Generic selectors
Exact matches only
Search in title
Search in content
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Studies
Study Letter
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF
Letter to the Editor
2015:81:3;318-320
doi: 10.4103/0378-6323.153513
PMID: 25791858

Extramammary Paget disease secondary to a transitional cell carcinoma of the bladder

Adriana Martn-Fuentes1 , Consuelo Snchez-Herreros1 , Jess Cuevas-Santos2 , Esther De Eusebio-Murillo1
1 Department of Dermatology, University Hospital of Guadalajara. C/Donantes de Sangre s/n, 19002, Guadalajara, Spain
2 Department of Pathology, University Hospital of Guadalajara. C/Donantes de Sangre s/n, 19002, Guadalajara, Spain

Correspondence Address:
Adriana Martn-Fuentes
C/Donantes de Sangre s/n, 19002, Guadalajara
Spain
How to cite this article:
Martn-Fuentes A, Snchez-Herreros C, Cuevas-Santos J, De Eusebio-Murillo E. Extramammary Paget disease secondary to a transitional cell carcinoma of the bladder. Indian J Dermatol Venereol Leprol 2015;81:318-320
Copyright: (C)2015 Indian Journal of Dermatology, Venereology, and Leprology

Sir,

Extramammary Paget′s disease is an intraepidermal proliferation of Paget cells, which are also seen in the classic areolar-type mammary Paget′s disease. It can be divided into primary (intraepithelial adenocarcinoma arising within the epidermis) and secondary disease (intraepithelial spread of a visceral carcinoma).

A 47-year-old male presented with a 4-month history of an erythematous, erosive, and asymptomatic lesion involving the glans and urethral meatus [Figure - 1]. He had a history of in situ transitional cell carcinoma of the bladder treated with a radical cysto-prostatectomy 9 years ago. Hematoxylin-eosin stained sections of a biopsy from the plaque showed intraepithelial proliferation of pleomorphic pagetoid cells in a buckshot pattern, involving the full thickness of the epithelium [Figure - 2]a. At higher magnification, cells showed pale cytoplasm with large and round nuclei with prominent nucleoli [Figure - 2]b. The mitotic index was high. These Paget cells stained positively for epithelial mucins with colloidal iron. Immunohistochemically, the cells expressed positivity for cytokeratin (CK) 7 [Figure - 3]a, low molecular weight CK [Figure - 3]b and p53 while they were negative for S-100, CK-20 [Figure - 3]c, CDX-2 and gross cystic disease fluid protein (GCDFP-15) [Figure - 3]d. The histomorphological and immunohistochemical features, with a history of bladder carcinoma allowed us to make a diagnosis of extramammary Paget′s disease secondary to this malignancy.

Figure 1: Erythematous and erosive lesion involving glans and urethral meatus
Figure 2: (a) Pleomorphic pagetoid cells involving the full thickness of the epithelium in a dotted pattern. (b) Large cells with pale cytoplasm and round nuclei with prominent nucleoli (H and E, A: ×50; B: ×400)
Figure 3: Immunohistochemical stain. (a) CK7 (b) Low weight CK (c) CK20 (d) GCDFP-15 (A: ×400; B: ×200, C: ×200, D: ×100)

Urethrectomy was performed and surgical pathology revealed a diffuse proliferation of cells with histological and immunohistochemical characteristics similar to the Paget cells observed in the glans biopsy. The cells were confined to the urothelium without invasion through the basement membrane (in situ urothelial carcinoma) and the surgical margins were free.

Paget′s disease was initially described by Crocker in 1889. [1] We were able to find only 15 previous reports of involvement of the glans associated with urothelial carcinoma. [2],[3],[4] The age ranged from 45 to 82 years (mean 61 years). In all but one case, the glans lesion was diagnosed after the urinary malignancy, after a mean interval of latency of 0.4 to 12 years (mean 6 years). In one patient, Paget′s disease of the glans allowed the diagnosis of an unsuspected transitional cell carcinoma of the bladder. [2] Most of the patients had aggressive tumors leading to death in 7 of the 15 patients.

Clinical presentation of Paget′s disease is often nonspecific (erosive, erythematous, eczematous, or circinate lesion) and can mimic many other dermatoses. Differential diagnoses include Bowen′s disease, Zoon′s balanitis, eczema, erythroplasia of Queyrat and psoriasis.

Microscopically, the two most important differential diagnoses include malignant melanoma and pagetoid Bowen′s disease. In melanoma we can see atypical melanocytes, which are positive for S100, HMB45, or Melan A. Pagetoid Bowen′s disease is a rare variant where the intraepithelial neoplastic squamous cells are arranged in nests, simulating the pattern of extramammary Paget′s disease. Epithelial mucins are negative in the neoplastic cells of pagetoid Bowen′s disease (in contrast, true Paget cells are positive for mucin stains). In general, the neoplastic cells of pagetoid Bowen′s disease are negative for CK7, CAM5.2, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA).

Histopathological features in Paget′s disease of the breast and in secondary extramammary Paget′s disease are similar and in both these diseases, Paget′s cells are noted in a buckshot pattern. However, we have observed that Paget cells show a glandular or adenoid pattern in primary extramammary Paget′s disease., We believe this is an important histological clue to differentiate these disorders but immunohistochemistry is required for a more definitive diagnosis.

Immunohistochemical study can help to differentiate primary extramammary Paget′s disease from the secondary form, but this technique is not always diagnostic [Table - 1]. Kohler et al.[5] studied 6 cases of secondary extramammary Paget′s disease and 20 cases of the primary form. Positive GCDFP-15 in a patient with this entity may indicate low probability of associated internal malignancy. Ohnishi et al.[6] described 15 cases of primary and 13 cases of secondary extramammary Paget′s disease. They demonstrated that most secondary forms showed the immunophenotype CK7-/CK20+. Since they only analyzed seven cases of secondary disease, they suggested that the existence of CK7+/CK20- is a possibility in this entity. Additionally, CDX2 may be useful in discriminating primary extramammary Paget′s disease from secondary extramammary Paget′s disease following anorectal adenocarcinoma. CDX2 is positive when extramammary Paget′s disease is to colorectal adenocarcinoma but is usually negative when the disease is secondary to urothelial transitional cell carcinoma.

Table 1: Histopathological and inmunohistochemical differential diagnosis between Paget's disease, primary extramammary Paget's disease and secondary extramammary Paget's disease

Finally, uroplakin is a transmembrane protein that is considered to be the most specific marker for urothelial differentiation. However, uroplakin III is reported to be expressed in 55% of cases. P63 is positive in 100% of conventional urothelial carcinoma. [7] Primary disease is uroplakin and p63 negative and the form secondary to urothelial transtitional cell carcinoma is uroplakin and p63 positive.

Despite the clinical similarities between primary and secondary extramammary Paget′s disease, treatment and prognosis are quite different. Prognosis of primary extramammary Paget′s disease is good but it has a high rate of recurrence after surgery due to its irregular and multicentric pattern. On the other hand, the prognosis and treatment of secondary extramammary Paget′s disease is determined by the nature of the internal malignancy and the presence or absence of metastatic disease. It is important to recognize secondary extramammary Paget′s disease because it may be the first manifestation of an occult carcinoma and because its co-existence indicates a worse prognosis than if the underlying carcinoma were present alone.

References
1.
Jones RE Jr, Austin C, Ackerman AB. Extramammary Paget's disease: A critical reexamination. Am J Dermatopathol 1979;1:101-32.
[Google Scholar]
2.
Salamanca J, Benito A, García-Peñalver C, Azorín D, Ballestín C, Rodríguez-Peralto JL. Paget's disease of the glans penis secondary to transitional cell carcinoma of the bladder: A report of two cases and review of the literature. J Cutan Pathol 2004;31:341-5.
[Google Scholar]
3.
Somers K, Iorizzo L, Scott G, Mercurio MG. Extramammary Paget disease of the penis as a manifestation of recurrent transitional cell carcinoma. Dermatol Online J 2012;18:3.
[Google Scholar]
4.
Kiyohara T, Ito K. Epidermotropic secondary extramammary Pagets disease of the glans penis from retrograde lymphatic dissemination by transitional cell carcinoma of the bladder. J Dermatol 2013;40:214-5.
[Google Scholar]
5.
Kohler S, Smoller BR. Gross cystic disease fluid protein-15 reactivity in extramammary Paget's disease with and without associated internal malignancy. Am J Dermatopathol 1996;18:118-23.
[Google Scholar]
6.
Ohnishi T, Watanabe S. The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Paget's disease. Br J Dermatol 2000;142:243-7.
[Google Scholar]
7.
Paner GP, Annaiah C, Gulmann C, Rao P, Ro JY, Hansel DE, et al. Immunohistochemical evaluation of novel and traditional markers associated with urothelial differentiation in a spectrum of variants of urothelial carcinoma of the urinary bladder. Hum Pathol 2014;45:1473-82.
[Google Scholar]

Fulltext Views
437

PDF downloads
90
Show Sections