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Resolving a global challenge in breast imaging: Efficacy of contrast-enhanced digital mammography in global asymmetry
*Corresponding author: Krishna Sai Chitta, Department of Radiology, Sri Ramachandra Medical Centre, Chennai, Tamil Nadu, India. krishnasaichitta@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Chitta K, Dev B, Gnanavel H, Kharat AS, Noronha GP. Resolving a global challenge in breast imaging: Efficacy of contrast-enhanced digital mammography in global asymmetry. Case Rep Clin Radiol. doi: 10.25259/CRCR_176_2025
Abstract
Global asymmetry is defined as asymmetry involving more than one quadrant of the breast without an associated mass, suspicious calcifications, or architectural distortion. While often benign, its diffuse nature frequently leads to diagnostic dilemmas, necessitating the exclusion of malignancies. This case series reviews four patients presenting with global asymmetry as vague areas of suspicious heterogeneity on conventional mammography, where initial assessment through mammography and ultrasound led to categorization as breast imaging-reporting and data system (BI-RADS) 3 or 4, raising suspicion for malignancy. To resolve these diagnostic ambiguities, all four patients subsequently underwent contrast-enhanced digital mammography (CEDM). The CEDM-subtracted images consistently demonstrated no enhancement in the regions of asymmetry, reflecting the definitive absence of neoangiogenesis. This confirmed the benign nature of the asymmetry, and consequently, the BI-RADS categories for all patients were revised to BI-RADS 2. Although a biopsy was ultimately performed in one case upon the patient’s strong request, the histopathology confirmed benign fibroglandular tissue, underscoring the technique’s utility. Hence, due to its very high negative predictive value for eliminating neoangiogenesis and the probability of malignancy, CEDM can be used as a crucial problem-solving tool in cases of indeterminate global asymmetry.
Keywords
Breast biopsy
Breast imaging reporting and data system
Contrast-enhanced digital mammography
Global asymmetry
Negative predictive value
INTRODUCTION
Global asymmetry is defined as an asymmetry involving more than one quadrant of the breast without an associated mass, suspicious calcifications, or architectural distortion.[1]Although it is a benign entity, it can mimic diffuse infiltrating cancers, such as invasive lobular carcinoma (ILC).
Initial imaging, including a mammogram and targeted ultrasound (USG), may often give inconclusive results.[2,3] This may lead to the lesion being categorized as breast imaging-reporting and data system (BI-RADS) 3 or 4A, in turn leading to unnecessary biopsies. Contrast-enhanced digital mammography (CEDM) is an advanced technique that combines standard digital mammography with intravenous iodinated contrast to highlight neoangiogenesis, which is associated with malignancy.[4,5] Multiple studies state that using CEDM significantly improves diagnostic accuracy compared to digital mammography alone, especially in women with dense breast tissue.[6,7] This case series demonstrates how the absence of enhancement on CEDM has led to the elimination of suspicion of carcinoma in cases with global asymmetry.
CASE SERIES
Case 1: The incidental screening finding (the index case)
A 71-year-old female came for a routine screening mammogram which showed multiple irregular, indistinct high-density areas in both breasts. Targeted USG showed heterogeneously hypoechoic areas in places. Based on mammogram and USG findings, the BI-RADS 4A category was assigned. CEDM was performed, which showed no evidence of early post-contrast enhancement in both breasts. There was an ill-defined area of subtle enhancement in the upper quadrant of the right breast in mediolateral oblique view, in the delayed phase done after 8 mins of contrast injection; however, this is non-significant as it is delayed enhancement and can be seen in normal fibroglandular tissue. Based on the CEDM, the diagnosis was revised to global asymmetry and was downgraded to BI-RADS 2. The patient was advised to continue with routine annual screening. However, the patient was apprehensive and wanted to get a biopsy done, hence an USG-guided core needle biopsy was performed, targeting a pocket of heterogeneous parenchyma in the left breast, and the histopathology result came as benign breast tissue, thus proving that CEDM can be used to effectively avoid unnecessary biopsies in cases of global asymmetry with no early post-contrast enhancement [Figure 1].
Case 2: Post-menopausal female with breast tenderness
A 42-year-old female presented with tenderness of the breasts. Mammogram revealed asymmetric, prominent glandular tissue in the upper central and outer quadrants of the left breast and in the upper outer quadrant of the right breast. Targeted USG showed pockets of prominent fibroglandular tissue in places. The BI-RADS 3 category was assigned based on the initial mammogram and USG findings. CEDM was performed to rule out any probability of malignancy; it showed no enhancement in either breast; hence, the case was downgraded to BI-RADS 2 [Figure 2].
Case 3: Asymmetry on post-operative follow-up
A 63-year-old with a history of fibroadenoma excision in the right breast came for post-operative follow-up. Mammogram showed post-operative changes as a subtle architectural distortion and contour deformity in the upper quadrant of the right breast corresponding to the scar site. In addition, asymmetric areas of increased density were seen in the upper central and outer quadrants of the left breast and the upper central quadrant of the right breast. USG performed, showing ill-defined, heterogeneously hypoechoic areas. BI-RADS 4A category was assigned owing to the imaging features seen on the mammogram and USG. CEDM was performed to evaluate these vague heterogeneous areas and the scar site. CEDM revealed no enhancement at the scar site and no enhancement in areas of doubt in either breast; thus, the case was also downgraded to BIRADS 2 [Figure 3].
Case 4: Screening recall solved with CEDM
A 60-year-old female was recalled following a camp mammogram, which showed a few dense pockets of asymmetric fibroglandular tissue in the right upper outer quadrant and left upper outer and inner quadrants. Targeted USG showed an ill-defined hypoechoic area with posterior acoustic shadowing corresponding to the dense pocket of fibroglandular tissue seen in the right upper outer quadrant on mammogram; no vascularity was evident on color Doppler. Based on initial mammogram and USG imaging findings, the BI-RADS 4A category was assigned, CEDM was performed, and it showed absolutely no enhancement in either breast, leading to a downgrade to BIRADS 2 [Figure 4].
RESULTS
In all four patients presenting with global asymmetry as vague areas of heterogeneity, CEDM provided definitive information related to neoangiogenesis, which is one of the key features of a suspicious lesion, resolving the diagnostic dilemma encountered on conventional imaging techniques such as mammogram and USG.[2,7] The most important feature in all four cases was the absence of contrast enhancement in the region corresponding to the mammographic and sonographic abnormality. This demonstrates the high negative predictive value (NPV) of CEDM in this specific diagnostic entity.[8,9]This finding led to a change in the final management course of the patients, as they were downgraded to BIRADS 2 (benign), thereby avoiding unnecessary biopsies.[10]
DISCUSSION
Table 1 and 2 Global asymmetry poses a diagnostic challenge as its imaging appearance may sometimes overlap with that of infiltrating diffusely involving malignant etiologies, ILC, making it difficult to distinguish from benign entities, such as inhomogeneous involution of glandular tissue (breast density) with increasing age.[1,3] Involution of breast parenchyma usually occurs from the lateral to medial quadrant and lower to upper quadrants; this pattern is also reflected in the asymmetric breast parenchyma observed in these four cases. In all four cases presented, the ambiguity created by conventional imaging (mammography and USG) led to biopsy recommendation under standard BI-RADS protocols, as they were categorized as BI-RADS 4A or 4B.[2] However, the information provided by CEDM – no post-contrast enhancement indicating the absence of tumor neoangiogenesis – served as a definitive imaging marker for ruling out malignancy, as malignant lesions typically show early contrast uptake.[4,5] The non-enhancing finding on CEDM has been reported to have a high NPV, approaching 100% in some texts, allowing for safe avoidance of invasive procedures.[8,9]
| S. No. | Age (years) | Presenting complaint/history | Initial imaging findings on MG and USG | CEDM finding | Final assessment and outcome |
|---|---|---|---|---|---|
| Case 1 | 71 | Routine screening | MG: Multiple irregular, indistinct, high-density areas of asymmetric breast parenchyma. USG: pockets of prominent fibroglandular tissue. BI-RADS 4A. | No significant enhancement. | Downgraded to BI-RADS 2. However, biopsy was done on the patient’s request, which showed benign fibroglandular tissue on histopathology. |
| Case 2 | 42 | Postmenopausal breast tenderness | MG and USG: Pockets of asymmetric and prominent glandular tissue. BI-RADS 3 | No enhancement. | Downgraded to BI-RADS 2. |
| Case 3 | 63 | Post-operative follow-up (fibroadenoma excision) | MG: post-operative changes; Areas of increased density on USG: heterogeneously hypoechoic areas. BI-RADS 4A | No enhancement. | Downgraded to BI-RADS 2. Biopsy avoided. |
| Case 4 | 60 | Screening recall | MG: Dense pockets of fibroglandular tissue. USG: Ill-defined hypoechoic area with posterior shadowing. BI-RADS 4A | No enhancement. | Downgraded to BI-RADS 2. Biopsy avoided. |
CEDM: Underwent contrast-enhanced digital mammography, BI-RADS: Breast imaging-reporting and data system, MG: Mammogram, USG: Ultrasound
| Differential diagnosis | Differentiating feature on CEDM/ultrasound |
|---|---|
| Invasive lobular carcinoma | Early enhancement with rapid washout in the delayed phase on CEDM, whereas global asymmetry shows no enhancement.[1,4] |
| Invasive mammary carcinoma | Multicentric and multifocal carcinomas can appear as asymmetric densities on mammogram; however, they show early intense enhancement with washout on delayed phase in CEDM. |
CEDM: Underwent contrast-enhanced digital mammography
CONCLUSION
This case series reinforces CEDM as a problem-solving imaging tool in cases of global asymmetry where conventional imaging is equivocal or suspicious, thereby preventing unnecessary biopsies.
TEACHING POINTS
CEDM can be used to troubleshoot cases of global asymmetry with suspicious or equivocal features on mammogram and/or ultrasound, to confidently rule out malignancy
If there is no enhancement in CEDM, the case can be downgraded to BI-RADS 2 and kept on routine annual follow-up.
MCQs
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What feature does CEDM primarily indicate to exclude malignancy confidently?
Tissue stiffness
Calcium density
Tumor neoangiogenesis
Fat content
Key: C
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Which type of contrast agent is used for intravenous administration in contrast-Enhanced Digital Mammography (CEDM)?
Gadolinium-based
Iodinated contrast agent
Barium sulfate
Non-iodinated contrast agent
Key: B
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Global asymmetry commonly mimics which type of breast cancer?
Ductal Carcinoma in situ (DCIS)
Invasive Lobular Carcinoma (ILC)
Invasive ductal carcinoma
Mucinous Carcinoma
Key: B
Author contributions:
KSC: Conceptualization, methodology, software, validation, formal analysis, investigation, resources, data curation, writing - original draft, visualization; BD: Validation, formal analysis, investigation, resources, data curation, writing -review & editing, visualization, supervision; HG: Formal analysis, data curation, writing - review & editing, supervision; ASK: Investigation, data curation, writing-review & editing; GPN: Validation investigation writing - review & editing.
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understands that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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