AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Radcliffe Crocker first recognized and reported extramammary Paget disease (EMPD) as a distinct clinical entity in 1889. EMPD is morphologically and histologically identical to mammary Paget disease of the nipple, which James Paget had described 15 years earlier. The primary difference is the anatomic location. Crocker described a patient with erythematous patches on his penis and scrotum. Since he made this distinction, the term EMPD is more commonly used to describe the condition in women. This process targets the genital skin, perianal skin, and other cutaneous sites rich in apocrine glands. EMPD is not a common disorder, but it must be considered in the differential diagnosis of patients with chronic genital or perianal dermatitis.

Pathophysiology

EMPD arises as a primary cutaneous adenocarcinoma in most cases. The epidermis becomes infiltrated with neoplastic cells showing glandular differentiation. Tumor cells may originate from apocrine gland ducts or from keratinocytic stem cells.

Approximately 25% of the cases of EMPD (range, 9-32%) are associated with an underlying in situ or invasive neoplasm. In all patients, the neoplasm most likely to be associated with EMPD is an adnexal apocrine carcinoma. This associated neoplasm probably represents infiltration of the deeper adnexa by epidermal Paget cells. In addition to cutaneous adnexal carcinoma, other associated malignancies include the following: carcinoma of the Bartholin glands, urethra, bladder, vagina, cervix, endometrium, or prostate.

The anatomic location of EMPD plays a role in predicting the risk of associated carcinoma. For instance, about 4-7% of patients with genital disease have an associated carcinoma. Perianal disease is associated with underlying colorectal carcinoma in 25-35% of cases.

Rare cases of EMPD associated with tumors arising in distant organs without direct epithelial connection to the affected epidermis have been reported. No clear evidence supports a causal link between these distant tumors and cutaneous EMPD.

Frequency

International

EMPD is a rare condition with only several hundred cases in the world literature.

Mortality/Morbidity

• The course of the disease may last 10-15 years without evidence of cancer or metastases.
• In a minority of patients, tumor cells infiltrate the dermis, adnexa, or lymph nodes. Both mortality and morbidity rates are increased in these patients because of the extensive surgical treatment and/or chemotherapy that they need.
• One study showed a mortality rate of 18% for patients without associated carcinoma and 46% for those with underlying carcinoma.

Race

EMPD is most commonly reported in white patients, but it may occur in other races.

Sex

Women are more commonly affected than men. The female-to-male ratio was 4.5:1 in one series of 55 patients and 3:1 in another series of 197 patients.¹

Age

The condition most commonly appears in individuals aged 50-60 years.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

Most patients have only pruritus in the affected area and no other symptoms.

• Patients with EMPD usually present with a nonresolving eczematous lesions in the groin, genitalia, perineum, or perianal area.
• The most common symptom is intense pruritus.
• Pain and bleeding may occur in longer-standing lesions.

Physical

At clinical examination, EMPD may appear as chronic intertrigo or presumed tinea cruris. EMPD may appear eczematous, and it has usually been present for a long time before biopsy is performed to confirm the diagnosis.

• The genitalia, perineum, axillae, and external auditory canal are rich in apocrine glands; therefore, these are the usual sites of EMPD involvement.
• Early skin changes may be subtle and vary according to location.
• Initially, only slight erythema, crusting, and increased maceration may be noted.
• Pruritus commonly leads to prominent excoriations and lichenification.
• Lesional progression leads to a unilateral sharply marginated plaque with distinct erythema.
• Superficial erosion or scaling may develop in mature lesions.

Causes

• The cause of primary EMPD is unknown.
• However, a minority of cases do represent a direct extension of an underlying carcinoma along contiguous epithelium.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• The diagnosis of EMPD requires a high degree of clinical suspicion followed by skin biopsy with pathologic correlation.
• Initially, a detailed review of systems and physical examination should be performed in all patients. The examination should include the following:
• • Full skin examination
  • Palpation of all lymph nodes
  • Rectal examination
  • Sigmoidoscopy
  • Cystoscopy
• Additionally, women require pelvic examination with a Papanicolaou test, breast examination, and colposcopy.
• Because EMPD extends beyond the visibly involved margins, obviously involved skin should be examined by using transverse frozen sections or serial vertical sections.

Imaging Studies

• Imaging studies should be directed by the anatomic location of the involved skin and the sex of the patient.
• Imaging studies should be used to augment physical and endoscopic examination in assessing possible undetected internal malignancy.¹
• Positron emission tomography may be helpful in assessing regional lymph nodes and locating distal disease, especially in patients with dermal invasion noted on initial skin biopsy specimens.²

Histologic Findings

The epidermis is diffusely infiltrated with large vacuolated cells that have a bluish cytoplasm; these are called Paget cells. These distinctive cells are found in the lower epidermis and may proliferate to the rete ridges and adnexa. The epidermis shows varying degrees of acanthosis, hyperkeratosis, and parakeratosis. With histochemical analysis, Paget cells stain with sialomucin by using periodic acid-Schiff (PAS) followed by diastase digestion.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Surgical Care

Margin-controlled surgical excision of all the involved epidermis is the most effective treatment.

• EMPD extends beyond the visibly involved margins. Obviously involved skin should be examined by using transverse frozen sections or serial vertical sections.  Multiple scouting biopsies performed prior to surgery may aid in planning a more precise initial excision.³
• Multifocal disease is a challenge for any surgical method, even micrographic surgery, which relies on contiguous tumor spread for effective margin control. However, Mohs micrographic surgery offers lower recurrence rates after excision of primary tumors with a smaller margin of normal skin removed.^{4, 5}
• • The recurrence rate of primary tumors using standard surgical excision is 30-60%. The rate following excision with Mohs micrographic surgery is 8-26%.
  • The average time to recurrence is 2.5 years, with case reports of more than 10 years follow-up.

Consultations

Depending on anatomic location, treatment should be coordinated with surgical subspecialists to include a urologist, a colorectal surgeon, or a gynecologist. Optimally, the consultant would have some experience treating this specific condition.

Further consultation with a radiologist and a gastroenterologist may also be required to order appropriate screening examinations for internal malignancy.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Patients with EMPD require follow-up examination every 3 months after surgery to assess possible recurrence. This routine should continue for at least 24 months and then annually.
• Consider repeating other endoscopic or imaging studies on a regular basis according to the specific recommendations of the consultants.

Prognosis

• The prognosis heavily depends on early diagnosis with definitive surgical treatment.
• Full recovery is possible in patients with purely epidermal disease and negative margins after micrographic surgery.
• One study showed a mortality rate of 18% for patients without associated carcinoma and 46% for those with underlying carcinoma.
• Perianal disease, dermal invasion, and lymph node metastasis are poor prognostic indicators.
• • The recurrence rate is 30%, even with margin control.
  • The average time to recurrence is 2.5 years, with case reports of more than 10 years follow-up.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to carefully consider the possibility of EMPD in any patient with chronic dermatitis of the groin, vulva, or perianal area
• Failure to perform skin biopsy to evaluate possible EMPD in patients in whom ongoing therapy is ineffective

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

1. Chanda JJ. Extramammary Paget's disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. Dec 1985;13(6):1009-14. [Medline].
2. Cho SB, Yun M, Lee MG, Chung KY. Variable patterns of positron emission tomography in the assessment of patients with extramammary Paget's disease. J Am Acad Dermatol. Feb 2005;52(2):353-5. [Medline].
3. Appert DL, Otley CC, Phillips PK, Roenigk RK. Role of multiple scouting biopsies before Mohs micrographic surgery for extramammary Paget's disease. Dermatol Surg. Nov 2005;31(11 Pt 1):1417-22. [Medline].
4. Coldiron BM, Goldsmith BA, Robinson JK. Surgical treatment of extramammary Paget's disease. A report of six cases and a reexamination of Mohs micrographic surgery compared with conventional surgical excision. Cancer. Feb 15 1991;67(4):933-8. [Medline].
5. Hendi A, Brodland DG, Zitelli JA. Extramammary Paget's disease: surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol. Nov 2004;51(5):767-73. [Medline].
6. Brainard JA, Hart WR. Proliferative epidermal lesions associated with anogenital Paget's disease. Am J Surg Pathol. Apr 2000;24(4):543-52. [Medline].
7. Jaworsky C, Miller SJ, Maloney ME. Extramammary Paget's disease. In: Cutaneous Oncology: Pathophysiology, Diagnosis, Management. London, England: Blackwell Science; 1998:789-95.
8. Kodama S, Kaneko T, Saito M, Yoshiya N, Honma S, Tanaka K. A clinicopathologic study of 30 patients with Paget's disease of the vulva. Gynecol Oncol. Jan 1995;56(1):63-70. [Medline].
9. Lloyd J, Flanagan AM. Mammary and extramammary Paget's disease. J Clin Pathol. Oct 2000;53(10):742-9. [Medline].
10. Marchesa P, Fazio VW, Oliart S, Goldblum JR, Lavery IC, Milsom JW. Long-term outcome of patients with perianal Paget's disease. Ann Surg Oncol. Sep 1997;4(6):475-80. [Medline].
11. Murata Y, Kumano K, Tani M. Underpants-pattern erythema: a previously unrecognized cutaneous manifestation of extramammary Paget's disease of the genitalia with advanced metastatic spread. J Am Acad Dermatol. Jun 1999;40(6 Pt 1):949-56. [Medline].
12. Parker LP, Parker JR, Bodurka-Bevers D, Deavers M, Bevers MW, Shen-Gunther J, et al. Paget's disease of the vulva: pathology, pattern of involvement, and prognosis. Gynecol Oncol. Apr 2000;77(1):183-9. [Medline].

Article Last Updated: Nov 30, 2007