Papillary Lesions of the Breast: MRI, Ultrasound, and Mammographic Appearances

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1 Women s Imaging Pictorial Essay Eiada et al. Imaging Papillary Lesions of the reast Women s Imaging Pictorial Essay Downloaded from by on 01/27/18 from IP address Copyright RRS. For personal use only; all rights reserved FOCUS ON: Riham Eiada 1 Jennifer Chong 1 Supriya Kulkarni 2 Frank Goldberg 1 Derek Muradali 1 Eiada R, Chong J, Kulkarni S, Goldberg F, Muradali D Keywords: breast, mammography, MRI, papillary lesions, ultrasound DOI: /JR Received September 3, 2011; accepted after revision November 8, Department of Medical Imaging, St. Michael s Hospital, 30 ond St, Toronto, ON, Canada M5 1W8. ddress correspondence to D. Muradali (muradalid@smh.ca). 2 Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women s College Hospital, Toronto, ON, Canada. JR 2012; 198: X/12/ merican Roentgen Ray Society Papillary Lesions of the reast: MRI, Ultrasound, and Mammographic ppearances OJECTIVE. The purpose of this article is to describe the different imaging appearances of benign and malignant papillary lesions of the breast as well as to point out potential errors of interpretation that can lead to misdiagnosis. CONCLUSION. There is a wide spectrum of appearances of papillary lesions of the breast on MRI, ultrasound, and mammography. This variable appearance of papillary lesions makes differentiation of benign from malignant pathologies difficult on imaging, and tissue sampling is usually warranted. T he differentiation of benign from malignant papillary tumors on imaging is often difficult because of the wide spectrum of appearances of these lesions on MRI, ultrasound, and mammography. In addition, some benign lesions and certain nonpapillary tumors may show imaging features that overlap with papillary lesions, further adding to the diagnostic challenge for the radiologist. n overwhelming number of terms and classifications are used to categorize these lesions. Papillary lesions may be classified as solitary intraductal papillomas, multiple intraductal papillomas, atypia-ductal carcinoma in situ (DCIS) within a papilloma, micropapillary DCIS, and papillary carcinoma. The objective of this article is to show the different imaging appearances of both benign and malignant papillary lesions of the breast as well as to point out potential errors of interpretation that can lead to misdiagnosis. Solitary and Multiple Intraductal Papillomas Solitary intraductal papillomas are usually located centrally or in the retroareolar region and, when symptomatic, present with bloody or clear nipple discharge. Traditionally, these lesions were most commonly observed in symptomatic perimenopausal patients. However, with the more widespread use of breast ultrasound, solitary intraductal papillomas are being detected with increasing frequency in younger asymptomatic patients. Multiple intraductal papillomas arise from the terminal ductal lobular units and therefore are usually peripherally located in the breast. They are less common than solitary intraductal papillomas and rarely associated with a nipple discharge, and they typically present as a palpable mass. Unlike solitary papillomas, multiple intraductal papillomas are usually associated with atypia, DCIS, or malignancy. Some studies have shown that in patients with multiple papillomas, up to 80.4% may have either coexisting atypical lesions (atypical ductal hyperplasia (DH), atypical lobular hyperplasia, lobular carcinoma in situ) or neoplastic lesions (DCIS, invasive carcinoma) [1]. On mammography, small papillomas can be occult, particularly when located in the retroareolar regions because of the breast density and relative lack of compression in that area. Larger lesions may appear as a round- or oval-shaped mass with well-circumscribed margins [2]. Up to 25% of solitary papillomas are associated with benignappearing mammographic calcifications [3]. On galactography, intraductal papillomas appear as well-defined mural-based filling defects with smooth or lobulated contours. ubbles of air inadvertently injected into the ductal system during galactography may erroneously be interpreted as intraductal papillary lesions. On ultrasound, intraductal papillomas may appear as well-defined solid nodules or mural-based nodules within a dilated duct (Figs. 264 JR:198, February 2012

2 Imaging Papillary Lesions of the reast Downloaded from by on 01/27/18 from IP address Copyright RRS. For personal use only; all rights reserved 1 3). On color Doppler imaging, flow may be detected within the papilloma arising from a vascular feeding pedicle [2]. Occasionally, papillomas within a focally dilated duct may be misinterpreted as intracystic nodules. However, meticulous scanning will usually show the adjacent nondilated feeding duct. There is minimal literature describing the MRI features of papillomas [4, 5]. On MRI, small intraductal papillomas may be occult whereas larger papillomas may appear as enhancing nodules with or without intraductal components [6]. The enhancement of these nodules may be uniform or irregular with either washout or plateau kinetics, making differentiation from invasive malignancies potentially difficult [5, 7] (Figs. 1 3). Studies have shown that the presence of an intraductal papilloma is associated with an increased risk of developing a breast carcinoma relative to the general population. This risk is higher with multiple papillomas compared with solitary papillomas and extends equally to both the ipsilateral and contralateral breasts [1, 8] (Fig. 4). typia-ductal Carcinoma In Situ Within a Papilloma typia within a papilloma refers to the presence of DH or atypical lobular hyperplasia. DH within a papilloma is defined by the presence of a uniform population of neoplastic cells in an area 3 mm, whereas DCIS is defined by the presence of such cells in an area > 3 mm. DH within a papilloma may represent a precursor lesion and is regarded as an increased risk factor for the development of breast cancer [1, 2]. Multiple terminologies have been used to describe papillomas with an atypical cell population. The term atypical papilloma has been used to describe papillomas containing less than one third of neoplastic cells, and the term carcinoma arising in a papilloma to describe those containing between one third and 90% of neoplastic cells. Other authors believe that once a neoplastic population of cells, regardless of extent, is present in a papilloma, the term in situ papillary carcinoma should be used [1]. Papillomas associated with DH or DCIS may appear identical to benign papillomas on all imaging modalities. lthough indeterminate calcifications within a papilloma could suggest the presence of DCIS, similar microcalcifications may also be observed with infarction, hemorrhage, or fibrosis [2] (Figs. 5 and 6). The role of MRI in evaluating these papillomas is uncertain [9]. However, in papillomas with DCIS, MRI may be useful in defining the extent of DCIS involvement in the surrounding tissues. Micropapillary Ductal Carcinoma In Situ Micropapillary DCIS is a rare subset of DCIS that tends to involve the ductal system extensively. It is more often associated with multicentricity, microinvasion, and a higher recurrence rate after excision when compared with other types of DCIS. The cause is unclear but may be related to micropapillae detaching and rolling through the duct to colonize other areas of the breast [10]. On mammography, micropapillary DCIS may be occult or only a portion of the lesion may show pleomorphic calcifications. On ultrasound, the regions involved with DCIS may be occult; may present with an ill-defined hypoechoic mass; or, if calcifications are present, show bright echogenic foci. On MRI, micropapillary DCIS may show no enhancement regardless of grade or extent or may show non-masslike enhancement [10, 11] (Fig. 7). Papillary Carcinoma Papillary carcinomas account for less than 2% of all breast carcinomas [1], are most commonly detected in postmenopausal women [12], and arise in the retroareolar region in almost 50% of patients. They are subdivided into solid, intracystic without invasion, intracystic with a focus of invasion (usually ductal carcinoma), and invasive papillary carcinoma [1]. On mammography, papillary carcinomas are usually round, oval, or lobulated in shape. The margins are most commonly well defined but may be indistinct in areas of invasion [13]. Spiculated margins are infrequently observed because there is usually only minimal surrounding fibrotic reaction [12]. Microcalcifications within the tumor are usually pleomorphic but may occasionally be coarse or stippled in appearance [2]. On ultrasound, papillary carcinomas can present as a hypoechoic solid mass or a complex cyst with septations or mural-based papilliform nodularity [2, 12, 13]. nechoic regions within the mass may denote cystic components or hemorrhage [2, 12] (Fig. 8). Doppler imaging often shows internal vascularity or large feeding vessels [2, 12, 13]. Information is limited regarding the MRI features of papillary carcinomas. On MRI, papillary carcinomas may appear as irregular enhancing nodules or enhancing complex cysts (Fig. 8). However, the morphologic features of papillary carcinomas on MRI as well as their kinetic curves are variable and may overlap with those of benign papillomas. lthough MRI cannot help to definitively diagnose a papillary carcinoma, it can be of value in the preoperative mapping of multiple papillary lesions, thereby facilitating optimal surgical planning [2, 6, 14]. Mimickers of Papillary Tumors oth benign and malignant lesions can mimic a papillary tumor. Inspissated material within a focally dilated duct can have an appearance similar to intraductal papillomas. Hematomas or fat necrosis may show mural nodularity or thick septations, similar to intracystic papillary carcinomas (Fig. 9). The absence of flow in these lesions on Doppler imaging as well as lack of enhancement on MRI often differentiates them from papillary tumors. Malignant nonpapillary tumors with central necrosis or duct extension can mimic papillary carcinomas, requiring tissue sampling for definitive diagnosis (Fig. 10). Conclusion There is a wide spectrum of appearances of papillary lesions of the breast on different imaging modalities. This variable appearance of papillary lesions makes differentiation of benign from malignant pathologies difficult on imaging. Tissue sampling with radiologic-pathologic correlation is usually warranted for diagnosis. References 1. Mulligan M, O Malley FP. Papillary lesions of the breast: a review. dv nat Pathol 2007; 14: rookes MJ, ourke G. Radiological appearances of papillary breast lesions. Clin Radiol 2008; 63: Cardenosa G, Eklund GW. enign papillary neoplasms of the breast: mammographic findings. Radiology 1991; 181: Lorenzon M, Zuiani C, Linda, Londero V, Girometti R, azzocchi M. Magnetic resonance imaging in patients with nipple discharge: should we recommend it? Eur Radiol 2011; 21: Daniel L, Gardner RW, irdwell RL, Nowels KW, Johnson D. Magnetic resonance imaging of intraductal papilloma of the breast. Magn Reson Imaging 2003; 21: Kurz KD, Roy S, Saleh, Diallo-Danebrock R, Skaane P. MRI features of intraductal papilloma of the breast: sheep in wolf s clothing? cta Radiol JR:198, February

3 Eiada et al. Downloaded from by on 01/27/18 from IP address Copyright RRS. For personal use only; all rights reserved 2011; 52: hattarai N, Kanemaki Y, Kurihara Y, Nakajima Y, Fukuda M, Maeda I. Intraductal papilloma: features on MR ductography using a microscopic coil. JR 2006; 186: Carter D. Intraductal papillary tumors of the breast: a study of 78 cases. Cancer 1977; 39: Schell M, Rosenkranz K, Lewis PJ. Role of breast MRI in the preoperative evaluation of patients with newly diagnosed breast cancer. JR 2009; 192: Castellano I, Marchio C, Tomatis M, et al. Micropapillary ductal carcinoma in situ of the breast: an inter-institutional study. Mod Pathol 2010; 23: Lee YS, Mathew J, Dogan E, Resetkova E, Huo L, Yang WT. Imaging features of micropapillary DCIS: correlation with clinical and histopathological findings. cad Radiol 2011; 18: C Fig. 1 Solitary intraductal papillomas in two patients., In 47-year-old woman who presented with palpable mass, ultrasound image shows well-defined oval-shaped nodule (arrow) adjacent to nipple (asterisk)., xial T1 gadolinium-enhanced subtraction MR image in same patient shows heterogeneous enhancement of nodule with well-circumscribed margins (arrow). C, In 40-year-old woman who presented with bloody nipple discharge, ultrasound image shows well-defined nodule (long arrow) in dilated duct (short arrows). D, xial T1-weighted gadolinium-enhanced subtracted MR image in same patient shows lobulated well-defined retroareolar nodule (arrow). 12. Liberman L, Feng TL, Susnik. Case 35: intracystic papillary carcinoma with invasion. Radiology 2001; 219: Schneider J. Invasive papillary breast carcinoma: mammographic and sonographic appearance. Radiology 1989; 171: Tominaga J, Hama H, Kimura N, Takahashi S. Magnetic resonance imaging of intraductal papillomas of the breast. J Comput ssist Tomogr 2011; 35: D 266 JR:198, February 2012

4 Imaging Papillary Lesions of the reast Downloaded from by on 01/27/18 from IP address Copyright RRS. For personal use only; all rights reserved C Fig. 2 Two patients with solitary intraductal papillomas and duct dilation., 58-year-old woman who presented with bloody nipple discharge. Ultrasound image shows hypoechoic nodule (long white arrow) with intraductal extension (short white arrows). Short black arrows mark dilated duct. and C, 62-year-old woman who presented with small palpable lump. Ultrasound image () shows simple cyst (short arrow) with adjacent subtle nodule (long arrow). xial T1-weighted gadolinium-enhanced subtraction MR image (C) shows heterogeneous enhancement of nodule (long arrow) with rim enhancement of adjacent cystic structure, which represents focally dilated duct (short arrow). C Fig. 3 Multiple intraductal papillomas in two patients. and, 46-year-old woman who presented with bloody nipple discharge. Ultrasound image () shows multiple well-circumscribed hypoechoic nodules (arrows) within dilated ducts. sterisk indicates nipple. Corresponding axial T1-weighted gadoliniumenhanced subtraction MR image () shows multiple enhancing retroareolar nodules (arrow). MR image has been cropped to show retroareolar region. C, 48-year-old woman who presented with palpable nodule. Ultrasound image (left) shows multiple muralbased nodules (long arrows) within dilated duct. Color Doppler image reveals vascularity (short arrows) within one of papillomas. JR:198, February

5 Eiada et al. Downloaded from by on 01/27/18 from IP address Copyright RRS. For personal use only; all rights reserved C Fig. 4 Invasive ductal carcinoma occurring in two patients with papillomas., 63-year-old woman who presented with palpable lump and nipple retraction. Mammogram shows two nodules. Retroareolar nodule (short white arrow) corresponds on ultrasound to complex cyst with mural based nodule (long white arrow), which at pathology was sclerosing papilloma. Second more posteriorly located mammographic nodule (short black arrow) corresponds on ultrasound to solid nodule (long black arrow) with irregular margins that was proven at pathology to be invasive ductal carcinoma. and C, 74-year-old woman who presented with brown nipple discharge. xial T1 gadolinium-enhanced subtraction MR image () shows heterogeneously enhancing nodule within right breast (short arrow), which was intraductal papilloma at pathology. Linear enhancement is also seen within left breast (long arrow). Ultrasound image (C) of left breast shows that linear enhancement on MR image corresponds to irregular hypoechoic nodule (arrow) that was proven at pathology to be invasive ductal carcinoma. Fig year-old woman who presented with palpable nodule. Histopathology of nodule showed invasive ductal carcinoma arising from focus of ductal carcinoma in situ within intraductal papilloma., Ultrasound image shows hypoechoic intraductal nodule (long arrows) with ill-defined margins. Proximal duct is dilated (short arrows). sterisk indicates nipple., Galactogram shows multilobulated filling defect (long arrows), which focally expands duct. Proximal duct is dilated (short arrows). 268 JR:198, February 2012

6 Imaging Papillary Lesions of the reast Downloaded from by on 01/27/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old woman who presented with bloody nipple discharge., Galactogram shows intraductal nodule (white arrows) with single fleck of calcification (black arrow)., Follow-up ultrasound shows corresponding solid intraductal nodule (white arrows) with single fleck of calcification (black arrow). Excision showed ductal carcinoma in situ arising in papilloma with extension into surrounding tissues. Fig year-old woman who presented with palpable nodule., Ultrasound image shows complex cystic structure with mural-based nodule (arrow) and intraductal extension (arrowheads)., xial T1-weighted gadolinium-enhanced subtraction MR image shows heterogeneous masslike enhancement (long arrow) and surrounding non-masslike enhancement (short arrows), which was significantly larger than lesion on ultrasound image (). Pathology showed papilloma, as seen on ultrasound, with micropapillary ductal carcinoma in situ in surrounding tissues, as shown by enhancement on MRI. JR:198, February

7 Eiada et al. Downloaded from by on 01/27/18 from IP address Copyright RRS. For personal use only; all rights reserved C E D F Fig. 8 Papillary carcinoma in three patients. and, Solid papillary carcinoma in 48-year-old woman, who presented with palpable breast lump. Ultrasound image () shows hypoechoic solid nodule (arrow). Corresponding axial T1-weighted gadolinium-enhanced subtraction MR image () shows heterogeneous enhancement of nodule with irregular margins (arrow). C and D, Intracystic papillary carcinoma detected in asymptomatic 65-year-old woman. Ultrasound image (C) shows complex cyst with thick muralbased nodules (long arrow) and nodular septation (short arrows). Corresponding axial T1-weighted gadolinium-enhanced subtraction MR image (D) shows heterogeneous enhancement of mural-based nodules (arrows). E G, Multicystic papillary carcinoma in 58-yearold woman, who presented with palpable lump. Ultrasound image (E) shows complex cyst with thick internal septations and solid central component (asterisk). xial T2-weighted MR image (F) shows complex cystic mass containing multiple fluid-fluid levels with extension along duct (arrowheads) to nipple. xial T1-weighted gadolinium-enhanced subtraction MR image (G) shows enhancement of walls of cystic mass and adjacent duct (arrowheads). G 270 JR:198, February 2012

8 Imaging Papillary Lesions of the reast Downloaded from by on 01/27/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig. 9 enign pathologies mimicking papillary lesions., Ultrasound image in 47-year-old woman shows debris (arrows) within dilated duct that has appearance of multiple intraductal papillomas. sterisk indicates nipple., Ultrasound image in 52-year-old woman shows fat necrosis with cystic and solid regions mimicking intracystic papillary lesion. Fig. 10 Tumors mimicking papillary lesions., 34-year-old woman who presented with palpable mass. Ultrasound image shows lobulated well-defined hypoechoic mass (white arrows) with cystic regions (black arrows) and extension in ductal pattern (arrowheads) to nipple (asterisk). Pathology showed this to represent phyllodes tumor with borderline malignancy., 37-year-old woman who presented with palpable nodule. Ultrasound shows well-circumscribed complex cyst (arrows). Pathology showed this to represent medullary carcinoma of breast with central necrosis. JR:198, February