Answer
Answer
In contrast to IDP (S/P ST), papillary DCIS usually has more delicate fibrovascular cores and is frequently involved by a clonal-appearing epithelial proliferation with mild to moderate cytologic atypia (see the following images). Most distinctively, however, papillary DCIS does not have a myoepithelial layer (see the 3rd and 6th images below). Immunostaining, therefore, can be useful in distinguishing between these 2 lesions. Many find it helpful to use a cytoplasmic marker, such as calponin or smooth muscle actin (SMA), along with the nuclear marker p63 (see Immunohistochemistry). It should be noted that occasional, scant expression of myoepithelial markers may be identified in papillary DCIS. This should not be taken as strong evidence of a benign papilloma if other features of the lesion favor papillary DCIS.
Pathology of small, peripheral intraductal papillomas. Papillary ductal carcinoma in situ (DCIS) (40×).
Pathology of small, peripheral intraductal papillomas. Papillary ductal carcinoma in situ (DCIS) (200×). Several fibrovascular cores show delicate branching, and the epithelium shows moderate cytologic atypia.
Pathology of small, peripheral intraductal papillomas. Papillary ductal carcinoma in situ (DCIS) (400×). Note the delicate fibrovascular cores and moderate cytologic atypia of the overlying epithelium. The epithelial cells directly abut the fibrovascular core, with no intervening myoepithelial layer (arrow).
Pathology of small, peripheral intraductal papillomas. Papillary ductal carcinoma in situ (DCIS) (40×).
Pathology of small, peripheral intraductal papillomas. Same papillary ductal carcinoma in situ (DCIS) as in the previous image (100×).
Pathology of small, peripheral intraductal papillomas. Same papillary ductal carcinoma in situ (DCIS) as in the previous two images (400×). The epithelial cells are moderately atypical and lie directly against the fibrovascular core without an intervening myoepithelial layer (arrow).
Cytokeratin (CK) expression also differs between IDP (S/P ST) and papillary DCIS in that CK5/6 and CK14 show stronger staining in IDP (S/P ST) than in papillary DCIS .
In a series by Tan et al, using a predetermined immunohistochemical cutoff score, the investigators were able to differentiate papillary DCIS from benign papilloma using CK5/6 and CK14 with a sensitivity of 95% and 85%, respectively, and a specificity of 86.8% and 94.3%, respectively. [22] The immunohistochemical score utilized percentage of cells stained multiplied by staining intensity, and both myoepithelial cell and epithelial cell staining was included in the evaluation. [22]
Tan et al's findings are similar to CK5/6 expression differences found between UDH and DCIS. [23, 24, 25, 26] However, it must be recognized that myoepithelial cells frequently express CK5/6 and CK14, and the staining differences between papilloma and papillary DCIS may largely be a result of the myoepithelial component of papilloma, and thus, they may not reflect differences in epithelial cytokeratin expression between IDP (S/P ST) and papillary DCIS.
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Media Gallery
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Pathology of small, peripheral intraductal papillomas. Comparison of the risk of developing invasive breast cancer (IBC) in patients with multiple papillomas relative to patients with a solitary papilloma.
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (40×). The fibrovascular core in this example shows extensive branching.
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) as in the previous image (200×). The fibrovascular core is lined by a layer of columnar epithelium. A layer of flat, pale myoepithelial cells is present between the epithelium and the fibrovascular core (arrow).
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (200×). This image shows slightly more complex branching than the sample seen two images ago.
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (100×) with dense fibrovascular core.
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (100×) within a cystic space.
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (200×) within a cystic space. Note the extensive branching of the fibrovascular core. Tissue folding artifact is present at the top of the image.
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (200×) within a cystic space.
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (400×) as in the previous image. Myoepithelial cells (arrows) are present beneath the epithelial layer.
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (100×). This example may represent two IDPs (S/P ST) or a single one involving a tortuous, dilated terminal duct-lobular unit (TDLU).
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (200×) as in the previous image. Myoepithelial cells are identified (arrows).
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (100×) within a cystic space. This papilloma is attached to the cyst wall by a relatively narrow base.
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (400×) as in the previous image. There is an abundant, hyperplastic-appearing proliferation of myoepithelial cells beneath the epithelium.
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (100×) involved by a usual ductal hyperplasia (UDH)-like epithelial proliferation.
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (200×) as in the previous image. A usual ductal hyperplasia (UDH)-like epithelial proliferation involves the IDP (arrow).
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Pathology of small, peripheral intraductal papillomas. Solid small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (100×).
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (400×) as in the previous image. The fibrovascular core branches are tightly packed. Myoepithelial cells (arrows) are identified beneath the epithelium. This example also has central calcification.
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Pathology of small, peripheral intraductal papillomas. Solid small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (40×).
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (200×) as in the previous image. At higher power, this IDP has an adenomalike appearance. Myoepithelial cells (arrowhead) can be seen beneath the epithelium.
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Pathology of small, peripheral intraductal papillomas. Mild usual ductal hyperplasia (UDH) with a micropapillary pattern (400×).
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Pathology of small, peripheral intraductal papillomas. More pronounced usual ductal hyperplasia (UDH) with a micropapillary pattern (200×).
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Pathology of small, peripheral intraductal papillomas. Usual ductal hyperplasia (UDH) (200×). This example consists of a benign epithelial proliferation that fills a considerable fraction of the duct lumen. The left aspect of the photomicrograph has vaguely papillary features (arrow).
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Pathology of small, peripheral intraductal papillomas. Usual ductal hyperplasia (UDH) (200×). This example shows a benign epithelial proliferation involving a fibrovascular process (arrow). The lesion consists primarily of proliferative epithelium, and the fibrovascular process shows no convincing branching.
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Pathology of small, peripheral intraductal papillomas. Usual ductal hyperplasia (UDH) (200×). This example consists of a proliferation of benign epithelium involving a fibrovascular process. The epithelial proliferation comprises the majority of this lesion, and the fibrovascular process shows no branching. Although this was diagnosed as UDH, it should be recognized that this lesion has compelling features of both UDH and small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]), and distinguishing between these two lesions in this case is somewhat artificial.
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Pathology of small, peripheral intraductal papillomas. Small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) involved by an abundant usual ductal hyperplasia (UDH)-like epithelial proliferation (arrow) (100×).
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (200×) as in the previous image. In this field, the lesion has the appearance of a common IDP (S/P ST).
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Pathology of small, peripheral intraductal papillomas. Same small, peripheral intraductal papilloma (IDP) (small/peripheral subtype [S/P ST]) (200×) as in the previous two images. This field shows the IDP (S/P ST) (black arrow) and the abundant usual ductal hyperplasia (UDH)-like proliferation (blue arrow) that involves it. Although this lesion was diagnosed as IDP (S/P ST), it should be recognized that it has strong features of both UDH and IDP (S/P ST), and strict distinction between these lesions is somewhat artificial in this case.
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Pathology of small, peripheral intraductal papillomas. Papillary ductal carcinoma in situ (DCIS) (40×).
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Pathology of small, peripheral intraductal papillomas. Papillary ductal carcinoma in situ (DCIS) (200×). Several fibrovascular cores show delicate branching, and the epithelium shows moderate cytologic atypia.
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Pathology of small, peripheral intraductal papillomas. Papillary ductal carcinoma in situ (DCIS) (400×). Note the delicate fibrovascular cores and moderate cytologic atypia of the overlying epithelium. The epithelial cells directly abut the fibrovascular core, with no intervening myoepithelial layer (arrow).
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Pathology of small, peripheral intraductal papillomas. Papillary ductal carcinoma in situ (DCIS) (40×).
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Pathology of small, peripheral intraductal papillomas. Same papillary ductal carcinoma in situ (DCIS) as in the previous image (100×).
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Pathology of small, peripheral intraductal papillomas. Same papillary ductal carcinoma in situ (DCIS) as in the previous two images (400×). The epithelial cells are moderately atypical and lie directly against the fibrovascular core without an intervening myoepithelial layer (arrow).
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Pathology of small, peripheral intraductal papillomas. Papillary apocrine metaplasia (100×). The cells have abundant pink cytoplasm. The papillary processes have no fibrovascular cores in this example.
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Pathology of small, peripheral intraductal papillomas. Same papillary apocrine metaplasia as in the previous image (200×).
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Pathology of small, peripheral intraductal papillomas. Myoepithelial cells are highlighted by p63, which has a nuclear staining pattern (400×).
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Pathology of small, peripheral intraductal papillomas. CD10 highlights the myoepithelial cells in this image (400×). Note the staining is cytoplasmic, in contrast to the nuclear staining seen with p63 in the previous image. Calponin would show a similar staining pattern.
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Pathology of small, peripheral intraductal papillomas. Smooth muscle actin (SMA) highlights the myoepithelial cells (400×). Note the cytoplasmic staining.
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Pathology of small, peripheral intraductal papillomas. Cytokeratin (CK) 8/18 highlights the luminal epithelial cells overlying the myoepithelial layer (400×).
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