Breast cancer differential diagnosis

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

Overview

Breast cancer 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 breast cancer different types of breast lumps are based on imaging findings and breast clinical exam results.

Differentiating Breast cancer from other Diseases

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	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	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	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	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	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	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	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	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	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)	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	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	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	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	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	Benign	Common among perimenopausal women	Usually resolve spontaneously	±	±	±	Usually asymptomatic	–	–	Distention of subareolar ducts	Ultrasound: Dilated milk ducts Fluid-filled ducts	Ultrasound
Intraductal papilloma	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	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	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	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	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	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	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	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	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