ORIGINAL ARTICLE Pathologic Nipple Discharge in Patients with Radiologically Invisible Mass: Review of 28 Consecutive Sub-areolar Explorations Mehmet Ali Kocdor, MD,* Ali Ibrahim Sevinc, MD,* Tulay Canda, MD,   Pinar Balci, MD, à Serdar Saydam, MD,* Ozgur Cavdaroglu, MD,* and Omer Harmancioglu, MD* *Department of Surgery, Dokuz Eylul University School of Medicine, Izmir, Turkey;   Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey; and à Department of Radiology, Dokuz Eylul University School of Medicine, Izmir, Turkey n 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 univer- sity 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. n Key Words: major duct excision, microdochectomy, pathologic nipple discharge, sub-areolar exploration N ipple discharge is a common complaint for recourse to breast cancer clinics and forms 5–7% of the symptoms associated with the breast (1,2). This symptom is considered as a ‘‘benign’’ nipple discharge when it occurs bilaterally, originates from multiple ducts, has a white ⁄ greenish color, and is of nonspon- taneous character (3). In particular, nipple discharges observed in women of reproductive age are mostly of this type and do not require further surgical and radiologic interventions. However, nipple discharges that are spontaneous, unilateral, of single ductal origin and have bloody, serous or serosanguineous character are regarded as ‘‘pathologic nipple discharges’’ (3,4). It is known that the frequency of cancer is 5–28% in spontaneous or pathologic nipple discharges (PND) (5,6). Hence, further diagnostic intervention is always required for these patients. In cases of PND accompanied by clinical and radio- logic anomalies, the probability of invasive carcinoma is remarkably high (3). In addition, it is relatively easier to diagnose or perform histopathologic sam- pling in these cases. For example, it is possible to reach an exact diagnosis using excisional or Tru-cut biopsy when the mass is palpable (7) and using stereo- tactic biopsy or wire-guided breast biopsy in cases of nonpalpable and radiologically suspicious lesions. However, histopathologic sampling is extremely diffi- cult, technically, in cases of PNDs that do not show clinical and radiologic findings. The limited number of publications available indi- cates a probability of carcinoma of 0–5% in PND cases that are clinically and radiologically negative (7,8). Uncertainty remains concerning the appropriate diagnostic and treatment approach in this special patient group for which mammography and ultraso- nography do not report any pathologic lesions, and surgery and close follow-up options are combined in existing algorithms (3,7). This study attempts to investigate the frequency of cancer in 28 consecutive sub-areolar explorations with PND where mammography and ultrasonography were completely normal. Also a classical surgical indication in these patients is examined. Address correspondence and reprint requests to: Mehmet Ali Kocdor, MD, Dokuz Eylul University Hospital, Department of Surgery, 35340, Inciralti, Izmir, Turkey, or e-mail: mehmet.kocdor@deu.edu.tr. Ó 2009 Wiley Periodicals, Inc., 1075-122X/09 The Breast Journal, Volume 15 Number 3, 2009 230–235