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Journal of the Chinese Medical Association 76 (2013) 583e587
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Original Article
Primary fallopian tube carcinoma: A clinicopathologic analysis and
literature review
Hei-Yu Lau a,b, Yi-Jen Chen a,b, Ming-Shyen Yen a,b, Ru-Fen Chen b,c, Shu-O Yeh b,c,
Nae-Fang Twu a,b,*
a
Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
b
Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan, ROC
c
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
Received November 22, 2012; accepted March 6, 2013
Abstract
Background: Primary fallopian tube carcinoma (PFTC) is a rare tumor, and it is very difficult to diagnose preoperatively. The aims of this study were
to evaluate the clinicopathologic features of primary fallopian tube carcinoma (PFTC) and to review the current available literature on PFTC.
Methods: The medical records of 16 patients who were diagnosed with PFTC at Taipei Veterans General Hospital between January 2001 and
December 2011 were analyzed retrospectively.
Results: The mean age at diagnosis was 63 years (range, 41e86 years), and the mean follow-up period was 39.8 months (range, 4.0e102.8
months). Fourteen (87.5%) patients were menopausal women. The most common clinical presentation was nonspecific pelvic pain (37.5%),
followed by abnormal vaginal bleeding (31.2%), pelvic mass (18.8%), and gastrointestinal symptoms (12.5%). One patient was diagnosed with
PFTC preoperatively; 11 (68.6%) patients were diagnosed as having adnexal mass of unknown origin, but primarily in the ovary. Other
diagnoses included endometrial cancer, cervical cancer, colon cancer, and rectum cancer in one patient each. Three (18.8%) patients were in
Stage I, two (12.5%) in Stage II, nine (56.2%) in Stage III, and two (12.5%) in Stage IV. The serous type was histologically predominant (75%),
and six patients were of a high grade (37.5%). The 5-year disease-free survival rate was 73.3%.
Conclusion: PFTC is infrequently diagnosed preoperatively or intraoperatively due to its rarity, and has a varied and nonspecific presentation.
Only 6.3% of the patients had typical symptoms suggestive of tubal carcinoma. This report may benefit surgeons by providing additional information about the clinicopathologic behavior of PFTC so that patients can be appropriately counseled.
Copyright Ó 2013 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.
Keywords: disease-free survival; intraoperative assessment; primary fallopian tube carcinoma; residual tumor
1. Introduction
Primary fallopian tube carcinoma (PFTC) is an uncommon
tumor and accounts for approximately 0.14e0.18% of female
genital malignancies.1 Based on data obtained from nine
population-based cancer registries in the USA, the average
annual incidence of PFTC is 3.6/million women/year.2
* Corresponding author. Dr. Nae-Fang Twu, Department of Gynecology and
Obstetrics, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road,
Taipei 112, Taiwan, ROC.
E-mail address: [email protected] (N.-F. Twu).
Recently, several studies have reported an increase in the
incidence of PFTC, especially among the higher social classes.3 A study from Finland reported that the incidence of
PFTC is increasing, with an age-adjusted incidence of 1.2/
million for 1953e1957 to 5.4/million for 1993e1997.4
Furthermore, from 1993 to 1997, an average of 21.6 cases of
PFTC/year were newly registered in the Finnish Cancer
Registry; during the year 2000, 46 cases were registered.
Nevertheless, most studies involve small cohorts, and few data
regarding a well-defined protocol for chemotherapy or the
influence of prognostic factors are available. Although the
treatment protocols follow those used in epithelial ovarian
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H.-Y. Lau et al. / Journal of the Chinese Medical Association 76 (2013) 583e587
cancer, owing to the similarities in clinical and pathologic
features, several distinct differences should be emphasized
based on additional clinical data.5
Because of the rarity of this disease and the low level of
suspicion of the attending physicians, this cancer is typically
not diagnosed preoperatively. The symptom complex of
hydrops tubae profluens, in which a patient presents with a
pelvic mass, profuse watery vaginal discharge, and pelvic pain
that is greatly relieved by the sudden disappearance of the
mass is rarely encountered, but is almost pathognomonic.
Patients with PFTC are rarely diagnosed preoperatively by a
positive Papanicolaou smear, negative endometrial/endocervical curettage, and the presence of a pelvic mass on ultrasonography.6 The aims of the present study were to analyze
the clinicopathologic features, assess the survival rate, and
identify the prognostic factors of women diagnosed with
PFTC in a single institute.
2. Methods
Patients who were eligible for enrollment in this study met
the diagnostic criteria of PFTC established by Hu et al7 and
later modified by Sedlis8 and Yoonessi.9 The exclusion criteria
included neoadjuvant chemotherapy, tumor with a low malignant potential, or primary debulking surgery performed at
another hospital. After obtaining approval from the Institutional Review Board, 16 patients who were diagnosed with
PFTC between January 2001 and December 2011 at Taipei
Veterans General Hospital were identified. Medical records
were analyzed for demographic characteristics (the age at
diagnosis, parity, presenting signs and symptoms, menopausal
status, preoperative diagnosis), surgical findings, and clinical
outcomes at follow-up.
Criteria of the International Federation of Obstetrics and
Gynecology (FIGO) were used for tumor staging. Histological
grading was based on the architectural feature of the tumor,
comprising Grade 1 for well-differentiated, Grade 2 for
moderately differentiated, and Grade 3 for poorly differentiated tumors. Complete resection was defined as no residual
tumor measuring >1 cm in maximal dimension after the initial
surgery.
Surgery was the first treatment for all patients, followed by
chemotherapy for 15 patients. There were two chemotherapy
protocols: paclitaxel plus platinum with carboplatin or
cisplatin; and cyclophosphamide plus platinum. KaplaneMeier curves were used to calculate the mean overall survival
(OS) and disease-free survival (DFS), and the log-rank test
was applied for univariate analysis. All statistical analyses
were carried out using SPSS 17 software (SPSS Inc., Chicago,
IL, USA). The differences were considered significant at a
level of p < 0.05.
3. Results
The mean age at the time of diagnosis was 63 years (range,
41e86 years). Patient demographics are shown in Table 1.
Only one of the 16 patients diagnosed with PFTC was
Table 1
Clinicopathologic features of 16 women with primary fallopian tube
carcinoma.
Characteristics
n (%)
Nulliparity
Menopause at diagnosis
Presenting signs and symptoms
Pelvic mass
Abnormal vaginal bleeding
Nonspecific pelvic pain
Gastrointestinal symptoms
Preoperative diagnosis
Adnexal massa
Endometrial cancer
Cervical cancer
Colon cancer or rectal cancer
Tubal cancer
Preoperative serum CA-125, median
FIGO stage
I
II
III
IV
Histologic grade
1/2
3
Histologic subtypes
Serous
Undifferentiated
1 (6.3)
14 (87.5)
3
5
6
2
(18.8)
(31.2)
(37.5)
(12.5)
11 (68.6)
1 (6.3)
1 (6.3)
2 (12.5)
1 (6.3)
133 U/mL
3
2
9
2
(18.8)
(12.5)
(56.2)
(12.5)
10 (62.5)
6 (37.5)
12 (75)
4 (25)
CA ¼ carbohydrate antigen; FIGO ¼ International Federation for Obstetrics and Gynecology.
a
Any adnexal mass of unknown origin, whether benign or malignant,
on imaging study.
nulliparous. None of the included patients had undergone
either hysterectomies or tubal sterilization, and 14 (87.5%)
were postmenopausal (i.e., cessation of menstruation for at
least 1 year). The most common clinical presentation was
nonspecific pelvic pain (37.5%), followed by abnormal vaginal
bleeding (31.2%), pelvic mass (18.8%), and gastrointestinal
symptoms (12.5%). One patient was accurately diagnosed
with PFTC preoperatively. The majority of preoperative diagnoses were adnexal mass of an unknown location (68.6%),
but mainly involved the ovary.
The serous type was histologically predominant (75%), and
six patients were high grade (37.5%). Details of management
are summarized in Table 2. Fifteen patients underwent adjuvant therapy after initial surgery with or without evidence of
recurrence. The preoperative serum carbohydrate antigen
(CA)-125 (enzyme immunoradiometric assay) levels of all
patients were evaluated. Antigen levels were < 35 U/mL in
four patients only: three patients with Stage I/II disease and
one with Stage III disease.
For the entire cohort, the 5-year DFS rate was 73.3%. The
mean OS was 95 months [95% confidence interval (CI)
81e109], but the median OS was not reached. The mean DFS
was 70 months (95% CI 49e91), and the median DFS was 87
months (95% CI 48e126; Fig. 1).
The differences in survival according to age, tumor stage,
histology type, differentiation, and residual tumor size using
Kaplan-Meier analysis are listed in Table 3. The DFS was
H.-Y. Lau et al. / Journal of the Chinese Medical Association 76 (2013) 583e587
Table 2
Types of management.
585
Table 3
Survival of patients with primary fallopian tube cancer in univariate analysis.
No. of patients
Surgical procedures
Complete staging
15
Incomplete staging
1
Positive pelvic lymph node
3
Positive para-aortic lymph node
3
Complete resection
Yes (residual tumor <1 cm)
14
No (residual tumor 1 cm
2
First-line chemotherapy
15
Paclitaxel þ cisplatin
8
Paclitaxel þ carboplatin
6
Cyclophosphamide þ cisplatin
1
No. of courses in first-line chemotherapy cycle
<6
1
6
14
%
93.7
6.3
18.8
18.8
87.5
12.5
93.8
53.3
40
6.7
6.7
93.3
significantly related to residual tumor size ( p ¼ 0.045); OS
was also related to residual tumor size, but without statistical
significance ( p ¼ 0.055).
In this series, the mean follow-up from the time of initial
surgery was 39.8 months (range, 4e102.8 months). Five patients (31.3%) had experienced recurrence at the time of the
review. One patient (6.3%) died due to the disease.
4. Discussion
PFTC is an uncommon gynecologic malignancy, and is
generally recognized as a disease of menopausal women.10
In the present study, 87.5% of the patients were in menopausal status. Unlike ovarian cancer, fallopian tube cancer is
Fig. 1. Disease-free survival for all patients with primary fallopian tube carcinoma (median 87 months, 95% confidence interval, 48e126).
OS (mo)
Age
50 y
>50 y
Stage
I/II
III/IV
Histology
Serous
Nonserous
Differentiation
Grade I/II
Grade III
Residual tumor
<1 cm
1 cm
DFS (mo)
Mean
95% CI
p
Mean
95% CI
p
53
40
0e112
21e59
0.596
59
71
22e97
47e85
0.843
38
47
15e62
21e72
0.420
56
75
28e85
50e100
0.678
30
75
12e49
64e87
0.113
55
87
26e84
87e87
0.216
34
55
size
47
12
12e56
28e82
0.388
50
87
21e80
87e87
0.137
29e66
0e24
0.055
75
18
55e96
18e18
0.045
CI ¼ confidence interval; DFS ¼ disease-free survival; OS ¼ overall survival.
not routinely suspected in a patient with a complex pelvic
mass. Because of the low incidence of PFTC, only about 4%
(0.3e15%) are diagnosed preoperatively,11 and up to 50%
are missed intraoperatively.12 In our study, one (6.3%) patient was diagnosed with PFTC preoperatively, and 14
(93.7%) patients were diagnosed with another cancer intraoperatively. Of these other cancers, 10 were ovarian cancer,
with the others including colon cancer, rectal cancer, cervical
cancer, and endometrial cancer. One patient underwent
incomplete surgery with initial misdiagnosis. Eleven patients
(68.7%) were diagnosed at Stage III/IV postoperatively.
Because of the rarity of the disease, it is difficult to accurately diagnose, especially in patients who are early stage
and symptom-free. Therefore, careful intraoperative assessment of the adnexa is necessary. Moreover, symptoms and
the serum CA-125 level may be helpful indicators. The
Latzko’s triad of typical symptoms consists of intermittent
profuse serosanguinous vaginal bleeding, colicky pain
relieved by discharge, and an abdominal or pelvic mass.
However, none of these symptoms are specific, and this triad
was reported in only 15% of PFTC cases.11 In addition,
numerous studies have described the correlation of CA-125
level with FIGO stage, but not with a PFTC prognosis.13 In
our study, the circulating CA-125 level was increased by
>35 U/mL in 75% of the population. It was also increased in
33%, 50%, 89%, and 100% of patients with Stage I, II, III, or
IV disease, with mean levels of 58.0 U/mL, 94.1 U/mL,
1357.6 U/mL, and 2712.5 U/mL, respectively.
The etiology of PFTC remains unclear. Some factors have
been postulated to increase the risk of this cancer, i.e., infertility, chronic tubal inflammation, endometriosis, nulliparity,
smoking, and genetic predisposition.14 Although some investigators have suggested that PFTC shares several biological
and clinical features with ovarian carcinoma,15,16 we did not
find an increased number of nulliparous women or a higher
incidence of tubo-ovarian abscess in our patient cohort.
Because of the relatively small number of patients in the
586
H.-Y. Lau et al. / Journal of the Chinese Medical Association 76 (2013) 583e587
Table 4
Review of the literature.
Authors
24
Patient no.
Age, y: Median (range)
Stage
I
II
III
IV
Unknown
5-year survival
Stage
I
II
I/II
III
IV
III/IV
All patients
Heintz et al
Kosary and Trimble25
Gadducci et al16
Baekelandt et al13
1576
64
176
416
88
58.5 (36e78)
151
61 (35e82)
553 (35)
186 (12)
393 (25)
392 (25)
52 (3)
51 (29.1)
40 (22.9)
67 (38.9)
12 (6.9)
5 (2.9)
102 (24.5)
29 (7.0)
52 (12.5)
151 (36.3)
82 (19.7)
21 (23.9)
21 (23.9)
43 (48.8)
3 (3.4)
0
49
33
52
17
0
81
65
81
67
95
75
73
37
64
36
41
33
69
45
29
12
Rosen et al
Wethington et al
143
5
10
(32)
(27)
(34.5)
(11.5)
59
19
56
57
44
Data are presented as % or n (%), unless otherwise indicated.
present study, it is unclear whether PFTC and epithelial
ovarian carcinomas share the same etiological factors. Some
studies have reported that pelvic serous carcinoma could
follow a defined precursor of the distal fallopian tube that has
been present for some time.17,18
Imaging studies such as ultrasound, computed tomography,
or magnetic resonance imaging may aid in diagnosing PFTC.
Although the imaging findings of tubal carcinoma are nonspecific, and mimic other pelvic diseases such as tubo-ovarian
abscess or ovarian tumor, several findings may provide a diagnostic clue preoperatively. A sausage-shaped mass or a multilobular mass with a cog-and-wheel appearance on ultrasound,19
or low-impedance vascular flow within the solid components on
ultrasound with color Doppler might lead to a suspicion of tubal
malignancy.20 Magnetic resonance imaging is considered a
better method than computed tomography or ultrasound for
detecting tumor infiltration of extratubal organs.21
The gold-standard treatment for managing PFTC is similar
to that for ovarian carcinomadcytoreductive surgery with the
removal of as much of the tumor as possible.21 However,
which chemotherapy regimen is optimum to address PFTC
remains unclear. More recently, paclitaxel-based chemotherapy has been used for PFTC based on the propensity to use
the same therapy for epithelial ovarian cancer. With the
introduction of cisplatin-containing chemotherapy regimens,
an objective response rate of about 80% can be achieved in
patients with advanced disease.22,23 In this study, the complete
response rate and partial response rate of the patients with
advanced disease were 60% and 90%, respectively. Age, tumor
stage, histology type, and grading were not significantly
related to survival. Only the residual tumor size was significantly related to DFS ( p ¼ 0.045). The lack of correlation of
prognosis with tumor stage maybe due to the small sample
size; a large multicenter study would help establish the
prognostic risk factors. A review of the literature with stage,
survival, and demographic data is provided (Table 4).
In conclusion, PFTC is a challenge to surgeons. It is very
difficult to diagnose intraoperatively or preoperatively due to
its rarity. Therefore, surgeons perform an additional staging
surgery after the initial incomplete surgery, which seems to
increase the morbidity of the patients. Therefore, PFTC should
be considered in patients complaining of lower abdominal pain
in association with vaginal bleedings/watery discharge; a
hydrosalpinx or adnexal mass of unknown location is shown
on imaging, especially in postmenopausal women. Moreover,
careful intraoperative assessment of the adnexa is necessary.
Further studies are warranted to increase understanding of the
correct diagnosis of PFTC, and a multicenter randomized
clinical trial is necessary determine the most favorable medical management protocols to be applied.
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