Fibroadenoma – Causes, Symptoms, Diagnosis, Treatment

fibroadenoma

A fibroadenoma is a painless, unilateral, benign (non-cancerous) breast tumor that is a solid, not fluid-filled, lump. It occurs most commonly in women between the age of 14 to 35 years but can be found at any age. Fibroadenomas shrink after menopause, and therefore, are less common in post-menopausal women. Fibroadenomas are often referred to as a breast mouse due to their high mobility. Fibroadenomas are a marble-like mass comprising both epithelial and stromal tissues located under the skin of the breast. These firm, rubbery masses with regular borders are often variable in size.

Fibroadenomas are the most common breast masses in adolescents. They may present a challenge for physicians as treatment guidelines are lacking in this population. Fibroadenomas generally present as 2 to 3 cm in size, but they may increase to > 10 cm and cause associated breast asymmetry and/or hypertrophy. Types of fibroadenoma include juvenile, cellular, or giant. Differentiation must be made between giant fibroadenoma and juvenile hypertrophy

Fibroadenomas present as firm, non-tender, clearly demarcated masses usually 2 to 3 cm in size, though they may range from < 1 cm to greater than 10. They are most commonly found in the upper-outer quadrant of the breast. These benign masses may enlarge slowly without associated pain or nipple and skin changes, but fluctuations in size may occur with the menstrual cycle; when symptoms are present, they last an average of 5 months. Patients may also have associated breast asymmetry. Multiple fibroadenomas occur in 10 to 25% of cases., In adolescents, the mass regresses completely between 10 and 40% of the time.,

Types of Fibroadenoma

The types of fibroadenomas are

  • Simple fibroadenomas – They look the same all over when you view them under a microscope.
  • Complex Fibroadenoma – Rapidly growing hyperplastic cells; the pathologist can establish diagnosis after carefully reviewing the biopsy of breast tissue
  • Juvenile Fibroadenoma – This fibroadenoma is commonly found in patients age 10 to 18 years. These fibroadenomas have a faster growth rate and eventually shrink or disappear.
  • Giant Fibroadenoma – This non-cancerous lesion is slightly larger than other types. It commonly needs excision because it compresses or replaces normal breast tissue.
  • Phyllodes Tumor – A stromal tumor of the breast that can be either benign or malignant. It is not a fibroadenoma, therefore; it needs to be watched closely. Most doctors recommend removing it.

Causes of Fibroadenoma

Causes of fibroadenoma are debatable, but professionals believe that the lesion has a hormonal etiology related to the increased sensitivity of breast tissue to the female reproductive hormone estrogen. Fibroadenoma usually grows during pregnancy and tends to shrink during menopause. This supports the hormonal etiologic theory. Females who take oral contraceptives before 20 years of age tend to suffer from fibroadenoma at higher rates than the general population.

  • Hormonal – Fibroadenoma arises from stromal and epithelial connective tissue cells that are functionally and mechanically important in the breast. These tissues contain receptors for both estrogen and progesterone. For this reason, fibroadenomas tend to proliferate during pregnancy because of the excessive production of female reproductive hormones. Hormone sensitivity causes excessive proliferation of breast connective tissues.
  • Genetics – The mediator complex subunit 12 (MED12) gene is also important in the pathophysiology of fibroadenomas.  The connection between fibroadenomas and reproductive hormones has been suggested which may explain why they present themselves during reproductive years, increase in size during pregnancy, and regress post-menopause.[rx] Higher intake of fruits and vegetables, a higher number of live births, lower use of oral contraceptives and moderate exercise are associated with a lower frequency of fibroadenomas.[rx]

Symptoms of Fibroadenoma

Fibroadenomas are benign (not harmful in effect) tumors of the breast, most often present in women in their 20s and 30s.[rx] Clinically, fibroadenomas are usually solid breast lumps that are:

  • Painless
  • Firm or rubbery
  • Mobile
  • Solitary-round with distinct, smooth borders
  • Round with distinct, smooth borders
  • Easily moved
  • Firm or rubbery

People who have a simple fibroadenoma have a slightly increased risk of developing malignant (harmful) breast cancer. Complex fibroadenomas may increase the risk of breast cancer.[rx]

In the male breast, fibroepithelial tumors are very rare and are mostly phyllodes tumors. Exceptionally rare case reports exist of fibroadenomas in the male breast, however these cases may be associated with antiandrogen treatment.[rx]

Diagnosis of Fibroadenoma

Histopathology

The histological diagnostic features of fibroadenoma can be described as sheets of uniformly distributed epithelial cells that are typically arranged in a honeycomb pattern. There is a presence of foam cells and apocrine cells and an absence of excessive mitotic activity or anaplasia. Calcification may also be present. Juvenile fibroadenoma has increased in stromal cellularity. The stroma is hypovascular as compared to the malignant neoplasms. The basement membrane also remains intact in fibroadenoma which reflects its benign feature.

Microscopic Features

Contains both stromal and epithelial tissues that are arranged in 2 patterns

  • Pericanalicular – Includes the proliferation of stromal cells around epithelial structures
  • Intracanaliccular – Includes the proliferation of stromal cells compressing epithelial cells into clefts
Unique Histological Features of Various Fibroadenomas
  • Complex fibroadenoma – Sclerosing adenosis, calcification, apocrine metaplasia.
  • Juvenile fibroadenoma – Epithelial and stromal hyperplasia, absence of mitoses, thin micropapillary
  • Myxoid fibroadenoma – Stroma has myxoid features

History and Physical

  • Age is the most important factor in the incidence of fibroadenoma. Therefore, when obtaining a medical history, age is the most important factor which should be considered.
  • A family history of breast cancer is also significant. Female patients who have first-degree relatives with breast cancer should be monitored and observed more carefully for malignant features than patients without this family history.

Physical Examination

  • Clinical examination of a breast lump – is the first stage in the triple-assessment approach. Both breasts and axillae should be examined meticulously by the clinician, as well as carrying out a physical examination of other body systems as indicated by the history. Although it can be tempting to bypass the physical examination in favor of other, more targeted investigation modalities such as mammography or sonography, the findings of the physical examination are crucial for effective diagnosis and management of breast disease. Repeated studies have indicated that only by combining all three assessments can optimal sensitivity and specificity be achieved.
  • Clinical breast examination – is often conducted with a chaperone present to make the patient feel more comfortable. The entirely of the chest and abdomen should be exposed, Each breast and axilla should undergo a visual inspection, looking for skin changes, nipple discharge, visible masses or asymmetry, and tethering to underlying structure; this feature can be exaggerated by asking the patient to place their hands on their hips or lift the arms.The breasts can most easily be palpated by asking the patient to lie back at approximately 30 degrees and rest their hand palm-up underneath their head. Palpation of the breast must proceed in a structured manner; generally, clinicians will use a four-quadrant approach (upper outer, upper inner, lower outer, lower inner quadrants), followed by palpating the areola and then the axillary tail. Particular attention should focus on the inframammary fold and the axillary tail. The normal breast is examined first, and the tissue assessed for its overall consistency. Masses are most often detected in the upper outer quadrant, as the majority of breast tissue is located here.
  • Palpable breast masses – should be described in terms of location, size, shape, tenderness, fluctuance, mobility, texture, and pulsatility. If the patient describes nipple discharge that is not immediately visualized, it is appropriate to ask the patient to try to express the discharge themselves before the clinician attempting to do so.
  • Following palpation of the breast – the clinician must always palpate the axilla and supraclavicular region for lymphadenopathy. This area may present with enlarged, tender, or firm nodes, the number, and nature of which should be documented. During the examination of the axilla, the weight of the patient’s arm should be taken by the clinician to relax the pectoralis muscles.

Fibroadenoma most commonly occurs in the upper outer quadrant of the breast. On physical examination, it has the following features:

  • Non-tender or painless
  • Mobile
  • Solitary
  • Rapidly growing solid lump with rubbery consistency and regular borders.

After a thorough history and physical examination, the following imaging modalities are used for the diagnosis of fibroadenomas.

  • Mammography – The yield of mammography in young women is low, and its role in the diagnosis of fibroadenomas is limited. However, it may disclose features of infiltrative lesions in older women. In the mammographic image, fibroadenomas appear as soft, homogenous, and well-circumscribed nodules, and inner coarse calcifications are often observed.
  • A mammogram uses x-rays – to evaluate the suspicious masses in women above 35 years of age. Fibroadenoma on a mammogram appears as a distinct area from other breast tissue, with smooth round edges.
  • Mammographic features – of fibroadenomas are variable from a well-circumscribed discrete oval mass hypodense or isodense of breast glandular tissue to amass with macro lobulation or partially obscured margins. Involuting fibroadenomas in older, typically postmenopausal patients may contain calcification, often producing the classic, coarse popcorn calcification appearance.
  • Breast Ultrasound – Ultrasound (US) uses sound waves to detect the features of fibroadenomas in women younger than 35 years of age. US easily differentiates solid from cystic masses. On US, a fibroadenoma is typically seen as a well-circumscribed, round to ovoid, or macrolobulated mass with generally uniform hypoechogenicity.
  • Triple testing – a combination consisting of clinical examination, imaging, and excision biopsy – is essential for all women with a clinical finding such as a discrete palpable mass. Nodularity in young women less than 30 years of age may have management with clinical surveillance and short term follow up examination in 2 to 3 months. An investigation may be necessary if the lump has changed on review or if at the initial presentation, there is a new change in her breasts. Nodularity or thickening that is asymmetric in women over the age of 30 years, further investigation utilizing mammography and ultrasound, is warranted.
  • Short-term follow-up – is an important part of the management of nodularity so that the progression in size of a mass of nodularity or other associated findings (e.g., skin or nipple changes) is detected.
  • Mammography – with ultrasound examination is required for all discrete palpable lesions in women over the age of 35 to distinguish cysts from solid lesions. Complex cysts containing both fluid and solid matter require biopsy. For solid lesions, radiographically or ultrasonically directed core biopsy provides further information regarding the presence or absence of malignancy.
  • Core excision biopsy – involves a cutting needle with a spring-loaded, automated biopsy instrument which allows sufficient specimen/ tissue for histologic analysis. If necessary, a minimally invasive biopsy may be performed via a core needle biopsy
  • FNA allows a cytopathologist – to evaluate cellular material. However, the amount of material retrieved during FNA procedures being sufficient for diagnosis is non-successful in 35 to 47% of non-palpable lesions. A core biopsy is then the recommendation.
  • Cytology of nipple discharge – has limited specificity and sensitivity to detect malignancy (35 to 47%). If the results of both clinical and diagnostic evaluations are benign, a 6 to 12-month clinical breast examination, ultrasound, and mammography is the suggested follow-up to confirm a stable appearance.
  • MRI – can also be useful in the assessment of a new breast lump. It is not routinely used as it is more expensive with longer wait times but shows high sensitivity for detecting and delineating breast masses. It is the preferred modality for patients who have had previous breast augmentation surgery as the breast implants can distort the underlying parenchyma in mammography or ultrasound. It may also be a recommended approach for high-risk patients, such as those with known underlying BRCA mutations.
  • Baseline blood tests –  are usually recommended in a patient who is likely to undergo surgery, with particular emphasis on hemoglobin, bone profile, and liver function tests in case of suspected hepatic metastasis. Inflammatory markers and blood cultures should be considered where a breast abscess is suspected. Tumor markers such as Ca27.29 and Ca15-3 can be used for prognostication and monitoring for recurrence.
  • Nuclear medicine PET scanning, and bone isotope scanning – may help to assess the metastatic disease. Genome-mapping may be an option, for example, if a patient is suspected of carrying the BRCA1 or BRCA2 gene.
  • Core needle biopsy – A radiologist with guidance from an ultrasound usually performs this procedure. The doctor uses a needle to collect tissue samples from the lump, which go to a lab for analysis.
  • Fine-Needle Aspiration Cytology (FNAC) or core biopsy – Cytology allows an analysis of cells in isolation, while histological examination of a biopsy can provide more detail about the architecture of tissues. Both of these are invasive procedures involving risks to the patient and should, therefore, only take place when the index of suspicion is present. The decision whether to perform FNAC or core biopsy depends on several factors, including the expertise of the clinician, available diagnostic equipment, and site of the lesion. However, FNAC is generally preferred as first-line since it is less invasive.The need for pathological analysis has undergone review and, in certain cases, is thought to be unnecessary if the physical examination and radiological assessments are negative in a patient of low risk (i.e., young patients under the age of 25). The decision to proceed with FNAC or core biopsy is a clinical one, but in all cases should not be undertaken without due consideration of the risk-benefit analysis.

Imaging reports are standardized using a tool called BIRADS – Breast Imaging Reporting and Data System (fifth edition). This standard allows breast imaging to be described according to a certain structure as follows: density of breast tissue, presence and location of a mass or masses, calcifications, asymmetry, and any associated features. This classification system divides patients into categories 0 to 6, depending on the likelihood of malignancy in the obtained images:

  • BIRADS 0 – insufficient or incomplete study
  • BIRADS 1 – normal study
  • BIRADS 2 – benign features
  • BIRADS 3 – probably benign (<2% risk of malignancy)
  • BIRADS 4 – suspicious features (divided into categories 4a, 4b and 4c depending on the likelihood of malignancy)
  • BIRADS 5 – probably malignant (>95% chance of malignancy)
  • BIRADS 6 – malignant (proven malignant on tissue biopsy)

The BIRADS system includes different classifications for masses depending on the imaging modality in question. In mammography, to be considered a mass, the lesion must be visible in two different projections, must have convex outer borders, and must be denser in the center than on the periphery. In ultrasound, a mass requires visualization in two different planes. Masses are defined according to their shape, margin, and density. In terms of shape, a mass can categorize as round, oval, or irregular. Circumscribed margins are more apt to be benign, whereas microlobulated, indistinct, or spiculated are more likely to be malignant. The margin may also appear obscured. Mass density is described in comparison to that of the surrounding normal tissues – higher, equal, or lower – or may reflect the presence of fat within the mass.

Treatment of Fibroadenoma

In the majority of cases, fibroadenomas need no treatment. They shrink and disappear over time, but if their size is large and they are compressing other breast tissues, they should be removed.

  • Management may involve education  – about the condition, a well-fitting bra, and pain medication.[rx]
  • Due to the role of estrogen and progesterone treatments – promoting fibrocystic changes in the breast, metformin has been suggested as a treatment method to reduce the excessive cell proliferation caused by associated hormones.
  • For patients presenting with mastalgia – the first-line options are lifestyle changes as well as the avoidance of caffeine-containing food and beverages. Other suggestions are the use of a supportive bra, as well as altering the dose of hormone replacement therapy regimen.
  • Analgesics – such as aspirin and ibuprofen are options.Many females decide against the surgery because the lesions are harmless and involve no long-term risk of malignancy. Surgery also distorts the shape of a breast.
  • Danazol, bromocriptine, and tamoxifen  – have been proven to be effective. Linoleic acid in the form of evening primrose oil has been shown effective in two randomized trials but not in the third, the largest trial. Its role in treatment therefore remains uncertain. Vitamin E is considered definitely ineffective and iodine and vaginal progesterone possibly effective.
  • Ormeloxifene – Some fibroadenomas respond to treatment with ormeloxifene.[rx]
  • Medroxyprogesterone acetate caffeine avoidance and progesterone – have not been sufficiently studied. Several other therapies have not been examined in randomized controlled trials but are likely to be beneficial since they are based upon physiologic principles. For example, precise fitting of a bra to provide support for pendulous breasts has been reported to relieve pain in observational studies. GnRH agonist analogs are used to lower LH, FSH, and estradiol levels and to create a temporary postmenopausal state. The onset of menopause is known to reduce the frequency of breast pain. This therapy is reserved for patients in whom all other measures fail and the pain is considered severe. Reduction of the dosage of estrogens in postmenopausal women or the addition of androgen to estrogen replacement therapy (e.g. Estrotestâ tablets) appears to be beneficial in reducing breast pain (personal observations of the author).
  • Relative efficacy of effective therapies – No large randomized, controlled studies have compared the relative efficacy of evening primrose oil and tamoxifen. Rank orders them according to efficacy based upon data from individual reports from the same clinic. Minimal data are available from clinical trials which involve direct head to head comparisons. It should be noted that overall responses to danazol, bromocriptine, and evening primrose oil are lower in those with non-cyclic pain than those with cyclic pain.
  • Check thyroid levels and suggest the use of iodine – Consider taking vitamin E, evening primrose oil, and B vitamins.

Surgery

Doctors might decide to remove fibroadenoma if it is massive and continues to increase in size. Indications for surgical intervention include rapid growth, size greater than 2 cm, and patient request.

There are 2 surgical procedures used to remove a fibroadenoma

  • Lumpectomy or excisional biopsy – In this procedure, the surgeon removes the fibroadenoma and sends it to the laboratory for further evaluation.
  • Cryoablation – Surgeons use a cryoprobe to freeze and destroy the cellular structure of fibroadenoma. A core needle biopsy must be performed before cryoablation to confirm the fibroadenoma.

Non-invasive Surgical Interventions

There are several non-invasive options for the treatment of fibroadenomas, including percutaneous radiofrequency ablation (RFA), cryoablation, and percutaneous microwave ablation.[rx] With the use of advanced medical imaging, these procedures do not require invasive surgery and have the potential for enhanced cosmetic results compared with conventional surgery.[rx]

Cryoablation

The FDA approved the cryoablation of a fibroadenoma as a safe, effective, and minimally-invasive alternative to open surgical removal in 2001.[rx] During cryoablation, ultrasound imaging is used to guide a probe into the mass of breast tissue. Extremely cold temperatures are then used to destroy the abnormal cells, and over time the cells are reabsorbed into the body.[rx] The procedure can be performed as an outpatient surgery using local anesthesia, and leaves substantially less scarring than open surgical procedures and no breast tissue deformation.

The American Society of Breast Surgeons recommends the following criteria to establish a patient as a candidate for cryoablation of a fibroadenoma:[rx]

  • The lesion must be sonographically visible.
  • The diagnosis of a fibroadenoma must be confirmed histologically.
  • The lesion should be less than 4 cm in diameter.

High-Intensity Focused Ultrasound

High-Intensity Focused Ultrasound (HIFU) is a newer technique for the treatment of malignant and benign tumors of the breast and has shown promising results in the form of complete radiological removal of tumors.[rx] An ultrasound beam is focused on a target in the breast and leads to tissue death and protein degradation by raising the temperature in that area.[rx] Currently, the use of radiation is recommended in some cases, but HIFU in particular is not part of treatment guidelines.[rx] Further research into the usefulness of HIFU, specifically in fibroadenoma, is required before more widespread use of the technique in fibroadenoma.[rx]

Prevention

Advice to be provided to patients for preventing and treating fibrocystic breast disease:

  • Increase the intake of complex carbohydrates as well as fiber.
  • Reduce the intake of methylxanthines.
  • Methylxanthines are present in products such as coffee, chocolate, black tea, and cola drinks.
  • Some women’s breast tissue is associated with cyclic mastalgia and cyst development, due to increased caffeine intake.
  • In previous studies, over 97% of women had a significant reduction in the sensitivity of breast tissue, following complete avoidance of methylxanthines.
  • The results in the study were reported after four months of avoiding caffeine.

Home Remedies

The following home remedies help to relieve the symptoms of fibrocystic breasts to some extent:

  • Prefer wearing a firm fitting sports bra
  • Consider wearing bra during exercise and while sleeping
  • Limit coffee consumption as it may affect the breast pain and other premenstrual symptoms
  • Reduce the fat in the diet; it helps to relieve discomfort caused by fibrocystic breast
  • If you are on hormonal therapy, discuss with doctor and substitute hormonal therapy with other alternatives
  • Apply a warm water bottle or heating pad in the areas of pain to relieve pain.

References