A Primer on Extramammary Paget's Disease for the Urologist

Joon Yau Leong; Paul H. Chung


Transl Androl Urol. 2020;9(1):93-105. 

In This Article

Surgical Treatment

Surgical excision with negative margins is the mainstay treatment for EMPD. Lesions may skip, be multifocal, or develop asymmetrically, which makes achieving negative surgical margins challenging.[20] Furthermore, margins cannot be clearly identified with visual inspection alone as malignant cells are capable of extending microscopically beyond the clinically evident lesion. Achieving negative margins is paramount for long-term survival as it has shown to prevent further invasion, metastasis and recurrence (Table 2).[17,78–81] Choi et al. identified that marginal status and lymphovascular invasion were the most valid prognosticating factors for EMPD recurrence, while Long et al. demonstrated that patients with positive margins had a four-fold increased risk of suffering local recurrence when compared to those with negative margins.[82,83]

Several techniques have been adopted to help achieve negative margins, including the use of preoperative mapping biopsies, wide margins, intraoperative frozen sections and immunohistochemical and fluorescein staining.[24,84,85,87–90] Yang et al. reported a 92% rate of obtaining negative margins with intraoperative frozen sections versus 26% without frozen sections. Misas et al. reported a 97.4% positive predictive value and 99.9% negative predictive value when assessing disease extent with fluorescein when compared to direct visualization.[84,88] Despite these efforts, obtaining negative margins remains challenging.[91] A study in 2005 found that 10 out of 19 patients (53%) were found to have positive margins despite undergoing intraoperative frozen sections during WLE.[11] This may occur when only limited amounts of pathology frozen sections are assessed intraoperatively and complicated by the presence of multicentric, multifocal disease.[83,86,92] Given the importance of obtaining negative margin status, we recommended surgical treatment to be performed at higher volume centers with the resources available to effectively perform adjunctive approaches.

The decision of surgical approach has been a long-standing debate among physicians. While MMS involves examining all the histological margins of the tumor during surgery, intraoperative frozen sections during WLE may sample a more limited area. Conceptually, MMS may seem like the preferred option over WLE for the treatment of EMPD. As such, certain investigations have shown that MMS may be superior to WLE in achieving negative margins.[8,90,93] Unfortunately, this disease develops multifocal and skip lesions, which may account for some of the treatment failures with MMS. Effective use of MMS requires specialized training and may not be appropriate for larger lesions or lesions located in sensitive genital locations.

Although composite rates of achieving negative margins with MMS (97%) was higher than WLE (65%), other studies have also demonstrated comparable outcomes in obtaining adequate cancer control with both methods.[6,11,17,83,94] Lesion size may play a role in selecting the surgical approach. A review of 38 cases of EMPD treated with MMS found that 76% of lesions were ≤10 cm while 97% of cases had lesion sizes ≤15 cm.[93,95,96] Conversely, 95% of lesions treated with WLE were found to be ≥10 cm with 70% of lesions treated by Chung et al. being ≥15 cm, with the largest lesion measuring 30 cm in diameter.[6,97] Several studies have demonstrated the ability of WLE to be performed safely and adequately and to yield equally satisfactory and durable outcomes to MMS with recurrence rates ranging from 21–60% in WLE and 0–26% in MMS (Table 3).[78,80,98–103] This suggests that while MMS may be effective in obtaining negative margins, it may be less amendable to treating larger EMPD lesions, in which case WLE may be the more favorable option.

Morbidity and complication rates differ between these two surgical approaches. MMS allows for maximal tissue sparing and decreased complication rates when compared to WLE which is associated with higher risk of neurovascular injuries, lymphedema and skin defects.[94] However, MMS is limited to smaller lesions, is performed under local anesthesia and may require closure of the defect at a separate encounter by another surgeon.[93] Conversely, WLE may be performed for larger lesions or lesions in sensitive areas. Patients undergoing WLE may also benefit from simultaneous primary closure or admission for inpatient wound care prior to delayed closure as final pathology is being reviewed.[97] Both MMS and WLE have their respective advantages and an individualized, shared-decision making approach is recommended.

EMPD defects may require reconstruction with the use of complex primary closures, skin grafts and flaps.[11] Skin grafts are a versatile reconstructive method with reported use as high as 44–80% in the management of EMPD. Advancement flaps, rotational flaps and myocutaneous flaps of the gluteal and thigh muscles may also be used for coverage and may require the assistance of a plastic surgeon.[104–108] In general, penile shaft lesions may best be covered with skin grafts to preserve cosmesis and reduce the risk of contracture or chordee formation. Suprapubic, scrotal, inguinal, and perineal lesions may be amenable to complex primary closure by aggressive mobilization of neighboring tissues, flaps, or skin grafts. Due to the skills needed to both excise and reconstruct the genitalia, a reconstructive urologist may be best suited to manage localized genital EMPD.

At our institution, WLE is the preferred method for excision of genital EMPD lesions (Figure 3).[97] Pre-operative mapping biopsies and intra-operative frozen sections are used in conjunction with a 2-cm margin to help overcome the insidious nature of EMPD. Murata et al. found that the distance between the resected edge of the EMPD lesion to the last lesional cell on histopathology measured 1.02 cm on average.[109] This, coupled with surgeon preference, justified our rationale for obtaining 2-cm margins when managing EMPD patients. Our protocol is to delay complex wound closure (skin grafting or flaps) until negative margins have been confirmed on final pathology. Patients requiring complex wound closure are admitted for inpatient wound care with wet-to-dry dressings or xenografts while permanent specimens undergo expeditious pathology review. If positive margins are identified, further excision of the corresponding region is performed. Once negative margins are confirmed, complex wound closure with or without split thickness skin grafting or local flaps is performed during the same admission.[97]

Figure 3.

Wide local excision with pre-operative mapping biopsies and intra-operative frozen sections is the preferred method for treating genital EMPD lesions at our institution. (A) A 2-cm margin is delineated around the clinically suspicious lesion as indicated by the dotted line; (B) Wide local excision was performed and (C) the defect was closed primarily after frozen sections were confirmed negative. Final pathological margins were confirmed to be negative and the patient did not require repeat excision. EMPD, extramammary Paget's disease.

Although there are no strict guidelines regarding the need and frequency of post-operative management, continued surveillance and follow-up is absolutely warranted due to the high incidence of recurrence with EMPD. We follow patients every 3 months in the first year, 6 months in the second and annually thereafter. A routine physical examination is required during each clinic visit, while cross sectional imaging of the abdomen and pelvis can be performed with either CT or MRI to rule out systemic metastasis. Mapping biopsies may be performed according to clinical suspicion for disease recurrence while serum CEA levels are obtained to monitor treatment response.