Breast diseases: Detection, Management, and Surveillance of Breast Disease

Nipple

Accessory nipples may occur along the breast or milk lines running from the axilla to the groin. Polythelia (supernumerary or accessory nipples) occurs in less than 1% (white European descent) to 2.5% (Jewish population) of women. They most commonly present in the inframammary region (90%), may be unilateral or bilateral, and occur in equal frequency in men and women. Development may be partial or complete, and the condition is both sporadic and familial. Obstructive or duplicative urologic anomalies may be present as well, and an increased risk of renal cancer has been reported. When present, accessory nipples have the same risk for disease as normal nipples. Treatment is generally restricted to managing irritation or improving cosmesis when necessary.

Congenital nipple inversion occurs in 2% of women, typically in those with a family history of the same condition. The cause is related to shortening and tethering of breast ducts or the development of fibrous bands during intrauterine life. Although nipple inversion may increase mechanical problems with breastfeeding, surgical correction often leads to loss of sensation and inability to breastfeed.

Athelia, complete unilateral or bilateral absence of nipple and areola, can be familial (autosomal dominant) and is associated with amastia (absent nipple, areola, and breast tissue) or other rare syndromes (e.g., Poland syndrome). Associated ectodermal abnormalities (such as absence of the pectoral muscles) should be excluded. Treatment includes nipple and areola reconstruction commonly using tissue flaps and tattooing.

Breast tissue

Aplasia is diagnosed when the nipple and areola are present but glandular tissue is absent. Amastia, complete absence of both breast tissue and the nipple-areola complex, occurs with regression or failure to develop the mammary ridge. It is often associated with other ectodermal defects, including cleft palate.

Polymastia , accessory breast tissue or supernumerary breasts, occurs in approximately 1% to 2% of the general population, with a female preponderance. Accessory breast tissue most commonly presents in the axilla, and multiple site occurrence is not uncommon (~33%). The initial diagnosis is often at puberty or during pregnancy, when the accessory breast tissue development and stimulation parallel that of normal breast tissue. Supernumerary breast tissue, be it rudimentary or fully developed, is customarily asymptomatic; however, it can cause discomfort and may be considered cosmetically unacceptable. Importantly, supernumerary breast tissue is subject to normal changes and is susceptible to the entire disease spectrum that occurs in the normal breast. Conservative management is encouraged because surgery can be associated with unattractive scars, restriction of movement, pain, and other complications. Liposuction may useful to decrease the fatty element of accessory breasts.

Asymmetric breast development, common in adolescence and in maturity, represents a benign, normal variation unless an associated palpable abnormality is present. In the extreme a breast can be hypoplastic or absent (aplasia), which can occur in isolation or in association with a defect in (one or both) pectoral muscles. Significant asymmetry can be deeply disturbing and may affect a teenager’s self-image. Full breast development usually occurs by age 18 to 21 years, and if deemed necessary, corrective augmentative or reduction surgery should be timed accordingly.

Breast hypertrophy may be related to excessive development of glandular tissue during puberty, weight gain, or naturally occurring fat deposition of breast tissue associated with aging. It may be asymmetric and is separated into pubertal (virginal hypertrophy), gestational (gravid macromastia), and adult types. Medical treatment is typically not successful, and reduction mammoplasty is not indicated until a significant volume of breast tissue requires removal to relieve associated symptoms such as headache, neck or back pain, upper extremity paresthesia, brassiere strap grooving, or intertrigo. The best surgical outcome can be expected when the planned procedure occurs after 6 to 12 months of breast size stabilization.

Tubular breasts or tuberous breast deformity is associated with a constriction in the lower pole of the breast. This unilateral or bilateral congenital breast abnormality occurs in both sexes. During puberty, breast development is stymied and the breasts fail to develop normally and fully. The transverse breast diameter is narrowed and the base constricted related to glandular hypoplasia with a deficiency in the circumferential skin envelope of the breast base. The breast appears to herniate into an oversized and protuberant areola. The exact cause of this condition is as yet unclear; however, a genetic link to a disorder of collagen deposition is suspected. Corrective procedures can be divided into operations that involve augmentation, mastopexy, combined augmentation/mastopexy, lipomodeling, and tissue expansion followed by augmentation ( ).

Benign breast disorders

Benign breast disorders (BBDs) and their wide range of symptoms represent the majority (~90%) of breast-related complaints and abnormalities evaluated in an obstetrician/gynecologist’s office. This heterogeneous group of lesions or abnormalities may be incidental or may be detected clinically or radiographically.

BBDs are often misdiagnosed and misunderstood secondary to their varied spectrum at presentation and associated anxiety concerning the possibility and fear of malignancy. Understanding the causes and management of BBD is essential to provide proper clinical management and to psychologically allay patients’ and families’ fears. Various terminology has been used to describe BBD. Most emphasize clinical signs, symptoms, or histologic findings. BBDs can be classified as follows:

• 1.

  Aberrations of normal development and involution (ANDI)

• 2.

  Pathologic classification

• 3.

  Clinical classification

• 4.

  Classification based on the risk for malignancy

The ANDI classification incorporates symptoms, signs, histology, physiology, pathogenesis, and degree of breast abnormality, classified in relation to the normal processes of reproductive life and involution through a spectrum of breast conditions that range from “normal” to “disorder” to “disease” ( ). Thus ANDI classification suggests that BBDs are a result of minor aberrations in the normal development process, hormonal response, and involution of the breast (see Table 15.1 ).

Commonly, BBDs are subdivided histologically by their potential future cancer risk (ACOG Practice Bulletin 164, 2016):

• Nonproliferative disorders: no increased risk

• Proliferative disorders without atypia: mild to moderate increase in risk

• Atypical hyperplasia: substantial increase in risk (relative risk 3 to 5×) ( Table 15.2 )

  TABLE 15.2

  Breast Lesions and Breast Cancer Risk

  Data from Morrow M, Schnitt SJ, Norton L Current management of lesions associated with an increased risk of breast cancer. Nat Rev Clin Oncol 2015;12:227–38.

  Lesion Type	Lesion Subtype *	Aggregate Relative Risk of Future Breast Cancer (95% CI)
  Nonproliferative	Simple cysts Mild hyperplasia (usual type) Papillary apocrine change	1.17 (0.94-1.47) †
  Proliferative without atypia	Fibroadenoma Giant fibroadenoma Intraductal papilloma Moderate/florid hyperplasia (usual type) Sclerosing adenosis Radial scar	1.76 (1.58-1.95) †
  Atypical hyperplasia	Atypical ductal hyperplasia Atypical lobular hyperplasia	3.93 (3.24-4.76) †
  Lobular carcinoma in situ		6.9-11 ‡

  * Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 1985;312:146–51.

  † Dyrstad SW, Yan Y, Fowler AM, Colditz GA. Breast cancer risk associated with benign breast disease: systematic review and meta-analysis. Breast Cancer Res Treat 2015;149:569–75.

  ‡ Confidence interval not reported.

Finally, a clinical classification is often used in which abnormalities can be subgrouped as follows:

• Physiologic swelling and tenderness

• Nodularity

• Breast pain (not usually associated with malignancy)

• Palpable breast lumps

• Nipple discharge including galactorrhea

• Breast infection and inflammation—typically associated with lactation

Most commonly BBD involves pain, discharge, or a mass. Infection or mastitis is less common. These symptoms and subsequent physical findings may result in denial, anxiety, and fear as patients worry that the symptoms represent cancer. The increase in size, density, and nodularity during the second half of the menstrual cycle is often associated with increased sensitivity or breast pain. Importantly, cancer-related breast pain is generally a late symptom and is a lone presenting symptom in less than 6% of women with malignant disease. Nipple discharge is also a less common sign of cancer. The correlation of a mass with malignancy is dependent on the patient’s age. The incidence of BBD begins to rise during the second decade of life and peaks in the fourth and fifth decades, as opposed to malignant diseases, whose incidence continues to increase after menopause.

Simple breast cysts, occurring in 35% of reproductive aged women, represent the most common nonproliferative breast lesion (ACOG Practice Bulletin 164, 2016). Radiologically simple breast cysts (without septa or mural thickening) are almost always benign and can be managed expectantly. Aspiration is typically reserved to alleviate symptoms. Mild hyperplasia and simple papillary apocrine change are relatively rare benign nonproliferative lesions.

Fibroadenomas , composed of fibrous and epithelial elements, are the most common benign solid breast neoplasms (15% to 20%) and are often noticed accidentally while bathing. They most often occur in adolescents and young women (peak incidence at age 20 to 24) and are related to an aberration in normal lobular development. They demonstrate hormonal dependence, lactate during pregnancy, and involute to be replaced by hyaline connective tissue during perimenopause. Fibroadenomas represent 12% of breast masses after menopause. Clinically they usually present as solitary, slow-growing, painless, freely mobile, firm, solid breast masses. The average size is 2.5 cm, and they usually remain fairly constant in size. Giant fibroadenoma, larger than 5 cm, are rare. Hyperplastic lobules histologically resembling fibroadenomas are present in virtually all breasts. All the cellular elements of fibroadenomas are normal on conventional and electron microscopy, and the epithelium and myoepithelium maintain a normal relationship.

On clinical examination it may be difficult to distinguish a fibroadenoma from a cyst. In fact, diagnosis based solely on CBE is correct 66% of the time. Importantly, imaged complex cysts and any cysts with solid areas should be biopsied or excised. Ultrasound is the initial noninvasive study to differentiate a solid versus a cystic mass because mammography is rarely indicated in a woman younger than 35 with fibroadenomas. Core needle biopsy is indicated when the cause of a palpable mass cannot be established. Surgical evaluation is appropriate for any mass (at any age) that exhibits a rapid increase in size. Fibroadenomas can be followed clinically. Surgical excision of fibroadenomas should be considered if they are symptomatic or to relieve anxiety related to the palpable mass. They have a “rubbery” consistency, are usually well circumscribed, and are easily delineated from surrounding breast tissue in approximately 95% of cases ( Fig. 15.6 ). Nonoperative management can be considered for small, asymptomatic fibroadenomas in women younger than 35 if clinical examination, imaging evaluation (either mammogram or ultrasound), and biopsy (usually core needle) results are 100% concordant. Approximately 35% of fibroadenomas will disappear, and approximately 10% shrink when followed. Conservative management requires continued surveillance at 6-month intervals for at least 2 years. Despite the option of conservative management, many women prefer to have the fibroadenoma excised. Excision should be performed through a cosmetically placed inframammary, axillary, or circumareolar incision. Fibroadenomas are a proliferative disorder, and particularly when accompanied by complex cysts larger than 3 mm in diameter, sclerosing adenosis, epithelial calcification, or papillary changes, are associated with an increased risk of breast cancer; the later development of invasive breast cancer risk also is increased (approximately twofold). Women with fibroadenomas should be made aware of this risk and encouraged to maintain continued close surveillance. The postoperative risk of recurrent fibroadenoma is approximately 20%. Studies support the successful use of ultrasound-guided high-intensity focused ultrasound or cryoablation as an alternative treatment to surgery ( ).

Phyllodes tumors , previously termed Cystosarcoma phyllodes, represent the opposite end of the spectrum of fibroepithelial tumors. Phyllodes tumors are rare, representing only 2.5% of fibroepithelial tumors and less than 1% of breast malignancies. The typical age of onset is 15 to 20 years later than fibroadenomas (fourth and fifth decades of life). They are almost exclusively seen in women and may be benign, borderline, or malignant. Differentiating benign from malignant phyllodes can be difficult and involves assessment of the size, histologic stroma/epithelium ratio, border of the lesion, stromal cellularity, number of stromal mitoses, and presence or absence of necrosis. All three generally present as a breast mass, often grow rapidly, and are typically larger at diagnosis than a fibroadenoma or ductal carcinoma. Histologically, stromal elements dominate and will invade the ducts in a leafy projection; hence the name phyllodes, or “leaf” ( Fig. 15.7 ). Even the most experienced pathologists may have difficulty distinguishing among fibroadenoma, benign phyllodes tumors, and malignant cystosarcoma phyllodes. Phyllodes tumors’ mammographic appearance as a rounded density with smooth borders is similar to that of fibroadenomas. Mammography and ultrasonography are therefore unreliable in differentiating among fibroadenomas, benign phyllodes tumors, and malignant phyllodes tumors.

These tumors can be locally aggressive and require wide local excision with 1-cm margins. Unlike fibroadenomas, phyllodes tumors should not be shelled out because this surgical technique will result in an unacceptably high recurrence rate. Unfortunately, the pathologic appearance of a phyllodes tumor does not always predict the neoplasm’s clinical behavior; however, risk of local recurrence of the tumor is associated with microscopic margin involvement. Malignant tumors metastasize hematogenously, and the risk of metastases is 25%; local recurrence is common (>20%), even with benign and borderline tumors.

Fibrocystic change

Many breast symptoms stem from fibrocystic changes , previously designated fibrocystic disease, which is a common and natural maturation of breast tissue over time. The functional unit of the breast (the lobule), the alterations associated with the interaction among hormones, and the epithelial and stromal components of the lobule are responsible for many cases of BBDs. Initial or immature lobules, primarily developing in the early reproductive years (ages 15 to 25 years), are typically replaced during pregnancy and subsequently by mature lobules. Lobular changes manifest most commonly during the menstrual cycle. Late cycle peak mitosis, followed by apoptosis, provides a milieu for stromal or ductal tissues to transform from a normal to an abnormal state. Over time these deviations produce marked differences in the structure and appearance of the breast tissue, which is histologically described as fibrosis or adenosis and is often observed in women with no clinical complaint or finding.

Involutional breast changes, clinically apparent before age 35 years, affect stromal and epithelial components of the lobules. Early stromal involution can result in the formation of microcysts from the remaining epithelial acini. Microcyst formation is common and is often present in healthy breasts. Ductule obstruction facilitates progression of microcysts to macrocysts. Loose, hormonally receptive connective tissue in the stroma is replaced by denser connective tissue, and epithelial involution results in gradual disappearance of the ductal elements. Epithelial involution is dependent on the continuing presence of surrounding specialized stroma. Thus cyclical and involutional changes are concurrently present for more than 30 years, and the involutional changes will be extensive, with few ductal and lobular structures spared by the time menopause occurs.

Fibrocystic change, is the most common of all benign breast conditions. Clinicians use the nonspecific term fibrocystic change to describe the clinical, mammographic, and histologic findings associated with multiple irregularities in contour and texture typically associated with cyclical breast pain. Fibrocystic change presents as a spectrum of changes throughout a woman’s reproductive age, with significant patient variation. Fibrocystic change has an extensive list of synonyms and terminology that includes more than 35 different names and terms. The 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) calls this diffuse cystic mastopathy.

The true frequency of fibrocystic change is unknown; however, autopsy evidence of histologic fibrocystic change is noted in 53% of normal breasts. Clinical evidence of fibrocystic change is evident in nearly one in two premenopausal women during breast examination; however, depending on the definition, some authors have noted that as many as 90% of women demonstrate some aspect of fibrocystic change. Although no consistent abnormality of circulating hormone levels has been proved, fibrocystic changes represent an exaggeration of the normal physiologic response of breast tissue to the cyclic levels or ovarian hormones. These changes, unusual in adolescence, are most common in women of reproductive age (20 to 50 years) and unusual after menopause unless associated with exogenous hormone replacement.

Cyclic bilateral breast pain is the classic symptom of fibrocystic breast change. Clinical signs include increased breast engorgement and density, excessive breast nodularity, fluctuation in the size of cystic areas, increased tenderness, and, rarely, spontaneous nipple discharge. Signs and symptoms are typically more prevalent during the premenstrual state.

Associated mastalgia is bilateral, often difficult to localize, and most common in the upper, outer breast quadrants. Pain may radiate to the shoulders and upper arms. Severe localized pain occurs when a simple cyst rapidly expands. The pathophysiology that produces these symptoms and signs includes cyst formation, epithelial and fibrous proliferation, and varying degrees of fluid retention. The differential diagnosis of breast pain includes referred pain from a dorsal radiculitis or inflammation of the costochondral junction (Tietze syndrome). The latter two conditions have symptoms that are not cyclic and are unrelated to the menstrual cycle.

The physical findings of excessive nodularity as a result of fibrocystic changes have been described as similar to palpating the surface of multiple peas. There may be multiple areas of seemingly ill-defined thickening or areas of palpable lumpiness that seem more two dimensional than the three-dimensional mass usually associated with a carcinoma ( Fig. 15.8 ). Larger cysts may be ballotable, analogous to a water-filled balloon.

There are three general clinical stages of fibrocystic change, with each stage having characteristic histologic findings. Clinically these stages are variable and overlap, but they are described to assist in the understanding of the natural history. The first stage, mazoplasia (mastoplasia), is associated with intense stromal proliferation and occurs in the early reproductive years (20s). Breast pain is noted primarily in the upper, outer breast quadrants, with most tenderness in the axillary tail.

The second clinical stage, adenosis, is characterized by marked proliferation and hyperplasia of ducts, ductules, and alveolar cells and typically occurs in women in their 30s. Premenstrual breast pain and tenderness is less severe. Multiple small breast nodules varying from 2 to 10 mm in diameter are present.

The cystic phase is the last stage and typically occurs another decade later, in women in their 40s. Typically there is no breast pain unless a cyst increases rapidly in size, with associated sudden pain, point tenderness, and a lump. Cysts are tender to palpation and vary from microscopic to 5 cm in diameter. Although breast cysts may occur at any age, they are generally simple and may be managed with aspiration alone. Complex cysts have internal septations, debris, or solid components and may require core needle biopsy if stability cannot be documented. The fluid aspirated from a large cyst is typically straw colored, dark brown, or green, depending on the chronicity of the cyst.

Women with a clinical diagnosis of fibrocystic change have a wide variety of histopathologic findings. The histologic aspect of fibrocystic change is characterized by proliferation and hyperplasia of the lobular, ductal, and acinar epithelium ( Fig. 15.9 ). Usually the proliferation of fibrous tissue occurs and accompanies epithelial hyperplasia. Many histologic variants of fibrocystic change have been described, including cysts (from microscopic to large, blue, domed cysts), adenosis (florid and sclerosing), fibrosis (periductal and stromal), duct ectasia, apocrine metaplasia, intraductal epithelial hyperplasia, and papillomatosis. Ductal epithelial hyperplasia with atypia and apocrine metaplasia with atypia are the most prominent histologic findings directly associated with the subsequent development of breast carcinoma. If either of these two conditions is discovered on breast biopsy, the chance of future breast carcinoma is increased fivefold.

Clinical management of fibrocystic change is age dependent and includes appropriate use of breast imaging. Initial evaluation should exclude malignancy, particularly in the presence of a mass or with a concerning or uncertain examination. Thereafter, successful symptom control may involve a number of medical options. Initial therapy for fibrocystic change involves mechanical support using a firm support or sports bra. Dietary changes to reduce methylxanthines or caffeine exposure have been helpful in relieving symptoms for some women. Although confirmatory medical studies evaluating the benefit of these dietary changes are lacking, there seems to be little harm to trying this inexpensive option for 3 to 6 months. The only dietary substance that seems to correlate with fibrocystic symptoms is dietary fat, particularly saturated fat. Studies have demonstrated a dose-related effect between increased saturated fat and fibrocystic breast symptoms. Incorporating a low-fat, nutrient-dense diet makes sense, and limiting intake of saturated fat intake should be considered as a simple therapeutic tool for the management of women with symptomatic, refractory fibrocystic changes. Additionally, some advocate limiting or eliminating alcohol consumption to lessen estrogen levels. Diuretics are sometimes prescribed during the premenstrual phase and may lessen symptoms of breast discomfort and engorgement.

Oral contraceptives or supplemental progestins administered during the secretory phase of the cycle have also been used to treat fibrocystic changes. Oral contraceptives are reported to decrease the incidence of fibrocystic changes by 30% ( ). Unfortunately, 40% of women will have recurrent symptoms after discontinuation.

Danazol, dosed at 100, 200, and 400 mg daily for 4 to 6 months, suppresses gonadotropins and effectively relieves symptoms and decreases breast nodularity in ~90% of patients. Unfortunately, virilizing side effects such as hirsutism, acne, and voice changes often limit its use. Danazol therapy for 6 months or more should be tapered to eliminate side effects. The beneficial effects of danazol persist for several months after discontinuation.

Oral tamoxifen, 20 mg daily, is superior to placebo in randomized, double-blind trials, and pain relief is reported to be sustained in 72% of women for more than 1 year after discontinuation. Tamoxifen administration restricted to the luteal phase of the menstrual cycle abolishes pain in 85% of women; however, adverse side effects are common (21%). After treatment, 25% of women suffer recurrent pain within 1 year. Tamoxifen 10 mg daily can be prescribed during the luteal phase of the menstrual cycle and results in similar improvements in symptoms but with a marked reduction in adverse effects.

The selective estrogen receptor modulator (SERM) centchroman (Ormeloxifene; 30 mg twice weekly), a weak estrogen receptor (ER) agonist and a strong ER antagonist, demonstrated significant efficacy in the management of breast pain and fibrocystic nodularity. On rare occasions, gonadotropin-releasing hormone (GnRH) agonists may benefit women with severe fibrocystic change.

Mastalgia (breast pain)

More than two-thirds of women will experience breast pain at some time during their reproductive years, most commonly in the perimenopausal years. Eleven percent experience moderate to severe cyclic breast pain and 58% experience mild discomfort. Breast pain commonly interferes with usual sexual activity in 48% and with physical (37%), social (12%), and school (8%) activity in others. Approximately 90% of conditions that cause breast pain are benign. Breast pain is typically divided into cyclic pain, related to the menstrual cycle, and noncyclic pain. Cyclic pain is diffuse and bilateral and most commonly associated with fibrocystic changes. Noncyclic breast pain is commonly localized and related to a cyst. Noncyclic breast pain should be evaluated, particularly in older women, because there is a small association with malignancy. Mammography and additional imaging can be valuable. The differential diagnosis includes a cyst, chest wall pain, radicular pain, costochondritis, mastitis, pregnancy-related pain, prolactinomas, and medication exposure ( Box 15.1 ). Laboratory evaluation should include human chorionic gonadotropin (HCG) and prolactin levels in premenopausal women. Breast cysts occur in as many as 7% of women during their lifetime and may be therapeutically aspirated if they are simple. A negative postaspiration breast examination is reassuring. Recurring simple cysts can be followed with ultrasound, typically withholding repeat aspiration for symptomatic cysts. For a more complex cyst, a more detailed workup is usually necessary. Patients with complex cysts should have a tissue diagnosis performed with a core needle biopsy if the cysts are symptomatic or show progressive changes on serial sonography. Pain as a presenting symptom of malignancy is uncommon in general and is extremely rare in the absence of mass or skin changes. Breast pain treatment is directed at the cause; however, nonsteroidal antiinflammatories are often useful when pain is idiopathic.

Mastitis and inflammatory disease

Breast infection is often subdivided into lactational, nonlactational, and postoperative. Although decreasing in overall incidence, mastitis, an infection of the ductal systems or smaller sebaceous glands, is most commonly related to Staphylococcus aureus. Empiric treatment with an agent that covers gram-positive organisms is appropriate. If there is poor response to the initial course of antibiotics, cultures for methicillin-resistant S. aureus (MRSA) should be performed and an agent such as a doxycycline or sulfamethoxazole/trimethoprim is indicated; however, these two agents are contraindicated if a woman is pregnant or lactating.

Lactational mastitis commonly occurs in the first pregnancy during the first 6 weeks of breastfeeding. Curiously, mastitis in pregnancy usually responds to first-line antibiotics such as a cephalosporin, even in the presence of MRSA; however, infection may progress to a breast abscess in 5% to 11% of patients. Continued breastfeeding or manual pumping of the affected breast is recommended to decrease engorgement.

Nonpuerperal mastitis is often associated with breast cysts and cyst rupture. Ultrasonography assists in excluding an abscess. Obviously, one should always consider and exclude the presence of malignant breast disease, particularly inflammatory cancer. Additional testing for diabetes and human immunodeficiency virus (HIV) may be indicated, particularly if yeast is the offending organism. Syphilis, tuberculosis, atypical bacterial, and fungal infections may rarely cause nonpuerperal mastitis. In patients with recurrent mastitis, consider choosing an antibiotic to cover MRSA, such as clindamycin, sulfamethoxazole/trimethoprim, doxycycline, or vancomycin. Nipple piercing, particularly in smokers, is associated with mastitis and a 20-fold increase in subareolar abscess formation. As with any infection, the clinician should strongly consider removal of the foreign body. The American College of Obstetricians and Gynecologists (ACOG) recommends counseling women who are planning to get piercings to have prepiercing hepatitis B and tetanus vaccinations.

Idiopathic granulomatous mastitis (IGM), also called idiopathic granulomatous lobular mastitis (IGLM) , is a rare cause of breast inflammation and may affect any age group. This disease may present with a mass, abscess, inflammation, or granuloma formation. The granulomas are often found within the lobules and on biopsy are noted to be sterile. Mammography may be equivocal or may be suspicious for malignancy. Steroid treatment has been reported to be effective in small series with equivocal results. The disease is usually self-limited, resolving within months. Skin scarring and residual small abscesses may remain, often necessitating surgical treatment. Chronic inflammatory diseases, such as lupus, sarcoidosis, and Wegner granulomatosis, are rare causes of noninfectious mastitis, and evaluation for these diseases should be performed if antibiotics are not effective. Importantly, any breast inflammation not responsive to adequate antibiotic treatment warrants a tissue diagnosis. Core needle biopsy is often performed when there is a lack of response to antibiotics. The diagnosis is commonly made when the biopsy specimen indicates sterile granulomas after excluding other causes of granulomatous mastitis such as tuberculosis.

Nipple discharge

Nipple discharge is responsible for 7% of physician visits involving breast complaints. The majority have a benign cause; however, 55% present with a coexisting mass, of which 19% are malignant. An underlying malignancy is more likely when the discharge is spontaneous (vs. induced with nipple pressure), arises from a single duct, is blood stained, and is unilateral and persistent (occurring more than twice weekly). Age is important because an underlying malignancy is present in 3% of women younger than 40, 10% of women between 40 and 60, and 32% of women older than 60 when nipple discharge is the only presenting symptom.

Intraductal papilloma and fibrocystic changes are the two most common causes of spontaneous nonmilky discharge. Galactorrhea is likely when breast discharge is bilateral, copious, milky pale in color, and occurs from multiple ducts. Importantly, numerous medications and conditions can affect the hypothalamic-pituitary axis and lead to prolactin secretion and galactorrhea. As many as 65% of premenopausal women may have a normal benign physiologic discharge with gentle squeezing of the nipple. Evaluation includes physical examination, mammography, and sonography. The patient’s history may not differentiate spontaneous discharge from elicited discharge because a woman may continually attempt to express the discharge, which causes more fluid to leak.

Evaluation and diagnosis include clinically separating the discharges into those that are spontaneous and those that only are expressed by pinching or squeezing the nipple ( Fig. 15.10 ). Nipple discharges range in color from milky to green, brown, purple, and bloody. Hemoccult testing for detection of blood in the discharge is neither sensitive nor specific. Malignancy should be excluded in any woman with a bloody discharge or any discharge associated with a mass or if the discharge originates from only one or two adjacent ducts.

Assessment of pathologic nipple discharge involves a careful breast examination to identify the presence or absence of a breast mass. Firm areola pressure can assist in identifying the site of any dilated duct (pressure over a dilated duct will produce the discharge); this finding helps to define where an incision should be made for any subsequent surgery. The nipple is squeezed with firm, gentle digital pressure, and if fluid is expressed, the site and character of the discharge are recorded. Although bloodstained breast discharge is more likely to be associated with malignancy, fewer than 20% of patients who have a bloodstained discharge or who have a discharge containing moderate or large amounts of blood will have an underlying malignancy. Importantly, the absence of blood in nipple discharge does not exclude an underlying malignancy. Cytologic examination of nipple discharge can be helpful but has a poor sensitivity (<50%).

Management of a suspicious discharge begins with a physical examination and mammography, ultrasound, or magnetic resonance imaging (MRI). Any mass associated with discharge requires appropriate biopsy. A number of techniques have been evaluated to determine the cause and avoid unnecessary extirpative surgery. Ductoscopy (using a microendoscope passed into the offending duct) allows direct visualization. Ductal lavage involves duct canalization, and collection of fluid for cytologic evaluation. This technique increases cell yield by 100 times that of simple discharge cytologic examination but can be uncomfortable for the patient. Ductography (imaging of the ductal system by infecting contrast into the symptomatic duct), also called a galactogram , has 60% sensitivity for detecting malignancy. This study can identify intraductal filling defects or cutoff lesions, which have a high positive predictive value for the presence of either a papilloma or a carcinoma. The procedure can be technically challenging and cause significant patient discomfort. Surgical excision of the duct and its associated lobular unit is both diagnostic and therapeutic. With the patient anesthetized, a 4-0 lacrimal probe is passed through the duct. A periareolar flap is then created, and the retroareolar duct with the probe can be identified and excised individually.

Intraductal papilloma

Intraductal papillomas are broad-based or pedunculated polypoid epithelial lesions that may obstruct and distend the involved duct. They are most commonly diagnosed in perimenopausal women. Classically their clinical presentation includes an intermittent but spontaneous discharge from one nipple involving one or two ducts. The associated discharge can be watery, serous, or bloody, and of variable volume. Approximately 75% of intraductal papillomas are located beneath the areola, are small and soft, and are often difficult to palpate, typically measuring 1 to 3 mm in diameter. During examination of the breast it is important to circumferentially put radial pressure on different areas of the areola. This technique helps to identify whether the discharge emanates from a single duct or multiple openings. When the discharge comes from a single duct, the differential diagnosis includes both intraductal papilloma and carcinoma.

Treatment of intraductal papilloma involves excisional biopsy of the involved duct and a small amount of surrounding tissue. Although these tumors tend to regress in postmenopausal women, excision should be considered to rule out malignancy. Careful surveillance at 3- to 4-month intervals is necessary if the papilloma is not surgically excised. Women with a solitary papilloma have a twofold increase in subsequent development of breast carcinoma.

Fat necrosis

Fat necrosis , a benign nonsuppurative inflammatory process of adipose tissue, is a condition with a wide variety of presentations on mammography, ultrasound, and MRI. The incidence of fat necrosis of the breast is estimated to be 0.6%, representing 2.75% of all breast lesions. Fat necrosis is found in 0.8% of breast tumors and 1% in breast reduction mammoplasty cases, and the average age of patients is 50 years. Fat necrosis is most commonly the result of trauma to the breast, although it can be associated with radiotherapy, anticoagulation (warfarin), infection, or breast procedures, including breast aspiration or biopsy, lumpectomy, reduction mammoplasty, implant removal, and breast reconstruction. Other rare causes for fat necrosis include polyarteritis nodosa, Weber-Christian disease, and granulomatous angiopanniculitis.

Patients commonly present with a firm, tender, indurated, ill-defined mass that may have coexisting ecchymosis, erythema, inflammation, pain, skin retraction or thickening, nipple retraction, and occasionally lymphadenopathy. As many as 70% present as an occult lesion without a history of trauma. The area of fat necrosis may liquefy and become cystic, forming an oil cyst with a characteristic calcified rim. Mammography may demonstrate coarse calcifications, focal asymmetries, or microcalcifications. Treatment of fat necrosis is excisional biopsy. There is no relationship between fat necrosis and the development of subsequent breast carcinoma.