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Breast malignant, males, children

In situ carcinoma

Pagetís disease


Reviewer: Dina Kandil, M.D. (see Reviewers page)
Revised: 10 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● Malignant epithelial cells randomly disposed within epidermis of nipple / areola
● A type of in situ carcinoma that arises in or involves the main excretory (lactiferous) ducts
● Associated with underlying DCIS or invasive disease in almost all cases (Breast Cancer Res Treat 2008;112:513, Ann Surg Oncol 2005;12:391)
● Described by Sir James Paget in 1874 as a crusted lesion of nipple caused by breast carcinoma
● May derive from Toker cells (clear cells in nipple), or from epidermotropism of existing carcinoma (Hum Pathol 2003;34:1321)
● Present in 1-4% of all patients with breast carcinoma; age ranges from 26 to 88, median age 54 years

Terminology
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● Differs from Pagetís disease of vulva (usually not associated with underlying carcinoma) and Pagetís disease of bone
● "Anaplastic Paget's", based on markedly atypical cells, is occasionally described (Am J Surg Pathol 1992;16:1085, J Cutan Pathol 2009;36:374, Turkish Journal of Cancer 2003;33:158 [PDF]), but not widely accepted as a distinct entity

Epidemiology
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● Present in 1-2% of all patients with breast carcinoma, median age 54 years

Treatment and prognosis
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● Mastectomy or possibly breast conserving surgery
● Prognosis depends on underlying DCIS or invasive carcinoma

Case reports
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● 53 year old woman with bilateral Pagetís disease derived from LCIS (Arch Pathol Lab Med 2002;126:90)
● 58 year old woman with vulvar and breast disease and invasive disease at both sites (Arch Gynecol Obstet 2009;280:313)
● 64 year old woman with nipple discharge and inverted nipple (Univ Pittsburgh Case #331)
● 83 year old woman with acinar pattern (Breast J 2007;13:520)

Clinical images
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Eczematoid lesion


Pigmented lesion

Gross description
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● Skin is fissured, oozing, ulcerated
● Resembles eczema (Breast Cancer Res Treat 2008;111:313)

Micro description
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● Single cells, groups or rarely tubules
● Cells are large, atypical and spread throughout epidermis
● Cells have abundant clear or light staining cytoplasm, abundant mucin and occasionally intracytoplasmic melanin (Melanoma Res 2004;14:S13, Am J Dermatopathol 2009;31:223)
● Nucleus is large and vesicular with prominent nucleolus
● DCIS is usually present and may also have invasive component
● Underlying breast carcinoma is usually adjacent to Pagetís disease if one takes enough sections

Micro images
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Large atypical cells in epidermis


With hyperkeratosis and dermal inflammation


With underlying comedo DCIS


H&E and stains


With melanin pigment


Derived from LCIS


CK7+, E-cadherin negative

       
CK7+


Involvement of entire thickness of epidermis, with pseudoepitheliomatous hyperplasia and
hyperkeratosis with involved area, but not in normal appearing area (AFIP)



Large atypical cells in epidermis have round nuclei and prominent nucleoli (AFIP)


Involvement of terminal portion of lactiferous duct (AFIP)


HER2+ (AFIP)

Contributed by Dr. Semir Vranic: Pagetís with underlying DCIS:
           
Pagetís (left to right): H&E, CK8+, HER2+, S100-

           
Underlying DCIS (left to right): H&E, ER alpha, CK8, HER2

Virtual slides
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Paget's disease

Videos
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Paget's disease

Positive stains
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● AE1/3, CK7 (also stains Toker and Merkel cells, Am J Surg Pathol 1999;23:212)
● Low molecular weight keratin (CAM 5.2, AE1, Am J Surg Pathol 1992;16:58)
● EMA, CEA / MUC1 (Am J Surg Pathol 2001;25:1469, Am J Surg Pathol 2002;26:617)
● HER2 and androgen receptor (Mod Pathol 2005;18:1283)
● GCDFP-15 (50%)
● Variable p53, ER and PR

Negative stains
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● MUC2, MUC5AC (mucin expressed in extramammary Pagetís disease), S100, HMB45

EM description
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● Intracytoplasmic lumina with microvilli, evidence of glandular differentiation

Differential diagnosis
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● Carcinoma in situ of skin / Bowenís disease: has individual cell keratinization and multinucleated giant cells, CK7-, mucin-, HER2-
● Superficial spreading melanoma: tumor cells invade dermis, S100+, HMB45+, AE1/3- (Dermatology Online Journal 13(2):18)
● Benign proliferative nipple duct lesions or Toker cells: mucin- (APMIS 2008;116:139, Breast J 2009;15:394)
● Pemphigus vulgaris: clinically different (Breast J 2003;9:319)
● Clear cell keratinocytes: image

Additional references
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eMedicine

End of Breast malignant, males, children > In situ carcinoma > Pagetís disease


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