Epidemiology and treatment of extramammary Paget disease in the Netherlands

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Abstract

Aim

To determine the incidence of EMPD and to describe its epidemiology, treatment, survival and the risk of developing other malignancies.

Method

All cases of EMPD, diagnosed between 1989 and 2001, were selected from the Netherlands Cancer Registry.

Results

In total, 178 cases of invasive and 48 cases of in situ EMPD had been registered. The overall relative 5-year survival for invasive tumours was 72%. Most patients with invasive as well as in situ cancer underwent surgery. Other malignancies were found in 32% of patients with invasive EMPD and 35% of patients with in situ EMPD. Patients had an increased risk of developing a second primary cancer (standardized incidence ratio: 1.7; 95% confidence interval 1.2–2.4). The most frequent localizations of the other cancers were the colorectum, the prostate, the breast and the extragenital skin.

Conclusions

For EMPD, which is a rare disease in the Netherlands, there are no clear diagnostic and treatment guidelines. The prognosis is fairly good. A thorough search for other tumours is recommended for these patients.

Introduction

There are two types of Paget disease (PD). Mammary Paget disease (MPD) is a special form of ductal carcinoma, which arises in the main excretory ducts of the breast and extends to the skin of the nipple and areola. It was first described by Sir James Paget in 1874.1 At the same time he mentioned the fact that the clinical entity could also involve other parts of the body. In 1889 extramammary Paget disease (EMPD) was defined by Crocker.2 He described lesions on the scrotum and penis which had histological features similar to those of MPD.

EMPD resembles MPD clinically as well as histologically. Clinically an eczema-like lesion is seen. The most common presenting symptom of EMPD is pruritis.3 Histologically the cancer can be described as a cutaneous adenocarcinoma with typical Paget cells, i.e. large cells with large nucleoli and abundant cytoplasm which usually stains pale. It develops predominantly in skin that is full of apocrine sweat glands, such as in the genital region or axilla, but it can be found anywhere on the skin or mucosa. EMPD occurs mainly among the elderly. Caucasian women in their 60s and 70s are more at risk than other populations.4

Up to now, no clear guidelines have been established for the diagnosis, treatment and follow-up of patients with EMPD. A possible association with internal malignancies, before or after the diagnosis of EMPD, has been described.5 Therefore a thorough physical examination of the patient with EMPD to discover other regional rectal, urothelial or vulvar malignancies has been recommended.6 The location of the underlying internal malignancy is linked to the location of the EMPD: a perianal location may signify a malignancy of the gastrointestinal tract and a penile, scrotal or groin location may be associated with an adenocarcinoma of the genitourinary tract.7

The aim of this population-based study was to describe the incidence, epidemiology, treatment, survival and risk of developing other malignancies for patients with EMPD.

Section snippets

Cancer registration in the Netherlands

In the Netherlands (16 million inhabitants) all newly diagnosed cases of invasive and in situ cancer have been registered in the Netherlands Cancer Registry (NCR) since 1989. The main sources of notification are the automated pathological archive (PALGA), as well as Haematology and Radiotherapy Departments. Furthermore, the National Registry of Hospital Discharge Diagnoses is an important source since it accounts for up to 8% of new cases.8 Death certificates are not available in an identifiable

Results

In the 13-year period 1629 cases of Paget disease were registered, 720 in situ and 909 invasive tumours. Out of the 1629, 226 tumours were EMPD. This yields an incidence rate of 0.11 per 100,000 person-years for EMPD (ESR = 0.10 per 100,000 person-years). Of the 226 cases of EMPD 178 were invasive and 48 were in situ (Table 1).

Discussion

In the present study, patients with PD were selected from the NCR over a 13-year period (from 1989 to 2001). The focus on EMPD yielded 226 cases. This was 14% of all patients with Paget disease in the registry. There were 178 invasive and 48 in situ EMPD. Compared to Paget disease, EMPD was less likely to be invasive; respectively 44% and 21% of the tumours were invasive. We do not have an explanation for this. All cancers were histologically confirmed, sometimes by immunostaining. Therefore,

Conclusion

The prognosis for patients with EMPD is fairly good. A thorough examination for other tumours is recommended, with a minimum follow-up time of at least 5 years. For EMPD on the male genital skin the most likely sites of other tumours are the colorectum and the prostate. For a patient with EMPD on the female genital skin, examination of the breast is recommended; for an EMPD tumour on the extragenital skin, the most common localizations for other tumours are the breast and the extragenital skin.

Acknowledgements

The authors would like to thank Professor Flora van Leeuwen and Willem Klokman of the Netherlands Cancer Institute (NKI/VU), Amsterdam, for their support with the risk assessment for second tumours. We thank the regional cancer registrations for providing the follow-up data.

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