DJ Complex - Infiltrate
The anatomic and histologic characteristics of the nipple-areolar complex make this breast region special. The nipple-areolar complex can be affected by abnormal development and a wide spectrum of pathological conditions, many of which have unspecific clinical and radiological presentations that can present a challenge for radiologists. The nipple-areolar complex requires a specific imaging workup in which a multimodal approach is essential. Radiologists need to know the different imaging modalities used to study the nipple-areolar complex, as well as their advantages and limitations. It is essential to get acquainted with the acquisition technique for each modality and the spectrum of findings for the different conditions. This review describes and illustrates a combined clinical and radiological approach to evaluate the nipple-areolar complex, emphasizing the findings for the normal morphology, developmental abnormalities, and the most common benign and malignant diseases that can affect this region. We also present a diagnostic algorithm that enables a rapid, practical approach to diagnosing condition involving the nipple-areolar complex.
DJ Complex - Infiltrate
The nipple-areolar complex is a region of the breast that has unique characteristics. It is composed of different cells and specific tissues whose main function is to facilitate the drainage and secretion of breast milk during lactation . A wide variety of abnormal conditions can affect the nipple-areolar complex, including developmental abnormalities, benign processes (e.g., inflammation, infection, tumors), and invasive and noninvasive cancers [2,3,4,5].
Many of these conditions have nonspecific clinical and radiological presentations that can delay diagnosis, so evaluating the nipple-areolar complex represents a challenge for radiologists. A detailed history and clinical examination are essential to guide the radiological management of the nipple-areolar complex. Recognizing the different clinical signs that can manifest in the nipple-areolar complex (e.g., skin involvement, pathological nipple discharge, retraction, inversion, palpable mass, etc.) is the first step in ensuring effective radiological management.
Imaging studies play an important role in diagnosing nipple-areolar complex conditions. Since this is a mobile, superficial region, it requires a specific approach to imaging evaluation. A meticulous radiological technique is fundamental to avoid artifacts and pitfalls. Furthermore, a multimodality approach is essential. The retroareolar region is difficult to evaluate in mammograms, so disease often goes undetected. For this reason, other techniques such as ultrasound (US) and even magnetic resonance imaging (MRI) are necessary to reach the diagnosis.
Lastly, it is very important to predict tumor involvement in the nipple-areolar complex before surgery. On the one hand, knowledge of nipple-areolar complex involvement is fundamental for staging disease (prognosis); on the other hand, thanks to improvements in breast-conserving techniques, it can be extremely helpful in planning the surgical management of breast cancer [6, 7].
In this review, we use a combined clinical/multimodal imaging approach for the nipple-areolar complex to describe and illustrate the singularities of the radiological techniques, the normal morphology, developmental abnormalities, and the main benign and malignant diseases. We discuss the characteristics of the different imaging techniques and provide guidance on how to avoid artifacts and pitfalls. Finally, we present a diagnostic algorithm for a rapid, practical approach to imaging to help ensure effective diagnosis.
The nipple-areolar complex is the pigmented area in the most prominent part of the breast where the lactiferous ducts draining the 15 to 20 lobes of the mammary gland converge . These lobes are oriented radially toward the nipple, and each lobe is made up of several lobules (Fig. 1) . Each lobule has a lactiferous duct that in turn branches and ends in the terminal ductal lobular unit (TDLU), which is the functional unit of the breast gland [8,9,10]. In the subareolar region, the ducts expand to form the lactiferous sinus . The ducts then drain through 5 to 9 orifices in the nipple .
In the 12th through the 16th weeks of gestation, the mesenchymal cells differentiate into smooth muscle in the areola and nipple [9, 11]. Between the 32nd and 40th weeks, parenchymal differentiation results in the development and pigmentation of the nipple-areolar complex .
The congenital absence of the nipple-areolar complex (athelia) is usually accompanied by the absence of breast tissue (amastia) [2, 17]; more rarely, the nipple is present but the mammary gland is absent (amazia) . Underdevelopment of the breast is called hypoplasia . Sometimes, these anomalies are found together with other developmental anomalies and can even form part of syndromes, such as Poland syndrome .
For the evaluation of the retroareolar area, mammography is less sensitive than ultrasound, partly owing to the greater density of this complex anatomic region and partly owing to technical difficulties due to the mobility of this part of the breast [21, 22].
Ultrasound is very useful in the study of the nipple-areolar complex. In addition to being widely available and not requiring ionizing radiation, ultrasound provides good spatial resolution of this superficial region, making it possible to characterize small lesions in the retroareolar region (especially in dense breasts). Ultrasound is also used to guide percutaneous biopsies .
Physiological uptake of contrast material in the nipple-areolar complex can manifest in different ways (Fig. 12). A thin symmetrical ring of enhancement is usually seen in both breasts; sometimes enhancement is asymmetrical in the early phase, becoming symmetrical in later phases . In a recent study of 530 normal nipples in 265 asymptomatic women, Gao et al.  described three areas of enhancement in subtracted T1-weighted images of the nipple-areolar complex acquired on a 3T scanner and their correlation with pathology findings: (a) superficial linear enhancement (SLE); (b) nonenhancing zone (NEZ); (c) internal nipple enhancement (INE).
Physiological enhancement in the nipple-areolar complex. Axial contrast-enhanced T1-weighted spoiled gradient-echo (subtracted) images show various degrees of enhancement in a normal nipple, including none (a), mild symmetric enhancement (b), intense symmetric enhancement (c), a thin symmetric ring of enhancement (d), and asymmetric early enhancement with symmetric late enhancement (e)
The nipple is everted in 75% of women, flat in 23%, and inverted in 2% . MIP images are very useful for assessing the morphology and symmetry of the nipple-areolar complex. On postcontrast images, the nipple should be hypointense or isointense to the enhanced parenchymal tissue in the background .
Pathological enhancement in the nipple-areolar complex. A 71-year-old woman. Axial contrast-enhanced T1-weighted spoiled gradient-echo (subtracted) images show asymmetric irregular nodular early enhancement (a) that is maintained in late phases (b) secondary to involvement by invasive ductal carcinoma. Irregular-shaped masslike enhancement in the middle third of the junction of the outer quadrants in the right breast with linear uptake and segmental distribution to the nipple-areolar complex, compatible with an intraductal component (arrows)
First described by Haagensen , mammary duct ectasia is a benign process characterized histologically by dilated ducts, variable degrees of periductal inflammation, and progressive fibrosis . Ductal ectasia can occur at any age, although it is most common after 50 years of age . Ectasia predominantly affects the ducts in the retroareolar region, bilaterally and symmetrically. Patients may be asymptomatic (most commonly) or have nipple retraction, secretion, or a palpable subareolar nodule . By definition, the duct measures greater than 2 mm in diameter and greater than 3 mm in the ampullary portion [8, 13]. Duct ectasia can be visible on mammograms, especially in predominantly fatty breasts. It manifests as radiodense tubular structures that converge in the nipple-areolar complex (Fig. 18). The presence of benign-appearing calcifications in the dilated subareolar ducts is a common mammographic finding .
Periductal mastitis is a suppurative inflammatory process that occurs mainly in non-lactating premenopausal women . It is characterized by periductal inflammation with an infiltrate consisting predominantly of plasma cells . Its etiology is uncertain, although it could be related to bacterial infection and obstruction of the subareolar ducts . Risk factors include smoking, obesity, and diabetes .
Subareolar abscess. Photograph of a 42-year-old woman with a painful erythematous palpable areolar mass in her left breast with mild involvement of the adjacent skin (a). Synthesized 2D mammogram shows marked skin thickening of the nipple-areolar complex without other underlying findings (b). Ultrasound shows a heterogeneous hypoechogenic intradermal collection compatible with an abscess (c). Fine-needle aspiration was able to drain the collection completely (purulent material), and the patient was prescribed antibiotics and follow-up (d, e)
Ductal carcinoma in situ is considered a precursor that might develop into invasive cancer. By definition, it is a noninvasive malignant cellular proliferation contained within a duct by the basement membrane . Generally, ductal carcinoma in situ is detected on screening mammograms in asymptomatic patients; these lesions can involve the nipple-areolar complex, in most cases by intraductal extension.
In cases involving the nipple-areolar complex, the most common clinical manifestation is unilateral nipple retraction and distortion of the areola (Fig. 36). It is important to differentiate between inversion and retraction of the nipple. Inversion refers to the complete invagination of the nipple, which is mostly symmetrical and physiological. Retraction refers to focal inversion of the nipple-areolar complex and is asymmetrical and acquired. Both inversion and retraction can have benign or malignant causes; the time course and the presence of underlying disease are important . 041b061a72