Educational Programs: Current
Topics in Oncology
Dr. Wei Yang
Session 3: Breast Imaging
Date: September 8, 2009
Time: 33:13
Wei Yang, M.D.
Associate Professor, Diagnostic Radiology
The University of
Return to Current Topics in Oncology
Dr. Wei Yang: Welcome to the breast imaging section in the global academic program that revolves around current topics in breast oncology 2009.
I've structured the following presentation in this format: we will be describing the role of diagnostic workup in asymptomatic women as well as symptomatic women. For the asymptomatic population, we will be talking about the abnormal screening mammogram, and for the symptomatic group we will be focusing on women who present with a palpable mass, the role of imaging in cancer workup, patients who present with skin thickening or skin erythema, patients who present with lymph node abnormalities and nipple discharge.
The pertinent findings in an abnormal screening mammogram include a mass, an area of architectural distortion or calcifications. Here is an example of a tiny sub-centimeter mass annotated by the arrows that are situated deep in the outer aspect of the breast of a young, 36-year-old female. The corresponding ultrasound shows a small irregular solid hypoechoic mass that measures 0.4 centimeters and demonstrates suspicious features by sonography. The distance measured from the nipple to the mass confirms mammographic, sonographic correlation and the patient underwent a biopsy that showed a small invasive ductal cancer that was picked up on screening mammography with ultrasound workup.
Next, an area of architectural distortion is seen in the outer aspect of the breast of this lady. The corresponding ultrasound shows an indeterminate mixed heterogeneous hyper-and hypoechoic mass with internal hypervascularity. An ultrasound-guided core needle biopsy, as shown on this slide with the needles traversing the mass, was necessary to obtain the final diagnosis, which in this case was a benign lesion and showed stromal fibrosis. The onus is on the radiologist to determine if there is radiologic, pathologic concordance, and in this case it was felt that the histologic diagnosis was appropriate and the patient went back to annual mammography.
The third example is of calcifications that can occasionally be seen on an abnormal screening mammogram. Here we see tiny amorphous calcifications in a segmental distribution. The BI-RADS category for this patient is a BI-RADS 4. The patient was set up for a stereotactic biopsy, which you see on the next slide.
Here we have the paired views prior to obtaining the tissue samples from the breast. And the third image shows a post-biopsy film that was captured after the clip marker was placed at the biopsy site. And we see that the calcifications that were present on the pre-biopsy slides have largely been removed. Digital radiographs or computer radiographs of the core specimens demonstrate the calcifications that were removed. And in this case, histology showed ductal carcinoma in situ.
The same patient went on to mammographic-guided needle localization using two guide wires shown on this film. And at surgery in M. D. Anderson, the en-bloc surgical specimen is imaged with digital technique. The sliced specimens are imaged with digital technique, and teleradiology allows the radiologists to do immediate reading and assessment of the sliced specimens to aid pathologists and surgeons in obtaining an accurate and clear surgical margin. As you see the circles and the arrows annotate the areas of interest representing cancer, and the margins are widely free of disease.
Moving on to the patient who presents with a palpable mass, the following considerations are common features that occur with this symptom. These include a cyst, fibro adenoma, occasionally normal breast tissue and cancer. This shows an example of a classic or typical cyst where we see a circumscribed mass that is largely anechoic or completely dark on sonography or ultrasound. We have sharp anterior and posterior walls. We have beautiful edge shadows and posterior acoustic enhancement all characteristic for a cyst, which requires no further intervention or follow up.
The second example is of a 45-year-old woman who presents for screening. The pertinent findings on imaging are multiple masses. These are usually benign, a Bi-RADS 3 category and frequently represents cysts or fibroadenomas. At baseline or first time point in imaging an ultrasound is reasonable to confirm benignity and in this patient demonstrated multiple solid circumscribed masses most consistent with fibroadenomata.
In the patient who presents for cancer workup, there are three main roles for the breast imager. The first is to interrogate or investigate the primary breast mass for staging and to look for additional satellite lesions. The second that we perform at M. D. Anderson is to evaluate the regional lymph nodes to contribute to nodal staging. This has practical implications for radiation therapy planning. And the third is to confirm the histologic diagnosis with biopsies and clip marker placements to facilitate subsequent medical or new adjuvant chemotherapy.
Here is an example of a lady who comes for ultrasound and this particular oblique image shows two abnormal foci within the breast consistent with multi-focal disease. Both lesions were biopsied and clip markers were placed. This will be the background mapping that will help the surgeon in the event that the patient elects for breast conservation surgery.
Moving on to nodal staging, this schematic shows the four main nodal chains that are routinely assessed by breast imaging radiologists at M. D. Anderson. These include the axillary nodal chain, the infraclavicular nodal chain, the internal mammary nodal chain and the supraclavicular nodal chains. These three nodal regions are not addressed by surgeons on a routine basis, but are important landmarks for radiation therapists to plan their radiation field after surgery.
Here is an example of an abnormal axillary lymph node that is round and hypoechoic.
This slide shows multiple abnormal infraclavicular lymph nodes that are abnormal and represent a metastasis.
The third patient shows abnormal supraclavicular lymph nodes that are sub-centimeter in size. This is a 5 millimeter mark.
And the fourth slide shows an abnormal lymph node in the first space of the internal mammary nodal basin. At the time of imaging, this less than 1 centimeter axillary lymph node that was captured at imaging was subjected to fine needle aspiration biopsy. Here we see the needle traversing the cortex of the lymph node. And an immediate diagnosis of metastasis was obtained and relayed to the patient at the time of imaging.
Moving on to patients who present with skin changes. The two main considerations in differential diagnosis include infection or mastitis and neoplastic causes such as inflammatory breast cancer. Post therapy change is common after patients have undergone surgery or radiation therapy. This first image shows a patient who presents with an angry, red breast with marked overlying skin thickening that is warm. Mammography shows global skin and trabecular distortion and no further information is obtained from this image. We do not see a discrete mass. We do not see abnormal calcifications.
The patient moves on to ultrasound, which shows an abnormal area that is extending right to the retroareolar position. A biopsy is necessary in these instances to differentiate an infection from cancer. In this case, three biopsies performed at different intervals showed granulomatous mastitis. The patient was treated conservatively and is currently well at eight months of follow up.
The differential diagnosis is a much-feared, highly lethal and aggressive
disease known as inflammatory breast cancer, as we discussed. This condition
presents clinically with diffuse erythema and edema
over a short time period of three months and obtaining histological diagnosis
for marker evaluation is frequently difficult due to the woody and indurated presentation of the breast. Imaging has
controversial roles and historically, the primary cancer has not been
detectable by mammography or ultrasound. In a recent publication by the group
at M. D. Anderson, the preliminary data from a retrospective review suggests
that magnetic resonance imaging and PET or
Here is an example of a 45-year-old female who presents with redness and swelling of the left breast for three weeks. We see gross asymmetry in the left breast when compared with the right. There is global skin thickening and trabecular distortion with marked increased density of the breast without a discrete mass. Note the contralateral abnormal axillary lymph nodes.
Ultrasound is more helpful in obtaining tissue diagnosis from a primary parenchymal abnormality. We see annotated bi-calipers, here a more than 10 centimeter mass. These are 5 centimeter skin marks. We see marked skin and subcutaneous edema and we see a markedly abnormal enlarged axillary lymph node on the same breast. This lesion was subjected to core needle biopsy for histological evaluation and biomarkers, which was critical in the clinician's and physician's planning for new adjuvant chemotherapy.
In essence, to summarize, it is often difficult clinically to differentiate the axis from the inflammatory breast cancer. Imaging has an emerging and evolving role. Sonography is useful and critical in finding and delineating a focal parenchymal abnormality to facilitate biopsy. It also has a role in regional nodal staging. And when in doubt, biopsy is necessary to differentiate a benign axis from a malignant cancer.
The third clinical condition that a woman may present with is nipple discharge. Clinical correlation is key. Imaging is only performed if the nipple discharge is spontaneous, uniorificial and bloody in nature. The most common cause for nipple discharge would be a clinical or hormonal imbalance. The purpose of imaging is to detect and delineate a papillary lesion. Nine out of ten women who present with spontaneous uniorificial bloody nipple discharge have benign findings.
The potential findings on imaging for a papilloma on mammogram include a solitary mass or clustered calcifications. On ultrasound, we can expect to see an intraductal mass which is usually hypoechoic but can be complex. Power Doppler or any form of Doppler imaging is useful in these situations to differentiate benign debris or fibrocystic change from a viable neoplasm which generally tends to be hypervascular.
The following are examples of intraductal lesions. This is the nipple on transverse view on grayscale color Doppler and Power-Doppler. There is very clearly an intraductal solid mass that is hypervascular in this patient. A second patient shows a solid hypoechoic mass that is 1 centimeter from the nipple that is extremely hypervascular and also represented a papilloma. The third example is of a complex mixed cystic, black as we saw earlier, and solid mass. Here we have an intramural component that is hypervascular. And all three patients showed a benign papilloma at biopsy.
Controversy persists on the management of papillary lesions. It should be emphasized that imaging is unable to differentiate a benign from a borderline from a malignant papillary lesion. Essentially all lesions that are seen within ducts require a biopsy which could be in the form of a fine needle aspiration biopsy, core needle biopsy or excisional biopsy to differentiate a benign from malignant cause. This is very much guided by institutional practice where pathologists and surgeons have their preferences. There are institutions which abhor any form of preoperative guided-needle biopsies and require such lesions to go directly to excision. At M. D. Anderson, our pathologists and surgeons prefer a pre-surgical biopsy to confirm benignity or malignancy.
To review, our current findings in terms of symptomatic patients, there are patients who present challenges for the imagist and where we fall short of perfection and are unable to do the best diagnosis for the patient. The following is a 32-year-old woman who has a strong family history of breast cancer and two images obtained approximately 18 months apart show that there is an intervening development of a large, circumscribed high-density mass in the left breast that was totally not present exactly 20 months prior to the 1997 mammogram. The following ultrasound showed suspicious features for malignancy. We see a solid hypoechoic mass with indistinct margins. The final histology was medullary cancer. This form of carcinoma occurs most frequently in BRCA mutation carriers and are generally circumscribed and of better prognosis than common garden invasive ductal cancers.
To summarize, mammographic sonographic correlation is always necessary and critical to determine if biopsy is necessary and if biopsy is concordant. This will guide the radiologists in giving final recommendations as to whether patient is okay to return to annual imaging or if excisional biopsy is the next recommended step of management.
Here is an example of a patient who presents with a palpable finding in the right breast. Mammography findings show highly suspicious findings of grouped, clustered, fine linear branching calcifications. Ultrasound shows a fairly oval mass with microlobulated margins that is rated as BI-RADS 4-B. Combining mammographic sonographic correlation, this finding is compatible with cancer until proven otherwise. So if biopsy shows anything other than cancer, it is discordant and patient should move on to excisional biopsy. In this case, an ultrasound-guided core needle biopsy demonstrated invasive ductal cancer, which provided a pre-operative mapping and planning.
The second case is in a 42-year-old woman who presented for screening mammography and mammogram describes BI-RADS 0 findings for a focal asymmetry. And if we move back to the corresponding ultrasound in this patient, it is fairly similar to the prior patient where we see an oval mass with slightly indistinct margins. This is a BI-RADS 4B category for ultrasound imaging. Patient underwent a core needle biopsy and showed a fibroadenoma. This was deemed concordant radiologic pathologically, and patient went on to a short-term follow up and subsequent annual mammography.
Moving on to a newer emerging technology for the breast. And I would like to spend a few minutes on dynamic contrast enhanced magnetic resonance imaging. This essentially exploits the concept of angiogenesis in malignant tumors where leaky vessels allow the extravasation of contrast agents locally and the technique of magnetic resonance imaging with a dynamic contrast administration is used to detect malignant tumors which demonstrate rapid contrast enhancement within these lesions and contrast enhancement in such tumors also shows rapid washout. The beauty and the advantage of magnetic resonance imaging is that it has capability of detecting early breast cancer with high sensitivity and the high morphologic resolution coupled with the kinetic information that is possible with this technique allows a sophisticated form of detecting breast cancer.
The following is an example of a small sub-centimeter lesion that is seen on MR on the early phase of a dynamic contrast enhanced study. And this shows rapid enhancement. And a second patient shows a small lesion in the superior aspect on the early dynamic contrast phase where the mass is enhancing rapidly and intensely. And where there was washout on the delayed phase. Contrast this small lesion that is suspicious and was finally shown to represent invasive cancer. With this more diffuse area of enhancement where we see multiple foci of contrast enhancement that becomes progressively more intense. And this was an area of fibrocystic change that has been present in the breast for the last three years. The following is a kinetic curve that shows the rapid enhancement of the lesion that we saw in the superior breast with rapid washout and that represented invasive ductal carcinoma.
The following slide delineates and outlines the indications for performing breast MRI, which we follow in M. D. Anderson. The most important indication for using breast MRI is for screening in the high-risk population. Other indications include the evaluation of a patient who presents with axillary adenocarcinoma of unknown primary, for further workup of the woman who presents with an equivocal mammogram, ultrasound or physical examination findings, for staging of breast cancer patients to delineate disease extent, invasion and chest wall involvement, to evaluate for residual disease post-lumpectomy or breast conservation surgery, to evaluate for recurrence in a woman with a past history of breast cancer and to monitor response in women who undergo neoadjuvant chemotherapy.
The first is an example of a patient in her 30s who presents for high-risk screening. The two-view mammogram shows no overt abnormality in terms of a mass, an area of architectural distortion or calcifications. The screening MR shows a small, 7 millimeter rapidly intensely enhancing mass that shows washout features on the delayed MR. And that was noted on the second look ultrasound to show a small hypoechoic mass corresponding to the location on the MRI. And biopsy showed invasive ductal cancer.
The conclusion for multiple high-risk screening studies using MRI both from the Canadian studies as well as the Dutch studies, and more recently the United Kingdom studies show that mammography is the gold standard for routine screening in the general population, but it's woefully inadequate for the high-risk population who are generally young and under 40 in age, where radiation exposure and false positive results as well as decreased sensitivity for these dense breasts in young women poses a problem.
The conclusions for high-risk population are that additional methods need to be evaluated. And by far over the last decade, MRI has been shown to be the emerging technique that has shown the most accuracy and the highest sensitivity. The other advantages of MRI for the breast for this population is that there are no limitations for the mammographically dense breast. It's a promising technique for screening young women at high-risk. And the major disadvantages of MRI are its relatively lower specificity and its high cost.
The following will demonstrate an example of a patient who presents with axillary adenocarcinoma of unknown primary. There were multiple abnormal lymph nodes in the right breast that showed adenocarcinoma. An MRI in this patient showed multiple abnormal enhancing foci in the upper breast that was biopsied and shown to represent cancer. Here we show the tumor marker clips that were placed after MRI-guided biopsy. Moving on to the third indication, which is the equivocal mammogram, ultrasound or physical examination finding. This patient, who has a history of a prior benign excisional biopsy shown by the scar mark, had a palpable finding in the right breast, 5 o'clock position, which was negative by mammography and also negative by initial ultrasound work up. The ultrasound did not show a finding at the site of palpable concern. Patient went on to an MR that showed an intensely enhancing mass with washout or malignant kinetic features. This is the kinetic graph that shows the rapid washout and a plateau, distal phase. A second look ultrasound performed in the same lady showed this small, hypoechoic mass corresponding to the MR finding and an ultrasound-guided core needle biopsy shows the needle traversing the mass and the final diagnosis was a small, invasive ductal cancer.
Staging of a patient with extensive breast cancer using MRI is an important function. Here is a patient who has an entire left breast replaced by tumor. The reason for performing MR was to better delineate or evaluate the posterior chest wall, which on this axial view is shown to be completely replaced by tumor. So the left breast has been tumor ridden and the left chest wall is also involved. This has surgical implications for the breast surgeon planning treatment for this patient. Importantly, the same patient showed a contralateral internal mammary lymph node metastasis, which puts her in a different staging category in overall treatment planning. In terms of staging for a patient with a known diagnosis of cancer, this is a known biopsy-proven cancer that presented as a palpable finding in the right upper outer quadrant. Because of the dense background parenchyma, the patient presented for MRI staging. And here we see on the axial post-contrast views, the biopsy-proven cancer on the right side. And this is an important platform to introduce the role of MRI-guided breast biopsies.
We feel that every facility that performs breast MR for patients should mandatorily have facilities for MR-guided biopsies, the reason being that lesions that are seen only on MR require MR-guided biopsy for final resolution of the abnormal findings and to guide and recommend patient management. In the same patient we saw earlier with the biopsy-proven right breast cancer, multiple other lesions were seen in both breasts that required biopsies.
The biopsies setup is as follows. We require a unit network. And here are several slides that demonstrate the biopsy procedure where a biopsy grid is used to lightly compress the breast. And using the biopsy network, the appropriate location of the lesion is calculated using coordinate technique and the needle is then advanced into the right location and the breast then imaged again to confirm that the tip of the needle is where the targeted lesion resides. And the biopsy procedure then proceeds with collection of the tissue core samples using a vacuum-assisted device.
In the same patient with the right breast cancer in the inferior lower part of the breast, there was a second lesion that showed to be a multi-centric focus of cancer confirmed on MRI-guided biopsy. However, in the same woman, she had a false positive left breast mass that showed fibrocystic changes and a fourth lesion that was also false positive in the same right breast that was a papillary lesion. This underscores the weaknesses of breast MR where a low-specificity can sometimes create further imaging and evaluation complications for a patient with breast cancer.
The fifth indication for breast MRI includes the evaluation for residual disease after breast conservation surgery. In this patient, who presented to M. D. Anderson after an outside excisional biopsy for cancer that was positive on all margins, mammography on this film shows no evidence of a suspicious residual mass. However, same patient underwent MR and multiple areas of abnormal enhancement were noted up to 3 centimeters from the seroma cavity and these were biopsy-proven to represent residual disease and patient went on to have extensive surgery. As a matter of fact, she elected to have total mastectomy after these MRI findings.
What about the role of breast MR in evaluation for recurrence? This is a 45-year-old physician who was planning her wedding in two months and had come for her 13-year follow up mammogram after a diagnosis of breast cancer in her 30s. The follow up mammogram showed no findings from prior mammograms. There were surgical clips, any scar and no evident mass. She elected to have a breast MR screening in order to make sure all was well prior to her big day. An MR showed florid abnormal enhancement throughout the right breast measuring up to 5 centimeters with malignant kinetics. An MR-guided biopsy showed cancer that had recurred in the right breast that was appropriately treated.
The final indication I would like to discuss is the role of breast MR in monitoring response for patients who undergo new adjuvant chemotherapy. Here we have a 33-year-old female who presents with a large squamous metaplastic cancer that measured more than 6 centimeters at diagnosis. At the point of diagnosis there were multiple areas that showed malignant kinetic features. And three months after therapy, the tumor has not only decreased in size but the kinetic curves have become more benign. We see a less rapid baseline enhancement and we see a progressive enhancement pattern as opposed to the washout kinetics seen on the earlier slides.
Finally, I would like to spend a few minutes discussing another more
sophisticated and emerging breast imaging technology that is not
standard-of-care today. And this is PET, or Positron Emission Tomography,
frequently now performed as
The following slides are to illustrate the role of this technique in monitoring response. This is a 31-year-old patient who presented with a left breast mass for one year. It was infiltrating ductal carcinoma at biopsy and patient was initially treated with AC chemotherapy that led to toxicity and had to be stopped. The patient was then switched to Herceptin and Xeloda therapy and the following are several images obtained during her response study. Here we see an extremely large left breast cancer that is hypermetabolic and shows increased uptake on the PET scan that is fused onto the CT scan so we have a registered image showing hypermetabolism within the cancer at the time of baseline imaging. Here we see the cancer in a coronal image and we see incidental artifacts which are related to brown fat that the nuclear medicine physicians are more familiar with. At follow up at 8 weeks of therapy, the original cancer has completely shrunk and we see now only a tiny area of hypermetabolism stressing that the patient has responded extremely well to her new chemotherapy of Herceptin and Xeloda.
Finally,
In this patient with breast cancer, we see multiple areas of increased uptake within the breast and frequently 12 slabs are obtained from a single breast. PEM, or Positron Emission Mammography is touted as an organ-specific molecular imaging device that will hopefully find a role in the analysis, treatment selection, and monitoring of breast cancer. The PEM Flex device has been studied and a single publication has described promising preliminary studies in evaluating patients with cancer. PEM was successful in delineating almost 90% of patients with ductal carcinoma in situ, 90% of patients with invasive breast cancers and importantly, almost 60% of cancers that were 1 centimeter or smaller in size. Here is another picture of a patient with multifocal breast cancer that is shown on PEM imaging. And that is my final slide.
I would like to thank you for your attention. Thank you very much.
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