Encapsulated Papillary Carcinoma of the Breast: Imaging Features with Histopathologic Correlation

Abstract

Encapsulated papillary carcinoma (EPC) is a rare, clinically indolent breast malignancy most common in postmenopausal women. Absence of myoepithelial cells at the periphery is a characteristic feature. Mammographically, EPC typically presents as a mostly circumscribed, noncalcified, dense mass that can have focally indistinct margins when there is associated frank invasive carcinoma. Ultrasound shows a circumscribed solid or complex cystic and solid mass, and occasional hemorrhage in the cystic component may produce a fluid-debris level; the solid components typically show intense washout enhancement on MRI. Color Doppler may demonstrate a prominent vascular pedicle and blood flow within solid papillary fronds. Encapsulated papillary carcinoma can exist in pure form; however, EPC is often associated with conventional ductal carcinoma in-situ and/or invasive ductal carcinoma, no special type. Adjacent in-situ and invasive disease may be only focally present at the periphery of EPC and potentially unsampled at core-needle biopsy. In order to facilitate diagnosis, the mass wall should be included on core-needle biopsy, which will show absence of myoepithelial markers. Staging and prognosis are determined by any associated frankly invasive component, with usually excellent long-term survival and rare distant metastases.

Introduction

Papillary carcinoma (PC) is a histologic subtype of breast carcinoma characterized by a malignant proliferation of epithelial cells supported by arborescent fibrovascular cores (1). Papillary carcinomas can be invasive or noninvasive (papillary ductal carcinoma in-situ [DCIS]) and can exist in localized, mass-forming variants such as encapsulated papillary carcinoma (EPC) and solid PC, with or without frank invasion, and DCIS. Encapsulated papillary carcinoma, also referred to as intracystic PC, is an uncommon breast malignancy representing less than 2% of all breast cancers (2). Encapsulated papillary carcinoma most often occurs in postmenopausal Caucasian women, with a median age at diagnosis of 67 years (2,3), and, though rare, is the second most common breast cancer in males (after invasive ductal carcinoma [IDC], not otherwise specified) (4). Clinically, EPC can present symptomatically as a palpable mass or bloody or serosanguinous nipple discharge, or it may be detected at screening mammography. Imaging typically shows a dense, circumscribed mass (1,2,5) or focally indistinct margin. These tumors are characterized by nonaggressive biological behavior, with low rates of local recurrence, axillary and distant metastases, and excellent long-term survival (2,3). Encapsulated papillary carcinoma has traditionally been managed with wide local excision (6). Breast-conserving surgery remains the mainstay of treatment, with increasing use of adjuvant hormonal and radiation therapy (2,3).

Radiologic Findings

Papillary carcinomas are located in the central portion of the breast in nearly 50% of patients (5). Mammographically, EPC commonly manifests as an equal- or high-density mass with a round or oval shape (Figures 1–4) (7–9). Margins are circumscribed in nearly 50% of cases but may be focally indistinct in areas of invasion (Figures 1 and 4) (7–9). Spiculated margins are infrequent unless there is frank invasion resulting in desmoplastic reaction. Calcifications may be associated with EPC but are relatively uncommon, reported in 4/31 (13%) cases of EPC in one series (8). When present, both pleomorphic and coarse heterogeneous calcification morphologies have been described (7–9).

Sonographically, EPC presents as a hypoechoic solid mass (Figure 4) or complex cystic and solid mass, with one or more mural nodules consisting of papillary fronds projecting into the central cystic component (Figures 2 and 3) (9). Margins of EPC are usually circumscribed (Figure 3). Focally indistinct and irregular margins have been described in the setting of associated invasive carcinoma (Figure 4) (2,7). In their review of EPC, EPC with invasion, and invasive PC, McCullouch et al (10) found no distinct mammographic or sonographic features to differentiate these pathologic subtypes of papillary tumors. Internal septations and posterior enhancement may be associated with the cystic component of EPC (Figure 2) (7,9,10). An echogenic rim is usually absent. Color Doppler imaging may show a large feeding vessel as well as vascularity within the solid mural nodule(s) (Figures 1 and 3) (9). Layering echogenic debris representing hemorrhage can be seen within the cystically dilated space secondary to hemorrhagic infarction of the papillary projections or ruptured capillaries in the cyst wall and may manifest as a fluid-debris level on ultrasound or MRI (Figure 2) (7,9).

On MRI, EPC can appear as an enhancing complex cystic or multicystic lesion with a solid central component (Figure 2) (11). Intrinsic T1 hyperintensity may be seen within the cystic component of EPC due to areas of hemorrhage (Figure 2) (11). After intravenous administration of gadolinium-based contrast material, the thickened wall of the cystically dilated duct, septa, and mural nodules of EPC demonstrate marked enhancement with washout kinetics (Figures 1 and 2) (11). Both homogeneous enhancement (Figure 1) and heterogeneous enhancement (Figure 2) of the solid components of the tumor have been reported (7,11). Triple-receptor-negative IDC, hematomas, and fat necrosis may display peripheral nodularity or thick internal septations and may mimic EPC (7). Lack of flow on Doppler imaging or lack of enhancement on MRI may help to differentiate benign entities from EPC (7) or triple-negative IDC.

Pathologic Findings

Histopathologically, EPC is characterized by delicate papillae lined with a monotonous population of neoplastic epithelial cells supported by thin fibrovascular stalks forming a circumscribed expansile mass (Figures 1 and 3) surrounded by a thick external fibrotic capsule (1,5,12). Hemorrhage often exists within the cystic space(s) (5). Encapsulated papillary carcinomas typically demonstrate low- or intermediate-grade nuclei and a low mitotic index (12,13). Ninety percent (1268/1405) of cases of EPC from a large cancer registry in the United States were estrogen receptor positive and 82% (1121/1370) demonstrated progesterone receptor expression (2). Human epidermal growth factor receptor 2 (HER-2) expression is exceedingly rare; in two series, all 70 cases of EPC with available immunohistochemistry results lacked HER-2 expression (1,12).

The absence of a complete myoepithelial cell layer at the periphery of EPC is a characteristic finding and can be confirmed by absence of immunohistochemical staining with myoepithelial markers, including p63, smooth muscle actin, calponin, and smooth muscle myosin heavy chain (Figure 1) (1,5,13). It is prudent to utilize more than one marker, as compressed stromal myoepithelial cells and vascular walls will also express these markers. In order to distinguish EPC from an atypical papillary lesion, the wall of the mass should be targeted at core-needle biopsy. Papillary lesions are often diagnostically challenging for the pathologist; across 600 pathologists in the UK National Health Service, two EPC cases were recognized as malignant by 92% of pathologists (14). A core-needle biopsy diagnosis of an atypical papilloma (papilloma with atypical ductal hyperplasia) or atypical papillary lesion merits excision, as such lesions are upgraded to DCIS or invasive carcinoma in about 37% of cases (Figure 2) (15).

Controversy exists in the literature as to whether to classify EPC as an indolent invasive carcinoma or an in-situ malignancy (1,5,13). The lack of myoepithelial cells at the peripheral stromal interface of these lesions has led some authors to consider EPC an invasive carcinoma (1). Others believe EPC represents in-situ malignancy, as these lesions demonstrate contiguous collagen type IV immunoreactivity, suggesting that they are confined within an intact basement membrane (13).

When frank invasion is associated with EPC, the invasive component is almost always IDC (5). Entrapped neoplastic epithelial cells within the fibrous capsule may be misinterpreted as invasive carcinoma (16). Ductal carcinoma in-situ associated with EPC is typically of a low or intermediate nuclear grade, with a cribriform or micropapillary pattern (16). In one series, the mean size of EPC was reported as 1.8 cm (range, 0.6–5.0 cm), and the mean size of invasive disease was 0.3 cm (range, 0.1–1.2 cm) (12); EPC size ranging up to 9.0 cm was reported in another series (1).

Discussion

Given its indolent nature, EPC has traditionally been staged and treated as in-situ disease unless frank invasion is evident outside of the fibrous capsule in the surrounding stroma (3). While EPC can exist as an isolated lesion, adjacent DCIS has been reported in up to 73% of cases and IDC in 48%–60% of cases (3,12). Only the frankly invasive component is considered as part of the tumor size for staging (5,16). Core-needle biopsy may fail to demonstrate invasive disease associated with EPC because the central, solid component of the mass is often targeted (17), whereas the invasive malignancy is often focally present at the periphery of the lesion. Therefore, when a diagnosis of EPC is made on core-needle biopsy, an occult, unsampled invasive malignancy needs to be excluded by submitting the entire lesion for histopathologic examination at the time of excision (13).

No evidence-based guidelines exist for the treatment of EPC. Both breast-conserving surgery and mastectomy have been used in the treatment of EPC, with a majority of patients undergoing breast-conserving surgery in recent series (2,3,6,12). Patients undergoing lumpectomy and mastectomy have been shown to have equivalent survival (2). In patients who undergo breast-conserving surgery, survival is improved in those who receive surgery with radiation compared with patients who receive surgery alone (2). Given the high rate (> 90%) of estrogen receptor positivity of these tumors, adjuvant endocrine therapy with either tamoxifen or aromatase inhibitors is often used, particularly in cases with associated DCIS or IDC (2,12).

No consensus exists regarding the use of axillary staging procedures in EPC. Sentinel lymph node biopsy (SLNB) has been advocated for cases of EPC only with frank invasion, as the incidence of lymph node involvement in pure EPC is exceedingly low, with few cases reported in the literature (5,6). Others suggest SLNB should be considered in all patients, including cases of pure EPC (2,3,12).

Encapsulated papillary carcinoma has a favorable prognosis, with low rates of local recurrence, axillary and distant metastases, and excellent long-term survival even when associated with invasive disease (2,3,12). A recent review of 2649 patients with EPC from a large cancer registry in the United States showed that approximately 89% of patients presented with clinically in-situ or stage I disease, with an extremely low incidence (< 1%) of distant metastases at the time of presentation (2). At 10-year follow-up, overall survival rates in pure EPC and EPC associated with invasive cancer, relative to age-matched controls, have been reported as 96.8% and 94.4%, respectively (P = 0.18) (3).

Funding

None declared.

Conflict of Interest Statement

Dr Berg receives research support from Koios Medical, Inc.

References