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Gynecologic Oncology
Fallopian Tube Carcinoma: A Review
Dimitrios Pectasides, Eirini Pectasides, Theofanis Economopoulos
Key Words. Primary fallopian tube carcinoma Diagnosis Staging Prognosis Treatment
Abstract
Purpose. Primary fallopian tube carcinoma (PFTC) is a
rare tumor that histologically and clinically resembles
epithelial ovarian cancer (EOC). The purpose of this
study is to review the current available literature data
on PFTC.
Patients and Results. Early clinical manifestation and prompt investigation often lead to diagnosis
at an early stage of disease. However, the diagnosis of
PFTC is rarely considered preoperatively and is usually first appreciated by the pathologist. Surgical staging/management and the use of chemotherapy follow
Introduction
Etiology
The etiology of this cancer is unknown. Hormonal, reproductive, and possibly genetic factors thought to increase
EOC risk might also increase PFTC risk. High parity has
been reported to be protective [7], and a history of pregnancy and the use of oral contraceptives decreases the PFTC
risk significantly [15]. It has been reported that there is no
statistically significant correlation between PFTC and age,
race, weight, education level, pelvic inflammatory disease,
infertility, previous hysterectomy, endometriosis, lactose
intolerance, or smoking [11, 15, 16]. Meng et al. [17] found
Correspondence: D. Pectasides, M.D., Second Department of Internal Medicine, Propaedeutic, Oncology Section, Attikon University Hospital, Rimini 1, Haidari, Athens, Greece. Telephone: 210-5831691, 210-6008610; Fax: 210-5831690, 210-6008610; e-mail:
pectasid@otenet.gr Received March 11, 2006; accepted June 22, 2006. AlphaMed Press 1083-7159/2006/$20.00/0 doi: 10.1634/
theoncologist.11-8-902
Clinical Manifestations
PFTC most frequently occurs between the fourth and sixth
decades of life [29, 30], with a median age of occurrence
of 55 years (range, 1788 years). However, PFTC has been
reported in young girls aged 1719 [3134]. Patients with
PFTC appear to have a shorter history of symptoms than
those with EOC [35]. The clinical symptoms and signs of
PFTC are shown in Table 1 [11, 30, 36 41]. These symptoms
are not specific. Latzkos triad of symptoms, consisting of
intermittent profuse serosanguinous vaginal discharge,
colicky pain relieved by discharge, and abdominal or pelvic
mass has been reported in 15% of cases [34]. Hydrops tubae
profluens, a pathognomonic feature, implies intermittent
discharge of clear or blood-tinged fluid spontaneously or
on pressure followed by shrinkage of an adnexal mass and
occurs in 5% of patients. PFTC is rarely asymptomatic, in
contrast to EOC. In many cases, the preoperative diagnosis
of PFTC is extremely rare [26, 29, 42, 43].
The rate of preoperative diagnosis was in the range of
0%10% [6, 44, 45]. Vaughan et al. [46] reported a rate
of 21% of preoperative diagnosis, Baekelandt et al. [28]
reported a rate of only 2%, and Meng et al. [17] reported
that an intraoperative diagnosis is missed in up to 50% of
patients. Some patients have been found to have extensive
pelvic tumor, perhaps manifested by a tubo-ovarian mass.
Even when such disease is resected, it is often impossible
on histopathologic examination to determine the origin
of the tumor. These cases are almost always classified as
ovarian in origin because ovarian cancer is more common
than PFTC [9]. When compared with EOC, PFTC is often
diagnosed at an earlier stage because of abdominal pain
secondary to tubal distention [4750]. However, a diagnosis of PFTC may be suspected in cases of postmenopausal
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Imaging
Imaging routinely carried out for suspected gynecologic
malignancies includes ultrasound, computed tomography
(CT) scan and magnetic resonance imaging (MRI) of the
abdomen. Of course, imaging techniques do not safely rule
out the presence of malignancy or conversely rule in that
possibility, and their findings cannot change the management of PFTC. Transvaginal and transabdominal ultrasound is an essential imaging technique in the diagnostic
workup of patients with possible tubal pathology [52, 53].
Timor-Tritsch and Rottem [54] demonstrated the benefits
of transvaginal over transabdominal ultrasound in the
imaging of fallopian tubes. The echographic appearance
of fallopian tubes is nonspecific, mimicking other pelvic
diseases, such as tubo-ovarian abscess, ovarian tumor,
and ectopic pregnancy. Echogram shows a cystic mass
with spaces and mural nodules, a sausage-shaped mass,
or a multilobular mass with a cog-and-wheel appearance
[5557]. Low-impedance vascular flow within the solid
components has been reported [58]. In addition, it was
demonstrated that transvaginal ultrasound examination
with color Doppler can detect areas of neovascularization
within the fallopian tube and thus may aid in the preoperative diagnosis of PFTC. Three-dimensional Doppler can
show tubal wall irregularities such as papillary protrusions and pseudosepta and depictions of vascular abnormalities (arteriovenous shunts, microaneurysms, tumor
lakes, blind ends, and dichotomous branching typical of
malignant tumor vessels) [59].
The lesion can have the appearance of a small, solid,
lobulated mass on CT scan or on MRI. On CT scan, the
lesion has an attenuation equal to that of other soft tissue
masses and enhances less than the myometrium. On T1weighted MR images, the tumor is usually hypointense;
on T2-weighted MR images the tumor is often homogeneously hyperintense. Imaging can most often detect solid
and cystic components with papillary projections, which on
MRI can be remarkably enhanced by the administration of
gadolinium [60]. Associated findings include peritumoral
ascites, intrauterine fluid collection, and hydrosalpinx
[61]. MRI seems to be better than CT scan or ultrasound in
detecting tumor infiltration of the bladder, vagina, pelvic
sidewalls, pelvic fat, and rectum.
903
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CA-125 Level
Cytology
Several authors state that the cervicovaginal smear is an
inadequate diagnostic tool and no one would consider using
it for the diagnosis of PFTC. Positive Pap smears have been
reported in only 0%23% of cases [6, 51, 6770]. The discrepancy between an abnormal Pap smear and negative
findings on colposcopy, cervical biopsy, and endometrial
curettage should be considered suspicious for PFTC.
Pathology
The diagnosis of PFTC is usually first made by a pathologist on histopathological examination. The most common
histological types are shown in Table 2 [50, 7175]. Serous
tumors are graded with respect to their differentiation and
extent of solid components: most tumors are poorly differentiated [48, 50, 71] (Table 3).
Because it is difficult to differentiate PFTC from EOC,
patients with at least one of the following criteria should
have the diagnosis of PFTC [72]: (a) The main tumor is in
PFTC
49.5%83.3%
8.3%50%
3.9%16.7%
7.8%11.3%
1.9%
11.7%
3%7.6%
EOC
75% (60%80%)
20% (15%24%)
3%
1%2%
5% (3.7%12.1%)
1%2%
2.4%19.9%
PFTC
15%20%
20%30%
50%65%
EOC
20%
30%
50%
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CA-125 is a useful tumor marker for the diagnosis, assessment of response to treatment, and detection of tumor
recurrence during follow-up. The CA-125 antigen is often
expressed by PFTC [62]. Although CA-125 per se is not
diagnostic for PFTC, >80% of patients have elevated pretreatment serum CA-125 levels [34, 49]. Elevated serum CA125 levels have been detected more frequently in advanced
or recurrent disease [10, 49, 6264]. Gadducci et al. [48]
reported that preoperative serum CA-125 levels were >35 U/
ml in 85.3% of cases (68.7% for stage III and 94.7% for stage
IIIIV). The pretreatment serum CA-125 level is an independent prognostic factor of disease-free survival and overall
survival (OS) in patients with PFTC [10, 34]. Serum CA-125
levels postsurgery have also been associated with response to
chemotherapy [19, 64, 65]. CA-125 is also a useful marker for
post-treatment follow-up. It is an early and sensitive marker
for tumor progression during follow-up [6366]. It has been
reported that the lead time (elevated serum CA-125 levels
prior to clinical or radiological diagnosis of recurrence) is 3
months (range, 0.57 months) [34].
Percentage
50%60%
30%49%
60% (range, 12%84%)
15%
Treatment
Surgery
Surgery is the treatment of choice for PFTC. Surgical principles are the same as those used for ovarian cancer. The
majority of patients in the literature had clearly suboptimal
staging by todays standards [46]. Aggressive cytoreductive
surgery with removal of as much tumor as possible is warranted in patients with advanced disease. If it is impossible
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to achieve optimal debulking despite maximum effort, surgery should be attempted again after a few courses of chemotherapy. Very aggressive forms of surgery should only be
considered in highly individualized patients [88]. Considering the strong tendency for lymphatic spread of the tumor,
a systematic pelvic and para-aortic lymphadenectomy is
preferred to lymph node sampling [48, 89, 90]. Klein et al.
[89] reported that the median survival times were 43 and
21 months, respectively, in patients with and without lymph
node dissection. In advanced disease, the bulk of extratubal disease and postoperative residual disease >2 cm are
adverse prognostic factors [13, 46]. In young patients who
want to retain fertility, limited surgery can be considered
for patients with an in situ carcinoma and in those women
with stage I and grade I carcinoma [34].
Second-Look Laparotomy
As in the case of EOC, second-look laparotomy does not
have a role in the management of PFTC [91]. In EOC, second-look laparotomy has not been proven to be beneficial
since 50% of patients with a surgical complete response still
go on to relapse. In addition, there is no curative second-line
therapy for those patients with positive findings at secondlook laparotomy. A review of 310 patients included in 13
literature series revealed that 32 (62.7%) of the 51 patients
submitted to second-look operation were found to be in
pathologic complete remission (pCR) [92]. Recurrence was
recorded for 22% of these 32 patients. A negative secondlook laparotomy is associated with longer survival. Secondlook laparotomy should currently be reserved for patients
enrolled in clinical trials.
Radiotherapy
Radiotherapy could possibly be considered either as adjuvant therapy for early-stage patients [2, 5, 28, 45, 46, 73,
85, 9396], for stage III residual negative patients, or in the
relapse setting. Although radiotherapy has been used traditionally in the past as an adjuvant therapy for PFTC, its role
in the era of effective chemotherapy is less well defined and
controversial. In view of its low efficacy and high rate of
serious complications, the use of postoperative radiotherapy in the treatment of patients with PFTC is no longer recommended. Intraperitoneal instillation of radioisotopes did
not seem to reduce the recurrence risk in early-stage disease
[12, 47].
Adjuvant Chemotherapy
Based on the propensity for microscopic distant spread and
the relatively high risk for recurrence despite complete surgical resection, chemotherapy seems to have a strong rationale
as adjuvant treatment for patients with early-stage disease;
905
906
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on small series showed the possible value of cyclophosphamide, doxorubicin, and cisplatin (the CAP regimen)
and paclitaxel-containing regimens [49, 70, 94, 100, 101].
Pectasides et al. [94] treated 14 patients with a CAP combination (10 patients) or carboplatin plus cyclophosphamide (four patients). Eight of these patients had a complete
clinical response, and two had partial responses. Among
the eight complete responders, five patients underwent a
second-look operation, and pCR was confirmed in four of
five of them.
Very few data exist on the activity of paclitaxel as firstline chemotherapy in patients with PFTC [100, 102, 103].
Gemignani et al. [104] reported their experience on the use
of paclitaxel-based chemotherapy after initial surgery in
24 patients with PFTC, of whom 17 had stage IIIIV disease. Twenty-three patients received paclitaxel at a dose of
135175 mg/m2 with carboplatin or cisplatin; the majority,
17 of 23 (74%), received carboplatin. One patient received
paclitaxel alone. The median disease progression-free
survival rate at 3 years was 67% in the optimally debulked
group, compared with 45% in the suboptimally debulked
group. They concluded that optimally cytoreduced patients
with PFTC treated with a paclitaxel-based chemotherapy
regimen have an excellent possibility of survival. Similarly, Baekelandt et al. [105] administered the combination
of carboplatin (area under the concentrationtime curve
[AUC] 6) plus paclitaxel (175 mg/m2) to eight patients with
PFTC, of whom four were chemotherapy-nave and four had
recurred after a platinum-free interval of at least 6 months.
Three (37.5%) patients achieved a complete response and
four (50%) had a partial response, for an overall response
rate of 87.5%.
With regard to relapse therapy, all the information
comes from EOC. Paclitaxel has been shown to have activity in platinum-pretreated patients with PFTC [104107].
Tresukosol et al. [106] reported that paclitaxel at a dose of
200 mg/m2 produced a complete response in a patient with
recurrent platinum-resistant disease, and Ichikawa et al.
[107] reported that the combination of carboplatin (AUC 6)
plus paclitaxel (180 mg/m 2) achieved a complete response
in a patient with a platinum-pretreated tumor. In EOC, there
is evidence that using intraperitoneal therapy as one component may be more effective than i.v. chemotherapy for
stage III, residual <1 cm, patients. Armstrong et al. [101]
reported a statistically significant prolongation of progression-free survival and OS in the intraperitoneal arm, associated with a 25% lower risk for death compared with i.v.
chemotherapy for patients with newly diagnosed stage III
ovarian carcinoma or primary peritoneal carcinoma, optimally debulked. [101]. Although data from intraperitoneal
therapy do not exist for PFTC, this type of treatment could
907
908
Hormonotherapy
Hormonal agents increasingly have been used in PFTC. The
rationale is that tubal epithelia undergo changes with hormonal fluctuation during the menstrual cycle. Embryologically and histologically the tubal epithelium is derived from
the same source as the endometrial epithelium. Progestational agents have been used because of the known cyclic
response of the normal tube to hormonal changes during
the menstrual cycle [5, 85, 95]. Because no randomized trials exist and nearly all patients treated with progestational
agents are also treated with combination chemotherapy, no
firm conclusions can be drawn with regard to their usefulness. Steroid receptors have been found in a few cases, but
their clinical role is unclear [28].
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Treatment
No further treatment
Carboplatin (AUC 6) plus paclitaxel (175 mg/m2) every 3 weeks for 36 cycles
Carboplatin (AUC 6) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles
Carboplatin (AUC 56) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles
Conclusion
PFTC is a rare tumor accounting for <1% of all female genital tract cancers. Histologically and clinically, it resembles
EOC. The diagnosis of PFTC is rarely considered preoperatively and is usually first appreciated at the time of operation or by a pathologist. Both carcinomas have a similar age
distribution, are more common among nulliparous women,
and are often of serous papillary histology. Surgery should
consist of total abdominal hysterectomy, bilateral salpingooophorectomy, omentectomy, and lymph node dissection
from the pelvic and para-aortic regions. Aggressive debulking surgery should be attempted in patients with advanced
disease. PFTC is similar to EOC in surgical staging, surgi-
References
1
Semrad N, Watring W, Fu YS et al. Fallopian tube adenocarcinoma: common extraperitoneal recurrence. Gynecol Oncol 1986;24:230235.
Brown MD, Kohorn EI, Kapp DS et al. Fallopian tube carcinoma. Int J
Radiat Oncol Biol Phys 1985;11:583590.
www.TheOncologist.com
cal management, and indications for adjuvant chemotherapy. Both carcinomas have a poor prognosis with stage and
residual tumor size and respond to platinum-based chemotherapy. However, there are two differences between the two
diseases: PFTC is more often diagnosed at an earlier stage,
and the role of routine lymphadenectomy is well established
and is mandatory in PFTC. Stage and residual tumor are the
most important prognostic factors for outcome. Patients
with stage I low-risk disease submitted to optimal surgical
staging may not receive postoperative treatment. In contrast, patients with stage I low-risk disease not submitted
to complete surgical staging, as well as those with stage I
high-risk disease or stage IIA disease, should receive 36
cycles of adjuvant carboplatin plus paclitaxel. Patients with
advanced disease should be treated with a combination of
carboplatin plus paclitaxel, as with EOC. Second-line treatment for persistent/recurrent disease should be based on the
platinum-free interval, whereas secondary cytoreduction
should be considered only for highly selected patients with
localized late relapse. More extensive clinical research must
be performed in order to have definite etiologic, diagnostic,
and management modalities, and prognostic markers.
Riska A, Leminen A, Pukkala E. Sociodemographic determinants of incidence of primary fallopian tube carcinoma, Finland 1953-97. Int J Cancer
2003;104:643645.
Rosenblatt KA, Weiss NS, Schwartz SM. Incidence of malignant fallopian tube tumors. Gynecol Oncol 1989;35:236239.
10 Rosen AC, Klein M, Hafner E et al. Management and prognosis of primary fallopian tube carcinoma. Austrian Cooperative Study Group for
Fallopian Tube Carcinoma. Gynecol Obstet Invest 1999;47:4551.
11 Henderson SR, Harper RC, Salazar OM et al. Primary carcinoma of the
fallopian tube: difficulties of diagnosis and treatment. Gynecol Oncol
1977;5:168179.
tube (fimbrial versus nonfimbrial), HER-2/neu expression, p53 alteration [76, 77], and elevated pretreatment
CA-125 level [28, 34, 48, 71, 117]. The importance of an
occlusion of the abdominal tubal ostium that could possibly prevent or delay local spread is not clear [123]. The role
of DNA-ploidy is negligible [124]. PFTC shares several
biologic and clinical features with EOC. However, when
compared with EOC, PFTC more often tends to recur in
retroperitoneal nodes and distant sites. Stage, patient age,
and among patients with advanced disease, residual tumor
after initial surgery are the most important prognostic factors for survival [124, 125].
910
12 Asmussen M, Kaern J, Kjoerstad K et al. Primary adenocarcinoma
localized to the fallopian tubes: report on 33 cases. Gynecol Oncol
1988;30:183186.
13 Woolas R, Jacobs I, Davies AP et al. What is the true incidence of primary
fallopian tube carcinoma? Int J Gynecol Cancer 1994;4:384388.
14 Wang PH, Yuan CC, Chao HT et al. Prognosis of primary fallopian
tube adenocarcinoma: report of 25 patients. Eur J Gynaecol Oncol
1998;19:571574.
15 Inal MM, Hanhan M, Pilanci B et al. Fallopian tube malignancies: experience of Social Security Agency Aegean Maternity Hospital. Int J Gynecol
Cancer 2004;14:595599.
16 Demopoulos RI, Aronov R, Mesia A. Clues to the pathogenesis of fallopian tube carcinoma: a morphological and immunohistochemical case
control study. Int J Gynecol Pathol 2001;20:128132.
33 Dodson MG, Ford JH Jr, Averette HE. Clinical aspects of fallopian tube
carcinoma. Obstet Gynecol 1970;36:935939.
34 Ajithkumar TV, Minimole AL, John MM et al. Primary fallopian tube
carcinoma. Obstet Gynecol Surv 2005;60:247252.
35 Markman M, Zaino R, Busowski J et al. Carcinoma of the fallopian tube.
In: Hoskins WJ, Perez CA, Young RC, eds. Principles and Practice of
Gynecologic Oncology. Philadelphia: JB Lippincott Co, 1992:783.
36 Obermair A, Taylor KH, Janda M et al. Primary fallopian tube carcinoma:
the Queensland experience. Int J Gynecol Cancer 2001;11:6972.
37 Nikrui N, Duska LR. Fallopian tube carcinoma. Surg Oncol Clin N Am
1998;7:363373.
38 Winter-Roach BA, Tjalma WA, Nordin AJ et al. Inguinal lymph node
metastasis: an unusual presentation of fallopian tube carcinoma. Gynecol
Oncol 2001;81:324325.
39 Courville XF, Cortes Z, Katzman PJ et al. Case report: Bone metastases
from fallopian tube carcinoma. Clin Orthop Relat Res 2005;(434):278281.
40 Hidaka T, Nakamura T, Shima T et al. Cerebral metastasis from a primary
adenocarcinoma of the fallopian tube. Gynecol Oncol 2004;95:260263.
41 Levite R, Fishman A, Kesler A et al. Paraneoplastic cerebellar degeneration heralding fallopian tube adenocarcinoma. Int J Gynecol Cancer
2001;11:169171.
42 Chalmers JA, Marshall AT. Carcinoma of the fallopian tube. Br J Obstet
Gynaecol 1976;83:580583.
43 Pfeiffer P, Mogensen H, Amtrup F et al. Primary carcinoma of the fallopian tube. A retrospective study of patients reported to the Danish Cancer
Registry in a five-year period. Acta Oncol 1989;28:711.
44 Podratz KC, Podczaski ES, Gaffey TA et al. Primary carcinoma of the fallopian tube. Am J Obstet Gynecol 1986;154:13191326.
45 Huber-Buchholz MM, Buchholz NP, Staehelin J. Analysis of 23 cases of
primary carcinoma of the fallopian tube over 50 years. J Obstet Gynaecol
Res 1996;22):193199.
46 Vaughan MM, Evans BD, Baranyai J et al. Survival of patients with primary fallopian tube carcinoma. Int J Gynecol Cancer 1998;8:1622.
47 Rose PG, Piver MS, Tsukada Y. Fallopian tube cancer. The Roswell Park
experience. Cancer 1990;66:26612667.
48 Gadducci A, Landoni F, Sartori E et al. Analysis of treatment failures and
survival of patients with fallopian tube carcinoma: a cooperation task
force (CTF) study. Gynecol Oncol 2001;81:150159.
49 McMurray EH, Jacobs AJ, Perez CA et al. Carcinoma of the fallopian
tube. Management and sites of failure. Cancer 1986;58):20702075.
50 Peters WA 3rd, Andersen WA, Hopkins MP et al. Prognostic features of
carcinoma of the fallopian tube. Obstet Gynecol 1988;71:757762.
51 Zreik TG, Rutherford TJ. Psammoma bodies in cervicovaginal smears.
Obstet Gynecol 2001;97:693695.
52 van Nagell JR Jr, Higgins RV, Donaldson ES et al. Transvaginal sonography as a screening method for ovarian cancer. A report of the first 1000
cases screened. Cancer 1990;65:573577.
31 Blaustein A. Tubal adenocarcinoma coexistent with other genital neoplasms. Obstet Gynecol 1963;21:6266.
32 Ross WM, Ward CV, Lindsay CC. Primary carcinoma of the fallopian
tube. A report of 8 cases. Am J Obstet Gynecol 1962;83:425429.
OTncologist
he
17 Meng ML, Gan-Gao, Scheng-Sun et al. Diagnosis of primary adenocarcinoma of the fallopian tube. J Cancer Res Clin Oncol 1985;110:136140.
90 Rauthe G, Vahrson HW, Burkhardt E. Primary cancer of the fallopian tube. Treatment and results of 37 cases. Eur J Gynaecol Oncol
1998;19:356362.
www.TheOncologist.com
911
912
114 Muggia FM, Hainsworth JD, Jeffers S et al. Phase II study of liposomal
doxorubicin in refractory ovarian cancer: antitumor activity and toxicity
modification by liposomal encapsulation. J Clin Oncol 1997;15:987993.
115 Gordon AN, Granai CO, Rose PG et al. Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. J
Clin Oncol 2000;18:30933100.
OTncologist
he
116 Markman M, Kennedy A, Webster K et al. Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol
Oncol 2000;78:369372.
Citations