Teaching Case

A 48-year-old premenopausal woman presented with unilateral spontaneous serohematic left nipple discharge for 12 months, painless. She had a healthy child, having breast fed for 2 months. She denied relevant past medical history, daily medications, allergies, or family history of cancers.

At examination, left nipple was hypertrophied, with hemorrhagic single-pore discharge.

Breast mammography and ultrasound were initially unremarkable. No previous breast exams were performed. Cytologic analysis of the nipple discharge revealed only benign cells including normal duct cells without atypia, histiocytes, and scarce inflammatory cells.

Subsequent galactography (7 months later) revealed a lobulated retroareolar filling defect extending into the nipple, measuring 16x8 mm (Figure 1). At breast inspection a protruding bright pink mass was visible in the nipple (Figure 2).

Magnetic Resonance Imaging (Figure 3) showed a well-defined mass located in the left nipple area, with intense, rapid, and early enhancement and wash-out (kinetic curve type III). There were no other abnormalities.

A new ultrasound revealed a slightly hypoechoic and hypervascular mass (Figure 4), submitted to biopsy, whose results suggested a papilloma without atypia.

The lesion was surgically excised. Specimen analysis revealed proliferation with papillary and occasionally pseudoglandular configuration, with thin branched fibrovascular axis, lined by epithelium without atypia (Figure 5). Immunohistochemical staining with p63 highlighted the preserved mioepithelial layer.

Background

Intraductal papillomas are benign tumours originated from lactiferous ducts epithelium, with an incidence of 2-3% in women. Those in the subareolar ducts are usually solitary, larger, and more frequent in perimenopause. Peripheral lesions from the terminal duct-lobular unit tend to be multiple, smaller, occur in younger ages and are associated with higher risk of atypia and carcinoma.[1,2]

Clinical Perspective

Clear or bloody nipple discharge is the typical manifestation, due to fibrovascular stalk twisting.[1,3]

Unilateral single-duct serohematic/hemorrhagic discharge is considered pathological and may be secondary to benign lesions such as papilloma, ductal ectasia, fibrocystic changes, or carcinoma.[4]

Imaging Perspective

When visible on mammography, intraductal papilloma appears as a round well-defined subareolar mass, that may be surrounded by a radiolucent halo and have calcifications in 25% of cases.[1,5] On galactography they appear as well-defined mural-based filling defects with smooth or lobulated contours.[2]

At ultrasound, they may present as well-defined solid intraductal nodules, often with duct dilatation, or as predominantly solid lesions within the duct. On Doppler, they show marked vascularization with a branching pattern arising from a highly vascular central core.[1,2,5]

Although sensitive, MRI has low specificity for diagnosing papillary lesions, being iso/slightly hypointense to the fibroglandular tissue on T1-weighted images and iso/slightly hyperintense on fat-saturated T2-weighted images. The patterns described include a small oval-shaped nodule partially filling the duct, a larger irregular mass completely filling the duct, or a solid or cystic mass attached to the duct wall and protruding outward.[1,2, 5-7] Enhancement patterns include homogenous, heterogeneous, and rimlike, frequently with wash-out. [6,8]

Differential diagnosis includes papillary or ductal carcinomas, which may share clinical and imaging features [9]. Histopathologic analysis is therefore crucial for the diagnosis, revealing proliferation of the ductal epithelium surrounded by myoepithelial cells and fibrovascular stroma with a central vessel.[1,4,10]

Outcome

Intraductal papillomas have been associated with an increased risk of atypia and malignancy, which is higher with peripheral ones.[2,11]

Surgery remains the gold standard in cases with atypia or coexisting malignancy. Without atypia, the need for excision remains controversial, supported by the risk of overlooked areas of atypia or carcinoma, whose incidence may reach 20%.[4,12] Local recurrence is reported as low as 2.4%.[8]

Vacuum-assisted core excision is a minimally invasive alternative for small benign lesions.[13]

Take Home Message / Teaching Points

Intraductal papillomas are benign but clinical and imaging findings may overlap with carcinomas.

Pathological confirmation is necessary.

Surgical excision is the gold standard in cases with atypia or coexisting malignancy.