usingthe Whole‐Breast Pathologic Examina on as a Gold Standard.AJR 2004; 183:1149‐1157.

19. Houssami N, Cia o S, Macaskill P, et al. Accuracy and surgicalimpact of magne c resonance imaging in breast cancerstaging: systema c review and meta‐analysis in detec on ofmul focal and mul centric cancer. J Clin Oncol 2008;26:3248‐3258.

20. Berg WA, Gu errez L, Ness Aiver MS, et al. Diagnos caccuracy of mammography, clinical examina on, US, and MRimaging in preopera ve assessment of breast cancer.Radiology. 2004;233:830‐849.

21. Bedrosian I, Mick R, Orel SG, et al. Changes in the surgicalmanagement of pa ents with breast carcinoma based on preopera ve magne c resonance imaging. Cancer.2003;98:468‐473.

22. Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evalua on of thecontralateral breast in women with recently diagnosed breastcancer. N Engl J Med. 2007;356:1295‐1303.

23. Samant RS, Olivo o IA, Jackson JS, et al. Diagnosis ofmetachronous contralateral breast cancer. Breast J2001;7:405‐410.

24. VanGoethem M, Schelfout K, Kersschot E, et al. Enhancingarea surrounding breast carcinoma on MR mammography:Comparison with pathological examina on. Eur Radiol.2004;14:1363‐1370.

25. Schnall M. MRI imaging of cancer extent: is there clinicalrelevance? Magn Reson Imaging Clin N Am 2006; 14:379‐381.

26. Turnbull L, Brown S, Harvey I, et al. Compara ve effec veness of MRI in breast cancer (COMICE) trial: arandomized controlled trial. Lancet 2010; 375:563‐571.

27. Kuhl CK, Schrading S, Bieling HB, et al. MRI for diagnosis ofpure ductal carcinoma in situ: a prospec ve observa onalstudy. Lancet 2007;370:485‐492.



28. Bilimoria KY, Cambic A, Hansen NM, et al. Evalua ng theimpact of preopera ve breast magne c resonance imaging onthe surgical management of newly diagnosed breast cancers.Arch Surg 2007;142:441‐445; discussion 445‐447.

29. Jatoil, Proschan MA. Randomized trials of breast‐conservingtherapy versus mastectomy for primary breast cancer: apooled analysis of updated results. Am J Clin Oncol2005;28:289‐294.

30. Poggi MM, Danforth DN, Sciuto LC, et al. Eighteen‐yearresults in the treatment of early breast carcinoma withmastectomy versus breast conserva on therapy: the Na onalCancer Ins tute randomized trial. Cancer 2003;98:697‐702.

31. Doyle T, Schultz DJ, Peters C, et al. Long‐term results of localrecurrence a er breast conserva on treatment for invasivebreast cancer. Int J Radiat Oncol Biol Phys 2001;51:74‐80.

32. vanDongen JA, Voogd AC, Fen man IS, et al. Long‐termresults of a randomized trial comparing breast‐conservingtherapy with mastectomy: European Organiza on forResearch and Treatment of Cancer 10801 trial. J Natl Cancer Inst 2000;92:1143‐1150.

33. Bonadonna G, Valagussa P. Primary chemotherapy inoperable breast cancer. Semin Ocol 1996;23:464‐74.

34. Shin HJ, Kim HH, Ahn, JH, et al. Comparison ofmammography, sonography, MRI and clinical examina on inpa ents with locally advanced or inflammatory breast cancerwho underwent neoadjuvant chemotherapy. The Bri shJournal of Radiology 2011;84:612‐620.

35. El Khoury C, Servois V, Thibault F, et al. MR quan fica on ofthe washout changes in breast tumors under preopera vechemotherapy: feasibility and preliminary results. Am JRoentgenol 2005;184:149‐1504.

36. Woodhams R, Ramadan S, Stanwell P, et al. Diffusion‐weighted imaging of the breast: Principles and clinicalapplica ons. Radiographics 2011;31:1059‐1084.

37. Hylton N, Blume C, Gatsonis R, et al. MRI tumor volume forpredic ng response to neoadjuvant chemotherapy in locallyadvanced breast cancer: Findings from ACRIN 6657/CALGB150007. Abstracts presented at the 2009 ASCO AnnualMee ng. Cita on: J Clin Oncol 27:15s, 2009 (supple; abstr529).

38. Yeh E, Slanetz P, Kopans DB, et al. Prospec ve comparison ofmammography, sonography, and MRI in pa ents undergoingneoadjuvant chemotherapy for palpable breast cancer. Am JRoentgenol 2005;184:868‐877.

39. Denis F, Desbiez‐Bourcier AV, Chapiron C, et al. Contrastenhanced magne c resonance imaging underes matesresidual disease following neoadjuvant docetaxel basedchemotherapy for breast cancer. Eur J Surg Oncol2004;30:1069‐1076.

40. McGuire KP, Toro‐Burguete J, Dang H, et al. MRI staging a erneoadjuvant chemotherapy for breast caner: does tumorbiology affect accuracy? Ann Surg Oncol 2011;18;3149‐54.

41. Dorrius MD, Pijnappel RM, Sijens PE, et al. The nega vepredic ve value of breast Magne c Resonance Imaging in thenoncalcified BIRADS 3 lesions. Eur J Radiol 2012;81:209‐213.

42. Cabiolglu N, Hunt KK, Singletary SE, et al. Surgical decisionmaking and factors determining a diagnosis of breastcarcinoma in women presen ng with nipple discharge. J AmColl Surg 2003;196:354‐364.

43. Dinkel HP, Trusen A, Gassel AM, et al. Predic ve value ofgalactorgraphic pa erns for benign and malignant neoplasmsof the breast in pa ents with nipple discharge. Br J Radiol2000;73:706‐714.

44. Daniel BL, Gardner RW, Birdwell RL, et al. Magne cresonance imaging of intraductal papilloma of the breast.Magn Reson Imaging 2003;21:887‐892.

45. Olson JA Jr, Morris EA, Van Zee KJ, et al. Magne c resonanceimaging facilitates breast conserva on for occult breastcancer. Ann Surg Oncol 2000;7:411‐415.

46. De Bresser J, de Vos B, van der Ent F, Hulsewe’ K. Breast MRIin clinically and mammographically occult breast cancerpresen ng with an axillary metastasis: a systema c review.Eur J Surg Oncol 2010;36:114.

47. Masinghe SP, Faluyi OO, Kerr GR, et al. Breast radiotherapyfor occult breast cancer with axillary nodal metastases – doesit reduce the local recurrence rate and increase overallsurvival? Clin Oncol (R Coll Radiol) 2011;23:95.

48. Hendrick RE, Helvie MA. Mammography screening: a newes mate of number needed to screen to prevent one breastcancer death. Am J Roentgenol 2012; 198: 723‐728.


DCIS, Ballard et al.

Introduc on

Ductal carcinoma in situ (DCIS) is a common pre‐invasive malignancy of the breast, represen ng approximately 20% of all breast cancer diagnoses.1,2 It is widely believed that DCIS is a precursor lesion to invasive ductal carcinoma, but the exact biologic nature is not completely understood and debated by some.3‐5 DCIS is unarguably a heterogeneous disease with variable malignant poten al. Evidence shows that high‐grade DCIS is an aggressive subtype with an overall poorer prognosis than non‐high‐grade disease. There have been many studies evalua ng the role of the radiologist in the diagnosis of high‐grade DCIS with emphasis on radiologic‐pathologic correla on using standard mammography and magne c resonance imaging. Our current understanding of the clinical importance of high‐grade DCIS from the perspec ve of a radiologist and characteris c imaging features are discussed in detail.

Clinical Implica on of DCIS

The diagnosis of DCIS has increased drama cally over the last several decades from an incidence of less than 2 per 100,000 in the early 1970’s to 32.5 in 2004.1 Much of this increase has been a ributed to the advent of screening mammography. Some advocates of screening see this as a victory, achieving one of the goals of a screening program: the preven on of life threatening invasive cancer by detec on and treatment at the in situ stage.6 Detractors, however, believe the detec on of DCIS leads to a substan al number of pa ents being over‐diagnosed and over‐treated for a non‐life threatening condi on.7 While large scale trials have shown survival benefit of screening mammography in the range of 30 percent, the screening debate goes on and is beyond the scope of this discussion.8‐11

Much of the controversy regarding the increase in diagnosis of DCIS over the years lies in our limited knowledge of the natural history of the disease. There

is li le argument that DCIS is likely a precursor to invasive ductal carcinoma. However, it is very clear that some ‐ but not all ‐ of DCIS will progress over the life me of a pa ent. The evidence well summarized by Erbas et al. showed that 14‐53% of DCIS mis‐diagnosed as benign will progress to invasive carcinoma over a 10‐15 year interval.4 In a study by Sanders et al., low‐grade DCIS progressed in 11 of 28 pa ents with most occurring within 10 years; 3 were diagnosed between 23 and 42 years a er the ini al biopsy; and 5 of 11 died of breast cancer.3

Autopsy studies suggest that a substan al number of DCIS cases may remain subclinical, although the interpreta on and significance of these findings is debated.12,13 Papers such as these underscore the concept that some DCIS is effec vely benign, but it remains evident that there is no way to prospec vely determine if and when DCIS will progress to invasive disease. Moreover, the available data are not representa ve of the full spectrum of DCIS and largely exclude high‐grade lesions. High‐grade DCIS is rarely misdiagnosed pathologically and is rou nely surgically excised, owing to the perceived malignant poten al. This has allowed for very limited long‐term observa ons.

In spite of the unknown, the overall prognosis for DCIS is excellent with appropriate surgical and oncologic management (approximately 98% long‐term survival).14 DCIS is typically treated with wide surgical resec on with or without radia on therapy; there is an evolving role for hormonal therapy.15,16 With a breast cancer specific mortality of less than 2%, it has proven difficult to demonstrate significant survival benefit with more advanced treatment op ons, such as radia on or hormonal therapy. This has led to considerable effort to stra fy pa ents with a diagnosis of DCIS, based on the risk of local recurrences, as invasive recurrence (either local or systemic) appears to be the primary source of breast cancer specific mortality in these pa ents. Approximately half of pa ents with recurrence a er breast conserva on

High‐Grade Ductal Carcinoma In Situ: An Overview for the Radiologist

Luke J. Ballard, M.D.,1 and Geneva R. Ballard M.D.2

1Division of Breast Imaging, Wilford Hall Ambulatory Surgical Center, San Antonio, TX 2Department of Radiology, San Antonio Military Medical Center, San Antonio, TX



surgery are diagnosed with invasive disease, and 12‐15% of these pa ents ul mately die of breast cancer.17,18 While the overall prognosis for conserva on therapy is good, the risk of recurrence or death is rela vely negligible when DCIS is treated with mastectomy.18,19

The pathologic evalua on of DCIS is one of the primary considera ons in stra fying pa ents and has shi ed from a purely architectural classifica on, which offered li le prognos c informa on, to a focus on the nuclear grade and degree of cellular necrosis. This is reflected in the Van Nuys system which simply divides DCIS lesions into high‐grade and non‐high‐grade; the la er group is further divided into those with or without necrosis.20 Moreover, the Consensus Conference on Classifica on of Ductal Carcinoma In Situ (1997) recommends stra fying DCIS first by nuclear grade (high, intermediate, and low) and then determining the presence or absence of necrosis due to the poten al treatment implica ons.16 The consensus reflects the current understanding of high‐

grade DCIS as an aggressive subtype of DCIS with an overall poorer prognosis than non‐high‐grade disease. Analysis of the data has shown that a high nuclear grade may increase the risk of local recurrence a er breast conserva on therapy, shorten the me to recurrence, increase the rate of distant metastases, increase the rate of recurrence with invasion, and increase mortality with recurrent invasion.17,19‐25 High‐grade DCIS at core needle biopsy also appears to be a significant risk factor for underes ma on of invasive breast cancer, a phenomena which occurs in approximately 25% of all DCIS diagnoses.26

High‐grade DCIS represents the majority of screening detected in situ lesions in mul ple series, further emphasizing the importance of this diagnosis.27‐29 Diagnosing high‐grade DCIS represents a rela vely frequent opportunity for radiologists to impact pa ent care. Thorough knowledge of the characteris c imaging features of high‐grade DCIS, as well as the limita ons of imaging, is impera ve.

Figure 1. Examples of linear and branching calcifica ons in

three cases of high‐grade ductal carcinoma in situ. (A)

shows classic cas ng type calcifica ons within a long ductal

segment that has one major branch. (B) reveals a cluster of

fine pleomorphic calcifica ons with several linear forms. (C)

demonstrates cas ng calcifica ons forming branching

shapes with addi onal adjacent pleomorphic calcifica ons.

A

C

B



Mammography of High‐Grade DCIS

Microcalcifica ons are found in an es mated 50‐75% of all DCIS diagnosed on mammography and in approximately 90% of clinically occult DCIS.30‐34 Radiologic‐pathologic correla on has shown that these calcifica ons develop as a consequence of calcified intraluminal cellular debris secondary to a high concentra on of calcium in adjacent necro c cells and from ductal secre ons, such as mucin or other calcific products.31,35

Many studies have demonstrated a correla on between the type of mammographic calcifica on and the pathologic diagnosis, sugges ng that certain calcifica on types are more likely to be associated with high‐grade lesions at histopathology. Specifically, linear branching calcifica ons are generally predic ve of high‐grade DCIS (Figure 1).21, 36‐38 These result from extensive intraluminal necrosis and calcifica ons which form “casts” of the ducts, yielding the characteris c linear branching pa ern. A variety of mammographic descriptors have been used that with nuanced differences appear to be synonymous to linear branching calcifica ons, including “fine linear branching,” “cas ng,” and “comedo” calcifica on. The range of non‐standardized microcalcifica on descriptors in the literature may indicate a measure of subjec vity in the analysis, although generally the differences can be reconciled.

While linear branching calcifica ons are characteris c of high‐grade DCIS, the significance of this finding as a histologic predictor of disease is debated. High‐grade DCIS appears to present with this finding in a majority of cases. In one study by Lee et al., 15 of 16 high‐grade DCIS lesions presented with linear calcifica ons and showed excellent correla on.36 In another study by Dinkel et al., 14 of 18 high‐grade DCIS lesions showed linear calcifica ons. This pa ern represented high‐grade DCIS 56% of the me. Though this is the majority, compared with intermediate and low‐grade DCIS, this was not a sta s cally significant result. The remaining 32% and 12% of linear calcifica ons represented intermediate and low‐grade DCIS, respec vely.39 First evaluated by Tabar et al., mul ple studies have provided evidence that cas ng calcifica ons import a poor prognosis when associated with small invasive cancers.38,40,41 Analysis shows that these cas ng calcifica ons consistently represent the presence of extensive high‐grade DCIS (Figure 2).

Unfortunately, as the Dinkel study illustrates, there remains considerable overlap in the imaging appearance of not only different grades of DCIS but also between DCIS and benign processes, as high‐grade DCIS is not confined to the linear branching pa ern of calcifica ons. While this morphology has shown good posi ve predic ve value for high‐grade DCIS, other calcifica on pa erns have not produced

Figure 2. Ectopic Cas ng type calcifica ons. (A) shows cas ng calcifica ons in a segmental distribu on, correspond to extensive high‐grade DCIS. (B) MRI reveals corresponding clumped segmental non‐mass‐like enhancement (white arrows) in the right breast in associa on with a circumscribed 2 cm invasive malignancy posteriorly (black arrowheads), which was mammographically occult. This pa ent presented with bloody nipple discharge, corresponding to the linear ductal fluid signal (white arrowhead). A benign fibroadenoma was visualized in the medial right breast (open black arrow).

A B



significant nega ve predic ve values or correla on with low‐grade disease that might be used to confidently reduce biopsy rates. Indeed, high‐grade DCIS is seen with varying degree in all of the ACR BI‐RADS suspicious calcifica on types, including amorphous or indis nct, coarse heterogeneous, and fine pleomorphic forms, though less frequently (Figure 3).30,36,37 The challenge for radiologists is most evident in early stages when high‐grade DCIS lesions are small and more confined; the appearance of associated calcifica ons is o en non‐specific. Appropriate biopsy technique and sampling provide an opportunity to limit under‐diagnosis in these situa ons .26

When not calcified, DCIS presents in numerous ways on mammograms, including masses, asymmetries, architectural distor on, and even as a nega ve exam.32 DCIS may present as a mass, either palpable or screen detected in up to 10% of cases of DCIS; this presenta on is seen more commonly in low‐grade lesions, rather than high‐grade DCIS.42,43 Presenta on

as a focal asymmetry may be especially challenging to radiologists when the finding is ques onable, not seen with ultrasound, or difficult to localize stereotac cally. Moreover, a nega ve mammogram may harbor DCIS, as demonstrated by occult cases iden fied only with the use of MRI. While such presenta ons are less common, it remains important to be aware that high‐grade DCIS may present as a non‐calcified mammographic abnormality.

Magne c Resonance Imaging of High‐Grade DCIS

The overall sensi vity of breast MRI for the detec on of all grades of DCIS was previously considered to be rela vely low with authors repor ng various sensi vity data for DCIS as low as 77%.44 However, with improved MRI techniques and high spa al resolu on, as many as 98% of DCIS cases are now detectable by MRI with an addi onal 6‐23% of mammographically occult DCIS lesions detectable only

Figure 3. Examples of high‐grade ductal carcinoma of varying

morphologies and distribu ons. (A) shows extensive

amorphous calcifica ons in a regional distribu on. (B)

reveals a rela vely innocuous looking cluster of pleomorphic

calcifica ons with some round and punctuate forms. (C)

demonstrates an example of fine pleomorphic and

amorphous calcifica ons without clear linear forms.

A

C B



by MRI.44,45 This is largely a ributed to the enhancement of non‐calcified DCIS which cannot be iden fied with a mammogram.45

The most common MR imaging finding in DCIS falls under the category of “nonmasslike enhancement” (NMLE) and is demonstrated in 60‐80% of cases.47,48 Though there is some variability in the literature regarding the exact descriptors, the NMLE seen with DCIS is typically in a segmental or linear distribu on. Morakkaba ‐Spitz et al. demonstrated a posi ve predic ve value of 34% and specificity of 96% for segmental and linear enhancement pa erns.49 The most commonly seen internal enhancement pa ern among NMLE lesions associated with DCIS is clumped or heterogeneous enhancement (Figure 4).48 Less commonly, purely DCIS lesions manifest as a mass (14‐34%) or focal enhancement (1‐12%).44

The kine c characteris cs of pure DCIS lesions are more heterogenous and less predic ve than those of invasive cancers, which are more likely to demonstrate early enhancement followed by rapid washout kine cs. The majority of pure DCIS lesions have rapid ini al phase of enhancement in up to 77% of cases.46,48,50 The type of delayed enhancement is variably reported, but most commonly described as plateau or washout. Less o en, DCIS lesions may demonstrate slow, progressive delayed enhancement (Figure 5). As with enhancing masses, a suspicious morphology, such as unilateral segmental or linear enhancement, will trump an associated benign appearing dynamic enhancement curve.

While one might expect that enhancement morphology and kine cs would reflect biologic behavior and by extension nuclear grade, there is no defini ve evidence to suggest that either can be used to predict the presence of high‐grade DCIS.46,48 When morphologic features of high‐grade versus non‐high‐grade DCIS are compared, there is simply no sta s cal difference that would separate these categories.51,52 However, some poten ally significant observa ons have been made regarding features of high‐grade DCIS on MRI. High‐grade DCIS appears to be more easily detected than low‐grade, sugges ng MRI may have a significant benefit in excluding high‐grade disease with a nega ve exam.49 Addi onally, high‐grade DCIS is significantly more likely to be detected with MRI than conven onal mammography, with as many as 48% of high‐grade cases detected with MRI alone.45

Figure 4. Clumped non‐mass‐like enhancement (NMLE) of high‐grade DCIS. (A) Sagi al MR post‐contrast subtrac on image shows clumped, segmentally distributed NMLE in the mid to lower breast. (B) Craniocaudal and (C) axial post‐contrast MIP images in a different pa ent with mammographically occult high‐grade DCIS reveal asymmetric, clumped segmental enhancement (white arrows) in the upper inner breast. The orienta on of the affected breast was posi onal, as it did not persist on the subsequent MRI guided biopsy.

A

C

B



Figure 5. Variable MRI enhancement kine cs of DCIS. (A) axial MIP and (B) sagi al subtrac on post‐contrast images reveal clumped, segmental non‐mass‐like enhancement (white arrows) in the right upper inner breast. (C) Sagi al CAD overlay demonstrates mixed plateau and persistent delayed enhancement curves represented by the green and blue color coding, respec vely.

Enhancement features of pure high‐grade DCIS, including a focal branching pa ern or irregular contour, may also be helpful in prospec vely differen a ng from pure invasive disease.52

Summary

Overall, pure DCIS has an excellent prognosis; however, high‐grade DCIS is an aggressive subtype with significantly greater morbidity and risk of mortality with recurrent invasive disease. Appropriate use of mammography and MRI affords radiologists an opportunity to iden fy this popula on and guide the most appropriate surgical and oncologic management based upon our current understanding of the disease. Research has extensively evaluated mammographic and MRI features of high‐grade DCIS, and its appearances are well documented. Unfortunately, imaging currently shows li le prospec ve value in cases of pure high‐grade DCIS beyond the ability to make the ini al diagnosis. Future research is necessary to determine the full impact of imaging pa ents with high‐grade disease and to further define the best clinical treatment strategies.

A

C

B

The views expressed in this material are those of the author, and do not reflect the official policy or posi on of the U.S. Government, the Department of Defense, or the Department of the Air Force.



References

1. LVirnig BA, Tu le TM, Shamliyan T, et al. Ductal Carcinoma In Situ of the Breast: A Systema c Review of Incidence, Treatment, and Outcomes. J Natl Cancer Inst 2010; 102: 170‐178.

2. Brinton LA, Sherman ME, Carreon JD, et al. Recent Trends in Breast Cancer Among Younger Women in the United States. J Natl Cancer Inst 2008; 100: 1643‐1648.

3. Sanders ME, Schuyler PA, Dupont WD, et al. The Natural History of Low‐Grade Ductal Carcinoma in Situ of the Breast in Women Treated by Biopsy Only Revealed Over 30 Years of Long‐Term Follow‐Up. Cancer 2005; 103: 2481‐4.

4. Erbas B, Provenzano E, Armes J, et al. The natural history of

ductal carcinoma in situ of the breast: a review. Breast Cancer Res Treat 2006; 97: 135‐144.

5. Espina V, Lio a LA. What is the malignant nature of human ductal carcinoma in situ? Nat Rev Cancer 2011; 11: 68‐75.

6. Cady B, Chung MA. Preven ng Invasive Breast Cancer. Cancer 2011 Jul 15; 117(14): 3064‐8.

7. Welch GH, Woloshin S, Schwartz LM. The sea of uncertainty surrounding ductal carcinoma in situ—the price of screening mammography. J Natl Cancer Inst2008; 100: 228‐9.

8. Tabár L, Vitak B, Chen TH, Yen AM, et al. Swedish two‐county trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology. 2011 Sep; 260(3):658‐63. Epub 2011 Jun 28.

9. Hellquist BN, Duffy SW, Abdsaleh S, et al. Effec veness of popula on‐based service screening with mammography for women ages 40 to 49 years: evalua on of the Swedish Mammography Screening in Young Women (SCRY) cohort. Cancer. 2011 Feb 15; 117(4): 714‐22. Epub 2010 Sep 29.

10. Kopans DB, Smith RA, Duffy SW. Mammographic Screening and “Overdiagnosis”. Radiology 2011; 260: 616‐620.

11. Jørgensen KJ, Keen JD, Gøtzsche PC. Is Mammographic Screening Jus fiable Considering Its Substan al Overdiagnosis and Minor Effect on Mortality? Radiology 2011; 260: 621‐627.

12. Welch HG, Black WC. Using Autopsy Series To Es mate the Disease “Reservoir” for Ductal Carcinoma in Situ of the Breast: How Much More Breast Cancer Can We Find? Ann Intern Med 1997; 127: 1023‐1028.

13. Kopans DB, Rafferty E, Georgian‐Smith D, et al. A Simple Model of Breast Carcinoma Growth May Provide Explana ons for Observa ons of Apparently Complex Phenomena. Cancer 2003; 97: 2951‐2959.

14. Ernster VL, Barclay J, Kerlikowske K, et al. Mortality Among Women With Ductal Carcinoma In Situ of the Breast in the Popula on‐Based Surveillance, Epidemiology andEnd Results Program. Arch Intern Med 2000; 160: 953‐958.

15. Zujewski JA, Harlan LC, Morrell DM, et al. Ductal carcinoma in situ: trends in treatment over me in the US. Breast Cancer Res Treat 2011; 127:251‐257.

16. Schwartz GF, Solin LJ, Olivo o IA, et al. Consensus Conference of the Treatment of In Situ Ductal Carcinoma of the Breast, April 22‐25, 1999. Cancer 2000; 88: 946‐954.

17. Lee LA, Silverstein MJ, Chung CT, et al. Breast cancer‐specific mortality a er invasive local recurrence in pa ents with ductal carcinoma‐in‐situ of the breast. Am J Surg 2006; 192: 416‐419.

18. Romero L, Klein L, Ye W, et al. Outcome a er invasive recurrence in pa ents with ductal carcinoma in situ of the breast. Am J Surg 2004; 188: 371‐376.

19. Silverstein MJ, Barth A, Poller DN, et al. Prognos c classifica on of breast DCIS; Ten‐year results comparing mastectomy to excision and radia on therapy for ductal carcinoma in situ of the breast. European Journal of Cancer 1995; 31:1425‐7.

20. Silverstein MJ, Poller DN, Waisman JR, et al. Prognos c classifica on of breast ductal carcinoma‐in‐situ. Lancet 1995; 345:1154‐57.

21. Lagios MD, Margolin FR, Westdahl PR, et al. Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognos c effect of nuclear grade on local recurrence. Cancer 1989; 63: 619–24.

22. Bijker N, Meijnen P, Peterse JL, et al. Breast‐conserving treatment with or without radiotherapy in ductal carcinoma‐in‐situ: ten‐year results of European Organisa on for Research and Treatment of Cancer randomized phase III trial 10853‐‐a study by the EORTC Breast Cancer Coopera ve Group and EORTC Radiotherapy Group. J Clin Oncol 2006; 24:3381‐7.

23. Hetelekidis S, Collins L, Silver B, et al. Predictors of local recurrence following excision alone for ductal carcinoma in situ. Cancer 1999; 85(2):427‐31.

24. Holmes P, Lloyd J, ChervonevaI, et al. Prognos c markers and long‐term outcomes in ductal carcinoma in situ of the breast treated with excision alone. Cancer 2011; 117: 3650‐7.

25. Schni SJ. Local outcomes in ductal carcinoma in situ based on pa ent and tumor characteris cs. J Natl Cancer Inst Monogr 2010; 2010: 158‐61.

26. Brennan ME, Turner RM, Cia o S, et al. Ductal carcinoma in situ at core‐needle biopsy: meta‐analysis of underes ma on and predictors of invasive breast cancer. Radiology 2011; 260:119‐28.

27. Evans AJ, Pinder SE, Ellis IO, et al. Screen detected ductal carcinoma in situ (DCIS): overdiagnosis or an obligate precursor of invasive disease? J Med Screen 2001; 8: 149‐51.

28. Kessar P, Perry N, Vinnicombe SJ, et al. How significant is detec on of ductal carcinoma in situ in a breast screening programme? Clin Radiol 2002; 57: 807‐14.

29. Kricker A, Goumas C, Armstrong B. Ductal carcinoma in situ of the breast, a popula on‐based study of epidemiology and pathology. Br J Cancer 2004; 90:1382‐5.

30. Barreau B, de Mascarel I, Feuga C, et al. Mammography of ductal carcinoma in situ of the breast: review of 909 cases with radiographic‐pathologic correla ons. Eur J Radiol 2005; 54: 55‐61.

31. Stomper PC, Connolly JL, Meyer JE, et al. Clinically occult ductal carcinoma in situ detected with mammography: analysis of 100 cases with radiologic‐pathologic correla on. Radiology 1989; 172: 235‐41.

32. Ikeda DM, Anderson I. Ductal Carcinoma in Situ: Atypical Mammographic Appearances. Radiology 1989; 172: 661‐666.

33. Cia o S, Catalio L, Distante V. Nonpalpable lesions detected with mammography: review of 512 consecu ve cases. Radiology 1987; 165: 99‐102.



34. Hall FM, Storella JM, Silverstone DZ, at al. Nonpalpable breast lesions: recommenda ons for biopsy based on suspicion of carcinoma at mammography. Radiology 1988; 167: 353‐8.

35. Egan RL, McSweeney MB, Sewell CW. Intramammary calcifica ons without an associated mass in benign and malignant diseases. Radiology 1980; 137: 1‐7.

36. Lee KS, Han BH, Chun YK, at al. Correla on between mammographic manifesta ons and averaged histopathologic nuclear grade using prognosis‐predict scoring system for the prognosis of ductal carcinoma in situ. Clin Imaging 1999; 23: 339‐46.

37. Holland R, Hendriks JH. Microcalcifica ons associated with ductal carcinoma in situ: mammographic‐pathologic correla on. Semin Diagn Pathol 1994; 11: 181–192.

38. Tabar L, Tony Chen HH, Amy Yen MF, et al. Mammographic tumor features can predict long‐term outcomes reliably in women with 1‐14‐mm invasive breast carcinoma. Cancer 2004; 101: 1745‐59.

39. Dinkel HP, Gassel AM, Tschammler A. Is the appearance of microcalcifica ons on mammography useful in predic ng histological grade of malignancy in ductal cancer in situ? Br J Radiol 2000; 73: 938‐44.

40. Zunzunegui RG, Chung MA, Oruwari J, et al. Cas ng‐type calcifica ons with invasion and high‐grade ductal carcinoma in situ: a more aggressive disease? Arch Surg 2003; 138: 537‐40.

41. Pálka I, Ormándi K, Gaál S, et al. Cas ng‐type calcifica ons on the mammogram suggest a higher probability of early relapse and death among high‐risk breast cancer pa ents. Acta Oncol 2007; 46: 1178‐83.

42. Evans A, Pinder S, Wilson R, et al. Ductal carcinoma in situ of the breast: correla on between mammographic and pathologic findings. Am J Roentgenol 1994; 162: 1307‐11.

43. Yang WT, Tse GM. Sonographic, mammographic, and histopathologic correla on of symptoma c ductal carcinoma in situ. Am J Roentgenol 2004; 182: 101‐10.

44. Yamada T, Mori N, Watanabe M, et al. Radiologic‐pathologic correla on of ductal carcinoma in situ. Radiographics 2010; 30: 1183‐98.

45. Kuhl CK, Schrading S, Bieling HB, et al. MRI for diagnosis of pure ductal carcinoma in situ: a prospec ve observa onal study. Lancet 2007; 370: 485‐92.

46. Kim JA, Son EJ, Youk JH, et al. MRI findings of pure ductal carcinoma in situ: kine c characteris cs compared according to lesion type and histopathologic factors. Am J Roentgenol 2011; 196: 1450‐6.

47. Rosen EL, Smith‐Foley SA, DeMar ni WB, et al.. BI‐RADS MRI en‐hancement characteris cs of ductal carcinoma in situ. Breast J 2007; 13: 545–550.

48. Jansen SA, Newstead GM, Abe H, Shimauchi et al. Pure ductal carcinoma in situ: kine c and morphologic MR characteris cs compared with mammographic appearance and nuclear grade. Radiology 2007; 245: 684‐91.

49. Morakkaba ‐Spitz N, Leutner C, Schild H, et al. Diagnos c usefulness of segmental and linear enhancement in dynamic breast MRI. Eur Radiol 2005; 15: 2010‐7.

50. Neubauer H, Li M, Kuehne‐Heid R, et al. High grade and non‐high grade ductal carcinoma in situ on dynamic MR mammography: characteris c findings for signal increase and morphological pa ern of enhancement. Br J Radiol 2003; 76: 3‐12.

51. Viehweg P, Lampe D, Buchmann J, et al. In situ and minimally invasive breast cancer: morphologic and kine c features on contrast‐enhanced MR imaging. MAGMA 2000; 11: 129‐37.

52. Groves AM, Warren RM, Godward S, et al. Characteriza on of pure high‐grade DCIS on magne c resonance imaging using the evolving breast MR lexicon terminology: can it be differen ated from pure invasive disease? Magn Reson Imaging. 2005 Jul; 23(6): 733‐8.


Case Report, Kreuer et al.

Peripherally Enhancing Breast Lesion With Central Fat

Sharon Kreuer, D.O., and Rocky C. Saenz, D.O.

Department of Diagnos c Radiology, Botsford Hospital, Farmington Hills, MI

Figure. Axial T1 image (A) demonstrates a triangular shaped lesion within the upper breast posterior depth with central high T1 signal.

Sagi al dynamic post‐gadolinium T1 subtrac on image with fat satura on from the sub‐peak phase (B) shows peripheral enhancement

with central hypointense signal. Sagi al dynamic post‐gadolinium T1 subtrac on image with fat satura on with color overlay (C)

demonstrates the lesion to have mixed kine cs, including type III washout.

Case Presenta on

67‐year‐old female presents with a palpable mass within her right breast. Review of systems revealed a breast procedure approximately 2 years prior. Physical exam demonstrated nipple inversion with confirma on of a deep palpable mass in the upper breast. Pa ent then underwent breast MRI imaging (Figures A ‐C).

A

B C



Key clinical finding

Palpable mass with history of prior surgical procedure or trauma.

Key imaging finding

Peripherally enhancing breast lesion with central fat signal on T1.

Differen al diagnoses

Fat Necrosis

Infiltra ng Ductal (IDC) Carcinoma

Radial Sclerosing Lesion (RSL)

Discussion

A key component in the evalua on of a breast lesion seen on mammography or ultrasound is obtaining a thorough pa ent history. Answers regarding personal and familial cancer history, as well as prior surgeries and trauma, should be elicited and may guide differen al considera ons. In indeterminate cases when the discrimina on between benign and malignant processes cannot be made, MRI may be an invaluable diagnos c tool, even though there is overlap in the MR appearance of many benign and malignant breast lesions.

Fat necrosis.

Fat necrosis most commonly is a consequence of surgery or accidental trauma but may also result from prior radia on therapy to the breast.1,2 Pa ents may or may not have grossly visible or palpable evidence of fat necrosis depending on the depth and size of the lesion.

On imaging, the varied appearances of fat necrosis is ascribed to various amounts of his ocy c infiltra on, hemorrhage, fibrosis, and calcifica on present a er breast insult and is dependent on the stage of evolu on.1 Lesion morphology can range from a well‐marginated appearance of an oil cyst to a spiculated appearance of robust fibrosis. This wide gamut of ssue changes produces a constella on of MRI signal abnormali es and enhancement pa erns.

T1 sequences are the most useful in evalua ng suspected fat necrosis, which typically has signal characteris cs consistent with fat elsewhere in the breast.2 Occasionally, necro c fat may demonstrate low TI signal secondary to the presence of hemorrhage and inflammatory content.1 Post‐contrast images show variable amounts of enhancement depending on the amount of inflamma on present, although a thin rim of enhancement is common.2

When increasing amounts of inflamma on and fibrosis are present, imaging findings can be easily confused with malignancy. Fibrosis may have hyperintense, intermediate, or hypointense signal on T1, and areas of thick nodular enhancement may persist for several years a er the ini al insult.2 Washout kine cs are as variable as the morphology and signal characteris cs; therefore, they are typically not very helpful.2

Infiltra ng ductal carcinoma (IDC).

IDC is the most common histologic variant of breast cancer and o en progresses from ductal carcinoma in situ. Pa ents presen ng with IDC may be asymptoma c, or may have a palpable mass, nipple discharge/ inversion, or overlying skin findings.

MRI is a valuable tool in diagnosing IDC with a sensi vity of 90‐100%.3 Its main uses in the se ng of IDC include evalua ng tumor extent and assessing for mul centric involvement and contralateral disease in pa ents with biopsy proven carcinoma.

The classic pre‐contrast T1 and T2 MRI appearance of IDC is signal intensity equal to or lower than that of fibroglandular ssue.4 Post‐contrast images typically reveal an irregular, spiculated, enhancing mass with early enhancement with delayed washout kine cs.5 Less common enhancement pa erns include heterogeneous mass‐like or rim enhancement; rim‐enhancement is highly sugges ve of malignancy when not otherwise consistent with fat necrosis.4

Radial sclerosing lesion (RSL):

RSLs, otherwise known as radial scars, are not truly scars and are not associated with prior surgery or trauma. They are typically asymptoma c and found incidentally. There is a known increased incidence of breast cancer when a radial scar is present; atypical



ductal hyperplasia and carcinoma are found in up to 50% of cases.6

In many cases it may be difficult or impossible to dis nguish sclerosing lesions of the breast from ductal carcinoma, even with MRI. Morphologically, these lesions have spiculated margins and secondary architectural distor on; post‐contrast enhancement pa erns are similar compared to IDC.

Percutaneous biopsy of these lesions remains controversial. One study suggests that core needle biopsy alone is sufficient if at least 12 ssue samples are obtained and there is no histologic evidence of atypical hyperplasia. 7 Otherwise, excisional biopsy is recommended due to the lesion’s high associa on with carcinoma and heterogenous histology.

Diagnosis

Fat Necrosis

Summary

Imaging findings of fat necrosis of the breast are varied and have several overlapping imaging characteris cs with other benign and malignant breast lesions, making it a par cularly challenging diagnosis. However, when characteris c features are present, such as fat signal intensity, thin peripheral enhancement, superficial loca on, history of trauma or surgery, oil cysts, or benign calcifica ons, short‐term follow‐up may be preferred to biopsy.2 In the absence of these classic findings, however, ssue sampling should be a considera on.

References

1. Taboada JL, Stephens TW, Krishnamurthy S, et al. The Many Faces of Fat Necrosis in the Breast. AJR 2009; 192:815–825.

2. Daly CP, Jaeger B, Sill DS. Variable Appearances of Fat Necrosis on Breast MRI. AJR 2008; 191:1374–1380.

3. Raza S, Vallejo M, Chikarmane SA, et al. Pure Ductal Carcinoma in Situ: A Range of MRI Features. AJR 2008; 191:689–699.

4. Kuhl CK. Concepts for Differen al Diagnosis in Breast MR Imaging. Clin N Am 2006; 14: 305–328.

5. Drukteinis JS, Gombos EC, Raza S, et al. MR Imaging Assessment of the Breast a er Breast Conserva on Therapy: Dis nguishing Benign from Malignant Lesions. RadioGraphics 2012; 32:219–234.

6. Alleva DQ, Smetherman DH, Farr GH et al. Radial Scar of the breast: Radiologic pathologic correla on in 22 cases. Radiographics 1999; 19: S27‐S35.

7. Brenner RJ, Jackman RJ, Parker SH, et al. Percutaneous Core Needle Biopsy of Radial Scars of the Breast: When Is Excision Necessary? AJR 2002;179(5):1179‐84.


Case Report, Gaffney

Unilateral Axillary Lymphadenopathy

Shannon Gaffney, D.O.

Department of Diagnos c Imaging, Wilford Hall Ambulatory Surgical Center, San Antonio, TX

Figure. Bilateral MLO (A) and magnified ML view of the le breast (B), demonstrate asymmetric le axillary adenopathy. Targeted

ultrasound of the le axilla (C) confirms enlarged axillary lymph nodes with irregular, thickened cortex and loss of the fa y hilum. Sagi al

T1 post‐contrast fat suppressed MR image (D) reveals an enhancing mass in the middle depth le breast that is mammographically occult.

Le axillary adenopathy is again demonstrated.

Case Presenta on

A 37‐year‐old woman presented with pain and ngling underneath and behind her le breast for the past two weeks intermi ently. She denied trauma or any inci ng event. Past medical history and review of systems were noncontributory. Physical exam of the breasts and le chest wall is nega ve. The pa ent was subsequently referred for diagnos c mammogram, ultrasound, and MRI breast (Figs A‐D).



Key imaging finding

Unilateral axillary lymphadenopathy

Differen al diagnoses

Breast carcinoma with axillary spread

Reac ve lymphadenopathy

Metastases/Lymphoma

Systemic disease

Granulomatous disease

Discussion

Unilateral axillary adenopathy can present a diagnos c and therapeu c dilemma. Differen a ng benign versus malignant causes can be a challenge. Features of axillary lymph nodes that may be considered abnormal include increased size (greater than 2 cm), homogeneously increased density, loss of normal architecture, and occasionally internal calcifica ons¹. When detected, a thorough history and physical exam may aid in excluding benign causes, such as reac ve adenopathy or granulomatous disease. In most cases, further imaging and o en biopsy are performed to determine the e ology. A typical workup for unilateral axillary adenopathy detected on mammogram includes bilateral axillary ultrasound and ssue sampling. Addi onally, MRI and nuclear medicine imaging may be contributory in the diagnos c and therapeu c approach.

Breast carcinoma with axillary spread.

Although primary breast carcinoma presen ng as axillary adenopathy is rela vely uncommon (some authors sugges ng ranges of 4‐12%²), it must considered in the differen al diagnosis of unilateral axillary adenopathy. Most women with axillary adenopathy due to metasta c disease have an obvious primary tumor. In fact, unilateral axillary adenopathy with an otherwise normal mammogram is a rare presenta on of breast cancer, occurring in less than 1% of cases.³ Axillary nodes in the se ng of metasta c breast cancer can appear dysmorphic with increased size and density and rarely have internal pleomorphic microcalcifica ons. If a mass is not seen

on mammogram, an ultrasound can be performed but is o en low yield without a suspicious mammographic finding. In such cases, lymph node biopsy is typically performed. Imaging with MRI is a another alterna ve to further evaluate for a mammographically occult mass.⁴

Reac ve Adenopathy.

Radiographic appearance of reac ve adenopathy is nonspecific but typically consists of enlarged lymph nodes that maintain normal architecture (i.e. reniform shape and preserved fa y hilum). Clinical evalua on for infec on or inflamma on in the ipsilateral breast, axilla, arm, and hand is recommended. Common causes of unilateral reac ve adenopathy include mas s, breast abscess, an infected skin lesion, and cat scratch disease.⁵

Metastases/Lymphoma.

Metastases and lymphoma may present with axillary adenopathy, which is more o en bilateral but may be unilateral as well. Some of the more common extramammary malignancies that may present with axillary adenopathy include thyroid, lung, gastrointes nal, and pancrea c cancers.³ Ovarian metastases can also present with unilateral axillary adenopathy, but this is quite rare.⁶ Past medical history and prior imaging may be beneficial in these cases.

Granulomatous disease.

Axillary adenopathy can be seen in pa ents with granulomatous diseases, such as tuberculosis or sarcoidosis. Imaging features include enlarged axillary lymph nodes with coarse internal calcifica ons.⁶ If granulomatous disease is suspected, prior chest radiographs or chest CTs can confirm pulmonary granulomas and/or calcified medias nal/hilar lymph nodes.



Collagen vascular disease.

Systemic diseases, such as systemic lupus erythematosus, rheumatoid arthri s (RA), and scleroderma can present with unilateral axillary adenopathy. The imaging characteris cs of axillary nodes in systema c diseases are o en nonspecific. One rare but unique imaging feature is gold deposits within the lymph nodes, which mimic internal calcifica ons; this feature is seen in RA pa ents treated with gold therapy.⁶

Diagnosis

Invasive ductal carcinoma with axillary spread.

Summary

Unilateral axillary adenopathy detected on imaging should be regarded as suspicious and warrants further inves ga on. Workup should include, at a minimum, diagnos c mammogram and axillary ultrasound (to confirm unilateral adenopathy); biopsy is o en necessary. MRI may be contributory to detect mammographically occult breast masses, as in the case presented here, and is widely being used in the diagnos c approach for malignant axillary adenopathy in the absence of a mammographic abnormality. Nuclear medicine studies (such as PET and BSGI) may also have some benefit in evalua ng for underlying breast malignancies.⁷ Although the diagnos c workup of unilateral axillary adenopathy remains variable, a prudent approach should make every effort to exclude a primary breast malignancy as the cause.

The views expressed in this material are those of the author, and do not reflect the official policy or posi on of the U.S. Government, the Department of Defense, or the Department of the Air Force.

References

1. Brant W, Helms C. Fundamentals of Diagnos c Radiology, Philadelphia: Lippinco Williams & Wilkins; 2007: pgs.

2. Leibman J, Kossoff M. Mammography in women with axillary adenopathy and normal breasts on physical examina on: value in detec ng occult breast carcinoma. AJR 1992 Sep; 159: 493‐495

3. Abe H, Naiton H, Umeda T, Shiomi H, Tani T, Kodama M, Okabe H. Occult breast cancer presen ng axillary nodal metastasis: a case report. Jpn J Clin Oncol 2000; 30(4): 185‐187.

4. Schelfout K, Kersschot E, Van Goethem M, Thienpont L, Van de Haute J, Roelstraete A, DeSchepper A. Breast MRI in a pa ent with unilateral axillary adenopathy and unknown primary malignancy. Eur Radiol 2003; 13: 2128‐2132.

5. D'Orsi CJ, Mendelson EB, Ikeda DM, et al: Breast Imaging Repor ng and Data System: ACR BI‐RADS – Breast Imaging Atlas, Reston, VA, American College of Radiology, 2003.

6. Singer C, Blankstein E, Koenigsberg T, Mercado C, Pile‐Spellman E, Smith, S. Mammographic appearance of axillary lymph node calcifica on in pa ents with metasta c ovarian carcinoma. AJR 2001 Jun; 176: 1437‐1440.

7. Cyrlak D, Carpenter P. Breast imaging case of the day. Radiographics 1999; 19: S73‐79.


JAOCR At the Viewbox


Amy Argus, M.D., and Arthur Ballard, M.D.

Breast Imaging Department, University of Cincinna Health/University Hospital, Cincinna , OH

Mondor’s Disease.

Can you tell why this pa ent presented?

The arrow on the mammogram points to an acutely painful, palpable, superficial tubular mass coursing toward the nipple. The ultrasound image demonstrates a superficial, anechoic, tubular structure with mul ple areas of narrowing and intraluminal echogenicity (arrowhead). Color Doppler analysis shows absence of flow within the tubular structure. These findings are consistent with superficial thrombophlebi s, also known as Mondor’s disease.

Mondor’s disease is a rare, self‐limi ng, generally benign condi on of thrombophlebi s of the superficial veins of the breast and anterior chest wall. This en ty is o en idiopathic; however, known causes include trauma, breast augmenta on, breast biopsy, breast cancer, inflamma on, and infec on. The classic presenta on of a painful, palpable, cord‐like structure o en aids in avoiding misdiagnosis of the enlarged vein as a dilated duct. Also, thrombosed veins are longer, have a beaded appearance, and do not terminate at the areola. Since there have been occasional cases of associated breast cancer, imaging is warranted to exclude underlying malignancy. Management includes warm compresses and pain relievers (NSAIDS) with a 6‐month follow‐up examina on. If findings are unresolved on follow‐up, surgical excision may be considered.

Right Breast Ultrasound With Color

Right MLO


JAOCR At the Viewbox


Mary C. Mahoney, M.D., and Arthur Ballard, M.D.

Breast Imaging Department, University of Cincinna Health/University Hospital, Cincinna , OH

Ductal Carcinoma in situ (DCIS).

Can you name the disease associated with this classic distribu on of enhancement on the sagi al breast MRI?

The arrows on the breast MR subtrac on image point to clumped, non‐masslike enhancement in a ductal distribu on, directed toward the nipple. These findings are most compa ble and concerning for ductal carcinoma in situ (DCIS).

DCIS is malignancy confined to the ducts of the breast. It is considered to be a preinvasive form of cancer. Mammographic screening has led to an increased frequency in the detec on of DCIS, which now accounts for approximately 20% of all detected breast cancers. Early detec on of this preinvasive form of breast cancer is one of the factors contribu ng to the decrease in breast cancer mortality. Most DCIS is detected mammographically in the form of pleomorphic microcalcifica ons. However, recent studies have shown that MRI is capable of detec ng not only calcified DCIS, but uncalcified DCIS as well. In fact, the sensi vity of MRI for DCIS is higher than that of mammography, especially for high grade lesions which are thought to be more prone to progress to invasive carcinomas.

MRI Breast, Sagi al, Subtrac on Image

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