Nipple Discharge Part 1

• Nipple discharge is a relatively frequent event in females:
  • Being the third most common breast symptom prompting medical care:
    • After breast pain and breast palpable mass
• Over 80% of females will develop an episode of nipple discharge during their fertile life:
  • Which can be categorized as:
    • Lactational
    • Physiological
    • Pathological 
      • According to the clinical history and the characteristics of the discharge
• Lactational nipple discharge:
  • Is considered as a normal milk production
  • It is expected during pregnancy and lactation:
    • May persist for up to one-year post-partum or after cessation of breastfeeding
• When a milky nipple discharge:
  • Occurs in females without recent history of pregnancy or lactation:
    • It is called galactorrhea:
      • Commonly involves bilateral multiple ducts
      • This is the result of an inappropriate increase in prolactin release:
        • Usually supported by a prolactinoma:
          • A prolactin-producing benign tumor of pituitary gland
• Physiological nipple discharge:
  • Is a benign entity:
    • Usually bilateral
    • White, green, or yellow in color
    • It involves multiple ducts
    • Is associated with nipple squeezing
  • Some causes of physiological nipple discharge are:
    • Hypothyroidism
    • Medication side-effects
• Pathologic nipple discharge (PND):
  • Is defined as a clear, serous, or bloody nipple secretion (not green or milky):
    • It is spontaneous
    • Discharging from a single duct and unilateral
  • It is frequently caused by:
    • A benign lesion, such as:
      • Intraductal papilloma(s):
        • 35% to 56% of the cases
      • Ductal ectasia:
        • 6% to 59% of the cases
    • An underlying malignancy can be present in a percentage of cases:
      • Reported to be variable from 5% to 33%
  • Because to differentiate between a benign from a malignant etiology of a PND based on clinical and diagnostic assessment is not easy:
    • Surgical excision has been considered the main way for getting both definitive diagnosis and eliminating the symptom
• Clinical History and Physical Examination:
  • Clinical history plays an important role:
    • For evaluating the probability of malignancy
  • Predicting factors for malignancy in the presence of PND are:
    • BRCA 1 / 2 mutations
    • History of ipsilateral cancer
    • Previous breast biopsy with diagnosis of atypia
    • Age over 50 years:
      • In a study including 318 patients with nipple discharge (any fluid from the nipple, spontaneous discharge or observed during breast examination):
        • Seltzer has reported a higher incidence of breast cancer:
          • Equal to 9% in females over 50 (95 patients and 9 cancers):
            • While the incidence was of only 1.3% in younger patients (223 patients and 3 cancers)
  • Physical examination:
    • Has the aim of distinguishing between benign and pathological discharge and of verifying the presence of palpable mass or other associated findings
    • It usually includes:
      • A complete breast evaluation:
        • With inspection and palpation
        • Followed by a focused inspection of the nipple area:
          • Using a magnifying lamp
    • The physical examination is essential to investigate the:
      • Color of discharge
      • The number of ducts involved
      • The frequency of discharge (persistent or intermittent)
      • If it is unilateral or bilateral
    • A spontaneous single-pore bloody and clear discharge:
      • Is suspect for pathological discharge
• Mammography:
  • Represents the first conventional imaging technique to investigate nipple discharge:
    • At least after 39 years old
  • For patients with PND, aged between 30 and 40 years old with high-family risk:
    • Mammography could be appropriated in order to exclude the presence of microcalcifications
  • As well as for females younger than 30 of age:
    • When initial ultrasound shows suspicious findings
  • The protocol includes:
    • The standard cranio-caudal and mediolateral oblique views
  • Mammography findings that are suspect to be associated to an occult malignancy can range from:
    • Microcalcifications
    • Masses
    • Focal density asymmetry
    • Architectural distortion or ductal ectasia
    • Otherwise no abnormality can be identified
  • Mammography has low sensitivity and limited accuracy:
    • In the detection of retroareolar lesions that are often small, intraductal, and without calcifications
  • Ductal ectasia:
    • May occur as a general increase in density of the retroareolar region and in order to better visualize the area:
      • Spot compression views could be performed
  • In order to improve spatial resolution:
    • Magnification mammography can be performed:
      • To identify microcalcifications and to distinguish between benign or malignant duct disease
  • Microcalcifications with:
    • Branching or linear pattern, variable density, or distributed in a segmental way:
      • Are all highly suspicious of malignancy
    • Whereas round or rod-like calcifications:
      • Suggest for benign disease
  • Bahl et al studied 252 patients with at least one pathological feature of nipple discharge (unilateral, clear or bloody, or spontaneous discharge) who underwent surgical excision or a 2-year follow-up:
    • Of 20 cancers diagnosed:
      • Only three were revealed by mammography:
        • With a 15% (3/20) sensitivity
  • In other studies, the sensitivity of mammography:
    • Ranged from 7% to 26%. 
• Ultrasound:
  • Offers a better performance than mammography:
    • For detecting intraductal lesions
  • Ductal ectasia:
    • Defined by a duct caliber greater than 3 mm
      • Is one of the most common findings seen on ultrasound:
        • It appears as dilated retroareolar ducts containing anechoid fluid or hypoecoic debris
  • An intraductal papilloma appears as:
    • A hypoechoic nodule with a central vascular pedicle on color Doppler:
      • Doppler ultrasound is helpful in differentiating:
        • Intraductal viscous secretion versus intraductal nodule with vascular sign
  • Ultrasound malignant features are:
    • Irregular duct margins
    • Wall thickening
    • Hypoechoic intraductal mass with acoustic shadowing 
  • In a study by Park et al:
    • The detection rate of malignant lesions occult on mammography and ultrasound-detected:
      • Was reported to be 8 of 53 females with PND examined (15%)
  • Yoon et al:
    • Have also reported that adding ultrasound to mammography in the pre-operative setting of PND:
      • Led to the detection of malignancies in 26% of patients (ultrasound detected fivebreast cancers in addition to the 19 breast cancers found by mammography)
  • The role of ultrasound elastography is disputable in predicting malignancy in patients with PND:
    • Guo et al have evaluated the diagnostic accuracy of elastography in patients with PND:
      • Affirming that it is a useful tool for predicting malignancy:
        • With sensitivity for malignancy of 90% and that it could be used as a helpful test before more invasive examination (such as ductoscopy or duct excision):
          • However, it is only a preliminary study and further studies are needed to verify the diagnostic perfor- mance of elastography
• Nipple discharge cytology:
  • Is performed by squeezing the nipple with a gentle compression of the areola area and spreading the secretion onto a glass slide:
    • After smearing, the slides are immediately fixed by spray fixation or by immersion in 95% ethyl alcohol:
      • Then stained with the Papanicolaou stain
  • It is a simple and fast examination, easy to perform and painless:
    • But strongly limited by a low sensitivity for cancer:
      • With a false negative rate over 50%
    • Moreover, it can be technically impossible when discharge is not present on the moment of the examination
    • According to the American College of Radiology:
      • This examination has not proven to be effective in differentiating benign from malignant lesions:
        • Therefore, discharge cytology is not routinely recommended
  • Nipple discharge smears are classified as abnormal if they contained:
    • Papillary, atypical, suspicious, or malignant cells:
      • Malignant nipple discharge cytology is correlated with higher specificity values

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