Paget's disease of the breast differential diagnosis

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

Overview

Paget's disease of the breast must be differentiated from atopic dermatitis, eczema, psoriasis, malignant melanoma, Bowen's disease, basal cell carcinoma, and pagetoid dyskeratosis.

Differential Diagnosis

Paget’s disease of the breast must be differentiated from other benign and malignant processes of nipple-areola complex such as:

• Atopic dermatitis
• Chronic contact dermatitis
• Lactiferous duct ectasia
• Chronic eczema
• Psoriasis
• Nipple duct adenoma
• Malignant melanoma
• Bowen’s disease
• Superficial basal cell carcinoma
• Benign intraductal papilloma
• Pagetoid dyskeratosis

Paget's disease of the breast is often misdiagnosed as nipple eczema

Category	Diseases	Benign or Malignant	Etiology	Clinical manifestations								Para-clinical findings	Gold Standard	Associated factors
				Symptoms						Physical examination
												Histopathology
				Rash	Nipple Discharge	Erythema		Involved areas	Mastalgia	Breast Exam	Other
Skin disorders	Paget's disease of the breast			Ulcerated, crusted, or scaling lesion on the nipple that extends to the areolar region									CE-MRI/ Doppler ultrasound to analyze nipple blood flow. The affected nipple show Increased blood flow signaling.
	Extramammary Paget's disease
	Atopic dermatitis (Eczema)	Benign	Epidermal barrier dysfunction Immune dysregulation	Erythema, exudates, papules,vesicles, scales and crusts Infiltrated erythema, prurigo, scales and crusts	–	–	+	Young children -Scalp, cheeks amd extensor surface Adolescents -flexural areas and buttock-thigh creases Adults - facial involvement and skin flexures	–		Centrofacial pallor Delayed blanch response Keratosis pilaris Palmar hyperlinearity Pityriasis alba Ichthyosis Infra-auricular and retro-auricular fissuring Nipple eczema White dermographism Perifollicular accentuation	Epidermal psoriasiform hyperplasia Marked intercellular edema with spongiotic vesiculation Hyperkeratosis Psoriasiform hyperplasia Dyskeratosis		Family history of atopy History of silicon implants or reconstruction of nipple areola complex or lactation. Personal history of atopy or extramammary Paget's disease or hematological diseases Combined usage of interferon alfa-2b and ribavirin.
	Allergic contact dermatitis	Benign	Delayed-type hypersensitivity response Skin inflammation mediated by hapten-specific T cells	Erythematous well-demarcated papules	–	–	+	Surrounding the area in contact with the offending agent	+		Stinging and burning Localized swelling Lichenified pruritic plaques	Eosinophilic spongiosis and microvesicles Exocytosis of eosinophils and lymphocytes Chronic - Hyperkeratosis and parakeratosis		Contact with allergens in the past 1-2 days Positive family history
	Psoriasis	Benign	Keratinocyte hyperproliferation Dysregulation of the immune system	Well-circumscribed, pink papules and symmetrically distributed cutaneous plaques with silvery scales	–	+	+	Scalp Trunk Gluteal cleft Extensor surface of elbows and knees	+		Auspitz's sign (pinpoint bleeding)	Epidermal hyperplasia Parakeratosis Neutrophils microabscesses (Munro microabscesses)		Risk factors include Smoking Skin trauma Alcohol abuse Stress Cold weather Vitamin D deficiency
	Malignant melanoma	Malignant	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogenealso involved	Macule Plaque with irregular border Variable size A lesion with ABCD Asymmetry Border irregularity Color variation Diameterchanges Bleeding from the lesion	– Bleeding from the lesion may be present			All UV radiationor sun exposed areas can be effected independently						UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi
	Bowen’s disease	Benign can turn malignant		Erythematous Skin colored Patch Plaque scaly variable size	–			Fair-skinned individuals: sun-exposed areas In black individuals: legs, anus, and areas of chronic inflammation			Presence of dotted and/or glomerular vessels White to yellowish surface scales Red-yellowish background	Keratinocytic dysplasia of the epidermis No infiltration into dermis Pleomorphic keratinocytes Hyperchromatic nuclei		Slow growth over the years
	Superficial basal cell carcinoma	Malignant		Erythematous Superficial scaly patch	–			Sun-exposed areas Head (cheek and nose) Trunk			Superficial fine telangiectasia Shiny white to red, translucent or opaque structureless areas Multiple small erosions	Large, hyperchromatic, oval nuclei Minimal cytoplasm Small basaloid nodules		Higher incidence in men
	Benign intraductal papilloma
	Pagetoid dyskeratosis
	Lactiferous duct ectasia	Benign	* Common among perimenopausalwomen Usually resolve spontaneously										Ultrasound: Dilated milk ducts Fluid-filled ducts
	Nipple duct adenoma
	Benign Toker cell hyperplasia
	Breast abscess	Benign							+	Localized inflammation of breast Tenderness			Ultrasound: Fluid collection
	Mondors disease
	Mastitis	Benign No increased risk of malignancy					+		±	Breasttenderness Swollen breasttissue		Breast parenchymainflammation: Acute mastitis: Staphylococcus infection Granulomatous mastitis: Tuberculosis or sarcoidosisinfection	Ultrasound: Ill-defined area with hyperechogenicity with inflamed fat lobules Skin thickening
	Inflammatory Breast Cancer	Malignant