Study Type
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Study Objective(Purpose of Study)
Study Results
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Study Quality
1. Onstad M, Stuckey A. Benign breast disorders. [Review]. Obstet Gynecol Clin North Am. 40(3):459-73, 2013 Sep. Review/Other-Dx N/A To review common benign breast problems in the manner whereby they are most likely to be presented to the clinician. A discussion of common breast symptoms is followed by a review of benign breast processes found incidentally on imaging and biopsies. Benign breast lesions are much more common than malignant lesions. Women may present with specific complaints related to their breasts, or may have abnormal screening mammograms that lead to the diagnosis of benign breast disease. Evaluation should include obtaining a relevant history, performing a physical examination, ordering imaging studies as appropriate, and obtaining a tissue diagnosis when indicated. Some benign breast diseases have been associated with an increased risk for developing breast cancer. 4
2. Alcock C, Layer GT. Predicting occult malignancy in nipple discharge. ANZ J Surg. 2010;80(9):646-649. Observational-Dx 49 patients To determine which investigations and patient factors could help predict which patients with pathological nipple discharge would later be found to have an underlying malignancy. Of the 49 patients undergoing surgery for nipple discharge, 21 were diagnosed with intraductal papilloma, 19 with duct ectasia, 6 with carcinoma, 2 with benign breast disease and 1 with lobular carcinoma in situ. In all of the patients determined to have malignancy, none demonstrated malignant changes on mammography or ultrasonography. Only 2 of the 6 patients with malignancy were found to have atypical cells on cytological analysis. The sensitivity of blood detected in nipple discharge at predicting malignancy was 0.83, specificity of 0.53, positive predictive value of 0.20 and negative predictive value 0.96. 3
3. Lorenzon M, Zuiani C, Linda A, Londero V, Girometti R, Bazzocchi M. Magnetic resonance imaging in patients with nipple discharge: should we recommend it? Eur Radiol. 2011;21(5):899-907. Observational-Dx 38 women To compare the sensitivity of Contrast-Enhanced Magnetic Resonance Imaging (CEMRI), mammography and ultrasonography in patients with nipple discharge (ND). 5/38 malignancies (13.2%; 3 invasive, 2 intraductal; 4 ipsilateral, 1 contralateral to ND), and 14/38 High-Risk Lesion (HRL--36.8%; 11 intraductal papillomas, 1 papilloma with LCIS, 1 sclerosing papilloma and 1 atypical intraductal hyperplasia, all ipsilateral) were found. CEMRI identified 5/5 cancers and 13/14 HRL (Overall Sensitivity-OSS = 94.7%; Overall Specificity-OSP = 78.9%). 3/5 cancers (1 invasive, 1 in-situ; 1 invasive contralateral) and 2/14 HRL were detected by CEMRI only. Mammography found 2/5 cancer and 3/14 HRL (OSS = 26.3%; OSP = 94.7%). Ultrasound identified 1/5 cancer and 11/14 HRL (OSS = 63.2%; OSP = 84.2). 1/14 HRL was detected by ultrasound only. Compared with mammography and ultrasound, CEMRI showed statistically significantly higher OSS values (p < 0.0001, p = 0.042 respectively). 3
4. Goksel HA, Yagmurdur MC, Demirhan B, et al. Management strategies for patients with nipple discharge. Langenbecks Arch Surg. 2005;390(1):52-58. Observational-Dx 13,443 patients To assess management strategies for patients with nipple discharge (ND). ND was the presenting symptom in 603 (4.5%) of the cases. Two hundred and eighty-seven (48%) of the 603 patients showed spontaneous nipple discharge (SND group) and the other 316 (52%) showed provoked nipple discharge (PND group). In the SND group, 124 (43%) tissue specimens were obtained by either biopsy or sub-areolar exploration. Histopathological examination revealed that the most frequent causes of ND in these cases were intraductal papilloma (49 patients; 40%), intraductal carcinoma (35 patients; 28%), and cystic disease (15 patients; 12%). Twenty tissue specimens were obtained from the group with PND. In these cases, the most frequently identified causes of ND were cystic disease (seven patients; 35%), intraductal papilloma (six patients; 30%), ductal ectasia (two patients; 10%), and carcinoma (one patient; 5%). The SND and PND groups differed significantly with respect to age (P = 0.001) and duration of ND (P = 0.008). The incidence of cancer was higher in the SND specimens than in the PND specimens (28% vs 5%, respectively; P = 0.01). The number of pregnancies was significantly higher and the duration of lactation was significantly longer in the SND group (P = 0.03 and P = 0.02, respectively). 4
5. Bahl M, Baker JA, Greenup RA, Ghate SV. Diagnostic Value of Ultrasound in Female Patients With Nipple Discharge. AJR Am J Roentgenol. 2015;205(1):203-208. Observational-Dx 327 female patients To assess the contribution of ultrasound to the evaluation of patients with pathologic nipple discharge at a large academic institution. Over a 3-year period, 327 females (mean age, 48 years; range, 13-88 years) presented with nipple discharge. Among these patients, 273 (83%) underwent surgical excision or clinical or radiographic follow-up at least 2 years after presentation and composed the study population. Among the 273 patients, 262 (96%) underwent mammography and 246 (90%) underwent sonography. Among 252 patients who had at least one pathologic feature of nipple discharge and underwent surgical excision or at least 2 years of follow-up, a total of 20 (8%) cases of ductal carcinoma in situ (DCIS) or invasive adenocarcinoma were diagnosed. DCIS or invasive adenocarcinoma was diagnosed in eight patients with normal sonographic findings. For the detection of DCIS and invasive adenocarcinoma, the sensitivity and specificity of ultrasound were 56% (10/18) and 75% (170/228); the sensitivity and specificity of mammography were 15% (3/20) and 98% (237/242). 3
6. Gray RJ, Pockaj BA, Karstaedt PJ. Navigating murky waters: a modern treatment algorithm for nipple discharge. Am J Surg. 2007;194(6):850-854; discussion 854-855. Observational-Dx 204 patients To define the risk of carcinoma among patients with defined clinical and imaging findings to create an evidence-based treatment algorithm. Nipple discharge was present in 204 patients. Carcinoma was identified in 7 patients (3% of all, 9% of those undergoing biopsy). Age > or = 50 years, abnormal mammography, and abnormal sonography were the only significant predictors of carcinoma. Among patients with unilateral, spontaneous, bloody, or serous discharge with a negative mammogram, the carcinoma risk was 3%. Among patients with unilateral, spontaneous, bloody, or serous discharge with a negative mammogram and subareolar ultrasound, the carcinoma risk was 0%. 3
7. Gulay H, Bora S, Kilicturgay S, Hamaloglu E, Goksel HA. Management of nipple discharge. J Am Coll Surg. 1994;178(5):471-474. Review/Other-Dx 448 patients To compile the clinical findings and course of patients with nipple discharge seen by one of the authors between 1959 and 1991. Nipple discharge was the presenting symptom in 448 (4.8 percent) of 9,312 women who consulted one of the authors with a complaint of disease of the breast. Nipple discharge was spontaneous in 243 (2.6 percent) and provoked in 205 (2.2 percent) of the patients. The ages of the patients ranged from 13 to 75 years (mean of 42.5 years) in the spontaneous and 16 to 70 years (mean of 37.8 years) in the provoked discharge group. When a palpable mass was found, biopsy was undertaken, while in instances of nipple discharge only, subareolar exploration was performed. Of the 115 patients in the spontaneous and 25 patients in the provoked groups who underwent biopsy, the most frequent cause of nipple discharge was intraductal papilloma (47.8 percent). Nipple discharge was the result of carcinoma in 35 patients (14.4 percent) in the spontaneous and six patients (2.9 percent) in the provoked group, respectively. In patients with a palpable mass, the incidence of carcinoma was 61.5 percent compared with 6.1 percent in patients with nipple discharge only. 4
8. Orel SG, Dougherty CS, Reynolds C, Czerniecki BJ, Siegelman ES, Schnall MD. MR imaging in patients with nipple discharge: initial experience. Radiology. 2000;216(1):248-254. Observational-Dx 23 patients To investigate the potential of contrast magnetic resonance (MR) imaging in patients with nipple discharge. In 11 of the 15 (73%) patients who underwent excisional biopsy, MR imaging findings correlated with histopathologic findings. MR imaging demonstrated four of six benign papillomas and one of two fibroadenomas as circumscribed, enhancing subareolar masses. Findings of one MR imaging examination were negative, and benign tissue was found at excisional biopsy. MR imaging findings were suspicious in six of the seven patients with excisional biopsy findings of malignancy (regional enhancement [n = 2], ductal enhancement [n = 2], peripherally enhancing mass [n = 1], and spiculated mass [n = 1]). In one of the seven patients, a benign-appearing intraductal mass was identified at MR imaging; excisional biopsy revealed a benign papilloma with an adjacent focus of DCIS. 3
9. Seltzer MH, Perloff LJ, Kelley RI, Fitts WT, Jr. The significance of age in patients with nipple discharge. Surg Gynecol Obstet. 1970;131(3):519-522. Review/Other-Dx 336 patients To determine if age of the patient has significant bearing on management, since patients in the older age groups with nipple discharge and no palpable mass had a high incidence of carcinoma of the breast. Among our total group of 3,787 patients, 336, or slightly less than 10 percent, had a history of nipple discharge. One hundred and thirty-six patients, 40 percent of those with nipple discharge, had no palpable mass. In this group, there were 16 instances of carcinoma, an incidence of 11.8 percent. Over the age of 60 years, nine out of the 28 patients with nipple discharge and no associated mass had carcinoma, an incidence of 32 percent. There were 62 additional instances of carcinoma in the 200 patients with both nipple discharge and a palpable mass. This represents a carcinoma incidence in this group of 31 percent, and results in an incidence of carcinoma for all patients with discharge of 23 percent or 78 out of 336. Of all patients with bloody discharge, 25 percent had carcinoma, while 21 percent of those with serous discharge had carcinoma. Patients over the age of 60 years are of interest in that 46 percent of those with bloody discharge had carcinoma while 56 percent of those with serous discharge had carcinoma. Cytologic examination of nipple discharge in our experience has not proved helpful in differentiating benign from malignant breast lesions. 4
10. Cabioglu N, Hunt KK, Singletary SE, et al. Surgical decision making and factors determining a diagnosis of breast carcinoma in women presenting with nipple discharge. J Am Coll Surg. 2003;196(3):354-364. Observational-Dx 146 patients To identify patient and nipple-discharge characteristics associated with the diagnosis of breast cancer and to determine the utility of mammography, sonography, ductography, and cytology in surgical decision making in patients presenting with pathologic nipple discharge. A total of 146 patients presented at our institution with nipple discharge during the study period. Of these, 52 had clinically benign discharge and were managed without surgical intervention; 94 patients had pathologic discharge and underwent a biopsy procedure for histologic diagnosis, treatment, or both. Logistic regression analysis identified mammographic (relative risk [RR] = 10.47, 95% confidence interval [CI] 2.36 to 46.39, p = 0.0002) and sonographic (RR = 5.54, 95% CI 1.27 to 25.40, p = 0.028) abnormalities as independent factors associated with a malignant diagnosis. Nineteen cancers, 62 papillomas, and 13 other benign lesions were identified among the patients with pathologic discharge. In 3 patients with cancer (15.8%) and 30 patients with a papilloma (48.4%), ductography was the only means of identifying lesions to be resected. Patients who underwent ductography-guided operation (n = 42, 50%) or any surgical procedure including a localization study (n = 66, 78.6%) were significantly more likely than patients who underwent central duct excision alone to have a specific underlying lesion identified (p = 0.045 and p = 0.033, respectively). 3
11. Kalu ON, Chow C, Wheeler A, Kong C, Wapnir I. The diagnostic value of nipple discharge cytology: breast imaging complements predictive value of nipple discharge cytology. J Surg Oncol. 2012;106(4):381-385. Observational-Dx 89 patients To determine the predictive value of nipple discharge cytology in conjunction with breast imaging. 89 patients identified. Sixty-five had positive cytology, with a false positive rate of 32.3%. They were associated with papillomas in 52%, benign non-papillary in 33% and malignant lesions in 9% of cases. Nipple discharge cytology was positive in 69.6% of papillomas and 92% of atypical/malignant lesions; 30% had abnormal breast imaging and positive cytology. Nipple discharge cytology had a sensitivity of 74.5%, specificity of 30%, and positive predictive value of 68%. The positive predictive value increased to 85% with associated abnormal breast imaging. 3
12. Morrogh M, Park A, Elkin EB, King TA. Lessons learned from 416 cases of nipple discharge of the breast. Am J Surg. 2010;200(1):73-80. Observational-Dx 475 patients To define clinical predictors of malignancy and examine the utility of common preoperative studies. Following standard evaluation (clinical breast examination/mammogram/ultrasound), 129 of 416 (31%) were considered to have physiological ND and were managed expectantly, whereas 287 of 416 (69%) underwent further evaluation (cytology/ductography/magnetic resonance imaging) followed by biopsy +/- surgery. Clinical features associated with pathological ND included bloody ND (adjusted odds ratio 3.7) and spontaneous ND (adjusted OR 3.2). Biopsy/surgery identified a causative lesion in 259 of 287 (90%), of which 37% were either malignant (n = 65) or high-risk (n = 30) lesions. The sole clinical predictor of malignant/high-risk lesion was a palpable mass (adjusted odds ratio 4.3). Preoperative evaluation identified 76 of 95 (80%) malignant/high-risk lesions, whereas 19 of 95 (20%) were identified by duct excision alone. 3
13. Adepoju LJ, Chun J, El-Tamer M, Ditkoff BA, Schnabel F, Joseph KA. The value of clinical characteristics and breast-imaging studies in predicting a histopathologic diagnosis of cancer or high-risk lesion in patients with spontaneous nipple discharge. Am J Surg. 2005;190(4):644-646. Observational-Dx 168 cases To determine the utility of breast-imaging studies in identifying cancer and high-risk lesions among patients with spontaneous, single-duct, nipple discharge (SSND). The sensitivity of mammography was 10%, the specificity 94%, the NPV 88%, and the PPV 18%. Ultrasonography had a sensitivity of 36%, specificity of 68%, PPV of 14%, and NPV of 89%. Ductography had a sensitivity of 75%, specificity of 49%, and NPV and PPV of 93% and 18%, respectively. 3
14. Morrogh M, King TA. The significance of nipple discharge of the male breast. Breast J. 2009;15(6):632-638. Review/Other-Dx 24 male patients The authors present their experience with male patients presenting with a chief complaint of nipple discharge. Among 24 male patients presenting for evaluation, 14 (58%) presented with a chief complaint of nipple discharge, while the remaining 10 (42%) presented for evaluation of a palpable mass in the absence of nipple discharge. Among 14 patients presenting with nipple discharge, subsequent clinical breast examination identified a breast mass +/- nipple changes in 7/14 patients. In total, 8/14 (57%) patients had an underlying malignancy; 2/7 patients with nipple discharge alone had DCIS (median interval from onset of nipple discharge to presentation 3 weeks, range 2–4 weeks), and 6/7 patients with nipple discharge and a palpable mass had invasive disease (median interval between onset of nipple discharge 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), 14/16 cancer patients remain free of disease and 2 have died as a direct result of metastatic disease. The incidence of cancer among males presenting with nipple discharge was 57%. 4
15. Munoz Carrasco R, Alvarez Benito M, Rivin del Campo E. Value of mammography and breast ultrasound in male patients with nipple discharge. Eur J Radiol. 82(3):478-84, 2013 Mar. Observational-Dx 26 men with 21 mammograms and 19 USs To assess the contribution of mammography and US in men with nipple discharge. The final diagnoses were: 6 carcinomas (23.1%), 10 gynecomastias, 2 pseudogynecomastias and 8 normal breast tissues. Mammograms and USs performed on all 5 patients with infiltrating carcinoma showed a mass (categories 4 and 5). In all these patients except 1, a breast mass was also noted and the physical examination was positive or suspected malignancy. In the patient with carcinoma in situ, the only conspicuous clinical sign was bloody nipple discharge and the mammography showed calcifications (category 4) that were not visible on US. Radiological findings of all patients without malignancy were classified as categories 1 and 2. The diagnostic performance of physical examination was lower than mammography and US (P>0.05). Mammography was more sensitive than US (100% vs 83.3%). Both techniques showed the same specificity (100%). 3
16. Fentiman IS, Fourquet A, Hortobagyi GN. Male breast cancer. Lancet. 2006;367(9510):595-604. Review/Other-Tx N/A Review management of male breast cancer. Surgery is usually mastectomy with axillary clearance or sentinel node biopsy. Indications for radiotherapy, by stage, are similar to female breast cancer. Because 90% of tumors are estrogen-receptor-positive, tamoxifen is standard adjuvant therapy, but some individuals could also benefit from chemotherapy. Hormonal therapy is the main treatment for metastatic disease, but chemotherapy can also provide palliation. National initiatives are increasingly needed to improve information and support for male breast cancer patients. 4
17. Mainiero MB, Lourenco AP, Barke LD, et al. ACR Appropriateness Criteria Evaluation of the Symptomatic Male Breast. J. Am. Coll. Radiol.. 12(7):678-82, 2015 Jul. Review/Other-Dx N/A To evaluate the appropriateness of imaging modalities for the assessment of male patients with breast symptoms No results stated in abstract. 4
18. Dinkel HP, Trusen A, Gassel AM, et al. Predictive value of galactographic patterns for benign and malignant neoplasms of the breast in patients with nipple discharge. Br J Radiol. 2000;73(871):706-714. Observational-Dx 351 galactograms To identify features of malignant and non-malignant neoplastic breast disease on galactography and to estimate their predictive value. Extravasation or incomplete filling precluded reading in 9.5% of examinations. Among the remaining 143 examinations there were 11 cancers (7.7%), 56 papillomas (39.2%), 19 cases of intraductal papillomatous proliferation (13.3%), 55 cases of fibrocystic or secretory disease (38.5%) and two normals. A "filling defect/cut-off" pattern (n = 90) was found in 6 cancers (6.7%) and 58 cases of papilloma or papillomatous proliferation (64.4%). A "leafless tree" pattern was found only in benign cases (n = 12; 8.4%). In 32 of 143 cases (22.4%) a "ductal ectasia" pattern was present, in one case of which (3.1%) cancer was found. Cancer was identified in two of four cases with an "architectural distortion" pattern. 3
19. Van Zee KJ, Ortega Perez G, Minnard E, Cohen MA. Preoperative galactography increases the diagnostic yield of major duct excision for nipple discharge. Cancer. 1998;82(10):1874-1880. Review/Other-Dx 46 cases To investigate the utility of preoperative galactography in targeting the causative lesion. Preoperative galactography was obtained in 7 of 31 patients (23%) with bloody nipple discharge and 9 of 15 patients (60%) with guaiac negative discharge. All patients undergoing preoperative galactography were found to have either a filling defect and/or duct cutoff (n = 13) or duct ectasia (n = 3). All patients with a filling defect and/or duct cutoff on galactogram were found to have a carcinoma or papilloma at surgery. In the three patients with duct ectasia observed on galactogram, the diagnosis was confirmed at surgery. All patients who underwent preoperative galactography were found to have specific pathology that accounted for the nipple discharge versus 20 of 30 patients (67%) who did not undergo preoperative galactography (P = 0.009). 4
20. Moriarty AT, Schwartz MR, Laucirica R, et al. Cytology of spontaneous nipple discharge--is it worth it? Performance of nipple discharge preparations in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. Arch Pathol Lab Med. 2013;137(8):1039-1042. Observational-Dx 2506 responses To evaluate participant responses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology to assess the accuracy of cytologic interpretation of nipple discharge preparation. Of 2506 responses, 1280 (51%) were malignant, 171 (7%) were papillary, and 1055 (42%) were benign. There were 222 discordant general category responses with a false-positive/suspicious rate of 12.8% and a false-negative rate of 3.4%. The most common false-negative diagnosis was mastitis/abscess (125 of 1272 responses; 9.8%). The most common false-positive response was papillary lesion (26 of 457 responses; 5.7%). There were no differences between stains or years. Cytotechnologists performed better than pathologists; pathologists had a higher false-negative rate than cytotechnologists (15.3% versus 7.9%, P < .001). 3
21. Dooley WC. Breast ductoscopy and the evolution of the intra-ductal approach to breast cancer. Breast J. 2009;15 Suppl 1:S90-94. Review/Other-Dx N/A To discuss breast ductoscopy and the evolution of the intra-ductal approach to 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. 4
22. Kapenhas-Valdes E, Feldman SM, Boolbol SK. The role of mammary ductoscopy in breast cancer: a review of the literature. Ann Surg Oncol. 2008;15(12):3350-3360. Review/Other-Dx N/A To review the literature for the role of mammary ductoscopy No results listed in abstract. 4
23. Lubina N, Schedelbeck U, Roth A, et al. 3.0 Tesla breast magnetic resonance imaging in patients with nipple discharge when mammography and ultrasound fail. Eur Radiol. 25(5):1285-93, 2015 May. Observational-Dx 50 patients, 56 breasts To compare 3.0 Tesla breast magnetic resonance imaging (MRI) with galactography for detection of benign and malignant causes of nipple discharge in patients with negative mammography and ultrasound. Sensitivity and specificity of MRI vs. galactography for detecting pathologic findings were 95.7 % vs. 85.7 % and 69.7 % vs. 33.3 %, respectively. For the supposed concrete pathology based on MRI findings, the specificity was 67.6 % and the sensitivity 77.3 % (PPV 60.7 %, NPV 82.1 %). Eight malignant lesions were detected (14.8 %). The estimated size at breast MRI showed excellent correlation with the size at histopathology (Pearson's correlation coefficient 0.95, p < 0.0001). 2
24. Morrogh M, Morris EA, Liberman L, Borgen PI, King TA. The predictive value of ductography and magnetic resonance imaging in the management of nipple discharge. Ann Surg Oncol. 14(12):3369-77, 2007 Dec. Observational-Dx 306 patients To determine the predictive value of ductography (DG) and magnetic resonance imaging (MRI) in this setting Among 306 patients, 186 (61%) underwent further evaluation with DG (n = 163) and/or MRI (n = 52), 35 (11%) underwent major duct excision alone (MDE), and 85 (28%) were followed clinically. Ultimately, 182/306 (59%) patients underwent surgery and/or biopsy. Overall incidence of malignant or high-risk pathology was 15% (46/306). DG was completed in 139/163 (85%) studies and detected 12 cancers and seven high-risk lesions (HRL), but failed to identify four cancers and 2 HRL (PPV 19%, NPV 63%). MRI detected seven cancers and three HRL, but failed to identify one cancer and one HRL (PPV 56%, NPV 87%). MDE alone (n = 35) detected five cancers and three HRL. Of all patients not having surgery, (142/306, 41%), one (0.01%) presented with an invasive cancer at 102 months (median follow-up, 6.3 months; range, 0-124 months). 3
25. Sarica O, Zeybek E, Ozturk E. Evaluation of nipple-areola complex with ultrasonography and magnetic resonance imaging. [Review] [97 refs]. J Comput Assist Tomogr. 34(4):575-86, 2010 Jul. Review/Other-Dx N/A To evaluate nipple-areola complex with ultrasonography and magnetic resonance imaging Because both benign and malignant nipple periareolar region lesions may present with similar clinical findings such as nipple discharge and retraction, they require a diagnostically specific imaging workup. Despite multidisciplinary clinical approaches, malignancy cannot be excluded without diagnostic modalities.Because of the intricacy of the anatomical structures and their superficial position, the diagnostic techniques routinely used to evaluate the different sides of the breast may often be inadequate. Adjunct use of multiple imaging modalities is necessary to evaluate this region. 4
26. Brandt KR, Craig DA, Hoskins TL, et al. Can digital breast tomosynthesis replace conventional diagnostic mammography views for screening recalls without calcifications? A comparison study in a simulated clinical setting. AJR Am J Roentgenol. 2013;200(2):291-298. Observational-Dx 146 women To evaluate digital breast tomosynthesis (DBT) as an alternative to conventional diagnostic mammography in the workup of noncalcified findings recalled from screening mammography in a simulated clinical setting that incorporated comparison mammograms and breast ultrasound results. Agreement between DBT and diagnostic mammography BI-RADS categories was excellent for readers 1 and 2 (kappa = 0.91 and kappa = 0.84) and good for reader 3 (kappa = 0.68). For readers 1, 2, and 3, sensitivity and specificity of DBT for breast abnormalities were 100%, 100%, and 88% and 94%, 93%, and 89%, respectively. The clinical workup averaged three diagnostic views per abnormality and ultrasound was requested in 49% of the cases. DBT was adequate mammographic evaluation for 93-99% of the findings and ultrasound was requested in 33-55% of the cases. 2
27. Gennaro G, Hendrick RE, Toledano A, et al. Combination of one-view digital breast tomosynthesis with one-view digital mammography versus standard two-view digital mammography: per lesion analysis. Eur Radiol. 2013;23(8):2087-2094. Observational-Dx 463 breasts of 250 patients To evaluate the clinical value of combining one-view mammography (cranio-caudal, CC) with the complementary view tomosynthesis (mediolateral-oblique, MLO) in comparison to standard two-view mammography (MX) in terms of both lesion detection and characterization. The 463 cases (breasts) reviewed included 258 with one to three lesions each, and 205 with no lesions. The 258 cases with lesions included 77 cancers in 68 breasts and 271 benign lesions to give a total of 348 proven lesions. The combination, DBT(MLO)+MX(CC), was superior to MX (CC+MLO) in both lesion detection (LDF) and lesion characterization (LCF) overall and for benign lesions. DBT(MLO)+MX(CC) was non-inferior to two-view MX for malignant lesions. 2
28. Waldherr C, Cerny P, Altermatt HJ, et al. Value of one-view breast tomosynthesis versus two-view mammography in diagnostic workup of women with clinical signs and symptoms and in women recalled from screening. AJR Am J Roentgenol. 2013;200(1):226-231. Observational-Dx 144 women To compare the diagnostic value of one-view digital breast tomosynthesis versus two-view full-field digital mammography (FFDM) alone, and versus a combined reading of both modalities. Eighty-six of the 144 patients were found to have breast cancer. The BI-RADS categories for one-view digital breast tomosynthesis were significantly better than those for two-view FFDM (p < 0.001) and were equal to those of the combined reading in both women admitted for diagnostic workup and women recalled from screening. The sensitivity and negative predictive values of digital breast tomosynthesis were superior to those of FFDM in fatty and dense breasts overall and in women admitted for diagnostic workup and in women recalled from screening. Only 11% of digital breast tomosynthesis examinations required additional imaging, compared with 23% of FFDMs. 3
29. Yang TL, Liang HL, Chou CP, Huang JS, Pan HB. The adjunctive digital breast tomosynthesis in diagnosis of breast cancer. Biomed Res Int. 2013;2013:597253. Observational-Dx 59 breasts of 57 patients. To compare the diagnostic performance of digital breast tomosynthesis (DBT) and digital mammography (DM) for breast cancers. A total of 59 breast cancers were reviewed, including 17 (28.8%) mass lesions, 12 (20.3%) focal asymmetry/density, 6 (10.2%) architecture distortion, 23 (39.0%) calcifications, and 1 (1.7%) intracystic tumor. Combo DBT was perceived to be more informative in 58.8% mass lesions, 83.3% density, 94.4% architecture distortion, and only 11.6% calcifications. As to the forced BIRADS score, 84.4% BIRADS 0 on DM was upgraded to BIRADS 4 or 5 on DBT, whereas only 27.3% BIRADS 4A on DM was upgraded on DBT, as BIRADS 4A lesions were mostly calcifications. A significant P value (<0.001) between the BIRADS category and index lesions was noted 3
30. Stavros AT. Breast anatomy: the basis for understanding sonography. In: Stavros AT, ed. Breast ultrasound. Philadelphia, PA: Lippincott Williams & Wilkins; 2004: 56–108. Review/Other-Dx N/A Book chapter. N/A 4
31. Stavros AT. Ultrasound indication and interpretation. In: Bassett LW, Mahoney MC, Apple SK, D'Orsi CJ, eds. Breast imaging. Philadelphia, PA: Elsevier Saunders; 2011. Review/Other-Dx N/A Book chapter N/A 4
32. Cardenosa G, Eklund GW. Benign papillary neoplasms of the breast: mammographic findings. Radiology. 1991;181(3):751-755. Observational-Dx 77 patients To evaluate the mammographic findings of benign papillary neoplasms of the breast Fifty-one patients (66%) had solitary papillomas. Thirty-seven of these patients were symptomatic; 36 had spontaneous nipple discharge, and one had a palpable mass. Ductography was positive in 32 of the 35 patients who underwent the procedure. In the 14 asymptomatic patients, subareolar (n = 10) and peripheral (n = 4) mammographic abnormalities prompted biopsy. Fourteen patients (18%) had multiple peripheral papillomas, and one patient also had bilateral central solitary papillomas. Eleven of these patients were asymptomatic, while two presented with palpable abnormalities and one with spontaneous bilateral discharge. Mammographic findings included microcalcifications (n = 5) and clustering nodules (n = 2). Associated atypical ductal hyperplasia was found in six (43%) of the 14 patients with multiple peripheral papillomas. Some of these patients also had lobular carcinoma in situ and radical scars. Twelve patients had multiple central papillomas; all presented with spontaneous nipple discharge and had positive ductograms. 4
33. Sickles EA. Galactography and other imaging investigations of nipple discharge. Lancet. 2000;356(9242):1622-1623. Review/Other-Dx N/A No abstract available No abstract available 4
34. Koskela A, Berg M, Pietilainen T, Mustonen P, Vanninen R. Breast lesions causing nipple discharge: preoperative galactography-aided stereotactic wire localization. AJR Am J Roentgenol. 2005;184(6):1795-1798. Review/Other-Dx 9 patients To assess the feasibility and diagnostic performance of these techniques in patients with spontaneous unilateral nipple discharge. No results stated in the abstract 4
35. Ballesio L, Maggi C, Savelli S, et al. Role of breast magnetic resonance imaging (MRI) in patients with unilateral nipple discharge: preliminary study. Radiol Med (Torino). 113(2):249-64, 2008 Mar. Review/Other-Dx 44 patients To assess the role of magnetic resonance imaging (MRI) in patients with unilateral nipple discharge. MRI identified 25 enhancing lesions Breast Imaging Reporting and Data Systems (BI-RADS) 3 or 4) and confirmed the galactographic findings (ductal ectasia, intraluminal filling defects). Five papillomatoses appeared as patchy, homogeneous enhancing areas, 15 intraductal papillomas as areas with well-defined margins and type II time-intensity curves, and two atypical ductal hyperplasias as diffuse nodular enhancement. One micropapillary ductal carcinoma in situ (DCIS), one papillary carcinoma and one infiltrating ductal carcinoma (IDC) were visualised as two segmental areas of enhancement and one mass-like enhancement with poorly defined margins (BI-RADS 4). The follow-up was negative, showing no pathological enhancement (BI-RADS 1) in 12 patients and benign enhancement (BI-RADS 2) in seven. 4
36. Mathieu I, Mazy S, Willemart B, Destine M, Mazy G, Lonneux M. Inconclusive triple diagnosis in breast cancer imaging: is there a place for scintimammography? J Nucl Med. 2005; 46(10):1574-1581. Observational-Dx 104 patients; 118 procedures Retrospective study to evaluate impact of scintimammography (SM) in patients with doubtful or discordant triple diagnosis—that is mammography, US, and FNAC. Breast cancer was proven in 69 cases. SM-SPECT had a sensitivity of 88.4% and a specificity of 67%. Eleven cancers were detected by SPECT, although planar images were negative. SM-SPECT was more sensitive in patients scanned at initial presentation (95%) than in those with suspected recurrence (81%). SM-SPECT correctly evaluated multicentricity or bilaterality in 8 of 11 patients and resulted in an increased tumor size in 8 patients. Overall, SM-SPECT modified the patient management in 58 of 118 cases (49%): SM made the diagnosis of cancer in 30 cases with doubtful or discordant triple diagnosis and ruled out malignancy in 28 cases. SM-SPECT had a sensitivity of 88.4% and a specificity of 67%. Overall, SM-SPECT modified patient management in 58/118 cases (49%). 3
37. Yutani K, Shiba E, Kusuoka H, et al. Comparison of FDG-PET with MIBI-SPECT in the detection of breast cancer and axillary lymph node metastasis. J Comput Assist Tomogr. 2000; 24(2):274-280. Observational-Dx 40 patients Compare (FDG) PET to Tc-99m methoxyisobutylisonitrile (MIBI) SPECT for breast cancer diagnosis and axillary lymph node metastasis in the same patients. 38 patients had breast cancer, and the remaining two had benign breast lesions.The sensitivities of FDG-PET and MIBI-SPECT were 78.9% and 76.3% for breast cancer and 50.0% and 37.5% for axillary lymph node metastasis, respectively. MIBI-SPECT is comparable with FDG-PET in detecting breast cancer. Neither FDG-PET nor MIBI-SPECT is sufficiently sensitive to rule out axillary lymph node metastasis. Results indicate that MIBI-SPECT is comparable with FDG-PET in detecting breast cancer. Neither FDG-PET nor MIBI-SPECT is sufficiently sensitive to rule out axillary lymph node metastasis. 2
38. Berg WA, Weinberg IN, Narayanan D, et al. High-resolution fluorodeoxyglucose positron emission tomography with compression ("positron emission mammography") is highly accurate in depicting primary breast cancer. Breast J 2006; 12(4):309-323. Observational-Dx 92 lesions in 77 women To prospectively assess the diagnostic performance of a high-resolution PET scanner using mild breast compression (positron emission mammography [PEM]). Of 48 cancers, 16 (33%) were clinically evident; 11 (23%) were DCIS, and 37 (77%) were invasive (30 ductal, 4 lobular, and 3 mixed; median size 21 mm). PEM depicted 10 of 11 (91%) DCIS and 33 of 37 (89%) invasive cancers. PEM was positive in 1 of 2 T1a tumors, 4 of 6 T1b tumors, 7 of 7 T1c tumors, and 4 of 4 cases where tumor size was not available (e.g., no surgical follow-up). PEM sensitivity for detecting cancer was 90%, specificity 86%, PPV 88%, NPV 88%, accuracy 88%, and area under the receiver-operating characteristic curve (Az) 0.918. In three patients, cancer foci were identified only on PEM, significantly changing patient management. Excluding eight diabetic subjects and eight subjects whose lesions were characterized as clearly benign with conventional imaging, PEM sensitivity was 91%, specificity 93%, PPV 95%, NPV 88%, accuracy 92%, and Az 0.949 when interpreted with mammographic and clinical findings. FDG PEM has high diagnostic accuracy for breast lesions, including DCIS. 2
39. Brem RF, Fishman M, Rapelyea JA. Detection of ductal carcinoma in situ with mammography, breast specific gamma imaging, and magnetic resonance imaging: a comparative study. Acad Radiol. 2007; 14(8):945-950. Observational-Dx 20 women with 22 biopsy-proven DCIS To evaluate the sensitivity of high-resolution breast-specific gamma imaging (BSGI) for the detection of DCIS based on histopathology and to compare the sensitivity of BSGI with mammography and MRI for the detection of DCIS. Pathologic tumor size of the DCIS ranged from 2 to 21 mm (mean 9.9 mm). Of 22 cases of biopsy-proven DCIS in 20 women, 91% were detected with BSGI, 82% were detected with mammography, and 88% were detected with MRI. BSGI had the highest sensitivity for the detection of DCIS, although this small sample size did not demonstrate a statistically significant difference. Two cases of DCIS (9%) were diagnosed only after BSGI demonstrated an occult focus of radiotracer uptake in the contralateral breast, previously undetected by mammography. There were two false-negative BSGI studies BSGI has higher sensitivity for the detection of DCIS than mammography or MRI and can reliably detect small, subcentimeter lesions. 3
40. Garg S, Mohan H, Bal A, Attri AK, Kochhar S. A comparative analysis of core needle biopsy and fine-needle aspiration cytology in the evaluation of palpable and mammographically detected suspicious breast lesions. Diagn Cytopathol. 35(11):681-9, 2007 Nov. Observational-Dx 50 patients To compare value of needle core biopsy and fine-needle aspiration cytology (FNAC) in the evaluation of palpable and mammographically detected suspicious breast lesions. Sensitivity and specificity of mammography for malignant diagnosis was 84.37% and 83.33%, respectively. Sensitivity and specificity of FNAC for malignant diagnosis was 78.15% and 94.44%, respectively, and of needle core biopsy was 96.5% and 100%, respectively. Needle core biopsy is superior to FNAC in the diagnosis of breast lesions in terms of sensitivity, specificity, correct histological categorization of the lesions and tumor grading. 3
41. Homesh NA, Issa MA, El-Sofiani HA. The diagnostic accuracy of fine needle aspiration cytology versus core needle biopsy for palpable breast lump(s). Saudi Med J. 2005; 26(1):42-46. Experimental-Dx 296 patients Prospective randomized controlled clinical trial to compare the accuracy of FNAC and core needle biopsy in patients with palpable breast masses. FNAC had sensitivity of 66.66%, specificity of 81.8% accuracy of 75.7%, PPV of 100% and NPV of 90%. Core needle breast biopsy had sensitivity of 92.3%, specificity of 94.8%, and accuracy of 93.4%, PPV of 100% and NPV 100%. Core needle biopsy is more accurate than FNAC. Both procedures are simple, easy, safe, cheap and reliable, but CNB is more accurate than the FNAC. 1
42. Barreau B, de Mascarel I, Feuga C, et al. Mammography of ductal carcinoma in situ of the breast: review of 909 cases with radiographic-pathologic correlations. Eur J Radiol. 2005;54(1):55-61. Observational-Dx 909 cases To analyse radiologic signs of ductal carcinoma in situ (DCIS) to appreciate the extension and there possible "agressivity". We retrospectively analysed mammographies of 909 ductal carcinoma in situ (DCIS) (1980–1999) and compared our results to those of literature. Microcalcifications were present in 75% of the cases, and soft-tissue abnormalities in 27% cases with association with calcifications in 14% of cases. Palpable masses were found in 12% of the cases and nipple discharge was present in 12% of the cases. The radiographic–pathologic correlation allowed to suspect the DCIS “aggressiveness” on radiologic signs. Granular, linear, branching and/or galactophoric topography of the microcalcifications were correlated with necrosis, grade 3, comedocarcinoma type. A number of microcalcifications higher than 20 was correlated with necrosis and grade 3. Mammographic size was correlated to histologic size. Masses were correlated with grade 1. A diagnosis strategy can be proposed with a multidisciplinar approach. 4
43. Apple SK, Overstreet JMJ, Bassett LW. Ductal carcinoma in situ and Paget's disease. In: Bassett LW, Mahoney MC, Apple SK, D'Orsi CJ, eds. Breast imaging. Philadelphia, PA: Elsevier Saunders; 2011. Review/Other-Dx N/A Book chapter. N/A 4
44. Harvey JA, Nicholson BT, Cohen MA. Finding early invasive breast cancers: a practical approach. Radiology. 2008;248(1):61-76. Review/Other-Dx N/A To provide a practical approach to the detection and management of breast masses and focal asymmetries. Invasive breast cancers typically manifest mammographically as focal asymmetries or masses. Strategies for detecting focal asymmetries and masses on screening mammograms include side-by-side comparison, looking for parenchymal contour deformity, close inspection of the retromammary fat, identifying the presence of associated findings, and comparison with prior mammograms. Focal asymmetries are often normal but are concerning when there is distortion of the normal breast architecture. Masses and focal asymmetries are best evaluated in the diagnostic setting by using spot compression and true lateral views and, frequently, ultrasonography. Management of a lesion depends on the worst imaging feature. Indications for an assessment of probably benign findings are very specific but are often misapplied. 4
45. Berg WA, Gilbreath PL. Multicentric and multifocal cancer: whole-breast US in preoperative evaluation. Radiology. 2000;214(1):59-66. Observational-Dx 40 patients To evaluate preoperative whole-breast ultrasonography (US) in the management of breast cancer. US depicted 45 (94%) of 48 invasive tumor foci and seven (44%) of 16 foci of ductal carcinoma in situ (DCIS). Mammography depicted 39 (81%) of 48 invasive tumor foci and 14 (88%) of 16 foci of DCIS. The nine (14%) of 64 malignant foci seen only at US included three infiltrating ductal carcinomas, two mixed infiltrating and intraductal carcinomas, two infiltrating lobular carcinomas, and two foci of DCIS. Two (18%) of 11 foci of infiltrating lobular carcinoma were missed at both US and mammography. Of 20 patients mammographically suspected of having unifocal disease, three (15%) required wider excision on the basis of US findings. Two additional foci were depicted only at US in one of 16 patients mammographically suspected of having multicentric or multifocal disease. Of four patients with mammographically occult disease, US correctly depicted the diffuse (n = 2) or unifocal (n = 2) extent of the cancer. 3
46. Nakahara H, Namba K, Watanabe R, et al. A comparison of MR imaging, galactography and ultrasonography in patients with nipple discharge. Breast Cancer. 2003;10(4):320-329. Observational-Dx 55 patients To assess the usefulness of three-dimensional contrast-enhanced magnetic resonance (MR) imaging, compared with galactography and ultrasonography (US). Contrast enhanced MR imaging demonstrated all malignant lesions including ductal carcinoma in situ (DCIS). Four cases of DCIS were not visualized by ultrasonography and three malignant lesions were missed by galactography. In the MR study, segmental clumped enhancement (positive predictive value =100 %), and focal mass with smooth border (negative predictive value =87.5 %) were the statistically significant predictive factors. 3
47. Skaane P, Bandos AI, Eben EB, et al. Two-view digital breast tomosynthesis screening with synthetically reconstructed projection images: comparison with digital breast tomosynthesis with full-field digital mammographic images. Radiology. 2014;271(3):655-663. Experimental-Dx 24,901 examinations To compare the performance of two versions of reconstructed two-dimensional (2D) images in combination with digital breast tomosynthesis (DBT) versus the performance of standard full-field digital mammography (FFDM) plus DBT. Cancer detection rates were 8.0, 7.4, 7.8, and 7.7 per 1000 screening examinations for FFDM plus DBT in period 1, initial reconstructed 2D images plus DBT in period 1, FFDM plus DBT in period 2, and current reconstructed 2D images plus DBT in period 2, respectively. False-positive scores were 5.3%, 4.6%, 4.6%, and 4.5%, respectively. Corresponding reader-adjusted paired comparisons of false-positive scores revealed significant differences for period 1 (P = .012) but not for period 2 (ratio = 0.99; 95% confidence interval: 0.88, 1.11; P = .85) 1
48. Rissanen T, Reinikainen H, Apaja-Sarkkinen M. Breast sonography in localizing the cause of nipple discharge: comparison with galactography in 52 patients. J Ultrasound Med. 26(8):1031-9, 2007 Aug. Observational-Dx 52 patients To evaluate breast sonography in localizing abnormalities in the discharging duct in patients with spontaneous nipple discharge. The final diagnosis was benign in 47 cases (90%) and malignant in 5 cases (10%). Sonography visualized an echogenic intraductal tumor in 36 (69%) of 52 cases, dilated duct(s) without an intraductal tumor in 6 cases (12%), and no abnormality in 10 cases (19%). Eighty percent of papillomatous lesions, 58% of other benign lesions, and 20% of malignant lesions were sonographically positive. The abnormal duct was surgically removed after methylene blue staining in 38 cases, after sonographically guided wire localization in 11 cases, after both wire localization and methylene blue staining in 1 case, and with review of the diagnostic galactographic images in 2 cases. 3
49. Simmons R, Adamovich T, Brennan M, et al. Nonsurgical evaluation of pathologic nipple discharge. Ann Surg Oncol. 2003;10(2):113-116. Observational-Dx 108 patients To evaluate the sensitivity and specificity of using mammography, ductography, cytology, and Hemoccult staining to detect malignant lesions causing pathologic nipple discharge. Of the 108 surgical histopathology specimens, 90 of 108 patients were benign, 5 of 108 patients were atypical, and 13 of 108 patients were malignant. The sensitivity of mammography was 57.1%, specificity was 61.5%, positive predictive value was 16.7%, and negative predictive value was 91.4%. Hemoccult sensitivity was 50%, specificity was 0%, positive predictive value was 20%, and negative predictive value was 0%. The sensitivity of ductography was 0%, specificity was 90%, positive predictive value was 0%, and negative predictive value was 81.8%. The sensitivity of cytology was 11.1%, specificity was 96.3%, positive predictive value was 50%, and negative predictive value was 76.5%. 3
50. Mahoney MC, Jackson VP, Bassett LW. Galactography. In: Bassett LW, Mahoney MC, Apple SK, D'Orsi CJ, eds. Breast imaging. Philadelphia, PA: Elsevier Saunders; 2011. Review/Other-Dx N/A No abstract available No abstract available 4
51. Comstock CE, Sung JS. Computer-aided detection for breast MRI. In: Molleran VM, Mahoney MC, eds. Breast MRI. Philadelphia, PA: Elsevier Saunders; 2014. Review/Other-Dx N/A Book N/A 4
52. Kleimeyer AE, Mahoney MC. MRI for breast implant evaluation. In: Molleran VM, Mahoney MC, eds. Breast MRI. Philadelphia, PA: Elsevier Saunders; 2014. Review/Other-Dx N/A Book N/A 4
53. Manganaro L, D'Ambrosio I, Gigli S, et al. Breast MRI in patients with unilateral bloody and serous-bloody nipple discharge: a comparison with galactography. Biomed Res Int. 2015;2015:806368. Observational-Dx 53 patients To assess the role of breast MRI compared to galactography in patients with unilateral bloody or serous-bloody nipple discharge. After surgery and follow-up, 8 patients had no disease (15%), 23 papilloma (43%), 11 papillomatosis (21%), 5 ductal cancer in situ (10%), and 6 papillary carcinoma (11%) diagnoses. Both techniques presented 100% specificity; MRI sensitivity was 98% versus 49% of galactography. Considering MRI, we found a statistical association between mass enhancement and papilloma (P < 0.001; AUC 0.957; CI 0.888-1.025), ductal enhancement and papillomatosis (P < 0.001; AUC 0.790; CI 0.623-0.958), segmental enhancement and ductal cancer in situ (P = 0.007; AUC 0.750; CI 0.429-1.071), and linear enhancement and papillary cancer (P = 0.011). 2
54. Mortellaro VE, Marshall J, Harms SE, Hochwald SN, Copeland EM, 3rd, Grobmyer SR. Breast MR for the evaluation of occult nipple discharge. Am Surg. 2008;74(8):739-742. Review/Other-Dx 2 case reports To document the capacity of MR to identify areas of associated pathology in patients with pathologic nipple discharge that could not otherwise be detected by conventional workup. Breast MR should be considered in the toolbox evaluation of occult nipple discharge when other available strategies have failed to demonstrate an underlying etiology for the pathologic discharge. The use of breast MR in this setting may permit directed evaluation and management of potentially malignant lesions. 4
55. van Gelder L, Bisschops RH, Menke-Pluymers MB, Westenend PJ, Plaisier PW. Magnetic resonance imaging in patients with unilateral bloody nipple discharge; useful when conventional diagnostics are negative?. World J Surg. 39(1):184-6, 2015 Jan. Observational-Dx 111 women To evaluate the diagnostic value of breast MRI in patients with unilateral bloody nipple discharge (UBND) in the absence of a palpable mass, with negative findings on mammography (MMG) combined with US. A total of 111 women (mean age 52 years; range 23–80) were included. In nine (8 %) patients, malignancy was suspected on MRI while conventional imaging was normal. In eight (89 %) of these patients, histology was obtained, two by core biopsy and six by terminal duct excision. Benign conditions were found in six patients (86 %) and a (pre-) malignant lesion in two patients. In both cases, it concerned a ductal carcinoma in situ, which was treated with breast-conserving therapy. Moreover, in two cases of (pre)malignancy, the MRI was interpreted as negative. Conclusion In patients with UBND who show no signs of a malignancy on conventional diagnostic examinations, the added value of a breast MRI is limited, since a malignancy can be demonstrated in\2 %. 3
56. Bahl M, Baker JA, Greenup RA, Ghate SV. Evaluation of Pathologic Nipple Discharge: What is the Added Diagnostic Value of MRI?. Annals of Surgical Oncology. 22 Suppl 3:S435-41, 2015 Dec. Observational-Dx 103 women To determine the diagnostic value of magnetic resonance imaging (MRI) for the evaluation of patients with pathologic nipple discharge. Over a 10-year period, 103 women (mean age 46 years, range 25-72 years) underwent MRI for evaluation of nipple discharge. Ninety-one patients (88 %) underwent surgical excision or had clinical and/or radiographic follow-up at least 2 years after presentation and thus comprise the study population. Eleven (30 %) of 37 patients with MRIs coded as American College of Radiology Breast Imaging-Reporting and Data System (BI-RADS) 4 of 5 were diagnosed with ductal carcinoma in situ (n = 6) or invasive adenocarcinoma (n = 5). Seven (64 %) of 11 patients diagnosed with malignancy had a negative mammographic and sonographic workup. None of the patients with MRIs coded as BI-RADS 1, 2, or 3 was diagnosed with malignancy immediately after presentation or during the 2-year follow-up period. The sensitivity and specificity of MRI for the detection of malignancy were 100 % (11 of 11) and 68 % (54 of 80), respectively. The positive predictive value and negative predictive value were 37 and 100 %, respectively. 3
57. Hirose M, Nobusawa H, Gokan T. MR ductography: comparison with conventional ductography as a diagnostic method in patients with nipple discharge. Radiographics. 2007;27 Suppl 1:S183-196. Review/Other-Dx N/A To review the causes of pathologic nipple discharge and discuss the diagnostic strategy; to demonstrate and explain the findings at conventional ductography, MR ductography, and fusion imaging with MR ductography and MR mammography in patients with pathologic nipple discharge; and to discuss the advantages and disadvantages of conventional ductography and MR ductography. No results stated in abstract. 4
58. Dennis MA, Parker S, Kaske TI, Stavros AT, Camp J. Incidental treatment of nipple discharge caused by benign intraductal papilloma through diagnostic Mammotome biopsy. AJR Am J Roentgenol. 2000;174(5):1263-1268. Observational-Tx 49 women To evaluate imaging-guided vacuum-assisted mammotome biopsy as a minimally invasive method of obtaining a satisfactory diagnosis and eliminating the bothersome symptoms in patients presenting with nipple discharge In all biopsied patients, satisfactory tissue for diagnosis was obtained. In patients biopsied with the mammotome probe, follow-up at a mean time of 13 months revealed resolution of the presenting problematic discharge in 97.2% of patients. Complications were mild and infrequent. Only one of 50 percutaneously biopsied lesions was not benign and required subsequent surgery. 2
59. Reiner CS, Helbich TH, Rudas M, et al. Can galactography-guided stereotactic, 11-gauge, vacuum-assisted breast biopsy of intraductal lesions serve as an alternative to surgical biopsy? Eur Radiol. 2009;19(12):2878-2885. Observational-Dx 18 patients To determine the value of galactography-guided, stereotactic, vacuum-assisted breast biopsy (VABB) for the assessment of intraductal breast lesions and its potential as a therapeutic tool that could eliminate the need for surgical excision After vacuum-assisted breast biopsy (VABB), histopathology revealed invasive ductal carcinoma (IDC) in three (17%), ductal carcinoma in situ (DCIS) in six (33%), high-risk lesions in six (33%) and benign lesions in three (17%) cases. After surgical biopsy, histopathology confirmed the previously established diagnosis in 11 lesions (61%). The underestimation rate for high-risk lesions and DCIS was 50% (6/12). The false-negative rate was 7% (1/14). Histopathology examination after surgery showed that not a single lesion had been completely removed at VABB. 3
60. Liberman L, Tornos C, Huzjan R, Bartella L, Morris EA, Dershaw DD. Is surgical excision warranted after benign, concordant diagnosis of papilloma at percutaneous breast biopsy? AJR Am J Roentgenol. 2006;186(5):1328-1334. Observational-Dx 3864 lesions To determine the cancer frequency in lesions yielding a benign, concordant diagnosis of papilloma at percutaneous breast biopsy. Cancer was found in five (14%) of the 35 lesions yielding a benign, concordant diagnosis of papilloma at percutaneous biopsy. Cancer histology was ductal carcinoma in situ in four (80%) and node-negative invasive cancer in one. Four (80%) of five cancers were identified due to interval change at follow-up (median, 22 months; range, 7-25 months). In six (17%) of 35 lesions, surgery revealed high-risk lesions including atypical ductal hyperplasia (n = 3), radial scar (n = 2), and lobular carcinoma in situ (n = 1). There was a significantly (p = 0.02) higher frequency of cancer or high-risk lesion in women with multiple versus solitary papillomas and a trend (p = 0.09) toward a higher cancer rate in women with versus without a family history of breast cancer. Breast cancer history, menopausal status, mammographic pattern, biopsy method, and removal of imaging target had no significant impact on cancer rate. 3
61. Sydnor MK, Wilson JD, Hijaz TA, Massey HD, Shaw de Paredes ES. Underestimation of the presence of breast carcinoma in papillary lesions initially diagnosed at core-needle biopsy. Radiology. 2007;242(1):58-62. Observational-Dx 57 women To retrospectively determine the degree of underestimation of breast carcinoma diagnosis in papillary lesions initially diagnosed at core-needle biopsy. In 38 of 63 lesions, surgical excision was performed; in 25 additional lesions (considered benign), follow-up mammography (24-month minimum) was performed, with no interval change. In 15 lesions, 14-gauge core needle was used; in 48, vacuum assistance (mean cores per lesion, 8.7). Carcinoma was found at excision in 14 of 38 lesions. Core pathologic findings associated with malignancy were benign papilloma (n=1), sclerotic papilloma (n=1), micropapilloma (n=2), and atypical papilloma (n=10). Frequency of malignancy was one (3%) of 38 benign papillomas, 10 (67%) of 15 atypical papillomas, two (50%) of four micropapillomas, and one (17%) of six sclerotic papillomas. Excisional findings included lobular carcinoma in situ (n=2), ductal carcinoma in situ (n=7), papillary carcinoma (n=2), and invasive ductal carcinoma (n=3). Low-risk group (micropapillomas and sclerotic and benign papillomas) was compared with high-risk atypical papilloma group. Core findings were associated with malignancy at excision for atypical papilloma (P=.006). Lesion location, mammographic finding, core number, or needle type were not associated (P>.05) with underestimation of malignancy at excision. 3
62. Georgian-Smith D, Lawton TJ. Controversies on the management of high-risk lesions at core biopsy from a radiology/pathology perspective. Radiol Clin North Am. 2010;48(5):999-1012. Review/Other-Dx N/A To discuss the controversies on the management of high-risk lesions at core biopsy from a radiology/pathology perspective No results listed in abstract. 4
63. Dupont SC, Boughey JC, Jimenez RE, Hoskin TL, Hieken TJ. Frequency of diagnosis of cancer or high-risk lesion at operation for pathologic nipple discharge. Surgery. 2015;158(4):988-994; discussion 994-985. Observational-Dx 311 subareolar duct excisions cases To stratify patients into groups most likely to benefit from operation as well as to reliably identify a group of patients for whom operation might be avoided. In 27 cases, cancer was diagnosed preoperatively. Among the remaining 284, 26 (9%) were diagnosed with cancer and 8 (3%) with atypia at operation. At greatest risk of upstage to cancer were patients with prior ipsilateral breast cancer (3/8; 38%), BRCA mutation (2/3; 67%) or atypia on core needle biopsy (CNB; 3/8 [38%]). Excluding these patients lowered cancer and atypia upstages (7% [18/265] and 3% [7/265]), with bloody (versus serous) discharge (P = .001), and focal imaging abnormality (P = .02), the strongest risk factors. Serous discharge and either normal imaging or a benign CNB had a 1.3% cancer upstage rate. 3
64. Dawes LG, Bowen C, Venta LA, Morrow M. Ductography for nipple discharge: no replacement for ductal excision. Surgery. 1998;124(4):685-691. Observational-Dx 91 patients To investigate whether ductography supplied additional information in the decision for surgery and/or the localization of pathologic lesion. Of 91 patients with nipple discharge, 49 met the criteria for physiologic discharge and 42 had pathologic discharge. Eleven with physiologic discharge had ductograms; none were abnormal. Four of 20 preoperative ductograms were normal but showed intraductal papillomas at the time of surgery; 6 of 20 (30%) had multiple lesions. Four lesions on ductograms did not demonstrate corresponding lesions in the surgical specimen. It is uncertain whether this is due to a missed lesion or a false-positive ductogram. 3
65. American Cancer Society. Cancer Facts and Figures 2012: Atlanta: American Cancer Society. 2012; Available at: Review/Other-Dx N/A Presents Breast Cancer Facts and Figures - 2012 N/A 4
66. Lehman CD, Lee CI, Loving VA, Portillo MS, Peacock S, Demartini WB. Accuracy and value of breast ultrasound for primary imaging evaluation of symptomatic women 30-39 years of age. AJR. 2012; 199(5):1169-1177. Observational-Dx 1208 cases in 954 patients To determine the accuracy and value of breast ultrasound for primary imaging evaluation of women 30-39 years of age who present with focal breast signs or symptoms. Outcomes were benign in 1185 of 1208 (98.1%) and malignant in 23 of 1208 (1.9%) cases. Sensitivities for ultrasound and mammography were 95.7% and 60.9%, respectively. Specificities for ultrasound and mammography were 89.2% and 94.4%, respectively. NPV was 99.9% for ultrasound and 99.2% for mammography. PPV was 13.2% for ultrasound and 18.4% for mammography. Mammography detected one additional malignancy in an asymptomatic area in a 32-year-old woman who was subsequently found to have a BRCA2 gene mutation. 3
67. Osako T, Iwase T, Takahashi K, et al. Diagnostic mammography and ultrasonography for palpable and nonpalpable breast cancer in women aged 30 to 39 years. Breast Cancer. 2007; 14(3):255-259. Observational-Dx 165 patients To investigate the relationship between the tumor size of breast cancer by palpation and the sensitivity of mammography (MMG) and US, and which modality can detect nonpalpable breast cancer in women aged 30 to 39 years. Of 165 patients, 147 patients (89%) showed mammographically dense breasts. Of 165 cancers, 14 (8%) were Tnp, 40 (24%) were T1p, 82 (50%) were T2p, and 29 (18%) were T3p. The sensitivity of MMG was 57% (8 of 14) for Tnp, 78% (31 of 40) for T1p, 90% (74 of 82) for T2p, and 97% (28 of 29) for T3p. The sensitivity of US was 43% (6 of 14) for Tnp and 100% for palpable cancers. Of 14 nonpalpable cancers, 4 (29%), 4 (29%), and 2 (14%) could be detected by only MMG, bloody nipple discharge, and US, respectively. The sensitivity of MMG depends on the tumor size and on palpation in this age range. MMG fails to detect relatively large palpable cancers. On the other hand, US can detect all palpable cancers. However, the sensitivity of US declines for nonpalpable cancers. For the detection of nonpalpable cancers, MMG, US, and nipple discharge are complementary modalities. 4
68. Ciatto S, Bravetti P, Bonardi R, Rosselli del Turco M. The role of mammography in women under 30. Radiol Med. 1990; 80(5):676-678. Observational-Dx 305 patients To determine the appropriate use of mammography in younger women with a solid palpable mass. Mammography missed 5/18 cancers (28%) and is not recommended in women under 30 except for preoperative cases with a strong suspicion of cancer. 3
69. Williams SM, Kaplan PA, Petersen JC, Lieberman RP. Mammography in women under age 30: is there clinical benefit? Radiology 1986; 161(1):49-51. Observational-Dx 76 patients; 2 observers Retrospective study to determine the utility of mammography in women less than 30 years of age referred for mammography. 55% had a palpable mass. In this group, no mass seen by mammography in 74%. But 14% had a definite lesion found by other means. No cancers were found. US may be best initial approach with mammography reserved for preoperative cases. 4
70. Yue D, Swinson C, Ravichandran D. Triple assessment is not necessary in most young women referred with breast symptoms. Ann R Coll Surg Engl. 2015;97(6):466-468. Observational-Dx 955 females aged under 25 years To see whether CB/FNA could be avoided in young women with benign findings on CE and imaging. The most common presenting complaint was a lump, followed by pain and nipple discharge. CE was normal or revealed benign findings in all except 15 patients, in whom it was indeterminate. Ultrasonography was performed in 692 patients (72%) and was normal (n=289) or benign (n=382) in all except 21 patients, in whom it was indeterminate. In six patients, both were indeterminate. A total of 317 patients (35%) had triple assessment: FNA in 106, CB in 239 and both in 9 cases. No cancers were diagnosed. 3
71. Ashfaq A, Senior D, Pockaj BA, et al. Validation study of a modern treatment algorithm for nipple discharge. Am J Surg. 208(2):222-7, 2014 Aug. Observational-Dx 192 patients To validate the proposed treatment algorithm after its implementation in our practice. A total of 192 patients, mean age 56 years, were studied. Risk of carcinoma among the entire cohort was 5%. Breast surgeon was consulted for 142 (74%) patients: 48 (34%) underwent initial subareolar excision and 94 (66%) were clinically followed. The rate of carcinoma was 17% (8/48) after initial subareolar excision, 0% (0/13) for those without imaging abnormalities, 23% (8/35) with imaging abnormalities, and 1% (1/94) with clinical follow-up. Of patients who underwent follow-up, 21% (n = 20) underwent subareolar excision because of imaging abnormality (n = 1, 1%) or persistent discharge (n = 19, 20%). Most patients had ductal carcinoma in situ (n = 5, 56%). 3
72. Skaane P, Sauer T. Ultrasonography of malignant breast neoplasms. Analysis of carcinomas missed as tumor. Acta Radiol. 1999;40(4):376-382. Observational-Dx 2,985 patients To analyze the clinical and pathological features of breast malignancies missed as tumor on ultrasonography (US) in a large consecutive series of patients and in a subpopulation manifesting with no suspicious microcalcifications on mammography. 42 (11.8%) of the 355 malignant neoplasms were missed as tumor on US, including 6 (2.5%) of the 243 palpable and 36 (32.1%) of the 112 nonpalpable malignancies. Most of the missed tumors were DCIS and microinvasive ductal carcinomas dominated by DCIS. In the subpopulation, 14 (5.7%) of the 245 malignancies were missed as tumor on US, including 4 (2.2%) of the 180 palpable and 10 (15.4%) of the 65 nonpalpable lesions. Of the 245 malignancies, 6 (2.4%) had a normal US finding, including 2 palpable retropapillary tumors and 4 incidental findings at histology. 3
73. Zuley ML, Guo B, Catullo VJ, et al. Comparison of two-dimensional synthesized mammograms versus original digital mammograms alone and in combination with tomosynthesis images. Radiology. 2014;271(3):664-671. Observational-Dx 123 patients To assess interpretation performance and radiation dose when two-dimensional synthesized mammography (SM) images versus standard full-field digital mammography (FFDM) images are used alone or in combination with digital breast tomosynthesis images. Probability of malignancy-based mean AUCs for SM and FFDM images alone was 0.894 and 0.889, respectively (difference, -0.005; 95% confidence interval [CI]: -0.062, 0.054; P = .85). Mean AUC for SM with tomosynthesis and FFDM with tomosynthesis was 0.916 and 0.939, respectively (difference, 0.023; 95% CI: -0.011, 0.057; P = .19). In terms of the reader-specific AUCs, five readers performed better with SM alone versus FFDM alone, and all eight readers performed better with combined FFDM and tomosynthesis (absolute differences from 0.003 to 0.052). Similar results were obtained by using a nonparametric analysis of forced BI-RADS ratings 3