A case of giant complicated intraductal papilloma of breast on MRI and literature review

Abstract

Background

With the increasing use of image‐guided biopsy, more breast intraductal papillomas are found than ever. Most intraductal papillomas are small, ranging from several milimeters to 2 cm.

Case

We described a case of giant intraductal papilloma of breast in a 19‐year‐old girl with nipple bloody discharge and rapid growth. Magnetic resonance imaging diagnostic evaluation and pathologic correlation along with review of relevant literatures are documented. The lesion was characterized by presence of mixture of cystic and solid component with cystic component occupying a large space. The solid component showed morphologic, kinetic, and diffusion weighted imaging features suggestive of malignancy. Infarction with no enhancement was noted. Cystic compartments contained hemorrhage with fluid‐fluid level formation. The patient undertook lumpectomy.

Conclusion

For a giant breast tumor with mixed solid and cystic component, intraductal papilloma should be considered in the differential diagnosis.

1. INTRODUCTION

With the use of image‐guided biopsy, more clinically occult breast intraductal papillomas (IDPs) are found. As the neoplasm arises in lactiferous duct, it is usually detected with a small size. Giant IDPs were rarely reported in literatures.1, 2 Herein, we presented a case of giant IDP, focusing on its magnetic resonance imaging (MRI) appearances and correlation with histopathology.

Informed consent of the patient and the approval from the institutional ethical committee have been obtained for this report.

2. CASE REPORT

A 19‐year‐old girl incidentally found a small painless mass in her right breast in January 2010. Since then, the mass appeared to increase in size over time. During the period, she had several episodes of spontaneous bloody nipple discharge. She reported no family history of breast or ovarian cancer. On physical examination, a firm mobile mass measuring about 12 × 8 cm was palpable in the right breast, extending from the upper to the lower aspect. A slight asymmetry was noticed on the upper aspect, and bloody nipple discharge was expressed from the nipple.

Precontrast T1‐weighted image showed a mass with heterogenous high signal intensity (Figure 1), which was measured 10.5 × 6.0 × 5.0 cm. After contrast agent administration, the lesion demonstrated enhanced solid component and unenhanced cystic component. The solid nodule was located on the anterior cyst wall measuring 3.2 × 4.6 × 2.5 cm, in which an irregular unenhanced area was seen on the postcontrast image, suggesting infarction. Reconstructed sagittal MRI image revealed “8” shape of the entire lesion (Figure 2). Kinetic analysis of the solid component revealed washout curve. Sagittal T2‐weighted image with fat suppression showed moderately high signal intensity of the solid component and several fluid‐fluid levels in the cystic compartments (Figure 3) with low signal in the dependent portions. Diffusion‐weighted imaging revealed restricted water diffusion in the solid component.

Figure 1.

Axial precontrast T1WI: A giant mass was seen in the right breast with heterogeneous high signal intensity in compartments on pre‐contrast enhanced magnetic resonance imaging

Figure 2.

Sagittal postcontrast T1WI: The lesion consisted of cystic and solid component with “8” shape. Nonenhanced area in the solid component represented infarction

Figure 3.

Sagittal postcontrast T2WI: moderately high signal nodule and fluid‐fluid levels

The patient underwent lumpectomy without implant placement. Histologically, an extremely dilated cystic space was seen with marked surrounding fibrosis and inflammatory infiltrate. The solid component showed a fibrovascular network in the center covered by outer epithelial and myoepithelial cells (Figure 4) with frond formation in the cystic space. The epithelia demonstrated usual hyperplasia, which connected with each other to form complex tubular and cribriform structures. Evident infarction, hemorrhage, and focal mild epithelial atypia were observed. A narrow stalk was seen on a single section that attached the solid tumor to the ductal wall. Multiple fibrotic septations were present in the cystic space.

Figure 4.

Pathology (hematoxylin and eosin stain, ×200): arborizing fronds of tissue with well‐developed central fibrovascular cores covered by epithelial cells and overlying myoepithelial cells within a duct. Evident hemorrhage was seen

Although the patient was young, focal mild epithelial atypia were found in the case. Hence, long‐term follow‐up was recommended. Now, the patient is disease‐free after nearly 8 years.

3. DISCUSSION

Papillary lesions in breast include IDP with or without atypical ductal hyperplasia (AH), IDP with in situ or invasive carcinoma, in situ or invasive papillary carcinoma, encapsulated papillary carcinoma, and solid papillary carcinoma.3 As the most common papillary lesion, IDP can be divided into central type (in the subareolar region) and peripheral type (in the terminal ductal lobular unit) based on location. Although nipple discharge and incidentally palpated nodules are the most common symptoms for patients with central IDPs, patients usually show no clinical manifestations before imaging detection, especially those with peripheral type.

Intraductal papilloma has been reported in a wide range of age, from adolescents to older people.1, 2 Majority of cases present during the fourth and fifth decade of life.4

Pathologically, breast IDP is characterized by fibrovascular core covered by overlying epithelia and myoepithelia, forming papillary fronds in the duct. Epithelia in IDP may undergo changes, such as usual, atypical, in situ, or invasive malignant transformation. Apocrine or squamous metaplasia and calcifications can be found sometimes.5 In this case, no calcifications were identified radiographically and pathologically. Other complications were noted, such as hemorrhage and infarction. It seemed that the giant size was a predisposing factor to development of complications.

In general, IDPs do not have pathognomonic appearances on conventional image, ranging from typically benign to malignant. On ultrasound, they are often seen as an intraductal nodule with or without ductal dilatation, intracystic nodule, or a solid pattern with the intraductal mass completely filling the duct.6, 7 On mammography, most cases are negative,8 although a few cases may demonstrate positive signs, such as small well‐defined nodules, asymmetric density, or clustered calcifications.5, 6, 9, 10 Most IDPs are less than 2 cm in size. Giant IDP, as our case, is rarely reported. Intraductal papillomas with size >5 cm available in English literature were summarized in Table 1.2, 9, 11, 12, 13 Among them, the largest IDP described was 15 cm in size, reported by Kihara. In literatures, most IDPs were examined by ultrasound and/or mammography. But for giant IDPs, MRI were used more often as shown in Table 1.

Table 1.

Large intraductal papillomas (>5 cm) from case reports

First Author	Year	Age (year)	Nipple Discharge	Size (cm)	Duration of Disease (year)	Imaging Modality	Epithelia	Surgery
Roy	1985	59	No	15.0	2	NAa	Normal	Mastectomy
Kavolius	2001	39	Yes, bloody	11.0	2	Mammography Ultrasound MRI	Normal	Lumpectomy
Kihara	2010	46	No	15.0	1	Mammography MRI	Normal	Lumpectomy
Fatemi	2015	80	Yes, bloody	13.0	2	Mammography Ultrasound MRI	Normal	Mastectomy
Vieira	2014	54	No	7.5	NA	Mammography Ultrasound MRI	DCISb	Mastectomy with SLNDc

^aNA, not available.

^bDCIS, ductal carcinoma in situ.

^cSLND, sentinel lymph node dissection.

The classic features of IDPs on MRI are a small enhanced nodule in a dilated duct,8, 14 but other imaging appearances can be confusing. These confusing findings include nodules without perceptible ductal dilatation, lesions with mixtures of solid and cystic component as this case, nonmass‐like enhancement of ductal pattern, as well as ductal dilatation with no enhanced nodules (occult IDPs). Studies by Zhu concluded that a low early‐phase enhancement rate and evolution of the MRI enhancement pattern from homogeneous or heterogeneous enhancement to rim enhancement is more likely to suggest IDPs.14 Occasionally, nodules without ductal dilatation may exhibit suspicious morphology, such as irregular shape, spiculated margins, and heterogeneous internal enhancement. As for kinetics, the time‐to‐intensity curve in IDPs shows washout, plateau, and persistent pattern in a descending order, posing a challenge for diagnostic radiologists. Combination of suspicious morphologic and kinetic features may lead to the misdiagnosis of IDP as primary breast cancer, which is described as “sheep in a wolf skin.”15 Furthermore, some authors also found increased 18F‐FDG uptake on positron emission tomography/computed tomography imaging scan, which can be explained by strong expression of glucose transporter‐1.16 When such IDPs are encountered, biopsy or resection seems to be the only choice. In our case, the key MRI feature was a mass within a large cystic portion (so‐called intracystic papilloma). The cyst might be formed by secretion and hemorrhage following duct obstruction; the neoplasm itself remained relatively small. All giant IDPs with MRI in Table 1 showed the similar radiologic appearances.

Hemorrhage is common during growth of IDPs as the neoplasm is so hypervascular that mild trauma may lead to bleeding, creating high‐signal‐intensity of various degrees on T1WI, and liquid‐liquid levels on T2WI in cystic compartments, as in our case. Infarction is less common than hemorrhage. In our case, the large cystic component made the solid nodule more prone to mobility, torsion on the stalk, and consequent infarction. Rapid growth and large size might also contribute to insufficient blood supply and infarction in the case. On MRI, no enhancement was identified in the infarcted area. The dilatation of the associated duct and cyst formation could be explained by hemorrhage and secretion following ductal obstruction. The thickened enhanced cyst wall was attributed to the chronic inflammation and fibrosis. It was postulated that, similar to mammary ductal ectasia, with increasing pressure, leaked secretory material gave rise to the inflammatory process.17

Focal AH was found in the present papilloma. The relative risk of invasive carcinoma for women with IDPs containing AH is >4× that of papillomas without AH within or surrounding the papilloma.18 Now most IDPs are diagnosed on core needle biopsy (CNB). Despite its advantages over surgical excision, CNB in IDPs has sampling error and underestimation. Significant changes, such as AH, in situ, or invasive cancer, may be missed on CNB. Previous investigators have reported that the upgrade rate of IDP to malignancy on surgical excision ranged from 2% to 10%.10, 19, 20 Therefore, some recommend clinical follow‐up and imaging surveillance, while others insist resection. Core needle biopsy proven benign IDPs with radiologic‐pathologic concordance are upstaged to malignancy infrequently,21 where observation is appropriate. And some studies found that patient age, a clinically palpable mass, lesion size, and calcification are significant predictors for upstage.5, 8, 10, 22 However, except 1 case in Table 1, most demonstrated no AH or DCIS, including 2 largest tumors. To our knowledge, no studies are available on the performance of MRI to predict upstaging of IDPs on excision. Further studies need to be conducted to investigate the predictive value of MRI on IDP upstaging.

Giant IDP should be differentiated from phyllode tumor (PT) because both entities have large size and rapid growth. Intraductal papilloma is more often associated with large cystic spaces. The cystic portion of IDP is attributed to lactiferous duct obstruction and hemorrhage, secretion retention, while cystic change in PT is due to degeneration, necrosis, and intracanalicular growth pattern. Therefore, solid component of IDP appears attached to cyst wall, while cystic spaces are intermingled with solid area in PT. Additionally, cleft‐like cystic spaces are more frequent in PT. Other entities that should be distinguished include cyst with a blood clot or encapsulated carcinoma. The former can be confidently diagnosed based on the specific signal of blood on MRI and no enhancement in clot; the latter is difficult to distinguished by imaging or cytologic examinations, but the combination assays of epidermal growth factor receptor 2 and carcinoembryonic antigen in cyst fluid have proved encouraging23 preoperatively.

The standard care for giant papilloma is excision. No deformity was observed after lumpectomy in this case. However, some patients may take mastectomy due to severe stretching of the skin and possible postsurgical deformity as shown by Fatemi and Roy.

It is reported that24 patients diagnosed with IDPs with atypia have a risk of developing breast cancer with 5‐year and 8‐year rates of 13.0% and 18.4%, respectively. Data regarding follow‐up outcome are limited in giant IDPs. Despite its size and mild AH, the patient is disease‐free after nearly 8‐year follow‐up.

4. CONCLUSION

In conclusion, such a giant IDP is uncommon. In our patient, its size and suspicious MRI findings gave clues to malignancy. This case expands our differential diagnosis for large breast masses, especially for that with a large cystic portion, and highlights the importance of considering the benign papilloma of the breast.

CONFLICT OF INTEREST

There are no conflicts of interest to declare in connection with this article.

AUTHOR'S CONTRIBUTIONS

All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Methodology, S.W. and J .L.; Resources, S.W.; Writing ‐ Original Draft, S.W.; Writing ‐ Review & Editing, J.L.; Visualization, J.L.; Supervision, J.L.

Wang S, Lou J. A case of giant complicated intraductal papilloma of breast on MRI and literature review. Cancer Reports. 2018;1:e1136. 10.1002/cnr2.1136