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[edit | edit source]

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[edit | edit source]

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

## References[edit | edit source]

1. ↑ Pinto, Joana; Aguiar, Ana Teresa; Duarte, Hálio; Vilaverde, Filipa; Rodrigues, Ângelo; Krug, José Luís (2014). "Simple and Complex Fibroadenomas". Journal of Ultrasound in Medicine. 33 (3): 415–419. doi:10.7863/ultra.33.3.415. ISSN 0278-4297.
2. ↑ Courtillot C, Plu-Bureau G, Binart N, Balleyguier C, Sigal-Zafrani B, Goffin V; et al. (2005). "Benign breast diseases". J Mammary Gland Biol Neoplasia. 10 (4): 325–35. doi:10.1007/s10911-006-9006-4. PMID 16900392.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
3. ↑ Templeman C, Hertweck SP (2000). "Breast disorders in the pediatric and adolescent patient". Obstet Gynecol Clin North Am. 27 (1): 19–34. PMID 10693180.
4. ↑ Yu JH, Kim MJ, Cho H, Liu HJ, Han SJ, Ahn TG (2013). "Breast diseases during pregnancy and lactation". Obstet Gynecol Sci. 56 (3): 143–59. doi:10.5468/ogs.2013.56.3.143. PMC 3784111. PMID 24327995.CS1 maint: Multiple names: authors list (link)
5. ↑ Sabate JM, Clotet M, Torrubia S, Gomez A, Guerrero R, de las Heras P; et al. (2007). "Radiologic evaluation of breast disorders related to pregnancy and lactation". Radiographics. 27 Suppl 1: S101–24. doi:10.1148/rg.27si075505. PMID 18180221.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
6. ↑ De Silva NK, Brandt ML (2006). "Disorders of the breast in children and adolescents, Part 2: breast masses". J Pediatr Adolesc Gynecol. 19 (6): 415–8. doi:10.1016/j.jpag.2006.09.002. PMID 17174833.
7. ↑ Tse GM, Law BK, Ma TK, Chan AB, Pang LM, Chu WC; et al. (2002). "Hamartoma of the breast: a clinicopathological review". J Clin Pathol. 55 (12): 951–4. PMC 1769817. PMID 12461066.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
8. ↑ D'Alfonso TM, Ginter PS, Shin SJ (2015). "A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples". J Pathol Transl Med. 49 (4): 279–87. doi:10.4132/jptm.2015.06.11. PMC 4508565. PMID 26095437.CS1 maint: Multiple names: authors list (link)
9. ↑ Dixon JM (2007). "Breast abscess". Br J Hosp Med (Lond). 68 (6): 315–20. doi:10.12968/hmed.2007.68.6.23574. PMID 17639835.
10. ↑ Dixon JM, Ravisekar O, Chetty U, Anderson TJ (1996). "Periductal mastitis and duct ectasia: different conditions with different aetiologies". Br J Surg. 83 (6): 820–2. PMID 8696751.CS1 maint: Multiple names: authors list (link)
11. ↑ Committee on Health Care for Underserved Women, American College of Obstetricians and Gynecologists (2007). "ACOG Committee Opinion No. 361: Breastfeeding: maternal and infant aspects". Obstet Gynecol. 109 (2 Pt 1): 479–80. PMID 17267864.
12. ↑ Siegel RL, Miller KD, Jemal A (January 2018). "Cancer statistics, 2018". CA Cancer J Clin. 68 (1): 7–30. doi:10.3322/caac.21442. PMID 29313949.
13. ↑ Li CI, Uribe DJ, Daling JR (October 2005). "Clinical characteristics of different histologic types of breast cancer". Br. J. Cancer. 93 (9): 1046–52. doi:10.1038/sj.bjc.6602787. PMC 2361680. PMID 16175185.
14. ↑ Parise CA, Bauer KR, Brown MM, Caggiano V (2009). "Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999-2004". Breast J. 15 (6): 593–602. doi:10.1111/j.1524-4741.2009.00822.x. PMID 19764994.
15. ↑ Virnig BA, Tuttle TM, Shamliyan T, Kane RL (February 2010). "Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes". J. Natl. Cancer Inst. 102 (3): 170–8. doi:10.1093/jnci/djp482. PMID 20071685.
16. ↑ Brinton LA, Sherman ME, Carreon JD, Anderson WF (November 2008). "Recent trends in breast cancer among younger women in the United States". J. Natl. Cancer Inst. 100 (22): 1643–8. doi:10.1093/jnci/djn344. PMC 2720764. PMID 19001605.
17. ↑ Sue GR, Lannin DR, Killelea B, Chagpar AB (October 2013). "Predictors of microinvasion and its prognostic role in ductal carcinoma in situ". Am. J. Surg. 206 (4): 478–81. doi:10.1016/j.amjsurg.2013.01.039. PMID 23791403.
18. ↑ Smith TB, Gilcrease MZ, Santiago L, Hunt KK, Yang WT (April 2012). "Imaging features of primary breast sarcoma". AJR Am J Roentgenol. 198 (4): W386–93. doi:10.2214/AJR.11.7341. PMID 22451578.
19. ↑ Geisler DP, Boyle MJ, Malnar KF, McGee JM, Nolen MC, Fortner SM, Broughan TA (April 2000). "Phyllodes tumors of the breast: a review of 32 cases". Am Surg. 66 (4): 360–6. PMID 10776873.
20. ↑ Chaney AW, Pollack A, McNeese MD, Zagars GK, Pisters PW, Pollock RE, Hunt KK (October 2000). "Primary treatment of cystosarcoma phyllodes of the breast". Cancer. 89 (7): 1502–11. PMID 11013364.
21. ↑ Brogi E, Harris NL (June 1999). "Lymphomas of the breast: pathology and clinical behavior". Semin. Oncol. 26 (3): 357–64. PMID 10375092.
22. ↑ Barişta I, Baltali E, Tekuzman G, Kars A, Ruacan S, Ozişik Y, Güler N, Güllü IH, Atahan IL, Firat D (2000). "Primary breast lymphomas--a retrospective analysis of twelve cases". Acta Oncol. 39 (2): 135–9. PMID 10859001.
23. ↑ Schwartz GF (June 1982). "Benign neoplasms and "inflammations" of the breast". Clin Obstet Gynecol. 25 (2): 373–85. PMID 6286199.
24. ↑ Wen X, Cheng W (January 2013). "Nonmalignant breast papillary lesions at core-needle biopsy: a meta-analysis of underestimation and influencing factors". Ann. Surg. Oncol. 20 (1): 94–101. doi:10.1245/s10434-012-2590-1. PMID 22878621.
25. ↑ Guray M, Sahin AA (May 2006). "Benign breast diseases: classification, diagnosis, and management". Oncologist. 11 (5): 435–49. doi:10.1634/theoncologist.11-5-435. PMID 16720843.
26. ↑ Jensen RA, Page DL, Dupont WD, Rogers LW (1989). "Invasive breast cancer risk in women with sclerosing adenosis". Cancer. 64 (10): 1977–83. PMID 2804888.CS1 maint: Multiple names: authors list (link)
27. ↑ Wang J, Costantino JP, Tan-Chiu E, Wickerham DL, Paik S, Wolmark N (2004). "Lower-category benign breast disease and the risk of invasive breast cancer". J Natl Cancer Inst. 96 (8): 616–20. PMID 15100339.CS1 maint: Multiple names: authors list (link)
28. ↑ Celliers L, Wong DD, Bourke A (2010). "Pseudoangiomatous stromal hyperplasia: a study of the mammographic and sonographic features". Clin Radiol. 65 (2): 145–9. doi:10.1016/j.crad.2009.10.003. PMID 20103437.CS1 maint: Multiple names: authors list (link)
29. ↑ Salvador R, Lirola JL, Domínguez R, López M, Risueño N (2004). "Pseudo-angiomatous stromal hyperplasia presenting as a breast mass: imaging findings in three patients". Breast. 13 (5): 431–5. doi:10.1016/j.breast.2003.10.011. PMID 15454202.CS1 maint: Multiple names: authors list (link)
30. ↑ Becker L, McCurdy LI, Taves DH (2001). "Superficial thrombophlebitis of the breast (Mondor's disease)". Can Assoc Radiol J. 52 (3): 193–5. PMID 11436415.CS1 maint: Multiple names: authors list (link)
31. ↑ Catania S, Zurrida S, Veronesi P, Galimberti V, Bono A, Pluchinotta A (1992). "Mondor's disease and breast cancer". Cancer. 69 (9): 2267–70. PMID 1562972.CS1 maint: Multiple names: authors list (link)
32. ↑ Kudva YC, Reynolds C, O'Brien T, Powell C, Oberg AL, Crotty TB (2002). ""Diabetic mastopathy," or sclerosing lymphocytic lobulitis, is strongly associated with type 1 diabetes". Diabetes Care. 25 (1): 121–6. PMID 11772912.CS1 maint: Multiple names: authors list (link)
33. ↑ Draghi F, Tarantino CC, Madonia L, Ferrozzi G (2011). "Ultrasonography of the male breast". J Ultrasound. 14 (3): 122–9. doi:10.1016/j.jus.2011.06.004. PMC 3558246. PMID 23397020.CS1 maint: Multiple names: authors list (link)
34. ↑ Braunstein GD (2007). "Clinical practice. Gynecomastia". N Engl J Med. 357 (12): 1229–37. doi:10.1056/NEJMcp070677. PMID 17881754.
35. ↑ Lower EE, Hawkins HH, Baughman RP (2001). "Breast disease in sarcoidosis". Sarcoidosis Vasc Diffuse Lung Dis. 18 (3): 301–6. PMID 11587103.CS1 maint: Multiple names: authors list (link)
36. ↑ Soo MS, Kornguth PJ, Hertzberg BS (1998). "Fat necrosis in the breast: sonographic features". Radiology. 206 (1): 261–9. doi:10.1148/radiology.206.1.9423681. PMID 9423681.CS1 maint: Multiple names: authors list (link)

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