Fibroadenoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2] Haytham Allaham, M.D. [3]

Fibroadenoma of the breast is a benign tumor characterized by proliferation of both glandular and stromal elements.

Fibroadenoma may be classified according to microscopic histopathological analysis into four subtypes, which include juvenile fibroadenoma, complex fibroadenoma, myxoid fibroadenoma, and cellular fibroadenoma.

Fibroadenoma is a common benign tumor of the breast. Fibroadenoma arises from connective tissue cells, which are cells that are normally involved in the functional and mechanical support of the surrounding tissues. Fibroadenoma demonstrate estrogen and progesterone sensitivity and may grow during pregnancy. The mediator complex subunit 12 (MED12) gene is the most common gene involved in the pathogenesis of fibroadenoma. On gross pathology, a rubbery, tan colored, and lobulated mass is a characteristic finding of fibroadenoma. On microscopic pathology, charectersitic findings of fibroadenoma include a biphasic proliferation of both stromal and epithelial components that can be arranged in two growth patterns; a pericanalicular growth pattern and an intracanalicular growth pattern.

There are no known direct causes for fibroadenoma. Common risk factors for fibroadenoma can be found here.

Fibroadenoma must be differentiated from other diseases that cause a similar clinical presentation, such as phyllodes tumor, hamartoma, and adenomyoepithelioma.

Fibroadenoma is the most common breast mass among adolescent women in the United States. There are no definite data regarding the exact incidence of fibroadenoma among the US general population. Fibroadenoma commonly affects individuals younger than 30 years of age. Females are more commonly affected with fibroadenoma than males. Fibroadenoma usually affects individuals of the African American race. Caucasian individuals are less likely to develop fibroadenoma.

Common risk factors in the development of fibroadenoma are obesity, estrogen replacement therapy, and nulliparity.

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for fibroadenoma.

Most patients with fibroadenoma are asymptomatic. If left untreated, patients with fibroadenoma may progress to develop a painless, mobile, and well-circumscribe breast lump. Fibroadenoma is a benign tumor that rarely develops any complications. Fibroadenomas commonly enlarge during pregnancy and involute after the age of menopause. The prognosis is generally excellent, and the 5-year survival rate of patients with fibroadenoma is almost equal to the normal population.

The majority of patients with fibroadenoma are asymptomatic. The hallmark of fibroadenoma is the presence of a painless, firm, solitary, mobile, slowly growing lump in the breast.

Patients with fibroadenoma usually appear averagely built and well nourished. Physical examination of patients with fibroadenoma is usually remarkable for a painless, firm, solitary, well-circumscribed, and mobile breast mass.

CT scan may be helpful in the diagnosis of fibroadenoma. Findings on CT scan suggestive of fibroadenoma include an oval mass with well defined borders, lobulated appearance, and localized calcification.

MRI may be helpful in the diagnosis of fibroadenoma. On a T1 weighted brain MRI image, fibroadenoma is characterized by a well-defined, isointense mass located at the upper-outer quadrant of the breast.

Ultrasound may be helpful in the diagnosis of fibroadenoma. Findings on ultrasound suggestive of fibrodenoma include a well-circumscribed, round to ovoid, macrolobulated mass that is generally uniformly hypoechogenic.

Breast mammogram may be helpful in the diagnosis of fibroadenoma. On breast mammogram, fibroadenoma is characterized by a well circumscribed, discrete, oval mass that is isodense to breast glandular tissue. The mass may contain coarse, popcorn calcification.

The definitive diagnosis of fibroadenoma is confirmed by an ultrasound guided biopsy. Characteristic findings for fibroadenoma on microscopic histopathological analysis can be found here.

The majority of cases of fibroadenoma are self-limited and only require close follow-up. The feasibility of surgery depends on the age of the patient at the time of diagnosis. Surgery is the mainstay of treatment for fibroadenoma among patients older than 35 years of age.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2] Haytham Allaham, M.D. [3]

Dupont et al described in 1994 the risk of invasive breast cancer in patients with fibroadenoma. Later in a study with Carter, atypia within a fibroadenoma was assessed for the risk of cancer development. In another study, the excision of a complex fibroadenoma discovered via core biopsy was advised.

• In 1994, Dupont et al addressed in their retrospective cohort study that fibroadenoma is associated with a long term risk of invasive breast cancer, with the risk further increased in women with complex fibroadenomas, a family history of breast cancer and those with proliferative disease. Later in a study with Carter in 2001, they found that the presence of atypia within a fibroadenoma cannot foretell the presence of one in the adjacent breast parenchyma. They also found that atypia within a fibroadenoma does not present a relevant risk of development of breast cancer greater than that of a fibroadenoma with no atypia within.^[1][2]
• In 2008, Solar-Levy et al reported the presence of invasive lobular carcinoma in about 1.6% of patients with complex fibroadenomas and advised that any complex fibroadenoma with a high risk lesion on core biopsy should be excised. They also recommended that simple fibroadenomas with a volume growth rate of less than 16% per month (in patients younger than 50 years of age) and less than 13% per month (more than 50 years) should be followed up with imaging studies.^[3][4][5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2] Haytham Allaham, M.D. [3]

Fibroadenoma may be classified according to microscopic histopathological analysis into four subtypes, which include juvenile fibroadenoma, complex fibroadenoma, giant fibroadenoma, myxoid fibroadenoma, and cellular fibroadenoma.

• Fibroadenoma may be classified according to microscopic histopathological analysis into five subtypes, which include:^[1]

• Juvenile fibroadenoma
• Complex fibroadenoma
• Giant fibroadenoma
• Myxoid fibroadenoma
• Cellular fibroadenoma

• The table below differentiates between the main subtypes of fibrodenoma according to microscopic histopathological analysis:^[1][2][3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2] Haytham Allaham, M.D. [3]

Fibroadenoma is a common benign tumor of the breast. Fibroadenoma arises from connective tissue cells, which are cells that are normally involved in the functional and mechanical support of the surrounding tissues. Fibroadenomas may demonstrate estrogen and progesterone sensitivity and may grow during pregnancy. The mediator complex subunit 12 (MED12) gene is the most common gene involved in the pathogenesis of fibroadenoma. On gross pathology, a rubbery, tan colored, and lobulated mass is a characteristic finding of fibroadenoma. On microscopic pathology, charectersitic findings of fibroadenoma include a biphasic proliferation of both stromal and epithelial components that can be arranged in two growth patterns; a pericanalicular growth pattern and an intracanalicular growth pattern.

• Hormones and growth factors act on connective tissue cells in the breast to regulate the development, maturation, and differentiation of mammary glands.^[1]
• Estrogen is responsible for mediation of the development of ductal tisuue. Progesterone promotes ductal branching and lobulo-alveolar development. While prolactin regulates the production of milk protein.
• Estrogen and progesterone levels increase at puberty and initiates breast development. This development results in the formation of a complex tree-like structure which comprises of primary milk ducts (about 5 to 10) that originate from the nipple, segmental ducts (about 20 to 40), and sub-segmental ducts (about 10 to 100) that end in terminal duct lobular units. The increase in these hormones during the menstrual cycle stimulates cell proliferation in the luteal phase.

• Fibroadenoma is a common benign tumor of the breast. The pathogenesis is not completely understood.
• Fibroadenoma is a proliferation of stromal and epithelial connective tissue cells (biphasic) originating from the terminal duct-lobular unit. Analysis of the stromal and epithelial cells showed that both are polyclonal, which supports the theory that fibroadenomas are hyperplastic lesions associated with a deviation from the normal maturation of the breast, rather than a true neoplasm.^[2][3]
• In some patients, fibroadenomas may express estrogen and progesterone receptors. These hormones stimulate the fibroadenomas via hormone-receptor mechanism leading to excessive proliferation of epithelial and stromal cells. They undergo atrophy during menopause.^[4]
• Some fibroadenomas may express epidermal growth factor (EGF) receptors.^[4]
• More than 70% of fibroadenomas present as a single mass, and 10%–25% of fibroadenomas present as multiple masses.^[5]
• Although fibroadenomas may be develop in any part of the breast, there is a significant predilection for the upper outer quadrant. The mass may enlarge slowly without associated pain or nipple and skin changes, but fluctuations in size may occur with the menstrual cycle. ^[2]

• The mediator complex subunit 12 (MED12) gene is involved in the pathophysiology of fibroadenoma. The MED12 gene helps in producing the MED12 protein which with other proteins, is essential for eukaryotic transcriptional regulation.^[6][7]

Conditions associated with fibroadenoma include:^[5]

• Beckwith-Wiedemann syndrome
• Maffucci syndrome
• Cowden syndrome

• On gross pathology, a painless, firm, solitary, mobile, and slowly growing breast lump is a characteristic finding of fibroadenoma.
• Other charectersitic findings on gross examination of fibroadenoma include:^{[8][9][10][11]}

• Rubbery texture
• Tan/white colored
• Lobulated appearance
• Short slit-like spaces present
• Calcifications

• Fibroadenomas may sometimes be referred to as a “breast mouse”, owing to the high mobility of the tumor through out the breast tissue.

• On microscopic pathology, charectersitic findings of fibroadenoma include:^{[8][9][10][11]}

• Uniformly distributed sheets of epithelial cells arranged in a honeycomb pattern
• Presence of foam and apocrine cells
• Intact basement membrane
• A hypovascular stroma
• Calcification may be present
• Absence of excessive mitotic figures or anaplasia
• Biphasic proliferation of both stromal and epithelial components that can be arranged in two growth patterns:

• Pericanalicular growth pattern: stromal proliferation around epithelial structures
• Intracanalicular growth pattern: stromal proliferation compressing the epithelial structures into clefts

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2] Haytham Allaham, M.D. [3]

There are no known direct causes for fibroadenoma.

The exact etiology of fibroadenoma is unknown/debatable. Nonetheless, professionals believe that it may be related to an increase in the sensitivity of the breast tissue to estrogen.^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shadan Mehraban, M.D.[2]

Fibroadenoma must be differentiated from other diseases that cause a similar clinical presentation. Malignancy, cysts, inflammation, and non-inflammatory solid lumps. Breast symptoms such as nipple discharge and mastalgia require assessment as well. Differentiating fibroadenoma from different types of breast lumps is based on imaging findings and breast clinical exam results.

ABBREVIATIONS
LAP=Lymphadenopathy, HRT=Hormonal replacement therapy, FNA=Fine needle aspiration, DCIS=Ductal carcinoma in-situ

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2] Haytham Allaham, M.D. [3]

Fibroadenoma is the most common breast mass in the adolescent population. There are no definite data regarding the exact incidence of fibroadenoma among the US general population. Fibroadenoma commonly affects individuals younger than 30 years of age. Females are more commonly affected with fibroadenoma than males. Fibroadenoma usually affects individuals of the African American race. Caucasian individuals are less likely to develop fibroadenoma.^[1][2]

• The incidence of fibroadenoma is approximately 2.2% in the adolescent population.^[3]

• Fibroadenoma is the most common benign breast tumor in women under the age of 30.^[3]
• Fibroadenoma constitutes about 50% of all breast biopsies, with this rate rising to 75% for biopsies in women under the age of 20 years.^[2]
• Multiple fibroadenomas occur in 10 to 25% of cases

• Fibroadenoma can be found most commonly in women between the age of 14 to 35 years but it can be found at any age. It is less commonly seen in postmenopausal women.^[4]

• Females are more commonly affected with fibroadenoma than males.^[1]

• Fibroadenoma usually affects individuals of the African American race. Caucasian individuals are less likely to develop fibroadenoma.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2] Haytham Allaham, M.D. [3]

Common risk factors in the development of fibroadenoma are obesity, young age, and oral contraceptives.

• Common risk factors in the development of fibroadenoma include:^[1][2][3]
  • Young age (<35 years)
  • Prior history of benign breast disease
  • Obesity
  • Family history of multiple fibroadenomas
  • Consumption of oral contraceptives before the age of 20

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for fibroadenoma.

There is insufficient evidence to recommend routine screening for fibroadenoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Odukwe, M.D. [2] Haytham Allaham, M.D. [3]

Most patients with fibroadenoma are asymptomatic. If left untreated, patients with fibroadenoma may progress to develop a painless, mobile, and well-circumscribe breast lump. Fibroadenoma is a benign tumor that rarely develops any complications. Fibroadenomas commonly enlarge during pregnancy and involute after the age of menopause. The prognosis is generally excellent, and the 5-year survival rate of patients with fibroadenoma is almost equal to the normal population.

• The peak age of women at the time of diagnosis of a fibroadenoma is in their twenties.^[1]
• It takes about 12 months for most fibroadenomas to gain a size of 2 to 3 cm, wherefore they remain unchanged for several years.^[2]
• The lifetime of a fibroadenoma is about 15 years.^[2]
• After 5 years, there is approximately 50% likelihood of resolution of a fibroadenoma. Among the 50% not likely to resolve spontaneously, about 25% will not change and 25% will enlarge in size during follow up.^[2]
• Most fibroadenomas decrease in size via loss of cellularity or infarction with resultant calcification and hyalinization.^[3]
• The incidence of fibroadenoma evolving into a carcinoma is reported to be 0.002 to 0.0125%.^[2]
• More than 70% of fibroadenomas present as a single mass, and 10%–25% of fibroadenomas present as multiple masses.^[3]
• Fibroadenomas tend to grow during pregnancy and shrink after menopause.^[4]

• Fibroadenoma is a benign tumor that rarely develops any complications.^[5]

• The prognosis is generally excellent, and the 5-year survival rate of patients with fibroadenoma is almost equal to the normal population.^[5]
• In adolescents, the mass regresses completely between 10 and 40% of the time.^[6]
• Though not yet quantifiable, patients with fibroadenoma may be at increased risk of developing invasive breast cancer later in life. This risk is increased in women with complex fibroadenomas (fibroadenomas with cysts, sclerosing adenosis, epithelial calcification, papillary apocrine changes, or more than 3mm in diameter), proliferative disease, or a family history of breast cancer.^[6][7]

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