Breast cysts are a very common diagnosis among women and one of the most common reasons for a referral to a breast clinic. They represent the most common cause of breast mass or breast symptoms in general. Breast cysts are part of a larger benign disease process known as fibrocystic disease of the breast. This disease process is a wide spectrum of both fibrous and cystic changes in the breast tissue. The simple breast cyst forms as an aberration in the natural breast development and is composed of an epithelium lined fluid-filled cavity within the surrounding breast parenchyma. They can vary from small microcysts to large macrocysts and can be single or multiple. These cysts can be entirely asymptomatic and only discovered incidentally, or can be symptomatic, presenting as lumps, pain, or associated nipple discharge. Many studies report that in women, the lifetime prevalence of fibrocystic breast disease might be between 70% and 90%.
Fibrocystic changes are classified as nonproliferative, proliferative without atypia, or proliferative with atypia. While the pain and palpable mass can be worrisome to patients, pain as a symptom of breast malignancy is exceedingly rare. Furthermore, fibrocystic disease by itself is not strictly a risk factor for the development of breast malignancy. While the simple breast cyst is a nonproliferative benign disease process, atypia (or atypical ductal hyperplasia) in fibrocystic disease does have a malignant potential, and there are other malignant cystic lesions which can occur and can appear very similar in nature. The relationship between fibrocystic changes and breast cancer is complicated and controversial. Because of this, proper diagnosis, treatment, and management of breast cysts are essential.
The etiology of breast cysts is unknown. However, most breast cysts are associated with the aberration of normal development and involution (ANDI). ANDI is based on the fact that most benign disorders of the breast are due to some minor abnormalities in the usual physiological processes of development of the breast following cyclical normal growth response and involution.
Many studies report a high lifetime prevalence of fibrocystic breast disease in women, showing that over 70% of all women develop fibrocystic changes during their lives, with 20% of these women being symptomatic and 10%-30% developing sclerosing adenosis. It is thought that 7% of all women in the United States will develop a palpable breast cyst at some point in their life. Breast cysts typically develop in 30 to 50-year-old females. The incidence of cyst development increases throughout these years then drops dramatically afterward. As cyst development is related to hormone levels in the body, most benign cysts disappear, and new cysts stop developing a year after menopause.
Cysts seem to form as a result of fibrosis in breast tissue development and subsequent failure in the continuous process of the lobule and terminal ductule formation. The physical mechanism is that fibrosis causes thickening of the epithelium, and thus the developing lobule involutes early in its development. This causes the typical surrounding stroma to disappear and the adjoining ductule to break down, resulting in an aberrant epithelial lined fold, which becomes walled off entirely. The epithelial fold becomes dilated with epithelial acinar secretions and matures into a self-contained fluid-filled cavity.
This underlying process of fibrosis likely stems from an overproduction of estrogen and suppression of progesterone, leading to hyperproliferation of the connective tissue, causing increased epithelial thickness. This theory is supported by the regression of fibrocystic changes in postmenopausal women. In addition, new cysts in older women are typically seen with exogenous hormone replacement and may have a higher risk of an underlying malignancy.
Fibrocystic changes are categorized into nonproliferative changes, proliferative changes without atypia, or proliferative changes with atypia. Nonproliferative changes include simple cysts and are entirely benign. Proliferative changes may include varying degrees of solid components like adenosis, sclerosis, fibrosis, as well as epithelial hyperplasia or metaplasia and apocrine metaplasia. Epithelial atypia is referred to as atypical ductal or lobular hyperplasia and is a risk factor for the development of breast cancer.
The microscopic features of a breast cyst are largely epithelial hyperplasia and ductal dilatation with pericanalicular patterns of stromal cells. It is important to rule out any feature of malignancy, which may include extensive cellular atypia, high mitotic index, nuclear changes, or extracellular invasion.
Fibrocystic changes are sometimes characterized by an increase in breast tenderness and/or pain just prior to menstruation, referred to as cyclic mastalgia. Breast cysts are usually discovered incidentally, with only 20% of cysts being found in women with cyclical mastalgia. The vast majority of symptomatic fibrocystic changes present not as pain but as as a palpable breast lump. Proper diagnosis of cystic disease in breast tissue is made by following the triple assessment approach: clinical evaluation, imaging, and histopathology from fine-needle aspiration or core needle biopsy.
Proper clinical evaluation should include a detailed history of the presenting complaint, a description of the pain and its relation to the menstrual cycle, any recent trauma to the area, nipple and skin changes, and/or nipple discharge. It also should include a full history of past medical and surgical problems, family and pertinent social history, current medications, and medication allergies. More specifically, the age of menarche, menopause, and any family or personal history of breast cancer should be explored. This history is then followed by a thorough physical examination, which should include the evaluation of both breasts as well as axilla, neck, and chest for palpable lymph nodes.
The next part of the triple assessment approach is imaging, which typically includes ultrasound or mammography as well as some form of tissue biopsy.
On ultrasound, a simple cyst is seen as a round, well-circumscribed, anechoic lesion with an imperceptible wall. This is a benign finding and usually does not require intervention unless symptomatic. The complex cyst is seen on ultrasound as heterogeneous echogenicity, with debris which mobilizes with a change in position. Complex cysts also are characterized by thick walls, intracystic masses, and/or discrete solid components. These cysts are further categorized into four types based on Berg et al. criteria: Type 1 have either a thick external wall, thick internal septa, or both; type 2 has one or more internal masses; type 3 has mixed cystic and solid components but predominantly cystic, and type 4 is predominantly (at least 50%) solid with eccentric cystic foci.
Mammography is not as helpful as ultrasound in determining between cystic or solid masses such as fibroadenomas but is more appropriate for breast evaluation in patients over 35 years old. Patients younger than 35 typically have denser breast tissue, which is better evaluated with ultrasound. Mammography can be helpful in the classification and identification of associated microcalcifications, as well as other suspicious features.
Magnetic resonance imaging (MRI) is also an imaging modality used. However, due to cost and availability is not as routinely used as ultrasound or mammography.
The American College of Radiology proposed a classification system: Breast imaging-reporting and data system (BI-RADS) provides a standardized classification system for the assessment of the findings of breast radiological imaging and has six classifications representing different levels of suspicion for malignancy.
The last part of the triple assessment approach is histopathology by fine-needle aspiration (FNA) or core needle biopsy (CNB). The FNA is performed directly or by ultrasound guidance in the presence of a symptomatic cyst or cysts with suspicious solid components. Typically, the aspirated contents appear straw-colored but can be opaque, dark green, or even thick and purulent in the case of a galactocele. If the aspirate appears purulent, it should be sent for antibiotic sensitivity and microbiology analysis. However, if it is a galactocele, these are typically sterile. Bloody aspirate should be sent for cytology.
The majority of simple cysts aspirated disappear after aspiration, and the treatment is considered complete. If the cyst recurs, then core needle biopsy should be considered to evaluate for unseen solid components. Core needle biopsies are done when the ultrasound shows the presence of solid components, presence of suspicious mammogram findings including architectural distortions or calcifications, or the presence of small solid components that are difficult to aspirate by a large-bore needle. If the adequate sample cannot be taken by core needle biopsy, or if the cyst continues to recur even after a core needle biopsy, then excisional biopsy should be considered.
The majority of simple cysts aspirated disappear after aspiration, and the treatment is considered complete. Follow-up exams and imaging vary based on the cyst and findings from aspiration or biopsy. For a simple cyst, repeat imaging should be done 4 to 6 weeks after aspiration. Rapidly reformed cysts following repeat imaging are suggestive of malignancy. However, due to the very low prevalence of malignancy in simple cysts, it has been suggested that the routine follow up imaging 4-6 weeks after aspiration can be safely abandoned with patients unless there are new symptoms or recurrent lumps.
Complex cysts are typically followed more closely. If the histopathology results appear benign after initial aspiration or biopsy, then follow-up imaging should be planned every 6 to 12 months for 2 years. If, after 2 years, there have been no changes to the cyst, then repeat imaging can be stopped. If there are any concerning changes, then repeat biopsy or surgical excision is indicated.
Most cystic breast lesions are benign and, therefore, do not require any oncological treatment. The rare malignant cystic lesions are treated as breast cancer would be treated. The treatment is a combination of surgical resection and adjuvant treatment. The adjuvant treatment includes hormonal therapy, chemotherapy, radiotherapy, immunotherapy, and the use of biological agents.
The differential diagnosis of breast cysts includes a wide variety of both benign and malignant disease processes. Larger papillomas can be seen within a cystic structure, which is essentially a very dilated duct and can be confused for a complex cyst. Papillomas do not carry an increased risk of breast cancer. An abscess can also present similar to a cyst. However, due to the infectious nature, it is a very different etiology than the simple cyst. While phyllodes tumors are typically solid, they can have cystic components which can confuse the diagnosis. Radial scars as well can have microcystic components.
It is very rare to have an intracystic carcinoma, with some studies reporting them making up less than 0.1% of all breast malignancies. A study by Rosemond reported that only three cancers were identified in more than 3000 cysts aspirated and studied. ACC, or adenoid cystic carcinoma, is actually derived from a salivary gland tumor and can occur in the breast. It accounts for 0.1 to 1% of all breast malignancies. While the malignancy is triple-negative and has a high recurrence rate, it very rarely metastasizes or travels to surrounding lymph nodes. Because of this, ACC has an excellent survival rate provided that the cancer is low-grade.
Malignant lesions will require a histology diagnosis with grading, analysis of biological markers, and cellular components. A complete staging of the disease guides the form of treatment to be instituted. Staging is achieved by a combination of clinical, radiological, and intra-operative findings. The TNM (tumor-nodes-metastases) is the best-accepted breast cancer staging system designed by the American joint Committee on Cancer.
The prognosis of breast cysts varies depending on the etiology of the underlying lesion. If the cyst is a simple breast cyst with no solid components which resolves with aspiration, then the cyst is entirely benign. If the cyst has solid components and/or is recurrent after aspiration, then this could reflect an underlying malignancy. While intracystic carcinoma is exceedingly rare, presenting as 0.1% to 1% of all breast malignancies, it must be kept in the differential when evaluating a breast cyst.
In discussing breast cyst complications, the most apparent complications would present after an attempt at aspiration. Local edema or hematoma can occur after aspiration, as well as the possibility of contamination of the site leading to abscess formation. The presence of a breast cyst and its changes to the surrounding tissue architecture, the fine needle aspiration, and edema, or hematoma that may complicate it, may all reduce the mammography performance and produce false-positive results. For these, it is best to postpone mammography by 2 weeks from the aspiration or the resolution of the edema and to clearly report to the radiologist the clinical details.
If not performed under sterile conditions, fine-needle aspiration can introduce contaminating organisms into the breast, predisposing the patient to mastitis and breast abscess. It is also important to note that fine-needle aspiration or other biopsies of the cyst can cause tumor seeding of the adjacent normal breast tissue if there is an underlying malignancy.
Early presentation is key when having symptoms of a breast condition. While the majority of these will be benign fibrocystic disease, it is important to maintain an appropriate workup to rule out malignancy. It is also important to remember that the majority of cyclic mastalgia is not related to an identifiable breast mass and thus can be very difficult to properly treat.
To ensure proper evaluation, women should undergo a triple assessment with any breast mass. This assessment includes history taking and physical examination, imaging by ultrasound or mammography, and finally, histological or cellular diagnosis.
Timely communication by all members of the interprofessional team is crucial to proper patient care. In the discussion of breast cysts and their evaluation, it is important for proper communication between the pathologist and the managing clinician to ensure that the patient is well cared for. In addition, personal patient concerns about breast cysts or breast masses, in general, are common. It is important for primary clinicians to have honest and open communication with their patients to ensure that no concerning breast symptoms are missed. Finally, proper communication between the referring clinician and the surgeon is important to facilitate the timely treatment of the breast cyst. While the vast majority of these breast cysts are benign, it is in the patient’s best interest to have the cyst addressed promptly to ensure no underlying malignancy exists.
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