Clinical Breast Problems and Unusual Breast Conditions

Chapter 10 Clinical Breast Problems and Unusual Breast Conditions

Various breast symptoms and clinical problems are encountered in both benign breast conditions and breast cancer. This chapter briefly describes these conditions and elucidates how to distinguish them from malignancy.

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).

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

Type Mammography Gynecomastia
Normal Fatty breast N/A
Pseudogynecomastia Fatty breast N/A
Dendritic Prominent radiating extensions Epithelial hyperplasia
Nodular Fan-shaped triangular density Later phase
Diffuse Diffuse density Dense fibrotic phase

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.

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.

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.

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).

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

Color Cause
Clear or creamy Duct ectasia
Green, white, blue, black Cysts, duct ectasia
Bloody or blood-related

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

Modality Finding
Magnetic resonance imaging

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.

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

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Dec 24, 2015 | Posted by in BREAST IMAGING | Comments Off on Clinical Breast Problems and Unusual Breast Conditions
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