Female, 85 years old, presents with right nipple itching and ulceration for some weeks. At physical examination, the nipple was eroded with red granulation surface and a little hematic exudate (Figure 1). The breast skin was otherwise normal. There were not palpable breast masses or enlarged axillary lymph nodes.
The patient was clinically diagnosed with Paget’s disease (PD) of the breast, without associated palpable mass. As recommended for these cases, imaging diagnostic workup included mammography, ultrasound and magnetic resonance imaging (MRI).
Mammography revealed a mammary pattern of scattered areas of fibroglandular density (pattern ACR-b). There was no significant nipple asymmetry, neither suspicious microcalcifications nor masses that could reveal an associated breast carcinoma (Figure 2). Complementary breast ultrasound was unremarkable, showing only mild peri-areolar skin thickening on the right breast.
MRI revealed a mammary pattern ACR-b, with minimal parenchymal enhancement. An extensive (6,5 x 1,7 cm of longitudinal and transversal diameters) segmental non-mass enhancement was present at the transition of the outer quadrants and lower outer quadrant (LOQ) of right breast, non-continuous with nipple-areolar complex (Figure 3). This was suspicious for ductal carcinoma in situ (DCIS). Right nipple showed marked enhancement, in relation to the diagnose of PD. No breast masses or enlarged lymph nodes were apparent.
In order to confirm the diagnosis of DCIS, an ultrasound-guided parenchymal core biopsy was directed to an area of tinny heterogeneity observed at LOQ during second-look ultrasound. Histological results confirmed DCIS. Total mastectomy with sentinel lymph node biopsy was proposed and accepted by the patient.
Pathologic analysis of the surgical specimen confirmed PD of the nipple associated with DCIS of high histologic grade in an extent of 35mm, without metastatic lymph node disease.
The extent of DCIS found at pathology was significantly smaller than what was assumed at MRI. Several factors can contribute to this. First non-mass enhancement at MRI can be due to different pathologic processes, including inflammatory changes, that can overlap with DCIS and give a spurious overestimation of tumour extent. In the other hand, some concerns exist about the realistic correlation of the small section histology technique with the real lesion size.
Paget’s disease is a relatively rare disease, accounting for about 0,5-5% of the total number of breast cancers, that occurs in the nipple and areola. Underlying DCIS of high histologic grade or invasive carcinoma (IC) is present in more than 90% of cases.
Clinically PD presents as eczema or psoriasis-like lesion of the nipple, with ulcers, haemorrhage and erythema. Symptoms include nipple pruritus, pain or burning sensation. The course of the PD is slow, without healing for a long time. In advanced cases, adjacent areola and surrounding skin may also be involved.
Delayed diagnosis is common since inflammatory dermatoses are often considered before PD. However, any unilateral nipple abnormality in an adult woman should be first considered malignant, and nipple biopsy performed[4,6].
Although PD is frequently associated with parenchymal breast cancer, about 60% of cases present without a palpable mass. Of these, up to two-thirds have a normal mammography as well. In this subset of patients, DCIS is more frequent than IC.
At diagnosis, ultrasound is recommended as an adjunct to mammography. In PD even subtle changes, such as parenchymal heterogeneity or hypoechogenicity, should be valorized. Changes of the nipple-areola complex, like skin thickening, are usually present.
MRI has the highest sensitivity to detect parenchymal disease, such as DCIS or IC, being particularly useful to establish extent and disease centricity. MRI is the most sensitive imaging modality for the detection of DCIS, that most commonly manifests as non-mass enhancement (NME). For this reason, MRI is being increasingly recommended for PD cases with normal clinical examination, mammography or ultrasound, frequently revealing occult parenchymal neoplastic changes[10,11]. Nipple and areolar enhancement are also evident on MRI.
Patients without palpable masses associated with PD have better prognosis, compared to those with palpable masses. Patients with ipsilateral axillary lymph node enlargement have worse prognosis.
PD treatment varies according to associated parenchymal disease (radiotherapy and chemotherapy), however, surgery is always performed. Options include breast-conserving surgery, extended resection or total mastectomy.
Written informed patient consent for publication has been obtained.
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