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Mammary Ductoscopy- Current and Future Applications (Breast Cancer and Benign Disease)
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Submitted By: Julian Kim, M.D., F.A.C.S.
Article by Julian A. Kim, M.D. F.A.C.S
Surgical Oncologist
Cleveland Clinic Foundation
Mammary ductoscopy refers to a procedure where a microendoscope is used to directly visualize the ductal lining of the breast as well as provide access for retrieval of epithelial cells by lavage. Due to the fact that the majority of both benign and malignant breast disease originates from the cells that line the ductal-lobular unit, development of a minimally-invasive procedure which can directly assess early changes has important applications to the detection and treatment of these conditions.
Although mammary ductoscopy is relatively new in the United States, the procedure has been performed in Japan and Europe for several years. The following article describes the evolution of the technique, and with the availability of technologic advances, the current and future applications.
Development of Mammary Ductoscopy Technique:
Several early reports of mammary ductoscopy were described over 10 years ago (1,2). The procedure at that time was performed using pediatric endoscopes or single-channel scopes, which had limited utility due to inability to cannulate small ductal openings which were millimeters in size, as well as the inability to insufflate and distend the ductal system during navigation of the ductal system. Several Japanese groups reported improved results using a single-chamber microendoscope, although the substantial expense and the inability to take tissue or cytology samples during the procedure limited patient benefit.
A newer generation of microendoscope is now commercially available and FDA-approved for use in humans. The ViaDuct mammary ductoscope (Acueity, Larkspur, CA.) advanced the field by its slim diameter (0.9 mm) and the development of an outer sheath, through which insufflation can occur during the procedure and aspiration can be performed to retrieve epithelial cells for cytologic analysis (Figure 1):
Mammary Ductoscope (Figure 1): The mammary ductoscope consists of a outer sheath with a 0.9 mm external diameter which has a working channel attachment for insufflation and aspiration. A gas sterilizable fiberoptic core is placed within the sheath and connected to a video system via the camera cord.
Patients can undergo the mammary ductoscopy procedure either in an office setting or in the operating room with minimal discomfort. A nipple block is performed either by administering topical lidocaine cream (EMLA) for 30 minutes prior to the procedure. This can be supplemented by 1% lidocaine intradermal injection around the nipple-areola complex and/or intraductal instillation of lidocaine once the duct has been cannulated. Under sterile conditions, the breast is massaged to promote nipple-aspirate fluid, a maneuver that helps to visually identify a ductal orifice. The ductal opening is gently dilated, and the mammary ductoscope can then be advanced using insufflation under direct visualization. The ductoscopy findings can be catalogued by videotape, and if any intraluminal pathology is identified, surgically removed or marked for image-guided core biopsy. Ductal washings are routinely obtained by aspirating fluid from the ductal system, and these are processed for cytologic analysis. Typical cytologic findings are illustrated below (Figure 2):
Cytologic findings from ductal washings. Clusters of ductal epithelial cells are readily obtained during ductoscopy for cytologic analysis. The cells seen in the photograph above exhibit a papillary appearance consistent with a benign intraductal papilloma, which was visualized and removed during ductoscopy-directed surgery.
Visual findings during ductoscopy for pathologic nipple discharge: Typical findings during ductoscopy in patients who present with pathologic nipple discharge include normal ductal bifurcation (figure 3a below)
Note the smooth epithelial lining of the ductal system. Intraductal papillomas (figure 3b below) are usually pedunculated and fleshy growths that may obstruct the ductal lumen.
Current indications for mammary ductoscopy:
There are three primary areas where ductoscopy is currently being evaluated in patients. These include: 1). Patients with pathologic nipple discharge 2). Patients with known breast cancer undergoing lumpectomy and 3). Patients who are at high-risk for developing cancer but have normal breast exam and imaging studies.
Patients with pathologic nipple discharge: The largest reported experience with mammary ductoscopy has been in patients with pathologic nipple discharge (3,4). This patient population is ideally suited for the ductoscopy procedure, as they generally demonstrate single-duct discharge, making identification of the ductal orifice easier. Additionally, many of these patients have ductal dilation or ectasia, which makes maneuvering of the scope easier, and over 70% of the patients will have an intraductal papilloma which can be localized and excised with the mammary ductoscope in place. An example of typical findings during mammary ductoscopy in a patient with pathologic nipple discharge are shown in Figure 3b above.
Advantages to the patient include the ability to intraoperatively localize and excise any intraductal abnormalities, which may obviate the need for pre-operative galactography or other imaging studies, as well as visual assessment of the remainder of the ductal system. For these reasons, there are several centers within the United States and abroad that are using mammary ductoscopy as a routine part of the surgical approach to patients with pathologic nipple discharge.
Patients with known breast cancer undergoing lumpectomy: There is an isolated report of a series of patients with known breast cancer who underwent intraoperative ductoscopy to assess surgical margins (5). The technique, termed routine operative breast endoscopy (ROBE), was performed in 55 women undergoing breast excision for either ductal hyperplasia, ductal carcinoma in situ (DCIS) or invasive ductal carcinoma. In 75% of cases, the intraductal lesion be identified, and in 38% of patients a wider breast excision was performed based upon occult findings visualized by ductoscopy alone. There are currently several centers that are formally testing the use of mammary ductoscopy as a method of detecting occult pathology and quantifying patient benefit as a result of the procedure. Below is an example of intraoperative mammary ductoscopy in a patient with known breast cancer undergoing lumpectomy where papillary DCIS is identified at the surgical margin (Figure 4):
Figure 4a
Figure 4b
Figure 4(above)Isosulfan blue dye was injected around the palpable breast tumor and ductoscopy was performed through the ductal orifice that yielded blue dye using continuous saline insufflation. The blue dye and bloody discharge direct the surgeon to the ductal branches that are involved by the tumor figure 4a. A papillary growth within the ductal lining is identified which represents papillary DCIS (figure 4b)
Patients who are at high-risk for developing breast cancer: The use of ductal lavage for risk assessment has generated a population of high-risk patients who have no imaged evidence of breast malignancy yet are found to have atypical cells within one or more ductal systems (6). Although the clinical significance of these findings has not yet been elucidated, there is evidence that atypical ductal cells identified from random periareolar fine needle aspiration is associated with a substantial near-term (within 3 years) risk of development of subsequent breast cancer (7). Until prospective follow-up is available on patients with atypical cytology obtained from ductal lavage, patients and physicians have a variety of options for follow-up. Current recommendations for these patients have been outlined and include additional imaging studies including ductography or MRI, chemoprevention or mammary ductoscopy (8). There are isolated reports of patients who have had mammary ductoscopy of the same ductal system that yielded atypical cytology from ductal lavage, and a variety of pathologic lesions have been identified which range from intraductal papillomas to DCIS and atypical ductal hyperplasia. Below is a collection of images from a patient who had atypical cytology from ductal lavage and underwent mammary ductoscopy of the same ductal system (Figure 5:
 
Figure 5: The patient underwent mammary ductoscopy in the operating room and an intraluminal growth was identified which was obstructing the lumen. This was surgically excised and the pathology report showed an infarcted papilloma with highly atypical cells with no evidence of malignancy.
Future applications:
The future applications of mammary ductoscopy are quite broad, as visual access to the mammary ductal system may allow for diagnostic and therapeutic interventions not previously possible. Current investigations are focused on biopsy and ablation techniques that can be performed during ductoscopy that can correlate visual findings with histopathology. In the future, the ability to ablate benign or premalignant lesions may obviate the need for surgical excision, and may also offer targeted delivery of therapeutics in a breast cancer prevention or treatment paradigm. Techniques which can enhance identification of atypical ductal epithelium which are fluorescence or spectrography-based may help to direct tissue sampling during ductoscopy to increase yield and reduce sampling error. Finally, there is emerging evidence that genetic analysis of ductal epithelial cells using techniques such as methylation-specific polymerase chain reaction or fluorescence in-situ hybridization may assist in the detection of rare cancer cells, which may improve detection of early cancers (9). In total, these ongoing investigations herald a bright future for mammary ductoscopy as a method that may find increasing utility in the management of patients with benign and malignant breast diseases.
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Additional Authors: |
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Works Cited: |
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1). Berna J.D., Garcia-Medina V. and Kuni C.C. Ductoscopy: a new technique for ductal exploration. Eur. J. Radiol. 1991. 12(2): 127-9.
2). Love S. M., Barsky S. H. Breast-endoscopy to study stages of cancerous breast disease. Lancet 1996. 348: 997-9.
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4). Yamamoto D., Shoji T., Kanawashi H., Nakagawa H., Haijima H., Gondo H. and Tanaka K. A utility of ductography and fiberoptic ductoscopy for patients with nipple discharge. Breast Cancer Res. Treat. 2001. 70(2) 103-8.
5). Dooley W. C. Endoscopic visualization of breast tumors (let). JAMA 2000. 284(12): 1518.
6). Dooley W. C., Ljung B. M., Veronesi U., Cazzaniga M., Elledge R. M., O’Shaugnessy J. A. et al. Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J. Natl. Cancer Inst. 2001. 93:1624-32.
7). Fabian C. J., Kimler B. F., Zalles C. M., Klemp J. R., Kamel S., Zeiger S. and Mayo M. S. Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail Risk Model. J. Natl. Cancer Inst. 2000. 92(15): 1217-27.
8). O’ Shaughnessy J. A., Ljung B. M., Dooley W. C., Chang J., Kuerer H. M., Hung D. T., Grant M. D., Khan S. A., Phillips R. F., Duvall K., Euhus D. M., King B. L., Anderson B. O., Troyan S. L., Kim J., Veronesi U. and Cazzaniga M. Ductal lavage and the clinical management of women at high risk for breast cancer: A commentary. Cancer 2002. 94(2): 292-8.
9). Evron E., Dooley W. C., Umbricht C. B., Rosenthal D., Sacchi N., Gabrielson E., Soito A. B., Hung D. T., Ljung B., Davidson N. E. and Sukumar S. Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet 2001. 358: 507.
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