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Extramammary Paget’s disease of the genitalia with clinically clear margins can be adequately resected with 1 cm margin

European Journal of Dermatology. Volume 15, Number 3, 168-70, May-June 2005, Clinical report

Summary

Author(s) : Y Murata, K Kumano, Department of Dermatology, Hyogo Medical Center for Adults13-70, Kitaoji-cho Akashi 673-8558, Japan.

Summary : For the treatment of extramammary Paget’s disease (EMPD), wide excision has been recommended because of unpredictable spread of tumor cells. EMPD lesions are often well circumscribed. Should all the lesions of EMPD be resected with a 3 cm margin? Forty-six patients with EMPD were surgically treated with a 1 cm margin. Width of tumor cell free area from the last lesional cells at the borders to the resected edge was measured with micro-oculometer. The microscopic gap between the histopathological tumor border and the clinical border scored by scalpel tract was also measured. The tumor cell free area measured 10.2 ± 2.48 mm. The microscopic gap between the histopathological and clinical borders measured 0.334 ± 1.183 mm. Thus, the clinically determined border of well-defined lesions of EMPD corresponded well to the histopathologic border. No local recurrence was observed in 24 to 115 months of follow-up. Well-demarcated lesions of EMPD can be adequately managed with 1 cm margin resection.

Keywords : cancer, dermatologic surgery, extramammary Paget’s disease, Paget’s disease

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ARTICLE

Auteur(s) :, Y Murata^*, K Kumano

Department of Dermatology, Hyogo Medical Center for Adults13-70, Kitaoji-cho Akashi 673-8558, Japan

accepté le 22 Decembre 2004

In 1889, Crocker provided the first description of extramammary Paget’s disease (EMPD) [1]. The histopathological appearance was the same as the eczematous lesion of the areola first described by Sir James Paget in 1895. Primary EMPD is now well recognized as a separate entity originating from covering epidermis, whereas secondary Paget’s diseases develop from underlining lesions such as mammary or rectal carcinomas. The treatment of EMPD has been primarily surgical. Wide excision of full thickness of involved skin with a margin more than 3 cm beyond the clinically involved area has been recommended [2-5]. The reasons for the wide resection are that silent peripheral extensions of EMPD may extend unpredictably for a long distance beyond the borders of the clinically involved skin and the difficulty of determining adequate resection results in a high recurrence rate [6, 7]. In practice, however, EMPD most often presents as a well-circumscribed plaque [7], especially after the lesions have been pre-operatively treated with appropriate dermatological care.Should all the lesions of EMPD be widely resected with 3-cm margin or more? It is cardinal to determine whether or not the carefully examined clinical margin of EMPD will correspond with the histopathological margin. There have been no empirical data concerning these questions. In an effort to clarify these issues, we followed 46 patients with EMPD whose lesions had been resected with a 1-cm margin.

Patients and methods

Until 1990, we had treated patients with EMPD by 3 cm-margined resection. Since 1991, we have treated them with narrower margins. From October 1991 to March 2001, 46 Japanese cases of EMPD of the genitalia were surgically treated with a 1cm border from the clinical tumor margin, where the margin was well defined. With regard to the depth of excision, subcutaneous tissue including dartos muscle of the scrotum and superficial fascia of the penis has been resected in male patients. Where the lesion was thought to be invasive, deeper fasciae, such as external spermatic, cremasteric or internal spermatic fasciae, may be included for excision. In female patients, subcutaneous tissue, including areolar and adipose tissue and dartos muliebris, have been resected.

The patients’ ages ranged from 48 to 91 years old with a mean of 71.8. There were 38 males and 10 females. After operative treatment, these cases were followed up every 3 months for the evaluation of local or systemic recurrence. The follow-up period ranged from 2 to 9.6 years (mean 3.9 ± 1.67 years).

Resected gross skin specimen was sectioned perpendicular to the planes of surgical excision along all margins. These slices of tissue were paraffin-embedded and stained with hematoxyline and eosin. On histologic examination, the width of tumor cell free area from the last lesional cells at the borders to the resected edge was measured with a micro-ocu1ometer. In 29 cases, the clinical margins were lightly scored with a scalpel after surgical resection so that when the tissue was processed into slides, the tracks denoted the clinically determined tumor margin. The microscopic gap between the histopathological tumor border and the clinical border scored by scalpel tract was measured with micro-ocu1ometer ( (figure 1) ). When the track was located on the normal skin outside the histological tumor border, the distance was expressed by a positive number. When the track was located within the tumor lesion histopathologically, the distance was expressed by negative number.

Results

The histopathologically determined width of tumor cell free area measured 10.2 ± 2.48 mm (range: 4.5 to 18.5 mm). The width was measured on 359 slides from 46 patients ( (figure 2) ). The microscopic gap between the histopathological tumor border and the clinical border scored by scalpel tract measured 0.334 ± 1.183 mm (range: –3.0 to +5.4 mm). The gap was measured on 137 slides from 29 patients ( (figure 3) ).

All 46 cases presented here have remained free of local recurrence for periods ranging from 24 to 115 months. Twelve cases died. Of these 12, 10 died of unrelated causes. Two developed fatal systemic carcinomas, but with no local recurrence.

Discussion

The present study showed that the clinically determined border of well-defined lesions of EMPD corresponds well to the histo-pathologically-determined border. There was scarcely any significant microscopic gap between the clinical border scored by scalpel incision and the histopathological border ( (figure 3) ). The microscopic distance from the histopathological tumor margin to the surgical resection-margin, determined with a micro-oculometer, measured about 1 cm ( (figure 2) ). At a mean follow-up of 3.9 years, there were no local recurrences, suggesting that the clinically well-demarcated lesions of EMPD can be adequately managed with resection with a 1 cm margin.

These results argue against tissue mapping with multiple biopsies [8, 9], Mohs’ technique, topical application of 5-FU [10], fluorescein visualization [11], and photodynamic diagnosis [12], all of which are based on the observation that the border of the EMPD lesion is indistinct and that silent peripheral extensions of Paget’s cells may extend unpredictably for a long distance beyond the borders of clinically involved skin. High rates of local recurrences, on the order of 43 to 50%, have been reported [12-14]. Further study is needed to explain the discrepancy between these results and those of the current study.

It seems most important to know how the borders of clinically involved skin were defined. Hitherto the preoperative care of the EMPD lesions has not been described nor how closely the EMPD lesions were observed to define the clinical borders. The lesional and perilesional skin may be irritated by copious discharge, maceration, eczematization due to scratching, exacerbated by avoidance of bathing and inappropriate application of topical agents such as antifungals. The irritation may be a long-standing event because patients with genital EMPD do not visit the physician because of embarrassment regarding the lesions. Time to diagnosis may also be a factor. In our institute, it is not uncommon to see an overlap of the red EMPD lesions and the inflammatory erythema of the perilesional skin at the time of their first visit ( (figure 4) ). At this point in time, the border could be obscured, and an inexperienced physician might consider elevated plaques to be part of the EMPD lesions and miss the less distinct changes of EMPD.

In our institute, we shave the pubic hair of patients with EMPD several days before the operation. Then, every dermatological effort is made to eliminate the secondary irritant inflammation other than the erythema directly related to EMPD, utilizing topical steroids, antifungals, emollients, or water-soluble ointment, applied singly or in combination ( (figure 5) ). On the day before the operation, we examine the lesions with sufficient time for close inspection utilizing a gynecological examination table instead of the usual examination on a flat bed. Changing the intensity and direction of the electric light makes it easier to identify the subtle differences of the skin texture caused by the infiltration. Tangential lighting may facilitate observation of faint surface torsion that otherwise may not be seen.

This slight infiltration may correspond histopathologically to the slight edema and cellular infiltration in the papillary dermis. The extent of these dermal changes is restricted to the area where the Paget’s cells can be identified in the epidermis. It should be noted that what we can see clinically at the periphery of the EMPD lesions is not the mass of proliferating Paget’s cells but the reactionary inflammatory changes against tumor cells. These changes may be clinically much more inconspicuous than well-established papillary and/or eroded lesions histopathologically composed of acanthotic epidermis, rich in nests of Paget’s cells. Hypopigmented lesions of EMPD may show exceptionally poor demarcation even after appropriate topical care. A pre-operative or intra-operative biopsy may be indicated for hypopigmented lesions in EMPD patients. In such circumstances of ill defined clinical margins, Mohs micrographic surgery, if available, may be useful to identify the histopathological margins and minimize tissue loss. Most lesions of EMPD, however, will show well-defined demarcation when adequate dermatological care and examination are carried out. The present study provides enough evidence to argue against indiscriminate wide resection for EMPD.

Dermatological surgeons treating EMPD should examine and evaluate the accuracy of the clinical border they define. For this purpose, sections taken perpendicular to the planes of surgical excision may be preferable to sections parallel to the margin. Examinations with sections taken parallel to the margin may provide information about the presence or absence of Paget’s cells at the resected margin. Examinations with sections taken perpendicular to the margin, however, will provide more information to surgeons about how accurately they defined the clinical margin. Patients with EMPD are typically elderly and suffer from many medical complications. Dermatological surgeons should make every effort to achieve adequate excision of EMPD lesions without unnecessary sacrifice of normal tissue.

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