Definitions

Skin
ICD-O-3 topography code:	C44
ICD10:	C44

Extramammary Paget disease (EMP) is a rare intraepidermal apocrine adenocarcinoma arising mainly in the female and male genital areas. A minority of cases involve axillae, eyelids and external auditory canals. The tumour may eventually invade the dermis and acquire metastatic potential. Primary EMP most likely originates from intraepidermal cells of apocrine gland ducts. Secondary EMP represents migration of an underlying internal malignancy to the epidermis.
EMP presents as a pruritic or burning, scaly, erythematous and sometimes ulcerated plaque. Histologically, the tumour is characterized by large, atypical neoplastic cells (Paget cells) featuring large nuclei with prominent nucleoli and abundant pale cytoplasm. They are scattered singly or in small clusters throughout the epidermis and are prone to track along skin appendages. The epidermis is often hyperkeratotic and acanthotic; the epidermal changes are accompanied by a dermal perivascular lymphohistiocytic infiltrate.
Extramammary Paget disease mainly affects patients >60 years of age. Genital EMP shows a predilection for women. Primary EMP has a recurrence rate of approximately 30%, but typically does not metastasize. Approximately 10% of patients develop invasive adenocarcinoma that may progress to metastatic disease. The prognosis for secondary EMP depends on the characteristics of the associated internal tumour¹

LeBoit PE, Burg G, Weedon D, Sarasin A (Eds.)
World Health Organization Classification of Tumours. Pathology and Genetics of Skin Tumours
3rd Edition
IARC Press: Lyon 2005

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Penis
ICD-O-3 topography code:	C60
ICD10:	C60

A malignant neoplasm in which there is infiltration of the skin by neoplastic large cells with abundant pale cytoplasm and large nuclei with prominent nucleoli (Paget cells).

Anus and anal canal
ICD-O-3 topography code:	C21
ICD10:	C21

Extramammary Paget disease usually affects sites with a high density of apocrine glands, such as the anogenital region, where it presents as a slowly spreading, erythematous eczematoid plaque that may extend up to the dentate line ²

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Sarmiento JM, Wolff BG, Burgart LJ, Frizelle FA, Ilstrup DM (1997)
Paget's disease of the perianal region--an aggressive disease?
Dis Colon Rectum 40: 1187-94

. Histologically, the basal part or whole thickness of the squamous epithelium is infiltrated by large cells with abundant pale cytoplasm and large nuclei. Occasional cells have the appearance of signet rings. Paget cells invariably react positively for mucin stains and nearly always for keratin 7, but Merkel cells and Toker cells may also be positive for the latter.

Paget disease of the anus appears to represent two entities:
> About half of the cases are associated with a synchronous or metachronous malignancy, most often a colorectal adenocarcinoma. Such cases can be regarded as a pagetoid extension of the tumour. They usually react positively for keratin 20 and negatively for gross cystic-disease fluid protein-15 (GCDFP-15), a marker for apocrine cells.
> This is in contrast to the other half of the cases, which are not associated with internal malignancies but have a high rate of local recurrence and may become invasive ³

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Marchesa P, Fazio VW, Oliart S, Goldblum JR, Lavery IC, Milsom JW (1997)
Long-term outcome of patients with perianal Paget's disease.
Ann Surg Oncol 4: 475-80

. Only the latter entity can be regarded as a true epidermotrophic apocrine neoplasm ⁴

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Armitage NC, Jass JR, Richman PI, Thomson JP, Phillips RK (1989)
Paget's disease of the anus: a clinicopathological study.
Br J Surg 76: 60-3

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Battles OE, Page DL, Johnson JE (1997)
Cytokeratins, CEA, and mucin histochemistry in the diagnosis and characterization of extramammary Paget's disease.
Am J Clin Pathol 108: 6-12

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Goldblum JR, Hart WR (1998)
Perianal Paget's disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma.
Am J Surg Pathol 22: 170-9

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Nowak MA, Guerriere-Kovach P, Pathan A, Campbell TE, Deppisch LM (1998)
Perianal Paget's disease: distinguishing primary and secondary lesions using immunohistochemical studies including gross cystic disease fluid protein-15 and cytokeratin 20 expression.
Arch Pathol Lab Med 122: 1077-81

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Recently, it has been proposed that this disease arises from adnexal stem cells residing in the infundibulo-sebaceous unit of hair follicles and adnexal structures, on the basis of expression of keratins 15 and 19 ⁸

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Regauer S (2006)
Extramammary Paget's disease--a proliferation of adnexal origin?
Histopathology 48: 723-9

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Vulva
ICD-O-3 topography code:	C51
ICD10:	C51

Extramammary Paget disease arising in the vulva is an uncommon, malignant intraepithelial neoplasm, most commonly of cutaneous origin, exhibiting glandular-like features and characterized by large neoplastic cells with abundant pale cytoplasm and large nuclei with prominent nucleoli (Paget cells).
Vulvar Paget disease usually affects postmenopausal women. 10-20% of cases have an invasive component or an underlying skin appendage adenocarcinoma ⁹

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Fanning J, Lambert HC, Hale TM, Morris PC, Schuerch C (1999)
Paget's disease of the vulva: prevalence of associated vulvar adenocarcinoma, invasive Paget's disease, and recurrence after surgical excision.
Am J Obstet Gynecol 180: 24-7

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Wilkinson EJ, Brown HM (2002)
Vulvar Paget disease of urothelial origin: a report of three cases and a proposed classification of vulvar Paget disease.
Hum Pathol 33: 549-54

¹¹

Tavassoli FA, Devilee P (Eds.)
World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs.
3rd Edition
IARC Press: Lyon 2003

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