Breast lumps

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

Breast lumps are considered as one of the prevalent symptoms among women. Breast lumps can be found by individuals or clinical breast examination. Although, breast lumps are often determined as benign masses, they could be the first common presentation of breast cancer and require more clinical and imaging studies and medical interventions. Benign breast disease includes wide range of lesions which originate from either mammary epithelium or other mammary tissues. Breast lumps may be related to vascular, inflammatory or traumatic pathologies. Breast lumps are usually palpable, nodular masses and could be associated with or without particular characteristics. Breast lumps could also be found in children, adolescents and hopefully they are considered as benign tumors.The first step for evaluation of breast lumps is clinical examination then if examination was suspicious later imaging studies such as mammography, ultrasound or magnetic resonance imaging are required for further evaluation. Breast lumps management depends on disease pattern, available facilities and specialist.

Throughout the history many women experienced breast diseases but there were not any courage to express their problem to the public. In 1970s, all women with malignant breast lumps underwent radical mastectomy rather than performing previous biopsies. Although fine needle aspiration biopsy was introduce in 1930, it was used for breast lumps in 1950s. Breast ultrasound was used in 1950s and mammography was found in 1975 to diagnose early stages of breast cancers.

Breast lumps may be classified according to epithelial hyperplasia into 3 subtypes: non-proliferative, proliferative disease and proliferative disease without atypia. Breast lumps may be classified into 3 sub-types based on histological regions: lobular region, ductal region, different origins.

Breast development is influenced by different hormones such as estrogen, progesterone, prolactin, and estradiol. The pathophysiology of breast lumps depends on the histological subtypes. Histological findings of breast lumps are different from each other which lead to diagnosis. It is thought that breast lumps are the result of hormonal events and genetic mutations. Estrogen and progesterone may increase risk of benign proliferative disease to 74% and benign breast lesion in post-menopausal women receiving estrogen with or without progesteron for more than 8 years raise by 1.7 fold. Gene mutations are classified into 3 categories based on cancer risk such as BRCA1, BRCA2, TP53 considered as high risk mutations, Homozygous ataxia-telangiectasia, somatic mutation in CHEK2, BRIP1, PALB2 moderate risk mutations, and low risk genes mutation are not determined yet.

Breast lumps causes can be classified to various groups according to gender and age. Causes of female breast mass could be cancer, inflammatory, infectious, hormonal imbalance, trauma. Male breast enlargement identified as gynecomastia. Causes of gynecomastia may be multifactorial, hormonal imbalance, genetic factors, endocrine factors.Breast lumps may develop among children and adolescents, however, there are probably benign ones and related to peripubertal and pubertal phases.

Breast lumps must be differentiated from other diseases such as malignancy, cysts, inflammation and non-inflammatory solid lumps. Breast symptoms such as nipple discharge and mastalgia require assessment as well. Differentiating different types of breast lumps are based on imaging findings and breast clinical exam results.

The incidence rate of breast lumps is not particularly clear due to the fact that breast lumps is not considered as a life threatening condition and majority of the women who receives medical therapies or surgeries come into account.The prevalence of benign breast disease is approximately 68% among all breast diseases and the incidence of breast diseases is higher on the left upper/outer quadrant of breast. Fibrocystic diseases are more frequent in age of 40-44 years and fibroadenoma is more frequent between 15-35 years. Fibroadenoma rate is higher in black women. African-American women have worse prognosis and higher mortality rate in comparison European American women.

Risk factors of breast lumps are generally age (higher cancer risk while aging), past history of breast disease or biopsy, positive familial history in first-degree relatives, genetic mutations such as BRCA1 and BRCA2, endogenous hormonal exposure such as age at menarch, first pregnancy, menopause, breast feeding, and parity, exogenous hormonal exposure such as usage of contraceptive pills and hormonal replacement therapy, and lifestyle factors such as alcohol consumption, inactivity, obesity, and previous history of radiation exposure.

Screening for breast lumps is recommended by breast examination, ultrasound, mammography, magnetic resonance imaging.

If benign breast lumps left untreated, those proved to be benign both by clinical examination and cytological diagnosis, do not become malignant and 68% of benign breast lumps resolve by time mostly after 2 years. Benign breast lumps should approved to be benign both clinically and cytologicaly. Because some of breast lumps which thought to be benign ones can turn to be malignant by cytological results. Breast lumps which approved to be benign both clinically and cytologicaly in women under 35 years can resolve over time if do not excised.

Mammography is the gold standard test for the diagnosis of breast lumps in women aged >40 years old. Ultrasound is the gold standard test for the diagnosis of breast lumps in women aged <40 years old. Management and medical therapy of breast lumps depends on women’s age (age> 40 or age <40) and mammography results in women aged > 40 years. In women aged > 40 years; no further evaluation is needed in case of clearly benign mass in mammography; however, ultrasound imaging is required for the rest of the findings mammography. Approach to breast lumps in women >40 years is depended on breast imaging reporting and data systems (BI-RADS) stages. Medical therapy of breast lumps in women< 40 years is depended on ultrasound results and BI-RADS categories.

The important key to breast lumps diagnosis is history and physical exams. History must be complete and include all details regarding to age, parity, pregnancy, past history of breast diseases, familial history, and drug history. Common symptoms of breast lumps include breast pain, palpable mass, nipple discharge, galactorrhea.

Physical examination of patients with breast lumps should perform both in sitting position and supine position to examine all 4 quadrants of breast. Careful physical examination may lead to diagnosis. Breast physical exam should include information about, number, size, location, shape, mobility, consistancy of masses, nipple discharge, and axillary lymph nodes.

There are no diagnostic laboratory findings associated with breast lumps.

There are no ECG findings associated with breast lumps.

There are no x-ray findings associated with breast lumps.

Breast ultrasound is the first imaging modality in patients with palpable masses under age 40 years old and is adjunctive modality to mammography for patients older than 40 years. Breast sonography is a type of imaging used to confirm abnormal findings on mammography or MRI. Breast ultrasound improves breast cancer detection rate.

There are no CT scan findings associated with breast lumps.

MRI is considered as the primary imaging modality in selected patients and may be used when results of other imaging modalities are indeterminate. Breast MRI has some indications and does not use regularly. Breast MRI is not the primary modality for diagnosis of breast lumps and does not provide any additional findings to ultrasound and mammographic results and has both false-positive and false-negetive results.

Mammography is considered as the first and mainstay for evaluation of palpable masses in women over the age of 40 years. Diagnostic mammogram contains particular views by focal compression of specific part of breast tissue.There is standard method for reporting mammographic findings which is called breast imaging reporting and database system (BI-RADS) which is classified into 7 categories.

The only certain method to approve the presence of breast malignancy is breast lump biopsy.The three types of biopsies are core-needle biopsy, open surgical biopsy, and fine needle biopsy. Core-needle biopsy has different types such as ultrasound guided-core needle biopsy, stereotactic-guided core-needle biopsy, MRI-guided core-needle biopsy, and freehand core-needle biopsy. Core-needle biopsy has high sensitivity and specificity. Triple test score is used by surgeons for assessment of palpable breast lumps. Classic type of triple test includes clinical breast examination, FNA, and mammography and modified version includes clinical breast examination, core-needle biopsy and ultrasound.

There is no specific medical therapy for breast lump. However, there are certain medications that may be used prophylactically to reduce the risk of transformation of breast lump into breast carcinoma.

Surgical management of breast lumps depends on the type of masses based on core-needle biopsy. Atypical ductal hyperplasia, atypical lobular hyperplasia, lobular neoplasia, lobular carcinoma in situ, flat epithelial atypia. Multiple, peripheral and atypic papillomas, large sclerosing adenosis and radical scar >10mm, atypic and enlargic fibroadenomas, desmoid tumor, mammary fibromatosis, phyllodes tumor, symptomatic and large pseudoangiomatous stromal hyperplasia requires surgical consultation and excision. The rest of breast lumps require observation and follow-up. The final decision for excisional biopsy is based on recommendations from pathologist, radiologist, and surgeons.

There are no established measures for the primary prevention of breast lumps.

Secondary prevention of breast lumps consists of modifiable risk factors and preventive factors to decrease the rates of breast cancer. The protective factors include controlling alcohol consumption, weight control, physical activity, healthy diet, breast feeding, prophylactic bilateral oophorectomy for BRCA1 and BRCA2 carriers, hormonal replacement therapy avoidance, and use of tamoxifen for high risk women aged > 35 years. In order to reduce breast cancer recurrence, surveillance and follow-up by either physical examination and mammography are required.

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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]

Throughout the history many women experienced breast diseases but there were not any courage to express their problem to the public. In 1970s, all women with malignant breast lumps underwent radical mastectomy rather than performing previous biopsies. Although fine needle aspiration biopsy was introduce in 1930, it was used for breast lumps in 1950s. Breast ultrasound was used in 1950s and mammography was found in 1975 to diagnose early stages of breast cancers.

• Breast cancer influenced women throughout the history; however, American women did not speak about the breast cancer till 20th century.^[1]
• The American Society for the Control of Cancer (ASCC) established in 1913 with Elsie Mead and Marjorie Illigand leadership and changed to American Cancer Society in 1945.^[2]
• Babette Rosmond and Shirley Temple Black who were both diagnosed with breast cancer wrote a book about finding right to decide for performing biopsy before other treatment for breast lumps.^[3][4]
• Martin and Ellis introduce fine needle aspiration biopsy (FNAB) in 1930.^[5]
• The Scandinavians used FNAB for diagnosis of palpable breast lumps in 1950s.^[6]
• Mammography technique for detection of early stage of breast cancer has found over 80 years ago especially in 1975.^[7][8]
• The first application for using breast sonography was in 1950. Wild and Neal explained acoustical findings of both benign and malignant breast tumor.^[9]

• In 1970, surgeons constantly did radical mastectomy for malignant breast lumps found on biopsies.^[2]
• Radical mastectomy approach for breast lumps was first presented by George Crile.^[3]

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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]

Breast lumps may be classified according to epithelial hyperplasia into 3 subtypes: non-proliferative, proliferative disease and proliferative disease without atypia. Breast lumps may be classified into 3 sub-types based on histological regions: lobular region, ductal region, different origins.

Classification of breast lumps based on epithelial hyperplasia:^[1][2][3]

• Approximately 65% of all benign breast disease considered as non-proliferative (NP) with relative cancer risk of 1.2 – 1.4 times:
  • Cyst (most common)^[4]
  • Fibrosis
  • Fibroadenoma (simple)
  • Columnar alteration (Simple)
  • Apocrine metaplasia (simple)
  • Mild ductal hyperplasia
• Approximately 30% of total are classified as proliferative disease (PD) with relative cancer risk of 1.7 – 2.1 times:^[5]
  • Usual ductal hyperplasia
  • Sclerosing adenosis
  • Columnar hyperplasia
  • Papilloma
  • Radical scar
• Approximately 5% to 8% of the rest are regarded as PD with atypia and relative cancer risk more than 4 times:^[6]
  • Atypical lobar hyperplasia
  • Lobular carcinoma in situ
  • Atypical ductal hyperplasia
• Unclear risk
  • Mucocele like tumor
  • Apocrine atypia
  • Secretory atypia

Classification of benign breast lesion according to histological region:^[7]

• Terminal and lobular ducts
  • Acinar distention
    • Cyst
  • Intralobular connective tissue proliferation
    • Sclerosing adenosis
    • Fibroadenoma
    • Phyllodes tumor
    • Hamartoma
  • Epithelial changes in terminal duct lobular units (TDLU)
    • Apocrine metaplasia
    • Ductal and lobular hyperplasia, usual and typical
    • Papillomatosis
    • Intracystic papilloma
• Ductal system
  • Ductal ectasia
  • Intraductal papilloma
• Lesion of different origin
  • Fatty tissue lesion
    • Lipoma
    • Liponecrosis
  • Fibrous tissue lesions
    • Focal fibrosis
    • Diabetic mastopathy or lymphocytic mastitis or lymphocytic mastopathy^[8][9]
    • Pseudoangiomatous stromal hyperplasia (PASH)
    • Myofibroblastoma
  • Vascular origin
    • Hemangioma
  • Inflammatory origin
    • Mastitis/abscess
    • Tuberculosis and sarcoidosis
    • Foreign body granuloma and siliconoma
  • Lymph node origin
    • Inflammatory lymph nodes

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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]

Breast development is influenced by different hormones such as estrogen, progesterone, prolactin, and estradiol. The pathophysiology of breast lumps depends on the histological subtypes. Histological findings of breast lumps are different from each other which lead to diagnosis. It is thought that breast lumps are the result of hormonal events and genetic mutations. Estrogen and progesterone may increase risk of benign proliferative disease to 74% and benign breast lesion in post-menopausal women receiving estrogen with or without progesteron for more than 8 years raise by 1.7 fold. Gene mutations are classified into 3 categories based on cancer risk such as BRCA1, BRCA2, TP53 considered as high risk mutations, Homozygous ataxia-telangiectasia, somatic mutation in CHEK2, BRIP1, PALB2 moderate risk mutations, and low risk genes mutation are not determined yet.

• Mammary gland development, maturation, and differentiation is controlled by hormones through their action on epithelial and stromal cells:^[1][2][3]
  • Estrogen: Development of ductal tissue
  • Progesterone: Ductal branching and lobulo-alveolar development
  • Prolactin: Milk protein production
  • Estradiol and progesterone: Breast development at puberty
  • Estrogen and progesterone: Cell proliferation during luteal phase

Histological changes of breast undergo continuous changes throughout the life:^[4]

• Fibrocystic disease
  • Histological apperance change from predominance of ducts, lobules to fibrous change, and cyst formation
  • Fibrocystic changes are not associated with breast cancer

• Specific changes during the period of times:
  • Early reproductive ages^[5]
    • Stromal hyperplasia, unilateral or bilateral macromastia
  • Middle reproductive ages^[6]
    • Substantial changes in glandular breast tissue result in adenosis
    • Stromal hyperplasia may result into ill-defined fullness areas called lumpy-bumpy consistency or firm areas which may require biopsy
    • No ductal changes
  • Late reproductive period^[6]
    • Hyperplastic glandular tissue with sclerosing adenosis or lobular hyperplasia
      • Hyperplastic glandular lesions may require biopsy
    • Hyperplastic ductal tissue

• Diagnostic subtypes and histologic subtypes are described according to their relative risk for cancer as below:^[7]

Diagnostic Subtypes

Diagnostic Subtypes	Breast cancer relative risk
Non-proliferative disease	1.17
Proliferative disease without atypia	1.76
Benign breast disease	2.07
Atypical hyperplasia	3.93

Histologic Subtypes

Histological subtypes	Relative risk|Breast cancer relative risk
Adenosis	2.00
Atypical ductal hyperplasia	3.28
Atypical lobular hyperplasia	3.92
Cysts	1.55
Fibroadenoma	1.41
Papilloma	2.06

Histological findings of breast lumps

Breast lumps	Histological findings
Atypical hyperplasia[8]	Clonal neoplastic proliferations is present.
Atypical ductal hyperplasia (ADH)[9]	Localized intraductal proliferations,having some microscopic features of ductal carcinoma in situ (DCIS), usually associated with calcification, duct spaces consist of complex proliferation of monotonous luminal-type cells by creating bridging feature. Differentiation of ADH from DCIS : ADH has less cytological atypia than DCIS. Distribution in severe ADH is restricted to less than 3 contiguous ducts and less than 0.2 cm in size.
Lobular neoplasia[10]	Associated to decrease expression or missing expression of E-cadherine, lobular neoplasia is considered to be as incidental findings in during microcalcification evaluation.
Atypical lobular hyperplasia (ALH)[11]	ALH is containing monomorphic cells and distend into lobular acini and adjacent terminal ducts. Differentiation between ALH and lobular carcinoma in situ (LCIS) associated with quantitative degrees about lobules and architecture feature.
Apocrine proliferative lesions[12]	Apocrine atypia is described by a 3-fold variation in nuclear size or by cribriform structures with nuclear atypia, associated with sclerosing adenosis or complex sclerosing lesion.
Columnar cell lesions (CCL)[13]	CCL has heterogeneous set of lesions distinguished by reduplication and microcystic changes in lobular acini, elevated estrogen receptor expression, increased proliferative rate, associated with sclerosing adenosis, clacification and pleomorphic appearnace.
Papillary lesions[14]	Arborescent fibrovascular stalk lined to the myoepithelium are present.
Radical scars and complex sclerosing lesions[15]	Radial scars are tumor like lesions with stellate nidus of dense elastotic collagen, surrounding with epithelial elements and sclerosing adenosis. Complex sclerosing lesions are kind of radial scars larger than 1 cm which has distorted glandular tissue.
Fibroadenoma[16]	Consist of disposed compressed glands within collagenous stroma. Complex fibroadenomas: containing sclerosing adenosis, calcifications, papillary hyperplasia.
Phyllodes tumor[17]	Prominent and hypercellular stromal feature expanded to epithelial of tumor. Classified to benign, borderline, and malignant on the basis of stromal mitotic rate, cytology and degree of stromal overgrowth.
Pseudoangiomatous Stromal Hyperplasia[18]	Composed of dense collagen, slit like spaces resulting from fibroblast proliferation resembling blood vessels in the stroma between lobular units.
Sclerosing adenosis[19]	Increase in lobular acini number, enriched in myoepithelial cells.

• It is understood that breast lumps are the result of hormonal events:^[20]
  • Prevalence of benign breast lesion in post-menopausal women receiving estrogen with or without progesteron for more than 8 years raise by 1.7 fold.
  • Estrogen and progesterone increase rate of benign proliferative breast disease to 74%.^[21]
  • Anti-estrogen drugs such as tamoxifen, decrease prevalence of breast lesions such as adenosis, cysts, hyperplasia, duct ectasia to 28%.^[22]

• Although estrogen receptors (ER) and progesterone-receptor (PR) attributed to weak prognosis, they may predict patients’ response to endocrine therapy.^[23]
  • Assessment of presence of ER and PR are required in invasive breast cancers.
  • ER-positive result is present in 70% of breast cancers and PR-positive result is present in 60% of breast cancers.^[24]
• HER2/neu is a proto-oncogene which involves in breast regulatory pathways such as proliferation, cell motility and invasion.^[25][26]
  • In 10% to 34% of breast cancers, overexpression and amplification of HER2 is reported.
  • In 90% of cases, overexpression, amplification, and surface membrane protein expressions of HER2/neu may be seen.

• Breast lumps is associated with deletion of small segments of DNA (loss of heterozigosity).^[27]
• The development of breast lumps is the result of multiple genetic mutations such as:
  • High risk genes mutations:^[28]
    • BRCA1
    • BRCA2
    • TP53 resulting in Li-Fraumeni syndrome
    • PTEN resulting in Cowden syndrome
    • STK11 resulting in Peutz-Jegher’s syndrome, Neurofibromatosis (NF1) and (CDH-1) E-Cadherin
  • Moderate risk genes mutations:^[29][30][31]
    • Homozygous ataxia-telangiectasia (ATM)
    • Somatic mutations in CHEK2
    • BRIP1: BRCA1 modifier
    • PALB2: BRCA2 modifier
  • Low risk genes mutations:^[32]
    • Clinical determination of these genes have not determined yet

• There are no other associated conditions with breast lumps.

Gross findings	Gross pathology
Fibrotic capsule and infiltrated the surrounding tissue[33] Gray-white color and moderately increased consistency
Stellate area of cancer 2cm in diameter Felt as a hard mobile mass Histology as a moderately well differentiated duct carcinoma

Pathologic findings	Microscopic image
Phyllodes tumor is a tumor of the intralobular breast stroma and it may be benign or malignant with large slit-like spaces. It is a type of fibroepithelial tumor.
Sclerosing adenosis microscopic pathology has increased numbers of small breast acini with collapsed lumens, fibrosis surrounds the acini, considered as benign lesion with increased risk of breast cancer.
ADH, based on a molecular basis, is a low-grade DCIS with localized proliferation.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jyostna Chouturi, M.B.B.S [2], João André Alves Silva, M.D. [3], Shadan Mehraban, M.D.[4]

Breast lumps causes can be classified to various groups according to gender and age. Causes of female breast mass could be cancer, inflammatory, infectious, hormonal imbalance, trauma. Male breast enlargement identified as gynecomastia. Causes of gynecomastia may be multifactorial, hormonal imbalance, genetic factors, endocrine factors.Breast lumps may develop among children and adolescents, however, there are probably benign ones and related to peripubertal and pubertal phases.

There are no life-threatening causes.^[1]

The most common causes of breast lumps in females are:^{[1][2][3][4][5]}

• Benign inflammatory periductal mastitis
• Breast abscess
• Breast cancer
• Breast adenoma
• Breast trauma
• Cysts of Montgomery
• Duct ectasia of breast
• Estrogen and progestin
• Etonogestrel and ethinyl estradiol
• Fibro-adeno-lipoma
• Galactocele
• Glandular thickening due to hormonal changes of pregnancy
• Gynecomastia
• Hematoma
• Hypertrophy
• Intramammary lymph node
• Lipoma
• Premenstrual syndrome
• Progestin
• Retroareolar cyst
• Simple cyst

Cardiovascular	Angiosarcoma of the breast, Mondor’s disease
Chemical/Poisoning	No underlying causes
Dental	No underlying causes
Dermatologic	Breast abscess,Cysts of Montgomery, epithelioma of the nipple, hives, intraductal papilloma, lymphocytoma cutis, Paget’s disease of the breast, retroareolar cyst, sclerosing adenosis, sebaceous cyst, skin lumps, Zuska’s disease
Drug Side Effect	Aldactone, aldomet (alphamethyldopa),alefacept, beta blockers, bicalutamide, casodex, chlorpromazine, cyclosporine, dalmane , digitalis, estazolam, etonogestrel, hormone replacement therapy, efalizumab, estradiol, estrogen, estrogen and progestin, etanercept, etonogestrel and ethinyl estradiol, flurazepam, flutamide, itraconazole, implanon, medroxyprogesterone, metoclopramide, norelgestromin and ethinyl estradiol, nilandron, nizoral, oral contraceptive pills,progestin
Ear Nose Throat	No underlying causes
Endocrine	Aberration of normal development and involution (ANDI), breast fibroadenoma, chronic cystic mastitis, fibro-adenosis of the newborn, fibroadenoma, galactocele, giant fibroadenoma, glandular thickening due to hormonal changes of pregnancy, hormone replacement therapy,hyalinized fibroadenoma, lactation, premenstrual syndrome, puberty, simple cyst
Environmental	No underlying causes
Gastroenterologic	No underlying causes
Genetic[5]	Aberration of normal development and involution (ANDI), adenoid cystic carcinoma, apocrine metaplasia, apocrine or squamous metaplasia, apocrine papillary carcinoma, ataxia-telangiectasia heterozygosity, breast cancer, cancer, colloidal breast cancer, Cowden syndrome, cyclosporine, cyst wall cancer, ductal carcinoma, extramedullary myeloid tumor, giant mammary hamartoma, hamartoma, hereditary diffuse gastric cancer, Hodgkin’s disease, inflammatory breast cancer, juvenile secretory carcinoma, Li-Fraumeni syndrome, lymphoma, malignant carcinoma, medullary carcinoma, metastatic breast cancer, metastatic cancer, mucinous carcinoma, Peutz-Jeghers syndrome, primary breast cancer, PTEN hamartoma tumor syndrome
Hematologic	Extramedullary myeloid tumor, Hodgkin’s disease, lymphoma, medullary carcinoma, rhabdomyosarcoma, sarcoma, venous thrombosis
Iatrogenic	Abscess, alefacept, breast abscess, breast fat necrosis, breast implant, complicated cyst, cyclosporine, efalizumab, estradiol, estrogen, estrogen and progestin, etanercept, etonogestrel and ethinyl estradiol, hematoma, medroxyprogesterone, norelgestromin and ethinyl estradiol, postoperative scar/hematoma, progestin, radial scar, radiation induced angiosarcoma of the breast
Infectious Disease[6]	Abscess, acute mastitis, benign inflammatory periductal mastitis, breast abscess, breast cyst, breast infection, tuberculosis of the breast
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	Ataxia-telangiectasia heterozygosity
Nutritional/Metabolic	ginseng
Obstetric/Gynecologic[7]	Aberration of normal development and involution (ANDI), adenoid cystic carcinoma, apocrine metaplasia, apocrine or squamous metaplasia, apocrine papillary carcinoma, benign inflammatory periductal mastitis, breast abscess, breast cancer, breast duct papilloma, breast fat necrosis, breast fibroadenoma, breast implant, breast injury,breast trauma, chronic cystic mastitis, colloidal breast cancer, complicated cyst, cowden syndrome, cyst wall cancer, cystosarcoma phyllodes, cysts of Montgomery, duct ectasia of breast, ductal carcinoma, epithelioma of the nipple, fat necrosis, fibro-adeno-lipoma, fibro-adenosis of the newborn, fibroadenoma, galactocele, giant fibroadenoma, giant mammary hamartoma, glandular thickening due to hormonal changes of pregnancy, gynecomastia, hyalinized fibroadenoma, intraductal papilloma, lactation, Li-Fraumeni syndrome, lobular neoplasia, lymphocytic mastitis, mammary duct ectasia, mastitis, metastatic breast cancer, mucinous carcinoma, nipple conditions., paget’s disease of the breast, periductal mastitis, phyllodes tumor, plasma cell mastitis, primary breast cancer, pseudoangiomatous stromal hyperplasia, retroareolar cyst, ruptured cyst or duct, sclerosing adenosis, tuberculosis of the breast, Zuska’s disease
Oncologic[8]	Adenoid cystic carcinoma, angiosarcoma of the breast, apocrine papillary carcinoma, ataxia-telangiectasia heterozygosity, benign breast disease, breast cancer, cancer, colloidal breast cancer, cyst wall cancer, cystosarcoma phyllodes, desmoplastic small round cell tumor, ductal carcinoma, epithelioma of the nipple, extramedullary myeloid tumor, hereditary diffuse gastric cancer, Hodgkin’s disease, inflammatory breast cancer, juvenile secretory carcinoma, Li-Fraumeni syndrome, lymphoma, malignant carcinoma, medullary carcinoma, metastatic breast cancer, metastatic cancer, metastatic cancer, mucinous carcinoma, paget’s disease of the breast, Peutz-Jeghers syndrome, phyllodes tumor, primary breast cancer, PTEN hamartoma tumor syndrome, radiation induced angiosarcoma of the breast, rhabdomyosarcoma, sarcoma, secretory breast carcinoma
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal/Electrolyte	No underlying causes
Rheumatology/Immunology/Allergy	Benign inflammatory periductal mastitis, cysts of Montgomery, desmoplastic small round cell tumor, hives, inflammatory breast cancer, intramammary lymph node, lymphatic obstruction, lymphocytoma cutis, lymphocytic mastitis, mastitis, Mondor’s disease, periductal mastitis, plasma cell mastitis, Zuska’s disease
Sexual	No underlying causes
Trauma	Breast fat necrosis, breast injury, breast trauma, blow on the breast, fat necrosis, hematoma, ruptured cyst or duct, traumatic fat necrosis,
Urologic	No underlying causes
Miscellaneous	Fibro-adeno-lipoma, hypertrophy, lipoma, lymphatic obstruction, oil cyst, postoperative scar/hematoma, radial scar, ruptured cyst or duct, venous thrombosis,

There are no life-threatening causes.

Breast enlargement in male adolescents is defined as gynecomastia. Common causes of breast lumps in male include:^{[9][10][11][12][13][14]}

• Adipose tissue
• Aging– more common in older men as male hormones reduce.
• Breast abscess
• Breast cancer
• Hepatoma
• Hyperthyroidism
• Hypogonadism
• Metastatic cancer
• Neurofibroma
• XXY males

Cardiovascular[15]	Cantalamessa-baldini-ambrosi syndrome
Chemical/Poisoning	No underlying causes
Dental	No underlying causes
Dermatologic	Cantalamessa-baldini-ambrosi syndrome, gingival fibromatosis hypertrichosis, H syndrome, Pachydermoperiostosis ,
Drug Side Effect	Aldactone, bicalutamide, chloropromazine, cimetidine, flutamide, itraconazole, metoclopramide, nizoral
Ear Nose Throat	Gingival fibromatosis hypertrichosis, H syndrome, Retinitis pigmentosa, deafness, mental retardation, hypogonadism- syndrome
Endocrine[16]	17-beta-hydroxysteroid dehydrogenase deficiency , Androgen insensitivity syndrome , Brugschs syndrome, Camera-marugo-cohen syndrome, Cantalamessa-baldini-ambrosi syndrome, Congenital adrenal hyperplasia 17-alpha-hydroxylase deficiency, 3-beta-hydroxysteroid dehydrogenase deficiency, Empty sella syndrome , Feminization, Forbes-Albright syndrome , luteinizing hormone releasing hormone deficiency, Gynecomastia, H syndrome, Hanhart syndrome, Heller-nelson syndrome, Hormone replacement therapy, Hyperprolactinemia, Klinefelter syndrome, Lactotroph adenoma, Newborn infant breast swelling, Obal syndrome, Partial androgen insensitivity, Primrose syndrome, pseudohermaphroditism male,Puberty, Salvioli syndrome, Sohval-Soffer syndrome, Summitt syndrome, Tang Hsi Ryu syndrome, Vasquez Hurst Sotos syndrome, Wilson turner syndrome, XX male syndrome, de la chapelle syndrome
Environmental	No underlying causes
Gastroenterologic	Cirrhosis of the liver, Hepatocellular carcinoma (fibrolamellar variant), Peutz-Jeghers syndrome, Tang Hsi Ryu syndrome
Genetic[12]	17-beta-hydroxysteroid dehydrogenase deficiency, 46,XX testicular disorder of sex development, Androgen insensitivity syndrome , Brugschs syndrome, Congenital adrenal hyperplasia 17-alpha-hydroxylase deficiency, 3-beta-hydroxysteroid dehydrogenase deficiency, Fragile X syndrome, Klinefelter syndrome, Lesch-Nyhan’s syndrome, Obal syndrome, Summitt syndrome, Tang Hsi Ryu syndrome, Vasquez Hurst Sotos syndrome, XX male syndrome, de la chapelle syndrome
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	Lymphatic filariasis,
Musculoskeletal/Orthopedic	Brugschs syndrome, Camera-marugo-cohen syndrome, Lesch-Nyhan’s syndrome, Salvioli syndrome, Sohval-Soffer syndrome,Summitt syndrome
Neurologic	Camera-marugo-cohen syndrome, Fragile X syndrome,progressive spinobulbar muscular atrophy, Retinitis pigmentosa, deafness, mental retardation, hypogonadism, Sohval-Soffer syndrome, Spinal muscular atrophy, Summitt syndrome, Tang Hsi Ryu syndrome, Vasquez Hurst Sotos syndrome, wilson turner syndrome,
Nutritional/Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	Breast cancer
Ophthalmologic	Cantalamessa-baldini-ambrosi syndrome, Obal syndrome, Retinitis pigmentosa, deafness, mental retardation, hypogonadism.
Overdose/Toxicity	No underlying causes
Psychiatric	sexual arousal
Pulmonary	No underlying causes
Renal/Electrolyte	No underlying causes
Rheumatology/Immunology/Allergy	No underlying causes
Sexual	sexual arousal
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	No underlying causes

• Neonates and infants ^[17]
  • Breast hypertrophy due to maternal hormones
• Prepubertal and pubertal children^[18][19]
  • Breast infection
  • Hemangiomas and lymphangiomas
  • Lipomastia
  • Premature Thelarche and Thelarche
  • Trauma

• Breast enlargement in male adolescents is defined as gynecomastia:^[20]
  • Persistent pubertal gynecomastia
  • Drugs^[21]
    • spironolactone
    • Cimetidine
    • Ketoconazole
    • Recombinant human growth hormone,
    • Estrogens
    • Antiandrogens
    • Gonadotropin-releasing hormone (GnRH) agonists
    • 5-alpha-reductase inhibitors
    • Human chorionic gonadotropin (hCG)
  • Idiopathic
  • Cirrhosis
  • Malnutrition
  • Hyperthyroidism
  • Hypogonadism
  • Testicular tumors
  • Chronic renal insufficiency

• Fibrocystic change^[22]
• Juvenille fibroadenoma^[23]
• Giant fibroadenoma^[17]
• Phyllodes tumor^[24][25]
• Mammary duct ectasia^[26]
• Cysts of montgomery^[19]

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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], Sadaf Sharfaei M.D.[3]

Breast lumps must be differentiated from other diseases such as malignancy, cysts, inflammation and non-inflammatory solid lumps. Breast symptoms such as nipple discharge and mastalgia require assessment as well. Differentiating different types of breast lumps are 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

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[1]	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[2]	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[3]	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[4][5]	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[6]	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[7]	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[8][9]	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[10][11]	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[12][13][14]	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)[15][16]	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[17]	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[18]	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[19][20]	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[21][22]	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[23]	Benign	Common among perimenopausal women	Usually resolve spontaneously	±	±	±	Usually asymptomatic	–	–	Distention of subareolar ducts	Ultrasound: Dilated milk ducts Fluid-filled ducts	Ultrasound
Intraductal papilloma[24]	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[25]	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[26][27]	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[28][29]	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[30][31]	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[32]	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[33][34]	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[35]	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[36]	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: Shadan Mehraban, M.D.[2]

The incidence rate of breast lumps is not particularly clear due to the fact that breast lumps is not considered as a life threatening condition and majority of the women who receives medical therapies or surgeries come into account.The prevalence of benign breast disease is approximately 68% among all breast diseases and the incidence of breast diseases is higher on the left upper/outer quadrant of breast. Fibrocystic diseases are more frequent in age of 40-44 years and fibroadenoma is more frequent between 15-35 years. Fibroadenoma rate is higher in black women. African-American women have worse prognosis and higher mortality rate in comparison European American women.

• The incidence rate of benign breast disease is unclear due to the fact that breast lumps is not considered as a life threatening condition.^[1]
• Majority of the women who receives medical therapies or surgeries come into account.
• Particular detection rate is unknown and not estimated.

• The prevalence of benign breast disease is approximately 68% among all breast diseases.^[2]
• Approximately 60% of benign breast diseases occur in left breast and 40% in the right breast.
• 100% of definite palpable lumps are characteristics of fibroadenoma, phyllodes tumor, and adenomyoepithelioma.
• 64% of lumps located in upper outer quadrant, 26% of lumps in lower outer quadrant, 10% of lumps in upper inner quadrant.

Age-specific incidence rate of benign breast diseases.^[1]

• The incidence rate of fibrocystic disease is 137 per 100,000 in women aged 25-29 years, 411 per 100,000 in age of 40-44 years and 387 per 100,000 in 45-49 years.
• The incidence rate of fibroadenoma is 115 per 100,000 in women aged 20-24 years.
• The peak incidence rate of fibroadenoma is between 15-35 years.^[3]
• Fibrocystic disease, phyllodes tumor, and adenomyoepithelioma are usually seen in 3rd and 4th decade of life.^[2]

• African American women have worse prognosis and higher mortality rate in comparison to European American women.^[4]
• European American women have higher incidence rate of breast cancers.
• The prevalence of fibroadenoma is higher in black women than white individuals.^[5]

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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]

Risk factors of breast lumps are generally age (higher cancer risk while aging), past history of breast disease or biopsy, positive familial history in first-degree relatives, genetic mutations such as BRCA1 and BRCA2, endogenous hormonal exposure such as age at menarch, first pregnancy, menopause, breast feeding, and parity, exogenous hormonal exposure such as usage of contraceptive pills and hormonal replacement therapy, and lifestyle factors such as alcohol consumption, inactivity, obesity, and previous history of radiation exposure.

Risk factors leading to female breast cancer:^[1][2]

• Age: probability of breast cancer during the age groups is as follows:
  • Birth to 39 years – 1 in 202
  • 40 to 59 years – 1 in 26
  • 60 to 69 years – 1 in 28.
• Personal history of benign breast biopsy associated with relative risk of 1.7 and history of atypical hyperplasia on biopsy with relative risk of 3.7.
• Breast pathology: Proliferative disease (PD) with atypia has greater risk of developing to breast cancer in comparison of PD.
• Family history: Greater breast cancer risk in women with first-degree relatives with breast cancer under 50 years old.
• Genetic predisposition
  • High risk (associated with relative risk about 3.0 to 7.0)
    • BRCA1
    • BRCA2
  • Moderate risk
    • Homozygous ataxia-telangiectasia (ATM)
    • Somatic mutation in CHEK2
    • BRCA1 modifier gene: BRIP1
    • BRCA2 modifier gene: PALB2
  • Low risk
    • These alleles have not designated yet
• Endogenous hormone exposure and reproductive factors:
  • Early menarche: Under age of 13 years
  • Parity: Nulliparus is associated with increased risk of breast cancer
  • Age at first full term pregnancy: Younger age ( under 20 years considered as low risk and after 30 years old considered as high risk ) may decrease risk of breast cancer
  • Breast feeding > 16 months decreased risk of breast cancer
  • Testosterone: Increased relative risk to 2.86-3.28
  • Age at menopause: Older menopausal age (aged > 55 years ) associated with greater risk of breast cancer
• Exogenous hormone exposure
  • Long term exposure> 5 years: increases chances of breast cancer
  • Time of usage: nearly menopausal age associated with development to breast cancer
  • Part or current use of contraceptive pills: relative risk of 1.07 to 1.2
  • Current use of hormonal replacement therapy: relative risk of 1.2
• Lifestyle: These factors may increase risk of developing breast cancers.
  • Alcohol consumption: approximately 2 to 5 drinks per day, developed with relative risk 1.4
  • Recreational exercise: relative risk of 0.70
  • Obesity: BMI = 25-29.9 and BMI >30 have relative risk of 1.28
  • Previous history of radiation: at the age < 35 years old

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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]

Screening for breast lumps is recommended by breast examination, ultrasound, mammography, magnetic resonance imaging.

The Screening methods of breast lesions:^[1]

• Breast examination
  • Self breast examination
    • Although this is controversial, most clinicians recommend women to perform self examination monthly.
  • Clinical breast examination
    • Women with age> 40 years is recommended to have clinical breast examination, annually.
• Ultrasound
  • Whole breast ultrasound detects lesions in dense breast tissue which could not be diagnosed by mammography.^[2]
• Mammography^[3]
  • Gold standard test of screening
  • Early detection of non-palpabale masses
  • According to 2013 NCCN guidelines
    • Annual screening in average risk women aged ≥ 40 years
    • Annual screening in high risk women from age of 25 years
  • Sensitivity of 0.33-0.39 and specificity of 0.95
• Magnetic resonance imaging^[3][4]
  • Significant method for detection, assessment, and management of breast cancer
  • Sensitivity of 0.77-0.79 and specificity of 0.86-0.89
  • According on 2013 NCCN guidelines
    • Annual MRI for individuals with > 20% risk of developing breast cancer in lifetime starting at age of 25 years
  • Beneficial modality for screening in high risk individuals
  • Valuable screening method in individuals with equivocal results from other screening tests
  • Usable for individuals with ineffective mammography results due to breast augmentation

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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]

If benign breast lumps left untreated, those proved to be benign both by clinical examination and cytological diagnosis, do not become malignant and 68% of benign breast lumps resolve by time mostly after 2 years. Benign breast lumps should approved to be benign both clinically and cytologicaly. Because some of breast lumps which thought to be benign ones can turn to be malignant by cytological results. Breast lumps which approved to be benign both clinically and cytologicaly in women under 35 years can resolve over time if do not excised.

• Natural history of breast lumps is not well-studied and the related information is limited. ^[1]
• In order to prevent missed malignancy and patient’s reassurance, benign breast lumps may be excised.
• The symptoms of benign breast lumps, especially fibroadenomas, usually develop in the second and third decade of life, and discrete breast lumps are considered to be benign on the basis of clinical examination.
• If left untreated, 68% of patients with benign breast lumps may regress over 2 years.
• The histological mechanism for resolution of breast lumps is associated with the fact that lumps may merge into stroma and hyalinize.^[2]
• The risk of malignancy in fibroadenoma is low.^[3]
• No adenocarcinoma reported in fibroadenoma yet, only lobular neoplasia was seen in fibroadenoma.^[4]

• Common complications of breast lumps include:
  • May develop into malignant lesion^[1]

The relative risk (RR) of following breast cancer in different types of breast lumps:^[5][6][7]

• Non-proliferative breast lesions have RR 1.2-1.4.
• Proliferative diseases (PD) have RR 1.7-2.1.
• Proliferative diseases (PD) with atypia have RR more than 4 for breast cancer.
• PD and PD with atypia may be considered as early stages of breast cancer.

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