Perianal Paget's disease—Report of a rare case

Abstract

INTRODUCTION

Perianal extra-mammary Paget's disease is a rare skin disorder of unknown aetiology, which is frequently associated with malignancy. This case report draws attention to this rare condition and comments upon its diagnosis and treatment.

PRESENTATION OF CASE

A 64-year-old otherwise fit man, presented to us in 2006 with one-year-long history of perianal irritation. On examination there was an erythematous discoid skin lesion in the right perianal area. The lesion was excised with wide margins and the defect closed with a local transposition flap. Histology confirmed extra-mammary Paget's disease (EMPD) with a focus of invasion showing a well-differentiated mucinous adenocarcinoma. Adjuvant therapy was not advised. On follow-up in 2011, a small irregular skin lesion, well away from the previous excision site was noted on the left perianal area. Biopsies from this lesion confirmed EMPD with no focus of invasion. Once again wide local excision with closure using local transposition flap was undertaken. Long term follow up has been advised.

DISCUSSION

The optimal treatment for Perianal Paget's disease (PPD) remains controversial. Surgery is the commonest modality used with wide local excision being the treatment of choice for resectable disease. We report herein a short review of various therapies reported so far in the management of this rare disorder.

CONCLUSION

A thorough initial evaluation and long-term follow-up is essential to identify recurrence and the development of other related malignancies.

1. Introduction

Extramammary Paget's disease (EMPD) is a rare skin disorder involving adult Caucasians. The disease usually involves skin areas rich in apocrine glands such as axilla and anogenital region. Vulva is by far the commonest anogenital site with perianal involvement being a distinct rarity. We report herein a recent case of Perianal Paget's disease (PPD) managed successfully at our unit.

2. Case report

A 64-year-old otherwise fit man, presented to us in 2006 with one-year-long history of perianal irritation and minimal rectal bleeding. He did not report any weight loss or other alarm gastrointestinal symptoms. His past medical history included banding for haemorrhoids and complete excision of a severely dysplastic rectal polyp in 2000. Surveillance colonoscopy in 2004 was normal and the patient was discharged. Local examination revealed an erythematous discoid skin lesion in the right perianal area measuring 2 cm × 2 cm with surrounding lichenification. Rectal examination was normal apart from small internal haemorrhoids. Abdominal examination was unremarkable and inguinal glands were not palpable. The perianal skin biopsy was consistent with EMPD. Subsequent colonoscopy and CT scan of the chest, abdomen and pelvis were negative. The lesion was excised with wide margins and the defect was closed using a local transposition flap. Histology confirmed EMPD with a focus of invasion showing a well-differentiated mucinous adenocarcinoma. Findings were discussed at the anal MDT meeting and a close follow-up with no adjuvant therapy was advised.

Follow-up visit in 2011 revealed healthy right perianal area with no evidence of recurrence. However a small irregular skin lesion was noted on the left perianal area. Biopsies from this lesion confirmed EMPD with no focus of invasion. Further workup including scans, endoscopy and tumour markers were unrewarding. He underwent an uneventful wide local excision of the left perianal area with reconstruction using a transposition flap. A close follow-up has been advised.

3. Discussion

Perianal Paget's disease (PPD) is a rare intraepithelial adenocarcinoma of unknown aetiology, characterised histologically by the presence of malignant Paget cells in the epidermis. PPD represents 20% of cases of extra-mammary Paget's disease and 6.5% of all cases of Paget's disease.¹ Recent work has supported the view that Paget cells in extramammary Paget's disease (EMPD) are glandular cells of apocrine origin as indicated by the expression of gross cystic disease fluid protein (GCDFP) antigen, low molecular weight cytokeratins and carcinoembryonic antigen.¹

The first report on EMPD was by Darier and Coulillaud in 1893,² almost two decades after Sir James Paget first described the characteristic mammary lesion. There has been much controversy as to whether Paget's disease is a primary disorder or a manifestation of an underlying subjacent or distant invasive carcinoma. Helwig and Graham studied 40 patients with anogenital Paget's disease, seven of whom had extra-cutaneous malignancy. Four of these had rectal adenocarcinoma.³ A case of PPD complicated by Grade 2 squamous carcinoma was reported by Nelson.⁴

PPD disease should be considered in middle-aged or elderly patients who present with a long history of pruritus ani refractory to local medical treatment. The typical finding on examination is an erythematous, well-circumscribed plaque that may be ulcerative, crusty or papillary. Full thickness biopsies of the affected perianal skin with mapping biopsies must be obtained for precise preoperative histological assessment.⁵ Subsequent workup such as scans and endoscopy to exclude any underlying primary malignancy is crucial for accurate diagnosis, prognosis and treatment.

The depth of invasion, lymph node involvement and metastatic spread of the disease define the management of PPD. The treatment of choice is wide local excision with at least 1 cm clearance.² Resultant defects generally require local or regional flaps to bridge the gap and secure a better functional outcome. Aggressive surgical approach with radical excision results in significant tissue loss and poses a cosmetic and functional challenge to surgeons. Lam et al.⁶ described staged excision and split-thickness skin graft for the management of circumferential perianal lesions. Favourable outcomes have been reported with the use of transposition or rotation skin flaps, bilateral myocutaneous flaps of the gluteal and thigh muscles and V-Y island flaps to cover the areas of tissue loss.⁷ Mohs micrographic surgery (MMS) has been reported to be an effective and superior technique compared to standard surgical management for circumferential PPD.⁸ The technique allows for maximal tissue sparing of critical anatomical structures and is performed under local anaesthesia as an outpatient. Nevertheless, local recurrence rates for both conventional excision and MMS are well documented in the literature with quoted figures of 23% and 31–61% respectively (Figs. 1–3).^9,10

Fig. 1.

5X HE image of extramammary Paget's disease with focus of stromal invasion.

Fig. 2.

Recurrence of Perianal Paget's disease on the left.

Fig. 3.

Wide local excision of the left perianal area and reconstruction with a transposition flap.

Despite their contentious role, the use of non-surgical modalities constitutes a reasonable alternative to surgery. Indications include elderly and high-risk patients, inoperable tumours, unwillingness for mutilating surgery and those with occult and multifocal disease. Radiotherapy may be employed as an adjunct to surgery (to reduce long term local recurrence) or to treat post-operative local recurrence.⁹ Use of radiotherapy as a primary therapeutic modality is also well established. Yanagi et al. reported their experience of genital EMPD managed successfully by radiotherapy (40–50 Gy) in elderly patients.¹¹ For patients with EMPD and adenocarcinoma, doses of >55 Gy or concurrent chemotherapy may be indicated. High dose radiotherapy to the perianal area is often associated with enteritis, proctitis and cystitis and may result in colostomy.⁹

EMPD has also been managed with topical chemotherapeutic agent such as 5-fluorouracil (5FU), bleomycin and imiquimod. Local 5-fluorouracil has been employed for symptomatic relief and cytoreduction before operative management.¹² Watring et al. achieved 57% complete remission with topical bleomycin in patients with recurrent non-invasive vulval EMPD.¹³ Case reports have recorded complete response to systemic mitomycin C and 5-FU.¹⁴ In cases where surgery and radiotherapy are contraindicated, chemotherapy can be the chosen mode of treatment. Over expression of HER-2 protein is seen in 20–60% cases of EMPD and signifies poor prognosis often due to deep dermal invasion or metastatic disease. Combination systemic therapy with paclitaxel and transtuzumab has been used in metastatic EMPD with HER-2 over-expression with high response rates.¹⁵

Recent literature demonstrates the therapeutic advantage of photodynamic therapy (PDT) in preserving the anus and its function when managing PPD. The size and margins of tumour can be identified by ALA/PpIX-mediated fluorescence examination (5 aminolevulinic acid/protoporphyrin IX) thus ascertaining PDT treatment of the entire tumour lesion.¹⁶ Advantages of PDT include: low toxicity, better cancer selectivity and ability to be repeated. Intralesional interferon (IFN alfa-2b) has been used successfully in neo-adjuvant setting to downgrade PPD enabling a less mutilating resection with long term remission.¹⁷

4. Conclusion

PPD is a rare disorder, which continues to pose a diagnostic and therapeutic challenge. Wide local excision remains the treatment of choice with an evolving role for various adjuvant therapies. Despite adequate resection long term out look remains guarded due to high recurrence rate.

Conflict of interest

We (the authors) declare no conflict of interest in regards to this article.

Funding

None.

Ethical approval

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Author contributions

Laura Martin and Faisal El-Madani contributed to the data collection. Veena Naik contributed to the provision of images of histology. Stephanos Papanastasiou contributed to the provision of operative images. Sanjay Gupta contributed to the advice and supervision in writing and design of case report.