Benign Breast Diseases: Classification, Diagnosis, and Management

The vast majority of the lesions that occur in the breast are benign. Much concern is given to malignant lesions of the breast because breast cancer is the most common malignancy in women in Western countries; however, benign lesions of the breast are far more frequent than malignant ones. With the use of mammography, ultrasound, and magnetic resonance imaging of the breast and the extensive use of needle biopsies, the diagnosis of a benign breast disease can be accomplished without surgery in the majority of patients. Because the majority of benign lesions are not associated with an increased risk for subsequent breast cancer, unnecessary surgical procedures should be avoided. It is important for pathologists, radiologists, and oncologists to recognize benign lesions, both to distinguish them from in situ and invasive breast cancer and to assess a patient’s risk of developing breast cancer, so that the most appropriate treatment modality for each case can be established.

The term “benign breast diseases” encompasses a heterogeneous group of lesions that may present a wide range of symptoms or may be detected as incidental microscopic findings. The incidence of benign breast lesions begins to rise during the second decade of life and peaks in the fourth and fifth decades, as opposed to malignant diseases, for which the incidence continues to increase after menopause, although at a less rapid pace.

In this review, the most frequently seen benign lesions of the breast are summarized as developmental abnormalities, inflammatory lesions, fibrocystic changes, stromal lesions, and neoplasms.

Developmental Abnormalities

Ectopic breast (mammary heterotopia), which has been described as both supernumerary and aberrant breast tissue, is the most common congenital abnormality of the breast. Supernumerary breast tissue is seen mostly along the milk line; the most frequent sites are the chest wall, vulva, and axilla. It may vary in its components of nipple (polythelia), areola, and glandular tissue (polymastia). However, an anatomic location outside the milk line should not preclude a diagnosis of ectopic breast tissue, because there are many well-documented, unusual sites of such tissue, including the knee, lateral thigh, buttock, face, ear, and neck. Aberrant breast tissue is usually located near the breast, most commonly in the axilla. They usually have a nipple and areola and a separate duct system from that of the normal breast. When the nipple is absent, the presence of the accessory breast tissue is difficult to identify. The accessory breast tissue responds in the same way as normal breast tissue to physiological influences. The absence of a duct system may cause symptoms of obstruction during lactation and may be mistaken clinically for a carcinoma. Accessory breast tissue and polymastia are more common among Asians, especially Japanese, than whites. Recognition of ectopic breast tissue is important because it can serve as a milieu for the development of a variety of benign and malignant lesions encountered in the normal breast. It has been reported that ectopic breast tissue is more prone to malignant change and that ectopic breast cancer occurs at an earlier age; however, malignancies in ectopic breasts are very rare. Excessive breast growth (macromastia) can be seen in pregnancy as well as during adolescence.

Underdevelopment of the breast (hypoplasia), when congenital, is usually associated with genetic disorders, such as ulnar-mammary syndrome, Poland’s syndrome, Turner’s syndrome, and congenital adrenal hyperplasia. Among these disorders, Poland’s syndrome is the congenital anomaly that has been reported to be associated with breast cancer most often. There are some recent studies suggesting the association of ulnar-mammary syndrome and breast cancer; however, breast cancer has not been recorded in patients with Turner’s syndrome. Acquired hypoplasia, on the other hand, is usually iatrogenic, most commonly subsequent to trauma or radio-therapy. The complete absence of both breast and nipple (amastia) or presence of only nipple without breast tissue (amazia) is rare.

Inflammatory and Related Lesions

A variety of inflammatory and reactive changes can be seen in the breast. While some of these changes are a result of infectious agents, others do not have a well-understood etiology and may represent local reaction to a systemic disease, or a localized antigen-antibody reaction, and are classified as idiopathic.

Inflammatory breast cancer, as the name suggests, mimics an infectious or inflammatory etiology. It often develops without a palpable mass lesion and is often initially misdiagnosed. In fact, most patients with inflammatory breast cancer are diagnosed after an initial treatment with antibiotics or anti-inflammatory therapies failed to show clinical improvement. Mammographic and sonographic evaluation are helpful in establishing the diagnosis. Image-guided biopsy of the abnormal breast parenchyma or skin biopsy confirms the diagnosis. A negative skin biopsy should not be used to exclude the diagnosis.

Acute Mastitis
Acute mastitis usually occurs during the first 3 months postpartum as a result of breast feeding. Also known as puerperal or lactation mastitis, this disorder is a cellulitis of the interlobular connective tissue within the mammary gland, which can result in abscess formation and septicemia. It is diagnosed based on clinical symptoms and signs indicating inflammation. Risk factors fall into two general categories: improper nursing technique, leading to milk stasis and cracks or fissures of the nipple, which may facilitate entrance of microorganisms through the skin; and stress and sleep deprivation, which both lower the mother’s immune status and inhibit milk flow, thus causing engorgement.

Because the duration of symptoms before starting treatment is found to be the only independent risk factor for abscess development, early diagnosis and early management of mastitis is of value. However, there is little consensus on the type or duration of antibiotic therapy and when to begin antibiotics. Because lactation mastitis is a process of subcutaneous cellulitis, detection of pathogens in breast milk may not always be possible, so breast emptying with frequent nursing or manual pumping and beginning empiric antibiotherapy seems to be the most appropriate approach. When puerperal mastitis-associated abscess occurs, incision and drainage are usually recommended; however, suitable patients assessed by ultrasonography can also be treated without surgery by needle aspiration and antibiotics with excellent cosmesis .

Granulomatous Mastitis
Granulomatous reactions resulting from an infectious etiology, foreign material, or systemic autoimmune diseases such as sarcoidosis and Wegener’s granulomatosis can involve the breast. Identification of the etiology requires microbiologic and immunologic testing in addition to histopathologic evaluation. Many different types of organisms can cause granulomatous mastitis.

Tuberculosis of the breast is a very rare disease. However, both clinical and radiological features of tuberculous mastitis are not diagnostic and easily can be confused with either breast cancer or pyogenic breast abscess by clinicians. Remembering the fact that traveling from one place to another in the global world has been increasing and that the prognosis for complete cure with appropriate antituberculous drug therapy is excellent, this entity should also be taken into consideration. Definitive diagnosis of the disease is based on identification of typical histological features under microscopy or detection of the tubercle bacilli with mycobacterial culture.

The term “idiopathic granulomatous mastitis” is used for granulomatous lesions without an identifiable cause. This diagnosis can be made only by excluding other possible causes of granulomatous lesions. An autoimmune localized response to retained and extravasated fat- and protein-rich secretions in the duct has been postulated, but the etiology of the disease remains largely unknown. Histologically, chronic noncaseating granulomatous inflammation is typically limited to lobuli. The recommended therapy of idiopathic granulomatous mastitis is complete surgical excision whenever possible plus steroid therapy. Even when idiopathic granulomatous mastitis is treated appropriately, in about 50% of the cases, persistence, recurrence, and complications such as abscess formation, fistulae, and chronic suppuration are encountered, so long-term follow-up is necessary in these patients.

Foreign Body Reactions
Foreign materials, such as silicone and paraffin, which are used for both breast augmentation and reconstruction after cancer surgery, may cause a foreign body-type granulomatous reaction in the breast. Silicone granulomas (“siliconomas”) usually occur after direct injection of silicone into the breast tissue or after extracapsular rupture of an implant. Foreign body granulomatous response associated with multinucleated giant cells surround silicone. Fibrosis and contractions may lead to clinically apparent firm nodules that may be tender.

Recurring Subareolar Abscess
Recurring subareolar abscess (Zuska’s disease) is a rare bacterial infection of the breast that is characterized by a triad of draining cutaneous fistula from the subareolar tissue; a chronic thick, pasty discharge from the nipple; and a history of multiple, recurrent mammary abscesses. The disease is caused by squamous metaplasia of one or more lactiferous ducts in their passage through the nipple, probably induced by smoking. Keratin plugs obstruct and dilate the proximal duct, which then becomes infected and ruptures. The inflammation eventuates in abscess formation beneath the nipple, which typically drains at the margin of the areola. Abscess drainage to allow for resolution of the acute inflammation and then complete excision of the affected duct and sinus tract is successful in most cases, but abscesses may recur when the process develops in another duct.

Mammary Duct Ectasia
Mammary duct ectasia, also called periductal mastitis is a distinctive clinical entity that can mimic invasive carcinoma clinically. It is a disease of primarily middle-aged to elderly parous women, who usually present with nipple discharge, a palpable subareolar mass, noncyclical mastalgia, or nipple inversion or retraction. The pathogenesis and the etiology of the disease are still being debated. Smoking has been implicated as an etiologic factor in mammary duct ectasia. This association appears to be more important in young women who smoke. Mammary duct ectasia is usually an asymptomatic lesion and is detected mammographically because of microcalcifications.

The most important histologic feature of this disorder is the dilatation of major ducts in the subareolar region. These ducts contain eosinophilic, granular secretions and foamy histiocytes both within the duct epithelium and the lumen. The inspissated luminal secretions may undergo calcifications that may be the presenting sign in many patients.

Mammary duct ectasia generally does not require surgery and should be managed conservatively. There is no evidence in the literature indicating that mammary duct ectasia is associated with an increased risk for breast cancer. In some patients, clinical presentation and mammographic findings may suggest malignancy, and biopsy may be required to exclude malignancy.

Fat Necrosis
Fat necrosis of the breast is a benign nonsuppurative inflammatory process of adipose tissue. It can occur secondary to accidental or surgical trauma, or it may be associated with carcinoma or any lesion that provokes suppurative or necrotic degeneration, such as mammary duct ectasia and, to a lesser extent, fibrocystic disease with large cyst formation.

Clinically, fat necrosis may mimic breast cancer if it appears as an ill-defined or spiculated dense mass, associated with skin retraction, ecchymosis, erythema, and skin thickness. Mammographic, sonographic, and magnetic resonance imaging findings may not always distinguish fat necrosis from a malignant lesion. Even the macroscopic appearance of the benign lesion can suggest a malignant tumor. Histologically, however, the diagnosis of fat necrosis presents no problem, as it is characterized by anuclear fat cells often surrounded by histiocytic giant cells and foamy phagocytichistiocytes. Excisional biopsy is required if carcinoma cannot be excluded preoperatively.

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