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Descriptors of Malignant Non-mass Enhancement of Breast MRI

Rationale and Objectives

This study aims to investigate the clinical significance of malignant non-mass enhancement (NME) descriptors in breast magnetic resonance images by assessing their correlation to the presence of invasion or lymph node metastasis.

Materials and Methods

Three radiologists independently reviewed magnetic resonance images with malignant NMEs between January 2008 and December 2009. Distribution was assessed first, and then each of four internal enhancement patterns—clumped, clustered ring, branching, and hypointense area—was evaluated dichotomously (yes or no). Because clustered rings and hypointense areas were thought to be major structural elements of heterogeneous NMEs, they were also evaluated by integrating them into one collective descriptor we called the “heterogeneous structures.” Chi-square test, Fisher exact test, or Student t test was used to analyze differences of variables by each reviewer. Positive predictive values (PPVs) of descriptors in predicting presence of invasion or lymph node metastasis were calculated. P < 0.05 was considered significant.

Results

We included 131 malignant NMEs (76 in situ and 55 invasive) in 129 patients (two bilateral). All three observers’ results showed clustered rings (PPVs 54.5%, 54.5%, 50.0%) ( P = 0.0005, 0.038, 0.029) and hypointense areas (PPVs 63.6%, 61.5%, 73.9%) ( P = 0.004, 0.024, 0.0006) to be significantly associated with invasion. When clustered rings and hypointense areas were integrated into heterogeneous structures, they were significantly associated with invasion (PPVs 54.3%, 53.3%, 51.8%) ( P = 0.0003, 0.016, 0.003).

Conclusions

The NME descriptors clustered rings, hypoechoic areas, and heterogeneous structures, assessed collectively, were associated with invasive breast cancer.

Introduction

Non-mass enhancement (NME) is one of the three lesion morphologies observed in magnetic resonance imaging (MRI) of breasts and is often associated with in situ lesions . However, NMEs with invasive components reportedly account for 10%–42% of total malignant NMEs . In situ and invasive lesions should be managed differently, especially when recent controversy about overtreatment of in situ breast cancer is taken into account .

Breast Imaging Reporting and Data System (BI-RADS) descriptors have been investigated in differentiating benign from malignant NME . However, few prior studies have investigated relationships between descriptors of NMEs and significant clinical factors, including invasion within NMEs . Furthermore, other internal structural patterns within NMEs, which are not widely recognized or have not been adopted into MR lexicon at this point, are also encountered in clinical practice. For example, fine branching structures within NMEs that suggest possible enhancement within or around ducts and their branches have been associated with malignancy ( Fig 1c , called “branching” in this study). In addition, within NMEs, relatively hypointense, confined areas that show fewer enhancements than surrounding areas are occasionally observed ( Figs 1d, 3b, 4b, 5b ; called “hypointense areas” in this study). We believe that this finding seems to add another major structural element of heterogeneous NMEs in addition to the clustered ring, given that heterogeneous NMEs are supposed to include areas of varying enhancement.

Figure 1, Sagittal contrast-enhanced T1-weighted images showing examples of internal enhancement patterns (IEPs). (a) 49-year-old woman with ductal carcinoma in situ (DCIS) of the left breast; non-mass enhancement (NME) includes a clumped IEP ( arrowheads ). (b) 38-year-old woman with invasive carcinoma of no special type (NST) of the right breast; NME includes a clustered ring IEP ( arrowheads ). (c) 47-year-old woman with DCIS of the right breast; NME includes branching IEP ( arrows ). (d) 48-year-old woman with invasive NST of the left breast; NME includes a hypointense area IEP ( circle ).

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Materials and Methods

Patients

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MRI Technique

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Observer Study

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Statistical Analyses

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Results

Study Subjects and Lesions

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Analysis Between MRI Descriptors and Clinical Factors

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TABLE 1

Analyses Between MRI Descriptors Assessed by Reviewer 1 and Clinical Outcomes

Invasive In Situ PPV (95%CI) NPV (95%CI)P Distribution 0.82 Diffuse 1 2 Focal 6 7 Linear 0 1 Multiple 0 0 Regional 0 0 Segmental 48 66 Clumped +/− 33/22 53/23 38.4% (28.1–48.7%) 51.1% (36.5–65.7%) 0.25 Branching +/− 39/16 58/18 40.2% (30.4–50.0%) 52.9% (36.2–69.7%) 0.49 Heterogeneous structure +/− 44/11 37/39 54.3% (43.5–65.2%) 78.0% (66.5–89.5%) 0.0003 Clustered ring +/− 42/13 35/41 54.5% (43.4–65.7%) 75.9% (64.5–87.3%) 0.0005 Hypointense area +/− 21/34 12/64 63.6% (47.2–80.0%) 65.3% (55.9–74.7%) 0.004

LNM + − PPV (95%CI) NPV (95%CI)P Distribution 0.77 Diffuse 0 1 Focal 2 4 Linear 0 0 Regional 0 0 Segmental 13 37 Clumped +/− 5/8 28/14 15.2% (2.9–27.4%) 63.6% (43.5–83.7%) 0.11 Branching +/− 7/6 32/10 17.9% (5.9–30.0%) 62.5% (38.8–86.2%) 0.23 Heterogeneous structure +/− 12/1 32/10 27.3% (14.1–40.4%) 90.9% (73.9–100.0%) 0.27 Clustered ring +/− 12/1 30/12 28.6% (14.9–42.2%) 92.3% (77.8–100.0%) 0.16 Hypointense area +/− 4/9 17/25 19.0% (2.3–35.8%) 73.5% (58.7–88.4%) 0.75

CI, confidence interval; LNM, lymph node metastasis; NPV, negative predictive value; PPV, positive predictive value.

TABLE 2

Analyses Between MRI Descriptors Assessed by Reviewer 2 and Clinical Outcomes

Invasive In Situ PPV (95%CI) NPV (95%CI)P Distribution 0.76 Diffuse 0 0 Focal 10 13 Linear 5 10 Multiple 0 1 Regional 3 2 Segmental 37 50 Clumped +/− 36/19 57/19 38.7% (28.8–48.6%) 50.0% (34.1–65.9%) 0.23 Branching +/− 29/26 39/37 42.6% (30.9–54.4%) 58.7% (46.6–70.9%) 0.87 Heterogeneous structure +/− 32/23 28/48 53.3% (40.7–66.0%) 67.6% (56.7–78.5%) 0.016 Clustered ring +/− 24/31 20/56 54.5% (39.8–69.3%) 64.4% (54.4–74.4%) 0.038 Hypointense area +/− 16/39 10/66 61.5% (42.8–80.2%) 62.9% (53.6–72.1%) 0.024

LNM + − PPV (95%CI) NPV (95%CI)P Distribution 0.18 Diffuse 0 0 Focal 3 7 Linear 0 5 Regional 2 1 Segmental 8 29 Clumped +/− 7/6 29/13 19.4% (6.5–32.4%) 68.4% (47.5–89.3%) 0.50 Branching +/− 7/6 22/20 24.1% (8.6–39.7%) 76.9% (60.7–93.1%) 0.93 Heterogeneous structure +/− 9/4 23/19 28.1% (12.5–43.7%) 82.6% (67.1–98.1%) 0.52 Clustered ring +/− 6/7 18/24 25.0% (7.7–42.3%) 77.4% (62.7–92.1%) 0.83 Hypointense area +/− 4/9 12/30 25.0% (3.8–46.2%) 76.9% (63.7–90.1%) 1.0

CI, confidence interval; LNM, lymph node metastasis; NPV, negative predictive value; PPV, positive predictive value.

TABLE 3

Analyses Between MRI Descriptors Assessed by Reviewer 3 and Clinical Outcomes

Invasive In Situ PPV (95%CI) NPV (95%CI)P Distribution 0.19 Diffuse 0 0 Focal 4 9 Linear 1 1 Multiple 0 0 Regional 0 5 Segmental 50 61 Clumped +/− 41/14 61/15 40.2% (30.7–49.7%) 51.7% (33.5–69.9%) 0.44 Branching +/− 42/13 49/27 46.2% (35.9–56.4%) 67.5% (53.0–82.0%) 0.14 Heterogeneous structure +/− 43/12 40/36 51.8% (41.1–62.6%) 51.8% (41.1–62.6%) 0.003 Clustered ring +/− 38/17 38/38 50.0% (38.8–61.2%) 69.1% (56.9–81.3%) 0.029 Hypointense area +/− 17/38 6/70 73.9% (56.0–91.9%) 64.8% (55.8–73.8%) 0.0006

LNM + − PPV (95%CI) NPV (95%CI)P Distribution 0.85 Diffuse 0 0 Focal 1 3 Linear 0 1 Regional 0 0 Segmental 12 38 Clumped +/− 10/3 31/11 24.4% (11.2–37.5%) 78.6% (57.1–100.0%) 1.0 Branching +/− 7/6 35/7 16.7% (5.4–27.9%) 53.8% (26.7–80.9%) 0.07 Heterogeneous structure +/− 12/1 31/11 27.9% (14.5–41.3%) 91.7% (76.0–100.0%) 0.26 Clustered ring +/− 12/1 26/16 31.6% (16.8–46.4%) 94.1% (82.9–100.0%) 0.045 Hypointense area +/− 5/8 12/30 29.4% (7.8–51.1%) 78.9% (66.0–91.9%) 0.51

CI, confidence interval; LNM, lymph node metastasis; NPV, negative predictive value; PPV, positive predictive value.

Figure 2, 61-year-old woman with invasive carcinoma of no special type (NST) of the left breast. Anteroposterior Maximum intensity projection (MIP) of subtraction image (a) and sagittal contrast-enhanced T1-weighted image (b) are shown. The distribution of this non-mass enhancement (NME) was interpreted as segmental by Reviewers 1 and 3 and as regional by Reviewer 2. Clustered ring internal enhancement pattern was detected by all three reviewers ( arrowheads ). Axillary lymph node metastasis was detected in the histopathological analysis.

Figure 3, 42-year-old woman with invasive carcinoma of no special type (NST) of the right breast. Coronal (a) and sagittal (b) contrast-enhanced T1-weighted images are shown. All three reviewers interpreted this non-mass enhancement (NME) as segmental distribution, with a hypointense area ( circle ). No metastasis was seen in histopathological analysis of biopsied sentinel lymph nodes.

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Interobserver Agreement of Descriptors

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TABLE 4

Interobserver Agreement of Descriptors Between Reviewers Expressed as Kappa Values

Reviewers Distribution Clumped Branching Heterogeneous Structure Clustered Ring Hypointense Area 1 vs 2 0.32 (0.19–0.45) 0.35 (0.18–0.52) 0.18 (0.02–0.33) 0.51 (0.37–0.64) 0.41 (0.28–0.54) 0.54 (0.37–0.71) 1 vs 3 0.26 (0.14–0.38) 0.41 (0.24–0.57) 0.29 (0.11–0.46) 0.51 (0.36–0.66) 0.42 (0.26–0.58) 0.37 (0.18–0.56) 2 vs 3 0.45 (0.31–0.59) 0.42 (0.25–0.60) 0.40 (0.25–0.54) 0.45 (0.31–0.59) 0.42 (0.29–0.55) 0.57 (0.39–0.75)

The 95% confidence intervals are shown in parentheses.

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Discussion

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Figure 4, 47-year-old woman with invasive carcinoma of no special type (NST) of the left breast. Anteroposterior MIP of subtraction image (a) and sagittal contrast-enhanced T1-weighted image (b) are shown. All three reviewers interpreted this non-mass enhancement (NME) as segmental distribution, with a clustered ring ( arrow ) and hypointense areas ( arrowheads ). No metastasis was seen in the histopathological analysis of biopsied sentinel lymph nodes.

Figure 5, 48-year-old woman with invasive carcinoma of no special type (NST) of the left breast. Anteroposterior MIP of subtraction image (a) and sagittal contrast-enhanced T1-weighted image (b) are shown. All three reviewers interpreted this non-mass enhancement (NME) as segmental distribution, with a clustered ring ( arrow ). Hypointense areas ( arrowheads ) were also pointed out by Reviewers 1 and 2 but were not indicated by Reviewer 3. No metastasis was seen in the histopathological analysis of biopsied sentinel lymph nodes.

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Acknowledgment

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