Clinical and imaging characteristics of encapsulated papillary carcinoma: a comparative analysis with intraductal papilloma

Abstract

Objective

Encapsulated papillary carcinoma (EPC) exhibits clinical and imaging characteristics that resemble those of the benign tumor intraductal papilloma (IDP). The differences between these two entities have not been extensively studied. The objective of this study is to evaluate and compare the clinical and imaging features of EPC and IDP.

Methods

A retrospective analysis was conducted using data from 36 patients diagnosed with EPC and 30 patients diagnosed with IDP at a single center between May 2016 and May 2023. Clinical parameters, including patient age and the presence of nipple discharge, as well as imaging parameters such as nodule size, shape, margins, aspect ratio, internal structure, calcifications, posterior acoustic enhancement, blood flow signals, and Breast Imaging Reporting and Data System (BI-RADS) classification, were compared between the two groups.

Results

The mean age of patients with EPC was significantly higher than that of those with IDP (60.39 years vs. 49.27 years, p < 0.01). EPC nodules were larger in size (3.00 ± 2.17 cm vs. 2.11 ± 0.85 cm) and more frequently exhibited a cystic-solid composition (61.11% vs. 36.67%, p < 0.05). Posterior acoustic enhancement was observed in 72.22% of EPCs compared to 40.00% of IDPs (p < 0.01). Additionally, EPCs were associated with a higher incidence of abundant blood flow signals (grade ≥ 2) than IDPs (63.89% vs. 36.67%, p < 0.05). No significant differences were noted in terms of nodule morphology, margins, or BI-RADS classification. Mammographic features, including calcifications, were comparable between the two groups.

Conclusion

This study presents the imaging characteristics of EPC and identifies potential clinical and imaging differences between EPC and IDP. These findings support clinicians in distinguishing EPC from IDP more effectively.

Key points

EPC is a rare form of breast cancer that has been not been researched adequately. This study presents an analysis of EPC with a detailed description of its imaging features.

The imaging characteristics of EPC and IDP shows considerable overlap. A retrospective investigation was conducted to compare both conditions, revealing newly observed differences that have not been previously reported.

Introduction

Breast cancer is the most prevalent malignant condition among women [1]. Encapsulated papillary carcinoma (EPC), previously referred to as intracapsular papillary carcinoma, is a rare subtype of breast cancer, comprising approximately 0.5–1% of all breast tumors [2]. EPC primarily affects middle-aged and older women, although it can occasionally occur in men [3, 4].

According to the 2019 WHO Classification of Tumors, EPC is recognized as a distinct subtype of papillary tumor, characterized by low-grade or minimal invasive potential [5]. Existing literature has predominantly focused on the pathological features, clinical management, prognosis, and related aspects of EPC [6–9].

Clinically, EPC often presents similarly to intraductal papilloma (IDP), a common benign breast tumor, with symptoms such as nipple discharge and palpable breast masses [10]. However, despite these clinical similarities, EPC and IDP differ considerably in terms of treatment approaches and prognostic outcomes [6]. Imaging plays a key role in the early diagnosis and management of breast cancer [11].

However, only a few limited studies have evaluated the specific imaging characteristics of EPC or the methods to distinguish it from other breast lesions [12, 13]. Moreover, the imaging features of EPC frequently overlap with those of IDP, particularly in terms of internal structure, blood flow signals and so on [10, 14]. A clearer understanding of the imaging differences between EPC and IDP is essential for accurate diagnosis and can support more informed clinical decision-making [15].

This study aimed to analyze the clinical and imaging characteristics of EPC and to identify key differences from IDP, thereby contributing to improved differential diagnosis and a deeper understanding of EPC.

Materials and methods

General information

A total of 36 patients with EPC and admitted to the breast department of a medical facility between May 2016 and May 2023 were retrospectively included in this study. For comparison, 30 patients diagnosed with IDP during the same period were randomly selected as the control group through a search of the pathology database of the institution. Diagnoses of EPC and IDP were made in accordance with the WHO Breast Tumor Classification system [16]. Demographic and clinical information, including sex, age, and the presence of nipple discharge, was extracted from medical records.

Inclusion criteria: participants aged 18 years or older, with complete medical records, preoperative breast ultrasound data, having undergone surgical treatment, and a confirmed pathological diagnosis of either EPC or IDP following surgical resection. Patients were excluded if they had incomplete medical records, lacked preoperative imaging data, did not undergo postoperative follow-up, or had a prior history of breast cancer (Fig. 1).

Fig. 1.

Flow chart diagram of the study population

Ethical approval

for the study was granted by the Ethics Committee of the institution (approval number: 2024406). Written informed consent was obtained from all participants.

Methods

Ultrasonography: Preoperative evaluations were conducted using a diagnostic color Doppler ultrasound machine equipped with a linear probe. Participants were arranged in the supine position, and radial scans of both breasts were performed with the nipple serving as the central reference point. Subsequently, the axillary and clavicular regions were examined. Two sonographers, each with more than 10 years of experience, assessed the ultrasound features based on the 2013 Breast Imaging Reporting and Data System (BI-RADS) standards, and they were unaware of the pathological results of the patients.

The documented parameters included nodule size, shape, margins, aspect ratio, internal structure, presence of calcifications, posterior acoustic enhancement, blood flow signal, and BI-RADS classification. Nodule structure was classified as solid if the fluid component accounted for ≤ 10%; otherwise, it was categorized as cystic-solid. Tumor size was recorded as the maximum diameter. Blood flow was graded according to the criteria established by Adler et al., ranging from grade 0 (no detectable blood flow) to grade 3 (extensive network or patchy blood flow signals, or the presence of at least two vessels with clearly defined walls) [17].

Mammography and other imaging: Mammographic evaluations were conducted using craniocaudal and mediolateral oblique positions. All imaging data, including mammography, computed tomography (CT), and magnetic resonance imaging (MRI) (if available), were transferred to the picture archiving and communication system of the medical facility for storage. Two imaging physicians, each with over 10 years of experience, independently reviewed the mammograms using a dedicated mammography monitor, and they were unaware of the pathological results of the patients. Tumor margins, morphology, and calcifications were assessed and categorized according to the 2013 BI-RADS standards. Specific equipment details could not be listed due to the use of multiple ultrasound and mammography devices during the study.

Statistical analysis: Statistical analysis was conducted using SPSS software (version 24.0). Quantitative data are expressed as means ± standard deviations and were compared between groups using the independent sample t-test. Categorical data are presented as percentages and analyzed using the chi-squared (χ²) test or Fisher’s exact test, depending on the data distribution. A value of p < 0.05 was considered statistically significant. Finally, we conducted a post-hoc power analyses using the statistical package G Power (3.1.9.7).

Results

Patient characteristics

All 36 patients in the EPC group were female, with ages ranging from 35 to 83 years and a mean age of 60.39 ± 13.36 years. Among these patients, 3 presented with nipple discharge, while the primary symptom for the remaining 33 patients was the presence of breast lumps. Similarly, all 30 patients in the IDP group were female, with ages ranging from 28 to 76 years and a mean age of 49.27 ± 11.95 years (Fig. 2a). Nipple discharge was reported in 8 patients, whereas the other patients presented primarily with breast lumps as the main symptom.

Fig. 2.

Age distribution and size distribution of EPC and IDP

A statistically significant difference in mean age was observed between the EPC and IDP groups (p < 0.01)(Post hoc power analysis: Power = 94.89%). Furthermore, the incidence of nipple discharge was significantly lower in the EPC group (8.33%) compared to the IDP group (26.67%) (p < 0.05)(Post hoc power analysis: Power = 51.21%).

Ultrasound imaging features

Size and structure

The size of nodules in the EPC group ranged from 0.70 to 12.50 cm, with a mean diameter of 3.00 ± 2.17 cm and a median diameter of 2.30 cm. In the IDP group, nodule sizes ranged from 0.70 to 4.20 cm, with a mean diameter of 2.11 ± 0.85 cm and a median diameter of 2.00 cm (p < 0.01) (Post hoc power analysis: Power = 100.00%) (Fig. 2b).

In terms of nodule composition, 61.11% (22/36) of nodules in the EPC group and 36.67% (11/30) of nodules in the IDP group were classified as cystic-solid, with the remaining nodules categorized as solid (p < 0.05) (Fig. 3). Overall, EPC nodules were significantly larger and more likely to exhibit a cystic-solid composition compared to IDP nodules (p < 0.05).

Fig. 3.

Ultrasound characteristics of EPC

a, The tumor appeared as a solid oval mass with circumscribed margin

b, The tumor appeared as a solid mass with irregular shape, circumscribed margin and abundant blood flow signals

c, the tumor appeared as a solid mass with irregular shape, indistinct margin, multiple lobulated, and several punctate blood flow signals

d, The tumor was cystic-solid with irregular shape, circumscribed margin, and no blood flow signal

e, The mass was almost cystic, with oval shape, circumscribed margin, floating particles and sediment in the cyst, with a small mural nodule of 0.19 cm

f, The tumor was cystic-solid, with oval shape and circumscribed margin. The echo of the cystic part was disorderly with sediment(△), and the mural nodule was irregular in shape with rich blood flow signals(*)

Posterior acoustic enhancement

Posterior acoustic enhancement was detected in 72.22% (26/36) of EPC nodules and 40.00% (12/30) of IDP nodules (p < 0.01) (Post hoc power analysis: Power = 75.18%). This feature was observed in the solid nodules of both groups. Further comparison of posterior acoustic enhancement in solid nodules revealed that solid EPC nodules exhibited significantly greater enhancement than solid IDP nodules (p < 0.05) (Post hoc power analysis: Power = 89.27%). These findings indicate that both solid and cystic-solid EPC nodules demonstrate more prominent posterior acoustic enhancement compared to IDPs.

Blood flow signal

In the EPC group, 23 out of 36 nodules (63.89%) were classified as having blood flow grades of 2 or 3, compared to 11 out of 30 nodules (36.67%) in the IDP group (p < 0.05) (Post hoc power analysis: Power = 59.54%). This indicates that EPC nodules were more likely to exhibit higher-grade (2 or 3) blood flow signals than IDP nodules. However, no statistically significant differences were observed between the two groups regarding nodule shape, margins, aspect ratio, or BI-RADS classification (Table 1).

Table 1.

General characteristics and ultrasound characteristics of EPC and IDP

	EPC(%)	IDP(%)	t/χ2	P
Age (years)	60.39 ± 13.36	49.27 ± 11.95	3.532	0.001
Size (cm)	3.00 ± 2.16	2.11 ± 0.85	2.122	0.038
Nipple discharge
Yes	3(8.33)	8(26.67)
No	33(91.67)	22(73.33)	3.960	0.047
Shape
Oval/round	16(44.44)	12(40.00)
Irregular	20(55.56)	18(60.00)	0.132	0.716
Margin
Circumscribed	26(72.22)	19(63.33)
Indistinct	10(27.78)	11(36.67)	0.596	0.440
Aspect ratio
>1	0(0.00)	3(10.00)
≤ 1	36(100)	27(90.00)	-	0.089
Nodule structure
Solid	14(38.89)	19(63.33)
Cystic-solid	22(61.11)	11(36.67)	3.911	0.048
Calcifications
Yes	3(8.33)	5(16.67)
No	33(91.67)	25(83.33)	-	0.452
Posterior acoustic enhancement
Yes	26(72.22)	12(40.00)
No	10(27.78)	18(60.00)	6.956	0.008
Solid mass with posterior acoustic enhancement
Yes	10(71.43)	6(31.58)
No	4(28.57)	13(68.42)	5.125	0.024
Blood flow grade
0–1	13(36.11)	19(63.33)
2–3	23(63.89)	11(36.67)	4.855	0.028
BI-RADS classification
≤ 4a	22(61.11)	14(46.67)
> 4a	14(38.89)	16(53.33)	1.377	0.241

Mammography and other imaging tests

One patient in the EPC group did not undergo mammography due to the risk of rupture associated with the large size of the tumor and was instead evaluated using CT and MRI (Fig. 4). Among the remaining 35 patients who underwent mammography, 3 had no detectable positive findings, resulting in 32 mammography images available for analysis. In the IDP group, all 30 patients underwent mammography, with 5 indicating no positive findings.

Fig. 4.

Imaging and pathological findings of a 62-year-old female patient with EPC

a, Ultrasound examination reveals a large cystic-solid mass in the left breast, with unclear cystic fluid and irregular solid components. Color Doppler blood flow imaging indicates abundant blood flow signals

b, A CT scan revealed a large low-density mass in the left breast with uneven internal density, unclear boundaries between the cystic and solid components, the skin thickens and depresses locally(white→), and no signs of metastases in the lungs

c, Axial T2-weighted MRI scan reveals a multilocular cystic-solid mass in the left breast with smooth margins and intracystic fluid planes and wall nodules.The skin around the tumor was sunken(white→)

d, Dynamic enhanced MRI scan showed multiple lobed tumors, and multiple significantly enhanced internal papillary prominences of varying sizes and irregular shapes in the capsule(white→)

e, MRI dynamic enhanced sagittal silhouette image shows left breast mass with multiple lobules, and significantly enhanced irregular nodule signals within the capsule.Simultaneous axillary enlargement of lymph nodes (*)

f, Photomicrograph (hematoxylin-eosin stain; original magnification, ×10) demonstrates lightly stained fibrous capsule(black→) and internal papillary prominences(*)

In the mammography, nodules in both groups exhibited varying appearances, including oval/round or irregular shapes, well-defined or poorly defined margins, and occasional calcifications. Most nodules were classified as BI-RADS ≤ 4a (Table 2). No statistically significant differences were observed between the two groups regarding nodule morphology, margins, presence of calcifications, or BI-RADS classification (p > 0.05).

Table 2.

Mammogram characteristics of EPC and IDP

	EPC(%)		IDP(%)	χ2	P
Number		32	25
Shape
Oval/round		15(46.88)	11(44.00)
Irregular		17(53.13)	14(56.00)	0.047	0.829
Margin
Circumscribed		15(46.88)	17(68.00)
Indistinct		17(53.13)	8(32.00)	2.544	0.111
Calcifications
Yes		3(9.38)	4(16.00)
No		29(90.63)	21(84.00)	-	0.687
BI-RADS classification
≤ 4a		25(78.13)	22(88.00)
> 4a		7(21.88)	3(12.00)	-	0.487

Discussion

EPC often presents with clinical and imaging features that are similar to those of IDP, a benign breast tumor. However, the differences between them have not been extensively elucidated. In this study, clinical presentations and imaging characteristics of patients were compared to identify distinguishing features of EPC and IDP. The analysis demonstrated that EPC has a significantly later age of onset compared to IDP (p < 0.01). On ultrasound, EPC nodules tended to be larger and more likely to exhibit cystic-solid structures, posterior acoustic enhancement, and increased blood flow signals, compared to IDP (p < 0.05). These findings help in reducing misdiagnosis and improving differentiation between EPC and IDP.

EPC is a rare subtype of breast cancer, predominantly affecting middle-aged and older women, whereas IDP can occur across a wider age range, from adolescence to old age, with a mean onset age of 40 to 60 years [3, 18, 19].

In this study, most patients with EPC were between 50 and 70 years of age, while patients with IDP were primarily aged 40 to 60 years, a difference that reached statistical significance. This indicates that EPC typically manifests at an older age than IDP. The clinical presentations of EPC and IDP are largely similar, with both conditions commonly involving breast lumps and nipple discharge, typically located beneath the nipple and areola. Axillary lymph node enlargement is infrequent in both conditions [10, 14]20– [22].

In this study, 8.33% (3/36) of patients in the EPC group presented with nipple discharge, which is slightly lower than the 10.6% reported by Xu et al. [23] In contrast, 26.67% (8/30) of patients in the IDP group experienced nipple discharge, a higher incidence than that observed in the EPC group. This indicates that nipple discharge is less common among patients with EPC than among those with IDP.

Data regarding the site of onset were not analyzed in this study due to the difficulty in consistently distinguishing if the mass was located in the central or peripheral zone of the breast.

The size of EPC nodules typically ranges from 0.5 to 12.4 cm, while IDP nodules are generally smaller, measuring from a few millimeters to approximately 2 cm [13, 21, 24]. In this study, EPC nodules were significantly larger than IDP nodules (p < 0.05). The EPC nodules measured between 0.7 and 12.5 cm, consistent with previous findings in the literature, whereas IDP nodules ranged from 0.7 to 4.2 cm. The larger size of IDP nodules observed in this study, compared to earlier reports, are attributed to the inclusion of adjacent dilated breast ducts during ultrasound measurements, potentially inflating the recorded nodule size.

On ultrasound, EPC typically appears as a solid or cystic-solid mass with smooth, well-defined margins. The cystic component often contains flocculent or amorphous deposits [4, 12, 22, 25]. In cases with both cystic and solid components, the cystic portion can vary considerably in size, ranging from minimal to extensive. One or more mural nodules, often lobulated, may protrude into the cystic cavity [26]. Both EPC and IDP nodules can present as solid or cystic-solid masses [27]. However, findings from this study indicate that EPC nodules are more likely to exhibit a cystic-solid composition, while IDP nodules tend to be predominantly solid.

The differing pathological structures of these tumors may explain this variation. EPC is characterized by fragile papillary tumors encased within a thick fibrous capsule, along with the absence of myoepithelial cells [28, 29]. In contrast, IDP is marked by a complex arrangement of epithelial cells without a distinct peritumoral capsule. Additionally, IDPs are often associated with hemorrhage, necrosis, and ductal dilatation, which can lead to the formation of cystic-solid nodules due to fluid accumulation within the ducts [30].

EPC demonstrated more frequent posterior acoustic enhancement than IDP, a finding associated with the higher prevalence of cystic-solid composition in EPC nodules. However, even when presenting as solid masses, both EPC and IDP exhibit posterior acoustic enhancement. In this study, solid EPC nodules depicted this feature more frequently than solid IDP nodules (p < 0.05), possibly due to the presence of a minor cystic component within the EPCs. Further pathological-imaging studies are necessary to confirm this hypothesis. EPCs are characterized by a well-developed fibrous vascular core with a rich blood supply [31].

Color Doppler flow imaging visualizes intratumoral blood flow, which is less frequently observed in IDPs [32]. In this study, 63.89% (23/36) of EPC nodules exhibited abundant blood flow signals (grade ≥ 2) in the solid component, compared to 36.67% (11/30) of IDP nodules. These findings indicate that the solid portions of EPC tumors are more highly vascularized than those of IDP tumors, highlighting the use of color Doppler imaging in assessing tumor vascularity. This assessment may help in distinguishing EPC from IDP in clinical practice.

On mammography, EPC typically appears as a well-defined, non-calcified, oval or round dense mass [12, 22, 33]. In cases of locally invasive diseases, mammography may reveal burr-like margins. However, in this study, no statistically significant differences were found between EPC and IDP with respect to morphology, margins, or the presence of calcifications. This indicates that mammography by itself may not be sufficient to differentiate between the two conditions. Although mammography provides visualization of the size of the tumor and contour from two views, it is limited in its ability to evaluate the internal structure and vascularity of the tumor, which restricts its effectiveness in assessing the biological behavior and invasiveness of EPC. However, mammography remains superior to ultrasound in detecting calcifications [34].

Bonnet et al. reported calcifications in 13% (4/31) of EPC cases, most of which were polymorphic or coarse [25]. In this study, calcifications were detected in 8.33% (3/36) of patients with EPC via ultrasound and in 9.38% (3/32) via mammography. These rates are slightly lower than those reported in literature.

Additionally, the use of advanced imaging techniques such as MRI enhances the diagnostic accuracy for EPC by providing a detailed visualization of tumor characteristics [35]. MRI is particularly effective in assessing the extent of the tumor, detecting wall nodules, and identifying intracapsular hemorrhage. In clinical practice, MRI is used not only for diagnostic purposes but also in treatment planning, helping in the decision-making process for surgical interventions [36].

In conclusion, this study described the imaging characteristics of EPC and identified potential clinical and imaging differences between EPC and IDP. These findings provide valuable insights that may help clinicians in differentiating EPC from IDP. Furthermore, the integration of other imaging modalities, such as MRI, elastography, and contrast-enhanced ultrasound offer more comprehensive data to further delineate the features of EPC and support the development of optimized management strategies for patients with this rare subtype of breast cancer.

There are some limitations in this study. Firstly, this study was conducted in a single center and adopted a retrospective design. This method may introduce selection bias and limit the external validity of the results.Secondly, the sample size of this study is relatively small, which may limit the statistical ability to detect significant differences between the two groups in certain parameters. Post hoc power analysis showed that some results did not reach the expected level of statistical power.Future research should give priority to multi-center collaboration and larger sample sizes to verify our findings and further understand the characteristics and differential diagnosis of EPC.

Abbreviations

EPC

Encapsulated papillary carcinoma

IDP

Intraductal papilloma

BI-RADS

Breast Imaging Reporting and Data System

CT

Computed tomography

MRI

Magnetic resonance imaging

Author contributions

Conception and design of the research: Zhi-long Liu, Qian Zhang Acquisition of data: Juan Chen, Qin Lu, Chao Zhang, Yan-yan Dong Analysis and interpretation of the data: Zhi-long Liu, Qian Zhang Statistical analysis: Juan Chen, Qin Lu Obtaining financing: Li-ping Liu Writing of the manuscript: Chao Zhang, Yan-yan Dong Critical revision of the manuscript for intellectual content: Li-ping Liu All authors read and approved the final draft.

Funding

This work was supported by the National Natural Science Foundation of China (82272026); the Research Project Supported by the Shanxi Scholarship Council of China (2022 − 193).

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the declaration of Helsinki.This study was conducted with approval from the Ethics Committee of Fifth Hospital of Shanxi Medical University (2024.No.406).A written informed consent was obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.