Diagnostic Accuracy of Nipple Discharge Fluid Cytology: A Meta-Analysis and Systematic Review of the Literature

Ann Surg Oncol. 2022 Mar;29(3):1774-1786. doi: 10.1245/s10434-021-11070-2. Epub 2021 Nov 27.


Background: Nipple discharge is the third most frequent complaint of women attending rapid diagnostic breast clinics. Nipple smear cytology remains the single most used diagnostic method for investigating fluid content. This study aimed to conduct a systematic review and meta-analysis of the diagnostic accuracy of nipple discharge fluid assessment.

Methods: The study incorporated searches for studies interrogating the diagnostic data of nipple discharge fluid cytology compared with the histopathology gold standard. Data from studies published from 1956 to 2019 were analyzed. The analysis included 8648 cytology samples of women with a presenting complaint of nipple discharge. Both hierarchical and bivariate models for diagnostic meta-analysis were used to attain overall pooled sensitivity and specificity.

Results: Of 837 studies retrieved, 45 fulfilled the criteria for inclusion. The diagnostic accuracy of the meta-analysis examining nipple discharge fluid had a sensitivity of 75 % (95 % confidence interval [CI], 0.74-0.77) and a specificity of 87 % (95 % CI, 0.86-0.87) for benign breast disease. For breast cancer, it had a sensitivity of 62 % (95 % CI, 0.53-0.71) and a specificity 71 % (95 % CI, 0.57-0.81). Furthermore, patients presenting with blood-stained discharge yielded an overall malignancy rate of 58 % (95 % CI, 0.54-0.60) with a positive predictive value (PPV) of 27 % (95 % CI, 0.17-0.36).

Conclusions: Pooled data from studies encompassing nipple discharge fluid assessment suggest that nipple smear cytology is of limited diagnostic accuracy. The authors recommend that a tailored approach to diagnosis be required given the variable sensitivities of currently available tests.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / pathology
  • Cytodiagnosis
  • Female
  • Humans
  • Nipple Discharge*
  • Nipples / pathology
  • Sensitivity and Specificity