Vulva, vagina & female urethra
Other carcinomas
Paget disease
Author: Priya Nagarajan, M.D., Ph.D.
Last author update: 1 March 2015
Last staff update: 16 August 2021
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Paget disease [title] vulva
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiopathogenesis | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Differential diagnosis | Additional referencesCite this page: Nagarajan P. Paget disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/vulvapagetsdisease.html. Accessed April 1st, 2023.
Definition / general
- First described in 1901 by Dubreuilh (Case Rep Oncol Med 2012;2012:854827)
- Constitutes < 1 - 2% of vulvar malignancies (Gynecol Oncol 2011;122:42)
- Based on origin, several classification schemes have been proposed:
- Type 1: primary vulvar cutaneous origin (Int J Gynecol Cancer 2006;16:1212)
- Type 2: secondary to primary anal or rectal adenocarcinoma
- Type 3: secondary to urothelial carcinoma
- OR
- Type I: Paget disease of primary cutaneous origin (Hum Pathol 2002;33:549)
- Ia: as a primary intraepithelial neoplasm
- Ib: as an intraepithelial neoplasm with invasion
- Ic: as a manifestation of underlying adenocarcinoma of skin appendage or vulval glandular origin
- Type II: Paget disease of noncutaneous origin
- IIa: secondary to anorectal carcinoma
- IIb: secondary to urothelial neoplasia
- IIc: as a manifestation of another noncutaneous carcinoma: endocervical, endometrial or ovarian adenocarcinoma, etc.
- Type I: Paget disease of primary cutaneous origin (Hum Pathol 2002;33:549)
Terminology
- Synonyms: extramammary Paget (Paget's) disease
Epidemiology
- Common in elderly, postmenopausal, Caucasian women
Sites
- Labia majora > clitoris
Etiopathogenesis
- Intraepithelial adenocarcinoma that can be:
- Primary, arising from intraepidermal glandular cells or pluripotent cells of epidermis / folliculosebaecous or eccrine units
- Secondary, due to either direct spread from an underlying in situ or invasive adenocarcinoma or rarely epidermotropic metastasis
- Underlying neoplasms may be colorectal, urothelial, ovarian, endometrial or cervical in origin
- May become invasive and eventually metastasize to regional lymph nodes
Clinical features
- Slowly expanding, erythematous or eczematous, focally eroded or crusted plaques
- Lesions are frequently sharply demarcated
- Often pruritic, may be painful or associated with burning sensation, rarely asymptomatic
- Often accompanied by discharge
- Frequently multifocal
Diagnosis
- Must be confirmed by histologic examination
- Underlying neoplasm should be ruled out by complete pelvic examination, colposcopy and radiologic examination
Prognostic factors
- Clinical detection of a nodule within the primary lesion, palpable lymphadenopathy, the level of tumor invasion and lymph node metastases are the most important prognostic indicators (Dermatol Surg 2012;38:1938)
- Following histologic features are associated with tumor progression and invasion:
- Increased expression of p53 (Hum Pathol 2003;34:880)
- Combined expression of cyclin D1 and increased Ki67 (J Dermatol Sci 2008;50:177)
- Reduced expression of E-cadherin (Mod Pathol 2008;21:1192)
- Clearance of disease with wide margins remains a challenge due to the multifocal nature of the disease
- However, positive margins and lesion size are not predictive of progression free survival (Int J Gynecol Pathol 1999;18:351, Int J Clin Oncol 2012;17:569)
- Patients with clitoral involvement may require more aggressive treatment (Gynecol Oncol 2000;77:183)
Case reports
- 43 year old woman with painful vulvar lesion and recurrent vaginal discharge (Case Rep Oncol Med 2012;2012:854827)
- 50 year old woman with pigmented extramammary Paget disease (Acta Derm Venereol 2011;91:380)
- 59 year old woman with vulvar Paget disease (J Dermatol Case Rep 2011;5:42)
- 60 year old woman with bladder Paget disease 18 years after vulvar Paget disease (Gynecol Oncol Case Rep 2014;8:27)
- 62 year old woman with pruritic plaque on perineal skin (Indian J Dermatol 2015;60:105)
- 65 year old women with vulvar Paget disease (Proc R Soc Med 1956;49:89, J Midlife Health 2012;3:100)
- 75 year old woman (BMJ Case Rep 2013 Nov 21;2013)
Treatment
- Mohs micrographic surgery (J Am Acad Dermatol 2013;68:632) or wide local excision
- Topical imiquimod (J Obstet Gynaecol 2013;33:479, South Med J 2006;99:396, J Low Genit Tract Dis 2012;16:59) or topical 5-fluorouracil (Cutis 2006;77:245)
- Radiotherapy, photodynamic therapy (Gynecol Oncol 2006;103:581) or CO2 laser ablation
- Trastuzumab (Gynecol Oncol 2008;111:568)
- References: Cochrane Database Syst Rev 2013;(10):CD009245, Australas J Dermatol 2013;54:9
Clinical images
Images hosted on other servers:
Lesion on perineal area
Preoperative
Erythemato-squamous lesion
Before and after treatment
Asymmetrical brown lesion
Gross description
- Sharply demarcated plaque
Microscopic (histologic) description
- Microscopic disease almost always extends well beyond the grossly visible lesion
- Epidermis is frequently acanthotic, accompanied by hyperkeratosis, parakeratosis, erosion or ulceration
- Intraepidermal scattering of single or clusters of large cells characterized by abundant eosinophilic, clear or amphophilic cytoplasm, round / ovoid vesicular nuclei, open chromatin and small nucleoli
- These cells may be seen in combinations of several histologic patterns: glandular, acantholysis-like, suprabasal nests, vertical nests, budding and sheet-like (J Dermatol 2011;38:1054)
- Basal layer is preserved but may be attenuated
- Clefting between tumor cells and the surrounding epidermis may be present, due to absence of desmosomes
- Fibroepithelioma-like hyperplasia or papillomatous hyperplasia may be seen (Am J Surg Pathol 2000;24:543)
- May resemble invasive disease due to marked intraepithelial proliferation within deep epithelial invaginations, tangential sectioning of rete and papillary dermal fibrosis (Arch Pathol Lab Med 1998;122:471)
- Sometimes, the glandular nature of the infiltrating cells is highlighted by mucinous differentiation and signet ring-like morphology
- Rarely, the cytologic atypia can be marked with anaplastic features; these are seen more frequently in secondary Paget disease
- Exceptionally, the cells may be pigmented
- There may be an associated lichenoid lymphohistiocytic inflammatory infiltrate in the superficial dermis
Microscopic (histologic) images
Contributed by Priya Nagarajan, M.D., Ph.D.
Low power - subtle disease on left
Eyeliner sign
Invasive
Medium power
High power
Cytology description
- Round to columnar, moderately enlarged atypical cells, dispersed or in loose groups, with abundant clear cytoplasm, vesicular nuclei and prominent nucleoli (Acta Cytol 2010;54:1007, Acta Cytol 2010;54:898, Diagn Cytopathol 2010;38:127)
Positive stains
- Special stains: diastase periodic acid Schiff (PASD), mucicarmine, rarely Alcian blue, colloidal iron
- CK7, CAM5.2, AE1 / AE3, EMA / MUC1, CEA, GCDFP-15, MUC5AC (positive more often in primary than secondary), androgen receptor, HER2, COX2, CD23
- Secondary Paget disease cells of colorectal origin are CK20+ and CK7+
- Secondary Paget disease cells of urothelial origin are positive for CK7, CK20 and uroplakin III
Differential diagnosis
- Clinical:
- Histologic:
- Benign mucinous metaplasia: difficult to distinguish but lacks cytologic atypia
- Clear cell papulosis: thought to represent benign Toker cell hyperplasia
- Intraepidermal spread of sebaceous carcinoma
- Melanoma
- Pagetoid dyskeratosis: suprabasal cells with abundant eosinophilc cytoplasm with no cytologic atypia and are not glandular in origin
- Squamous cell carcinoma in situ
