The Role of Breast Ductoscopy in Evaluation of Nipple Discharge: A Chinese Experience of 419 Patients

The aim of this study is to report our experience with ductoscopic evaluation for screening patients with nipple discharge and evaluate any potential indications and benefits of ductoscopy. From January 2010 to December 2012, 419 female patients with nipple discharge were enrolled in this study. All patients involved in this study showed no mass in ultrasound and mammography. Data concerning age, clinical characteristics of nipple discharge, nipple discharge cytology, ductoscopic and postsurgical diagnosis, and complications were statistically analyzed. Ductoscopy examinations were completed in 405 patients (96.66%). For these 405 patients, there were 519 ductoscopic investigations. 112 (27.65%) patients were found to have intraductal papillary lesions of which 62 were operated in our hospital. Postsurgical diagnosis showed 8 (12.9%) malignancy including 6 DCIS and 2 invasive ductal carcinomas. All of the 8 patients meet at least two criteria of pathologic nipple discharge (single duct, spontaneous, bloody nipple discharge). The other patients with nonpapillary lesions are still under surveillance. By univariate analysis, patients with unilateral, single duct, spontaneous and bloody nipple discharge were more likely to have intraductal papillary lesions. By multivariate analysis, unilateral, spontaneous, and bloody nipple discharge showed statistically significant correlations with intraductal papillary lesions revealed by ductoscopy. Ductoscopy is a safe and efficient investigation in preoperative screening of the patients with nipple discharge. Clinical characteristics have predictive value in selection of patients for ductoscopical investigation. Patients with clinical characteristics of unilateral, spontaneous, and bloody nipple discharge were more likely to have intraductal papillary lesions revealed by ductoscopy.     

Breast Ductoscopy and the Evolution of the Intra-Ductal Approach to Breast Cancer

Abstract:  Interest in breast endoscopy came from Oriental investigators in the early 1990s where bloody nipple discharge is a more common presentation of breast cancer. The early techniques using a single microfiber scope without ductal distension was successful in navigating only the first 1–3 cm of the ducts and fraught with technical problems such as scope breakage and poor image quality. In spite of these barriers there has been increasing use of this technology in Japan and more widespread acceptance as the technology of scope design improved. Dooley and others tested a new method of obtaining a rich cytologic specimen from the ducts of high-risk women known as ductal lavage recently. The success of this procedure was that it detected severe cytologic and malignant atypia in clinically and radiographically normal breasts. Reproducibly, the same breast duct could be cannulated and severely atypical cytology obtained. The problem arose in identifying the lesion within the breast, which was the source for the atypia. New American multi-fiber microendoscopes were applied to solve this problem in an initial series of patients with abnormal cytology to identify the lesions. Success of that series lead to wider application of the imaging technology and eventual adoption of this imaging modality help to guide during all non-mastectomy breast surgery where fluid could be elicited from the nipple to identify the duct connecting to the lesion for which surgery was being performed. Initial reports have demonstrated the types of operative findings in certain sub-populations early in the use of this technology.     

The Significance of Nipple Discharge of the Male Breast

Abstract: Although male breast cancer typically presents as a palpable mass, failure to recognize the significance of other symptoms may lead to a delay in diagnosis. Here we present our experience with male patients presenting with a chief complaint of nipple discharge (ND). Using the ICD‐9 code for “breast symptoms,” we identified 2,319 patients without a current cancer diagnosis who presented to Memorial Sloan‐Kettering Cancer Center for evaluation; 24 (1%) patients were male (1995–2005). Data were collected by retrospective review. Among 24 male patients presenting for evaluation, 14 (58%) presented with a chief complaint of ND, while the remaining 10 (42%) presented for evaluation of a palpable mass in the absence of ND. Among 14 patients presenting with ND, subsequent clinical breast examination identified a breast mass ± nipple changes in 7 of 14 patients. In total, 8 of 14 (57%) patients had an underlying malignancy; two of seven patients with ND alone had DCIS (median interval from onset of ND to presentation 3 weeks, range 2–4 weeks), and six of seven patients with ND and a palpable mass had invasive disease (median interval between onset of ND and presentation 16 weeks, range 2–52). The remaining 10/24 patients presented with a painless palpable mass of whom 8 (80%) were found to have underlying invasive disease (median interval between onset of mass, and presentation was 4 weeks, range 2–20 weeks). All patients with invasive disease were node‐positive. At 23.7 months median follow‐up (range, 7.7–88.3 months), 14 of 16 cancer patients remain free of disease and two have died as a direct result of metastatic disease. The incidence of cancer among males presenting with ND was 57%. In the absence of additional clinical findings, ND may be a herald for early, non‐invasive disease. Increased awareness of subtle features of malignancy may represent a window of opportunity for early diagnosis and improved outcomes for male breast cancer patients.     

Mammary Ductoscopy and Ductal Washings for the Evaluation of Patients with Pathologic Nipple Discharge

Abstract:  The majority of breast diseases result from lesions of the ductal epithelium. Mammary ductoscopy allows for visualization of intraductal abnormalities, and ductoscopic lavage provides thousands of cells for analysis. We reviewed our experience of 89 cases of patients with pathologic nipple discharge (PND) undergoing ductoscopy-directed duct excision and collection of ductal washings. Patients undergoing ductoscopy-directed duct excision with ductal washings had an 88% abnormal pathology rate. Most abnormalities were benign (71% papillomas), but the atypia rate for this group was 62%. The combination of visualization and pathologic analysis of washings provided the highest predictive value for the diagnosis of papilloma. Cellular yields for this technique were excellent with most specimens yielding >5,000 epithelial cells per high powered field and with evaluable ductal cells in 82% of specimens. Mammary ductoscopy offers the advantage of a high lesion localization rates with intraoperative guidance. The most accurate tool was the combination of ductal washings and ductoscopic visualization, but preoperative use of these techniques is not helpful in most cases. Greater than 90% of patients with PND are found to have a lesion on pathologic examination when using this technique for directed duct excision. Of interest, ductal washings obtained from symptomatic patients with benign diseases are often atypical.     

Mammary Ductoscopy for Evaluation of Nipple Discharge

Background  Most breast cancers originate in the ductal epithelium with normal cells progressing to atypia and finally to carcinoma. Ductoscopy enables one to visualize and sample the ductal epithelium and therefore identify early changes cytologically. This report describes our experience with mammary ductoscopy as a tool for evaluation of nipple discharge at Beth Israel Medical Center. Methods  A prospective review of all patients who have undergone ductoscopy for evaluation of persistent nipple discharge was performed. The Acueity ductoscopy system with .9-mm scope and a video monitor with ×60 magnification were used. Brush biopsy samples and lavage fluid were obtained from some patients and were sent for cytologic analysis. A subset of patients underwent ductoscopically guided duct excision. Results  Ninety-three patients underwent ductoscopic evaluation of 110 ducts. Of these, 67 patients had abnormal findings and therefore underwent ductoscopically guided duct excision. The remaining 26 patients (28%) had normal ductoscopic examinations. The depth at which intraductal abnormalities were visualized was from 3 to 8 cm with an average of 4.4 cm for cancer cases and from 1 to 10 cm with an average of 4.5 cm for papillomas. Forty-two patients were diagnosed with papilloma/papillomatosis, six patients were diagnosed with atypical papilloma/atypical ductal hyperplasia/atypical lobular hyperplasia, and six patients were diagnosed with cancer. Of the six patients diagnosed with cancer, 67% had normal breast imaging, and other than nipple discharge, 67% had normal breast examinations. Conclusion  Mammary ductoscopy is a useful tool in the evaluation of patients with nipple discharge. Although the most common cause of nipple discharge is an intraductal papilloma, nipple discharge can be the presenting symptom for cancer. Our experience revealed a papilloma rate of 45% (42 of 93), cancer rate of 6.5% (6 of 93), and an atypia rate of 6.5% (6 of 93) among the patients with nipple discharge. Mammary ductoscopy allows for accurate visualization, analysis, and excision of intraductal abnormalities. Many deeper intraductal abnormalities could be missed by blind surgical excision. Poster presentation at the 29th Annual Symposium of American Society of Breast Diseases, April 14–16, 2005, Las Vegas, Nevada.     

Fiberoptic Ductoscopy-Guided Intraductal Biopsy Improve the Diagnosis of Nipple Discharge

Abstract:  Fiberoptic ductoscopy (FDS)-guided intraductal biopsy is a minimally invasive technique developed to obtain pathologic diagnoses for patients with spontaneous nipple discharge. We performed biopsies of 53 intraductal lesions from March 2006 to April 2007 followed by surgical microdochectomy. FDS-guided intraductal biopsy was shown to be a minimally invasive, safe, and convenient technique with a high ability (90.6%) to get adequate samples. Twenty-seven solitary papillomas, 12 multiple intraductal papilloma, five ductal hyperplasia, three ductal carcinoma in situ, and one invasive ductal carcinoma were diagnosed. Compared with conventional microdochectomy, FDS-guided intraductal biopsy can significantly increase the detection rate of solitary papilloma (40.7% versus 92.6%, p < 0.05). It should be a routine procedure after intraductal lesion found by screening FDS. Since it would underestimate all multiple intraductal papilloma and some (50%) cancer, microdochectomy is inevitable if biopsies show atypical ductal hyperplasia.     

Endoscopic and Histologic Findings of Intraductal Lesions Presenting with Nipple Discharge

Abstract:   To improve the utility of mammary ductoscopy, we investigated the correlation between endoscopic findings and histologic findings using intraductal biopsy specimens. Seventy-one intraductal biopsy specimens obtained from 63 patients between October 2001 and March 2004 were analyzed retrospectively. All specimens were obtained from monotonous intraductal lesions immediately after observation by mammary ductoscopy and were composed of a pure histologic subtype. With regard to endoscopic findings, color was classified as yellow, red, white, or colorless, and morphology was classified as spherical, lobular, mulberry, or amorphous. The histologic subtype was classified as papillotubular, papillary, degenerated, papillary cancer, solid-type ductal carcinoma in situ (DCIS), or cribriform cancer. The relationship between histologic diagnosis, color, and morphology was investigated. Intraductal biopsy specimens included 25 specimens of carcinoma and 46 specimens of papilloma. There was no significant correlation between color and diagnosis. Fourteen of 25 carcinoma specimens were amorphous, and amorphous morphology was significantly suggestive of malignancy (p < 0.001). Further, cribriform cancer was associated with amorphous morphology and yellow color. Morphology may be a useful endoscopically delineated parameter for differentiating intraductal lesions.      

乳管镜诊治乳头溢液206例报告

目的探讨乳管镜诊治乳头溢液的效果。方法2001年5月-2006年10月,对206例乳头溢液行乳管镜检查221次。结果乳管镜诊断为乳管内非隆起样病变58例,行冲洗治疗,随访3—18个月,平均12个月,无复发。隆起样病变148例,其中125例手术治疗,乳管镜诊断单发乳管内乳头状瘤115例、乳头状瘤病7例、导管内癌3例,术后病理证实乳管内乳头状瘤112例,乳头状瘤病10例,导管原位癌3例。其中120例行乳腺定位针下病变乳管切除术,1例行区段乳腺腺体切除术,1例行“腺体置换”手术,1例行保留乳头的象限切除术联合腋窝淋巴结清扫,2例行不保留乳头的象限切除联合腋窝淋巴结清扫。随访4—20个月,平均10个月,无复发。3例导管原位癌随访12—18个月,无瘤生存。结论乳管镜检查对乳头溢液乳管内肿瘤术前诊断准确,而且对手术方式的选择具有重要临床意义。利用乳腺定位针直视下对乳管内病变定位,指导手术治疗。     

The Rightful Role of MRI after Negative Conventional Imaging in the Management of Bloody Nipple Discharge

Nipple discharge is a frequent presenting complaint at breast clinics. Bloody nipple discharge (BND) has the highest risk of malignancy, albeit low. If mammogram and ultrasound are unrevealing, central duct excision (CDE) has been considered the gold standard in its management. Magnetic resonance imaging (MRI) has been widely confirmed as a highly sensitive test for detection of breast cancer, with an accompanying high negative predictive value. This article presents a retrospective review of patients with BND and negative conventional imaging, comparing outcome of patients who went directly to CDE without MRI to those patients who underwent preoperative MRI. Of 115 patients who underwent mammography and US alone prior to CDE, eight cancers were detected (seven ductal carcinoma in situ [DCIS] and 1 IDC, 7 mm [T1b]; incidence: 7%). Of 85 patients who underwent conventional imaging followed by MRI prior to surgery, eight cancers were detected (all DCIS; incidence: 9.4%), seven of which were identified by MRI. The one false‐negative MRI had subtle findings which, in retrospect, were misinterpreted; however, a clinically apparent nipple lesion prompted surgical biopsy. Of 56 patients with a negative or benign MRI, CDE was negative for malignancy in all but that one patient. Sensitivity and specificity were 87.5%/71.4%. Positive predictive value and negative predictive value (NPV) were 24.1%/98.2%. MRI should be performed in all patients with BND and negative conventional imaging. The extremely high NPV of MRI suggests that a negative study could obviate CDE in most patients unless overriding clinical factors prevail.     

The Role of Galactography in Patients with Postoperative Nipple Discharge

Abstract: Spontaneous nipple discharge presenting temporally after breast surgery may be due to ductal communication with the biopsy site or to a second abnormality in the breast. Galactography is useful in excluding an intraductal lesion and documenting a communication between the discharging duct and the biopsy site, in cases where the discharge persists for more than a few weeks after surgery. In this clinical setting, galactography averted a second surgical procedure.     

纤维乳腺导管内镜辅助诊治乳头溢液632例报告

目的探讨纤维乳腺导管内镜对Tis期乳腺癌的临床诊断价值。方法 2001年5月～2010年5月,对632例乳头溢液进行乳腺导管内镜检查702次,并对其中310例隆起性病变行乳腺导管内镜辅助定位手术。结果 475例诊断为隆起性病变,包括乳管内乳头状瘤388例（61.4%）,乳管内乳头状瘤病79例（12.5%）,导管内癌8例（1.3%）;157例为非隆起性病变,包括导管扩张症82例（13.0%）,慢性乳管炎73例（11.6%）和导管内癌2例（0.3%）。310例行乳腺导管内镜辅助定位手术,内镜诊断对导管内癌的阳性预测值为83.3%（10/12）。结论 纤维乳腺导管内镜检查弥补了伴有乳头溢液的Tis期乳腺癌诊断的空白,对乳腺癌的早期诊断有积极的意义。     

Feasibility and Technical Considerations of Mammary Ductoscopy in Human Mastectomy Specimens

Abstract: Recent advances in endoscopic technology have made visualization of human mammary ducts possible. The purpose of this study was to assess the feasibility and technical factors influencing the ability to successfully visualize the epithelium of the human mammary ductal system. Lacrimal duct probes were used to dilate nipple orifices to 1.2 mm on 42 mastectomy specimens. The Depth of Field Imaging Micro-Minimally Invasive (DOFI® MMI) system consisting of a 1.2 mm rigid ductoscope with a 350 μm working channel was introduced into mammary ducts under air insufflation or saline irrigation. At least one major duct could be dilated and cannulated in all 42 specimens. Visualization of the proximal duct was accomplished in 34 of 42 (81%) specimens, whereas more extensive navigation through the distal subsegmental ducts was achieved in 22 of 42 (52%) specimens. Ductoscopy into the terminal ducts was accomplished in all patients with a previous history of nipple discharge or discharge at the time of the procedure (10 of 10). In three patients with no history of nipple discharge prior to ductoscopy, incidental papillomas were discovered and confirmed by the pathologist. In conclusion, mammary ductoscopy is technically feasible and may have an application as an additional diagnostic modality for patients with pathologic nipple discharge.     

Pathologic Nipple Discharge in Patients with Radiologically Invisible Mass: Review of 28 Consecutive Sub-areolar Explorations

Abstract:  The carcinoma frequency of clinically and radiologically negative pathologic nipple discharges (PNDs) and the optimum management strategy of these cases are still unclear. In this study, the frequency of cancer and the situation of the classic surgical intervention in patients with PND and invisible mammographic and ultrasonographic results are reviewed. The data pertaining to the cases of sub-areolar exploration and major duct excision in a surgery clinic of university hospital from December 2002 to June 2007 have been examined in detail. In 28 cases with PND, which did not have any findings during conventional radiologic examinations, 21% of cases had malignant, and 7% of cases had atypical ductal hyperplasia. The frequency of invasive or in situ carcinoma is not low in clinically and radiologically negative PNDs. Sub-areolar exploration and major duct excision seems to be an appropriate and definitive diagnostic and therapeutic option in this special patient group.     

乳管镜对乳腺导管内疾病的诊断及介入治疗--附100例临床分析

目的:探讨乳管镜在乳腺疾病诊断和治疗中的作用.方法:应用乳腺纤维导管内视镜对100例伴乳头溢液的乳腺导管性疾病进行诊断或介入治疗.结果:13例导管内占位性疾病得到了正确诊断,87例渗出性导管病经治疗后治愈.结论:乳管镜对乳管内病变的正确诊断及手术方式可提供依据,并可对渗出性病变进行介入治疗.     

乳腺超声及乳管内窥镜检查临床应用

目的：从现代医学的角度讨论乳腺超声及乳管内窥镜检查在乳头溢液疾病中的应用价值。方法：520例患者均按中医诊断标准辨病后行乳腺超声检查及乳管内窥镜检查,并进行对比分析。结果：乳腺超声检查对乳管僵硬狭窄、乳管内占位性病变的检出率低,而正常乳管、乳管扩张的检出率远远高于内窥镜诊断;乳管内窥镜对乳管内占位的检出率及确诊率高于乳腺超声检查。结论：乳管内窥镜检查可直接观察乳腺导管上皮及管腔内的情况,能显示不同疾病的特征性改变,特别是对早期癌的检出方面优于乳腺超声检查。     

纤维乳管镜临床应用新进展

目的 介绍纤维乳管镜在乳腺疾病的临床应用现状、价值及发展前景。方法 综述纤维乳管镜在乳腺疾病临床应用的研究进展。结果 纤维乳管镜在乳腺疾病尤其是伴乳头溢液者应用广泛，已显示出较乳管造影等常规检查方法更高的诊断准确率，且可同时行乳管冲洗和镜下定位、活检、治疗。结论 纤维乳管镜具有较高的诊断和治疗价值，是一种很好的内镜技术，相信能被更好地应用和发展。     

A review of mammary ductoscopy in breast cancer

Breast carcinoma and hyperplasia are thought to start in the lining of the breast duct. Mammary ductoscopy is an emerging technique allowing direct visual access of the ductal system of the breast through the nipple. This article reviews and discusses the utility of mammary ductoscopy. Abnormalities can be identified successfully by mammary ductoscopy, and intraductal biopsy can be used when the tumor is a polypoid type. Ductal lavage using microcatheters is effective in identifying malignant cells in high-risk women and this has stimulated interest in exploring the role of mammary ductoscopy in breast cancer screening. Mammary ductoscopy combined with ductal lavage may have a role in the management of patients with nipple discharge, the guiding of breast-conserving surgery for cancer, and in screening for high-risk women. The addition of molecular and genetic analysis of cells obtained by mammary ductoscopy are likely to enhance the use of this technique. Mammary ductoscopy techniques are safe and appear useful for detecting abnormalities in the breast. The additional molecular biologic study or ductal lavage may enhance the ability to direct and limit subsequent surgery when removing the offending lesions.     

纤维乳管镜对乳头溢液患者的诊断价值——附104例报告

目的 评价纤维光导乳管镜检查对乳头溢液的应用价值. 方法 应用德国Scholly Fiberoptic GmbH 42.0500型半硬性纤维光导乳管镜检查系统对104例乳头溢液进行诊断,并与术后病理诊断作对比分析. 结果 104例均成功检查.对乳管内占位性病变的检出率94%（49/52）.乳管镜诊断乳腺导管癌的敏感性为50%（1/2）,特异性为91%（43/47）,阴性预测值为98%（43/44）,阳性预测值为20%（1/5）,准确性为90%（44/49）.乳头状瘤病镜下诊断5例,其中3例与病理诊断符合,符合率60%;另2例为多发性乳头状瘤,均行腺叶切除.镜下诊断乳头状瘤38例,均行含病变乳管的腺叶部分切除术.55例乳管炎性疾病未行手术,3例（3%,3/104）因继续溢液行乳管镜复诊检出先前漏检之乳头状瘤后经手术证实. 结论 乳管镜能明确乳头溢液病因,确定病变部位,是乳头溢液的首选检查方法;使乳管炎与乳管扩张症免于手术.     

乳管内视镜对乳腺导管内新生物的诊断价值

目的：评估乳腺导管内视镜对乳腺导管内新生物的诊断价值。方法：对乳头溢液病人行乳管内视镜检查,选择乳管镜发现新生物并行手术治疗的病例,分析乳腺肿块或结节扪诊、乳头溢液细胞学诊断及乳管镜诊断与病理组织学诊断间相互关系。结果：乳管镜诊断新生物的７９例中,肿块／结节形态、细胞学诊断及乳管镜诊断均与病理组织学诊断相关（Ｐ＜０．０１）。病理诊断管内乳头状瘤伴肿块者占１２．９％（９／７０）,诊断导管内癌伴肿块者占导管内癌组的５５．６％（５／９）;细胞学对管内乳头状瘤及导管内癌的诊断与病理切片诊断符合率分别为２０％（１４／７０）及７５％（６／８）,而乳管镜则分别为６０．６％（４３／７０）及８８．９％（８／９）。结论：轧管镜是术前诊断以乳头溢液为表现的乳腺管内乳头状瘤和导管内癌的有效手段。     

乳管镜对以病理性乳头溢液为首发症状乳腺癌诊断价值分析

目的 评估乳管镜在以病理性乳头溢液为首发症状乳腺癌中的诊断价值。方法 回顾性分析2016年8月至2019年8月中国医科大学附属第四医院（380例）和新疆塔城地区人民医院（30例）收治的共410例以病理性乳头溢液为首发症状病人的临床资料,所有病人术前均行乳管镜、超声及钼靶检查。分析乳管镜检查中与乳腺癌诊断密切相关的因素,比较不同检查方式对乳腺癌诊断的敏感度、特异度、阳性预测值及阴性预测值。结果 410例病人均接受手术治疗,并进行术后病理学诊断,其中乳腺癌31例（7.6%）。乳管镜检查结果中,良性病例与恶性病例的溢液颜色、溢液量及病灶深度差异有统计学意义（P<0.05）。乳管镜对于乳腺癌术前评估诊断的敏感度为90.3%,明显高于超声（61.3%）和钼靶检查（48.4%）,三者特异度差异无统计学意义（P>0.05）。超声联合钼靶检查敏感度为71.0%,而在此基础上联合乳管镜检查可使诊断的敏感度提高至93.5%。结论 在以病理性乳头溢液为首发症状乳腺癌的诊断中,乳管镜检查的敏感度显著高于超声和钼靶,增加乳管镜检查能够显著提高乳腺癌诊断的敏感度,避免漏诊。