GYNECOLOGIC ONCOLOGY 33, 351-355 (1989)

Fallopian Tube Carcinoma: A Clinicopathological Study of 17 Cases ALAN KING, M.D., IBRAHIM M. SERAJ,’ M.D., THAIS THRASHER, M.D., JAMES SLATER, M.D., AND

ROBERT J. WAGNER, M.D.

Departments of Obstetrics and Gynecology, and Radiation Sciences, Loma Linda University Medical Center, Loma Linda, California 92354

Received December 30, 1987

From 1969 through 1986, 17 patients with primary adenocar- cmoma of the fallopian tube were treated at the Loma Linda University Medical Center. Stages I, II, and III of the disease were present in 6, 5, and 6 patients, respectively. The mean age of the patients was 59.9 years. Vaginal bleeding or discharge (57%), followed by abdominal pain or discomfort (29%), was the most common symptom in our patients. A palpable pelvic mass was detected in two-thirds of the patients. One case of carcino- sarcoma, one case of mixed mesodermal tumor, and one case of endometrioid carcinoma are included. No patient in this series had a correct preoperative diagnosis. Therapy consisted of surgical resection, usually followed by various combinations of adjuvant radiation therapy and/or chemotherapy. The overall S-year survival rate was 31%. Five patients (29%) are alive without evidence of disease. This study supports the need for collaboration among large centers to deline the optimal adjuvant therapy of this disease. In the absence of the desired treatment protocols, such lesions should be approached in a manner similar to that used for ovarian cancers. 0 1989 Academic Press, Inc.

INTRODUCTION

Primary carcinoma of the fallopian tube comprises the least common malignant tumors of the female genital tract, with a reported incidence of 0.3 to 1.1% [l-4]. The insidious onset, the usually asymptomatic nature, and the inaccessibility of the oviduct for diagnostic in- vestigation make its early diagnosis a matter of chance, and the majority of the patients have advanced, metastatic disease when diagnosed. Since the diagnosis is made very often during surgery and sometimes after histologic examination of the resected specimen, meticulous op- erative evaluation and careful histopathological exami- nation are necessary for accurate staging and to differ- entiate between this lesion and primary ovarian carcinoma, especially if both organs are involved.

Surgery is regarded as the initial treatment for carcinoma

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351

of the uterine tube. Although complete removal of disease is the objective of surgical treatment, additional adjuvant treatment is often required since the tumor is frequently in an advanced stage. In this study we review our clinical experience with special reference to different histological patterns of this very rare disease.

MATERIALS AND METHODS

The medical records of patients with primary fallopian tube carcinoma presented at the Loma Linda University Medical Center from January 1969 through December 1986 were reviewed. Detailed microscopic descriptions and pathology slides were available for review. Seventeen cases satisfied the diagnostic criteria for primary fallopian tube carcinoma as proposed by Hu et al.: “(1) Grossly, the main tumor is in the tube. (2) Microscopically, chiefly the mucosa should be involved and should show a papillary pattern. (3) If the tubal wall is found to be involved to a great extent, the transition between benign and malignant tubal epithelium should be demonstrable” [5].

Staging was done in accordance with the modified FIG0 surgical classification similar to that for ovarian cancer [3,6,71.

Tumors were histologically graded by modifying the grading system described by Hu and associates [5], which is similar to the FIG0 grading system for endometrial adenocarcinoma: Grade 1, highly differentiated pure pap- illary tumor; Grade 2, moderately differentiated with partly solid areas; Grade 3, predominately solid or entirely un- differentiated carcinoma.

RESULTS

Clinical Data

The patients studied ranged in age from 44 to 83 years; their mean age was 59.9 years and their median age was 58. Fourteen patients (82%) were parous and three (18%)

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352 KING ET AL.

were nulliparous. Fifteen patients (88%) were postmen- opausal and two (12%) were premenopausal.

Presenting Symptoms

Two patients (12%) were asymptomatic. The most common symptoms were vaginal bleeding or discharge in 10 patients (59%), and abdominal pain or distension in 5 cases (29%). A palpable pelvic mass was found in 11 patients (65%). The pelvic examination was negative in 6 patients (35%), but in 2 patients in this group a pelvic mass was discovered by ultrasonography. The du- ration of symptoms was determined and was available for 15 patients (88%). The duration varied from weeks (2 patients), to several months (11 patients), to more than 1 year (2 patients).

The result of cervical cytology was available in 11 patients (65%). Two patients had positive Papanicolaou smears. One patient had a benign polyp with negative cervical biopsies, and the other patient had a microfocal, well-differentiated adenocarcinoma of the endocervix with early invasion. Eight patients (47%) had endometrial samplings and none showed abnormal endometrial curettings.

No patient in this series had a correct preoperative diagnosis; in only one instance was the tubal carcinoma suspected preoperatively. In four instances (24%) the diagnosis of fallopian tube carcinoma was made at the time of laparotomy. The most common operative diagnosis was carcinoma of the ovary in six cases (35%). In two cases (12%) the diagnosis of hydrosalpinx or pyosalpinx was made, and in four instances (23%) the operative diagnosis was not available. In one patient (6%) the primary site of the tumor could not be determined during surgery (Table 1).

Ten patients (59%) were operated on, staged, and had any residual tumor measured in this institution; seven patients (41%) had their initial surgery outside this center. We accepted the degree of extension and the amount of residual tumors after reviewing the operative summary and discussing the findings with the referring physician.

Table 2 shows the various types of operative procedures.

TABLE 1 Carcinoma of the Fallopian Tube: Operative Diagnosis

Operative diagnosis

Carcinoma of the fallopian tube

Carcinoma of the ovary Hydro/pyosalpinx Undetermined Not available

Total

Number of patients

4

6 2 1 4

17

Percentage

24

3.5 12 6

23 100

TABLE 2 Carcinoma of the Fallopian Tube: Surgical Procedures

Number of Procedure” patients Percentage

TAH, BSO 13 76 Vaginal hysterectomy 2 12 BSO 1 6 us0 1 6

Total 17 100

a TAH, total abdominal hysterectomy; BSO, bilateral salpingo- oophorectomy; USO, unilateral salpingo-oophorectomy.

Two patients who had vaginal hysterectomy and bilateral or unilateral salpingo-oophorectomy because adnexal neoplasm was not suspected had a subsequent laparotomy. In seven instances the above procedures were associated with complete or partial removal of the omentum. In two cases a sigmoid colon resection was performed, completely excising the tumor mass. One patient also had a sple- nectomy due to the serosal involvement of the spleen. There were residual tumor masses after surgery in four patients (24%). The largest residual tumor measured 2 cm in one patient. In three patients the tumor measured less than 1 cm.

Pathologic Findings and Stagings

Gross. The right fallopian tube was involved in ten cases (59%) and the left in seven instances (41%). In eight cases the tumor was situated in the ampulla; for four patients it was in the fimbria; in five patients the site of the tumor in the tube was not recorded. The lumen was patent in eight cases and closed in seven cases, and the patency was not recorded in two cases. The sizes of the tumors ranged from 2 to 10 cm. Perforation of the tubal wall was evident in three cases.

Microscopic. Fifteen patients (88%) had adenocarcinoma with papillary configuration as the dominant histologic pattern. One patient (7%) had grade 1 tumor, delicate papillae, moderately hyperchromatic epithelial cells showing mild cellular and nuclear pleomorphism and forming few acini, with a rare area of more solid epithelium. Five patients (33%) had grade 2 tumor, complex papillary arrangement of pleomorphic columnar cells, with marked nuclear pleomorphism and frequent mitotic activity. Some solid areas were also present. In two cases there were also psammoma bodies. Nine patients (60%) had grade 3 tumor, mainly solid, with sheets and nests of large pleomorphic tumor cells with high mitotic rates, a few papillary fronds, and rare gland formation. In the latter group there was one case of primary endometrioid car- cinoma of the fallopian tube, with solid proliferation of uniform cells forming small, crowded glands. Associated areas of cellular stoma also revealed a few areas of he-

FALLOPIAN TUBE CARCINOMA 353

mosiderin-laden macrophages. One patient (6%) had a malignant mixed mesodermal tumor characterized by a highly cellular tumor with definite papillary and glandular configurations as well as solid areas of spindle cells in- terlacing fascicles. Some areas showed wildly pleomorphic tumor giant cells. A prominent feature was cartilaginous proliferation with both benign and malignant elements. Another patient (6%) had carcinosarcoma of the oviduct, with well-defined epithelial tumor and a bizarre stromal neoplasm (Table 3).

Of the nine tumors (53%) that showed invasion of the tubal wall, one was superficially invasive; and in two instances the tumor invaded through 50 and 70% re- spectively of the wall thickness. In the remaining six cases the spread was beyond the muscularis, extending through the wall to the serosal surface. A close correlation between tumor grade and depth of invasion could not be established, but patients with advanced-stage disease had a higher-grade tumor. In 16 cases (94%) the tumors were unilateral, with metastasis to the opposite tube in 2 cases. One patient presented with an invasive carcinoma of one fallopian tube, penetrating 50% of the wall, and an adenocarcinoma in situ, in the opposite tube. This consisted of a few neoplastic glands protruding into the lumen, without invasion of the wall.

Associated Pathology

One patient was found to have a microfocal, well- differentiated adenocarcinoma of the endocervix with early invasion; one patient had a large follicular cyst; another patient had uterine leiomyomas; three patients had as- sociated hydrosalpinx (same side in two cases, bilateral in one case). One patient presented with a ruptured pyo- salpinx containing the tumor in one side and a benign tubo-ovarian abscess in the opposite side. Three patients had tubal endometriosis (opposite side in one case, bilateral in two cases). The patient with endometrioid carcinoma did not have tubal endometriosis in the affected oviduct nor in the contralateral tube.

Stage

Six patients (35%) with tumor confined to the tube had stage I disease. Five patients (30%) with direct involvement of an adjacent pelvic organ presented with stage II disease.

TABLE 3 Carcinoma of the Fallopian Tube: Histologic Type and Grade

Histologic type Grade I Grade II Grade III Total

Adenocarcinoma 1 5 9 15 Mixed mesodermal 1 Carcinosarcoma 1

Total 17

Six patients (35%) with intraabdominal metastases and one with metastases to the serosal surface of the spleen had stage III disease.

Adjuvant Therapy

Fourteen patients (82%) received postoperative adjuvant therapy. Three patients (21%) received postoperative ra- diation for curative intent. In four patients radiation ther- apy was required for palliation of recurrent disease after initial chemotherapy. Eleven patients (64%) were treated with a variety of chemotherapeutic regimens after surgery, and another two patients underwent chemotherapy for recurrent disease. The regimens and the number of patients receiving each are shown in Table 4.

Survival

The median survival for all patients was 36 months, and the overall 5-year survival rate for the entire group of patients was 29%. Five patients (29%) are well with no evidence of disease after 7, 8, 12, 41, and 46 months, respectively. Death from recurrent disease occurred in ten patients (59%). In five cases the tumor recurred after 5 years. These recurrences were in the pelvis and/or abdomen. One patient (6%) is still living with her recurrent disease after 26 months. One patient (6%) died after 190 months from metastatic bronchogenic carcinoma.

Analysis of the Results of Treatment

Stage I. Two of the stage I patients did not receive adjuvant postoperative treatment. One patient had re- currence and was living after 26 months. One patient died after 190 months from bronchogenic carcinoma. One patient who received postoperative radiation (strip and pelvic boost) died of recurrence after 99 months. Two patients who received Melphalan and Megace after surgery and one patient who received Cytoxan, cis-platinum, and Megace postoperatively had no evidence of disease 8, 41, and 12 months, respectively, following chemotherapy.

Stage ZZ. One stage II patient refused postoperative adjuvant therapy. She received Alkeran and Megace for

TABLE 4 Carcinoma of the Fallopian Tube: First-Line Chemotherapy

Number of Chemotherapeutic agent patients

Melphalan 1 Melphalan + Megace 4 c&Platinum + Cytoxan 1 c&Platinum + Adriamycin 2

+ Cytoxan Other 3

Total 11

354 KING ET AL.

recurrence. She died 60 months following surgery. Two patients received postoperative radiation. One patient died of recurrence after 60 months. One patient in whom the radiation therapy was discontinued due to her in- tolerance received Melphalan, Cytoxan, and 32P, after cessation of irradiation, but died of recurrence after 82 months. One patient received c&platinum and Cytoxan and is alive with no evidence of disease after 7 months. One patient who received Melphalan alone died of re- currence 36 months following chemotherapy.

Stage ZZZ. Two of the stage III patients received cis- platinum, Adriamycin, Cytoxan (PAC) following surgery. One (carcinosarcoma) died of recurrence after 12 months; the other patient is still alive with no evidence of disease 46 months following chemotherapy. One patient (mixed mesodermal) received DTIC, Adriamycin, Cytoxan, and vincristine. She died of recurrence after 18 months. Two patients who received Megace and Melphalan died of recurrence after 17 and 46 months, respectively. One patient who received 5-fluorouracil, hexamethylmelamine, Melphalan, and vinblastine died of recurrence after 11 months. No patient with stage III disease survived 5 years.

Due to the small number of patients and the multitude of postoperative, adjunctive therapies used in this series of patients, the role of postoperative irradiation and the efficacy of postoperative chemotherapy cannot be es- tablished. Our cases are too few for statistical evaluation.

DISCUSSION

The clinical features in this series are not significantly different from the findings of previous investigators. The mean age of 59.9 years, though slightly higher, is similar to that in the large series reported by Roberts and Lifshitz [8]. Fifteen patients (88%) were postmenopausal, a pro- portion somewhat higher than that of the series previously reported by other authors. The main disagreement is in the reported incidence of infertility. The 18% incidence of nulliparity in this series is far below that reported by others [3,6,8-111. This report is in complete agreement with the findings of other investigators [8,1 l-151 that the preoperative diagnosis of carcinoma of the fallopian tube is one of the most difficult to make. The diagnosis is usually made retrospectively after laparotomy and, more often, after histological examination of the resected spec- imen. In our series the preoperative diagnosis was not made in any patient and was made during surgery in only four cases. The remaining patients were correctly di- agnosed after pathologic examination of the specimen.

Vaginal bleeding or discharge followed by abdominal pain or discomfort were the most common symptoms in our patients. The classic “diagnostic triad” (pelvic pain, vaginal discharge, and palpable pelvic mass, all three in

the same patient) noted in 6% of the cases by Sedlis [16] was not observed in this series. Hydrops tubae profluens (characterized by intermittent, profuse, clear, watery dis- charge, followed by relief of colicky abdominal pain and disappearance of pelvic mass) was not encountered in this series.

Exfoliative cervical cytology for the detection of tubal cancer is disappointing. Positive cytology has been re- ported in as high as 60% [17] of the patients, but most reports are in the range of 10 to 20% [6,11,18]. In our series cervical cytology was available in 11 cases, but the test was positive in only 2 patients; one patient had an associated microfocal, well-differentiated adenocar- cinema of the endocervix with early invasion diagnosed by cervical cone, but the resected hysterectomy specimen did not reveal any residual tumor. Cytologic smears of cervical material are not reliable for the detection of fallopian tube malignancy [6,11,19]. The endometrial samplings in 8 patients were negative. Negative endo- metrial and cervical samplings in the presence of positive cytology should arouse suspicion of fallopian tube cancer.

Precise histological documentation of primary carcinoma of the fallopian tube is very important. The decision on the primary site of the tumor is often difficult and par- ticularly complicated if both tube and ovary are heavily involved by tumor. A prominent clue that one is dealing with a tubal carcinoma is the retort shape of the fallopian tube and, generally, the normal size of the ovary. The oviduct will become occluded as the tumor blocks the lumen, and a cystic configuration will occasionally ensue that confuses the observer into thinking this is a cystic papillary carcinoma of the ovary. With careful dissection most of these cases can be traced along the tube lumen, and the bulk of the tumor can be demonstrated to be within a markedly dilated or cystic area. This gives the appearance of the tumor arising in a previous hydrosalpinx in some instances. It is rare for the ovary to be enlarged except by external tumor implants. After careful dissection of the tube, the remaining adnexal structures can be sectioned to show an ovary deeply embedded in tumor implants.

Primary fallopian tube endometrioid carcinoma is an extremely rare cell type, first described by Scully [201 at the Clinicopathologic Conference in 1967. His patient did not have endometriosis of the tube, and the tumor was attached to the wall of the oviduct. The patient also had an adenocarcinoma of the endometrium, but there was no continuity between the two tumors.

The case presented here, in contrast to the Scully case, was not accompanied by adenocarcinoma of the corpus uteri; that the primary site was in the fallopian tube could not be questioned. One case of carcinosarcoma and one case of mixed mesodermal tumor of the fallopian tube with carcinomatous elements are included in this study.

FALLOPIAN TUBE CARCINOMA 355

They are found predominantly in postmenopausal women, and they most frequently arise in the uterus, with me- tastasis to the fallopian tube. There was superficial me- tastasis to both ovaries and endometrium in one case and to the opposite ovary in the other case, and the primary site of the tumors in the tubes could be demonstrated.

In summary, the preoperative diagnosis of carcinoma of the fallopian tube is next to impossible because of its rarity and its inaccessibility for diagnostic investigation. The operative diagnosis is difficult, especially if the ovary is involved and the neoplasm presents as a tubo-ovarian mass. The histologic diagnosis is subtle and sometimes complex if the adjacent ovary is buried in advanced tumor disease.

Since most studies of fallopian tube cancer in the lit- erature are based on case reports or on collections of few cases, the treatment approach remains to be estab- lished, and the collaboration of many large centers is needed to define the optimal therapy of this disease. Short of this, such lesions should be approached in a manner similar to that used for ovarian cancers.

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