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Fat Necrosis of the Breast

Fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of the breast is an inflammatory, benign Benign Fibroadenoma condition resulting from injury to the breast tissue. Forms of injury include blunt traumatic injury as well as trauma from surgical procedures, biopsies, and radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy. Fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of the breast is characterized by the presence of an ill-defined breast mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast that is usually accompanied by overlying skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions changes. Oil cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change may also form as fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans and calcification trap oil from degenerating fat cells. Fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of the breast may be clinically and radiographically difficult to distinguish from a malignant mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast. Diagnosis relies on a history consistent with trauma, breast imaging Breast Imaging Female breasts, made of glandular, adipose, and connective tissue, are hormone-sensitive organs that undergo changes along with the menstrual cycle and during pregnancy. Breasts may be affected by various diseases, in which different imaging methods are important to arrive at the correct diagnosis and management. Mammography is used for breast cancer screening and diagnostic evaluation of various breast-related symptoms. Imaging of the Breast, and, less commonly, a core needle biopsy Core Needle Biopsy Fibrocystic Change for definitive diagnosis. Treatment is usually not required. The primary clinical significance of this condition is its possible confusion with breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer on exam and imaging.

Last updated: 25 Feb, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage is a benign Benign Fibroadenoma breast lesion that results from injury to the breast tissue.

Epidemiology

  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 0.6%
  • 2.75% of all benign Benign Fibroadenoma breast lesions
  • Average age at diagnosis: 50 years

Etiology

  • Trauma:
    • Direct injury to the chest (including abuse)
    • Up to 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may not report/recall trauma.
  • Fine and core needle breast biopsies
  • Surgical procedures:
    • Lumpectomy
    • Breast reconstruction
    • Breast reduction
    • Mastectomy
    • Free flaps
    • Fat grafting
  • Silicone injections
  • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy
  • Mastitis Mastitis Mastitis is inflammation of the breast tissue with or without infection. The most common form of mastitis is associated with lactation in the first few weeks after birth. Non-lactational mastitis includes periductal mastitis and idiopathic granulomatous mastitis (IGM). Mastitis/breast infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Risk factors:
    • Large or pendulous breasts Breasts The breasts are found on the anterior thoracic wall and consist of mammary glands surrounded by connective tissue. The mammary glands are modified apocrine sweat glands that produce milk, which serves as nutrition for infants. Breasts are rudimentary and usually nonfunctioning in men. Breasts: Anatomy
    • Older age
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
    • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity

Pathophysiology and Clinical Presentation

Pathophysiology

Mechanisms of injury:

  • Laceration Laceration Torn, ragged, mangled wounds. Blunt Chest Trauma of breast tissue blood supply during procedures → ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • Traumatic hemorrhage within breast adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form. Adipose Tissue: Histology

Tissue response:

  • Aseptic saponification:
    • Fatty acids Fatty acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated. Fatty Acids and Lipids are released from triglycerides Triglycerides Fatty Acids and Lipids by the blood or tissue lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion
    • Fatty acids Fatty acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated. Fatty Acids and Lipids form a complex with calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes (calcification).
    • Reactive inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation around saponified tissue results in fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans and scarring Scarring Inflammation.
  • Another mechanism is cystic Cystic Fibrocystic Change degeneration:
    • Adipose cells release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology their contents.
    • Calcification and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans can form around the degenerated fat → oil cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

  • Firm, irregular breast mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast (mimics breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer)
  • May be tender, painful, or painless
  • Usually located in the periareolar area, but may occur anywhere on the breast
  • May be accompanied by erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion and/or ecchymosis Ecchymosis Extravasation of blood into the skin, resulting in a nonelevated, rounded or irregular, blue or purplish patch, larger than a petechia. Orbital Fractures
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions or nipple retraction Nipple Retraction Mastitis
Fat necrosis of the right breast

Fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of the breast with an area of skin necrosis Skin Necrosis Rocky Mountain Spotted Fever secondary to injection of methylene blue dye

Image: “ Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of the right breast” by St Georges Hospital, London, UK. License: CC BY 2.0

Diagnosis

History

  • Trauma (e.g., motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology vehicle accidents, assault)
  • Breast surgery/ biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease/ mastitis Mastitis Mastitis is inflammation of the breast tissue with or without infection. The most common form of mastitis is associated with lactation in the first few weeks after birth. Non-lactational mastitis includes periductal mastitis and idiopathic granulomatous mastitis (IGM). Mastitis
  • Breast/chest radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma

Physical exam

  • Thorough breast exam:
    • Firm irregular mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast, fixed to dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions
    • Nipple retraction Nipple Retraction Mastitis/ skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions tethering
  • Axillary lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node palpation Palpation Application of fingers with light pressure to the surface of the body to determine consistency of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. Dermatologic Examination: Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy may point toward breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer.

Imaging

  • Mammogram Mammogram Fibrocystic Change
  • Ultrasonography:
  • Breast magnetic resonance imaging (MRI):
    • May be helpful in cases with significant fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
    • Differentiates fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage from carcinoma
    • Fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage usually appears identical to adjacent fat on MRI.
G3 fat necrosis

Mammography Mammography Radiographic examination of the breast. Breast Cancer Screening demonstrating fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage

Image: “G3 fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage” by Department of Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma Oncology, Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy. License: CC BY 2.0

Management

  • Observation and reassurance Reassurance Clinician–Patient Relationship
  • Natural history: Lesions may enlarge, remain unchanged, or regress.
  • Surgical management usually not required, but may be chosen if the mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast:
  • Aspiration of oil cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change with a needle if the cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change cause discomfort

Differential Diagnosis

  • Breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer: the most important diagnosis to rule out when a patient presents with a breast mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast or evidence of calcifications and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans on imaging, as fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage may present in a very similar way. If the diagnosis cannot be made based on imaging alone, core needle biopsy Core Needle Biopsy Fibrocystic Change is required. Management may involve surgery, chemotherapy Chemotherapy Osteosarcoma, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, and hormonal treatment.
  • Fibrocystic Fibrocystic Fibrocystic Change changes of the breast: a non-specific term referring to several types of benign Benign Fibroadenoma breast conditions that usually occur as a result of cyclic hormonal stimulation from estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy and progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones. The most common types of changes are non- proliferative lesions Proliferative Lesions Fibrocystic Change including cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change within the ducts and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans resulting from chronic inflammation Chronic Inflammation Inflammation after these cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change rupture. Diagnosis is made with mammogram Mammogram Fibrocystic Change and ultrasound imaging. Treatment is supportive.
  • Mastitis Mastitis Mastitis is inflammation of the breast tissue with or without infection. The most common form of mastitis is associated with lactation in the first few weeks after birth. Non-lactational mastitis includes periductal mastitis and idiopathic granulomatous mastitis (IGM). Mastitis and/or breast abscess Breast Abscess Benign Breast Conditions: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the breast tissue, most commonly due to infection with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions or oral flora introduced during breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding. A purulent abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease may form. Occasionally, non- lactational mastitis Lactational Mastitis Mastitis and abscesses are also possible. Cases usually present with a fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema of the breast, with or without a tender fluctuant Fluctuant Dermatologic Examination mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast ( abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease). Management involves antibiotics, continued expression of breast milk if lactating, and incision and drainage Incision And Drainage Chalazion of an abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease.
  • Galactocele Galactocele Benign Breast Conditions: a cystic Cystic Fibrocystic Change collection of fluid usually caused by an obstructed milk duct. A galactocele Galactocele Benign Breast Conditions presents as a palpable, firm mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast in the subareolar region and may show a classic fat-fluid level Fat-Fluid Level Imaging of the Mediastinum on imaging. Diagnosis is based on history and aspiration, yielding milky fluid. These lesions do not require excision.
  • Fibroadenoma Fibroadenoma Fibroadenomas are the most common benign tumor of the female breast and the most common breast tumor in adolescent and young women. The tumors are well-circumscribed, mobile, and unencapsulated, with a rubbery or firm consistency. Fibroadenoma: a benign Benign Fibroadenoma solid breast mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast composed of fibrous Fibrous Fibrocystic Change and glandular tissue, which presents as a small, well-defined, mobile mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast with a rubbery or firm consistency Consistency Dermatologic Examination. The exact etiology is unknown. Diagnosis is confirmed with a core needle biopsy Core Needle Biopsy Fibrocystic Change. Management is either excision or observation.
  • Phyllodes tumor Phyllodes Tumor A type of connective tissue neoplasm typically arising from intralobular stroma of the breast. It is characterized by the rapid enlargement of an asymmetric firm mobile mass. Histologically, its leaf-like stromal clefts are lined by epithelial cells. Rare phyllodes tumor of the prostate is also known. Benign Breast Conditions: a fibroepithelial tumor Tumor Inflammation similar to fibroadenomas, usually characterized by rapid growth. These tumors may behave like benign Benign Fibroadenoma fibroadenomas or may become malignant and metastasize. Phyllodes tumors are associated with Li-Fraumeni syndrome. Diagnosis is by core needle biopsy Core Needle Biopsy Fibrocystic Change and management involves complete resection, with adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma in malignant cases.

References

  1. Laronga, C., Tollin, S., and Mooney, B. (2019). Breast cysts: clinical manifestations, diagnosis, and management. In Chen, W. (Ed.), UpToDate. Retrieved February 3, 2021, from https://www.uptodate.com/contents/breast-cysts-clinical-manifestations-diagnosis-and-management
  2. Lester, S.C. (2005). The breast. In Kumar, V., Abbas, A.K., and Fausto, N. (Eds). Robbins and Cotran Pathologic Basis of Disease (7th ed., pp. 1127).
  3. Genova, R. (2020). Breast fat necrosis. In Garza, R. (Ed.), StatPearls. Retrieved 3 February  2021 from https://www.statpearls.com/articlelibrary/viewarticle/21634/ 
  4. Sabel, M.S. (2020). Overview of benign breast disease. In Chen, W. (Ed.), UpToDate. Retrieved 3 February 2021, from https://www.uptodate.com/contents/overview-of-benign-breast-disease

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