The Male Breast: Gynecomastia and Male Breast Cancer

The incidence of breast cancer in males is less than 1% of all breast cancers and less than 1% of all male cancers in the United States. Male breast patients seek clinical attention for unilateral or bilateral breast enlargement, breast pain, or a palpable breast lump. Most of these complaints are related to benign gynecomastia and are not due to breast cancer. Gynecomastia is an abnormal proliferation of benign ducts and supporting tissue that causes breast enlargement or a subareolar mass, with or without associated breast pain. It is reversible in its early stages if the cause of the gynecomastia is corrected. Unchecked, the reversible phase of gynecomastia progresses to late periductal edema with irreversible stromal fibrosis.

Broad categories of conditions causing gynecomastia include high serum estrogen levels from endogenous or exogenous sources, low serum testosterone levels, endocrine disorders (hyperthyroidism or hypothyroidism), systemic disorders (cirrhosis, chronic renal failure with maintenance by dialysis, chronic obstructive pulmonary disease), drug-induced (cimetidine, spironolactone, ergotamine, marijuana, anabolic steroids, estrogen for prostate cancer), tumors (adrenal carcinoma, testicular tumors, pituitary adenoma), or idiopathic (Box 10-1). Gynecomastia can occur at any age, but it may be seen in particular in neonates as a result of maternal estrogens circulating to the fetus through the placenta, in healthy adolescent boys 1 year after the onset of puberty because of high estradiol levels, or in older men as a result of decreasing serum testosterone levels.

The normal male breast contains major breast ducts only and otherwise has mostly fatty tissue. Under a stimulus producing gynecomastia, breast enlargement occurs as a result of ductal proliferation and stromal hyperplasia, occasionally accompanied by ductal multiplication and elongation, which may be reversible in the active phase if the stimulus is removed. If the stimulus persists, irreversible stromal fibrosis and ductal epithelial atrophy develop, and the breast enlargement may decrease but not completely resolve. Pseudogynecomastia is a fatty proliferation of the breasts without proliferation of glandular tissue that simulates gynecomastia clinically, but unlike true gynecomastia, proliferation of glandular breast tissue does not occur.

Mammography is performed in men in the same fashion as in women. On the mammogram, the normal male breast consists of fat without obvious fibroglandular tissue, and the pectoralis muscles are usually larger than in women (Fig. 10-1A to D). In both pseudogynecomastia and in women with Turner syndrome, mammograms consist mostly of fat, similar to the normal male breast (see Fig. 10-1E and F).

Figure 10-1 A to D, Mammograms in a man showing normal findings. Right (A) and left (B) mediolateral oblique (MLO) views and right (C) and left (D) craniocaudal (CC) mammograms show mostly fatty tissue and normal, scant, flamelike strands of glandular tissue in the subareolar regions. In some men, only normal fatty tissue is seen; in others, there are more faint strands of retroareolar tissue. In either case there is never as much tissue as in a woman in the normal male. E and F, Turner syndrome. MLO (E) and CC (F) views show mostly fatty tissue, similar to the normal male breast, in this female patient with Turner syndrome.

On the mammogram, gynecomastia is shown as glandular tissue in the subareolar region that is symmetric or asymmetric, unilateral or bilateral. In a large series by Gunhan-Bilgen and colleagues, gynecomastia was unilateral in 45% and bilateral in 55% of 206 cases on mammograms. In the early phases of gynecomastia, the glandular tissue takes on a flamelike dendritic appearance consisting of thin strands of glandular tissue extending from the nipple, similar to fingers extending posteriorly toward the chest wall (Table 10-1). With continued proliferation of breast ducts, the glandular tissue takes on a triangular nodular shape behind the nipple in the subareolar region that can be symmetric or asymmetric (Fig. 10-2). If the etiology of the gynecomastia is not eliminated, the proliferation may progress to the appearance of diffuse dense tissue in the later stromal fibrotic phase that is irreversible (Fig. 10-3). On ultrasound, gynecomastia shows hypoechoic flamelike, fingerlike, or triangular structures extending posteriorly toward the chest wall from the nipple (Fig. 10-4). Pseudogynecomastia shows only fatty tissue on the mammogram and is distinguished from gynecomastia by the absence of glandular tissue.

Table 10-1 Mammographic Appearance of Gynecomastia

Figure 10-2 A to D, Triangular nodular gynecomastia. Mediolateral oblique (MLO) (A) and craniocaudal (B) mammograms show triangular, focally dense breast tissue behind the nipple. Ultrasound of the left (C) and right (D) breast shows hypoechoic dark strands of tissue extending from the nipple in a fingerlike triangular distribution in this male with gynecomastia. E to H, Asymmetric nodular gynecomastia. Right (E) and left (F) MLO mammograms show triangular focal asymmetric subareolar glandular breast tissue behind the right nipple, representing right gynecomastia, and a left normal mammogram. Ultrasound of the right retroareolar region on transverse (G) and longitudinal (H) scans show the typical, normal “fingerlike” hypoechoic dark strands of tissue from gynecomastia extending from the right nipple.

Figure 10-3 Diffuse gynecomastia. Craniocaudal (A) and mediolateral oblique (B) mammograms show triangular, focally dense breast tissue behind the nipple. Ultrasound of the left (C) and right (D) breast reveals hypoechoic dark triangular strands of tissue extending down from the nipple.

Figure 10-4 A and B, Varying appearance of gynecomastia on ultrasound. A, Ultrasound of painful, but nonpalpable left gynecomastia shows a triangle of hypoechoic tissue extending to the chest wall from the nipple. B, The right breast ultrasound is normal appearance and shows no glandular tissue. Longitudinal (C) and transverse (D) ultrasounds show triangular ductlike gynecomastia in a right retroareolar region that contains a painful lump. E, Corresponding right craniocaudal mammogram shows a focal glandular tissue in the right subareolar region, compatible with gynecomastia.

Male breast cancer accounts for less than 1% of all cancers found in men and is usually diagnosed at or around age 60, older than the mean age for the diagnosis of breast cancer in women (Box 10-2). Male breast cancer has the same prognosis as breast cancer in women, but it is often detected at a higher stage than in women because of delay in diagnosis; up to 50% of men have axillary adenopathy at initial evaluation. Risk factors include Klinefelter syndrome, high estrogen levels such as from prostate cancer treatment, and the development of mumps orchitis at an older age. Male breast cancer is generally manifested as a hard, painless, subareolar mass eccentric to the nipple. When not subareolar, cancers in men are usually found in the upper outer quadrant. Clinical symptoms of nipple discharge or ulceration are not rare in association with male breast cancer.

On mammography, male breast cancers are generally dense noncalcified masses with variable margin patterns located in the subareolar region (Figs. 10-5 and 10-6). Calcifications are less common in male than female breast cancer, although calcifications may be present. On ultrasound, male breast cancers are described as masses with well-circumscribed or irregular margins. Concomitant findings of skin thickening, adenopathy, and skin ulceration are associated with a poor prognosis. Breast cancers in men have the histologic appearance of invasive ductal cancer in 85% of cases, with most of the remaining tumors being medullary, papillary, and intracystic papillary tumors. An associated component of ductal carcinoma in situ (DCIS) may be present. Invasive lobular carcinoma is rare. Treatment of breast cancer is the same for men as for women and consists of surgery, axillary node dissection, chemotherapy, radiation therapy for invasive tumors, or any combination of these treatments; the prognosis is identical as that for women.

Figure 10-5 Male breast cancer. In a patient with a palpable mass in the retroareolar region of the left breast, craniocaudal (A) and mediolateral oblique (B) mammograms show diffuse bilateral gynecomastia with a large oval retroareolar mass on the left. Contrast the gynecomastia on the right, which shows indistinct breast tissue interfacing with fat, with the sharp smooth-bordered mass of the left breast cancer. Ultrasound-guided fine-needle aspiration of a portion of the mass showed invasive ductal cancer.

Figure 10-6 Male breast cancer. In a patient with bilateral gynecomastia and a palpable mass in the left breast, right (A) and left (B) mediolateral oblique (MLO) and right (C) and left (D) craniocaudal mammograms show bilateral benign-appearing gynecomastia, with markers on the right nipple and on an invisible palpable left breast mass that is obscured by the glandular tissue. E, Longitudinal ultrasound shows a round, homogeneous, hypoechoic mass corresponding to the palpable finding within the gynecomastia. Biopsy showed invasive ductal cancer. In another patient, right (F) and left (G) MLO mammograms show a palpable asymmetric spiculated mass superior to the right nipple that looks like cancer. Gynecomastia is usually directly behind the nipple; because the mass is in the upper breast, away from the nipple, it most likely represents cancer. Biopsy showed invasive ductal cancer. Longitudinal (H) and transverse (I) ultrasounds of a palpable mass in a man shows a suspicious hypoechoic oval mass with calcifications. J, The mammogram shows a round, irregular mass with faint calcifications in the left breast. Biopsy showed invasive ductal cancer.

Pregnant Patients and Pregnancy-Associated Breast Cancer

Pregnancy produces a proliferation of glandular breast tissue that results in breast enlargement and nodularity; rarely, the condition progresses to gigantomastia or enlargement of multiple fibroadenomas. Breast masses are difficult to manage in a pregnant patient because of the surrounding breast nodularity and size increase over time. Most masses occurring in pregnancy are benign and include benign lactational adenomas, fibroadenomas, galactoceles, and abscesses (Box 10-3), but the diagnosis of exclusion is pregnancy-associated breast cancer.

Pregnancy-associated breast cancer is defined as breast cancer discovered during pregnancy or within 1 year of delivery (Box 10-4). The incidence of breast cancer in pregnant women is 0.2% to 3.8% of all breast cancers, or 1 in every 3000 to 10,000 pregnancies. Most pregnancy-associated breast cancers are invasive ductal cancer. These cancers are generally manifested as a hard mass, but they may be associated with bloody nipple discharge or findings of breast edema. The usual initial imaging test in a pregnant patient is breast ultrasound. Many patients are reluctant to undergo mammography because of concern about the effect of radiation on the fetus. However, if cancer is a clinical concern, it is important to perform mammography as part of the evaluation and in particular to detect the presence of suspicious calcifications that are often nonpalpable. The amount of scattered radiation delivered to the fetus is minimal and can be further reduced with lead shielding. Swinford and colleagues showed that breast density on mammography ranges from scattered fibroglandular density in pregnant patients to heterogeneously dense or dense breasts in a lactating patient. In their series, mammography was as useful as it is in nonpregnant women with clinical signs and symptoms of breast disease. In lactating patients, breast density can be reduced on the mammogram by pumping milk from the breasts before the study.

Mammography revealed signs of pregnancy-associated breast cancer in 78% of 23 pregnant women reported by Liberman and colleagues and in 86% of 15 cases reported by Ahn and colleagues. Mammograms showed masses, pleomorphic calcifications (or both masses and calcifications), asymmetries, and breast edema, but occasionally they were negative because of dense breast tissue. Axillary lymphadenopathy, asymmetries, and skin or trabecular thickening have been reported as primary or associated findings. In both series, ultrasound was positive in all cases in which it was performed and showed irregular solid masses with irregular margins. In the series by Ahn and colleagues, four masses also contained “complex echo patterns” or cystic components, and most showed acoustic enhancement.

Magnetic resonance imaging (MRI) of a normal lactating breast shows dense, enhancing, diffuse glandular tissue and widespread high signal throughout the tissue on T2-weighted images. Breast cancer in a lactating breast on MRI shows higher signal intensity in the initial enhancement phase than in the surrounding lactational breast tissue, with a washout or plateau pattern in the late phases in the rare reported cases in the radiology literature.

Pregnancy-associated breast cancers have a prognosis similar to that in nonpregnant women when matched for age and stage. In pregnancy, diagnostic delays may cause breast cancer to be detected at a later stage, thereby leading to a worse prognosis. Modified radical mastectomy was the usual treatment for pregnant women, but more recently, breast-conserving surgery is becoming more common. Chemotherapy has been used safely in women after the first trimester. Pregnancy is an absolute contraindication for radiation therapy.

Benign conditions are the most frequent cause of breast masses in pregnant or lactating patients, and cancer is much less common. Lactational mastitis is a common complication of breast-feeding in which the breast becomes painful, indurated, and tender, usually as a result of Staphylococcus aureus infection. A cracked nipple may be the port of entry for the infecting bacteria, but it can be prevented by good nipple hygiene and care, along with frequent nursing to avoid breast engorgement. Treatment is administration of antibiotics and continuation of breast-feeding. On occasion, antibiotic therapy is not sufficient to treat mastitis. If a hot, swollen, painful breast does not respond to antibiotics, ultrasound may identify an abscess and guide percutaneous drainage. On mammography, an abscess is a developing asymmetry or mass in a background of breast edema; it does not usually contain gas and is frequently located in the subareolar region (Fig. 10-7A and B). On ultrasound, abscesses are fluid-filled structures with irregular margins in the early phase, but circumscribed margins develop in the later phase as the walls of the abscess form. The abscess may contain debris or multiple septations, which may be drained under ultrasound guidance, but some residua may remain because of thick debris. Ultrasound-guided percutaneous drainage may be curative in small abscesses or palliative until surgical drainage can be performed in large abscesses. Some investigators report using ultrasound-guided aspiration, with abscess irrigation and instillation of antibiotics directly into the abscess cavity, to aid in resolution of the abscess.

Figure 10-7 Pregnancy-associated findings: abscess and lactating adenoma. A, Mediolateral oblique mammogram in a lactating patient shows dense tissue. B, After the development of mastitis and a lump near the chest wall, the mammogram shows a developing density representing an abscess near the chest wall. Longitudinal (C) and transverse (D) ultrasounds in a patient with a palpable mass during pregnancy show an oval, homogeneous, well-circumscribed, palpable mass in the right breast that was larger during pregnancy and smaller after pregnancy. The differential diagnosis included fibroadenoma, adenoma of pregnancy, and well-circumscribed cancer. Biopsy showed lactating adenoma.

Both fibroadenomas and lactating adenomas are solid benign tumors diagnosed during pregnancy. Growth of preexisting fibroadenomas may be stimulated by the elevated hormone levels of pregnancy, and the fibroadenoma may become clinically apparent. Infarction of fibroadenomas has been reported in the literature during pregnancy as well. Presenting as a firm, painless palpable lump that occurs late in prgenancy or during lactation, the lactating adenoma is a circumscribed, lobulated mass containing distended tubules with an epithelial lining. The mass can enlarge rapidly and regress after cessation of lactation. Ultrasound typically shows an oval, well-defined hypoechoic mass that may contain echogenic bands representing the fibrotic bands seen on pathology (see Fig. 10-7C and D). Whether lactating adenoma represents change stimulated by hormonal alterations in a fibroadenoma or tubular adenoma or whether the tumors arise de novo has not been resolved.

Sampling of solid masses for histologic examination in a pregnant or lactating patient can be accomplished by either percutaneous core biopsy or surgery. Milk fistula produced by damage to the breast ducts is an established, but uncommon complication of these biopsy procedures in women in the third trimester of pregnancy or those who are lactating.

A galactocele produces a fluid-filled breast mass that can mimic a benign or malignant solid breast mass. On mammography, a galactocele is a round or oval, circumscribed mass of equal- or low-density (Fig. 10-8A and B). Because a galactocele is filled with milk, the creamy portions of the milk may rise to the nondependent part of the galactocele and produce a rare, but pathognomonic fluid-fluid or fat-fluid appearance on the horizontal beam image (lateral-medial view) at mammography. Ultrasound shows a fluid-filled mass that can have a wide range of sonographic appearances, depending on the relative amount of fluid and solid milk components within it. Galactoceles that are mostly fluid-filled have well-defined margins with thin echogenic walls (see Fig. 10-8C to E). Galactoceles containing more solid components of milk show variable findings, ranging from homogeneous medium-level echoes to heterogeneous contents with fluid clefts. Both distal acoustic enhancement and acoustic shadowing may be seen. The diagnosis is made by an appropriate history of childbirth and lactation, with aspiration yielding milky fluid and leading to resolution of the mass. Aspiration is usually therapeutic.

Figure 10-8 Galactocele. A, Mediolateral oblique mammogram in a lactating patient with a marker over a palpable mass shows a low-density mass in the upper portion of the left breast. B, Aspiration produced milky fluid with a fat-fluid level. C to E, Ultrasound of galactocele shows septated fluid-filled structure with enhanced through-sound transmission in transverse (C) and longitudinal (D) scans. This galactocele had very little solid material in it. Prominent fluid-filled ducts during lactation are seen on ultrasound (E), showing the milk in the ducts before galactocele formation.

Probably Benign Findings (Bi-Rads® Category 3)

Mammography detects small cancers, but it can also uncover nonpalpable benign-appearing lesions indeterminate for malignancy. Fine-detail diagnostic mammographic views and ultrasound in appropriate cases show that some indeterminate findings are typically benign and the patient can therefore resume screening. Other findings have a low probability (<2%) of malignancy after an appropriate workup that serves as a baseline for follow-up studies (Box 10-5). Sickles, Varas and colleagues, and Yasmeen and colleagues have independently provided data that Breast Imaging Reporting and Database System (BI-RADS®) category 3, or probably benign, findings carry a less than 2% chance of malignancy. Probably benign BI-RADS® category 3 lesions were found in 5%, 3%, and 5% of all screening studies after recall in their series, respectively. Probably benign findings included single or multiple clusters of small, round or oval calcifications; nonpalpable and noncalcified, round or lobulated, circumscribed solid masses; and nonpalpable focal asymmetry containing interspersed fat and concave scalloped margins that resemble fibroglandular tissue at diagnostic evaluation (Fig. 10-9).

Figure 10-9 Probably benign findings on mammography. Findings included scattered and clustered, round punctate, sharply demarcated calcifications (A) and a nonpalpable, round, well-circumscribed solid mass (B). C to F, Asymmetries. Craniocaudal (CC) (C) and mediolateral oblique (MLO) (D) views show global asymmetry consisting of a nonpalpable greater volume of tissue in the upper outer portion of the left breast than in the right. In another patient, a focal asymmetry resembling fibroglandular tissue is seen in the upper part of the left breast on the CC (E) and MLO (F) views.

For a mass to be considered circumscribed, at least 75% of the mass margin must be visualized as circumscribed; the remaining 25% may be obscured but must not show any signs of malignancy, such as ill-defined or spiculated margins. Rather than assessing as probably benign, multiple bilateral similar-appearing circumscribed or partially circumscribed masses may be considered BI-RADS® category 2 (benign), because it has been shown that the rate of malignancy among multiple masses is 0.14%, which was lower than the age-matched U.S. incident breast cancer rate of 0.24%. Importantly, if a focal asymmetry is to be considered probably benign, it should not be associated with any mass, suspicious calcifications, or architectural distortion. Probably benign findings are often detected on a baseline screening mammogram without comparison films and are managed by short-term mammographic follow-up (usually at 6-month intervals), but only after full diagnostic evaluation, including diagnostic mammographic views and (in some cases) ultrasound.

The 6-month mammographic follow-up serves as an alternative to percutaneous core or surgical biopsy for probably benign findings, with subsequent yearly follow-up for 2 to 3 years. Because the average breast cancer has a tumor volume doubling time of 100 days, growth should be detectable in 2 to 3 years. However, probably benign breast lesions are selected on the basis that they will most likely not change in the time interval. Lesions in which growth is anticipated should undergo biopsy.

Other inclusion criteria for the probably benign category include a lesion that is nonpalpable and identifiable at imaging, as well as a patient who is likely to complete the follow-up imaging surveillance regimen. Criteria that may exclude patients from short-term follow-up include extreme anxiety affecting the patient’s quality of life, pregnancy or planned pregnancy, or a likelihood of noncompliance with follow-up.

Rosen and colleagues reviewed the findings of cancers initially subjected to short-term follow-up to identify imaging criteria that should exclude initial assessment as BI-RADS® category 3 (probably benign). Their series of cancers that were mistakenly classified in the probably benign category included palpable findings, developing densities, architectural distortion, irregular spiculated masses, growing masses, pleomorphic calcifications, workups showing motion blur on magnification, and lesion progression of any type since the previous mammogram. Their results emphasize that lesions should only be assessed as probably benign and assigned to short-term follow-up (instead of immediate biopsy) after optimal diagnostic workup. Data from the Breast Cancer Surveillance Consortium show that the few cancers that were initially assessed as probably benign are of early-stage and favorable prognosis, but only if full diagnostic imaging evaluation was initially performed. In contrast, cancers that were initially assessed as probably benign based on screening mammographic views only were of later-stage (and less favorable prognosis). Recall imaging is indicated before assessing a screen-detected lesion as probably benign for two reasons: to identify subtle features of malignancy that can only be seen through fine-detail diagnostic mammographic views or ultrasound (i.e., such lesions should be interpreted as suspicious and biopsied immediately), or to identify definitively benign findings through fine-detail diagnostic mammographic views or ultrasound (i.e., such lesions should be interpreted as benign and followed with routine rather than short-term interval imaging).

Data on probably benign lesions are derived from women in the screening mammography population, who are nominally asymptomatic. In other words, probably benign lesions identified in this cohort are (at least nominally) nonpalpable. Hence, a paucity of data are available regarding palpable lesions that otherwise fulfill the imaging criteria for probably benign assessment. In other words, rather than data existing indicating that palpable lesions cannot be safely considered probably benign, there is no sufficient data examining whether or not palpable findings that otherwise satisfy the imaging criteria for probably benign lesions may be assessed as BI-RADS® category 3. Indeed, more recent studies found that palpability did not affect the probability of malignancy in lesions that otherwise satisfied the probably benign imaging criteria.

Despite the use of these strict criteria, a small number of cancers invariably emerge from BI-RADS® category 3 lesions. It is accepted that such lesions carry a probability of malignancy of less than 2%. In the series by Varas and colleagues, 0.4% of cases that were initially classified as probably benign were determined to be cancer at follow-up. Despite that probably benign lesions were associated with a possibility (albeit small) of malignancy, it is important to note that the few cancers identified were stage 1 or less, of favorable prognosis, and similar to the cancers detected in their mammographic screening series.

The probably benign category was based on imaging features and longitudinal data derived from mammography, which is a well-established imaging modality that has published well-defined standards for the acquisition of images, qualifications of personnel, and criteria for interpretation. In clinical practice, the probably benign category has been used with ultrasound and MRI. However, no specific image criteria, definition of lesions, or longitudinal data that are comparable to mammographic studies have been established for ultrasound or MRI. Emerging data suggest that a round, oval, or gently lobulated mass that appears circumscribed at mammography and ultrasound may be safely followed with short-term interval surveillance imaging, regardless of palpability. Few published reports on the use of the probably benign assessment category in MRI exist, and the probability of malignancy among such lesions ranges widely, from 0.6% to 10%. Caution should be paid regarding inappropriate overuse of the probably benign category in MRI, particularly because MRI is a costly test. Among three single-institutional studies, 17% to 24% of the MRI cases were assessed as probably benign with recommendation for short-term follow-up MRI. These numbers are substantially higher than those reported for mammographic lesions.

Nipple Discharge and Galactography

Nipple discharge is a common reason for women to seek medical advice. Benign nipple discharge usually arises from multiple ducts, whereas nipple discharge from a papilloma or DCIS usually occurs from a single duct. Nipple discharge is of particular concern if it is spontaneous and from a single duct or if the discharge is bloody. Women may describe intermittent discharge producing tiny stains on their brassiere or nightgown, or they may be able to elicit the discharge themselves. Some women present for imaging evaluation after positive findings from ductal lavage in conjunction with an abnormal cytologic evaluation.

The most frequent causes of both nonbloody and bloody nipple discharge are benign conditions. The most common mass producing a bloody nipple discharge is a benign intraductal papilloma, with only approximately 5% of women found to have malignancy at biopsy. The bloody nipple discharge associated with papillomas is due to twisting of the papilloma on its fibrovascular stalk and subsequent infarction and bleeding. Other causes of bloody discharge are cancer, benign findings such as duct hyperplasia/ectasia, and pregnancy as a result of rapidly proliferating breast tissue. Causes of nonbloody nipple discharge are fibrocystic change, medications acting as dopamine receptor blockers or dopamine-depleting drugs, rapid breast growth during adolescence, chronic nipple squeezing, or tumors producing prolactin or prolactin-like substances (Table 10-2).

Table 10-2 Nipple Discharge

Papillomas are benign masses that consist of a fibrovascular stalk with an attachment to the wall and breast duct epithelium; they have a variable cellular pattern and can produce nipple discharge. Papillomas may be single or multiple and may extend along the ducts for quite a distance. When large, papillomas can appear to be encysted and multilobulated. Some pathologists support the theory that peripheral papillomas have an increased risk for the subsequent development of carcinoma, whereas solitary or central papillomas do not. Peripheral papillomas are associated with epithelial proliferation, which may have atypical features, thus raising the possibility that atypia within a peripheral papilloma increases the risk of malignancy rather than the location of the papilloma itself.

The mammogram is frequently negative in the setting of nipple discharge (Table 10-3). Mammographic findings described in association with nipple discharge include a negative mammogram, a single dilated duct in isolation, or a small mass containing calcifications in either papilloma or malignancy (Fig. 10-10A to D). Ultrasound is frequently negative in women with nipple discharge, or fluid-filled dilated ducts without an intraductal mass in the retroareolar region may be seen. Solid masses in a fluid-filled duct may represent debris, a papilloma, or cancer.

Table 10-3 Imaging of Nipple Discharge

Figure 10-10 Papilloma in a dilated duct on mammography and ultrasound. A, The mammogram shows a markedly dilated duct (without contrast) extending into the breast from the nipple. B, Ultrasound revealed a fluid-filled dilated duct containing a mass, which was found to be a papilloma on biopsy. A papilloma in a contrast-filled duct in another patient has a filling defect (C); ultrasound shows the papilloma as a solid mass surrounded by the distended, contrast-filled duct (D). A blood vessel is seen in its fibrovascular component on color Doppler ultrasound (E).

Papillomas on MRI deserve special mention because they mimic cancer by producing a round enhancing mass that frequently has rapid initial early enhancement and a late plateau or washout on kinetic curve analysis, indistinguishable from invasive cancer (Fig. 10-11). For this reason, papillomas are a common cause of false-positive MRI-guided breast biopsies. On MRI, intraductal papillomas can have three patterns. The first pattern is a small circumscribed enhancing mass at the terminus of a dilated breast duct, corresponding to the filling defect seen on galactography. The second pattern is an irregular, rapidly enhancing mass with occasional spiculation or rim enhancement in women without nipple discharge; this is the pattern that cannot be distinguished from invasive breast cancer. Finally, despite the presence of a papilloma, MRI may be negative, with the papilloma undetected on both contrast-enhanced and fat-suppressed T1-weighted studies.

Figure 10-11 Papilloma on magnetic resonance imaging (MRI) and ultrasound. A, In a patient with nipple discharge, noncontrast T2-weighted sagittal MRI shows a bright fluid-filled duct extending from the nipple into the midbreast. B, Noncontrast sagittal 3-D spectral-spatial excitation magnetization transfer (3DSSMT) MRI shows high signal fluid within the lower breast ducts before contrast enhancement. C, Postcontrast sagittal 3DSSMT MRI shows a round enhancing mass in a duct (arrow), which previously had slight high signal fluid within it on part B. ROI over the mass on spiral dynamic scan (D) and the corresponding kinetic curve (E) show rapid initial enhancement and late washout, identical to kinetic curves in invasive cancer. ROI over the heart on spiral dynamic scan (F) and the corresponding kinetic curve (G) show rapid initial enhancement and late washout occurring in the same timeframe as the enhancing mass, indicating increased vascularity of the mass. H, Breast ultrasound shows a mass within a fluid-filled duct. I, Doppler ultrasound shows a pulsating blood vessel (arrow) within the mass, accounting for the rapid enhancement and washout. Biopsy showed intraductal papilloma.

Galactography is used to investigate single-duct nipple discharge; when positive, it is helpful in subsequent surgical planning by identifying filling defects and their location and distance from the nipple. Galactography may also show normal duct anatomy, duct ectasia, or fibrocystic change. To perform galactography, the radiologist identifies the discharging duct visually by expressing a small amount of the discharge and pinpointing the location of the discharging duct. The radiologist cleans the nipple, may use a topical anesthetic, and with sterile technique, cannulates the discharging duct with a 30-gauge blunt-tipped sialogram needle connected to tubing and a syringe filled with contrast. Usually, the needle will fall painlessly into the duct, but on occasion, warm compresses are needed to relax the duct opening. A small amount of contrast (0.2–1 mL) is injected into the duct until resistance is felt or the patient feels a sense of fullness in the breast. Because the ducts are quite fragile, pain or burning may indicate perforation or extravasation of contrast, but neither the cannulation nor the injection should be painful. Either symptom is an indication to stop the procedure and re-evaluate the situation.

After the injection, the needle is withdrawn, and the contrast-filled duct is sealed with collodion or the blunt-tipped catheter is taped in place to the nipple. Standard craniocaudal and mediolateral mammograms are obtained; some facilities use magnification views to confirm and evaluate the filling defects. After the mammogram, the contrast is expressed from the breast by gentle massage. If duct filling is incomplete, the contrast is diluted by retained secretions, or if an air bubble is simulating an intraductal filling defect, then the duct can be reinjected immediately for a second study.

A normal duct arborizes from a single entry point on the nipple into smaller ducts extending over almost an entire quadrant of the breast. Normal ducts are thin and smooth-walled and have no filling defects or wall irregularities (Fig. 10-12A). Ductal ectasia is not uncommon; occasionally, normal cysts or lobules fill from the dilated ducts (see Fig. 10-12B). Ectatic ducts without a filling defect are usually normal. However, despite a normal galactogram, surgical excision of the discharging duct may reveal papillomas or cancer (i.e., false-negative study; see Fig. 10-12C).

Figure 10-12 Normal galactograms. A, Normal galactogram showing contrast filling nondilated ducts without an abrupt cutoff or intraductal filling defects to suggest cancer or a papilloma. B, Normal galactogram demonstrating acinar filling. The galactogram shows two normally filling ducts, thin in diameter and without filling defects, and rounded acini filling in the periphery. C, Normal galactogram showing nondilated contrast-filled ducts in a patient with nipple discharge. Ductoscopy revealed two microscopic papillomas (false-negative galactogram).

Ducts containing malignancy or papillomas are typically dilated between the tumor and the nipple. Positive galactograms show a filling defect, an abrupt duct cutoff, or luminal irregularity and distortion. Tumors causing the abnormal findings may be located inside a fluid-filled dilated duct or may compress the duct from outside the duct walls (Fig. 10-13A to D). On occasion, masses, either papilloma or intracystic cancer, may become encysted (see Fig. 10-13D and E). Air bubbles produce filling defects that mimic papilloma or cancer, but they are usually sharply defined and round and change position inside the duct on repeat injection, unlike fixed intraductal tumors. On the galactogram, extravasation is seen as contrast extending outside the duct lumen into the breast tissue and obscuring the underlying breast tissue and ducts (see Fig. 10-13F). In the rare instance of lymphatic or venous uptake of extravasated contrast, a draining tubular structure leading away from the extravasation site can be seen.

Figure 10-13 A to C, Abnormal galactograms. A, Papilloma on galactography. A filling defect on the galactogram corresponded to a retroareolar papilloma at surgery. B, Galactogram with an abrupt cutoff in a proximal duct. Biopsy showed papilloma. C, Galactogram showing cancer. A magnification view of a galactogram reveals an irregular filling defect in the retroareolar region. Biopsy showed ductal carcinoma in situ. D, Magnified right lateral mammogram after contrast injection into the duct shows the papillary filling defect, representing a papilloma. E, Encysted papilloma seen as a filling defect in a cyst. F, Photomicrograph of the encysted papilloma. G, Extravasation on galactography. The mammogram shows extravasation of contrast outside the normal thin ducts.

A positive galactogram usually leads to biopsy, either by preoperative needle localization or by ductoscopy. Preoperative needle localization of filling defects after galactography under x-ray guidance may be helpful for surgical planning, especially if the intraductal mass is deep in the breast. Negative galactograms despite the presence of a papilloma on biopsy have been reported, and galactography has a sensitivity ranging from 69% to 78% for tumors.

In the early 1990s, surgeons reported using a tiny ductoscope to cannulate a discharging duct for identification of papillomas or other intraductal masses intraoperatively to guide surgery. Dooley reported that 16% of women undergoing ductoscopy at surgery had lesions detected by ductoscopy that were not seen on either ductograms or mammograms before surgery.

Breast Edema

On clinical examination, breast edema may be evident as peau d’orange (a term signifying thickening and elevation of the skin around tethered hair follicles, similar in appearance to an orange peel), and the edematous breast may be larger than the contralateral side. The differential diagnosis for breast edema depends on whether the edema is unilateral or bilateral (Box 10-6). Unilateral breast edema is due to mastitis, inflammatory cancer, local obstruction of lymph nodes, trauma, radiation therapy, or coumarin necrosis (Fig. 10-14). Bilateral breast edema is due to systemic etiologies, such as congestive heart failure, liver disease, anasarca, renal failure, or other conditions that can cause edema elsewhere in the body. Alternatively, bilateral lymphadenopathy or superior vena cava obstruction for any reason may cause bilateral breast edema (Fig. 10-15).

Figure 10-14 A, Unilateral breast edema on the right breast secondary to inflammatory cancer. Note the larger and whiter appearance of the right breast than the left, as well as marked coarsening of the trabeculae. B, Breast edema. A cropped, magnified mammogram shows skin thickening and atypical engorgement of the subdermal lymphatics in subcutaneous fat causing a trabecular pattern similar to Kerley B lines on a chest radiograph. Inflammatory cancer was the diagnosis. C, Unilateral breast edema from Hodgkin lymphoma and obstruction of the right axillary lymphatics. Note the chemotherapy port on the left. Normal mammogram before the development of inflammatory cancer (D) and mammogram with breast edema 8 months later (E). F, Focal edema and hematoma from trauma. G to I, Breast cancer, nipple retraction, and breast edema on MRI. G, In a patient with a large retroareolar breast cancer, precontrast sagittal 3-D spectral-spatial excitation magnetization transfer (3DSSMT) MRI shows skin thickening, nipple retraction, and dense tissue behind the nipple. H, Sagittal precontrast T2-weighted fat-suppressed MRI shows breast edema with fluid in the periareolar region and within thickened skin. I, Postcontrast sagittal 3DSSMT MRI shows marked enhancement of a large cancer in the retroareolar region, skin thickening, and enhancement of the areola and skin, which is abnormal. Biopsy showed inflammatory cancer.

Figure 10-15 Bilateral breast edema from superior vena cava (SVC) compression secondary to granulomatous disease. A, A bilateral mammogram shows bilateral breast edema, worse on the right because the patient preferentially lies on her right side. B, Contrast-enhanced computed tomography shows SVC syndrome from mediastinal adenopathy, collateral vessels in the left chest, and right pleural effusion.

The key to diagnosis is to obtain an accurate clinical history and evaluate the breast for any signs of cancer. The mammogram shows breast edema as skin thickening greater than 2 to 3 mm and coarsening of trabeculae in subcutaneous fat because of fluid within subdermal lymphatics. On the mammogram, the subcutaneous fluid produces thick white lines in subdermal fat just below the skin line that have an appearance similar to Kerley B lines at the periphery of the lung on chest radiographs in congestive heart failure. An edematous breast will be much denser and more difficult to penetrate and will appear whiter than the contralateral side because of fluid in the breast tissue.

The differential diagnosis for increased bilateral breast density on mammography includes breast edema, exogenous hormone therapy, and weight loss. Increased breast density from edema is due to fluid overload. Increased breast density from exogenous hormone therapy is due to hormonally driven proliferation of stromal and epithelial breast tissue (Fig. 10-16). Increased breast density due to weight loss is not due to any increase in breast tissue, but is due to loss of fat (Fig. 10-17). A history of recent weight loss should lead to the correct diagnosis.

Figure 10-16 Exogenous hormone replacement therapy. Bilateral mediolateral oblique mammograms before (A) and after (B) hormone replacement therapy show increased glandular tissue bilaterally in locations where glandular tissue previously existed. Unlike breast edema, there is no skin thickening or coarsening of trabeculae in subcutaneous fat.

Figure 10-17 Weight loss. Bilateral craniocaudal mammograms before (A) and after (B) weight loss show increased breast density on the mammogram because of loss of fat.

To disinguish between breast edema and exogenous hormone therapy or weight loss, the radiologist looks for skin thickening, which is found only with breast edema (Box 10-7). The increased breast density from breast edema can occur anywhere; skin thickening in dependent portions of the breast is often seen. The increased breast density from exogenous hormone therapy is usually bilateral, occurs in regions where breast tissue was previously present, and shows no skin thickening.

On ultrasound, breast edema is characterized by skin thickening, loss of the normal sharp margins of Cooper ligaments, increased echogenicity of surrounding tissues and, in severe cases, fluid in dilated subdermal lymphatics, which are seen as tubular fluid-filled structures just under the skin line. In inflammatory cancer, breast ultrasound may detect a hypoechoic shadowing mass that may represent an invasive ductal cancer hidden on the mammogram by overlying breast edema.

On MRI, breast edema is manifested as skin thickening and coarsening of breast trabeculae and Cooper ligaments. Locally advanced cancer is usually seen as an irregular mass with rapid initial enhancement, a late plateau or washout phase, and enhancement within the skin if skin invasion has occurred.

Inflammatory cancer, a rare (1% of all cancers) aggressive breast cancer with a poor prognosis, is the most important differential diagnosis for unilateral breast edema. The definition of inflammatory cancer varies, but it usually has the clinical signs of an enlarging erythematous breast with peau d’orange, and it should be distinguished from locally advanced breast cancer, producing a focal, red, raised skin metastasis. Inflammatory cancer is often mistaken for mastitis because of its clinical features, but it does not respond to antibiotics. Mammography of inflammatory cancer reveals findings of breast edema (skin thickening, diffuse increased breast density, trabecular thickening), but it may also demonstrate findings of cancer, including a breast mass, asymmetric focal density, microcalcifications, nipple retraction, or axillary adenopathy. Ultrasound may show findings of breast edema in 96% of cases, masses in 80%, and dilated lymphatic channels in 68%. On MRI, one report of inflammatory cancer described a “patch enhancement” pattern with some “areas of focal enhancement” and washout on the late phase of the dynamic curve. The enhancement rate on MRI for inflammatory cancer is reported to be quite rapid in the initial postcontrast phase and slightly less rapid in mastitis. The MRI shows breast edema, skin thickening, and skin enhancement (see Fig. 10-14G to I). On biopsy, breast cancer is present in the dermal lymphatics in 80% of cases. The usual management is biopsy to make the diagnosis of inflammatory cancer, neoadjuvant chemotherapy with or without subsequent surgery, and radiation therapy, depending on tumor response, or any combination of these modalities.

Mastitis is a common cause of unilateral breast edema, and clinical findings of pain, erythema, and peau d’orange are typically noted. The most common cause of mastitis is S. aureus. Rare causes of breast infection include tuberculosis, syphilis, hydatid disease, and molluscum contagiosum. Clinically, mastitis produces breast cellulitis, which if untreated, may progress to small focal microabscesses or a larger abscess collection that may become walled off. On mammography, mastitis appears as unlateral breast edema. When mastitis progresses to abscess, abscesses are tender palpable masses, usually in the retroareolar region, on physical examination. On mammography the abscess is an ill-defined or irregular mass without calcifications. Usually, no gas is present in the abscess on the mammogram. Rarely, an abscess contains gas, but most commonly after aspiration has been attempted. On ultrasound, the abscess is an irregular, ill-defined hypoechoic mass, sometimes containing septations or debris, with enhanced through-transmission of sound. Because antibiotics cannot cross abscess walls, larger abscesses require either percutaneous or operative drainage. For this reason, ultrasound is particularly helpful in the setting of mastitis to detect and define abscesses requiring drainage.

A recurrent subareolar abscess is a special entity caused by plugging of the major breast ducts and subsequent infection; it is commonly associated with a fistulous tract that forms from the abscess inside the breast and drains to the skin. The resulting abscess is chronic and may be drained percutaneously or operatively many times without resolution or with frequent recurrence. A recurrent subareolar abscess is treated by surgically removing both the abscess and the fistulous tract.

An extremely rare cause of unilateral breast edema is necrosis of the breast from coumarin (warfarin [Coumadin]) therapy. Necrosis occurs more commonly in the abdomen, buttocks, and thighs, rather than in breast, and it occurs in 0.01% to 1% of coumarin-treated patients (Box 10-8). Although it has been associated with protein C or protein S deficiency, the exact mechanism of coumarin-induced necrosis is unknown. Painful lesions, swelling, and petechiae from thrombosis of small vessels and inflammation occur after the initiation of coumarin treatment; large hemorrhagic bullae result and develop to full-thickness fat and skin necrosis. Discontinuing the use of coumarin is recommended. Heparin or other anticoagulants may be necessary in patients who require sustained anticoagulation in the short term. Heparin-induced skin necrosis has also been reported in association with type II heparin-induced thrombocytopenia, but heparin is often used in the setting of coumarin necrosis. In some cases, the skin lesions heal spontaneously after shallow tissue sloughing. In other cases, skin grafts are required; in extreme cases, mastectomy is required.

Hormone Changes

Normal women have extremely dense breast tissue when young that is replaced by fat during the aging process. On mammography, the breasts usually appear very white in younger patients and become darker and darker as glandular tissue is replaced by fatty tissue with age. The overall breast density at any time in the patient’s life depends on the patient’s age, her genetic predisposition for glandular tissue, and her hormonal status.

Exogenous hormone replacement therapy, pregnancy, and lactation reverse the trend toward fatty breast tissue by causing a proliferation of the glandular elements and periductal stroma of the breast, thereby resulting in a denser mammogram. Unlike breast edema, only the breast tissue becomes denser, and the skin does not become thickened more than 2 to 3 mm as it does with breast edema (Fig. 10-18).

Figure 10-18 Exogenous hormone replacement therapy. Mediolateral oblique mammograms before (A) and after (B) hormone replacement therapy show a denser breast where breast tissue previously existed.

Some women report breast tenderness, pain, fullness, and lumpiness with exogenous hormone replacement therapy. The frequency of increased breast density on mammography in women undergoing exogenous hormone therapy varies from 23% to 34%. The highest percentage of women with increased density were receiving continuous-combined hormone therapy consisting of conjugated equine estrogen, 0.625 mg/day, plus medroxyprogesterone acetate, 2.5 mg/day, or other combinations, with the progestin component most affecting the increase in breast density. In another report, continuous-combined hormone therapy produced increased breast density on mammography, but estrogen-only therapy did not.

Other medications also have effects on breast density. Raloxifene hydrochloride, a drug used for bone mineral density, has been reported to produce increased breast density on mammography in a very small number of women. Case studies of two women undergoing injections of medroxyprogesterone (Depo-Provera) for contraception reported a decrease in breast density on mammograms during the injections and an increase in breast density when the injections were discontinued. Tamoxifen used for adjuvant or prophylactic treatment of breast cancer has been reported to decrease mammographic tissue density in some women, with one case report describing a return to baseline breast density after termination of drug therapy. Isoflavones are phytoestrogens contained in soy foods and have been reported to have both estrogenic and antiestrogenic effects. A double-blind, randomized trial of women undergoing mammography after isoflavone supplements showed no significant decrease in breast density or change in dense tissue over a 12-month period.

Because breast density changes with hormone therapy, new or focal densities on mammograms are correlated with older films and the clinical history, in addition to being evaluated for a new mass or a developing density as a result of cancer. In questionable cases, spot compression, fine-detail views, and ultrasound may be helpful to exclude the presence of a mass. If questions still remain after additional workup, discontinuing exogenous hormone therapy for 3 months and re-imaging may exclude a mass. Similarly, the increased breast enhancement noted on contrast-enhanced breast MRI in women receiving exogenous hormone replacement therapy is reversible when the therapy is discontinued.

Breast Pain

Breast pain is an extremely common complaint. However, in the absence of an associated palpable lump, it is a very infrequent sign of breast cancer. Nevertheless, because both breast pain and breast cancer are common, the purpose of the workup is to reassure the patient and exclude a coexistent cancer. Breast pain may be focal or diffuse. It may vary with the menstrual cycle (i.e., cyclic) or not (i.e., noncyclic). In general, diffuse and cyclic breast pain is a benign symptom that does not warrant imaging evaluation.

Patients with focal breast pain should be evaluated with mammography and breast physical examination. Although focal breast pain is worrisome to the patient, studies have shown that it is most often not caused by cancer. However, because both breast pain and cancer are common, mammography is reasonable to exclude cancer and reassure the patient. Consideration should be given to ultrasound in women with focal pain to exclude a breast cyst that may be causing the pain.

Cyclic mastalgia has many causes, including cyclic enlargement as a result of menses or multiple cysts. Relief from breast pain may be achieved in some cases by aspiration of the cyst, decrease in caffeine intake, or analgesics. Home remedies for breast pain have included 400 U of vitamin E per day, vitamin B₆, analgesics, decrease in fat and salt intake, use of sports brassieres, and evening primrose oil. In extreme cases, progestins, danazol, tamoxifen, or bromocriptine is used to relieve mastodynia.

Axillary Lymphadenopathy

Axillary lymphadenopathy is visualized on mammography as replacement of the fatty hilum of lymph nodes by dense tissue, a rounded shape of the lymph nodes, and an overall generalized increased density with or without lymph node enlargement (Fig. 10-19). Abnormal lymph nodes may also contain calcifications, gold deposits mimicking calcifications from treatment of rheumatoid arthritis, or silicone from a previously ruptured breast implant. The differential diagnosis for axillary adenopathy without a definite breast mass varies for unilateral versus bilateral findings (Box 10-9). Causes of unilateral axillary adenopathy include metastatic breast cancer and mastitis. Bilateral axillary adenopathy is usually due to systemic etiologies, such as infection, collagen vascular diseases such as rheumatoid arthritis, lymphoma, leukemia, or metastatic tumor.

Figure 10-19 Axillary lymphadenopathy. A, Abnormal dense round lymph nodes in the axilla have lost their fatty hila and are rounder and bigger than normal lymph nodes as a result of lupus and rheumatoid arthritis. B, Abnormal round lymph nodes in another patient with lymphoma on digital mammography. C, Left mediolateral oblique view shows a mass in the upper breast representing an invasive ductal cancer with an abnormal lymph node (arrow) in the left axilla. Even though the lymph node still has its fatty hilum, it is worrisome for cancer metastases because it is rounder, denser, and has a thicker cortex than a normal lymph node. Metastatic disease was found in the lymph node at sentinel lymph node biopsy.

“Calcific” particles in abnormal axillary lymph nodes may represent calcified metastasis from breast cancer or calcifying infections such as tuberculosis (Box 10-10). In the case of tuberculous mastitis, patients have axillary swelling and breast enlargement without a breast mass, as well as enlarged dense or matted axillary lymph nodes or breast edema with or without findings of pulmonary tuberculosis. The finding of macrocalcifications rather than pleomorphic microcalcifications in the lymph nodes may suggest tuberculous mastitis, but biopsy is necessary to exclude metastatic breast cancer. Migration of silicone into axillary lymph nodes from ruptured silicone breast implants or migration of gold particles from therapy for rheumatoid arthritis may mimic calcifications in lymph nodes, but the clinical history should provide clues to the correct diagnosis.

Detection of lymphadenopathy on mammography in women with no underlying palpable breast mass or clinical reason for the abnormal lymph nodes should prompt a critical review of the breast for pleomorphic calcifications or other signs of breast cancer. In one clinical series of 21 women with lymphadenopathy detected at screening mammography, 50% was due to malignancy (lymphoma, metastatic carcinoma, leukemia), and the other 50% was due to benign causes (reactive changes, healed granulomatous disease, rheumatoid arthritis, amyloid, infection).

Primary breast cancer presenting as isolated lymph node metastasis in the setting of normal mammographic and physical examination findings is an uncommon clinical problem that accounts for less than 1% of all breast cancers (Fig. 10-20). Both breast ultrasound and contrast-enhanced breast MRI have been used to detect the primary breast cancer in this scenario, with improved results in comparison to mammography, and breast conservation rather than mastectomy is a potential option once the primary tumor is found (Fig. 10-21). Diagnosis of a primary cancer within the breast is clinically contributory, because an occult primary malignancy in the breast would be considered locoregional rather than metastatic disease in patients who present with axillary lymphadenopathy of unknown primary. In some cases the primary breast cancer is never identified. In a pathology series by Haupt and colleagues, in which 43 women with this clinical dilemma were reviewed, the primary tumor was found in 31 (72%) specimens but never identified in the remaining 12. Survival rates between the two groups were similar, and the 12 women in whom a tumor was never discovered did have another primary malignancy detected in the follow-up period.

Figure 10-20 Breast cancer presenting as axillary lymphadenopathy. Normal right (A) and abnormal left (B) mammograms show adenopathy in the left axilla, which was consistent with the diagnosis of breast cancer. Additional views of the left breast by mammography and ultrasound did not demonstrate any masses. Examination after mastectomy showed no primary breast cancer. The patient was treated for breast cancer empirically. No breast cancer in the opposite breast and no additional tumors were found elsewhere in 5 years of follow-up.

Figure 10-21 A shaded, cut-surface display of contrast-enhanced magnetic resonance imaging of the breast shows an irregular-enhancing suspicious mass in the upper part of the breast representing an occult malignancy not seen on mammography.

(Image courtesy of Bruce L. Daniel, MD, Stanford University, Stanford, CA.)

Paget Disease of the Nipple

Paget disease of the nipple is a distinct clinical entity that heralds an underlying breast cancer. Ductal carcinoma almost always coexists with Paget disease, either in the ducts beneath the nipple or elsewhere in the breast, and it has a high rate of overexpression of the c-erb-B2 oncogene. The underlying pathology is almost always high-grade DCIS, but an invasive component may also be present. Affected women have a bright, reddened nipple and eczematous nipple changes that may extend to the areola, with subsequent ulceration and nipple destruction if the process is unchecked. A delay of several months often occurs before women seek advice, unless associated nipple discharge is present. Paget disease of the nipple may mimic dermatitis of the nipple, resulting in delayed diagnosis. If the patient’s symptoms do not respond to a trial of topical steroids, the diagnosis of Paget disease should be considered.

The nipple and mammogram are normal in almost 50% of cases despite clinical signs of Paget disease and the presence of an underlying breast cancer (Box 10-11). On abnormal mammograms, the underlying malignancy has the appearance of suspicious microcalcifications, a spiculated mass, or both. The cancer is often located in the subareolar region or deep in the breast and does not necessarily lie directly adjacent to the nipple or areola (Fig. 10-22A). In women with Paget disease, skin or areolar thickening, nipple retraction, subareolar masses, or calcifications leading to the nipple should be viewed with suspicion on mammography (see Fig. 10-22B). Spot compression magnification mammography of the nipple and retroareolar region is often helpful in identifying subtle abnormalities. Conversely, nipple–areolar abnormalities or thickening detected at mammography should be correlated with the physical examination to exclude clinical findings of Paget disease.

Figure 10-22 Paget disease. A, Craniocaudal mammogram shows nipple retraction and a second invasive ductal cancer deep in the breast in a patient with Paget disease. B, Mediolateral oblique mammogram in a patient with Paget disease shows destruction of the nipple covered with a radiopaque salve and a retroareolar dense mass producing retraction.

Sarcomas

Sarcomas are rare tumors of the breast or the underlying chest wall, and their classification depends on the cell type involved (Fig. 10-23). Ultrasound shows a hypoechoic mass and may be helpful in determining whether the origin of the sarcoma is from the breast or chest wall (Fig. 10-24A and B). Mammography shows high-density masses without calcifications or spiculation, unless the tumor has osseous elements (Fig. 10-25). MRI is useful for demonstrating pectoralis muscle or chest wall involvement, because sarcomas tend to be large and locally invasive.

Figure 10-23 Carcinosarcoma. Craniocaudal (A) and mediolateral oblique (B) mammograms in a 37-year-old woman with a palpable mass show a dense lobulated mass in the right breast with an obscured lower border. Pathologic examination demonstrated the epithelial and mesenchymal differentiation required to make the diagnosis.

(From Smathers RL: Mammography: diagnosis and intervention, Medical Interactive [compact disc]. Copyright Mammography Specialists Medical Group, Inc. Contribution from Suzanne Dintiz, MD, Stanford, CA.)

Figure 10-24 Chondrosarcoma of the rib. A, Mediolateral oblique mammogram shows a marker over a slowly growing mass, which proved to be only dense tissue. B, Ultrasound reveals a complex heterogeneous mass invading the chest wall, predominantly posterior to the pectoralis muscle and measuring 6 cm. C, Pathologic examination showed a grade 1 chondrosarcoma containing mature hyaline cartilage and reactive bone in continuity with the rib.

(From Smathers RL: Mammography: diagnosis and intervention, Medical Interactive [compact disc]. Copyright Mammography Specialists Medical Group, Inc. Contribution from Suzanne Dintiz, MD, Stanford, CA.)

Figure 10-25 Fibrosarcoma of the breast with osseous trabeculae. Craniocaudal mammogram shows a dense mass containing dense calcification resembling bone.

(From Elson BC, Ikeda DM, Andersson I, Wattsgard C: Fibrosarcoma of the breast: mammographic findings in 5 cases, AJR 158:994, 1992.)

MRI of angiosarcoma shows low signal intensity on T1-weighted images, higher signal intensity on T2-weighted images, and enhancement of the mass with a low-intensity central region. At pathology, sinusoids containing red blood cells are present. Angiosarcoma of the breast may be primary or secondary to radiation, usually received as adjunctive therapy after breast conservation surgery (i.e., lumpectomy). Secondary angiosarcoma usually occurs approximately one decade after the initial radiation therapy.

Mondor Disease

Mondor disease is acute thrombophlebitis of the superficial veins of the breast (Box 10-12). It is rare, is often associated with trauma or recent surgery, and has been reported to occur after sonography-guided or stereotactic core biopsy, but may also be idiopathic in origin. Patients report acute pain, discomfort, and tenderness along the lateral aspect of the breast, the chest wall, or the region of the thrombosed vein; they may also report a cordlike, painful elongated mass just below the skin. Extension of the arm may produce a long narrow furrow in the skin as a result of retraction from the thrombosed vein, similar to skin dimpling from breast cancer.

Physical examination shows a tender palpable cord extending toward the outer portion of the breast that is produced by fibrosis and obliteration of the superficial vein; in the acute phase, it is occasionally accompanied by discoloration of the overlying skin. Thereafter, the vein diminishes in painfulness over a period of 3 to 4 weeks as a result of either recanalization or complete obliteration of the vein by phlebosclerosis and hyalinization. Because Mondor disease is self-limited and the palpable finding resolves over a 2- to 12-week period, supportive care is the appropriate treatment.

Case reports describe negative mammographic findings in women with Mondor disease or, rarely, a long linear or tubular density on the mammogram corresponding to the thrombosed vein (Fig. 10-26). Case reports of ultrasound in Mondor disease show a noncompressible hypoechoic tubular cord in the subcutaneous tissue, with or without flow on color Doppler imaging, depending on the degree of recanalization.

Figure 10-26 Mondor disease. Craniocaudal (A) and mediolateral oblique (MLO) (B) mammograms of a marker over a tender, elongated, dilated ductlike structure in the right axilla of a young woman. C, Spot compression on the MLO view shows a tubular mass representing the superficial thrombophlebitis that results in the nodular, superficial tender vein typical of Mondor disease.

Granulomatous Mastitis

Granulomatous mastitis is a rare disease that occurs in young premenopausal women after their last childbirth. It has been correlated with breast-feeding and oral contraceptive use, and a possible autoimmune component has been implicated in its etiology. Affected patients may have galactorrhea, inflammation, a breast mass, induration, and skin ulcerations.

Women undergoing mammography are found to have asymmetric density, focal asymmetric or ill-defined breast masses, or negative results. Calcifications are not a feature. On ultrasound, findings include irregular masses, focal regions of inhomogeneous patterns associated with hypoechoic tubular/nodular structures, or decreased parenchymal echogenicity with acoustic shadowing, all suggestive of malignancy (Fig. 10-27A to D).

Figure 10-27 A to D, Granulomatous mastitis. Mediolateral oblique (A) and craniocaudal (B) mammograms show a marker over a palpable right breast mass shown as a focal asymmetry. Radial (C) and antiradial (D) ultrasounds show a complex irregular heterogeneous mass corresponding to the palpable finding and the mammographic mass. Biopsy showed granulomatous mastitis. E and F, Diabetic mastopathy. Ultrasound scans of diabetic mastopathy in longitudinal (E) and transverse (F) images show an ill-defined shadowing mass mimicking breast cancer. Biopsy showed diabetic mastopathy.

Because the mammographic and sonographic features suggest breast cancer, biopsy is frequently performed on women with this condition. Biopsy shows a chronic granulomatous inflammation composed of giant cells, leukocytes, epithelioid cells, macrophages, and abscesses. Treatment consists of surgical excision, oral steroid therapy, anti-inflammatory drugs or colchicines, or methotrexate, as well as antibiotic treatment of any associated abscesses. Recurrence rates of up to 50% have been reported, but they can be reduced by immunosuppressive treatment until complete remission.

Diabetic Mastopathy

Diabetic mastopathy produces hard, irregular, sometimes painful mobile breast masses that may be recurrent or bilateral in patients with a history of long-term insulin-dependent diabetes, in younger premenopausal diabetic women, or in rare patients with thyroid disease (Box 10-13). Diabetic mastopathy is due to an autoimmune reaction to the accumulation of abnormal matrix proteins caused by hyperglycemia. It leads to atrophy and obliteration of glandular breast tissue and the production of fibrosis, which forms a hard mass simulating breast cancer. Because of the hardness of the mass, needle biopsy is often performed, but it may be insufficient for diagnosis and therefore may necessitate histologic sampling. Pathologic examination reveals fibrosis with a dense lymphocytic infiltration around breast lobules and ducts.

Mammography shows a regional asymmetric density with ill-defined margins but no microcalcifications or dense glandular tissue. Ultrasound demonstrates a hypoechoic mass or region displaying marked acoustic shadowing in most cases, findings suggestive of scirrhous breast cancer (see Fig. 10-27E).

Case reports of diabetic mastopathy on MRI describe a decreased area of signal intensity with “poor” or “heterogeneous” enhancement or “nonspecific” enhancement in the initial postcontrast phase. Heterogeneous “spotting enhancement” or a “benign gradual-type dynamic curve” is reported in the late enhancement phase.

On biopsy, fibrosis with perivascular, periductal, or perilobular lymphocytic infiltrates is seen. Frequently, patients will undergo surgical excisional biopsy. Unfortunately, surgery may exacerbate the disease, with recurrences developing in the same location.

Desmoid Tumor

Desmoid tumor, or extra-abdominal desmoid, is also known as fibromatosis. Desmoid tumor is an infiltrative, locally aggressive fibroblastic/myofibroblastic process that may recur locally, may be multicentric, has been associated with previous trauma or surgery, and has been reported in women with breast implants. In the breast, desmoid tumor is manifested as a solitary, hard painless mass, occasionally fixed to the skin or pectoral fascia. Because treatment involves wide surgical excision, the primary tumor is evaluated for its origin within either the breast or the underlying musculo-aponeurotic structures. The extent of invasion into surrounding structures is also evaluated to facilitate surgical planning.

On mammography, desmoid tumors are spiculated masses. Ultrasound shows a hypoechoic shadowing mass. Because these masses simulate spiculated breast cancer, biopsy is required (Fig. 10-28).

Figure 10-28 Computed tomography scan shows a soft-tissue mass adjacent to the pectoralis muscle in the left breast. Biopsy revealed a desmoid tumor.

Treatment of desmoid tumors is complete local surgical excision. Recurrence of desmoid tumor is less likely with wide excision and clear histologic margins. Tumor recurrence usually occurs within 3 years of excision, and for this reason breast reconstruction is generally delayed for 3 years. Because surgical trauma has been associated with recurrence, informed consent is necessary before breast reconstruction. Recurrences are treated by radical excision, just as the primary tumor is. Radiation therapy is used as an alternative to surgery for tumors in which complete excision would result in a poor functional outcome or for some tumors with positive margins (Box 10-14).

Trichinosis

Trichinosis is caused by the ingestion of raw or undercooked meat containing encysted larvae of the Trichinella genus. Diarrhea is produced during the intestinal phase of adult development, and then myositis, fever, and periorbital edema develop during larval migration (Box 10-15). After gastric digestion releases the encysted larvae, the larvae migrate into the intestinal mucosa, mature, and mate. The adult female releases new larvae into mucosal blood vessels, and the larvae are distributed throughout the body over a period of 4 to 6 weeks. The larvae enter skeletal muscles, most commonly the diaphragm, tongue, periorbital muscles, deltoid, pectoralis, gastrocnemius, and intercostal muscles, where the larvae encyst and calcify in 6 to 18 months, with a further life span of 5 to 10 years in the encysted form. During migration, larvae may also produce myocarditis, pneumonitis, or central nervous system symptoms from vasculitis of small arteries or capillaries, but encystment does not usually occur in these locations. Ingestion of the encysted larvae by a new host perpetuates the life cycle of the organism. In the United States, most Trichinella infections are asymptomatic and are acquired by ingesting undercooked pork, feral meat, wild boar, bear, or walrus.

On mammography, the calcified encysted larvae are seen as tiny linear calcifications smaller than 1 mm that are aligned along the long axis of the pectoralis muscle, parallel to the muscular fibers (Fig. 10-29). Because the calcifications are within the muscle, they should not be mistaken for breast cancer. At this point patients are asymptomatic.

Figure 10-29 Trichinosis. A magnified mediolateral oblique view of the upper part of the breast shows innumerable tiny calcifications aligned along the pectoralis muscle that represent the calcified encysted larvae of Trichinella.

Parasitic diseases that have been reported to calcify in breast tissue include hydatid disease, paragonimiasis, Dirofilaria repens infection, schistosomiasis, myiasis, and loiasis.

Dermatomyositis

Dermatomyositis and some collagen vascular diseases can rarely produce calcifications within the soft tissues of the arms and legs. In the breast, bizarre sheetlike calcifications form in a configuration similar to that of fat necrosis; the calcifications align along the breast tissues and generally point at the nipple (Fig. 10-30). Dermatomyositis is not a specific indicator of breast cancer. However, mammography is often performed because of an association of dermatomyositis with malignancies.

Figure 10-30 Mammograms showing dystrophic calcifications in patients with collagen vascular disease. Craniocaudal (A) and mediolateral oblique (B) mammograms show extensive dystrophic calcifications in both breasts. C, Dystrophic calcifications seen in another patient on craniocaudal mammogram. Dermatomyositis with calcifications was the diagnosis.

Foreign Bodies

Foreign bodies can be seen within the breast on mammography. Some acupuncture practitioners break acupuncture needle tips off in the breast tissue after placement, and the tiny sheared-off metallic needle tip fragments can be seen inside the breast tissue (Fig. 10-31A and B).

Figure 10-31 Foreign bodies. Mediolateral oblique (MLO) (A) and craniocaudal (CC) (B) mammograms show dense small masses throughout the breast tissue representing silicone injections, as well as thin metallic slivers in the peripheral breast parenchyma representing retained acupuncture needles. C to J, Metallic clip and ultrasound-visible pellets for marking the biopsy site after percutaneous needle biopsy. C, Pellets and a metallic marker. D, Echogenic ultrasound appearance after a gel marker is placed. E, Magnetic resonance imaging signal void from a metallic marker. F, Cropped digital mammogram shows an opaque tubelike structure in the upper right breast representing a retained cuff from a prior catheter. G, Another retained Dacron Hickman catheter cuff in the upper part of the right breast is seen as a radiopaque tube. H, Mammography shows sutures containing knots and a small calcified suture fragment. I, A needle was iatrogenically placed by this patient into her own breast, and it subsequently broke and calcified. J, Cropped chest radiograph shows a bullet projected over the left breast. K, To remove the bullet, the patient underwent needle localization, shown here in the alphanumeric grid. MLO (L) and CC (M) mammograms show the bullet at the end of the hookwire.

The most common foreign bodies seen in the breast on mammography are metallic markers placed percutaneously after core needle biopsy guided by stereotaxis, ultrasound, or MRI (see Fig. 10-31C to E). The markers have different shapes, depending on the manufacturer, and may contain a pellet or pellets that are visible by ultrasound. For patients who desire removal of the markers, case reports describe the use of an 11-gauge stereotactic vacuum-assisted probe technique that can remove the markers percutaneously. Percutaneous breast biopsy devices may produce tiny residual metallic shavings or fragments from the biopsy probe or needle itself and are usually not seen on the mammogram. These fragments are ferromagnetic and can occasionally cause signal voids on MRI.

Fragments of preoperatively placed hookwires have been reported in the breast after preoperative needle localization; these fragments may have been transected at surgery or may be due to breakage of the wire at the hooked end. Specimen radiography is used to determine whether the lesion prompting biopsy has been removed, as well as whether the hookwire and hookwire tip are included in the specimen. Information regarding the lesion, hookwire, and hookwire tip should be conveyed to the surgeon in the operating room to ensure complete removal of both the lesion and the hookwire tip. Although some hookwire fragments have been reported to be stable within the breast 1.5 to 11 years after surgery, other fragments become symptomatic as a result of migration within and through the breast into the soft tissues of other parts of the body.

Round Dacron Hickman catheter cuffs may be left inside the breast after removal of a Hickman catheter. The rounded, short tubelike structure made of Dacron has a characteristic appearance in the upper part of the breast on mammography (see Fig. 10-31F and G).

Sutures used to close breast cancer biopsy sites may calcify after lumpectomy and radiation therapy, thereby delaying absorption of the suture material and promoting calcification. The result is linear or curvilinear calcification of the suture; the diagnosis can be made if the suture still contains a knot (see Fig. 10-31H).

Surgeons occasionally place metallic surgical clips in breast cancer biopsy cavities to delineate the extent of the tumor site for radiation oncologists to plan electron beam boosts. This practice is becoming less common because of the increasing use of MRI for follow-up and the use of ultrasound to delineate the breast biopsy cavity to guide planning for electron beam boost therapy.

Other materials may lodge in the breast, and the clinical history may help in the diagnosis (see Fig. 10-30I to M).

Hidradenitis Suppurativa

This condition involves hidradenitis of the apocrine sweat glands, which are usually located in the axilla and the inguinal region. In the breast, these glands are also found in the inframammary folds, between the breasts, and around the areola. Hidradenitis suppurativa has been reported in obese patients in regions where the skin surfaces of the breasts or chest wall rub together. Severe hidradenitis causes masses with local inflammation. Severe cases are treated by excision of local disease, but local recurrence is common after treatment.

Neurofibromatosis

This autosomal dominant disease is composed of two main types, the most common of which is also known as von Recklinghausen disease (type I) and is found in 90% of patients. Affected patients may have café au lait skin lesions, neurofibromas of the neural plexus or peripheral nerve sheaths, and neurilemmomas.

The skin lesions of neurofibroma can mimic a deep breast tissue mass and limit evaluation of the breast. However, like any skin lesion, neurofibromas may be outlined with air, and correlation with the breast history form is advisable. Furthermore, the description of cutaneous findings on the technologist’s sheet should enable the radiologist to distinguish neurofibromas on the skin from masses of ductal origin inside the breast (Fig. 10-32).

Figure 10-32 Neurofibromatosis simulating breast masses. Right lateral (A) and left lateral (B) mammograms show a neurofibroma simulating a retroareolar mass on the left and a long neurofibroma extending from inferior to the nipple on the right.

Poland Syndrome

Poland syndrome is an absence of the pectoralis muscle on x-ray. It is usually unilateral. The mammogram shows absence of the pectoralis muscle on one side (Fig. 10-33).

Figure 10-33 Poland syndrome. Right (A) and left (B) mediolateral oblique (MLO) implant-displaced mammograms show a pectoralis muscle on the left and absence of the pectoralis muscle on the right. C, Side-by-side MLO implant-displaced mammograms shows symmetry of the glandular tissue to greater advantage.

Breast Cancer Missed by Mammography

Nondetection of breast cancer on mammography is of concern to the patient, the referring physician, and the radiologist. Detection of cancer on mammography is the result of a variety of factors, including the mammographic technique, experience of the radiologist, morphology of the breast tumor, and the background on which it is displayed. Cancers can best be displayed by good mammographic technique, optimal positioning, and a tumor location that can be displayed on the film. Approximately 10% to 15% of breast cancers are mammographically occult, even on good images, and will not be detected on mammography in the best of hands.

Cancer may not be detected on previous mammograms for several reasons (Box 10-16). First, the tumor may have a morphology that is undetectable on the mammographic background on which it is displayed and is therefore mammographically occult.

Second, the tumor may display findings that are visible, but below the threshold of any radiologist for consideration as cancer. Such findings have been termed nonspecific, examples of which include mammographic findings suggesting normal islands of fibroglandular tissue, a few benign-appearing calcifications, or a benign-appearing mass among many other benign-appearing masses that do not represent cancer.

Third, the tumor may show subtle findings that represent cancer but are atypical, such as a single dilated duct, a developing density, or other less common features of breast cancer that are perceptible but may have been unrecognized.

Fourth, signs that are classic for breast cancer may have been present on the mammogram but either were not perceived or were misinterpreted at the time of diagnosis.

Box 10-17 shows factors that may contribute to cancer being missed on previous mammograms. Birdwell and colleagues reviewed possible reasons why tumors were not identified on previous mammograms. They postulated that findings were hidden among many other findings (“busy breasts”) or that distracting findings other than the cancer were present on the film. Other contributing factors included dense breast tissue, small calcifications or masses that may have been overlooked, cancers hiding in the axilla and simulating lymph nodes, linear microcalcifications simulating vascular calcifications, findings seen on only one mammographic view, and findings at the edge of the film or at the edge of the glandular tissue, producing either a tent sign or concavity that was missed at the time of screening. Of note, most of these cancers were located in the upper outer quadrant, where 50% of all cancers occur. Also of note, not all the cancers that were missed were small, inasmuch as at least half the tumors were 1 cm or larger at the time that they were missed.

To decrease the number of missed breast cancers, the radiologist should use a systematic approach to reviewing the mammogram that minimizes distractions, paper shuffling, or other busy work in the reading room at the time of interpretation. Next, comparison to older films may reveal subtle changes not apparent on only the current examination. Finally, the radiologist should be aware of subtle or nonspecific findings of breast cancer.

Asymmetries

Asymmetries differ from true masses in that they may be seen primarily in one of two standard mammographic views, display concave-outward (rather than convex-outward) margins, and have lucent fat interspersed rather than being densest in the center (Box 10-18). Asymmetries are often normal findings in the breast, but they may occasionally represent a subtle malignancy, particularly lobular carcinoma. Hence, appropriate imaging evaluation is crucial in diagnosing these often subtle cancers while avoiding an unacceptably high false-positive rate.

In the fourth edition of the BI-RADS® lexicon, published in 2003, the terms used to describe asymmetries were changed. Currently, there are four categories of breast asymmetry: asymmetry, global asymmetry, focal asymmetry, and developing asymmetry. Formerly known as density, an asymmetry is a focus of fibroglandular tissue seen on only one of two standard mammographic views at screening. It is likely the result of superimposition of normal fibroglandular tissues, or a summation artifact. This determination may be made by either examination of the other mammographic view or at recall imaging with diagnostic mammographic views, such as spot compression mammography. Ultrasound is usually not warranted in such cases. Formerly known as asymmetric breast tissue, a global asymmetry is asymmetric breast tissue in one breast when compared with a corresponding region in the other breast. It is a sizable finding, usually occupying at least one quadrant of the breast. It is almost always a normal variant, reported in approximately 3% of mammographic examinations. Asymmetric breast tissue has additional clinical significance in possibly denoting malignancy when it is palpable.

Formerly known as focal asymmetric density, a focal asymmetry mimics a mass in that it is seen in at least two mammographic projections, but lacks the convex-outward margins of a mass and three-dimensionality of a mass. In the absence of associated calcifications, architectural distortion, sonographic correlate, or palpability, the chance of malignancy in a focal asymmetry is less than 1%. In a retrospective study, Sickles reported that 3% of 300 consecutive nonpalpable breast cancers were initially identified as focal asymmetries. Formerly known as developing density or neodensity, a developing asymmetry is a focal asymmetry that is new or increasing in size or conspicuity when compared with prior mammographic examinations. This finding differs from hormone-induced increase in density because developing asymmetry is a focal, unilateral finding. In the Sickles study of 300 consecutive nonpalpable breast cancers, 6% were reported as developing asymmetries. Developing asymmetry is a much more alarming finding than focal asymmetry; reported probability of malignancy in a developing asymmetry ranges from 13% when identified at screening versus 27% when identified at diagnostic mammography. Benign causes of developing asymmetry include fibrocystic change, focal fibrosis, pseudoangiomatous stromal hyperplasia, and fibroadenoma.

Once a focal asymmetry or a developing asymmetry has been confidently identified in at least two (ideally orthogonal) projections, ultrasound is helpful in further evaluation. The presence of a sonographic finding will guide management. For example, if a simple cyst is found to correlate to the mammographic finding, only routine mammographic follow-up is indicated. If a suspicious solid sonographic mass is identified, biopsy should be performed, almost always guided by ultrasound. In the absence of any sonographic finding (i.e., lack of a sonographic correlate), a nonpalpable focal asymmetry (without prior mammographic examinations for comparison) may be considered probably benign and assigned to short-term interval imaging surveillance, but a developing asymmetry would still require biopsy. In the latter case, the likelihood of malignancy is less than the case of a developing asymmetry with a sonographic correlate that is not clearly benign. The role of MRI in evaluating asymmetries is unclear at this time, but may be helpful in equivocal cases if the MRI examination is positive in demonstrating a correlate to the mammographic finding. It has not been established with certainty that biopsy may be obviated if MRI is negative.

Key Elements