Radiology

Class Act: The Use of MRI in Breast Cancer Screening

August 28, 2008

breastmri.jpgClass act is a feature of Clinical Correlations written by NYU 3rd and 4th year medical students. Prior to publication, each commentary is thoroughly reviewed for content by a faculty member.

Commentary by Daniel Green MSIV and Boris Kobrinsky MD, Assistant Professor, NYU Division of Oncology

In 2008, an estimated 182,460 women in the United States will be diagnosed with invasive breast cancer, and 40,480 women will die of the disease as it remains the demographic’s second leading cause of cancer mortality.(1) Fortunately, breast cancer is one of the screenable cancers, and screening mammography has been shown to detect asymptomatic breast cancer at an early stage and reduce all-cause mortality when followed with appropriate treatment.(2,3) However, plain mammography has a sensitivity of about 85 percent, resulting in an estimated 21.8% of cases that are node positive at the time of diagnosis.(4)

The use of MRI in breast cancer screening is receiving increased attention, and the American Cancer Society has recently recommended it as an adjunct to plain mammography in the screening of high risk patients.(5) These patients include women with dense breast tissue, a personal history of breast cancer or lobular carcinoma in situ, prior mantle irradiation for Hodgkin’s lymphoma, and a strong family history of breast cancer.

Women with inherited BRCA1 and BRCA2 mutations have the greatest risk of breast cancer. Though only five to ten percent of women with breast cancer have one of the two mutations, those with a BRCA genotype have a lifetime risk of 65 to 80 percent of developing the disease.(5) This population tends to develop more aggressive breast cancers with significant risk of disease starting as early as age 30.

Several large, prospective, nonrandomized trials have been conducted to evaluate the use of MRI as an adjunct to plain mammography in screening high risk women for breast cancer. The largest of these studies, conducted in The Netherlands and published in 2004, evaluated both MRI and mammography in 1,909 high risk women.(6) The investigators found high sensitivity of MRI (80 percent) compared to that of mammography, whose sensitivity plummets to 33 percent in this high risk population. On the other hand, MRI had lower specificity than mammography (90 and 95 percent, respectively). Several other studies in North America and Europe have recapitulated these results.(7-11)

These studies were included in a recently published meta-analysis of 11 prospective studies on screening women at high risk of breast cancer with a combination of MRI and plain mammography. The investigators concluded that screening with mammography plus MRI may exclude breast cancer better then mammography alone in a population of women with a strong genetic predisposition to breast cancer.(12)

Enhancement of invasive breast carcinomas in contrast studies with gadolinium enables the increased sensitivity of MRI. However, many benign breast lesions enhance with gadolinium, resulting in a lower specificity. In women not characterized as high risk, the likelihood of false positives may lead to an unacceptable amount of recalls and biopsies. Because of the increased cancer rate in high risk women, the incidence of benign biopsy following MRI is similar to that of a population-based study using plain mammography.(13) In these patients, the benefit of high sensitivity MRI may outweigh the effects of lower specificity, though data on survival are not yet available.

A recent study from Stanford University evaluated the cost-effectiveness of supplementing screening mammography with MRI for carriers of BRCA mutations.(14) Health benefits were measured in terms of total health-related costs and quality-adjusted life years. The researchers found that screening MRI was more cost-effective in BRCA1-positive women compared to BRCA2-positive women because BRCA1 mutations confer a higher risk of breast cancer. However, they did not find that women with BRCA1 mutations aged 25-34 were at high enough risk to justify annual MRI screening. In addition, women with BRCA1 mutations over the age of 55 suffered from declining quality of life and competing risks for death, thus rejecting MRI as cost-effective for this age group. This leaves women with BRCA1 mutations aged 35-54 as the group most likely to benefit from MRI while taking cost into account.

MRI is also being utilized for screening of both the ipsilateral and contralateral breasts in women recently diagnosed with breast cancer. The prevalence of synchronous MRI detected breast cancer is considered to be between 1 and 9.5 percent, and these cancers are often both mammographically and clinically occult.(15,16) As is the case with standard breast cancer screening, the false positive rate is high due to limited specificity.

Current evidence suggests that MRI can benefit women at high risk, while there is much weaker evidence supporting its use in women of normal risk. Further research is necessary to develop the best method to improve screening in women at an intermediate level of risk, in whom the benefit of MRI remains unclear.

REFERENCES

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58(2):71-96.

2. Nyström L, Andersson I, Bjurstam N, et al. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet 2002;359(9310):909-19.

3. Glass AG, Lacey JV Jr, Carreon JD, Hoover RN. Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst 2007;99(15):1152-61.

4. Weaver DL, Rosenberg RD, Barlow WE, et al. Pathologic findings from the Breast Cancer Surveillance Consortium: population-based outcomes in women undergoing biopsy after screening mammography. Cancer 2006;106(4):732-42.

5. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007;57:75-89.

6. Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351:427-437.

7. Kuhl CK, Schrading S, Leutner CC, et al. Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 2005;23:8469-8476.

8. Leach MO, Boggis CR, Dixon AK, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 2005;365:1769-1778.

9. Lehman CD, Blume JD, Weatherall P, et al. Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer 2005;103:1898-1905.

10. Sardanelli F, Podo F. Breast MR imaging in women at high risk of breast cancer. Is something changing in early breast cancer detection? Eur Radiol 2007;17(4):873-87.

11. Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 2004;292:1317-1325.

12. Warner E, Messersmith H, Causer P, et al. Systematic Review: Using magnetic resonance imaging to screen women at high risk for breast cancer. Ann Intern Med 2008;148:671-79.

13. Warren RM, Pointon L, Caines R, et al. What is the recall rate of breast MRI when used for screening asymptomatic women at high risk? Magn Reson Imaging 2002;20(7):557-65.

14. Plevritis SK, Kurian AW, Sigal BM, et al. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA 2006;295:2374-2384.

15. Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007;356(13):1295-303.

16. Lee SG, Orel SG, Woo IJ, et al. MR imaging screening of the contralateral breast in patients with newly diagnosed breast cancer: preliminary results. Radiology 2003;226(3):773-8.

Mystery Quiz

June 19, 2008

Posted by Athena Kritharis MS-3, Vivian Hayashi MD, Instructor of Clinical Medicine, Division of General Internal Medicine and Robert Smith MD, Associate Professor of Medicine, Division Pulmonary and Critical Care Medicine

The patient is a 42 year old Caucasian woman with no significant past medical history who presents with diffuse abdominal pain for two months that progressed to acute epigastric pain followed by nausea and vomiting. The vomitus was “milky” and contained only food particles. Symptoms were not relieved with over-the-counter antacids. The patient recalls eating scallops the night before presentation. The patient’s history is also significant for an umbilical hernia repair and three uncomplicated vaginal deliveries. The patient takes Chinese herbs and drinks alcohol socially, but no elicit drugs nor tobacco use. A CT scan with contrast of the abdomen was obtained.

myteryquiz6082.png


What is your leading diagnosis?

View Results

Grand Rounds: “Nephrogenic systemic fibrosis”

June 5, 2008

Bellevue Amphitheater

Commentary by Jatin Roper MD, PGY-3

Medical Grand Rounds today was presented last week by Dr. Shawn Cowper, Assistant Professor of Dermatology and Pathology at Yale University School of Medicine. Grand Rounds began with the presentation of a case from Tisch Hospital:

A 46 year old female with a history of end-stage renal disease secondary to diffuse-proliferative glomerulonephritis on hemodialysis, systemic lupus erythematosis, antiphospholipid antibody syndrome, and IVC thrombosis presents to a dermatology consultant for progressive hardness, tightness, and tenderness of skin of the legs and forearms for 3-4 months. Physical examination reveals brawny, indurated, cutaneous plaques on the legs and forearms. The differential diagnosis included morphea, scleromyxedema, and nephrogenic systemic fibrosis. Based on this differential further history is obtained which reveals a history of five gadolinium-containing MRI studies in the past two years, with two in the last month. Skin biopsy (read by Dr. Shawn Cowper) demonstrates diffuse proliferation of thin spindle cells, minimal inflammation, abundant collagen, and CD34+ spindle cells.

Final diagnosis: Nephrogenic systemic fibrosis due to gadolinium administration in the setting of end-stage renal disease.

So what is nephrogenic systemic fibrosis (NSF), and why should we care about it?

Read more »

Noninvasive Cardiac Imaging: Coronary CT Angiography

March 26, 2008

heart.pngCommentary by Matt LaBarbera MD, PGY-3 and Rob Donnino, MD Instructor of Medicine, Division of Cardiology

Coronary CT angiography (CCTA) is a noninvasive imaging modality which can be used to evaluate the anatomy of the coronary arteries. Unlike coronary artery calcium scoring, which utilizes noncontrast CT to assess atherosclerotic disease burden, CCTA allows direct visualization of the coronary artery wall and lumen with the administration of intravenous contrast. The degree of coronary luminal stenosis can be reliably estimated, as can the presence or absence of both calcified and non-calcified plaques. When compared to invasive quantitative coronary angiography, newer-generation CT scanners have been found to have sensitivities and specificities of over 90%, and negative predictive values of up to 100% for the exclusion of obstructive coronary artery disease (CAD) for both native arteries as well as bypass grafts.[1-5] With recent advances in CT technology and increased availability, CCTA has become a non-invasive alternative for imaging the coronary arteries in an increasing number of patients, and may obviate the need for coronary artery catheterization in some patients. Read more »

Mystery Quiz

January 29, 2008

Posted By: Vivian Hayashi, MD, Instructor of Clinical Medicine, Division of General Internal Medicine and Robert Smith, MD Associate Professor of Medicine, Division Pulmonary and Critical Care Medicine

A 78 year old man with a history of ankylosing spondylitis and known cardiac disease associated with congestive heart failure, presented with breathlessness one year prior to admission.  Over the most recent months, the patient complained of cough productive of voluminous frothy, watery sputum.  Medications included digoxin, furosemide, irbesartan, isosorbide, metoprolol, spirinolactone, simvastatin, and warfarin.  The patient had worked as a photographer, mixing his own chemicals.  He was an ex-smoker who quit 45 years earlier.

Chest CT 1

Prone imaging showed no changes in the location of the abnormalities

Several months later, the patient reported worsening symptoms.  Repeat imaging showed the following:

Chest CT 2

Transbronchial biopsy did not reveal infection nor malignancy and PAS staining was negative.  An open biopsy was performed.


What is your leading diagnosis?

View Results

X Ray Visions Mystery Quiz- The Answer

August 30, 2007

Before you read the answer, you may want to review the initial Mystery Quiz posted last week.

Commentary by Andrew Hardie MD, Fellow, NYU Department of Radiology

Although this patient’s symptoms were not the most typical of this entity, the CT findings in this case are diagnostic of a perforated anterior duodenal ulcer. The most essential observation, and the one that alters management, is the presence of intraabdominal free air (arrows). The small collections of air in this case are not unusual for bowel perforations, especially proximally. One can see how occasionally these small volumes of free air may not be able to be seen on plain films, especially inadequately positioned films.

The specific location of the free air in this case directs one to suspect a duodenal perforation. Air is seen in the periportal region, around the duodenum (green arrows), and in this case, at the site of the perforation in the duodenal wall (red arrow).

ansewr2.jpganswer1.jpg

A point of interest is that only the anterior duodenal bulb wall is intraperitoneal. Therefore, this must be an anterior wall ulcer. A posterior wall ulcer will lead to gastrointestinal bleeding, because, if you remember your anatomy, the gastroduodenal artery lies directly posterior to the duodenal bulb. Although very rare, a perforated posterior wall ulcer would cause retroperitoneal air, not intraperitoneal air.

The patient in this case reported severe epigastric pain, which could be indicative of peptic ulcer disease. However, physical exam was not suggestive of peritonitis. It is important to remember that atypical presentations of perforated ulcers can occur, although this is more commonly seen in elderly patients. Also, in this case, the perforation could have occurred in the interval between admission and abdominal imaging. The patient was taken to the OR for immediate repair of the perforation and postoperative clinical course was uneventful. Upon further questioning, he did admit to heavy weekend alcohol use as well as recent increased NSAID use for some low back pain.

X-Ray Visions: Mystery Quiz

August 22, 2007

A 46 year old male with a past medical history of hypertension presents to the emergency room complaining of constant throbbing epigastric pain for one day. He rates the pain as 7/10, with some radiation to his chest. He reports some mild nausea, but denies diarrhea or constipation.  He does endorse a bloated sensation for the past few days. He has not had any fevers and denies melana or hematochezia.  He is an avid biker and reports unlimited exercise tolerance. He denies any previous history of chest pain.

The patient works as a landscaper. He does not smoke and drinks socially on the weekends. His only medication is hydrochlorothiazide 25 mg daily. He has never had any surgeries. His father died of lung cancer at age 72, his mother is alive and well.

Pt appears mildly anxious but is otherwise in no distress. He is afebrile, BP 150/90, pulse 98, respiration rate 16.  Physical exam is remarkable only for some mild epigastric tenderness without rebound tenderness or guarding.

ECG is sinus rhythm, no st or t changes.

WBC is 16 (82% neutrophils), h/h 14/42, plt 247

Basic metabolic panel is within normal limits. Liver function tests, amylase, lipase are also all within normal limits.

Initial cardiac enzymes are negative.

The patient is admitted to the medicine service by the emergency room as a “r/o MI.”

A CT A/P with po and IV contrast is ordered by the medical team:

 

air_i0022_1.jpg

air_i0025_1.jpgair_i0030_1.jpg


What is your leading diagnosis?

View Results

 

 

X-Ray Visions: Update on Nephrogenic Systemic Fibrosis and Gadolinium Contrast MRI

July 24, 2007

Commentary by Andrew Hardie MD, Body MRI Fellow, NYU Dept of Radiology

The recent discovery of a link between Nephrogenic Systemic Fibrosis (NSF) and the administration of gadolinium contrast for MRI examinations has sent the imaging world scrambling. NSF is a debilitating fibrosing reaction primarily involving the skin and, to a variable degree, internal organs. While longitudinal studies currently do not exist to help determine which patients can be safely administered gadolinium, it is clear that severe renal dysfunction, including those patients on dialysis, are at risk. (CJASN 2007;2:264) An additional factor which may increase the risk of NSF is the total dose of gadolinium. Unfortunately, MRI has previously been the imaging method of choice in patients with poor renal function to avoid the use of nephrotoxic iodinated contrast agents used in CT. Although well ingrained in the medical consciousness, this practice has been forced to change.

Radiologic examinations most affected by this change in practice are the evaluation of solid tumors (liver and kidney in particular) and MR angiograms (MRA). At the current time, although MR sequences can visualize solid tumors without gadolinium, the sensitivity and particularly the specificity of the exam is reduced. Further, gadolinium is essential for high quality MRA. The hope is that continued technical advancements in the field will made gadolinium less essential in the future. For now, the risks of NSF vs. contrast nephrotoxity from CT contrast must be weighed for each individual patient.

As no standardized national guidelines for the administration of gadolinium are in place, individual radiology departments have adopted individual guidelines based on the available information. The guidelines in the MRI department at NYU categorize patients based on calculated glomerular filtration rate (GFR) using serum creatinine, age, and weight. Patients with a normal GFR can receive any gadolinium contrast agent. Nevertheless, gadolinium dose is minimized when possible. Patients with a moderately reduced GFR (30-60) should be considered for alternative imaging but can still receive gadolinium. These patients are specifically consented for the risk of NSF and doses are minimized. Patients with a severely reduced GFR (< 30) should only be administered gadolinium under extreme medical necessity. When it is necessary, consent is obtained from the patient and ordering physician. Also, a gadolinium chelate which can be administered in a reduced dose with minimal reduction in image quality, gadobenate dimeglumin (Multihance), may be used.

Because serial dialysis even immediately following gadolinium administration has been shown not to reduce the risk of NSF, patients with end stage renal disease on dialysis should not receive gadolinium. Peritoneal dialysis is an absolute contraindication. In most cases, dialysis patients should undergo CT since nephrotoxicity is no longer an issue. However, non-contrast MR may also be appropriate in some patients.

The medical understanding of NSF is rapidly changing. Clinicians and imagers must continue to closely monitor the progress of ongoing studies and the implications on patient care.

Image courtesy of Wikimedia Commons

Breaking News: FDA Advises Caution with Gadolinium Based Contrast

December 27, 2006

Commentary By: Minisha Sood PGY-3

The FDA has received reports of 90 patients with moderate to end-stage kidney disease who have undergone MRI or MRA with a gadolinium-based contrast agent and subsequently developed a new disease known as Nephrogenic Systemic Fibrosis (NSF).

Scientists first identified NSF, also known as Nephrogenic Fibrosing Dermopathy (NFD), in 1997 and its cause has not yet been identified.  There have been approximately 200 reports of NSF/NFD only in people with kidney disease.  Neither the duration of kidney disease nor its underlying cause is related to the development of NSF.

Patients with NSF report swelling and tightening of the skin, which usually affects the extremities and leads to an inhibition of flexion and extension.  Muscle weakness is a common symptom as well.  Approximately 5% of patients experience a rapidly progressive course, which may result in death due to widespread fibrosis.  The pathogenesis of NSF is thought to be linked to the circulating fibrocyte (CF), a recently characterized cell that is distinct from a fibroblast.  The CF leaves the circulation, the mechanism of which is still being investigated, and differentiates in the dermis where it resembles normal fibroblasts and leads to a systemic disorder.

Many approaches to treatment are currently under investigation including oral steroids, physical therapy, plasmapheresis, high-dose IVIG therapy, and renal transplantation.

Here is some important information for health care providers:

  • When a patient with moderate to end-stage kidney disease requires an imaging study, a modality other than MRI or MRA with a gadolinium-based contrast agent should be chosen whenever feasible.
  • If MRI or MRA with a gadolinium-based contrast agent is necessary, it may be prudent to arrange prompt dialysis for patients with advanced kidney dysfunction.
  • The FDA requests that health care providers and patients report adverse event information to the FDA online at http://www.fda.gov/medwatch/report.htm, by phone (1-800-FDA-1088) or by fax (1-800-FDA-0178).