








































Key Words Competing Interests Article Information

Biopsy, extramammary Paget disease, 
recurrence, oncology

None declared. Received on May 17, 2022 
Accepted on August 19, 2022 
This article has been peer reviewed.

Soc Int Urol J. 2023;4(1):34–38

DOI: 10.48083/LCME5237

Oncologic Outcomes of a Novel Mapping Biopsy 
Technique Before Surgical Excision in the 
Management of Extramammary Paget Disease

Kyle M. Rose,1 Rosalie Zurlo,2 Roger Li,1 Gerard Mosiello,3 Philippe E. Spiess1

1 Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, United States 2 University of South Florida, Morsani College of Medicine, Tampa, United States  
3 Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, United States

Abstract

Objective To analyze oncologic outcomes of patients with extramammary Paget disease (EMPD) undergoing a 
novel mapping biopsy before tumor excision (WLE).

Methods We analyzed 19 consecutive patients with EMPD treated with biopsy and/or surgical excision at Moffitt 
Cancer Center from 2013 to 2021. Biopsy technique, patient demographics, pathology, and oncologic outcomes were 
analyzed.

Results In total, 19 patients were included in the analysis. Median age at diagnosis was 72. No patients were 
diagnosed with secondary malignancy during mandatory workup. Of the 17 patients receiving novel mapping biopsy, 
8/17 had at least one positive core biopsy site, with a mean of 7% positivity of the total core sites (4/60). Mapping 
biopsy positive sites helped shape perimeters for wide local excision (WLE) for patients opting for surgical treatment. 
Although an extensive mapping biopsy was performed, WLE margins were positive in 11/17 patients. Although 
positive pathologic margins following surgical excision were prominent, only one patient experienced recurrence of 
EMPD during a median follow-up period of 38 months.

Conclusions We have demonstrated a standardized mapping biopsy before surgical excision in the management of 
EMPD in men. Despite extensive mapping biopsies, positive surgical margin rates are high, and this may reflect the 
occult nature of the disease process. Close follow-up is warranted in patients regardless of margin status, but those 
with positive surgical margins may benefit from more aggressive regimens.

Introduction

Extramammary Paget disease (EMPD) is a rare neoplasm presenting in the genital and perianal regions of men and 
women. It is characterized by a chronic erythematous plaque and is commonly associated with pruritis and pain[1]. 
The discomfort associated with the lesions often leads to mischaracterization as eczema or fungal infection, which 
may further delay treatment. Unfortunately, despite standard of care measures, recurrence rates as high as 16% to 61% 
have been reported[2–5]. Surgical excision with negative margins is the gold standard in management, but topical and 
systemic chemotherapy can also be used if there are contraindications to surgery[6].

34

This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited.  
© 2023 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

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https://orcid.org/0000-0001-7728-1144
mailto:Kyle.rose%40moffitt.org?subject=SIUJ
https://orcid.org/0000-0003-1274-7200
https://orcid.org/0000-0002-5723-1972
http://SIUJ.org


EMPD is treated by a variety of specialties including 
urologists, colorectal surgeons, and dermatologists, 
depending on location and patient access to care. As a 
result, there is no standardized biopsy or wide local 
excision (WLE) technique for EMPD to ensure negative 
resection margins. Dermatologists frequently utilize 
Mohs micrographic surgery to provide pathological 
confirmation of negative margins intraoperatively. In 
contrast, WLE is traditionally employed by urologists 
and colorectal surgeons, and requires a pre-resection 
biopsy. In either case, standardization of biopsy and 
excision technique is lacking.

The establishment of a global strategy for mapping 
before excision is paramount in the surgical management 
of EMPD. Herein, we describe a novel standardized 
technique in the mapping and treatment of EMPD at our 
institution. Our objective was to determine the efficacy 
of this mapping technique before excision by analyzing 
recurrence rates of EMPD, thereby assessing the accuracy 
of surgical margin delineation.

Materials and Methods
After obtaining institutional review board approval, 
we performed an analysis on patients undergoing 
surgical excision for EMPD at our facility between 
2013 and 2021. For inclusion, patients were required 
to have had a mapping biopsy and/or WLE . A l l 
cases were per for med by a si ng le su rgeon. A l l 
pat ients u nder went ma nd ator y c ystoscopy a nd 
colonoscopy, which were required to be negative. 
Patient demographics, clinicopathologic outcomes, 
and perioperative outcomes were collected. Patient 
clinical stage was determined using the TNM staging 
system for EMPD as described by Ohara et al.[7]. 
Perioperative complications were scored using the 
modified Clavien-Dindo scale[8].

The technique for mapping biopsy before excision 
involves 60 total biopsy sites, taken in a clockwise 
fashion around the lesion. The biopsies are typically 
1.5 mm in size, and 5 are taken for each “hour” of the 
clock face, spaced 1 cm apart. This technique allows 
the surgical team to clearly demarcate the required 
tissue needed to achieve a negative margin at the time 
of WLE. All biopsy specimens were reviewed by a 
dedicated dermatopathologist.

Results
From 2013 to 2021, 19 patients underwent mapping 
biopsy followed by WLE. The median age (IQR) at 
surgery was 72 (66.5 to 76.0). Table 1 details baseline 
patient characteristics. Of note, 13 (65%) had a history 
of malignancy before EMPD diagnosis, the most 
common of which was a dermatologic carcinoma in 
12 patients, followed by prostate cancer in 4 patients. 

Eleven patients (58%) had a past or current history 
of smoking. Most patients had at least one medical 
comorbidity, with 14 diagnosed with hypertension, 8 
with hyperlipidemia, 7 with CAD, and 7 with BPH.

Three patients were treated with topical chemotherapy 
before presentation, while 6 patients were treated with 
topical antifungals due to misdiagnosis. Preoperative 
irritative symptoms were reported in 9 patients (47%) 
at a median (IQR) duration of 2.5 (1.0 to 3.0) years, and 
included erythema in 17 (89%), itching in 10 (53%), pain 
in 8 (42%), and drainage in 2 (11%). EMPD occurred 
in  the scrotum-alone in 8 (42%), the perineum in 1 
(5%), the groin in 3 (16%), the penis in 2 (11%), and was 
multifocal in 6 (32%).

Seventeen patients received mapping biopsy, and 2 
had shave biopsies. Two patients decided against surgical 
excision of lesion after biopsy, opting for conservative 
monitoring. Eight mapping biopsies (47%) were positive 
for EMPD in at least one core, with an average of 7% 
of cores positive (4/60). Mapping biopsy results were 
used to delineate WLE borders, and negative results 
typically indicated a smaller resection site. Of the 17 
patients undergoing surgical excision, 16 had WLE. For 
wound closure, 8 patients required split thickness skin 
graft (STSG), in 3, local tissue mobilization was used to 
assist in closure, 2 patients required creation of a thigh 
flap, and in 1 case, primary re-approximation was used 
(Figure 1).

All patients were staged as primary pT1 EMPD on 
final pathology. Margins were positive in 65% of lesions 
(11/17). Of the 13 patients with immunohistochemistry 

TABLE 1. 

Clinical characteristics of patients before mapping 
biopsy 

Age (median, IQR) 72 (76.0–66.5)

Prior cancer diagnoses 13 (68%)

Smoking history 11 (47%)

Prior failed treatment 3 (16%)

Symptomatic at presentation 9 (47%)

Presence of multifocality 1 (5%)

Positive mapping biopsy 10 (53%)

Cores positive on mapping biopsy 4 (6.7%)

35SIUJ.ORG SIUJ  •  Volume 4, Number 1  •  January 2023

Oncologic Outcomes of a Novel Mapping Biopsy Technique Before Surgical Excision in the Management of Extramammary Paget Disease

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staining, Ck7 was positively stained in 10 cases (77%). 
Lymphovascular and adnexal invasion were uncommon, 
both occurring in 3 of 7 patients. The median follow-up 
for the cohort was 14 months, during which time  
1 patient experienced recurrence with osseous metasta-
sis 6 years following WLE, and is currently undergoing 
chemoradiation therapy. During follow-up, there was  
1 death of unrelated etiology.

Complications occurred in 5 patients (29%), all 
related to wound healing. There were 2 episodes of 
wound dehiscence, one episode of skin necrosis requiring 
debridement, one episode of tension discomfort requiring 
repeat STSG, and one episode of prolonged wound heal-
ing with abnormal drainage. Table 2 illustrates the size 
of excised lesions in patients with and without wound 
complications, for which there were no differences 
between groups.

Discussion
In this series, we describe a standardized mapping 
biopsy process for EMPD. Our central finding is the 
high positive WLE margin rate despite extensive 
preoperative punch biopsy mapping. While surgical 
excision with negative resection margins remains the 
gold standard treatment in EMPD, barriers to achieving 
negative margins include the multifocal nature of this 

FIGURE 1.  

TABLE 2. 

Postoperative wound issue and size of primary lesion 

Wound Complications 
Post-WLE

P -value

Yes No

Median size of lesion (cm) 121 124.6 0.74

IQR 66–168 85–147

Patients with extramammary Paget disease (EMPD)
n = 19

Patients with EMPD undergoing
shave biopsy

n = 2

Rotational thigh �aps
n = 2

Split thickness 
skin grafts

n = 8

Patients EMPD undergoing surgical excision
n = 17

Primary closure with
tissue mobilization

n = 7

Diagnosis

Biopsy

Treatment

Closure

Patients with EMPD undergoing 
novel mapping biopsy

n = 17

Patients deferring
surgical excision

n = 2

disease process, as well as the presence of skip lesions. 
Positive margins have been identified as risk factors 
for tumor invasion, recurrence, and metastasis in prior 
EMPD series[9,10]. In a recently published review 
by Leong and Chung, the investigators complied 
composite scores for recurrence based on margin 
status at the time of excision. Patients with positive 
margins at WLE demonstrated a higher recurrence 
rate of 48% versus 15% in those with negative margins. 
Similarly, the authors compared composite scores of 
WLE and Mohs micrographic surgery, and identified 
Mohs as having a lower positive margin rate (18% 
versus 33%). The use of Mohs surgery may be a limiting 

36 SIUJ  •  Volume 4, Number 1  •  January 2023 SIUJ.ORG

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factor depending on resources available to certain 
institutions, but microdissection and pathologic review 
in real time appear to be beneficial. Additional surgical 
augmentations include the use of intraoperative frozen 
sections, which has demonstrated a higher negative 
margin rate (92% versus 26%)[11]. Additionally, surgeons 
have utilized f luorescein to augment visualization 
during excision, which has a 97% positive predictive 
value and 99.9% negative predictive value[12]. Both of 
these tools add value in the surgeon’s armamentarium.

The high positive surgical margin rate in our series 
is unfortunately a common, with previous studies 
reporting rates as high as 40% to 60% after surgical 
excision[13–17]. However, while recurrence rates are 
higher in margin-positive patients, the direct impact 
on cancer specific survival is less clear, especially in the 
non-invasive malignancy setting. In a survival analysis 
using the Surveillance, Epidemiology, and End Results 
(SEER) program, worse survival was associated with 
increased age and male sex, and in patients who did not 
receive surgery as primary therapy, especially those who 
had received radiotherapy[18]. A similar SEER study 
performed by Herrel and colleagues reported an over-
all survival of 60% at 120 months post diagnosis[19]. 
The authors identified that patient age and presence of 
EMPD in the perianal and truncal regions portended 
a worse prognosis[19]. However, it is important to note 
the limitations of these 2 large-sample studies, in that 
the SEER database does not allow for analysis by margin 
status. Alternatively, tumor invasion was identified as a 
significant contributor to survival, as described in the 
study by Hegarty et al. of 20 patients, in which patients 
with invasive EMPD demonstrated a lower survival rate 
of 14.5 months versus 55 months in those with intra- 
epidermal adenocarcinoma[9].

Our findings suggest that positive surgical margins 
may not correlate as strongly with recurrence as 
previously thought. The presence of positive surgical 
margins does place the patient in a higher risk group, 

which prompts the surgical team to escalate outpatient 
follow-up and surveillance. In clinical practice,   this 
could include more frequent examinations, repeat biop-
sies for recurrent disease, and photograph documenta-
tion. The novel mapping biopsy and WLE in our study 
were performed by a single surgeon to improve unifor-
mity and consistency. Importantly, surgeons should be 
aware of the potential for wound complications following 
WLE, which occurred in 5 patients in our series.

Limitations of our study include its retrospective 
natur e, presenting the potential for selection bias among 
patients with localized disease. The novel mapping 
biopsy and WLE utilized in our study was performed 
by a single surgeon to improve uniformity and consis-
tency. Additionally, our patients were exclusively male, 
and therefore extrapolation of our findings to the gyne-
cologic field should be limited. Further, the median 
follow-up in our cohort was relatively short at 14 months. 
Long-term follow-up data are needed to solidify the rela-
tionship between positive surgical margins and disease 
recurrence. Due to the rarity of this disease process, 
large-scale randomized trials will be unlikely to accrue, 
and thus there is a need for uniform mapping biopsies 
and surgical techniques, as previously described.

Conclusions
In this study, we have demonstrated a standardized 
mapping biopsy before surgica l excision in t he 
management of EMPD in men. Despite extensive 
mapping biopsies, positive surgical margin rates are 
high, and this may ref lect the occult nature of the 
disease process. Close follow-up is warranted in patients 
regardless of margin status, but those with positive 
surgical margins may benefit from more aggressive 
regimens. Long-term follow-up is needed to determine 
the impact of microscopically positive margins on 
disease specific survival, which will aid the surgical team 
in determining aggressiveness of resection.

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References

1. McDaniel B, Brown F, Crane JS. Extramammary Paget disease. In: 
StatPearls. Treasure Island (FL)2022 Jan. Available at: https://pubmed.
ncbi.nlm.nih.gov/29630276/. Accessed November 12, 2022.

2. Hendi A, Brodland DG, Zitelli JA. Extramammary Paget’s disease: 
surgical treatment with Mohs micrographic surgery. J Am Acad 
Dermatol.2004;51(5):767-773. doi: 10.1016/j.jaad.2004.07.004.

3. Lee K Y, Roh MR, Chung WG, Chung K Y. Comparison of Mohs 
micrographic surgery and wide excision for extramammary Paget’s 
disease: Korean experience. Dermatol Surg.2009;35(1):34-40.

4. Pierie JP, Choudr y U, Muzikansk y A, Finkelstein DM, Ott MJ. 
Prognosis and management of extramammar y Paget’s disease 
and the association with secondary malignancies. J Am Coll Surg. 
2003;196(1):45-50.

5. Wong DS-Y Ko LW-L, Cheung T-H. Extramammary Paget’s disease: surgical 
control from the plastic surgery perspective. Surg Pract.2016;20(3):110-
113. doi.org/10.1111/1744-1633.12188

6. NIH, National Center for Advancing Translational Sciences. 
Extramammary Paget disease.2021. Available at: https://rarediseases.
info.nih.gov/diseases/4192/extramammary-paget-disease. Accessed 
September 17, 2021.

7. Ohara K, Fujisawa Y, Yoshino K, Kiyohara Y, Kadono T, Murata Y, et al.  
A proposal for a TNM staging system for extramammary Paget disease: 
retrospective analysis of 301 patients with invasive primary tumors.  
J Dermatol Sci.2016;83(3):234-239. doi: 10.1016/j.jdermsci.2016.06.004.

8. Mitropoulos D, Artibani W, Biyani CS, Bjerggaard Jensen J, Roupret 
M, Truss M. Validation of the Clavien-Dindo grading system in urology 
by the European Association of Urology Guidelines Ad Hoc Panel.  
Eur Urol Focus.2018;4(4):608-613.

9. Hegarty PK, Suh J, Fisher MB, Taylor J, Nguyen TH, Ivan D, Prieto 
VG, et al. Penoscrotal extramammary Paget’s disease: the University 
of Texas M. D. Anderson Cancer Center contemporary experience.  
J Urol.2011;186(1):97-102. doi: 10.1016/j.juro.2011.02.2685

10. Leong JY, Chung PH. A primer on extramammary Paget’s disease for 
the urologist. Transl Androl Urol.2020;9(1):93-105.

11. Yang WJ, Kim DS, Im YJ, Cho KS, Rha KH, Cho NH, et al. Extramammary 
Paget’s disease of penis and scrotum. Urology.2005;65(5):972-975. doi: 
10.1016/j.urology.2004.12.010

12. Misas JE, Cold CJ, Hall FW. Vulvar Paget disease: fluorescein-aided 
visualization of margins. Obstet Gynecol.1991;77(1):156-159.

13. Fanning J, Lambert HC, Hale TM, Morris PC, Schuerch C. Paget’s 
disease of the vulva: prevalence of associated vulvar adenocarcinoma, 
invasive Paget’s disease, and recurrence after surgical excision. Am J 
Obstet Gynecol.1999;180(1 Pt 1):24-27.

14. 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.1997;4(6):475-480.

15. Sarmiento JM, Wolff BG, Burgart LJ, Frizelle FA, Ilstrup DM. Paget’s 
disease of the perianal region--an aggressive disease? Dis Colon 
Rectum.1997;40(10):1187-1194.

16. Yugueros P, Keeney GL, Bite U. Paget’s disease of the groin: report of 
seven cases. Plast Reconstr Surg.1997;100(2):336-339.

17. Zollo JD, Zeitouni NC. The Roswell Park Cancer Institute experience 
with extramammary Paget’s disease. Br J Dermatol.2000;142(1):59-65.

18. Yao H, Xie M, Fu S, Guo J, Peng Y, Cai Z, et al. Survival analysis of 
patients with invasive extramammary Paget disease: implications 
of anatomic sites. BMC Cancer.2018;18(1):4 03. doi: 10.1186/
s12885-018-4257-1

19. Herrel LA, Weiss AD, Goodman M, Johnson TV, Osunkoya AO, Delman 
KA, et al. Extramammary Paget’s disease in males: survival outcomes 
in 495 patients. Ann Surg Oncol.2015;22(5):1625-1630. doi: 10.1245/
s10434-014-4139-y

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https://rarediseases.info.nih.gov/diseases/4192/extramammary-paget-disease
https://rarediseases.info.nih.gov/diseases/4192/extramammary-paget-disease
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