This document summarizes a paper on endosalpingiosis, a rare benign condition where fallopian tube-like epithelium grows outside the fallopian tubes. It can mimic cancers. The paper presents two case studies of endosalpingiosis found in patients' uteri and fallopian tubes. Endosalpingiosis is thought to be related to the development of serous tumors and some evidence suggests it may be a precursor to low-grade serous carcinoma. Accurate diagnosis is important to avoid overtreatment or undertreatment of patients.

1. ORIGINAL PAPER
Endosalpingiosis (A Rare Pathology that Mimic Others): Could it
be a Precursor of Cancer?
Ahmed Samy El-Agwany1
Received: 17 June 2016 / Revised: 15 July 2016 / Accepted: 16 July 2016 / Published online: 8 August 2016
Ó Association of Gynecologic Oncologists of India 2016
Abstract
Introduction Endosalpingiosis has a close relationship
with the development of serous tumors, especially low-
grade serous carcinoma. It is often found accidently during
surgery. ‘‘Endosalpingiosis’’ refers to the presence of fal-
lopian tube-like epithelium outside fallopian tubes. It
merits attention by both clinicians and pathologists since it
is a benign, non-neoplastic condition which may be easily
misjudged as carcinoma mainly due to the rarity of its
occurrence and lack of awareness owing to paucity of its
documentation in the literature. Further, salpingiosis can
undergo massive cystic change, thereby mimicking a tumor
(cystic endosalpingiosis).
Patients We present such extremely rare endosalpingiosis
of uterus and fallopian tube in two reproductive age ladies.
Conclusion Endosalpingiosis is an independent entity both
clinically and pathologically. Though right now the
underlying mechanisms of its development are poorly
understood, a body of evidence demonstrates that both
chronic tubal inflammation and genetic compositions con-
tribute to the proliferation, shedding and seeding of tubal
cells. The recognition of the lesion lies in its quiet and
continuous evolution that may lead to a dreadful outcome
of serous carcinoma in addition to other problems. Accu-
rate pathologic diagnosis and proper management of the
patients to avoid overtreatment or substandard care.
Keywords Endosalpingiosis Á Serous tumors Á Uterus Á
Fallopian tube
Introduction
The term ‘‘Endosalpingiosis’’ implies the presence of fal-
lopian tubal type of ciliated low cuboidal epithelium in
ectopic sites. It is a non-neoplastic lesion which is
homologous to endometriosis and endocervicosis [1]. All
these three entities are together grouped under the umbrella
of ‘‘Mullerianosis’’ which includes epithelial proliferations
of normal structures of the female genital tract involving
tissues such as uterus, ovaries, fallopian tubes, urinary
bladder, appendix, colon, omentum, and pelvic/retroperi-
toneal and para-aortic lymph nodes [2, 3]. Endosalpingiosis
was first described by Sampson in 1930. The ovary is the
most common site though the lesion has been reported to
appear in many tissues and organs both inside and outside
pelvic cavity [3–14].
Several theories about the development or origin of
endosalpingiosis have been proposed. Among them two are
more popular. One is as metaplasia of peritoneal
pleuripotential coelomic epithelium into fallopian tube-
like, ciliated, low cuboidal epithelium [6]. The alternative
theory, based on numerous observations and laboratory
investigations, is tubal-cell origin [4, 9, 15, 16]. The theory
of tubal-cell origin is plausible in that it is able to explain
why the lesion is exclusively seen in women [16] and why
the lesion is most frequently seen in the ovaries [17].
Chronic tubal inflammation is considered to contribute to
the process [16].
Most often, the lesion exhibits few symptoms and signs
and is accidently found during surgery [18]. One meticu-
lous study shows that 40 % of the endosalpingiosis occur in
& Ahmed Samy El-Agwany
ahmedsamyagwany@gmail.com;
ahmed.elagwany@alexmed.edu.eg
1
El-Shatby Maternity University Hospital, Department of
obstetrics and gynecology, Faculty of Medicine, Alexandria
University, Alexandria, Egypt
123
Indian J Gynecol Oncolog (2016) 14:47
DOI 10.1007/s40944-016-0072-2

2. postmenopausal patients and 34.5 % coexist with
endometriosis [19]; a condition probably makes the coex-
isting endometriosis refractory or partially responsive to
hormonal therapy [18].
Endometriosis is significantly correlated with infertility
and chronic abdominal pain, while endosalpingiosis is not
[19]. Morphologically both endosalpingiosis and
endometriosis can cause tissue adhesion; however, the
remote and recent hemorrhage is not observed on the site of
endosalpingiosis [6]. When inclusions of endosalpingiosis
are large in number and/or cystic, the lesion may present as
a tumorlike mass [20–22]. The lining cells of the inclusions
may undergo proliferation, which exhibits as multilayers of
cells, cell clusters, papillary structure, and even free
papillae. Occasionally the proliferation is profound and
accompanied by cellular atypia, a condition defined as
atypical endosalpingiosis. Psammoma body-like calcifica-
tion can appear on site.
A body of evidence shows that endosalpingiosis is the
precursor of serous tumors, especially low-grade serous
carcinoma [4, 7]. Li et al. [4] claim that 78 % of the
ovarian inclusions are of tubal-cell origin. The proliferative
index is higher in lining cells of the inclusions than in those
of the fimbriae. The morphologic and immunohistochem-
ical phenotypes resemble more like ovarian cystadenoma
and borderline serous tumor. In fact, transitional changes
from hyperplasia, dysplasia to carcinoma can often be
observed [23–29].
Endosalpingiosis is considered to have an association
with the relapse of ovarian serous tumors [30–34].
Based on the tubal-cell theory and the way of its for-
mation, most often endosalpingiosis is not solitary. Once
the lesion is found in one site, there is a great possibility
that it exists in other sites, especially the ovaries. Since
endosalpingiosis is hard to be defined before and during
surgery unless it causes significant pathologic changes,
such as adhesion, calcification or cyst, it is indeed a chal-
lenge for those who want to preserve the ovaries in dealing
with their gynecologic problems.
The diagnosis of endosalpingiosis will be made during
conventional pathologic observations if a pathologist is
aware of the lesion. Under tough circumstances, immuno-
histochemical analysis is used for differential diagnoses.
PAX-8 positive and calretinin negative indicate the tubal-
cell origin.
Based on its relationship with the development of serous
tumors, we feel that the morphologic presentations of the
lining cells need to be addressed in details in routine
pathologic reports.
At the moment, the lines between ovarian serous cys-
tadenoma and cystic endosalpingiosis are obscure. In daily
practice, a cyst in the ovary lined with cuboidal cells is
logically diagnosed as a serous cystadenoma if large
enough. Perhaps there is little necessity to differentiate the
one from the other for they may be very close in nature [4].
However, one may face a dilemma when a cyst presents
with focal papillary structure lined by atypical cells [24].
Case 1
A 45-year-old lady (G4P4) presented to Gynecology
Department with vaginal bleeding. Ultrasound revealed
bulky uterus with picture of adenomyosis. MRI was not
done as not indicated. Serum tumor markers were not done
as were non-indicated. Total abdominal hysterectomy with
bilateral salpingo-oophorectomy was done. The specimen
was submitted for histopathological examination. There
were multiple small clear vesicles over the uterine wall on
the lateral side which may indicate the tubal theory and the
fallopian tube (Fig. 1). IHC cell staining and histological
markers to assist in differential diagnosis were not per-
formed as unaffordable to our patients.
The cyst wall lining was with embedded fallopian tubal
epithelium. Multiple tiny cystic spaces and glandular
structures lined by low cuboidal epithelium were seen in
the cyst wall. Histopathological diagnosis was endosalp-
ingiosis with adenomyosis in the uterine wall.
Case 2
A 30-year-old lady (G0P0) presented to Gynecology
Department with infertility and was scheduled for laparo-
scopy. Ultrasound revealed nothing abnormal. MRI was
not performed as not indicated and unaffordable in our
country. Serum tumor markers were not performed pre-
operative as were not indicated. Laparoscopy revealed
moderate endometriosis with black spots and endosalpin-
giosis over the tube. The vesicle specimen was submitted
for histopathological examination. There were multiple
Fig. 1 Hysterectomy specimen with multiple tiny clear vesicles on
the lateral side of the uterus at the upper part near the tubes
47 Page 2 of 5 Indian J Gynecol Oncolog (2016) 14:47
123

3. small clear vesicles over the fallopian tube (Fig. 2). IHC
cell staining and histological markers to assist in differ-
ential diagnosis were not performed as unaffordable to our
patients.
Histopathological diagnosis revealed endosalpingiosis.
The patient was advised to have serial ultrasound and
tumor markers every 6 months. Her follow-up ultrasound 6
months after surgery was within normal limits.
Clear ‘‘amenorrheic’’ lesions of endometriosis have
been confused in clinical practice with psammoma bodies,
endosalpingiosis and ovarian cancer. The difference
between these must be made on the basis of histology and
appearance. The presence of psammoma bodies in an
infertility population is more compatible with post-in-
flammatory changes from chlamydia than with cancer. The
diagnosis of cancer is based on epithelium and not the
appearance of calcification.
Discussion
Endosalpingiosis is the presence of ectopic, cystic glands
outside the fallopian tube that are lined with fallopian tube-
type ciliated epithelium. Endosalpingiosis may occur in
pelvic organs, including ovaries, fallopian tube serosa,
uterine serosa, myometrium, or pelvic peritoneum. It may
also occur in the bladder or in a retroperitoneal or axillary
lymph node. Endosalpingiosis is diagnosed only through
surgical biopsy, so it is unknown if there are asymptomatic
cases.
Another notable feature of endosalpingiosis is its his-
tologic relationship with pelvic serous neoplasms (e.g.,
low-grade pelvic serous carcinoma). However, the role of
endosalpingiosis as a risk factor or as part of the patho-
genesis of these conditions is unknown.
Clement and Young reported four cases of cystic
endosalpingiosis of the uterus with tumorlike manifesta-
tions in 1999. One of their four cases had transmural
uterine involvement by endosalpingiosis which was the
first reported case of transmural uterine endosalpingiosis
[35]. Cil et al. [36] have reported tumorlike cystic
endosalpingiosis in the uterine myometrium throwing
light on the fact that salpingiosis could assume huge
proportions in size by undergoing cystic changes and
mimic neoplasms.
A similar case of tumorlike multilocular cystic endos-
alpingiosis of the uterine serosa has been reported by Lee
et al. [37] and also by Heatley et al. [38], and a case of
omental endosalpingiosis has been documented by San-
teusanio et al. [39]. Endosalpingiosis in association with
ovarian surface epithelial tumor of borderline malignancy
has been reported by Ryoko et al. [40]. Tumorlike foci of
endosalpingiosis have been rarely described in the vermi-
form appendix and the urinary bladder [41].
Sometimes, endosalpingiosis may present with non-
specific symptoms including pelvic pain, hyper or dys-
menorrhea or infertility [42]. They have been found in
association with endometriosis and uterine leiomyomas.
Endosalpingiosis closely resembles endometriosis from
which it can be differentiated by the absence of charac-
teristic endometrial stroma and cyclical hemorrhage. The
other differential diagnoses include endocervicosis (char-
acterized by tall, columnar, mucin secreting epithelium),
deep glands in the uterine cervix (which show continuity
with the uterine canal), multiple peritoneal inclusion cysts
or benign cystic mesothelioma which are distinguished by
the presence of mesothelial lining.
Papillary tubal hyperplasia has been suggested as a
putative precursor of endosalpingiosis and of low-grade
serous ovarian carcinomas. Low-grade serous ovarian
carcinomas are molecularly distinct from the more com-
mon high-grade pelvic serous carcinomas, but the notion
that the fallopian tube may serve as a site of origin for
serous carcinomas is gaining some favor. High-risk women
(HR), in particular those carrying BRCA mutations, are at
risk of development of high-grade pelvic (ovarian, fallop-
ian tube, primary peritoneal) serous carcinomas. There is
not yet a clear or consistent association of low-grade serous
carcinomas with the HR status. Moreover, to date, there are
no previous reports examining the association of endos-
alpingiosis with being HR. A potential link between
ovarian ES and the development of pelvic serous carci-
noma in women who are BRCA mutation carriers has been
observed in 1 case report. Malignancy has been reported to
occur significantly more in premenopausal women with ES
than without it [44, 45].
Conclusion
The recognition of the lesion lies in its quiet and continu-
ous evolution that may lead to a dreadful outcome of serous
carcinoma in addition to other problems. Accurate
Fig. 2 Laparoscopy showed multiple tiny clear cysts over fallopian
tubes
Indian J Gynecol Oncolog (2016) 14:47 Page 3 of 5 47
123

4. pathologic diagnosis and proper management of the
patients to avoid overtreatment or substandard care are the
main purposes of this article. This article highlights the
importance of microscopic examination in resolving the
crucial diagnostic dilemma that a rare, simple, benign and
seldom reported entity like cystic endosalpingiosis could
create. Uterine cystic endosalpingiosis can be serosal or
intramural, differential diagnosis to be made with
adenomyosis.
The diagnosis of endosalpingiosis will be made during
conventional pathologic observations if a pathologist is
aware of the lesion. Under tough circumstances, immuno-
histo-chemical analysis is used for differential diagnoses.
Based on its relationship with the development of ser-
ous tumors, we feel that the morphologic presentations of
the lining cells need to be addressed in detail in routine
pathologic reports.
The data regarding this condition wether management
and treatment or follow-up is not much, so we invite others
to show their experience in practice to set a guideline for it.
Compliance with Ethical Standards
Conflict of interest None.
Ethical Approval All procedures performed in studies involving
human participants were in accordance with the ethical standards of
the institutional and/or national research committee and with the 1964
Declaration of Helsinki and its later amendments or comparable
ethical standards.
Informed Consent Informed consent was obtained from the patient
included in the study.
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