Gynecomastia

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

Gynecomastia is a benign male breast enlargement. Gynecomastia occurs due to increase estrogen to androgen ratio. Increased estrogen to androgen ratio can be physiological, such as seen during infancy, puberty and old age or pathological, which is due to obesity, steroid use, pharmacologic agents, medical conditions including chronic liver and renal failure or hypogonadism. However, most cases of the gynecomastia are idiopathic and asymptomatic. The diagnosis is primarily clinical. Other modalities used to diagnose gynecomastia include laboratory investigations such as blood hormone levels, renal function tests and liver function tests and imaging such as ultrasound or mammography. The treatment is usually supportive. Antiestrogens and surgical intervention can be considered in certain cases depending on physician and patient preference.

Gynecomastia is derived from Greek words, gyne which means woman and mastos which means breast. The term was originally coined by Galen, a Greek physician. Gynecomastia has been a known concept since the days of Aristotle (384–322 BC). The surgical management was initially discussed by Paulus, a Greek physician and later modified by Al-Zahrawi or Albucasis, an Andalusian surgeon.

Gynecomastia has been classified by various systems mainly based on surgical management, the severity of gynecomastia, physical appearance, and etiology.

The main pathophysiology behind gynecomastia is increased estrogen to androgen ratio which can occur through multiple mechanisms. These mechanisms can be physiological, pathological or pharmacological.

Common known causes of gynecomastia include physiological hormonal changes, use of medications and pathological entities such as cirrhosis, hyperthyroidism, testicular tumors and hypogonadism. Less common causes include androgen insensitivity syndrome, Kallmann syndrome, defects of testosterone pathway and tumors.

Gynecomastia must be differentiated from other diseases that cause breast enlargement in men. These diseases include pseudo gynecomastia, breast cancer, breast abscess, and lipoma.

Gynecomastia has the highest prevalence in elderly and neonatal age. Gynecomastia has trimodal age distribution with no racial preference.

Common risk factors in the development of gynecomastia include the use of medications, cirrhosis, and hyperthyroidism. The less common risk factors include aromatase overexpression, androgen insensitivity syndrome and testosterone pathway defects.

There is insufficient evidence to recommend routine screening for gynecomastia.

If left untreated patients with gynecomastia may progress to develop psychosocial stresses and rarely breast cancer. The majority of physiological gynecomastia is self-limited. Pathological gynecomastia has an excellent prognosis and responds well to treatment. Pharmacological gynecomastia responds very well to the cessation of the the offending agent.

There are no established criteria for the diagnosis of gynecomastia. Gynecomastia is diagnosed clinically after a thorough history and physical examination. Laboratory investigations, imaging and exclusion of other conditions like pseudogynecomastia and breast cancer, is also helpful in the diagnosis of gynecomastia.

The hallmark of gynecomastia is breast enlargement. The majority of patients with gynecomastia are asymptomatic. Pain is the most common symptom of gynecomastia. Less common symptoms depend on the underlying cause.

Common physical examination findings of gynecomastia include breast enlargement with or without tenderness. Patients with gynecomastia are otherwise asymptomatic.

Gynecomastia is diagnosed clinically after a thorough history and physical examination. Gynecomastia which is recent in onset and tender on the examination should have serum concentrations of human chorionic gonadotropin (hCG), LH, testosterone, and estradiol measured. The hormonal levels may vary depending on the underlying cause.

There are no ECG findings associated with gynecomastia.

There are no x-ray findings associated with gynecomastia.

There are no CT scan findings associated with gynecomastia.

There are no MRI findings associated with gynecomastia.

Gynecomastia is diagnosed clinically after a thorough history and physical examination. Ultrasound can be done in patients with gynecomastia when physical findings raise suspicion of a lump, abscess or breast cancer.

Gynecomastia is diagnosed clinically after a thorough history and physical examination. Mammogram can be done in gynecomastia when physical findings of a patient raise suspicion of breast cancer.

Gynecomastia is diagnosed clinically after a thorough history and physical examination. Laboratory investigations and imaging studies can be helpful in the diagnosis of gynecomastia. Other diagnostic study in the work up for gynecomastia include biopsy, which helps to confirm the diagnosis of breast cancer.

Gynecomastia is usually a self-limited condition, reassurance and follow-ups are recommended. Causative medications should be withheld and any underlying condition leading to gynecomastia should be throughly investigated and treated. Pharmacologic therapy is beneficial for the first several months until fibrous tissue replaces the glandular tissue. Pharmacologic options include SERMs, androgens and aromatase inhibitors.

Surgery is not the first-line treatment option for patients with gynecomastia. Surgery is usually reserved for patients with either psychological stresses, extensive gynecomastia or failure of medical treatment. The type of surgical technique depends on the extent of gynecomastia.

There are no established methods for the primary prevention of gynecomastia.

There are no established methods for the secondary prevention of gynecomastia.

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

Gynecomastia is derived from Greek words, “gyne” which means woman and “mastos” which means breast. The term was originally coined by Galen, a Greek physician. Gynecomastia has been a known concept since the days of Aristotle (384–322 BC). The surgical management was initially discussed by Paulus, a Greek physician and later modified by Al-Zahrawi or Albucasis, an Andalusian surgeon.

The most important historical events related to gynecomastia diagnosis and treatment include:^{[1][2][3][4][5][6][7]}

• The term gynecomastia was coined by Galen (130–200 AD), a Greek physician who described gynecomastia as an abnormal increase in fat within the male breast.
• Gynecomastia is derived from Greek words; “gyne” which means woman and “mastos” which means breast.
• Gynecomastia has been a known concept since the days of Aristotle.
• In the 7th century, there is some evidence of surgical treatment of gynecomastia by Paulus, a Greek physician. He is known for suggesting surgical treatment of gynecomastia for the first time in his Epitome of Medicine (Seven Books).
• Haly Abbas later in the Islamic age described the surgical management of gynecomastia in his Kitab al-Maliki (The Royal Book). His work was based on that of Paulus of Aegina.
• Al-Zahrawi or Albucasis, an Andalusian surgeon also provided the surgical treatment of gynecomastia after Paulus.
• Four centuries later, Şerefeddin Sabuncuoğlu illustrated the surgical techniques for the management of gynecomastia. These techniques were based on the work by Paulus and Al-Zahrawi.
• Al-Zahrawi’s surgical management was thought to be based on those of Paulus. The modification of surgical approach and use of medicinal substances might be indicative of Al-Zahrawi’s own practice of the procedure.
• Al-Zahrawi’s surgical management was practiced for many centuries.
• The probable etiology of gynecomastia was not discussed by Paulus and Al-Zahrawi in their work. In current practice, surgery for gynecomastia is reserved after the underlying cause is treated or after the failure of medical treatment.
• In the 18th century, Olpan, Schuchardt, and Gruber were among the prominent people who worked on gynecomastia.
• In 1919, Dr. Helen Ingleby published two cases of gynecomastia.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2], Omodamola Aje B.Sc, M.D. [3]

Gynecomastia has been classified by various systems mainly based on surgical management, the severity of gynecomastia, physical appearance, and etiology.

Different gynecomastia classification systems are:^{[1][2][3][4][5][6]}

Classification system	Criteria		Description
	Physical	Tissue type
Nydick’s		Physical	Gland limited to the retro areolar region and it does not reach the edge of the areola Gland extends as far as the edge of the areola The increase in gland volume extends beyond the edge of the areola
Tanner’s		Physical	Stage 1: Nipple prominence Stage 2: Mammillary button stage. The breast and the nipple-areola complex are slightly swollen and diameter of the areola increases Stage 3: Further swelling of the breast and areola without separation of their edges Stage 4: Areola and nipple become protrusive and form a secondary protrusion above the breast Stage 5: There is protrusion of the nipple only after retraction of the areola from the breast surface
Simon’s		Physical	Grade 1: Small visible breast enlargement and no skin redundancy Grade 2a: Moderate breast enlargement without skin redundancy Grade 2b: Moderate breast enlargement with skin redundancy Grade 3: Marked breast enlargement with marked skin redundancy
Deutinger’s and Freilinger’s		Physical	Grade 1: Thoracic wall poor in the flesh with mammary tissue localized behind and around the nipple without skin excess Grade 2: Adipose thoracic wall with widespread alterations and breasts similar to feminine ones during puberty Grade 3: Widespread alterations with excess adipose tissue, skin redundancy and inframammary fold and ptosis
Cohen’s		Physical	Group 1: Glandular gynecomastia Group 2: Glandular gynecomastia with ptosis Group 3: Adipose gynecomastia Group:4 Adipose gynecomastia with a slight glandular component
Rohrich’s		Physical/Tissue type	Grade 1: Minimal hypertrophy, (less than 250g of tissue) without ptosis 1a: Primarily glandular 1b: Primarily fibrous Grade 2: moderate hypertrophy (250-500g of breast tissue) without ptosis 2a: Primarily glandular 2b: Primarily fibrous Grade 3: Severe hypertrophy (>500g of breast tissue with grade 1 ptosis glandular or fibrous Grade 4: Severe hypertrophy with grade 2 or 3 ptosis glandular or fibrous
Gusenoff’s		Physical	Grade 1: Minimal excess skin and fat with minimal alteration of nipple-areola complex (NAC) and inframammary fold (IMF) 1a: No lateral skin roll 1b: Lateral skin roll Grade 2: Nipple-areola complex (NAC) and inframammary fold (IMF) below the ideal IMF with lateral chest roll and minimal upper abdominal laxity Grade 3: Nipple-areola complex (NAC) and inframammary fold (IMF) below the ideal IMF with lateral chest roll and significant upper abdominal laxity
Barros’s		Physical	Grade I: Increased diameter and slight protrusion limited to the areola region Grade II: Moderate hypertrophy of the breast with the nipple-areola complex (NAC) above the inframammary fold (IMF) Grade III: Major hypertrophy of the breast with glandular ptosis and the NAC situated at the same height as or as much as 1 cm below the inframammary fold (IM) Grade IV: Major breast hypertrophy with skin redundancy, severe ptosis, and the NAC positioned ≥1 cm below the inframammary fold (IMF)
Çi̇l’s		Imaging (computed tomography)	Gynecomastic adipose tissue/total gynecomastic tissue is <0.3 Gynecomastic adipose tissue/total gynecomastic tissue is 0.3–0.5 Gynecomastic adipose tissue/total gynecomastic tissue is >0.6
Cordova’s		Physical	Grade I: Increase in diameter and protrusion limited to the areolar region Grade II: Hypertrophy of all the structural components of the breast and the nipple-areola complex (NAC) is above the inframammary fold (IMF) Grade III: Hypertrophy of all the structural components with nipple-areola complex (NAC) at the same height as or approximately 1 cm below the inframammary fold (IMF). In this group we can also include male tuberous breast Grade IV: Hypertrophy of all the structural components with nipple-areola complex (NAC) >1 cm below theinframammary fold (IMF)
Fruhstorfer’s		Physical	Small-to-moderate gynecomastia Moderate-to-large gynecomastia
Mladick’s		Physical	No sagging Slight sagging Moderate sagging Extensive sagging
Monarca’s		Physical/tissue type	Grade I: Minimal hypertrophy (<250 g) IA: Primarily fatty breast tissue IB: Primarily fibrous breast tissue IC: Nipple malposition (upright) ID: Gynoid (rounded) shape of the chest IE: Absence of sternal notch II: Moderate hypertrophy (250–500 g) Grade IIA: Primarily fatty breast tissue IIB: Primarily fibrous breast tissue with peripheral fat IIC: Nipple malposition (upright or upward) IID: Moderate gynoid shape of the chest IIE: Absence of sternal notch Grade III: Severe hypertrophy with grade I ptosis (>500 g) IIIA: Fatty and fibrous tissue with ptosis of grade I IIIB: Nipple malposition (upright or upward) IIIC: Severe gynoid shape of the chest IIID: Absence of sternal notch Grade IV: Severe hypertrophy with grade II or III ptosis (>500–700 g) IVA: Fatty and fibrous tissue with ptosis of grade II IVB: Fatty and fibrous tissue with ptosis of with nipple reorientation grade III IVC: Nipple malposition (upright or upward) IVD: Severe gynoid shape of the chest IVE: Absence of sternal notch
Ratnam’s		Physical	Type 1: Enlarged breasts with elastic skin and no fold Type 2: Enlarged breasts with elastic skin and an inframammory fold (IMF) Type 3: Ptotic breasts with inelastic skin
Webster’s		Tissue type	Class 1: Periductal connective tissue hypertrophy without adipose tissue change Class 2: Increase in the amount of both connective and adipose tissue Class 3: Adipose tissue hypertrophy alone

*NAC, nipple-areola complex; IMF, inframammary fold

Gynecomastia can be classified on the basis of severity as:

• Grade I: Minor enlargement with no skin excess
• Grade II: Moderate enlargement with no skin excess
• Grade III: Moderate enlargement with skin excess
• Grade IV: Marked enlargement with skin excess

• Physiological
• Pathological
• Pharmacological
• Idiopathic

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

The main pathophysiology behind gynecomastia is increased estrogen to androgen ratio which can occur through multiple mechanisms. These mechanisms can be physiological, pathological or pharmacological.

• Estrogen and progesterone act in a coordinated manner to support breast development. Estrogen helps duct growth and progesterone promotes alveolar development which only occurs in female as gynecomastia doesn’t have alveolar development. ^[1][2]
• Growth hormone which acts through IGF-1 acts as a mediator in the presence of estrogen and progesterone for ductal breast duct development.^[3] The IGF-1 levels have been found higher in boys with pubertal gynecomastia which shows the role of GH and IGF-1 in the pathogenesis of gynecomastia.^[4]
• Prolactin in the presence of estrogen and progesterone also supports breast development. It also plays an indirect role as it causes central hypogonadism which alters the androgen/estrogen balance.^{[5] [6]}
• Aromatase catalyzes the conversion of androgens to estrogen and promotes the breast development. So, gynecomastia can also result from overexpression of aromatase.^[7][8]

Breast Tissue

Stimulatory Action

Inhibitory Action

Estrogen

Androgens

GH & IGF-1

• It is thought that gynecomastia can result from any condition, drug or disease state that causes an increase in circulating estrogen, a decrease in androgen or the sensitivity of the breast tissue to the circulating estrogen.^[5]
• The imbalance of estrogen/androgen can be due to increased levels of free estrogen secreted by the adrenals or testes, decreased estrogen breakdown, increased availability of estrogen precursors, exposure to estrogen like products or use of drugs that displaces more estrogen than androgen from sex hormone-binding globulin (SHBG).
• On the other hand, the imbalance can result from altered androgen metabolism, decreased androgen production, increased androgen binding (relative to estrogen) by SHBG, or androgen receptor defects.^{[9] [10] [5]}

Conditions causing increased estrogen	Conditions causing decreased testosterone
Chronic liver disease	Androgen-insensitivity syndrome
Hyperthyroidism	Five alpha-reductase deficiency
Extragonadal germ cell tumors	Hypopituitarism
Large cell carcinoma of the lung	Kallman Syndrome
Chronic kidney disease	Klinefelter Syndrome
	Testicular trauma

Genes involved in the pathogenesis of aromatase overexpression form of gynecomastia is encoded by a chromosome 15q21.2.^[8] As a result, any mutation in the mentioned loci result in aromatase overexpression.

Gynecomastia is associated with psychological stress such as:^{[11][12][13][14]}

• Depression
• Decreased self-esteem
• Body dissatisfaction

On gross pathology, characteristic findings of gynecomastia include:

• Excessive breast tissue and subareolar mass
• Well circumscribed borders
• Firm surfaces

On microscopic inspection, gynecomastia histology shows:^[15]

• Ductal hyperplasia
• Lengthening of the ducts
• inflammation surrounding the ducts
• Increase in periductal connective tissue

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

Common known causes of gynecomastia include physiological hormonal changes, use of medications and pathological entities such as cirrhosis, hyperthyroidism, testicular tumors and hypogonadism. Less common causes include androgen insensitivity syndrome, Kallmann syndrome, defects of testosterone pathway and tumors.

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no known life-threatening causes of gynecomastia.

• Drugs:^[1][2][3][4]
  • Antiandrogens
  • 5-Alpha reductase inhibtors
  • Cimetidine
  • Estrogen
  • Gonadotrophin releasing hormone (GnRH) agonist
  • Human chorionic gonadotropin (hCG)
  • Recombinant human growth hormone
  • Other drugs
• Idiopathic^[2][5]
• Physiologic:^[2][6]
  • Adolescence
  • Aging
  • Infancy
• Pathologic:^[7][6][8][9]
  • Cirrhosis
  • Chronic Renal disease
  • Hyperthyroidism
  • Primary hypogonadism
  • Persistent pubertal gynecomastia
  • Secondary hypogonadism
  • Testicular tumors

• Aromatase overexpression
• Androgen insensitivity syndrome
• Drugs
• Kallmann syndrome
• Testosterone pathway defects
• Tumors
  • Gastric carcinoma
  • Hepatic Tumor
  • Large cell carcinoma of lung
  • Pituitary Tumor
  • Renal cell carcinoma

To review a complete list of gynecomastia causes, click here.

• Familial prepubertal gynecomastia^[10]

Causes of gynecomastia in alphabetical order:^[11][12]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2] Shadan Mehraban, M.D.[3]

Gynecomastia must be differentiated from other diseases that cause breast enlargement in men. These diseases include pseudo gynecomastia, breast cancer, breast abscess, and lipoma.

Gynecomastia can be differentiated from other pathologies by detailed history taking and physical examination.^[1][2][3]

Diseases	Laboratory Findings			Physical Examination				Other physical exam findings	Age of onset
	Estrogen-to-androgen ratio	Cholesterol levels	WBC count	Tenderness	Enlargement	Nipple discharge	Lymphadenopathy
Gynecomastia	↑	N/A	–	+/-	+	+/-	N/A	Round discrete mass felt under areola and usually bilateral	Physiological gynecomastia is seen in newborns, adolescents and elderly
Pseudo gynecomastia	Normal	N/A	N/A	+/-	+	+/-	N/A	Increased adipose rather than glandular tissue on examination	Any age
Breast Cancer	N/A	N/A	N/A	+/-; mostly painless	+	+	+	Usually painless mass	Middle age to elderly
Lipoma	N/A	↑	N/A	+/-	+	+/-	N/A	Soft and mobile	Middle age to elderly
Sebaceous cyst	N/A	N/A	N/A	+/-	+	+/-	+/-	Asymmetric enlargement and swelling feels closer to the skin	Any age
Mastitis	N/A	N/A	↑	Tender	+/-	+/-	+/-	Systemic clinical features of infection	Any age

Differentiation of gynecomastia from other types of breast lumps: ABBREVIATIONS
LAP=Lymphadenopathy, HRT=Hormonal replacement therapy, FNA=Fine needle aspiration, DCIS=Ductal carcinoma in-situ

Diseases	Benign or Malignant	Clinical manifestation								Paraclinical findings		Gold standard diagnosis
		Demography	History	Symptoms			Signs			Histopathology	Imaging
				Mass	Mastalgia	Nipple discharge	Breast exam	Skin changes	LAP
Fibroadenoma[4]	Benign Very slight increased risk of breast cancer in complex fibroadenoma	Most common benign tumor, women aged 20-30 years	Increases in size during pregnancy or with estrogen therapy, and regress after menopause	+	±	–	Solitary Well-defined Mobile mass	–	–	Proliferative breast lesion without atypia	Ultrasound: Well-defined Solid mass	Mammography Ultrasound Biopsy
Breast cyst[5]	Benign No increased risk of malignancy for simple cyst <1% for complicated cyst <1% to 23% for complex cyst	Common masses found in premenopausal, perimenopausal, and postmenopausal women Mostly seen among HRT users	May resolve after aspiration Further evaluation for unresolved masses	+	±	–	Solitary Cluster of small masses or an ill-defined mass Smooth, firm, and frequently tender	–	–	Nonproliferative breast lesions	Ultrasound: Simple cyst: Well circumscribed, posterior acoustic enhancement without internal echoes Complicated cyst: Homogenous low-level internal echoes due to without solid components Complex cyst: Thick walls greater than 0.5 mm with solid component	Ultrasound Fine needle aspiration (FNA)
Fibrocystic change[6]	Benign No increased risk of malignancy Slightly increased risk of malignancy in presence of positive familial history of breast cancer	Unknown prevalence among adolescents >50% in women of reproductive age	Present before menses and improve during menstruation	+	+	±	Painful breast tissue Tender, nodular swelling	–	–	Nonproliferative breast lesions	Ultrasound: Small cysts in mammary zone Fibroglandular tissue around the mass	Ultrasound Mammography (it is not recommended for adolescents)
Galactocele[7][8]	Benign No increased risk of malignancy	Milk retention cysts with fluid collection among pregnant women and during breast-feeding	After ending lactation, the cysts resolve	+	±	±	Soft masses Cystic masses	–	–	Inflammation of lactate ducts due to extension, results in wall fibrosis	Mammography: Intermediate mass in absence of classic fat-fluid level Ultrasound: Complex mass	Ultrasound* Mammography
Cysts of montgomery[9]	Benign No increased risk of malignancy	Most common in age of 10-20 years old	More than 80% resolve spontaneously Drainage is essential in rare cases	+	±	±	Asymptomatic subareolar mass Drainage of clear to brownish fluid	±	–	Acute inflammation due to obstruction of the Montgomery’s gland	Ultrasound: Single cystic lesion in retroareolar area	Ultrasound
Hamartoma[10]	Benign Coexisting malignancy may be present	Common in women older than 35 years old	Asymptomatic ones found incidentally or painless breast lump Usually excised	±	–	–	Soft breast lump Breast enlargement without palpable mass	±	–	Benign proliferation of fibrous, glandular, and fatty tissue Thin capsule of connective tissue	Mammography: Well-described Discrete, solid, and encapsulated lesion	Ultrasound Mammography
Breast abscess[11][12]	Benign No increased risk of malignancy	Complication of lactational mastitis in 14% of cases Common among African-American women, heavy smokers , and obese patients	Resolve after drainage/antibiotic therapy	+	+	–	Localized inflammation of breast Tenderness	+	–	Mixed inflammatory feature by neutrophils. Granulation tissue and chronic inflammation feature caused by Gram-positive cocci	Ultrasound: Fluid collection	Ultrasound
Mastitis[13][14]	Benign No increased risk of malignancy	Common among lactating women (first three months of breast-feeding) Periductal mastitis among smokers and associated with squamous metaplasia	Resolve after drainage/antibiotic therapy	±	+	±	Breast tenderness Swollen breast tissue	+	–	Breast parenchyma inflammation: Acute mastitis: Staphylococcus infection Granulomatous mastitis: Tuberculosis or sarcoidosis infection	Ultrasound: Ill-defined area with hyperechogenicity with inflamed fat lobules Skin thickening	Ultrasound
Diseases	Benign or Malignant	Demography	History	Mass	Mastalgia	Nipple discharge	Breast exam	Skin changes	LAP	Histopathology	Imaging	Gold standard diagnosis
Breast carcinoma[15][16][17]	Malignant	Most common diagnosed cancer among women Leading cause of cancer death in women 40-49 years old	Positive family history	+	–	±	Hard Immobile Solitary Irregular margin	±	±	Molecular alteration in epithelial cells Ductal Lobular Ductal/lobular Mucinous Tubular Medullary Papillary	Mammography: Spiculated soft tissue, mass microcalcification Ultrasound: Spiculated, hypoechoic lesion, shadowing, internal calcification	Ultrasound Mammography
Ductal carcinoma in situ (DCIS)[18][19]	Malignant	Approximately 25% of all breast cancers Increase risk with ageing	Positive family history Nulliparity Obesity	±	–	±	May have normal physical exam	–	–	Noninvasive breast cancer Heterogenous group of neoplastic lesions	Mammography: Suspicious microcalcification	Mammography
Microinvasive breast cancer[20]	Malignant	Rare Commonly referred to DCIS with microinvasion Average age 50-60 years old	Nulliparity Positive family history	+	–	±	Solitary Firm palpable mass	–	±	Associated with high grade DCIS	Mammography: A mass with or without calcification Stromal reaction	Mammography
Breast sarcoma[21]	Malignant	Rare type, < 1% of all breast malignancies Average age of between 45-50 years	Positive history of breast cancer Rapid increase in size	+	–	–	Well-defined Firm mass	±	–	Heterogeneous nonepithelial malignancies from connective tissue of breast	Mammography: Noncalcified oval mass Indistinct margins	Mammography
Phyllodes tumor[22][23]	Benign or Malignant	Most common in premenopausal women (40-50 years)	Represent 1% of breast tumors Grow aggressively Classify in benign, borderline, and malignant groups	±	–	–	Smooth and multinodular Well-defined Firm mass Mobile	–	–	Nonepithelial breast neoplasm with average size of 5 cm	Ultrasound: Solid mass Hypoechoic Well-circumscribed Mammography: Smooth mass Polylobulated mass	Ultrasound Mammography
Lymphoma[24][25]	Malignant	Extremely rare ( 0.04%-0.5%) Average age 55-60 years	Unilateral mass in older women In childbearing women, bilateral and similar to inflammatory breast cancer, possibly having Burkitt lymphoma	+	–	–	Well-defined, firm mass Multiple	–	±	Diffuse growth pattern with large cells like immunoblast associated with neutrophils	Mammography: Nonspecific circumscribed masses Without calcification	Mammography Core biopsy
Duct ectasia[26]	Benign	Common among perimenopausal women	Usually resolve spontaneously	±	±	±	Usually asymptomatic	–	–	Distention of subareolar ducts	Ultrasound: Dilated milk ducts Fluid-filled ducts	Ultrasound
Intraductal papilloma[27]	Benign	Common in women between 35-55 years old	Possibly benign Harbor areas of atypia or DCIS Surgical excision is recommended	+	±	±	Solitary or multiple lesion Large lump near nipple	–	–	Growth of papillary cell into a lumen	Ultrasound: Well-defined Solid nodule	Core needle biopsy
Lipoma[28]	Benign	Common between age of 40-60 years old	Benign tumors May experience recurrence	+	–	–	Solitary Mobile Soft mass	–	–	Mature adipocytes without lipoblasts or atypia	Ultrasound: Well-Circumscribed Hypoechoic lesion	Core needle biopsy Excisional biopsy
Sclerosing adenosis[29][30]	Small risk of malignancy	Recurrent pain during mensturation	May present as a mass or incidental finding on mammogram No treatment is needed	±	+	–	Multiple lesion Firm Tender nodules	±	–	Proliferative disease	Mammography: Well-defined or irregular mass Microcalcification	Mammography
Pseudoangiomatous stromal hyperplasia[31][32]	Benign	Common in reproductive age women	Benign stromal proliferation Stimulation of vascular lesion	+	–	–	Solitary firm mass Thickening	–	–	Slit-like spaces between glandular units Maybe confused with mammary angiosarcoma	Mammography and ultrasound: Well-defined Solid mass Noncalcified	Ultrasound Mammography
Mondor’s disease[33][34]	Benign	Uncommon benign disease Occur on outer side of breast or under nipple	Benign and self-limiting disease Resolve after 4-6 weeks	+	+	–	Thick and tender cord on breast skin	+	–	N/A	Ultrasound: Tubular anechoic structure Multiple narrowing areas	Clinical examination Ultrasound
Diseases	Benign or Malignant	Demography	History	Mass	Mastalgia	Nipple discharge	Breast exam	Skin changes	LAP	Histopathology	Imaging	Gold standard diagnosis
Diabetic mastopathy[35]	Benign	Lymphocytic mastitis or mastopathy Common among premenopausal women Longstanding diabetes mellitus type 1	Suspicious breast mass After diagnosis, excision is not required	+	–	–	Ill-defined mass Immobile	–	–	Dense keloid-like fibrosis Periductal, lobular, and perivascular lymphocytic infiltration	Ultrasound: Irregular mass Hypoechoic Dense lesion	Ultrasound Core needle biopsy
Gynecomastia[36][37]	Benign	Benign breast tissue swelling among men and boys around puberty	Benign proliferation of the male breast glandular tissue Usually underlying nipple mass At least 0.5 cm	+	±	±	Unilateral or bilateral firm mass Breast swelling Rubbery mass	–	–	Glandular breast changes	Ultrasound: Nodular pattern Dendritic pattern Diffuse glandular pattern	Ultrasound
Sarcoidosis[38]	Benign	Rare in patients with systemic involvement	Benign palpable mass May mimic malignancy feature	+	–	–	Firm mass Hard mass	–	–	Epithelioid granulomas with multinucleated giant cell with rare necrosis	Mammography: Irregular Ill-defined Spiculated solid mass	Biopsy
Fat necrosis[39]	Benign	Common among women May mimic malignancy features	Benign breast lumps develop after trauma/ surgery Suspicious lumps required biopsy No excision in established diagnosis	+	±	–	Hard or smooth mass Solitary mass Mobile	–	–	Collections of liquefied fat	Ultrasound: Collections of liquefied fat Oil cysts	Ultrasound

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

Gynecomastia has the highest prevalence in elderly and neonatal age. Gynecomastia has trimodal age distribution with no racial preference.

• The prevalence of gynecomastia in infants ranges from 60,000 per 100,000 to 90,000 per 100,000.^[1]
• The prevalence of gynecomastia in pubertal age ranges from 4,000 per 100,000 to 69,000 per 100,000.^[2]
• The prevalence of gynecomastia in elderly (50-80 years) ranges from 24,000 per 100,000 to 65,000 per 100,000.^[3]

• Gynecomastia has trimodal distribution.^[1]
• The first peak is found in the neonatal period affecting 60-90 percent of all newborns. Infant transient gynecomastia regresses in two to three weeks after delivery. The second peak is during puberty and it declines in the late teenage years. The last peak is found in elderly with age ranging from 50 to 80years olds.^[4]

• Gynecomastia has no racial predilection.^[5]

• Gynecomastia is a benign male breast tissue condition.

• There is insufficient evidence of gynecomastia distribution on geographical basis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]; Omodamola Aje B.Sc, M.D. [3]

Common risk factors in the development of gynecomastia include the use of medications, cirrhosis, and hyperthyroidism. The less common risk factors include aromatase overexpression, androgen insensitivity syndrome and testosterone pathway defects.

Risk factors in the development of gynecomastia include:^{[1][2][3][4][5][6][7][8]}

• Idiopathic
• Drugs
  • Spironolactone
  • Cimetidine
  • Recombinant human growth hormone
  • Estrogens
  • Human chorionic gonadotropin
  • Anti-androgens
  • Gonadotropin releasing hormone (GNRH) agonists
  • 5-alpha reductase inhibitors
  • Ketoconazole
• Cirrhosis
• Hypogonadism
• Testicular neoplasms
• Hyperthyroidism
• Chronic kidney disease

• Feminizing adrenal tumors
• Ectopic hCG excretion
• Familial prepubertal gynecomastia

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

There is insufficient evidence to recommend routine screening for gynecomastia.

There is insufficient evidence to recommend routine screening for gynecomastia.

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

If left untreated patients with gynecomastia may progress to develop psychosocial stresses and rarely breast cancer. The majority of physiological gynecomastia is self-limited. Pathological gynecomastia has an excellent prognosis and responds well to treatment. Pharmacological gynecomastia responds very well to the cessation of the offending agent.

• The signs and symptoms of gynecomastia typically develop in neonatal, pubertal age or in the elderly.^[1][2][3]
• Without treatment gynecomastia has some associated risk of breast cancer, however, the majority of physiological gynecomastia resolves in months to years.

Complications of gynecomastia include:^[4][5][6]

• Persistent pubertal gynecomastia
• Breast cancer
• Psychological stress like:
  • depression
  • Reduced self-esteem
  • Body dissatisfaction

Gynecomastia prognosis is good overall:^[7][8][9]

• Physiological gynecomastia has an excellent prognosis and the majority of physiological gynecomastia resolve spontaneously.
• Pathological gynecomastia also responds well to treatment or removal of the underlying cause.
• Pharmacological gynecomastia responds very well to the cessation of the offending agent.
• Persistent gynecomastia can cause psychological stress and increases the risk of breast cancer.

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