A 43-year-old woman presents with blood-tinged discharge from her right nipple. She indicates that this problem has been occurring intermittently over the past several weeks. Her past medical history is significant for hypothyroidism. She has no prior history of breast complaints. The patient is premenopausal and currently not lactating. Her medications consist of oral contraceptives and levothyroxine. On physical examination, she is found to have minimal fibrocystic changes in both breasts. There is evidence of thickening in the right retroareolar region. Small amounts of serosanguineous fluid can be expressed from the right nipple. There is no evidence of nipple discharge or a dominant mass in the left breast.
What should be your next step?
What is the most likely diagnosis?
ANSWERS TO CASE 32: Nipple Discharge (Serosanguineous)
Summary: A 43-year-old premenopausal, nonlactating woman presents with unilateral nipple discharge that is serosanguineous.
• Next step: The examination should begin with bilateral mammography to evaluate for suspicious lesions and ultrasonography to evaluate the retroareolar thickening; a ductogram or biopsy should also be considered.
• Most likely diagnosis: Intraductal papilloma.
1. Become familiar with an approach to the evaluation of nipple discharge by categorizing the condition as physiologic, pathologic, or galactorrheic.
2. Appreciate the relative cancer risks of patients presenting with nipple discharge.
This patient’s history indicates that a pathologic etiology for nipple discharge should be investigated. Characteristics of concern include being spontaneous (not produced by manipulation—patients often find the discharge on their clothing), being bloody or blood tinged (as opposed to milky, purulent or—as is characteristic of fibrocystic changes—yellow, brown, or green), and being unilateral (Table 32–1). Although the most common pathologic cause of bloody nipple discharge is intraductal papilloma, prompt evaluation of this patient must be performed to exclude carcinoma. Solitary papillomas are benign and do not increase the risk of cancer; in half of all cases, they are characterized by a serous rather than a bloody discharge. Duct ectasia (also benign) is the next most common cause of bloody nipple discharge. Carcinoma and infection follow, with the former being one of the main reasons to pursue a diagnosis. After the history is obtained and a physical examination is completed, bilateral mammography should be performed to evaluate for suspicious lesions and ultrasonography to evaluate the patient’s retroareolar thickening. Ultrasonography can diagnose duct ectasia or further characterize the thickening and fibrocystic changes. Mammography is indicated in women older than 40 years. In this case, it can be used for both screening and diagnostic purposes. When nipple disease is suspected, such as squamous carcinoma (Bowen disease) or ductal carcinoma (Paget disease), or when a solitary mass is present, these lesions should be biopsied.
Table 32–1 • DIFFERENTIAL DIAGNOSIS FOR NIPPLE DISCHARGE
APPROACH TO: Bloody Nipple Discharge
DUCTOGRAM: A radiologic test with contrast injected into the duct causing the discharge.
INTRADUCTAL PAPILLOMA: A benign epithelial lesion most commonly arising from major ducts near the nipple that is usually microscopic but may grow to 2 to 3 mm. These lesions present clinically as spontaneous blood-tinged nipple discharge from the involved breast. Intraductal papillomas could contain areas of atypical hyperplasia or ductal carcinoma in situ.
GALACTORRHEA: Milky breast discharge that is often related to hyperprolactinemia.
DUCT ECTASIA: These are duct dilatations that occur due to elastin loss in the duct walls. Ectasia may occur following chronic inflammation of the duct wall. Nipple discharges associated with duct ectasia are frequently associated with bacterial growth. Duct ectasia is the common cause of recurrent breast abscesses in nonlactating women. The treatment consists of identification of the involved duct(s) by ductography, followed by complete excision of the involved areas.
Nipple discharges are broadly categorized as physiologic and pathologic. Physiologic discharges are typically bilateral, clear, involve multiple duct orifices, and occur nonspontaneously (in other words, with stimulation or massaging of breast or nipple). Patients with physiologic discharge should undergo breast imaging with mammography or ultrasound, depending on the age of the patients. If imaging results are normal, follow-up and reassurance may be appropriate. If diagnostic imaging reveals abnormalities, standard diagnostic workups are indicated.
The approach to women presenting with pathologic (nonphysiologic) nipple discharges is initially directed by the characteristic of the discharge (milky, bloody, etc), and whether the discharge is unilateral or bilateral. Bilateral and milky discharges require an endocrine evaluation and an evaluation to rule out pregnancy. Appropriate breast imaging such as mammography and/or ultrasonography should be obtained in the initial assessment of patients with unilateral discharge. Patients with abnormalities identified by imaging should undergo appropriate biopsy and/or follow-up as indicated, and patients without abnormalities identified during initial breast imaging should undergo ductography to help identify localized ductal pathology.
Occasionally the discharge of fibrocystic changes can be difficult to differentiate from old blood; however, this drainage is rarely spontaneous. A Hemoccult test can help differentiate the two. Although some advocate cytologic examination of the discharge, false-negative and false-positive results are common. Awaiting results can produce further delay and cost without providing data that would change the evaluation process. Therefore, it is reasonable to forgo cytological testing and proceed to a ductogram. A patient must have ongoing discharge for this test to be performed. It requires a skilled radiologist, and the patient may experience discomfort during the examination. A lesion can be identified by the presence of a filling defect (a “cutoff”), an abrupt end to the duct rather than normal confluent arborization. An abnormal ductogram generally mandates surgical biopsy. A ductogram can also help localize the lesion for the surgeon performing the biopsy. If the ductogram is normal, the patient can be judiciously observed for the possibility of underlying carcinoma. A dominant mass, a newly inverted nipple, skin changes, or mammographic abnormalities generally necessitate surgical biopsy.
Surgery is performed by either a partial or a complete duct excision, recognizing that complete excision will affect the patient’s ability to breast-feed in the future. Undergoing the procedure in the operating room will help in the planning of the excision. The duct is cannulated with a fine lacrimal probe, which is used as a guide for excision. The injection of methylene blue dye into the duct with a fine angiocatheter may also serve as a guide in directing the excision, which is done through a circumareolar incision.
32.1 A 35-year-old woman with two children and no previous operations has noticed increased fatigue and a whitish nipple discharge. Which of the following is the best next step?
A. Determination of the thyroid-releasing hormone level
B. Imaging of the sella turcica
C. Measurement of the human chorionic gonadotropin level
D. Ultrasonography of the breasts
E. Initiation of treatment with bromocriptine
32.2 A 32-year-old woman is noted to have nipple discharge. She is concerned about the possible association with breast cancer. Which of the following etiologies of nipple discharge most likely increases the risk of breast cancer?
A. Fibrocystic changes
B. Blood-tinged discharge
C. Intraductal papilloma
E. Diffuse papillomatosis
32.3 A 44-year-old woman is seen by her physician for breast discharge. Blood tests and imaging tests are performed. Which of the following findings in a workup for nipple discharge must be further evaluated?
A. An ultrasonogram of the nipple showing duct ectasia
B. A ductogram with no filling defects or abnormalities
C. An ultrasonogram with fibrocystic changes and a 2-mm simple cyst
D. Diffuse fibrocystic changes
E. A prolactin level of 100 ng/mL
32.4 A 65-year-old woman who takes tricyclic antidepressants and metoclopramide has a serosanguineous discharge from her right nipple. She has no palpable masses, normal bilateral mammograms, and a right breast ultrasonogram that does not demonstrate any masses. Her ductogram shows a cutoff in an inferior lateral duct 2 cm from the right nipple. Of the following choices, which is the most appropriate approach?
A. Observation and instructions not to manipulate the nipple during self-examination
B. Changing her medications
C. Checking the prolactin level
D. Duct excisional biopsy
E. Mammographic guided core-needle biopsy
32.1 C. This patient likely has galactorrhea. Although these can also be symptoms of hypothyroidism or the presence of a pituitary microadenoma, the first step is to exclude pregnancy as an etiology. Bromocriptine is used in the treatment of pituitary microadenoma but it is not indicated without definitive biochemical and/or radiographic indications of disease presence.
32.2 E. Diffuse papillomatosis increases the risk of cancer.
32.3 E. A prolactin level in the range of 100 ng/mL or more is suggestive of a pituitary adenoma, whereas the other findings are benign and can be observed. Ductal ectasia could produce duct obstruction and breast abscesses; therefore surgical excision could be considered.
32.4 D. Abrupt cutoff of the ductogram is associated with breast cancer and necessitates biopsy. Other features of ductography that are suspicious for breast cancer include multiple irregular filling defects or external compression of the duct. A ductogram that shows a well-filled duct except for a solitary lobulated filling defect is more consistent with intraductal papilloma.
The causes of nipple discharge can be grouped as pathologic or physiologic. This grouping may be useful in directing evaluation and therapy. Patients who require surgical evaluation have spontaneous, unilateral, and recurrent discharges.
Nipple discharge is a disturbing complaint for the patient; notably, only 4% to 6% of patients with nipple discharge without an associated breast mass are found to have a breast cancer. The risk for cancer is increased if the patient is postmenopausal, discharge is associated with abnormal findings on breast imaging, or if a mass is found.
The most common cause of unilateral serosanguineous nipple discharge in the absence of a mass is an intraductal papilloma. Nevertheless, breast cancer must be considered.
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