Diagnosis and Treatment of Vulvo-Perineal Endometriosis: A Systematic Review

Abstract

Objective: To describe the available knowledge on vulvo-perineal endometriosis including its diagnosis, clinical management and recurrence rate.
Methods: We followed the PRISMA guidelines for Systematic Reviews and our study was prospectively registered with PROSPERO (CRD42020202441). The terms “ Endometriosis” and “ Perineum” or “ Vulva” were used as keywords. Cochrane Library, Medline/Pubmed, Embase and Clinicaltrials.gov were searched. Papers in English, Spanish, Portuguese, French or Italian from inception to July 30, 2020 were considered. Reference lists of included articles and other literature source such as Google Scholar were also manually scrutinized in order to identify other relevant studies. Two independent reviewers screened potentially eligible studies according to inclusion criteria.
Results: Out of 539 reports, 90 studies were eligible including a total of 283 patients. Their mean age was 32.7 ± 7.6 years. Two hundred sixty-three (95.3%) presenting with vulvo-perineal endometriosis have undergone either episiotomy, perineal trauma or vaginal injury or surgery. Only 13 patients (4.7%) developed vulvo-vaginal endometriosis spontaneously i.e., without any apparent condition favoring it. The reasons that motivated the patients to take medical advice were vulvo-perineal cyclical pain increasing during menstruations (98.2% of the patients, n = 278). Out of the 281 patients for whom a clinical examination was described, 274 patients (97.5%) showed a vulvo-perineal nodule, mass or swelling while six presented with bluish cutaneous lesions (2.1%) and 1 with bilateral polyps of the labia minora (0.4%). All but one patients underwent surgical excision of their lesions but only 88 patients (28.1%) received additional hormonal therapy. The recurrence rate was 10.2% (29 patients) considering a median follow-up period of 10 months (based on 61 studies).
Conclusion: In conclusion, vulvo-perineal endometriosis is a rare entity with approximately 300 cases reported in the literature since 1923. With the available knowledge shown in this systematic review, we encourage all practitioners to think about perineal endometriosis in case of perineal cyclical pain with or without previous perineal damage. Diagnosis should be done with clinical exam, perineal ultrasound and pelvic MRI when available. In case of anal sphincter involvement, perianal ultrasound should be performed. Surgical excision of the lesion should be realized in order to remove the lesion and to confirm the diagnosis histologically. Hormonal treatment could be proposed to attempt to decrease the size of a large lesion before surgery or to avoid recurrence of the lesion. As evidence-based approach to the diagnosis, treatment and recurrence rate of affected patients remains a challenge given its low prevalence, the variations in management found in the articles included and the limited quality of available studies, we suggest that a prospective database on vulvo-perineal endometriosis should be generated to increase knowledge but also awareness among healthcare professionals and optimize patients' care.
Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ , identifier: CRD42020202441.

Full text

SYSTEMATIC REVIEW
published: 11 May 2021
doi: 10.3389/fsurg.2021.637180
Frontiers in Surgery | www.frontiersin.org 1May 2021 | Volume 8 | Article 637180
Edited by:
Salim Alfred Bassil,
Al-Arz Hospital, Lebanon
Reviewed by:
Mohd Faizal Ahmad,
National University of
Malaysia, Malaysia
Svend Lindenberg,
Copenhagen Fertility Center, Denmark
*Correspondence:
Charlotte Maillard
charlotte.maillard@uclouvain.be
Specialty section:
This article was submitted to
Obstetrics and Gynecology,
a section of the journal
Frontiers in Surgery
Received: 02 December 2020
Accepted: 06 April 2021
Published: 11 May 2021
Citation:
Maillard C, Cherif Alami Z,
Squifflet J-L, Luyckx M, Jadoul P,
Thomas V and Wyns C (2021)
Diagnosis and Treatment of
Vulvo-Perineal Endometriosis: A
Systematic Review.
Front. Surg. 8:637180.
doi: 10.3389/fsurg.2021.637180
Diagnosis and Treatment of
Vulvo-Perineal Endometriosis: A
Systematic Review
Charlotte Maillard 1
*, Zineb Cherif Alami 2, Jean-Luc Squifflet 1, Mathieu Luyckx 1,3 ,
Pascale Jadoul 1, Viju Thomas 4and Christine Wyns 1,5
1Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels,
Belgium, 2Department of Obstetrics and Gynecology, Clinique Saint-Jean, Brussels, Belgium, 3Tumor Infiltrating
Lymphocytes Group - De Duve Institute, Université Catholique de Louvain, Brussels, Belgium, 4Department of Obstetrics
and Gynecology, Tygerberg Hospital, University of Stellenbosch, Cape Town, South Africa, 5Institut de Recherche
Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
Objective: To describe the available knowledge on vulvo-perineal endometriosis
including its diagnosis, clinical management and recurrence rate.
Methods: We followed the PRISMA guidelines for Systematic Reviews and our
study was prospectively registered with PROSPERO (CRD42020202441). The terms
“Endometriosis” and “Perineum” or “Vulva” were used as keywords. Cochrane Library,
Medline/Pubmed, Embase and Clinicaltrials.gov were searched. Papers in English,
Spanish, Portuguese, French or Italian from inception to July 30, 2020 were considered.
Reference lists of included articles and other literature source such as Google Scholar
were also manually scrutinized in order to identify other relevant studies. Two independent
reviewers screened potentially eligible studies according to inclusion criteria.
Results: Out of 539 reports, 90 studies were eligible including a total of 283 patients.
Their mean age was 32.7 ±7.6 years. Two hundred sixty-three (95.3%) presenting
with vulvo-perineal endometriosis have undergone either episiotomy, perineal trauma or
vaginal injury or surgery. Only 13 patients (4.7%) developed vulvo-vaginal endometriosis
spontaneously i.e., without any apparent condition favoring it. The reasons that motivated
the patients to take medical advice were vulvo-perineal cyclical pain increasing during
menstruations (98.2% of the patients, n=278). Out of the 281 patients for whom
a clinical examination was described, 274 patients (97.5%) showed a vulvo-perineal
nodule, mass or swelling while six presented with bluish cutaneous lesions (2.1%)
and 1 with bilateral polyps of the labia minora (0.4%). All but one patients underwent
surgical excision of their lesions but only 88 patients (28.1%) received additional hormonal
therapy. The recurrence rate was 10.2% (29 patients) considering a median follow-up
period of 10 months (based on 61 studies).
Conclusion: In conclusion, vulvo-perineal endometriosis is a rare entity with
approximately 300 cases reported in the literature since 1923. With the available
knowledge shown in this systematic review, we encourage all practitioners to think about
perineal endometriosis in case of perineal cyclical pain with or without previous perineal
damage. Diagnosis should be done with clinical exam, perineal ultrasound and pelvic

Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
MRI when available. In case of anal sphincter involvement, perianal ultrasound should
be performed. Surgical excision of the lesion should be realized in order to remove the
lesion and to confirm the diagnosis histologically. Hormonal treatment could be proposed
to attempt to decrease the size of a large lesion before surgery or to avoid recurrence
of the lesion. As evidence-based approach to the diagnosis, treatment and recurrence
rate of affected patients remains a challenge given its low prevalence, the variations in
management found in the articles included and the limited quality of available studies,
we suggest that a prospective database on vulvo-perineal endometriosis should be
generated to increase knowledge but also awareness among healthcare professionals
and optimize patients’ care.
Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier:
CRD42020202441.
Keywords: endometriosis, perineum, vulva, episiotomy, perineal pain, cyclical pain, perineal nodule, extrapelvic
endometriosis
INTRODUCTION
Endometriosis is a complex benign disease characterized by an
estrogen-dependent chronic inflammatory process and is defined
as the presence of endometrial glands and stroma-like tissue
outside the uterine cavity, most often located in the pelvis (1),
although extrapelvic sites have been described, including the
urinary and gastro-intestinal tracts, the nervous system, the
thoracic cavity and diaphragm as well as some (sub-)cutaneous
sites (2–5). It occurs in ∼10% of women of reproductive-age
and in 35–50% of women with infertility and chronic pelvic
pain (6–8).
While extrapelvic endometriosis is a relatively uncommon
condition, accounting for ∼12% of all cases of endometriosis
(9), perineal endometriosis is an even rarer entity. Cutaneous
and subcutaneous endometriotic lesions have been observed in
surgical scars following laparoscopy, laparotomy, vulvo-vaginal
surgery, episiotomy and obstetrical lacerations whether surgically
repaired or not (3). Perineal endometriosis may involve the skin
and/or subcutaneous tissue of the vulva and perineum but also
the perianal sphincteric muscular tissue (10). Following the first
case of perineal endometriosis reported in 1923 (11), most of
what is known of this commonly misdiagnosed entity comes
from case reports published over the past 60–70 years.
Our study aims to identify all reported cases of vulvo-perineal
endometriosis published in the literature in order to describe
diagnostic processes, treatments and recurrence rates of this
uncommon type of endometriosis and help practitioners to
achieve prompt diagnosis and optimize patients’ outcomes.
METHODS
This study followed the principles of the Preferred
Reporting Items for Systematic Reviews and Meta-
Analysis (PRISMA) statement (12) and was prospectively
registered within the International Prospective Register of
Systematic Review (PROSPERO) on the 4th of August 2020
(number CRD42020202441).
The following search engines and electronic databases were
searched on July 30, 2020 by one author (CM): Cochrane
Library, Medline/Pubmed, Embase and Clinicaltrials.gov. The
terms “Endometriosis” and “Perineum” or “Vulva” were used as
keywords to recover all possible publications. Table 1 shows the
queries and record numbers for the different databases used. No
restrictions regarding language, type or date of publication were
initially applied. Reference lists of included articles and other
literature sources such as Google Scholar were also manually
scrutinized in order to identify additional relevant studies.
Articles in English, Spanish, Portuguese, French or Italian were
considered. Review articles and studies describing exclusively
lesions involving the abdominal wall or the inguinal area, or
malignant transformation of endometriosis were excluded. Two
reviewers (CM, ZCA) independently screened titles and abstracts
of the search output to identify potentially eligible studies and
cross-examined their results.
RESULTS
Figure 1 shows the flow chart of the literature search. Our
search strategy yielded a total of 457 potentially eligible studies.
Ninety articles published between 1956 and 2020 were eventually
included in our review. Eighty-three articles were case reports or
case series including one to eight patients (2,9,11,13–90) and
seven studies described retrospective cohorts of 14–36 patients
(10,91–96). The main results of the eight retrospectives studies
can be found in Table 2.
Two hundred and eighty-three patients, with a mean age of
32.7 ±7.6 years and an age range from 14 to 69 years at diagnosis,
were included. While 263 patients (95.3%) had undergone
previous episiotomy, obstetrical lacerations, whether repaired or
not, perineal trauma or vaginal surgery or injury, only 13 patients
(4.6%) developed spontaneous vulvo-vaginal endometriosis i.e.,
in the absence of the most frequently associated conditions
(Table 3). Among the latter, lesions developed in the Bartholin
gland in 6 cases (21,44,48,62,70,80). Previous history wasn’t
described for seven patients (40,45,47,74).
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Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
TABLE 1 | Description of queries in the different databases.
Query Results
Pubmed/Medline (“Endometriosis”[MeSH Terms] OR “Endometriosis”[All Fields]) AND (“perineum”[MeSH Terms] OR “perineum”[All Fields] OR “vulva”
[MeSH Terms] OR “vulva”[All Fields])
171
Embase (“Endometriosis”/exp OR endometriosis) AND (“perineum”/exp OR perineum OR “vulva”/exp OR vulva) 362
Cochrane Library (endometriosis):ti,ab,kw AND perineum):ti,ab,kw (Word variations have been searched) 1
(endometriosis):ti,ab,kw AND vulva):ti,ab,kw (Word variations have been searched) 2
ClinicalTrials.gov (“Endometriosis” AND “Perineum” OR “vulva”) 3
539
FIGURE 1 | Flow diagram for study selection. *Seven articles could not be retrieved despite contacting the corresponding author.
The median latent period i.e., the time between perineal
trauma or surgery and occurrence of symptoms was 2.5 years,
ranging from 1 month to 14 years.
Incidence rates were reported in two studies, ranging between
0.01 and 0.06% after vaginal deliveries (84,92). The incidence of
anal sphincter involvement was reported only by Chen et al. who
described a 0.37% incidence of perineal endometriosis among
women treated surgically for endometriosis regardless of its
location with 0.18% of patients presenting with anal sphincter
involvement (10).
Main complaints were vulvar and/or perineal cyclical pain
increasing during menstruations for 278 patients (98.2%). Five
patients (1.8%) presented exclusively with other symptoms, e.g.,
painful bilateral polyps of the labia minora, cyclical bleeding, anal
pruritus or infertility. Concurrent pelvic endometriosis occurred
in 19 patients (6.1%). The median duration of symptoms before
medical care was 12 months, ranging from 2 weeks to 20 years.
Out of the 281 patients for whom a clinical examination was
described, 274 patients (97.5%) showed a vulvo-perineal nodule,
mass or swelling, including one with vulvar ulceration, while
6 presented with bluish cutaneous lesions (2.1%) and one with
bilateral polyps of the labia minora (0.4%).
The different workups conducted in the 283 patients are
described in Table 4. The most common workup assessment
was the serum level of cancer antigen 125 (CA125), measured
in 105 patients (37.1%), followed by pelvic ultrasound (34.9%)
and perineal ultrasound (27.%). Other workup examinations
were performed in <10% of the cases. Slightly elevated serum
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Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
TABLE 2 | Data of the literature about vulvo-perineal endometriosis describing more than 10 cases.
Number of
cases
Mean age
(range)
Symptoms Vulvo-
perineal
scar (n)
IAS Work-up
(n)
Duration of
symptoms
(range)
(months)
Latent period
(range)
(months)
Treatment Other
endometriosis
spots
Recurrence Follow-up
period
(months)
Perineal
nodule
(%)
Progressive
and cyclical
pain (%)
Other (%) Surgical Medical
Paull
et al. (91)
15 28 (19-34) 100 100 NA Episiotomy
scar (15)
NA NA NA 21 (1-60) Excision No NA 0 9: 12–48,
6: NA
Nominato
et al. (92)
21 30.8 (1-48) 79 80 NA Episiotomy
scar (19),
perineoplasty
(2), perineal
surgery (1)
NA NA 44 Excision No NA 1 NA
Zhu et al.
(93)
36 30.67 (23-44) 100 100 Dysmenorrhea
(13.9),
dyspareunia
(5.6)
Episiotomy
(24), perineal
tear (12)
26 CA 125 (30),
color doppler
perineal
ultrasound
(36)
NA 42.8 (4-156) Complete
excision (28),
uncomplete (7),
hormonal (1)
GnRHa 3–6
months pre or
post surgery (20
with IAS)
3 7 (with
incomplete
excision) 1
with
hormonal
treatment
alone
0.5–168
Chen
et al. (10)
31 33.4 (26-43) 100 100 NA Episiotomy
scar (20),
perineal
lacerations
(11)
31 CA 125,
pelvic U/s,
perineal U/s
(5)
NA 36 (1-204) Complete narrow
excision (30),
incomplete
excision (1)
NE: 10 pre- and
post-op 1–6
months (GnRHa,
Nemestran,
DMPA), 1 GnRHa
3 months
preop-Mirena
post-op, 9 GnRH
a pre-op 3–5
months, 2 GnRHa
4 months
post-op, 8 no
treatment, IE:
DPMA pre- and
post-op 3–6
months
2 (ovarian
endometrioma)
2 (NE with
GnRHa 3
months, IE)
18 (6-78)
Li et al.
(94)
17 34.35 (26-57) 100 100 NA Episiotomy
scar (17)
6 CA 125 (15),
doppler U/s
(8), pelvic U/s
(17), MRI (2)
37.82
(3-152)
46.82 (2-204) Excision Post-op: 4
GnRHa (3
months), 2
mifepristone 1
month, 1
progesterone
1 1 74.23
(5-151)
Matalliokis
et al. (95)
14 32.5 (±2.9) 92.8 92.8 NA Episiotomy
scar (14)
NA U/s (3), CT
(6), MRI (7)
NA NA Excision NA 3 2 NA
Liu et al.
(96)
35 33.44 (25-48) 100 100 NA Episiotomy
scar (33),
opposite side
of episiotomy
(1), mons
pubis (1)
10 CA125 (11),
perineal U/s
(15), pelvic
U/s (35)
NA 42.44 (1-120) Complete
excision ±
primary
sphincteroplasty
preop (7) (5 GnRHa, 1 Marvelon, 1
mifepristone), post op (17) (2
mifepristone, 15 GnRHa)
3 (18.75%) in
non GnRHa
group, 1 in
the gnRHa
group
7–86
U/s, ultrasound; CT-scan, computerized tomography; IAS, involved anal sphincter; CNE, complete narrow excision surgical margin: 0.3–0.5cm; DMPA, depot pedroxyprogesterone acetate; GnRHa, gonadotropin-releasing
hormone agonists; NE, narrow excision.
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Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
TABLE 3 | Description of previous vulvo-perineal history.
Vulvo-perineal endometriosis Number of
patients (/283)
%
Spontaneous 13 4.6
Previous vulvo-perineal lesion 263 92.9
Episiotomy or obstetrical laceration 249 88
Bartholin cystectomy 4 1.4
Laparotomy (for ovarian endometriosis) 1 0.4
Laparotomy (for ovarian endometriosis) with hernia repair 1 0.4
Laser vulvar surgery 1 0.4
Vaginal hysterectomy 1 0.4
Manchester surgery for prolapse 1 0.4
Mile’s procedure for rectal cancer 1 0.4
Vulvar abrasion 1 0.4
Vulvar hematoma post trauma 1 0.4
Vulvar ulceration 1 0.4
Removal of Nuck canal remnant 1 0.4
Not specified 7 2.5
TABLE 4 | Work-up for vulvo-perineal endometriosis.
Number of patients (/283) %
Serum level of CA 125 105 37.1
Pelvic Ultrasound 99 34.9
Perineal ultrasound 78 27.6
MRI 19 6.7
Biopsy 17 6
CT-scan 9 3.2
Endoanal ultrasound 8 2.8
Sigmoidoscopy 7 2.5
Anal Manometry 4 1.4
FNAC 2 0.7
Dermoscopy 1 0.4
CA 125, cancer Antigen 125; MRI, magnetic resonance imaging; CT-scan, Computerized
Tomography scan; FNAC, fine needle aspiration cytology.
levels of CA125 were found in 6.5–46.7% of patients with
perineal endometriosis (10,93,94,96). Pelvic ultrasound was
mostly performed to exclude pelvic endometriosis. Perineal
and endoanal ultrasound (50,93,94,96), as well as magnetic
resonance imaging (MRI) (94,95) helped to describe precisely
the size of the lesions and to diagnose and assess the extent of
the anal sphincter involvement. Well-defined hypoechoic solid
or cystic masses with hyperechoic spots or strands representing
fibrosis within the scar tissue have been described (79,97).
Increased vascularity and spiculated borders with a single vessel
entering the nodule from the periphery has also been observed
(98). Fine needle aspiration cytology (FNAC) or biopsy of the
lesions was reported in 19 patients (6.1%) and confirmed the
diagnosis before surgical excision in 16 patients (84.2%) while
it didn’t confirm the presence of endometriosis in two patients
[granulation tissue and old hemorrhage (22,63)]. One biopsy
result was not described (36).
All but one patients (282/283) underwent surgical excision
of the perineal mass. In the patient where the perineal
lesion was left, a total abdominal hysterectomy with bilateral
salpingo-oophorectomy was performed to induce menopause
and decrease pain-related symptoms (69). The detailed technique
of the different surgical procedures was usually not described,
except in two studies mentioning the following specifications
i.e., narrow excision with deep surgical margins of 0.3–0.5 cm
(10) or complete excision with a surgical margin of 0.5–1 cm
(94). “Excision” or “surgical excision” without further details was
mentioned for 148 patients (52.5%). Amongst the remainder,
73 had a “complete excision” (25.6%), 32 benefited from a
“complete narrow excision” (11.3%) and 10 patients from a “wide
excision” (3.5%). Eight surgeries were described as “incomplete”
(2.8%). Histological findings confirmed endometriosis in all
cases. Eighty-eight patients (28.1%) received hormonal therapy,
either pre-or post-operatively for 3–6 months (Table 5).
A follow-up period was mentioned in 61 studies, with a
median value of 10 months (range from 1 to 108 months).
Recurrent lesions have been reported in 29 patients (10.2%) and
are presented in Table 6. Out of these patients with recurrence,
13 benefited from hormonal treatment pre-or post-operatively
(44.8%) (nine GnRHa, three oral contraceptives, and one DMPA)
while 16 didn’t receive any additional treatment.
DISCUSSION
While vulvo-perineal endometriosis presents mostly after
perineal trauma, its exact etiology remains unclear, even if
major progress has been achieved in the field over the last
decades. Etiopathogenesis of endometriosis has generally been
related to endometrial implantation, coelomic metaplasia,
lymphatic dissemination and hematogenous spread (1)
and the origin of extrapelvic endometriosis is not well-
deciphered. As pelvic endometriosis can be considered as
three separate entities (peritoneal, ovarian and recto-vaginal
(deep) lesions) with different pathogeneses (99,100), vulvo-
perineal endometriosis could potentially also be separated
between cystic and nodular lesions with distinct etiologies and
treatment. Direct mechanical implantation seems to be the
most plausible hypothesis for explaining scar endometriosis
after obstetrical and gynecological procedures. According to
this theory, mechanical dissemination during normal vaginal
delivery, for example, allows transplantation of viable decidual
endometrial cells into the episiotomy wound or perineal tear
(2,34,53,93,101). We must note that scar endometriosis
may as well-rarely be seen after a number of general surgical
procedures like appendicectomy, inguinal hernial repair,
laparoscopic cholecystectomy or even laparoscopic gastric
by-pass (9). Nevertheless, perineal endometriosis has also
been described in patients without any previous vulvo-vaginal
trauma. In that respect, we found 13 cases of primary perineal
endometriosis without vaginal birth, previous perineal injury
in the literature. Different explanations of the pathogenesis of
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Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
TABLE 5 | Hormonal therapy.
Année Number
of
patients
Age Rx Pre-surgery Time (month) Traitement Rx Post-surgery Time Follow-up
(months)
Récurrence
Shin et al. (67) 1 33 Danazol and GnRHa 2 Radical hysterectomy +bilateral
oophorectomy with partial excision
with cautherization of perineal lesions
local estrogens NA 6 No
Liang et al. (2) 1 30 Danazol 800 mg 1 Excision / / 12 No
1 33 Danazol irregularly NA Excision / / 12 No
Katz et al. (61) 1 14 Oral contraceptives NA Excision / / 4 No
Kang et al. (31) 1 32 GnRHa 3 Excision / / NA NA
Yogini et al. (35) 1 34 / / Drainage and excision GnRHa NA NA NA
Kahraman et al. (38) 1 19 / / Complete excision Oral contraceptives 3 3 1
Zhu et al. (93) 13 30.67 GnRHa 3–6 Complete excision GnRHa 3–6 9–168 No
7 GnRHa 3– 6 Incomplete excision GnRHa 3–6 4–12 7
1 Contraceptives
17alpha-hydroxyprogesterone caproate
250 mg im/28 days and tamoxifen 10 mg
twice a day
15 Complete excision Contraceptives
17alpha-hydroxyprogesterone
caproate 250 mg im/28 days and
tamoxifen 10mg twice a day
8 84 1
Hazard et al. (14) 1 15 / / Excision Oral contraceptivew NA NA No
Ngu et al. (63) 1 30 GnRha 3 Excision / / NA NA
Ruiz de Gauna et al. (20) 1 32 / / Wide excision GnRHa 3 NA No
Chen et al. (10) 10 33.4 GnRHa, Nemestran, DMPA 1– 6 Narrow excision GnRHa, Nemestran, DMPA 1–6 NA No
1 GnRHa 3 Narrow excision IUD-LNG NA NA No
9 GnRHa 3–5 Narrow excision / / 12 1
2 / / Narrow excision GnRHa 4 NA No
1 DMPA 3–6 Incomplete excision DPMA 3–6 72 1
Hakimi et al. (80) 1 28 / / Excision (difficult) LHRH 6 NA NA
Grimstad et al. (24)1 29 / / Excision Oral contraceptives 65 72 1
Jeyaseelan et al. (83) 1 38 / / Excision GnRHa 3 NA NA
Li et al. (94)4 34.35 / / Surgical excision GnRHa 3 12 1
2 / / Surgical excision Mifepristone 1 NA No
1 / / Surgical excision Progesterone NA NA No
Sharp et al. (90) 1 39 / / Large biopsy Dienogest 2mg 6 months NA NA
Baba et al. (55) 1 35 / / Complete excision GnRH NA NA NA
Sharm et al. (89) 1 37 / / Wide excision GnRHa 1 6 No
Saloum et al. (58) 1 34 / / Excision GnRHa 3 NA No
Wallace et al. (17) 1 42 / / Excision Oral contraceptives 12 12 No
Liu et al. (96) 1 34 Marvelon NA Complete excision GnRHa 3 85 No
12 31.8 / / Complete excision GnRHa 3–6 45.5 1 (12
months)
1 37 Mifepristone 3 Complete excision Mifepristone 3 75 No
1 38 GnRHa 3 Complete excision Mifepristone 3 62 No
2 34.5 GnRHa 3 Complete excision GnRH 3 46 No
2 30.5 GnRHa 3 to 5 Complete excision / / 23.5 No
88
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Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
TABLE 6 | Recurrences of perineal endometriosis after initial treatment.
Number of
patients
ASI Initial treatment Follow-up
(months)
Surgical Hormonal Duration
Prince et al. (41) 1 No Excision No NA 6
Trampuz et al. (76) 1 yes Excision No NA 3
Swerdlow et al. (69) 1 No TAH +BSO No NA 3
Gordon et al. (22) 1 yes Excision No NA 5
Liang et al. (2) 1 NA Excision No NA 12
Kahraman et al. (38) 1 No CE Oral contraceptives NA 3
Nominato et al. (92) 1 NA Excision No NA NA
Eyvazzadeh et al. (19) 1 No Biopsy No NA 60
Iqbal et al. (28) 1 No Incision and drainage No NA 6
Zhu et al. (93) 7 Yes IE GnRHa pre or post op 3–6 months 4–12
1 NA CE Postop contraceptive pills
17alpha-hydroxyprogesterone
caproate 250 mg intramuscular
injection per 28 days and tamoxifen
10 mg twice a day for 8 months
8 months 84
Chen et al. (10) 1 Yes NE GnRHa Pre-op 3 months 12
1 Yes IE DMPA pre- and post-op 3–6 months 72
Jain et al. (32) 2 No Excision No NA 3–7
Grimstad et al. (24) 1 No (clitoris) Excision Oral contraceptives NA 72
Li et al. (94) 1 NA CE GnRH 3 12
Matalliotakis et al. (95) 2 NA Excision NA NA NA
Liu et al. (96) 3 No CE No NA 12–36
1 No CE GnRHa post-op 3 months 12
29
IE, incomplete excision; CE, complete excision; NE, narrow excision; TAH +BSO, total abdominal hysterectomy +bilateral salpingo-oophorectomy; GnRHA, gonadotropin-releasing
hormone analog; DMPA, Depot medoxyprogesterone acetate; NA, not available.
TABLE 7 | Summary of recommendations about vulvo-perineal endometriosis.
Early diagnosis and treatment are recommended in order to prevent adverse complications.
Adetailed medical and surgical history associated with a thorough clinical exam should be realized (vulvar and vaginal examination with rectal examination
in case of suspicion of ASI).
Pelvic and perineal ultrasound as well as pelvic MRI should be performed in all patients and associated with endoanal ultrasound when there is a suspicion of
ASI.
Histology is the hallmark of diagnosis.
Complete excision should be the treatment of choice as it decreases the risk of recurrence and could reduce consequently the risk of malignant degeneration.
Hormonal treatment could be proposed to attempt to decrease the size of a large lesion before surgery or to avoid recurrence of the lesion.
Long-term follow-up is recommended, as malignant transformation appears uncertain, unpredictable and may be very delayed.
Every case of vulvo-perineal endometriosis should be reported describing in details the previous history, the clinical management and the treatment
received.
spontaneously developing perineal endometriotic lesions have
been put forward with the most likely being lymphovascular
dissemination (39,53). However, the presence of endometriosis
in the labia majora could also be explained by the direct spread
of pelvic endometriosis along the round ligaments or Nuck
canal’s remnants while a solitary focus in the Bartholin’s gland
could theoretically be attributed to coelomic metaplasia (57).
Eventually, other factors, such as immunological, genetic and
familial factors, could be involved in the pathogenesis of this
disease (94,102).
Few studies have reported the incidence or prevalence of
vulvo-perineal endometriosis. After vaginal delivery, the highest
incidence rate of perineal endometriosis was reported by
Nominato et al. representing 0.06% of patients, compared to 0.2%
abdominal scar endometriosis after cesarean section (92), while
perineal endometriosis only represents a proportion of 0.37% of
women treated surgically for endometriosis (10).
Besides the rarity of vulvo-perineal endometriosis, its
variability in clinical presentation makes this condition hardly
recognized by some healthcare professionals leading to a delayed
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Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
TABLE 8 | Data to report in case of vulvo-perineal endometriosis.
Patient
Age
BMI
Ethnicity
Obstetrical History
Gravidity - Parity
Type of delivery
Episiotomy - Perineal laceration - Perineal tear (degree) - Perineal repair
Timing of any history
Medical or surgical history
Previous vulvo-perineal lesion, surgery or trauma
Previous abdominal surgery
Timing of any history
Symptoms
Beginning
Duration
Type (pain, localization, cyclical or not, …)
Latent period since trauma
Other symptoms
Clinical exam
Presence of a perineal mass or nodule
Size
Tenderness
Color of the Skin color
Detailed localization
Speculum examination
Rectal examination
Anal Sphincter Involvment
Work-up
Perineal ultrasound
Pelvic ultrasound
Pelvic MRI
Perianal ultrasound
Biopsy or FNAC
Other
Association with pelvic endometriosis
Treatment
Surgery
Excision or biopsy
Detailed procedure
Margins
Spillage
Type of closure
Type of repair in case of ASI
Hormonal
Pre-or post-surgery
Type
Duration
Comparison of symptoms and clinical exam before and after treatment
Histology
Follow-up
Recurrence
Type
Timing after treatment
Malignant transformation
diagnosis. Misdiagnoses have also been reported such as herpes
outbreak or perianal sepsis in the presence of vulvar pain
with ulcerations or perianal swelling, respectively (14,28). For
instance, we showed a mean duration of symptoms of 12 months,
ranging from 2 weeks to 20 years in our review meaning that half
of them had to endure their pain for more than a year before
being correctly diagnosed (94).
Early diagnosis and treatment are however recommended
in order to prevent adverse complications such as long-
term psychological distress, progressive involvement of the
surrounding and adjacent tissues such as anal sphincter or
rectum and potential malignant degeneration.
A detailed medical and surgical history associated with a
thorough clinical exam are of great importance for accurate
diagnosis. Good clinical vulvar and vaginal examination,
including speculum and bimanual examination, are primordial
to fully describe the perineal lesions. Rectal examination should
be performed routinely in case of perineal lesions especially
if suspicion of anal sphincter involvement (ASI). Clinically,
endometriosis of the perineum and vulva presents as ill-defined
papule or nodule, generally hard, usually located near a surgical
scar, potentially skin-colored, dark-red, brown, or blue-black
cystic (10,103). It is mainly accompanied by cyclic pain and
swelling, or periodic leakage of dark colored fluid during menses
attributable to the fact that endometrial implants behave like
normal endometrium. Some cases show neither discoloration
of the perineal skin, nor local swelling nor intermittent leakage
(32). Other symptoms can include dyspareunia. Interestingly,
Zhu et al. described three criteria i.e., history of past perineal
tear of episiotomy during vaginal delivery, presence of a tender
nodule or mass at the perineal lesion on clinical exam and
history of progressive and cyclic perineal pain which when all
met provide a 100% positive predictive value (93). Concomitant
pelvic endometriosis was found in 6.1% of patients in our
systematic review. These results concord with the literature
suggesting that scar endometriosis is not a risk factor for pelvic
endometriosis (104,105).
The differential diagnosis in such patients includes, but is not
limited to, anal fistula, abscesses, suture granulomas, Bartholin
cysts or bartholinitis, hernias, hematoma, sebaceous cyst, lipoma,
herpes, neoplastic tissue or metastatic carcinoma, traumatic
neuroma, desmoid tumor and anal melanoma (9,28,42,45,
46). A perineal mass discovered in menopaused women should
be considered as malignant until proven otherwise. Malignant
degeneration occurs infrequently for cutaneous endometriosis
representing 0.3–1% of endometriosis located in surgical scars
(106). It is difficult to distinguish benign from malignant perineal
endometriosis based on symptoms and clinical examination and
a biopsy or surgical excision will always be necessary to confirm
the diagnosis of malignant transformation (13). Histological
observations are dominated by endometrioid carcinoma and
sarcoma (107), but can also present as dermatosarcoma, clear
cell carcinoma and serous papillary cystadenocarcinoma (87,
106,108–116). As malignant transformation appears uncertain,
unpredictable and may be very delayed, long-term follow-up
is recommended.
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Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
The work-up appeared to be very variable depending on
the medical team dealing with the patients. It was therefore
difficult to evaluate the sensibility and specificity of each exam
for perineal endometriosis as most of them have been realized
in only a tiny proportion of the patients in this study. Levels
of serum CA125 did not seem to be effective in diagnosing
perineal endometriosis since it was usually normal or slightly
increased. With regard to perineal ultrasonography, variable
sonographic features were seen, as it is the case for abdominal
wall endometriosis, which could make the diagnostic process
more challenging but it remains useful to describe precisely the
size of the lesions and to assess the extent of the ASI. Preoperative
endoanal ultrasonography has also been described as a reliable
technique for visualizing perianal endometriosis and diagnosing
ASI, enabling the surgeon to determine the extent of an operative
procedure and the possible need for a sphincteroplasty (46,86).
Ultrasonographic features of the lesion are usually similar to
those observed with perineal ultrasonography with the advantage
that it better reveals the involvement of the anal sphincter (10).
Even if only 6.1% of the patients in this review benefited from
this exam, magnetic resonance imaging (MRI) could become
the modality of choice for perineal imaging (117,118) as pelvic
MRI has greater sensitivity (90–92%) and specificity (91–98%) for
the diagnosis of endometriomas when compared to other non-
invasive methods (119,120). Vulvo-perineal localizations are
easily identified on T1-weighted fat-suppressed images as hyper-
intense spots within the perineum. Multilobular mass with inner
hemorrhage, localized or diffuse vulvovaginal wall thickening,
hemorrhagic or spiculated masses and distortion can also be
observed (94,117). MRI also helps in assessing the extent of the
anal sphincter involvement (35). Depending on the availability
in each center, we suggest that pelvic and perineal ultrasound as
well as MRI should be performed in all patients and associated
with endoanal ultrasound when there is a suspicion of ASI.
Histology is the hallmark of diagnosis which shows
endometrial glands, stroma, and hemosiderin pigment.
Generally, diagnosis is easy with a microscopic examination
of a standard hematoxylin and eosin (H&E)-stained slide.
Immunostaining for CD10 (neprilysin, a cell-surface
metalloendopeptidase expressed in normal and ectopic
endometrial stroma) increases the sensitivity compared to
H&E staining (17,19). Evidencing the estrogen receptor (ER)
and progesteron receptor (PR) may help to identify endometrial
glands (121). Furthermore, it is important to keep in mind
that cutaneous endometriotic lesions show a broad spectrum of
metaplastic changes and that all types of müllerian differentiation
can be discovered (122) which make the diagnosis on FNAC or
biopsy challenging for the unexperimented histologists.
Treatment of vulvo-perineal endometriosis includes usually
surgical excision with or without hormonal suppression (GnRHa,
oral contraceptives, progestins) (2,10,15,123). It seems that
complete excision should be the treatment of choice as it
decreases the risk of recurrence (10,93) and could reduce
consequently the risk of malignant degeneration (109). Care must
be applied to avoid rupturing the mass during surgery with
its consecutive risk of re-implantation or leaving endometriotic
remnants. To this end, excision of surrounding fibrous tissue has
been suggested (94) although recommendations with respect to
the surgical technique, e.g., surgical margins needed to decrease
the risk of recurrence, are not available so far. Precise description
of the surgical procedure including technique and margins is
most often missing and awaited in future studies. When the
anal sphincter is involved, complete narrow excision or wide
excision of the endometrial tissue with a good healthy margin
have been proposed with primary sphincteroplasty using the
apposition or overlapping technique (10). Although symptomatic
relief could be achieved with hormonal intervention, complete
surgical excision still remains the best treatment for perineal
endometriosis and often leads to permanent cure (71). As
expected, large and deep lesions to the muscle or the fascia
might be more difficult to excise completely. In large lesions,
complete excision of the lesion may entail a synthetic mesh
placement, tissue transfer for closure after resection (124) or
combined surgery with gynecologic and plastic surgeons (125).
It is however important to keep in mind that endometriosis
remains a benign condition allowing conservative surgery and
that decaying surgery is not recommended even in very large
lesions. The type of resection should be based on the patient’s
age and desire for future pregnancy and the decision should be
made only after possible outcomes of the different approaches
have been discussed with the patient (86). Some authors have
suggested that wide excision with primary sphincteroplasty could
be optimal in younger patients, obviating the need for additional
therapy, while narrow or incomplete excision with subsequent
hormonal therapy could be advantageous in older patients
closer to menopause to lessen the risk of incontinence due to
sphincter resection (93). 28.1% of patients in this review received
hormonal treatment pre-or post-operatively. As described in
pelvic endometriosis, hormonal treatment could stabilize the
size of cystic lesions and reduce pain as endometriosis is an
estrogen-dependent process (126–129). Some authors suggested
that massive lesions with anal sphincter involvement should
be treated by hormonal therapy before surgery to reduce the
size of the perineal mass (63). It should be noted that perineal
endometriosis persists with medical treatment alone as it was
always found on histology when hormonal treatment was
followed by surgical excision. Various authors have reported the
administration of a gonadotropin-releasing hormone analog to
prevent recurrence (10,31,96). When complete wide excision,
as reported by Zhu et al. (14), was performed, the recurrence
rate was lower (3.3%) than the overall rate of 9.3% found in
our review compiling all kinds of excisions, suggesting that
recurrence was presumably due to incomplete removal of the
lesions rather than to the absence of hormonal treatment (14).
In addition, preoperative hormone therapy did not improve
outcomes compared to surgery alone in patients with ASI (10).
Results on hormonal therapy for abdominal wall or abdominal
scar endometriosis are similar to those presented in this review
showing a possible temporary relief of symptoms or potential
slight reduction of the lesions’ size easing the surgical resection
but the bulk of evidence shows a low degree of efficacy.
Currently, available data do not comment on best practices for
the perioperative management of cutaneous endometriosis (104,
105,130–134).
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Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
The limitations of this systematic review include the level of
evidence due to the nature of the studies i.e., retrospective and
case reports and the important variations in clinical management
of vulvo-perineal endometriosis described in the available studies
such as methods of diagnosis, surgery procedure’s details and
hormonal therapy. At present, there are no comparative studies
to provide accurate and evidence-based guidelines regarding
optimal diagnostic methods, treatment options and outcomes for
endometriosis involving the perineum.
Although evidence-based guidelines cannot be retrieved from
this systematic review due to the reasons mentioned above,
Table 7 summarizes all the suggested recommendations based
on our results and on the available literature. To improve
our knowledge on this rare condition, we suggest developing
a international database on vulvo-perineal endometriosis. Any
future study regarding this type of endometriosis should include
the data described in Table 8.
In conclusion, vulvo-perineal endometriosis is a rare entity
with ∼300 cases reported in the literature since 1923. With
the available knowledge shown in this systematic review, we
encourage all practitioners to think about perineal endometriosis
in case of perineal cyclical pain with or without previous
perineal damage. Diagnosis should be done with clinical
exam, perineal ultrasound and pelvic MRI when available.
In case of anal sphincter involvement, perianal ultrasound
should be performed. Surgical excision of the lesion should
be realized in order to remove the lesion and to confirm
the diagnosis histologically. Hormonal treatment could be
proposed to attempt to decrease the size of a large lesion
before surgery or to avoid recurrence of the lesion. As
evidence-based approach to the diagnosis, treatment and
recurrence rate of affected patients remains a challenge given
its low prevalence, the variations in management found in the
articles included and the limited quality of available studies,
we suggest that a prospective database on vulvo-perineal
endometriosis should be generated to increase knowledge but
also awareness among healthcare professionals and optimize
patients’ care.
DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be
made available by the authors, without undue reservation.
AUTHOR CONTRIBUTIONS
CM: search strategy, screening of studies, data extraction,
manuscript writing, and final revision. ZC: screening of studies.
J-LS, ML, and PJ: final revision. VT: screening of studies and
language revision. CW: search strategy, manuscript writing, and
final revision. All authors contributed to the article and approved
the submitted version.
REFERENCES
1. Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis:
pathogenesis and treatment. Nat Rev Endocrinol. (2014)
10:261–75. doi: 10.1038/nrendo.2013.255
2. Liang CC, Tsai CC, Chen TC, Soong YK. Management of
perineal endometriosis. Int J Gynecol Obstet. (1996) 53:261–
5. doi: 10.1016/0020-7292(95)02592-8
3. Davis AC, Goldberg JM. Extrapelvic endometriosis. Semin Reprod Med.
(2017) 35:98–101. doi: 10.1055/s-0036-1597122
4. Andres MP, Arcoverde FV, Souza CC, Fernandes LF, Simoes Abrao
MS, Kho RM. Extrapelvic endometriosis: a systematic review. J
Minim Invasive Gynecol. (2020) 27:373–89. doi: 10.1016/j.jmig.201
9.10.004
5. Jubanyik KJ, Comite F. Extrapelvic endometriosis. Obstet Gynecol Clin North
Am. (1997) 24:411–40. doi: 10.1016/S0889-8545(05)70311-9
6. Bulun SE. Endometriosis. N Engl J Med. (2009) 360:268–
79. doi: 10.1056/NEJMra0804690
7. Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, et al.
Endometriosis. Endocr Rev. (2019) 40:1048–79. doi: 10.1210/er.2018-00242
8. Giudice LC. Clinical practice. Endometriosis. N Engl J Med. (2010) 362:2389–
98. doi: 10.1056/NEJMcp1000274
9. Cinardi N, Franco S, Centonze D, Giannone G. Perineal scar endometriosis
ten years after Miles’ procedure for rectal cancer: case report and review of
the literature. Int J Surg Case Rep. (2011) 2:150–3. doi: 10.1016/j.ijscr.2011.
04.001
10. Chen N, Zhu L, Lang J, Liu Z, Sun D, Leng J, et al. The clinical
features and management of perineal endometriosis with anal sphincter
involvement: a clinical analysis of 31 cases. Hum Reprod. (2012) 27:1624–
7. doi: 10.1093/humrep/des067
11. Dougherty LS, Hull T. Perineal endometriosis with anal sphincter
involvement: report of a case. Dis Colon Rectum. (2000) 43:1157–
60. doi: 10.1007/BF02236565
12. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for
systematic reviews and meta-analyses: the PRISMA statement. PLoS Med.
(2009) 6:e1000097. doi: 10.1371/journal.pmed.1000097
13. Catherwood AE, Cohen ES. Endometriosis with decidual
reaction in episiotomy scar. Am J Obstet Gynecol. (1951)
62:1364–6. doi: 10.1016/0002-9378(51)90068-3
14. Hazard DB, Harkins GJ. A case of cutaneous endometriosis following vulvar
injury. J Endometr. (2011) 3:171–3.
15. Cheng DL, Heller DS, Oh C. Endometriosis of the perineum; report of two
new cases and a review of literature. Eur J Obstet Gynecol Reprod Biol. (1991)
42:81–4. doi: 10.1016/0028-2243(91)90165-H
16. Demir M, Yildiz A, Ocal I, Yetimalar MH, Kilic D, Yavasi O. Endometriosis
in episiotomy scar: a case report. J Cases Obstet Gynecol. (2014) 1:8–10.
17. Wallace E, Marin S, Elkattah R. Vulvar endometriosis in the setting
of a traumatic neuroma. J Endometr Pelvic Pain Disord. (2019) 11:49–
51. doi: 10.1177/2284026519828909
18. Kirk EW. Endometrioma in the posterior half of the labium majus. J Obstet
Gynaecol Br Emp. (1950) 57:237–9. doi: 10.1111/j.1471-0528.1950.tb05233.x
19. Eyvazzadeh AD, Smith YR, Lieberman R, Quint EH. A rare case of
vulvar endometriosis in an adolescent girl. Fertil Steril. (2009) 91:929.e9–
11. doi: 10.1016/j.fertnstert.2008.10.026
20. Ruiz de Gauna B, Rodriguez D, Cabré S, Callejo J. A case of endometriosis
in episiotomy scar with anal sphincter involvement. Int J Clin Med. (2011)
2:624–6. doi: 10.4236/ijcm.2011.25104
21. Gocmen A, Inaloz HS, Sari I, Inaloz SS. Endometriosis in
the Bartholin gland. Eur J Obstet Gynecol Reprod Biol. (2004)
114:110–1. doi: 10.1016/j.ejogrb.2003.07.004
22. Gordon PH, Schottler JL, Balcos EG, Goldberg SM. Perianal
endometrioma: report of five cases. Dis Colon Rectum. (1976)
19:260–5. doi: 10.1007/BF02590916
23. Gorkem U, Efeturk T, Guney G, Gungor T. A case of vulvar endometrioma
mimicking a bartholin cyst. J Cases Obstet Gynecol. (2016) 3:57–
60. doi: 10.1093/jscr/rjv169
Frontiers in Surgery | www.frontiersin.org 10 May 2021 | Volume 8 | Article 637180

Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
24. Grimstad FW, Carey E. Periclitoral endometriosis: the dilemma of a chronic
disease invading a rare location. J Minim Invasive Gynecol. (2015) 22:684–
6. doi: 10.1016/j.jmig.2015.02.002
25. Healy JJ, Hills FH. Bilateral endometriosis of the vulva. Am J Obstet Gynecol.
(1956) 72:1361–3. doi: 10.1016/0002-9378(56)90801-8
26. Heller DS, Lespinasse P, Mirani N. Endometriosis of the perineum: a rare
diagnosis usually associated with episiotomy. J Low Genit Tract Dis. (2016)
20:e48–9. doi: 10.1097/LGT.0000000000000203
27. Gözükara I, Karapinar OS, HakverdiI AU. Endometriosis of episiotomy scar.
J Turkish Ger Gynecol Assoc. (2016) 17:S166.
28. Iqbal M, Thumbe V, Dhange R, Chan SY, Bhalerao S. Perianal endometriosis
mimicking recurrent perianal abscess. Case Rep Gastroenterol. (2009) 3:414–
7. doi: 10.1159/000250787
29. Cheleden J. Endometriosis of the perineum. Report of two cases. South Med
J. (1968) 61:1313–4. doi: 10.1097/00007611-196812000-00011
30. Kouach J, El Hassani M, Moussaoui DR, Mohamed D.
Vulvar endometriosis. J Obstet Gynaecol Canada. (2008)
30:1095. doi: 10.1016/S1701-2163(16)33014-6
31. Kang SK, Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Cutaneous
endometriosis: a combination of medical and surgical treatment. J
Dermatolog Treat. (2002) 13:189–92. doi: 10.1080/09546630212345677
32. Jain D. Perineal scar endometriosis: a comparison of two cases. BMJ Case
Rep. (2013) 2013:bcr2013010051. doi: 10.1136/bcr-2013-010051
33. AbdullGaffar B, Keloth TR, Raman LG, Mahmood S, Almulla A,
AlMarzouqi M, et al. Unusual benign polypoid and papular neoplasms
and tumor-like lesions of the vulva. Ann Diagn Pathol. (2014) 18:63–
70. doi: 10.1016/j.anndiagpath.2013.11.005
34. Luterek K, Barcz E, Bablok L,Wierzbicki Z. Giant recurrent perineal
endometriosis in an episiotomy scar - a case report. Ginekol Pol. (2013)
84:726–9. doi: 10.17772/gp/1631
35. Yogini KD, Balasubramaniam D, Karunanithi S, Parthasarathi R. Perianal
endometriosis: a rare presentation of extrapelvic endometriosis. J SAFOG.
(2019) 11:138–9. doi: 10.5005/jp-journals-10006-1659
36. Natale KE, Royer MC, Rush WL, Luption GP. Cutaneous deciduosis: a
report of two cases of an unusual pseudomalignancy. J Cutan Pathol. (2012)
39:777–80. doi: 10.1111/j.1600-0560.2012.01907.x
37. Kanellos I, Kelpis T, Zaraboukas T, Betsis D. Perineal endometriosis in
episiotomy scar with anal sphincter involvement. Tech Coloproctol. (2001)
5:107–8. doi: 10.1007/s101510170009
38. Kahraman K, Sonmezer M, Gungor M. Recurrent vulvar-perineal
endometriosis. Artemis. (2003) 4:77−9.
39. Zhu L, Lang J, Wong F, Guo L. Perineal endometriosis without perineal
trauma: a case report. Chin Med J (Engl). (2003) 116:639–40.
40. Ferreira LA. Endometriosis as a differential diagnosis on vulvar lump: a case
report. Int J Gynecol Obstet. (2018) 143:742.
41. Prince LN, Abrams J. Endometriosis of the perineum; review of
the literature and case report. Am J Obstet Gynecol. (1957) 73:890–
3. doi: 10.1016/0002-9378(57)90402-7
42. Laadioui M, Alaoui F, Jayi S, Bouguern H, Chaara H, Melhouf MA. Deep
perineal endometriosis on episiotomy scar: about a rare case. Pan Afr Med J.
(2013) 16:112. doi: 10.11604/pamj.2013.16.112.3415
43. Maheswari L. Case report of epidiotomy scar endometriosis. Univ J Surg Surg
Spec. (2017) 3.
44. Aydin Y, Atis A, Polat N. Bilateral endometrioma of Bartholin glands
accompanying ovarian endometrioma. J Obstet Gynaecol. (2011) 31:187–
9. doi: 10.3109/01443615.2010.541303
45. Corazza M, Schettini N, Pedriali M, Toni G, Borhi A. Vulvar endometriosis.
A clinical, histological and dermoscopic riddle. J Eur Acad Dermatology
Venereol. (2020) 34:e321–2. doi: 10.1111/jdv.16257
46. Watanabe M, Kamiyama G, Yamazaki K, Hiratsuka K, Takata M, Tsunoda
A, et al. Anal endosonography in the diagnosis and management of
perianal endometriosis: report of a case. Surg Today. (2003) 33:630–
2. doi: 10.1007/s00595-003-2545-z
47. Marcos MF, Marchitelli C, Sluga C, Secco G, Gorgoza S, Martinez MM.
Vulvar endometriosis: A series of 4 cases. J Low Genit Tract Dis. (2017)
21:S5–6. doi: 10.1097/LGT.0000000000000269
48. Matseoane S, Harris T, Moscowitz E. Isolated endometriosis in a Bartholin
gland. N Y State J Med. (1987) 87:575–6.
49. Mazzeo C, Gammeri E, Foti A, Rossitto M, Cucinotta E. Vulvar
endometriosis and Nuck canal. Ann Ital Chir. (2014) 85:1–4.
50. Mi¸sina A, Zaharia S, Harea P, Fuior-Bulhac L, Petrovici V, ¸sor E, et al.
Endometriosis of the vulva and perineum. Arta Medica. (2020) 1:4–8.
51. Nussbaum W, Motyloff L Endometriosis of the vulva during pregnancy. Am
J Obstet Gynecol. (1957) 73:215–6. doi: 10.1016/S0002-9378(16)37286-6
52. Mahmud N, Kusuda N, Ichinose S, Gyotoku Y, Nakajima H, Ishimaru T, et al.
Needle aspiration biopsy of vulvar endometriosis: a case report. Acta Cytol.
(1992) 36:514–6.
53. Nasu K, Okamoto M, Nishida M, Narahara H. Endometriosis of the
perineum. J Obstet Gynaecol Res. (2013) 39:1095–7. doi: 10.1111/jog.12003
54. Odobasic A, Pasic A, Iljazovic-Latifagic E, Arnautalic L, Odobasic
Ad, Idrizovic E, et al. Perineal endometriosis: a case report and
review of the literature. Tech Coloproctol. (2010) 14(Suppl. 1):S25–
7. doi: 10.1007/s10151-010-0642-8
55. Baba AA, Dar AM, Parray AA, Khan MA, Laway MA, Chowdri
NA. Perineal scar endometriosis. Indian J Colo-Rectal Surg. (2018)
1:30. doi: 10.4103/IJCS.IJCS_2_18
56. Brug P, Gueye N-A, Bachmann G. Vulvar endometriosis presenting with
dyspareunia: a case report. J Reprod Med. (2012) 57:175–7.
57. Singh P, Bhutia K, Gudi MA, Chuan HH. Endometriotic foci in bartholin’s
cyst. J Gynecol Surg. (2017) 33:111–3. doi: 10.1089/gyn.2016.0061
58. Saloum NM, Qureshi S, Ibrahim SA, Alrashid A. A rare case report of
endometriosis in an episiotomy scar without anal sphincter involvement. EC
Gynaecol. (2018) 12:466–70.
59. Kistner RW, Younge PA.E ndometriosis occurring in a vaginoperineal fistula.
Am J Obstet Gynecol. (1952) 63:455–7. doi: 10.1016/S0002-9378(15)32847-7
60. Ramsey WH. Endometrioma involving the perianal tissues: report of a case.
Dis Colon Rectum. (1971) 14:366–7. doi: 10.1007/BF02553424
61. Katz Z, Goldchmit R, Blickstein I. Post-traumatic vulvar endometriosis. Eur
J Pediatr Surg. (1996) 6:241–2. doi: 10.1055/s-2008-1066519
62. Robotti G, Canepari E, Torresi M. Premenstrual inguinal swelling and pain
caused by endometriosis in the Bartholin gland: a case report. J Ultrasound.
(2015) 18:71–2. doi: 10.1007/s40477-014-0076-7
63. Ngu SF, Cheung VY. Vulvar endometriosis. J Obstet Gynaecol Canada. (2011)
33:891. doi: 10.1016/S1701-2163(16)35007-1
64. Sayfan J, Benosh L, Segal M, Orda R. Endometriosis in episiotomy scar with
anal sphincter involvement - Report of a case. Dis Colon Rectum. (1991)
34:713–6. doi: 10.1007/BF02050357
65. Shanmuga Jayanthan S, Shashikala G, Arathi N, S. Perineal
scar endometriosis. Indian J Radiol Imaging. (2019) 29:457–
61. doi: 10.4103/ijri.IJRI_366_19
66. Barisic GI, Krivokapic Z V, Jovanovic DR. Perineal endometriosis
in episiotomy scar with anal sphincter involvement: report of two
cases and review of the literature. Int Urogynecol J. (2006) 17:646–
9. doi: 10.1007/s00192-005-0022-5
67. Shin HC, Kim TH, Kim SW, Kim DS, Park CH, Huh CK. Perineal
endometriosis. Ann Dermatol. (1994) 6:196–9. doi: 10.5021/ad.1994.6.2.196
68. Sully L. Endometrioma of the perineum associated with episiotomy
scars. Scott Med J. (1977) 22:307–9. doi: 10.1177/003693307702
200422
69. Swerdlow DB. Endometrioma masquerading as an anorectal abscess: report
of a case. Dis Colon Rectum. (1975) 18:620–2. doi: 10.1007/BF02587146
70. Heijink T, Bogers H, Steensma A. Endometriosis of the Bartholin gland:
a case report and review of the literature. J Med Case Rep. (2020)
14:85. doi: 10.1186/s13256-020-02424-7
71. Tam T, Huang S. Perineal endometriosis in an episiotomy
scar: case report and review of literature. J Endometr. (2012)
4:93–6. doi: 10.5301/JE.2012.9410
72. Tornqvist B. Endometriosis in vaginal, vulvar and perineal scars. Acta Obstet
Gynecol Scand. (1949) 28:485–9. doi: 10.3109/00016344909155706
73. Torres-Cepeda D, Reyna-Villasmil E, Santos-Bolívar J. Endometriosis vulvar.
Reporte de Caso (Vulvar Endometriosis. Case Report). Av en Biomed.
(2014) 3:38–41.
74. Ümit C, Kokanali MK, Erkilinç S, Doganay M. Spontanous vulvar
endometriosis: report of a case. Gynecol Obs Reprod Med. (2014) 20:119–21.
75. Dadhwal V, Sharma A, Khoiwal K, Nakra T. Episiotomy scar endometriosis.
Med J Armed Forces India. (2018) 74:297–9. doi: 10.1016/j.mjafi.2017.06.004
Frontiers in Surgery | www.frontiersin.org 11 May 2021 | Volume 8 | Article 637180

Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
76. Trampuz V. Endometriosis of the perineum. A report of 5 new cases. Am J
Obstet Gynecol. (1962) 84:1522–5. doi: 10.1016/S0002-9378(16)35801-X
77. Buda A, Ferrari L, Marra C, Passoni P, Perego P, Milani R.
Vulvar endometriosis in surgical scar after excision of the
Bartholin gland: report of a case. Arch Gynecol Obstet. (2008)
277:255–6. doi: 10.1007/s00404-007-0458-6
78. Turan V, Ergenoglu M, Yeniel O, Emiroglu G, Ulukus M, Zekioglu O.
Vulvar endometrioma: a case report. J Nepal Med Assoc. (2011) 51:87–
9. doi: 10.31729/jnma.250
79. Gunes M, Kayikcioglu F, Ozturkoglu E, Haberal A. Incisional endometriosis
after cesarean section, episiotomy and other gynecologic procedures. J Obstet
Gynaecol Res. (2005) 31:471–5. doi: 10.1111/j.1447-0756.2005.00322.x
80. Hakimi I. Endometriosis in the Bartholin gland: a case report. J Gynecol
Obstet. (2014) 2:75. doi: 10.11648/j.jgo.20140205.12
81. Hamdi A, Gharsa A, Jaziri D, Sfar E, Chelli D. Perineal endometriosis
without perineal trauma: a case report. Chin Med J. (2015) 6:1–
3. doi: 10.4172/2155-9554.10000293
82. Canlorbe G, Laas E, Cortez A, Daraï E. Spontaneous hymeneal
endometriosis: a rare cause of dyspareunia. BMJ Case Rep. (2014)
2014:bcr2013202299. doi: 10.1136/bcr-2013-202299
83. Jeyaseelan S, Kwatra N. A rare case of episiotomy scar endometriosis. J Obstet
Gynecol India. (2016) 66(Suppl. 2):654–5. doi: 10.1007/s13224-015-0800-z
84. Leite GKC, De Carvalho LFP, Korkes H, Guazzelli TF, Kenj G, Viana ADT.
Scar endometrioma following obstetric surgical incisions: retrospective study
on 33 cases and review of the literature. São Paulo Med J. (2009) 127:270–
7. doi: 10.1590/S1516-31802009000500005
85. Rajesh Kamble V, Gawande MS. Preoperative magnetic resonance
evaluation of perineal endometriosis in episiotomy scar with anal sphincter
involvement. Panacea J Med Sci. (2016) 6:170.
86. Toyonaga T, Matsushima M, Tanaka Y, Nozawa M, Sogawa N, Kanyama H,
et al. Endoanal ultrasonography in the diagnosis and operative management
of perianal endometriosis: report of two cases. Tech Coloproctol. (2006)
10:357–60. doi: 10.1007/s10151-006-0309-7
87. Xu S, Wang W, Sun LP. Comparison of clear cell carcinoma and benign
endometriosis in episiotomy scar - two cases report and literature review.
BMC Womens Health. (2020) 20:11. doi: 10.1186/s12905-020-0880-5
88. Cai S-Q, Zheng M, Man X-Y. Perineal endometriosis: a case report. Int J Clin
Exp Med. (2014) 7:2939–40.
89. Sharma N, Khan DA, Jethani R, Baruah S, Dey B. Perineal endometriosis in
an episiotomy scar: a case report and review of literature. Gynecol Obs Case
Rep. (2018) 4:66. doi: 10.21767/2471-8165.1000066
90. Sharp C, Kulkarni M, Rosamilia A, Tsaltas J. Vulval endometriosis
following vaginal hysterectomy. J Minim Invasive Gynecol. (2020) 27:1453–
4. doi: 10.1016/j.jmig.2020.02.006
91. Paull T, Tedeschi LG. Perineal endometriosis at the site of episiotomy scar.
Obstet Gynecol. (1972) 40:28–34. doi: 10.1097/00006250-197207000-00006
92. Nominato NS, Victor Spyer Prates LF, Lauar I, Morais J, Maia L, Geber S.
Endometriose de cicatriz cirúrgica: estudo retrospectivo de 72 casos Scar
endometriosis: a retrospective study of 72 patients. Rev Bras Ginecol Obstet.
(2007) 29:403–7. doi: 10.1590/S0100-72032007000800007
93. Zhu L, Lang J, Wang H, Liu Z, Sun D, Leng J, et al. Presentation and
management of perineal endometriosis. Int J Gynecol Obstet. (2009) 5:230–
2. doi: 10.1016/j.ijgo.2009.01.022
94. Li J, Shi Y, Zhou C, Lin J. Diagnosis and treatment of perineal
endometriosis: review of 17 cases. Arch Gynecol Obstet. (2015) 292:1295–
9. doi: 10.1007/s00404-015-3756-4
95. Matalliotakis M, Matalliotaki C, Zervou MI, Krithinakis K, Goulielmos GN,
Kalogiannidis I. Abdominal and perineal scar endometriosis: retrospective
study on 40 cases. Eur J Obstet Gynecol Reprod Biol. (2020) 252:225–
7. doi: 10.1016/j.ejogrb.2020.06.054
96. Liu Y, Pi R, Luo H, Wang W, Zhao X, Qi X. Characteristics and long-term
outcomes of perineal endometriosis: a retrospective study. Medicine. (2020)
99:e20638. doi: 10.1097/MD.0000000000020638
97. Park SB, Kim JK, Cho KS. Sonography of endometriosis in infrequent sites. J
Clin Ultrasound. (2008) 36:91–7. doi: 10.1002/jcu.20431
98. Guerriero S, Conway F, Pascual MA, Graupera B, Ajossa S, Neri M, et al.
Ultrasonography and atypical sites of endometriosis. Diagnostics. (2020)
10:345. doi: 10.3390/diagnostics10060345
99. Donnez J, Nisolle M, Casanas-Roux F, Brion P, Da Costa Ferreira N.
Stereometric evaluation of peritoneal endometriosis and endometriotic
nodules of the rectovaginal septum. Hum Reprod. (1996) 11:224–
8. doi: 10.1093/oxfordjournals.humrep.a019024
100. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and
adenomyotic nodules of the rectovaginal septum are three different entities.
Fertil Steril. (1997) 68:585–96. doi: 10.1016/S0015-0282(97)00191-X
101. Steck WD, Helwig EB. Cutaneous endometriosis. JAMA. (1965) 191:167–
70. doi: 10.1001/jama.1965.03080030011002
102. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC.
Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril.
(2019) 111:327–40. doi: 10.1016/j.fertnstert.2018.10.013
103. Haley JC, Mirowski GW, Hood AF. Benign vulvar tumors. Semin Cutan Med
Surg. (1998) 17:196–204. doi: 10.1016/S1085-5629(98)80014-X
104. Tatli F, Gozeneli O, Uyanikoglu H, Uzunkoy A, Yalcin HC, Ozgonul A,
et al. The clinical characteristics and surgical approach of scar endometriosis:
a case series of 14 women. Bosn J Basic Med Sci. (2018) 18:275–
8. doi: 10.17305/bjbms.2018.2659
105. Horton JD, Dezee KJ, Ahnfeldt EP, Wagner M. Abdominal wall
endometriosis: a surgeon’s perspective and review of 445 cases. Am J Surg.
(2008) 196:207–12. doi: 10.1016/j.amjsurg.2007.07.035
106. Han L, Zheng A, Wang H. Clear cell carcinoma arising in previous
episiotomy scar: a case report and review of the literature. J Ovarian Res.
(2016) 9:1. doi: 10.1186/s13048-016-0211-5
107. Heaps JM, Nieberg RK, Berek JS. Malignant neoplasms arising in
endometriosis. Obstet Gynecol. (1990) 75:1023–8.
108. Kwon YS, Nam JH, Choi G. Clear cell adenocarcinoma arising in
endometriosis of a previous episiotomy site. Obstet Gynecol. (2008) 112 (2 Pt
2):475–7. doi: 10.1097/AOG.0b013e318179475b
109. Chene G, Darcha C, Dechelotte P, Mage G, Canis M. Malignant
degeneration of perineal endometriosis in episiotomy scar, case report
and review of the literature. Int J Gynecol Cancer. (2007) 17:709–
14. doi: 10.1111/j.1525-1438.2007.00822.x
110. Hitti IF, Glasberg SS, Lubicz S. Clear cell carcinoma arising in extraovarian
endometriosis: report of three cases and review of the literature. Gynecol
Oncol. (1990) 39:314–20. doi: 10.1016/0090-8258(90)90259-N
111. Kholová I, Ryska A, Dedic K. Composite tumor consisting of
dermatofibrosarcoma protuberans and giant cell fibroblastoma
associated with intratumoral endometriosis. Pathol Res Pract. (2001)
197:263–7. doi: 10.1078/0344-0338-00045
112. Kojima N, Yoshida H, Uehara T, Ushigusa T, Asami Y, Shiraishi K,
et al. Primary clear cell adenocarcinoma of the vulva: a case study with
mutation analysis and literature review. Int J Surg Pathol. (2019) 27:792–
7. doi: 10.1177/1066896919848823
113. Mesko JD, Gates H, McDonald TW, Youmans R, Lewis J.
Clear cell (’Mesonephroid’) adenocarcinoma of the vulva
arising in endometriosis: a case report. Gynecol Oncol. (1988)
29:385–91. doi: 10.1016/0090-8258(88)90241-7
114. Bolis GB, Maccio T. Clear cell adenocarcinoma of the vulva arising in
endometriosis. A case report. Eur J Gynaecol Oncol. (2000) 21:416–7.
115. Todd RW, Kehoe S, Gearty J. A case of clear cell carcinoma arising
in extragonadal endometriosis. Int J Gynecol Cancer. (2000) 10:170–
2. doi: 10.1046/j.1525-1438.2000.00024.x
116. Buppasiri P, Kleebkaow P, Tharanon C, Aue-Aungkul A, Kietpeerakool C.
Clear cell carcinoma arising in vulvar endometriosis. Case Rep Pathology.
(2018) 2018:4263104. doi: 10.1155/2018/4263104
117. Ssi-Yan-Kai G, Thubert T, Rivain AL, Prevot S, Deffieux X, De Laveaucoupet
J. Female perineal diseases: spectrum of imaging findings. Abdom Imaging.
(2015) 40:2690–709. doi: 10.1007/s00261-015-0427-7
118. Hosseinzadeh K, Heller MT, Houshmand G. Imaging of the
female perineum in adults. Genitourinary Imaging. (2012)
32:E129–68. doi: 10.1148/rg.324115134
119. Bazot M, Darai E, Hourani R, Thomassin I, Cortez A, Uzan S, et al. Deep
pelvic endometriosis: MR imaging for diagnosis and prediction of extension
of disease. Radiology. (2004) 232:379–89. doi: 10.1148/radiol.2322030762
120. Kinkel K, Frei KA, Balleyguier C, Chapron C. Diagnosis of
endometriosis with imaging: a review. Eur Radiol. (2006)
16:285–98. doi: 10.1007/s00330-005-2882-y
Frontiers in Surgery | www.frontiersin.org 12 May 2021 | Volume 8 | Article 637180

Maillard et al. Vulvo-Perineal Endometriosis: Systematic Review
121. Cazacu E. Histological and immunohistochemical study of extragenital
endometriosis. Virchows Arch. (2014) 465:S356.
122. Kazakov D V, Ondic O, Zamecnik M, Shelekhova K V, Mukensnabl P,
Hes O, et al. Morphological variations of scar-related and spontaneous
endometriosis of the skin and superficial soft tissue: a study of 71 cases with
emphasis on atypical features and types of müllerian differentiations.
J Am Acad Dermatol. (2007) 57:134–46. doi: 10.1016/j.jaad.2006.
11.036
123. Zhu L, Wong F, Lang JH. Perineal endometriosis after vaginal delivery -
Clinical experience with 10 patients. Aust New Zeal J Obstet Gynaecol. (2002)
42:565–7. doi: 10.1111/j.0004-8666.2002.548_12.x
124. Uzunçakmak C, Gülda¸s A, Özçam H, Dinç K. Scar endometriosis: a case
report of this uncommon entity and review of the literature. Case Rep Obstet
Gynecol. (2013) 2013:1–4. doi: 10.1155/2013/386783
125. Galdino JDL, Costa RSC, De Oliveira JG. Reconstruction of abdominal wall
and vulvar defects after endometriosis resection. Rev Bras Cir Plást. (2019)
34:355–61. doi: 10.5935/2177-1235.2019RBCP0208
126. Sauvan M, Chabbert-Buffet N, Canis M, Collinet P, Fritel X, Geoffron
S, et al. Medical treatment for the management of painful endometriosis
without infertility: CNGOF-HAS endometriosis guidelines. Gynecol Obstet
Fertil Senol. (2018) 46:267–72. doi: 10.1016/j.gofs.2018.02.028
127. Geoffron S, Legendre G, Daraï E, Chabbert-Buffet N. Traitement médical de
l’endométriose : prise en charge de la douleur et de l’évolution des lésions par
traitement hormonal et perspectives thérapeutiques. Press Medicale. (2017)
46 (12P1):1199–211. doi: 10.1016/j.lpm.2017.10.005
128. Bedaiwy MA, Allaire C, Alfaraj S. Long-term medical management of
endometriosis with dienogest and with a gonadotropin-releasing hormone
agonist and add-back hormone therapy. Fertil Steril. (2017) 107:537–
48. doi: 10.1016/j.fertnstert.2016.12.024
129. Ferrero S, Evangelisti G, Barra F. Current and emerging treatment
options for endometriosis. Exp Opin Pharmacother. (2018) 19:1109–
25. doi: 10.1080/14656566.2018.1494154
130. Kulkarni N, Patil A, Patel R. Study of preoperative GnRh agonist in
cutaneous scar endometriosis. Int J Reprod Contracept Obstet Gynecol. (2016)
5:3191–4. doi: 10.18203/2320-1770.ijrcog20163010
131. Mistrangelo M, Gilbo N, Cassoni P, Micalef S, Faletti R, Miglietta
C, et al. Surgical scar endometriosis. Surg Today. (2014) 44:767–
72. doi: 10.1007/s00595-012-0459-3
132. Purvis RS, Tyring SK. Cutaneous and subcutaneous
endometriosis. J Dermatol Surg Oncol. (1994) 20:693–
5. doi: 10.1111/j.1524-4725.1994.tb00456.x
133. Raffi L, Suresh R, McCalmont TH, Twigg AR. Cutaneous endometriosis. Int
J Womens Dermatol. (2019) 5:384–6. doi: 10.1016/j.ijwd.2019.06.025
134. Rivlin ME, Das SK, Patel RB, Rodney Meeks G. Leuprolide acetate in
the management of cesarean scar endometriosis. Obstet Gynecol. (1995)
85:838–9. doi: 10.1016/0029-7844(94)00270-N
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