Gynecologic Oncology 117 (2010) 2731

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Gynecologic Oncology
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y g y n o

Original Research Article

Does risk-reducing bilateral salpingo-oophorectomy leave behind residual tube?

Ilana Cass a,, Ann Walts b, Beth Y. Karlan a
a
b

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite #160 West, Los Angeles, CA 90048, USA
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA

a r t i c l e

i n f o

Article history:
Received 16 October 2009
Available online 27 January 2010
Keywords:
BRCA
Risk-Reducing Surgery

a b s t r a c t
Objective. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is an effective option for women with
BRCA mutations however there is limited information as to how much tubal epithelium remains after RRSO.
Methods. Twenty hysterectomy specimens were prospectively evaluated after both tubes were fulgurated
and transected at the uterine cornua in an attempt to remove the complete fallopian tube simulating the
RRSO procedure. Unxed specimens were processed by a single pathologist who took sequential 3 mm cross
sections perpendicular to the long axis of each residual tube beginning at the tubal resection line (or uterine
cornua if prior adnexectomy) proceeding toward the uterine cavity. The presence and length of residual tube
was recorded and sections were examined for preserved tubal epithelium. For each case with residual tube,
the surface area of residual epithelium was calculated.
Results. A tubal remnant was identied in 29 of 40 (73%) uterine cornual sites. The median length of
residual tube was 6 mm (range 321 mm). Each tubal remnant had some preserved columnar epithelium.
The median surface area of tubal remnant was 14 mm2 (range 2117 mm2). Prior adnexectomy did not affect
the frequency of having a tubal remnant or the length of remnant tube. Neither menopausal status,
indication for hysterectomy nor type of hysterectomy correlated with presence of residual tube.
Conclusion. The majority of the uterine cornua had a tubal remnant which suggests that RRSO may leave
behind residual tubal epithelium. The clinical signicance of this tubal remnant is unclear given the current
understanding of tubal carcinogenesis.
2009 Elsevier Inc. All rights reserved.

Introduction
Hereditary BRCA mutations confer an increased risk of both
ovarian and tubal carcinoma. The lifetime risk of ovarian cancer
associated with BRCA1 mutation is 3646% and with BRCA2 mutation
is 1027% [14]. The precise risk of fallopian tube cancer among BRCA
mutation carriers is unknown. While fallopian tube carcinoma
accounts for approximately 0.5% of all gynecologic malignancies, it
has been reported to occur at signicantly higher frequencies in
women with hereditary BRCA mutations. Among women with
fallopian tube carcinoma who underwent genetic testing, 1643%
were found to harbor a deleterious BRCA mutation [57]. A large study
of BRCA1 mutation carriers found that BRCA1 mutation carriers had a
120-fold higher relative risk of developing tubal cancer compared to
the general population [8].
Despite efforts to develop comprehensive screening programs for
these high-risk women, prophylactic surgery remains the most
effective method of cancer risk reduction. A recent comprehensive
analysis of the risk reducing estimates of RRSO showed that the risk of
Presented at the Society of Gynecologic Oncologists 39th Annual Meeting, March 9,
2008 Tampa, Florida.
Corresponding author. Fax: +1 310 423 0155.
E-mail address: cassi@cshs.org (I. Cass).
0090-8258/$ see front matter 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.ygyno.2009.12.023

subsequent ovarian and fallopian tube cancer was reduced by 80% in

BRCA mutation carriers following RRSO [9]. The frequent nding of
occult primary tubal carcinomas at the time of risk-reducing bilateral
salpingo-oophorectomy (RRSO) further underscores the importance
of removing as much of this at-risk tubal epithelium as possible and
comprehensive histological analysis of the entire specimen [1013].
Examination of serial sections of the entire adnexa has shown that
approximately 60% of the occult carcinomas detected at prophylactic
surgery are of tubal origin and that these tumors originate
predominantly in the distal tube [1024]. The higher frequency of
occult tubal carcinomas noted in RRSO specimens compared to the
frequency of tubal carcinomas in BRCA mutation carriers might reect
the more complete assessment of the adnexa through serial
sectioning of the ovaries and tubes and the earlier window into
serous carcinogenesis afforded by the small tumor volume and
preserved anatomy.
It remains controversial whether the optimal risk reducing
procedure for the BRCA mutation carrier should include concomitant
hysterectomy at the time of RRSO [25,26]. The current procedure for
the RRSO is to maximize removal of the entire adnexa by ligating the
inndibulo-pelvic ligament 2 cm proximal to the ovary and to remove
as much tube as possible [12]. There is limited information as to
whether any residual tube and at-risk epithelium remains after
standard RRSO. The fallopian tube is lined by predominantly two

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I. Cass et al. / Gynecologic Oncology 117 (2010) 2731

types of epithelial cells, ciliated and secretory, whose distribution

varies by anatomic location [27,28]. Approximately 1 cm of fallopian
tube is intramural (within the uterine cornua) but the composition of
the epithelium that denotes the transition to the isthmic portion is
unclear [29]. Ciliated cells usually predominate in the distal tube;
however, a shift toward the secretory phenotype with a loss of cilia
has been reported in early, non-invasive serous neoplastic lesions
[24,28,30].
To better characterize the length of tube and the amount of tubal
epithelium remaining after RRSO, we prospectively examined unxed
hysterectomy specimen after typical tubal fulguration by bipolar
electrocautery and transection technique had been performed by
gynecologic oncology surgeons thus mimicking an RRSO prior to each
hysterectomy.
Methods
In an institutional review board-approved study at Cedars-Sinai
Medical Center, twenty women undergoing hysterectomy for a
variety of benign and malignant indications were prospectively
identied from November 2006 through May 2007. The type of
hysterectomy performed was determined at the surgeon's discretion
based upon the patient's indication for surgery, body habitus, and
anatomy. Patients with signicant distortion of the cornual anatomy
or signicant uterine enlargement due to broids (uterus N250 g)
were excluded from the study.
In order to simulate the RRSO procedure and attempt to remove
the entire fallopian tube, both tubes were fulgurated using electrocautery and transected at the uterine cornua. All procedures were
performed by a gynecologic oncologist. Each unxed specimen was
immediately transported to the pathology department. Each surgical
specimen was processed according to a uniform protocol and one
gynecologic pathologist reviewed all slides. After the uterine dimensions and weight had been obtained from each specimen, a probe was
placed into each tubal cornua and serial, sequential 3 mm cross
sections were taken perpendicular to the long axis of the tube

beginning at the line of resection (or at the uterine cornua in cases

with a prior salpingo-oophorectomy) proceeding toward the uterine
cavity (Figs. 1A, B). The transition from fallopian tube to uterus was
dened by the presence of endometrial stroma and the loss of
circumferential tubal epithelium. The presence and length of any
residual tube was recorded and sections were examined for residual
preserved tubal epithelium. The length of residual tube was calculated
from the number of serial 3 mm sections that were obtained at each
cornual site. Preserved tubal epithelium was dened as the presence
of intact ciliated columnar epithelium.
In addition to measuring the length of tubal remnant, we
attempted to measure the amount of residual tubal epithelium. We
calculated the circumference of the tubal lumen using the maximum
dimensions of the tubal lumen in a cross section of residual tube with
preserved tubal epithelium and a formula that accommodates for the
irregular shape of the tubal lumen. The luminal circumference was
approximated using the quadratic equation based upon Euler's
formula: [2(a2 + b2)] in which a (the major radius) is larger than
b (the minor radius) and the eccentricity of the ellipse is N0 and b1
(Fig. 2) [31]. The total surface area of each tubal remnant was
approximated by multiplying the length of tubal remnant by the
luminal circumference of the tube.
Epidemiologic data and surgicopathologic characteristics were
extracted from hospital records and patient interviews. Surgical stage
and histologic grade of lesions were determined according to the
International Federation of Gynecology and Obstetrics and World Health
Organization standards for those patients with gynecologic malignancies.
Results
Forty cornual sites were evaluated in the 20 hysterectomy specimens.
A tubal remnant was identied at 29 of the 40 (73%) uterine cornual sites.
The median length of tubal remnant was 6 mm (range 321 mm). The
median surface area of residual tube was 14 mm2 (range 2117 mm2).
Each tubal remnant contained some preserved columnar epithelium.
Table 1 summarizes the clinicopathologic characteristics of the study

Fig. 1. (A, B) Example of processing of unxed hysterectomy specimen. A probe is placed into each tubal cornua to identify the origin of the serial sections of residual fallopian tube.

I. Cass et al. / Gynecologic Oncology 117 (2010) 2731

29

Fig. 2. Cross-section of a tubal remnant indicating measurements utilized to calculate the circumference of the tube.

group including: indication for surgery, procedure, length of remnant tube

and surface area of any residual tubal epithelium. Thirteen patients had a
gynecologic carcinoma, ve patients had benign indications for hysterectomy/salpingo-oophorectomy and two patients had colon cancer without
any adnexal involvement but desired concurrent hysterectomy/salpingooophorectomy. The median age of the cohort was 54. Five patients were
pre-menopausal and the remaining 15 were postmenopausal. Two of the
four patients with hereditary BRCA mutations had tubal carcinoma-in-situ
(CIS) noted in the distal tube at the time of prior laparoscopic bilateral
RRSO and subsequently underwent hysterectomy. The remaining two
BRCA mutation carriers had hysterectomy performed at the time of RRSO.
No patient had any tubal dysplasia/tubal in-situ carcinoma (TIC) or any
signicant tubal pathology in their hysterectomy specimen. Fifteen
patients had both tubes intact at the time of hysterectomy, three patients
had undergone prior unilateral salpingo-oophorectomy via laparotomy
and two patients had undergone prior laparoscopic bilateral salpingooophorectomy as described above. Only one premenopausal patient with
adenocarcinoma-in-situ of the cervix retained her tubes and ovaries after
hysterectomy. The median uterine weight was 85 g (range 19230 g).

As shown in Table 2, prior adnexectomy did not affect the

frequency of a tubal remnant being present nor the length of tubal
remnant in this small cohort of patients. The time interval between
the prior unilateral (USO) or bilateral salpingo-oophorectomy (BSO)
and the hysterectomy varied among the 5 patients who had prior
adnexectomy. The prior BSO were performed 7 days earlier and 2
years earlier in patients with a diagnosis of ovarian cancer (cases 6
and 19, respectively), 2 months earlier in the case of the two riskreducing surgeries (cases 4 and 5) and approximately 20 years earlier
in the patient with endometrial cancer (case 8). A comparison of the 5
patients who had undergone prior adnexectomy with those whose
adnexa were intact at the time of hysterectomy revealed no
signicant difference in the median length. Neither menopausal
status, indication for hysterectomy, nor type of hysterectomy
(laparoscopic or abdominal) correlated with the presence nor the
length of residual tube or with the surface area of residual tubal
epithelium in this mixed population. Patients with benign diagnoses
were more likely to have no residual tube, although this was not
statistically signicant in this limited cohort.

Table 1
Clinicopathologic characteristics of study cohort.
Patient

Age

Procedure

Indication

Menop.

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20

52
65
51
57
76
32
55
65
54
57
68
53
52
62
52
65
37

TAHBSO
TAHBSO
TAHBSO
LAVH
TAH
TAHRSO
TAHBSO
TAHLSO
LAVHBSO
TAHBSO
TAHBSO
LARHBSO
TAHBSO
LAVHBSO
LAVHBSO
LAVHBSO
LAVHBSO
LARH
TAHLSO
LAVHBSO

Fibroids
Stage IC endometrial CA
Colon CA, broids
BRCA2 prior LSC BSO, TIC
BRCA2 prior LSC BSO, TIC
Stage IC ovarian CA, prior LSO
Colon CA, pelvic mass
Stage IC endometrial CA, remote RSO
Pelvic pain
CIS cervix
Stage IA ovarian sarcoma
Stage IA2 cervix CA
Stage IIIB ovarian CA
Stage IB endometrial CA
Complex endometrial hyperplasia
BRCA1 prophylaxis
BRCA1 prophylaxis
ACIS
Stage IB ovarian dysgerminoma, IB prior RSO
Stage IA ovarian LMP

Post
Post
Pre
Post
Post
Pre
Post
Post
Post
Post
Post
Post
Post
Post
Post
Post
Pre
Pre
Pre
Post

20
51

Residual tube
length (mm)

Surface area residual

tube (mm2)

Right

Left

Right

Left

3
0
18
6
21
6
3
0
3
6
6
0
0
0
18
9
6
9
3
12

0
0
9
3
12
0
9
0
3
3
6
0
3
0
6
9
6
9
18
12

14
0
42
8
47
7
2
0
12
15
7
0
0
0
37
12
14
13
8
15

0
0
15
3
17
0
20
0
3
7
20
0
22
0
11
11
4
21
117
30

TAHBSO total abdominal hysterectomy, bilateral salpingo-oophorectomy, LAVH laparoscopic assisted vaginal hysterectomy, LARH laparoscopic assisted radical hysterectomy, LSC
laparoscopic, TIC tubal in situ carcinoma, ACIS adenocarcinoma in situ cervix, LMP low malignant potential tumor, CIS cervical carcinoma-in-situ, Menop. menopausal status.

30

I. Cass et al. / Gynecologic Oncology 117 (2010) 2731

Table 2
Impact of clinical parameters on the presence or absence of residual tubes.
Number Number of residual p
tubes absent
of
residual
tubes
present
Adnexa intact
Prior adnexectomy
Premenopausal
Postmenopausal
Benign pathology
Gynecologic cancer diagnosis
Laparoscopic hysterectomy
Abdominal hysterectomy

24
5
9
20
13
16
14
15

9
2
1
10
1
10
4
7

OR[CI]

1.0 1.07[0.17,6.5]
1.0

4.5[0.5,40]

0.1

8.3[0.9,72]

0.7

1.6[0.39,6.8]

Discussion
The standard surgical procedure for RRSO that fulgurates both tubes
using bipolar electrocautery and transects them at the uterine cornua left
behind some residual fallopian tube in the majority (73%) of cases in this
small prospective study of hysterectomy specimens. Clinical factors did
not affect the frequency of identifying residual tube in this group of
patients suggesting that there is a fair amount of uniformity in the
procedure performed and in the uterine cornua anatomy within this
cohort of women. Nonetheless, up to 21 mm of proximal tube remained at
the cornual sites examined and every tubal remnant had some preserved
tubal epithelium. In three of the four longest tubal remnants (N17 mm),
the surface area of remnant tubal epithelium exceeded than 37 mm2
(maximum residual tubal surface area of 117 mm2).
Gerritzen et al. reported a median tubal remnant 12 mm in length
after RRSO in hysterectomy specimens from 14 pre-menopausal
women. The lack of cautery of the utero-ovarian ligament, the absence
of information regarding the procedure (laparoscopic versus open
surgery) and failure to address any observed impact of concomitant
hysterectomy on tubal remnants limit interpretation of their ndings
with respect to laparoscopic bilateral salpingo-oophorectomy, the
RRSO procedure most commonly performed by gynecologic surgeons.
The study was also limited to pre-menopausal women [29]. Benets of
our prospective study design include the uniform surgical technique
employed that incorporates both electrocautery and ligation and most
closely replicates the RRSO currently recommended to remove the
maximal amount of fallopian tube as well as the uniform processing
and thorough evaluation of the hysterectomy specimens by a single
gynecologic pathologist.
Although in theory this residual proximal tubal epithelium is at
increased risk for neoplastic transformation in the BRCA mutation
carrier, the clinical signicance of this residual epithelium is unclear
given our current understanding of tubal carcinogenesis. The body of
evidence to date suggests the distal tube/mbria is the preferred site
of origin for tubal carcinoma in both sporadic as well as BRCAassociated cases [11,24,32,33]. Our own data on sporadic and BRCAassociated tubal carcinoma found no case of exclusively proximal tubal
carcinoma, and there have been no reported cases of tubal carcinoma
occurring in the tubal remnant following RRSO [5]. Neither of the two
largest series of primary tubal cancer patients with undetermined
BRCA mutation status identied any cases of primary tubal carcinoma
that involved exclusively the proximal/cornual tube [34,35].
Whether this residual proximal tubal epithelium could be the site of
tumor origin in the rare cases of primary peritoneal carcinoma that follow
RRSO is unknown at this time. To answer this question a multiinstitutional collaboration with lengthy follow up of women who have
and do not have a hysterectomy performed at the time of risk-reducing
surgery would be required [9,21,36]. In the largest reported prospective
series of BRCA mutation carriers who developed primary peritoneal
carcinoma following RRSO, three of the seven women had concomitant

hysterectomy [21]. Another study of women in a familial ovarian cancer

registry found that all six women who developed primary peritoneal
carcinoma following RRSO had concomitant hysterectomy [37]. Case
reports suggest that occult tubal or ovarian carcinoma not recognized at
the time of prophylactic surgery is the more likely source of subsequent
primary peritoneal carcinomas [25,38].
The distal tube may be the preferred site of origin for tubal carcinoma
because it has a larger surface area of susceptible epithelium at risk for
neoplastic transformation or because it is in close proximity to potential
carcinogenic factors such as interleukins and other cytokines, and/or
higher relative levels of hormones released from the ovarian surface
during ovulation or from the peritoneal cavity. Immunohistochemical
staining has identied a potential precursor lesion to tubal carcinoma, the
p53 signature that shares many features of tubal intraepithelial
carcinoma (TIC) and exists almost exclusively in the distal tube. P53
signatures (dened as 12 consecutive nuclei that stain positive for p53
protein) have been localized predominantly to secretory cells within the
mbriae [28]. These p53 signatures, even when observed in morphologically normal epithelium, have been reported to share some characteristics
of TIC including evidence of DNA damage and p53 sequence mutations.
Detailed histological analysis of the fallopian tube using the serialextensively examining the mbrial end (SEE-FIM) technique found that
67% of ovarian serous carcinomas had coexisting TIC that predominantly
involved in the distal tube [24,32].
There is still controversy regarding the optimal prophylactic surgical
procedure for BRCA mutation carriers. Based upon available data and in
the absence of compelling clinical indicators, concomitant hysterectomy
at the time of RRSO does not appear to provide signicant additional risk
reduction [12,25,26]. One argument for concomitant hysterectomy cites
small inconclusive studies that suggest uterine cancer, especially uterine
papillary serous carcinoma, may be part of the spectrum of BRCAassociated disease [3941]. To the contrary, other studies found no
increased prevalence of hereditary BRCA mutations among 200 Jewish
women with endometrioid endometrial carcinoma or 56 unselected
women with uterine papillary serous carcinoma [42,43]. The cumulative
risk of endometrial cancer in BRCA-mutation carriers with ER positive
breast cancer treated with Tamoxifen may be an additional consideration
when counseling this subset of women about prophylactic surgery
[44,45]. Another scenario in which hysterectomy might be considered
involves the young, unaffected BRCA mutation carrier who may prefer
hormone replacement therapy and for whom hysterectomy would offer a
simplied regimen of estrogen alone.
In conclusion, based upon our small prospective study, riskreducing surgery left behind some residual fallopian tube in the
majority of cases. In counseling a BRCA mutation carrier regarding
optimal risk reducing surgical options, aggregate data suggests that
the risk of carcinoma from residual tubal tissue following RRSO is the
least compelling reason for hysterectomy. Our data support the
current recommendation for RRSO as the most efcacious and least
morbid risk-reducing procedure for BRCA mutation carriers.
Conict of interest statement
The authors declare there are no conicts of interest.

Acknowledgments
Financial support for this study was received by the Womens
Cancer Research Institute, Cedars-Sinai Medical Center, Los Angeles,
California.
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