Gynecologic Oncology 129 (2013) 412–416

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Gynecologic Oncology
journal homepage: www.elsevier.com/locate/ygyno

Primary extramammary Paget's disease of the vulva: The clinicopathological features

and treatment outcomes in a series of 43 patients
Yipin Cai a, 1, Weiqi Sheng b, 1, Libing Xiang a, Xiaohua Wu a, Huijuan Yang a,⁎
a
Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
b
Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

H I G H L I G H T S

• Intraepithelial EMPDV is a predominant subtype with better prognosis.

• Surgery is the standard treatment for EMPDV; however, a positive margin is common.
• Recurrence was common and repeated excision or radiotherapy was necessary.

a r t i c l e i n f o a b s t r a c t

Article history: Objective. To characterize the clinicopathological features and evaluate the treatment outcomes for cases
Received 26 November 2012 of primary extramammary Paget's disease of the vulva (EMPDV).
Accepted 20 February 2013 Methods. The medical records and pathology slides were reviewed and analyzed for 43 patients with pri-
Available online 27 February 2013 mary EMPDV.
Results. The mean age of the patients was 68.6 years (range, 52–85). Intraepithelial EMPDV, invasive
Keywords:
EMPDV and EMPDV with adnexal adenocarcinoma were observed in 33 (76.7%), 7 (16.3%) and 3 (7.0%)
Extramammary Paget's disease of the
vulva (EMPDV)
cases, respectively. Varied surgical procedures were initially performed in 35 (81.4%) cases. A positive inci-
Surgery sion margin was observed in 16 cases (47.0%). Definitive radiotherapy at a median dose of 60 Gy was
Radiotherapy performed in 8 (18.6%) patients. Six patients received postoperative radiotherapy due to a positive margin
Recurrence or lymph node metastasis after surgical excision. During a follow-up period of 6–169 months (median,
54), recurrence was observed in 12 (34.3%) patients. Nine (75.0%) patients underwent repeated surgery
and 3 (25.0%) patients received radiotherapy. Long-term overall survival was observed in patients with
intraepithelial EMPDV. The median overall survival was 124.5 months in intraepithelial cases, 70.8 months
in invasive cases and 21.3 months in cases with adnexal adenocarcinoma (log rank, P = 0.032).
Conclusions. Intraepithelial EMPDV accounted for the majority of primary cases and had a better progno-
sis. Surgical excision was the standard curative treatment for EMPDV. Radiotherapy was an alternative choice
for patients with medical contradiction or surgical difficulties. Postoperative radiotherapy could be consid-
ered in cases with positive surgical margin or lymph node metastasis. Recurrence was common and repeated
excision was often necessary.
© 2013 Elsevier Inc. All rights reserved.

Introduction with dermal invasion or with an underlying primary adenocarcino-

Since Sir James Paget first described Paget's disease in 1874 as an
intraepithelial carcinoma of the nipple [1], this carcinoma has been
found in the skin at other sites, which is known as extramammary
Paget's disease (EMPD). The precise pathogenesis of EMPD remains
controversial; however, the primary and secondary mechanisms of
the origin of Paget cells have been well-accepted [2]. According to
Wilkinson and Brown, primary EMPD originates from epidermal
basal cells commonly with adnexal involvement and occasionally
⁎ Corresponding author. Fax: +86 21 64174774.
E-mail address: yanghj1@shca.org.cn (H. Yang).
1
The first two authors contributed equally to this article.
ma of a skin appendage or a subcutaneous vulvar gland. Secondary
EMPD arises from an underlying non-cutaneous adenocarcinoma,
which is most commonly an anal, rectal or urothelial adenocarcino-
ma that is detected synchronously or metachronously [2].
The most common site of involvement is the vulva, which accounts for
up to 60% of primary EMPD cases but less than 2% of vulvar malignancies
[3]. Primary EMPD of the vulva (EMPDV) predominantly occurs in
women between 50 and 80 years of age (mean = 70 years) [4,5].
Patients commonly complain about pruritus, irritation or burning
in the vulvar area, which has an erythematous and/or eczematoid
appearance. Whitish islands or ulcerations can be present. Because
of the non-specific clinical presentation, primary EMPDV is often
misdiagnosed as various eczematous dermatitides or superficial

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http://dx.doi.org/10.1016/j.ygyno.2013.02.029
 Y. Cai et al. / Gynecologic Oncology 129 (2013) 412–416
fungal infections and is treated by multiple topical therapies [6]. The
median interval from the onset of symptoms to a histological diagno-
sis was approximately 20 months [4,7].
Wide surgical excision is the standard treatment for primary
EMPDV. However, microscopic positive margins have been frequently
found in 40–70% of cases [4,5]. Adjuvant radiotherapy may be consid-
ered in patients with dermal invasion, lymph node metastasis or posi-
tive surgical margins. Definitive radiotherapy can be used in elderly
patients with medical contraindications [8,9]. Long-term survival is
common in the majority of patients without invasion [10]. However,
local recurrence has been observed in 15%–61% of patients after initial
surgery [4,5]. The risk factors that are associated with local recurrence
remain controversial, such as a positive surgical margin, dermal inva-
sion, and adnexal involvement [4,5]. Other issues, such as surgical
extent, choice of lymphadenectomy, the value of radiotherapy, and
management of recurrent diseases remain inconclusive due to limited
cases. In this study, we presented the clinicopathological features of
43 Chinese patients with primary EMPDV and analyzed their clinical
outcomes.
Materials and methods
After institutional review board approval, a total of 44 cases of
EMPDV, which were treated at Fudan University Shanghai Cancer
Center from 1996 to 2009, were retrieved from the institutional
databases. The pathological diagnoses were confirmed under micro-
scope by conventional hematoxylin and eosin staining. Immunohis-
tochemical staining for antibodies, including CK7, CK20, GCDFP-15,
CEA, Uroplakin-III, S-100 protein and HMB45 was performed using
EnVision, PAS (diastase-resistant) and Alcian blue for a diagnosis
and a differential diagnosis. The histopathological parameters, in-
cluding the depth of invasion, adnexal involvement, the presence
of a synchronous malignancy, the surgical margin status and lymph
node metastasis were further analyzed.
The clinical data were retrieved from the medical records, which
included age at initial diagnosis, a history of a secondary malignancy,
the interval from the onset of symptoms to the confirmed diagnosis,
the location and the extent of disease, the surgical procedure, the
postoperative treatment, the date of recurrence, the treatment
after recurrence, and the duration of follow-up. For the patients
who were treated with radiotherapy, the data included the radiation
field and dose. Patients were followed up at approximately 3-month
intervals in the first two years, 6-month intervals in the following
3 years, and annually thereafter. Recurrence was defined as the
reappearance of Paget's disease 6 months after initial treatment.
Persistent disease was diagnosed within 6 months after the comple-
tion of treatment.
Fisher's exact test and a t-test were used to analyze the categorical
and numerical parameters among the different groups, respectively.
Disease-free survival (DFS) was defined as the period between the com-
pletion of the last treatment and the date of the first documented evi-
dence of recurrent or persistent disease. Overall survival (OS) was
calculated from the date of diagnosis until death. The survival curves
were calculated using the Kaplan–Meier method, and the differences
between the groups were determined using the log-rank test. All of
the statistical analyses were performed using SPSS for Windows, ver-
sion 16.0 (SPSS Inc., Chicago, IL, USA). The statistical significance was
defined as P b 0.05.
Results
Primary EMPDV was confirmed in 43 cases, including 33 cases of
intraepithelial EMPDV, 7 cases of invasive EMPDV and 3 cases with un-
derlying adenocarcinomas of the sweat glands. One case was diagnosed
as secondary EMPDV because of an accompanying vulvar squamous cell
carcinoma; however, this patient was excluded from this study.
413
For all of the cases, hematoxylin and eosin staining revealed large
cells with a prominent pale cytoplasm in the squamous epithelium.
These cells had large nuclei with prominent nucleoli and a finely gran-
ular or vacuolated cytoplasm (Fig. 1). The cells were clustered in groups,
were dispersed as single cells with basal and parabasal areas, or were
spread across various layers of the epithelium. Tumor cells that involved
the surrounding hair shafts and appendages were found in 10 cases.
Among these cases, 3 cases were associated with the underlying inva-
sive adenocarcinoma. Invasive lesions were identified beneath the
Paget's disease in two cases and in an adjacent area in one case that
presented as a signet ring cell carcinoma (Fig. 2).
All of the patients were postmenopausal, and the mean age at diag-
nosis was 68.6 years (range = 52–85 years). Pruritus was the most
common symptom and occurred in the majority of patients (95.3%).
Other symptoms included vulvar pain (18.6%), bleeding (16.3%) and
discharge (13.9%). The median interval between the onset of symptoms
and a histological diagnosis was 36 months (range = 3–240 months).
Among 42 informative patients, 26 (61.9%) patients were treated with
topical antifungals or corticosteroids before the diagnosis. The majority
of these patients presented with erythematous lesions (81.4%) and
some had ulceration (32.6%) or erosion (30.2%). Twenty-four (55.8%)
patients had a single lesion, and 19 (44.2%) patients had two or more
lesions. The labia majora (76.7%) were the most common site of
involvement. The mean diameter of the largest lesion was 4.8 cm
(range = 1.0–10.0 cm).
Definitive surgery was performed in 35 patients. Table 1 summa-
rizes the surgical procedures and the surgical outcomes among the pa-
tients according to the three types of EMPDV. Radical surgery, including
radical vulvectomy +/− inguinal lymphadenectomy, was performed
in 100.0% of the patients with adnexal adenocarcinomas, 44.0% of the
patients with intraepithelial EMPDV and 42.8% of the patients with in-
vasive EMPDV. Conservative surgery, including wide excision and sim-
ple vulvectomy, was performed in 57.2% of the patients with invasive
EMPDV and 56.0% of the patients with intraepithelial EMPDV. A positive
surgical margin was common among the three types of EMPDV (45.8%
for type 1A, 42.8% for type 1B and 66.7% for type 1C). Five patients
underwent inguinal lymphadenectomy. Lymph node metastasis was
found in 3 (60.0%) patients (1 case with invasive EMPDV and 2 cases
with adnexal adenocarcinomas). All the 3 patients had palpable en-
larged inguinal lymph nodes at presentation.
Table 2 presented the details of radiotherapy in 17 cases with
EMPDV. Eight patients (Cases 5, 6, 17, 18, 19, 20, 21 and 22) underwent
radiotherapy with radical intention to the local tumor site through Co60
Fig. 1. Primary Paget disease of vulvar. Paget cells with large nuclei, prominent nucleoli
and large amount pale cytoplasm, extended in the basal and parabasal areas of the epithe-
lium (HE ∗ 200).
414 Y. Cai et al. / Gynecologic Oncology 129 (2013) 412–416

radiotherapy at a dosage of 4330cGY followed by two cycles of chemo-

therapy before surgery. One patient with intraepithelial EMPDV
underwent palliative radiation for tibia metastasis (Case 9). Another
intraepithelial case received radiotherapy at a dosage of 63 Gy for the
treatment of a secondary recurrence at the incision area (Case 1).

Treatment outcomes

During a follow-up period of 7–169 months (median =

Fig. 2. Signet ring cell carcinoma presented adjacent to the primary Paget disease of vulvar
(HE ∗ 100).
or 9 MeV electrons because of medical inoperable disease or extensive
disease. Before RT, distant metastasis and retroperitoneal/inguinal
lymph node metastasis were excluded by pelvic and abdominal mag-
netic resonance imaging (MRI), computed tomography (CT), abdominal
ultrasonography and chest X-ray. During radiation, one patient
discontinued treatment because of toxicity. In the remaining 7 patients,
the radiation fields were set up according to the tumor size with a
2–3 cm margin. A median dose of 60 Gy (range = 60–63 Gy) was de-
livered in 20–29 fractions (median = 20 fractions) with a fraction
dose of 300 Gy for 5 days/week. The median treatment duration was
70 days (range = 64–92 days).
A total of 6 patients underwent postoperative adjuvant radio-
therapy. Three patients received radiation to the tumor bed at a me-
dian dosage of 57 Gy (range = 39–60 Gy) due to a positive surgical
margin (Cases 14, 15, &16). Radiation to the tumor bed and regional
pelvic and inguinal lymph nodes was delivered to 2 patients with
adnexal adenocarcinomas who had both positive margin and ingui-
nal lymph node metastasis (Cases 11 & 12). In addition, another
patient underwent radiation to pelvic and para-aortic region because
of lymph node metastasis confirmed by CT scan subsequently after
excision of the primary tumor (Case 2).
Preoperative radiation was given to a patient with invasive
EMPDV, who had extensive retroperitoneal lymph node metastasis
confirmed by CT scan (Case 13). She underwent pelvic external-beam
Table 1
The surgical procedures and surgical outcomes among the 35 patients according to the
three types of EMPDV.
54.3 months), recurrence data were available for 35 patients
(77.3%), including 27 patients with intraepithelial EMPDV, 5 pa-
tients with invasive EMPDV and 3 patients with adnexal adenocar-
cinomas. Recurrence was observed in 12 (34.3%) patients. Among
them, 10 patients (28.6%) received initial surgery and 2 patients
(25.0%) received definitive radiotherapy. Recurrence was more
common in cases with adnexal adenocarcinomas (66.7%), com-
pared with intraepithelial cases (33.3%) and invasive cases
(20.0%), but without statistical significance (P = 0.395, Fisher's
exact test). A local recurrence was also not associated with a posi-
tive resection margin (+/−: 38.5% vs. 18.8%, P = 0.223). Nine
(75.0%) of the 12 patients underwent repeated surgical excision
for treatment of a recurrence, and 3 (25.0%) patients underwent ra-
diotherapy. A repeated local recurrence was observed in 3 patients.
Table 3 lists the details of the 12 recurrent cases. Seven (58.3%) pa-
tients exhibited evidence of a local recurrence in the incision areas
or in the radiation areas after initial treatment (Cases 1, 3, 6, 7, 8, 10
& 12). Three patients had local recurrence, but outside of the inci-
sion and radiation areas (Cases 4, 5 & 11). One case had a local re-
currence at the external urethral orifice and inguinal lymph node
metastasis 4 years after simple vulvectomy (Case 2). This patient
underwent radical vulvectomy, partial urethrectomy, vaginectomy
and bilateral inguinal lymphadenectomy; however, she presented
with pelvic and para-aortic lymph node metastasis 16 months
later. Then, she underwent modulated-intensity radiation to the
para-aortic area (4500 cGy) and the left external iliac lymph node
(5750 cGy) but presented with metastasis in the thoracic and lum-
bar vertebrae 9 months later. The remaining recurrent patient
presented with right inguinal lymph node metastasis 24 months
after local excision but was not treated and presented with metas-
tasis in the right tibia 3 months later (Case 9). This patient received
palliative radiotherapy.
Survival data were available for 36 (83.7%) patients, including 27 pa-
tients with intraepithelial EMPDV, 6 patients with invasive EMPDV and
3 patients with an adnexal adenocarcinoma. Long-term overall survival
was observed in patients with intraepithelial EMPDV. The median over-
all survival was 124.5 months in intraepithelial cases, 70.8 months in
invasive cases and 21.3 months in cases with adnexal adenocarcinoma
(Log rank, P = 0.032).

Intraepithelial Invasive EMPDV EMPDV with adnexal

Discussion
EMPDV (type 1B) adenocarcinoma
(type 1A) (type 1C)
Primary EMPD of the vulva was first described by Dubreuilj in 1901
Cases 25 7 3
Surgical procedures 7 3 [11]. This disease is uncommon in Caucasian women and in Chinese
WEC 9 1 0 women. The majority of publications from China on EMPDV are case
SVC 5 3 0 reports or retrospective studies with a limited number of patients
RVC 10 1 1 [12–14]. This study was the largest analysis of EMPDV in the Chinese
RVC + ILA 1 2 2
Adnexal involvement 12/24 4/7
population to date and included a series of 43 patients.
Positive incision margin 11/24 3/7 2/3 According to Wilkinson and Brown, primary EMPD is classified
Lymph node metastasis 0/1 1/2 2/2 into three subtypes, including intraepithelial Paget's disease (type
Recurrencea 7/22 1/5 2/3 1A), intraepithelial Paget's disease with invasion (type 1B) or with
OS (median, months)b 124.5 70.8 21.3
underlying adenocarcinoma of a skin appendage (type 1C) [2]. In
EMPDV: extramammary Paget's disease of the vulva; WEC: wide excision; SVC: simple our series, the three types of EMPDV accounted for 76.7%, 16.3%
vulvectomy; RVC: radical vulvectomy; ILA: inguinal lymphadenectomy. and 7.0% of the 43 patients, respectively. In a series of 100 cases, Fan-
a
Recurrence information was not available for 3 intraepithelial cases and 2 invasive
cases.
ning et al. reported that the prevalence of the three types of EMPDV
b
Survival information was not available for 2 intraepithelial cases and 1 invasive was 84%, 12% and 4% respectively [15]. Recently, Jones et al. demon-
case. strated that the majority (76%) of the 50 cases treated between 1986
 Y. Cai et al. / Gynecologic Oncology 129 (2013) 412–416 415

Table 2
Summarization of radiotherapy in 17 cases with EMPDV.

Casea Age (years) Type Intentionb Location Areac (cm2) Dosagec (cGY) Beam energyc

Case 5a 70 Intraepithelial A Vulvar 11 × 10 6300 Co60

Case 6a 71 Intraepithelial A Vulvar 8×6 6000 Co60
Case 17 67 Intraepithelial A Vulvar 16 × 18 6000 Co60
Case 18 80 Intraepithelial A Vulvar 8 × 10 6000 Co60
Case 19 79 Intraepithelial A Vulvar 8 × 10 6000 Co60
Case 20 82 Intraepithelial A Vulvar 8 × 10 6000 Co60
Case 21 80 Intraepithelial A Vulvar 8 × 10 1200 Co60
Case 22 61 Intraepithelial A Vulvar 8×6 6000 Co60
Case 14 59 Intraepithelial B Vulvar 8×6 3900 Co60
Case 15 70 Invasive B Vulvar 8×6 6000 Co60
Case 16 75 Invasive B Vulvar 8×6 5700 9 MeV
Case 2a 68 Intraepithelial B Pelvic, para-aortic – – –
Case 11a 71 Adnexal adenocarcinoma B Vulvar, inguinal, pelvic 8×6 6000 Co60
Case 12a 74 Adnexal adenocarcinoma B Vulvar, inguinal, pelvic 8 × 10 6000 9 MeV
Case 13 59 Invasive C Pelvic – – –
Case 9a 80 Intraepithelial D Tibia – – –
Case 1a 57 Intraepithelial E Vulvar 8×6 6300 9 MeV

EMPDV: extramammary Paget's disease of the vulva.

a
The recurrence information could be found in Table 3 for these cases marked (a). Case 13 had extensive retroperitoneal lymph node metastasis at presentation and dead of the
disease. Other cases had no recurrence and were alive at the end of follow-up.
b
A: Definitive radiotherapy; B: postoperative radiation for positive margin or lymph node metastasis; C: preoperative radiation; D: palliative radiation; E: radiation for recurrence.
c
Radiation to the vulvar area is presented.

and 2009 were intraepithelial EMPDV, 10% were invasive EMPDV
and 6% were EMPDV with adnexal adenocarcinomas [10]. Therefore,
intraepithelial disease was the predominant type of primary EMPD
in the vulva.
Surgical excision has been accepted as the standard treatment for
the three types of EMPDV; however, the extent of resection has not
been standardized. Surgical procedures for the management of primary
lesions vary among patients and include wide local excision, radical
hemivulvectomy, and simple or radical vulvectomy depending on the
lesion size, lesion location, the presence of invasion, underlying adeno-
carcinomas or adjacent skin abnormalities. Conservative resection
(wide excision) with a gross margin of 2–3 cm and resection to the fas-
cia may be considered for intraepithelial lesions. Radical procedures
may be considered for invasive lesions and for patients with adnexal ad-
enocarcinomas; however, the addition of these procedures is not asso-
ciated with less recurrence [15]. Because the lesions are multifocal
and the margins are irregular, involvement of microscopic margins
occurs in approximately 40%–75% of patients following surgical exci-
sion [4,5,10,16]. Therefore, an intraoperative frozen section analysis
is suggested to evaluate the surgical margins. However, the
intraoperative frozen section of the surgical margin did not decrease
the involvement of the permanent positive margin [17]. Mohs micro-
graphic surgery (MMS) is a surgical technique that is performed
under microscopic control to remove tumor lesions and conserve tis-
sue loss and function [18]. A lower recurrence rate in those patients
with Mohs surgery has been documented compared with patients
who were treated with conventional resection [19,20]. Recently,
two studies in Korea demonstrated that the recurrence rates of
EMPD in males and females after Mohs surgery ranged from 12.5%
to 18.2%, which are lower than the rates of 33.3%–36.4% in patients
who were treated with wide excision [21,22]. However, additional
clinical trials are warranted to determine whether MMS could be
used as a standard surgical technique for EMPDV.
In our study, positive lymph node metastasis at presentation was
observed in 2 (66.7%) of the 3 cases of EMPDV with a sweat gland ade-
nocarcinoma and in one case (14.3%) with subcutaneous invasion but
not in any of the cases of intraepithelial EMPDV. The invasive case
consisted of an extensive lesion in the vulvar area and a palpable en-
larged right inguinal lymph node and extensive retroperitoneal lymph
node metastasis. After resection, all 19 inguinal lymph nodes were con-
firmed to be positive for metastasis. Hanawa et al. presented a similar
advanced case with two extensive Paget's lesions in the vulvar area
and multiple lymph node metastases at presentation, including the
left inguinal lymph node, the pararenal artery lymph node and the
subclavian axillary lymph nodes [23]. Zhang et al. reported that
lymph node metastasis was present in a patient with minimal stro-
mal invasion (10/10 inguinal lymph nodes) and in a patient with
frank invasion (2/32 inguinal lymph nodes) [24]. Therefore, inguinal
lymph node dissection at initial treatment should be considered for
invasive lesions and for patients with underlying adenocarcinomas.
Sentinel lymph node biopsy for EMPD has been described in a case
report; however, additional clinical trials are needed for the valida-
tion of this procedure in the management of the three types of
EMPD [25].
Local recurrence in the incision areas and in the inguinal lymph
nodes after surgical excision was common despite of the types of
EMPDV with recurrence frequencies that ranged from 20% to 70%
[4,5,10,15,16]. Fanning et al. found that the recurrence rates were
35%, 33% and 25% for the intraepithelial type, invasive type and ad-
nexal adenocarcinoma type, respectively [15]. In this study, the re-
currence rate was higher in patients with adnexal adenocarcinoma
compared with the other two types of EMPDV, but without statistical
significance. More cases are needed to get a conclusion. In patients
with intraepithelial EMPDV, recurrence was more common in cases
with a positive margin compared with cases without a positive mar-
gin; however, no statistical significance has been found in most stud-
ies including the present study [4,5]. In addition, recurrence is also
not associated with age, lesion size, and surgical procedures [4,15].
Recently, Shaco-levy observed a higher recurrence rate and a shorter
recurrence time in patients with perineal involvement, which may
be associated with larger lesions that lead to difficult excision [4].
Distant metastasis is uncommon in EMPD during disease progression
but has been reported in the literatures [23,26]. Cappuccini reported
a case of intraepithelial EMPD with periaortic lymph node metastasis
and bone metastasis that involved the lumbar and sacral vertebrae
one year after the management of inguinal lymph node metastasis
and local recurrence [26]. Similar cases have been noted in this
study (Table 3, Cases 2 & 9). Repeated excision is the standard treat-
ment choice for local recurrence; however, other treatment choices
include conservative treatments, such as topical imiquimod or 5-FU
therapy, photodynamic therapy and Co2 laser therapy [3]. Systemic
chemotherapy may be considered in advanced cases of disease and
in cases of metastatic disease although the standard regimens have
not been validated.
416 Y. Cai et al. / Gynecologic Oncology 129 (2013) 412–416

Table 3
Clinical features of the 12 recurrent patients.
b
Case number Age Type Initial Treatment Incision marginc Times of Recurrence site
(years) recurrence

Case 1 57 Intraepithelial WEC – 2 1st & 2nd: incision area

Case 2 68 Intraepithelial SVC N 3 1st: vagina, urethra and inguinal lymph node;
2nd: inguinal, pelvic and periaortic lymph node;
3rd: lumbar and thoracic vertebra
Case 3 72 Intraepithelial RVC P 1 Incision area
Case 4 74 Intraepithelial WEC P 2 1st: incision area; 2nd:perianal
Case 5 70 Intraepithelial RAD – 1 Vagina
Case 6 71 Intraepithelial RAD – 1 Radiation field
Case 7 72 Intraepithelial RVC + ILA N 1 Incision area
Case 8 76 Intraepithelial WEC P 2 1st & 2nd: incision area
Case 9 80 Intraepithelial WEC – 2 1st: inguinal lymph node; 2nd: tibia
Case 10 59 Invasive SVC N 1 Incision area
Case 11 71 Adnexal adenocarcinoma RVC + ILA P 1 Incision area, perineum, mons pubis and inguinal area
Case 12 74 Adnexal adenocarcinoma RVC + ILA P 1 Incision area
b
WEC: wide excision; SVC: simple vulvectomy; RVC: radical vulvectomy; ILA: inguinal lymphadenectomy; RAD: definitive radiotherapy.
c
N: negative; P: positive.

Radiotherapy is an alternative treatment for patients with a medical
contradiction for surgery and for patients with recurrent disease. In ad-
dition, it could be considered as an adjuvant therapy for patients with a
positive margin after surgical excision. However, the optimal radiation
dose and radiation field have not been standardized. In this study, a me-
dian dosage of 60 Gy and 57 Gy was respectively delivered to patients
with definitive intention and patients as an adjuvant treatment for a
positive margin, which was consistent to the conclusion by Hata et al.
[9]. Their study also suggested that a radiation area that covered the
gross tumor site with a 2–5 cm margin has been used in most patients
for optimal local control; however, this margin cannot be accepted as a
standard without further investigation with a larger sample size and a
longer follow-up. In addition, their study and the present study sup-
ported that radiation of the inguinal, pelvic or para-aortic lymph node
should be considered only for the cases with lymph node metastases
within these areas.
In conclusion, the intraepithelial type accounted for the majority of
primary EMPDV cases and had a better clinical course and outcomes.
Wide excision of vulvar lesions remains the standard curative treatment
for the three types of EMPDV; additional inguinal lymphadenectomy
should be included in the treatment of the cases with invasive diseases
and adnexal adenocarcinomas. Definitive radiotherapy is an alternative
choice for patients with medical contraindication or surgical difficulties
because of extensive diseases or tumor location. Postoperative radio-
therapy could be considered for the cases with positive surgical margin
or lymph node metastasis. Local recurrence was common regardless of
the primary mode of treatment, surgical excision was often necessary.
Clinical trials are required to explore other non-surgical treatments in
the treatment of recurrent or metastatic diseases.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
The authors wish to acknowledge Prof. Hextan YS Ngan for her
critical review of the manuscript.
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