British Journal of Radiology (2004) 77, 1036-1039
© 2004 British Institute of Radiology
doi: 10.1259/bjr/94607773
Usefulness of MRI in detecting occult breast cancer associated with Paget's disease of the nipple–areolar complex
J J Echevarria, MD
1
J A Lopez-Ruiz, MD
1
D Martin, MD
2
I Imaz, MD
3 and
M Martin, MD
4
Section of Breast Imaging of the 1 Department of Radiology, 2 OSATEK MRI, 3 Department of Pathology and 4 Department of Gynaecology, Galdakao Hospital, Barrio Labeaga s/n 48960 Galdakao, Vizcaya, Spain
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Abstract
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MRI allows for the detection of mammographically and clinically occult breast neoplasms. We analysed the ability of MRI to detect occult breast cancer in three patients with Paget's disease of the nipple–areolar complex, proven histologically. In all three cases we observed differences in the morphological and dynamic features of healthy and pathological nipples, and we also found enhancement foci in breast tissue, with suspicious kinetic and morphological characteristics, which in the case of two patients corresponded to ductal carcinoma in situ. The detection and location with MRI of underlying neoplastic foci may be of help in choosing the most reasonable and conservative treatment in these patients.
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Introduction
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Paget's disease of the breast consists of the infiltration of the nipple–areolar complex epidermis by adenocarcinoma cells and accounts for approximately 2% or 3% of breast carcinomas. Clinically, this is seen as an eczematous eruption of the nipple that may be associated with erosion or ulceration [1]. It is often, although not invariably, associated with underlying ductal carcinoma in situ (DCIS), which may also have an infiltrating component [2, 3]. Nevertheless, very often (in some series, reaching 50% of cases), conventional imaging studies do not detect the underlying neoplasia [2, 4, 5] and therefore, traditionally, the treatment of this pathology has been based on mastectomy, occasionally with axillary dissection [1, 5].
In spite of attempts to develop less aggressive treatments, especially for those cases of Paget's disease with normal physical examination and mammograms [3, 6], local recurrence rates represent a restraint to their implementation [7].
As MRI is known to be useful in detecting occult breast neoplasias [8] we have used this examination technique in histologically-confirmed cases of Paget's disease of the nipple–areolar complex, in women with normal physical examination and mammograms, in order to try to locate any associated neoplastic lesion.
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Patients and methods
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We report three women of 67 years, 71 years and 77 years of age, with biopsy-proven Paget's disease.
The women underwent physical examination of the breast and axilla and routine two-view mammmography. Ultrasound examination was not performed at the time. MRI was undertaken with a 1.5 T Siemens Symphony system (Siemens, Erlangen, Germany) using a dedicated breast coil. T1 weighted (repetition time, 556 ms; echo time, 14 ms (556/14)) and T2 weighted (4500/97) transverse turbo spin-echo images were obtained. A dynamic study was carried out (six acquisition sets, acquisition time 60 s) before and five times after intravenous administration of gadolinium-DTPA at a dose of 0.1 mmol kg–1 of body weight, with a fat-suppressed gradient-echo three–dimensional (3D) T1 weighted ((4.5/1.7), flip angle: 12°, section thickness: 1.2 mm) coronal sequence. Lastly, a gradient-echo 3D with water excitation T1 weighted ((26/6.4), flip angle: 30°, section thickness: 0.8 mm) sequence was made. The post-processing procedure included the obtaining of subtraction images, maximum intensity projections (MIP) and multiplanar reconstruction (MPR). Time-intensity curves were plotted for any areas of enhancement, and the evaluation was made according to the percentage of signal intensity increase within the first 2 min after administering the contrast agent relative to the pre-contrast signal intensity, and later, the morphology of the curve was assessed according to the three traditional models: continued enhancement, wash-out or plateau [8].
The nipple–areolar complexes were evaluated in the MRI and a comparative analysis was made of the complexes of both breasts of each patient, as in the case of healthy breasts, these anatomical areas show a clear symmetry in their characteristics [9]. In addition, an assessment was made of the enhancement foci in breast tissue making a note of the place, size and relationship with regards to the nipple in all linear and nodular areas with greater enhancement than the adjoining tissue.
After a period of not more than 30 days counted from the end of the diagnostic process, all three patients were subjected to a mastectomy with axillary dissection. The microscopic analysis of the specimen was made jointly by the radiologist and pathologist in order to attempt to locate adequately in the mastectomy specimens the areas of significant enhancement detected in the MRI scan. Each mastectomy specimen was divided in accordance with the sagittal anatomical plane in sections with an approximate thickness of no more than 20 mm, and afterwards each of the sections was divided into smaller fragments. All of the divisions obtained were identified and classified.
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Results
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All three women had typical Paget's disease of one of their breasts, and in one case a swelling of the skin of the areola and nipple retraction was visible. In none of the three cases could a mass or other suspicious sign of neoplastic disease be detected.
There was no evidence of malignancy on mammography, though one patient had skin thickening, evident clinically.
At MRI, a clear asymmetry with regard to the morphology and enhancement pattern between healthy and pathological nipple–areolar complexes was observed in all three patients (Figure 1
). During the first 2 min after intravenous contrast medium, the pathological complexes showed early enhancement with signal increments between 50% and 100%, while on the healthy sides the signal increment was only 20–30%. Subsequently, the curves adopted a plateau morphology on the pathological sides, while on the healthy sides, progressive enhancement was seen with lower percentage signal increments (Figure 2).
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Figure 1. Maximum intensity projections in axial projection. The left breast demonstrates prominent vascularization and the nipple–areolar complex is seen as an intensely enhanced discoidal mass (arrow), when compared with the contralateral normal side (arrowhead).
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Figure 2. Study of the enhancement of the (a) left and (b) right nipple. Subtraction sequence in coronal projection. The left nipple is enlarged and there is intense early enhancement of 90% during the first 2 min after contrast medium (vertical line on the curve), followed by a plateau. On the right, healthy side, the enhancement curve is progressive and the late enhancement peak reaches approximately 60%.
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In two cases, one of whom was the patient with clinical thickening of the areola, the major lactiferous ducts underlying the nipple were ectatic and demonstrated a continued enhancement pattern. Furthermore, in these two cases, there were ductal-type clumped foci of enhancement with progressive enhancement curves and maximum percentage enhancement of 70–120%, in the deep retroareolar tissue of the pathological breasts (Figure 3). Lastly, in the case in which no retroareolar duct ectasia was observed, two well-defined nodules were detected, both 5 mm diameter and with progressive enhancement curves with late enhancement percentages of nearly 40% (Figure 4).
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Figure 3. Gradient echo water excitation 3D T1 weighted sequence. Thickening of the skin of the areola and nipple and ectasia of the major lactiferous ducts (arrowheads) is observed, as well as clumped linear enhancing foci in deep breast tissue (arrow).
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Figure 4. Multiplanar reconstruction in oblique-lateral projection. Gradient echo fat suppressed 3D contrast enhanced T1 weighted sequence. Two smooth oval homogeneous masses (arrows). Although the characteristics indicated probably benign nodules, the presence of Paget's disease suggested the possibility of two small neoplastic foci.
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In none of these cases were there features suggestive of axillary nodal metastases.
Histopathological analysis of mastectomy specimens demonstrated Paget's disease of the areola and nipple in all three cases. In both cases in which retroareolar duct ectasia was observed, pathological analysis demonstrated the presence of foci of DCIS. Likewise, in the histological analysis of all the sections made of the mastectomy specimens of both patients, foci of DCIS were detected in the areas indicated by MRI. On the other hand, the two well-defined enhancement foci detected in the third case corresponded to fibroadenomas, and in this breast neoplasia was found only at the level of the skin of the areola and nipple. No axillary nodal metastatic disease was found in any of the cases.
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Discussion
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Mammary Paget's disease is an infrequent neoplastic process and until recently, it was thought that the neoplastic alteration of the nipple was almost invariably associated with underlying ductal carcinoma [2]. Since clinical examination and mammography are normal in 10% to 50% of cases [1, 2, 4, 5], and do not demonstrate the underlying neoplasia, the traditional treatment consisting of mastectomy with axillary dissection continues to be widespread [1, 5]. Nevertheless, it is now known that some cases of Paget's disease are confined to the skin of the nipple–areola without underlying neoplastic foci [3]. In such cases, more conservative treatments, consisting of the removal of the nipple–areolar complex with the underlying breast tissue and subsequent radiotherapy, have been developed [3, 6]. The problem with this approach is the increased risk of local recurrence [7], sometimes in the form of infiltrating carcinoma. For this reason, this therapy should be limited to those cases with few clinical and mammographic anomalies, in which the recurrence rates are low, at about 5% [3].
In order to rationalize the therapeutic approach in cases of Paget's disease, it may be necessary to apply more sensitive diagnostic techniques. The value of MRI in examining the nipple–areolar complex has been described and it is useful even when pathological involvement is not suspected clinically. The assessment is based on the comparative analysis of both breasts, in view of the fact that in the presence of pathology, there are clear differences and asymmetries in the characteristics of the nipple–areolar complexes, between the normal and abnormal sides. These characteristics include the morphology and kinetics of the enhancement, so that the thickening, sometimes nodular, of these structures, as well as an abnormal degree of enhancement, appear in pathological nipple–areolar complexes [9]. However, these are not specific characteristics, as they may appear both in Paget's disease and in other entities such as nipple adenoma or in the extension of breast neoplasias towards the nipple [10]. In the three cases presented, we found an earlier and more intense enhancement pattern in pathological nipple–areolar complexes, compared with healthy ones. In none of the three cases did the late enhancement peak obtained in healthy nipples reach the signal intensities of pathological nipples. This pronounced asymmetry has also been noted by other authors, and can be taken as a sensitive indicator of pathology [9].
The absence of a palpable mass in a breast in which a histological diagnosis of Paget's disease has been made, may be due to an absence of neoplastic pathology, or more probably, a limited neoplastic process, such as DCIS. MRI has been proven to be useful in the diagnosis of occult mammary neoplasias, not detectable by conventional means, and therefore it may be useful in identifying tumour foci associated with Paget's disease that cannot be detected clinically or mammographically. This technique enables both a morphological analysis and a study of vascularization through the kinetics of enhancement of small processes capable of inducing angiogenesis [8]. In view of the fact that almost all infiltrating carcinomas and between 70% and 83% of DCIS are capable of developing neovascularization [11], this vascular proliferation may be detected in a high percentage of cases, even in very small lesions. There are several morphological and kinetic patterns associated with DCIS, and since DCIS can very often result in progressive enhancement, not typical of malignancy [11–13], any enhancement on MRI should be regarded with suspicion in a patient at high risk of breast neoplasia. In an attempt to solve the MRI false-positive problem, allowing for conservative treatment to be performed, we believe that the use of techniques such us MRI-guided percutaneous biopsy before surgical treatment, or MRI-guided wire localization procedures before surgical biopsy, may allow for the histological examination of the majority of suspicious breast foci.
We encountered suspicious findings in all three cases presented, although only in two of them was neoplasia confirmed. This re-inforces the above comments, as although it was possible to detect all the neoplastic lesions, MRI did not allow for the identification of all the benign processes in a clear and indisputable manner. In these three cases of Paget's disease, treated by mastectomy, there was a high level of concordance between the MRI results and the histological analyses of specimens. This raises the possibility that MRI may be useful in the diagnostic algorithm when a less aggressive therapy is contemplated in women with no clinical or mammographic signs of malignancy.
To sum up, we believe that MRI is useful for assessing the cutaneous alteration of Paget's disease, as well as detecting possible associated underlying neoplastic foci, enabling, a reasoned choice to be made about conservative treatment.
Received for publication August 29, 2003.
Revision received July 30, 2004.
Accepted for publication August 18, 2004.
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Abstract
Introduction
