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10.1245/ASO.2005.04.013
Annals of Surgical Oncology 12:546-551 (2005)
© 2005 Society of Surgical Oncology
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Original Article

Pathologic Nipple Discharge: Surgery Is Imperative in Postmenopausal Women

Steffi Lau, MD1, Ingrid Küchenmeister, MD2, Angrit Stachs, MD1, Bernd Gerber, PhD3, Annette Krause, MD3 and Toralf Reimer, MD1

1 Department of Obstetrics and Gynecology, University of Rostock, Universitä tsfrauenklinik, Suedring 81, 18059, Rostock, Germany
2 Institute of Radiology, University of Rostock, P.O. Box 100888, 18055, Rostock, Germany
3 Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Campus Innenstadt, Maistr. 11, 80337, Munich, Germany

Correspondence: Address correspondence and reprint requests to: Steffi Lau, MD; E-mail: slau{at}med.uni-rostock.de.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: A total of 10% to 15% of pathologic nipple discharge in women is due to malignant lesions of the breast. The purpose of this study was to discover the rate of breast cancer in women who present with this symptom and undergo ductal excision, to evaluate the different diagnostic methods used before surgery, and to discover whether there are specific factors with regard to dignity.

Methods: We analyzed 118 ductal excisions in 116 patients performed at the women’s hospital of the University of Rostock, Germany, between 1995 and 2002. The discharging duct was identified by preoperative galactography.

Results: The rate of cancer in these patients was 9.3% (n = 11). The most frequent benign lesion was intraductal papillomatous proliferation (36.4%; n = 43). Solitary papillomas were shown in 21.2% (n = 25), and other specific benign histologic findings were shown in 27.1% (n = 32). Women with malignancies were significantly older (P = .009) and were more often postmenopausal (P = .095) compared with patients with benign histology. Galactography was the method that reached the highest sensitivity (73%), and clinical examination showed the highest specificity (85%) in distinguishing between benign and malignant lesions.

Conclusions: Because 94.1% of all cases presented with specific histological findings causing pathologic nipple discharge, ductal excision combined with preoperative galactography was proven to be a sufficient method for diagnosis and therapy. This procedure should be performed in all postmenopausal women with this symptom because of a cancer rate of 12.7% among this age group and the unsatisfactory quality of other diagnostic methods.

Key Words: Nipple discharge • Duct excision • Galactography • Breast cancer • Age


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Most nipple discharge is due to a benign etiology.1 It is the second most common complaint presented by women who have breast surgery. It ranks second only to a lump, which is presented by 85% of these patients.2 Nipple discharge is the major complaint of 3% to 6% of women who visit breast speciality units3; 1% to 5% of all breast cancers present as nipple discharge.4 Approximately 50% of all cases are physiological or secondary secretions with an underlying systemic cause, and the other half are pathologic secretions that are due to a lesion in the breast.5 A significant pathologic discharge is true, spontaneous, persistent, and nonlactational.6 Previous studies have shown that 10% to 15% of such pathologic secretions of mammary etiology are caused by malignancy.1,7 It is assumed that the risk for cancer is higher when the discharge is accompanied by a lump, when there are adverse cytological or mammographic findings, when the woman is older than 50 years, and when the discharge is of the serous, serosanguineous, sanguineous, or watery type.2 When a pathologic secretion from the nipple occurs, a clinical workup is recommended that includes an adequate case history, a physical examination, mammography, ultrasound of the breast, galactography, and exfoliative cytology.8 The aims of this study were to investigate the rate of malignancies of the breast in women who present with pathologic nipple discharge, to investigate the quality of the different diagnostic methods used, and to investigate whether there are predictive factors for developing breast cancer.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The data of 116 women who underwent ductal excision after a preoperative ductogram to localize the precise site of intraductal lesions at the women’s hospital of the University of Rostock, Germany, from January 1995 to December 2002 were analyzed retrospectively. Two patients had to undergo two operations during this period.

To investigate the quality of the diagnostic methods used before surgery for distinguishing benign and malignant lesions of the breast, the charts of the patients were reviewed. Clinical examination was performed in all cases (n = 118). If a lump or a retraction of the nipple was found, especially if this was accompanied by a swelling of the axillary lymph nodes, the palpation was considered to suggest malignancy. For exfoliative cytology, galactography, mammography, and ultrasound of the breast, the results were classified as shown in Table 1Go.


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  		TABLE 1. Classification of cytology, galactography, mammography, and ultrasound results
 
The performance of the diagnostic modalities was described in terms of sensitivity, specificity, and receiver operating characteristic curve. The Breast Imaging Reporting and Data System for mammography was not used before 2003 and was therefore not integrated into the analysis.

The ductogram was performed on the day of surgery by using a small amount (.5–1 mL) of a 1:1 solution of sterile, water-soluble contrast material (Solutrast; Altana Pharma GmbH, Konstanz, Germany) and toluol blue, which was injected into the discharging duct. Mediolateral and craniocaudal mammograms were obtained to visualize the secreting duct on a Mammomat 3000 unit (Siemens, München, Germany; Fig. 1Go). Ductal excision was made via circumareolar incision within the areolar border, followed by preparation of the blue-stained duct (Fig. 2Go). The resection area was broadened to include the terminal ductal/lobular unit with the surrounding tissue, because the cause for secretion can be situated behind a duct cutoff shown by the ductogram. Nevertheless, in our experience, most histological findings that cause nipple discharge are found directly behind the nipple. The removed tissue was sent to the pathologist for further investigation, but no intraoperative histology was performed. If invasive cancer was found histologically, then the patient underwent a second operation.


Figure 1
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  		FIG. 1. Identification of the discharging duct by preoperative galactography.

 

Figure 2
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  		FIG. 2. Intraoperative preparation of the blue-stained duct.

 
Demographic characteristics of the patients were tested for significant differences between patients who had benign or malignant lesions of the breast. For qualitative data, {chi}2 analysis was used, and for quantitative data, the Mann-Whitney U-test was used. P values of < .05 were considered to be significant. Statistical investigations were performed with SPSS version 10.0 (SPSS Inc., Chicago, IL).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Nipple discharge was caused by malignancy in 11 (9.3%) of 118 cases. The investigated 116 women ranged in age from 34 to 85 years, with a mean age of 56.7 years at the time of surgery. The mean body mass index was 28.3 kg/m2 (range, 19.2–44.5 kg/m2). No significant differences were found between patients with benign- and malignant-caused pathologic nipple discharge regarding the number of children and pregnancies, body mass index, menopausal status, intake of hormones at the time of surgery, duration, or side and color of nipple discharge (Table 2Go).


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  		TABLE 2. Characteristics of patients who present with nipple discharge
 
The only statistically significant difference between benign and malignant histological groups was found for patient age (P = .009). Patients with malignant findings were nearly 10 years older than patients with benign lesions (65.3 vs. 55.8 years). Patients with malignant lesions were more frequently postmenopausal (P = .095). Among all postmenopausal women (n = 79), the breast cancer rate was 12.7% (n = 10), compared with a corresponding value of only 2.8% (1 of 36) for premenopausal patients.

The secretion was unilateral in 112 cases (right side, n = 49; left side, n = 63) and bilateral in 5 cases. In these patients, a functional cause was excluded. All patients who presented with bilateral secretions had benign breast lesions.

A malignant lesion was seen in 11 women (9.3%): 7 invasive cancers and 4 carcinomas-in-situ (Table 3Go). Invasive cancers were relatively small (.1–1.3 cm). The histological type was either invasive ductal (n = 5) or invasive papillary (n = 2) and was accompanied by carcinoma-in-situ in five cases. Six cancers were highly or moderately differentiated, and hormone receptors were positive in 85.7% of cases for progesterone and 57.2% of cases for estrogen. Metastatic cells in the axillary lymph nodes were detected only in the one case that showed a poorly differentiated tumor. The four carcinomas-in-situ were of the ductal type (two were papillary). All showed positive hormone receptors for estrogen and progesterone. The most common lesion causing nipple discharge was intraductal papillomatosis (43 cases; 36.4%). The second most common was solitary papilloma (21.2%). Other benign specific lesions (especially fibrocystic disease) were found in 27.2% of the patients, whereas no specific lesions could be shown in seven cases (5.9%).


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  		TABLE 3. Histological findings in cases of pathologic nipple discharge
 
The sensitivity and specificity of the different diagnostic tools used are listed in Table 4Go and are shown as a receiver operating characteristic curve in Fig. 3Go. Palpation of the breast and axillary region was performed in all 118 cases. In 10 cases of malignant histological findings, the clinical examination was false-negative, and therefore it had a low sensitivity of only 9% for distinguishing between malignant and benign lesions. In 91 women who had no suggestive palpatory finding, this result was confirmed by histology. This led to the highest specificity (85%) for this method, whereas galactography had the lowest (61%), because only 60 women without malignancy had nonsuspicious ductograms. However, galactography had the highest sensitivity (73%): only 3 of 11 patients had false-negative results. Conversely, exfoliative cytology, performed in 83 cases (not performed in 4 cases of malignant histology), detected malignant lesions in only 57%, whereas it had a low rate of false-positive results and, therefore, a high specificity. Mammography showed false-negative results in 5 cases and false-positive results in 27 cases. Four patients with malignancy had normal ultrasound findings, and 28 patients with benign lesions had suspicious ultrasound results.


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  		TABLE 4. Evaluation of the different diagnostic methods with respect to sensitivity, specificity, and area under the receiver operating characteristic curve (AUC-ROC)
 

Figure 3
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  		FIG 3. Receiver operating characteristic curve (representing specificity and sensitivity) for diagnostic modalities in patients with pathologic nipple discharge.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The rate of malignant lesions of the breast in women with nipple discharge among patients attending our hospital was 9.3% overall. However, the breast cancer rate is age dependent; this led to an increased rate (12.7%) among postmenopausal patients. Other authors have found malignancies in 4% to 31% of cases of significant nipple discharge, and most report an incidence of 10% to 15%, in accordance with our results.1,2 Conversely, in male patients, the reported cancer rate is 20%.4

Current guidelines on breast cancer detection recommend that patients with nipple discharge have further evaluation. However, it should be mentioned that pathologic discharge is defined as a spontaneous, persistent, and nonlactational secretion from the nipple, and only 1% to 5% of cancers show secretion from the nipple.4 We found that the most common benign cause for secretion was intraductal papillomatosis (more than one third of all patients), and this confirmed the results of earlier studies.9,10 Other authors have described a higher frequency of solitary papilloma.6–8,11 The clinical meaning of intraductal papillomatosis is the potential risk of degeneration in 5% to 25% of cases.11

A patient who presents with nipple discharge should undergo a complete history and a clinical investigation. During the palpation of both breasts and axillary lymph nodes, the type of secretion must be judged (spontaneous or on pressure; unilateral or bilateral; and color). Leis et al.2 indicated that the risk for cancer is higher when secretion is accompanied by a lump, when it is unilateral, and when it is watery. We found a very low sensitivity but a high specificity of clinical examination in our study for detecting malignant breast lesions. Therefore, in our opinion, palpation is absolutely helpful when it suggests malignant disease, especially when a lump, a swelling of axillary lymph nodes, or nipple retraction is detected. Still, we agree with previous investigations that showed that the color of the secretion does not add significant information.5,10,12 Furthermore, the duration of discharge does not play an important role.

Some authors report that older women tend to have breast cancer more frequently when nipple discharge occurs.13 Our study confirms this. Postmenopausal status also seems to be associated with malignant histology. Seltzer14 reviewed data on 10,000 consecutive new surgical referrals for breast complaints, with attention to age. Only 4% of patients <50 years old were found to have breast cancer, and 17% of those ≥50 years old had breast cancer. Nine percent of patients ≥50 years old with a chief complaint of discharge had a breast carcinoma.

During the clinical examination, a drop from the secretion should be taken for exfoliative cytology. Earlier studies confirmed a low value for the sensitivity of cytology8,10–12,15; this is caused by a high rate of false-negative results. Negative cytology cannot exclude malignancy. However, when it is positive, in most cases the underlying lesion is not benign. This test should be performed, because when it is positive it can be helpful for the planning of surgery. Also, mammography and ultrasound of the breast are useful—despite their low sensitivity and specificity—for detecting breast lesions that are not duct related. As expected, considering the results of recent investigations,6–8,11,12,15 the diagnostic method with the highest breast cancer detection rate in the case of nipple discharge was galactography. However, this method was also insufficient in approximately 27% of all malignancies, and it should not be used for determining whether surgery is indicated. Its value is to locate the precise site of the intraductal lesions. With the help of ductography, it was possible to find the secretion-causing lesion in 94% of cases. Van Zee et al.1 reported specific pathologic findings in 100% of cases of preoperative ductography, in contrast to only 67% when it was not performed. We conclude that preoperative ductography should be mandatory.

Fiberoptic ductoscopy offers a promising alternative to ductography in guiding subsequent breast surgery in the treatment of nipple discharge.16 Its detection rate of intraductal abnormal lesions was 97%.17 Malignant lesions appear irregular and roughly shaped and tend to bleed, whereas benign tumors have smooth surfaces without bleeding.18 Nevertheless, ductoscopy is a specific method for diagnosing breast cancer, although it is not sufficiently sensitive to be used alone.19 In our opinion, this quite expensive and time-consuming procedure cannot replace preoperative ductography at the moment, but combined with ductal lavage, it may have a role in the management of patients with nipple discharge.

Magnetic resonance imaging (MRI) was not performed in cases of pathologic nipple discharge, although several authors have reported that MRI can be a useful diagnostic tool with a high sensitivity for detecting breast cancer.20,21 However, there are known difficulties in distinguishing papilloma from invasive cancer, because parts of papilloma demonstrate rapid or rim contrast enhancement or spiculation and therefore mimic breast cancer on MRI.22

Finally, no recurrence of the nipple discharge was observed in any case during follow-up, so we consider ductal excision after preoperative ductography to be the method of choice for the diagnosis and treatment of nipple discharge. In case of malignancy, histology revealed mostly early tumor stages that were associated with a good prognosis. Therefore, women who present with pathologic nipple discharge should be reassured, because in most cases it is due to a benign lesion, and even if it is cancer, they can often be treated successfully.

In conclusion, women with breast symptoms usually do not have breast cancer. There is a need to inform the public that only a minority of complaints result in a cancer diagnosis. However, a complaint of nipple discharge in older patients requires careful evaluation. The rate of malignancy in women with pathologic nipple discharge is approximately 10%, and considering the absence of sufficient diagnostic methods and predictive factors (except for patient age) for detecting cancer, every postmenopausal patient with nipple discharge should undergo duct excision after preoperative ductography.

Received for publication April 7, 2004. Accepted for publication November 12, 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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