Fallopian Tube Carcinoma

CANCERS UNIQUE TO WOMEN

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FALLOPIAN TUBE CARCINOMA Najmosama Nikrui, MD, and Linda R. Duska, MD

HISTORICAL OVERVIEW

Carcinomas of the fallopian tube are uncommon gynecologic malignancies. Accordingly, there is no large experience with these cancers at any single institution. Contributing to our lack of insight is the difficulty in making a preoperative diagnosis. Even at the time of surgery, the diagnosis can be unsuspected or confused with ovarian cancer. The first reports of fallopian tube carcinoma came from Renaud and Rokitansky in 1846 and 1861, respectively. A few years later, Orthmann33•34 definitively substantiated "fallopian tube cancer" as a pathologic entity. Likewise, Nurnberger32 in 1932 and Meigs in 1936 wrote extensively above tubal malignancies. The pathologic distinction of fallopian tube carcinoma was addressed in a classic work by Hu in 1950. 20 In 1970, Dodson et al1 2 concluded that chemotherapy should be used as adjuvant treatment after surgery. They also emphasized the importance of accurate staging of tubal carcinoma. In 1981, for the first time, Tamimi and Figge47 revealed the pattern of lymph node metastases and the role of lymph node metastases as a prognostic factor. Finally, International Federation of Gynecologists and Obstetricians (FIGO) in 1991 stated a classification and staging system for fallopian tube cancer. EPIDEMIOLOGY

Primary fallopian tube carcinoma represents less than 1% of all gynecologic malignancies. It is, therefore, the rarest cancer of the female From Vincent Gynecology, Division of Gynecologic Oncology, Massachusetts General Hospital, Boston, Massachusetts SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA VOLUME 7 • NUMBER 2 •APRIL 1998

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genital tract. The incidence of fallopian tube cancer ranges from 0.15% to 1.8%, with a peak incidence in the fifth to sixth decade of life. The mean age is 55 years, with a range from 18 to 87 years. White women are affected more often than African-American women. More than 2000 cases offallopian tube cancer have been reported since 1950. Currently, 3400 cases per year or 2.9 to 3.6 cases per million women are estimated to occur in the United States each year. 14• 19 This incidence has been stable over the past fifty years. The "low incidence" may be attributed to the rarity of the tumor and the failure to recognize and diagnose tubal cancer in deference to its ovarian counterpart. By convention, cancer that simultaneously involves the ovary and the tube is formally designated as being ovarian, not tubal. Tubal cancers are associated with low parity, infertility and chronic salpingitis. However, because pelvic infections are common and tubal cancers are rare, it is difficult to quantify this last association.

HISTORY AND SYMPTOMS

The most common symptoms associated with tubal carcinoma are abdominal pain, vaginal bleeding, and an abdominal or pelvic mass. In a series of cases of fallopian tube carcinoma, abnormal vaginal bleeding is described in 50% to 61 % of patients, pain in 30% to 49%, and a mass in 12% to 61 %.7· 14•37•41 The triad of hydrops tubae profluens is pathognomonic of tubal cancer and consists of a profuse watery vaginal discharge associated with colicky abdominal pain (which may be relieved by discharge) plus an abdominal or pelvic mass. 36 Despite this classic description, only 5% to 10% of cases are associated with the triad. Fifteen percent of cases present with ascites. Acute abdomen caused by torsion or intra-abdominal bleeding or both has been reported as a presenting symptom.37•38 Other rare presenting symptoms include respiratory insufficiency, urinary urgency, bowel movement dysfunction, ureteral obstruction, back pain, abnormal neurologic findings, and exfoliative dermatitis. Finally, 14% of patients seen in one series were completely asymptomatic. 14

Table 1. PERCENT 5-YEAR SURVIVAL FOR FALLOPIAN TUBE CARCINOMA BY STAGE Stage

Denham 10*

n= I II

Ill IV

40 68 39 21

Podratz 39,t

n=

47 64 60 18 25

Barakat•·*

n=

38 83

Morris 2M

n=

28

*Surgery, radiation, and chemotherapy. tSurgery and radiation. :j:Surgery and chemotherapy; overall survival of 41% to 56% for all stages.

86 51

18

Muntz 29

n=

12 100 68 45 20

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365

DIAGNOSIS

The diagnosis of fallopian tube carcinoma is rarely made preoperatively. Physical examination can be misleading. Fallopian tube cancers have been misdiagnosed as myomata uteri, ovarian masses, and tuboovarian abscesses. The Papanicolaou smear can detect only 10% of cases.44 Only 5% of the cases reported by Frick16 were diagnosed correctly preoperatively. Even at exploratory laparotomy it can be difficult to make the diagnosis correctly. This difficulty is a result of the similarities between the spread and pathology of tubal and ovarian cancers as well as advanced endometrial cancers. In a postmenopausal woman with vaginal bleeding and a negative endometrial curettage, the diagnosis of tubal cancer should be suspected. The clinical history and physical examination are, as always, an important part of the patient evaluation but rarely are capable of making the diagnosis of fallopian tube cancer before surgery. Ultrasonography and MR imaging or CT can be useful in confirming the finding of a pelvic mass or ascites but are not diagnostic of tubal carcinoma per se. Likewise, tumor markers (e.g., CA 125) are also not specific for the diagnosis, although when elevated they can be used for following patients' response to therapy. In rare cases, laparoscopy or hysteroscopy should be a part of patient evaluation before the laparotomy.15 Hysteroscopy and laparoscopy have been suggested as part of the examination for suspected fallopian tube carcinoma. Finikiotis et al1 5 diagnosed one patient with fallopian tube carcinoma based on a finding on hysteroscopy of a yellowish patch. Unfortunately ultrasonography, either vaginal or abdominal, is not specific. In association with clinical suspicion, however, ultrasonography can give an accurate diagnosis. 1• 2 Preliminary results suggest that whole-body positron emission tomography with (fluorine-18)-2-deoxyglucose can detect metastatic carcinoma of the fallopian tube. 23 Preoperative diagnosis of eight early stage tubal carcinomas were made by color Doppler transvaginal Sonography. The vascular resistance index (RI) was noted to be 0.29- 0.40. These eight cases were early stage cancer, and the largest series diagnosed preoperatively. PATHOLOGY

The typical appearance of a localized fallopian tube cancer is subtle, a dilated tube that when opened contains an intraluminal, often papillary mass. Many variations in gross finding are encountered, including discrete solid nodules and lesions characterized by marked thickening of the tubal wall. Occasionally tumors are confined to the fimbrial portion of the tube. 3 Finally, there is the gross, diffuse intra-abdominal spread of disease, in a pattern not unlike epithelial ovarian cancer. Microscopically, most tubal carcinomas resemble serous carcinoma of the ovary, exhibiting varying combinations of papillarity, slit-like glandular spaces, cellular budding, and solid masses of carcinoma cells with frequent psammoma bodies. Another histology is endometrioid appear-

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ing, morphologically similar to that of the endometrium. 9 Endometrioid tumors tend to be less invasive of the wall than serous tumors. Occasional tubal carcinomas are of the transitional types and rarely they can be clear cell or mucinous. Other rare tumors of the fallopian tube include squamous carcinomas, adenosquamous carcinomas, lymphoma, malignant mixed Muellerian tumors, choriocarcinomas, and leiomyosarcomas.17,21,34,48 The pathologic criteria for diagnosing carcinoma primary to the fallopian tube were established by Hu et al in 1950. 20 They include (1) grossly, the main tumor is in the tube; (2) microscopically, the mucosa is involved, and (3) in the case of wall involvement, there should be a transition between benign and malignant change. Sedlis46 in 1978 then modified these criteria as follows: (1) tumor must arise from the endosalpinx, (2) histologic pattern is of mucosal tubal epithelium, (3) transition from benign to malignant epithelium must be present, and (4) the endometrium and ovaries are either normal or the tumor in these organs is smaller than the tumor in the tube. NATURAL HISTORY AND PATTERNS OF SPREAD

Tubal cancer spreads first by exfoliation of the clonogenic cells into the lumen of the fallopian tube, expanding and distending it. It may then involve, by direct extension, the adjacent uterus and ovaries and migrate into and throughout the intraperitoneal cavity, as does epithelial ovarian cancer. Many fallopian tube carcinomas obliterate the fimbriated end of the fallopian tube preventing peritoneal spread. Other patterns of spread include lymphatic and less likely vascular routes. 24·51 The incidence of bilaterality with fallopian tube cancer has been cited at 21 %. When unilateral, either side may be involved. At the time of diagnosis, one third of cases are local and two thirds are advanced. 6 Tumors that involve the proximal portion of fallopian tube can metastasize in the lymphatic of the round ligament to the inguinal nodes. In contrast, tumors that involve the fimbriated end more often metastasize to the para-aortic nodes. If the broad ligament is involved, both pelvic and para-aortic nodes are at risk. For apparent stage I disease, surgical staging reveals a 33% risk of positive para-aortic nodes. In stages III and IV, involvement rises to 85%. Among other factors, survival has been correlated with the nodal status- 76 months when nodes are negative and 33 months when nodes are positive. STAGING

Fallopian tube cancer is staged surgically, in a fashion analogous to ovarian cancer. Because the rules of staging require unclear cases to be assigned an ovarian origin, most cases of fallopian tube cancer are confined to the pelvis (i.e., low stage). Such findings are unlikely to be consistent with reality but are the result of staging convention. In that context,

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20% to 25% of cases are stage I, 20% to 25% are stage II disease, and 40% to 50% of cases have disease beyond the pelvis (Appendix A). SURGERY

The surgical management of this malignancy parallels that of epithelial ovarian cancer. The 5-year survival rate for stage I has been cited as 60% to 80%; survival rate decreases to 29% for advanced disease if the residual disease exceeds 2 cm. Cytoreductive surgery to a tumor size of less than 2 cm improves survival. 4•37-39·41 Complete surgical staging may result in the upgrading of an apparent stage I tumor to a stage III if the lymph nodes are positive. Incompletely staged apparent stage I tumors therefore may account for the lower end of the 5-year survival rate previously mentioned. Occasionally, young women of reproductive age are diagnosed with an early stage tubal cancer. If the patient is desirous of saving her uterus and ovaries for the purpose of fertility, it becomes mandatory to perform a complete surgical staging. Assuming the contralateral tube appears normal, some experts have suggested its removal and then for the patient to achieve pregnancy by embryo transfer. The necessity of this approach, although intuitive, is not certain. POSTOPERATIVE TREATMENT

Consistent with the disease biology and again in a fashion analogous to epithelial ovarian cancer, most cases of fallopian tube cancer are managed with surgery and then chemotherapy. Understandably, the data regarding the response of tubal carcinoma to chemotherapy are scant. Still there is an impression that the need for chemotherapy is relatively greater in fallopian tube cancer than in the ovarian counterpart. Rosen et al43 compared early stage fallopian tube carcinomas with early stage ovarian cancers and noted the former to predict poorer survival. Consequently, it is recommended that early and advanced stage fallopian tube cancers be treated with adjuvant chemotherapy. Single agent chemotherapy has given disappointing results. 37 Combination platinum-based chemotherapy has been shown to be more effective.5·28·29 Response rates have been reported to range from 51 % to 71 %, with a median 5-year survival rate of 51 % to 86% in the treated group after surgery. The recommended treatment consists of cisplatinum 50 mg/ m 2, cytoxan 500 mg/m 2, and Adriamycin 50 mg/m2. The duration of therapy was typically 6 to 12 courses. Taxotere and other new agents are currently being used. Most of these studies on fallopian tube cancers are retrospective without a control group. Because the tumor is so rare, one institution sees few cases. This accounts for the majority of reports containing only 12 to 18 cases over long durations. Therefore, the management of tubal cancer requires an understanding of analogous but more prevalent cancers and a sense of ongoing evolving insight and options.

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PROGNOSIS

By convention, carcinoma of the fallopian tube presents in an early stage more often than ovarian cancer. The prognosis of an early stage disease is proportional to the involvement of the tubal wall. For example, 100% 5-year survival rate drops to 60% in the presence of wall invasion.38 A confounding factor in such survival statistics is the distinct possibility of understaging disease. That is, the disease appears confined to the tube but is occultly advanced. Other important prognostic factors are the size of the residual tumor at the termination of the surgery, nodal status, and type of treatment postoperatively.28• 29 In stage I disease, the depth of invasion of the tubal wall has been shown to be a significant prognostic factor. 37 When the tubal wall is involved, mortality increases to 50%. In Muntz et al's study,29 progression-free survival of 38 patients studied was 1.6 years for patients who received chemotherapy. Overall 5-year survival rate was 20% to 45% with the use of adjuvant chemotherapy. Other prognostic factors currently under investigation include p53 gene alteration, immunohistochemical staining for CA-125, K-ras codon 12, c-erb-2, and p53 gene expression. P gene alteration in primary carcinoma of the fallopian tube has been found in 31of52 cases (60%) regardless of stage and grade. 52 This finding correlated with histology of the tumor. Decreased survival was noted in the patients whose tumor contained the altered gene (RR= 6.8, 95% CI= 2.9-16.2).52 Residual disease that contained p53 genetic alteration also had a decreased survival. These data suggest that the p53 gene alteration might in the future serve as a marker for those patients who are at higher risk for recurrence and therefore appropriate candidates for adjuvant therapy.

FOLLOW-UP

The common time to first recurrence is within the first 2 years after diagnosis. Patients are often monitored every 3 months for the first few years, then at increasing intervals. CA-125 may be useful.

SALVAGE THERAPY

The pattern of relapse of fallopian tube carcinoma is similar to that of ovarian cancer. Mortality from recurrence is high, indeed likely absolute. Few reports describe meaningful responses to additional surgery and chemotherapy. Several studies have reported 30% 5-year survival rates in salvage therapy. 5•48 Paclitaxel (200 mg/m2 ) was noted to yield a complete response and resulted in a complete 18-month disease-free survival and normalization of the CA-125.8

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FUTURE It is hoped that better insight into fallopian tube cancer will be forthcoming by (1) inclusion of only patients who have had complete staging in calculation of survival rates; (2) molecular determination of prognostic factors; (3) uniform chemotherapy and large prospective chemotherapy regimen trials, with particular attention to the new drugs Taxotere and Topotecan; and (4) defining the role (or lack of a role) for radiation therapy.

SUMMARY Primary fallopian tube carcinoma represents less than 1 % of all gynecologic malignancies and is therefore one of the less common malignancies of the female genital tract. Fallopian tube carcinoma is rarely diagnosed preoperatively and is often mistaken for benign pelvic disease or ovarian cancer. Compared with ovarian carcinoma, fallopian tube cancer more often presents in early stage but seems to have a worse prognosis, stage for stage. Treatment consists of surgical debulking followed by chemotherapy, adjuvant or otherwise. New studies are needed to better delineate the clinical course, prognostic factors, and appropriate chemotherapy recommendations. References 1. Ajjirnakorn S, Bhamarapravati Y, Israngura N: Ultrasound appearance of fallopian tube carcinoma. J Clin Ultrasound 16:516, 1988 2. Ajjimakorn S, Bhamarapravati Y, Singhal S, et al: Transvaginal ultrasound and the diagnosis of fallopian tubal carcinoma. J Clin Ultrasound 19:116, 1991 3. Alvarado-Cabrero I, Navani S, Young R, et al: Tumors of the fimbriated end of the fallopian tube: A clinicopathologic analysis of 20 cases. Int J Gynecol Pathol 16:189-196, 1997 4. Barakat RR, Rubin SC, Saigo PE, et al: Second-look laparotomy in carcinoma of the fallopian tube. Obstet Gynecol 82:748, 1993 5. Barakat RR, Rubin SC, Saigo PE, et al: Cisplatin-based combination chemotherapy in ' carcinoma of the fallopian tube. Gynecol Oncol 42:156, 1991 6. Benedet JL, White GW, Fairey RN, et al: Adenocarcinoma of the fallopian tube: Experience with 41 patients. Obstet Gynecol 50:654, 1977 7. Cormia G, Maneo A, Gabriele A, et al: Treatment of fallopian tube carcinoma with cyclophosphamide, Adriamycin, and cisplatin. Am J Clin Oncol 20:143, 1997 8. Darnrong T, et al: Primary fallopian tube adenocarcinoma: Clinical complete response after salvage treatment with high dose paclitaxel. Gynecol Oncol 58:258-261, 1995 9. Daya D, Young RH, Scully RE: Endometrioid carcinoma of the fallopian tube resembling an adnexal tumor of probable wolffian origin: A report of six cases. Int J Gynecol Pathol 11:122, 1992 10. Denham JW, Maclennan KA: The management of primary carcinoma of the fallopian tube. Experience of 40 cases. Cancer 53:166, 1984 11. Deppe G, Bruckner HW, Cohen CJ: Combination chemotherapy for advanced carcinoma of the fallopian tube. Obstet Gynecol 56:530, 1980 12. Dodson MG, Ford JH Jr., Averette HE: Clinical aspects of fallopian tube carcinoma. Obstet Gynecol 36:935, 1970

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13. Eddy GL, Copeland LJ, Gershenson DM: Second-look laparotomy in fallopian tube carcinoma. Gynecol Oncol 19:182, 1984 14. Eddy GL, Copeland LJ, Gershenson DM, et al: Fallopian tube carcinoma. Obstet Gynecol 64:546, 1984 15. Finikiotis G, O'Shea RT, Sanders RR: An unusual hysteroscopic finding in association with primary carcinoma of the fallopian tube. Br J Hosp Med 44:124, 1990 16. Frick I: Cancer of the fallopian tube. In Gusberg SBaF II (ed): Corscaden's Gynecologic Cancer, ed 5. Baltimore, Williams and Wilkins, 1978, p 363 17. Harrison CR, Averette HE, Jarrell MA, et al: Carcinoma of the fallopian tube: Clinical management. Gynecol Oncol 32:357, 1989 18. Hertig A, Gore H: Tumors of the ovary and fallopian tube: Tumors of the female sex organs. Tumors of the ovary and fallopian tube. In Atlas of Tumor Pathology. Washington, DC, Armed Forces Institute of Pathology, 1960 19. Holleb Al: Cancer statistics. CA Cancer J Clin 37:2, 1987 20. Hu C, Taymor M, Hertig A: Primary carcinoma of the fallopian tube. Am J Obstet Gynecol 59:58-67, 1950 21. Jacoby AF, Fuller AF Jr, Thor AD, et al: Primary leiomyosarcoma of the fallopian tube. Gynecol Oncol 51:404, 1993 22. Jones 0: Primary carcinoma of the uterine tube. Obstet Gynecol 26:122-129, 1965 23. Karlan BY, Hoh C, Tse N, et al: Whole-body positron emission tomography with (fluorine-18)-2-deoxyglucose can detect metastatic carcinoma of the fallopian tube. Gynecol Oncol 49:383, 1993 24. Klein M, Rosen A, Lahousen M, et al: Lymphogenous metastasis in the primary carcinoma of the fallopian tube. Gynecol Oncol 55:336, 1994 25. Klein M, Rosen A, Lahousen M, et al: Radical lymphadenectomy in the primary carcinoma of the fallopian tube. Arch Gynecol Obstet 253:21, 1993 25a. Kurjak A, Kupesic S, Ilijas M, et al: Preoperative diagnosis of primary fallopian tube carcinoma. Gynecol Oncol 68:29-34, 1998 26. Lacy MQ, Hartmann LC, Keeney GL, et al: c-erbB-2 and p53 expression in fallopian tube carcinoma. Cancer 75:2891, 1995 27. Mizuuchi H, Mori Y, Sato K, et al: High incidence of point mutation in K-ras codon 12 in carcinoma of the fallopian tube. Cancer 76:86-90, 1995 28. Morris M, Gershenson DM, Burke TW, et al: Treatment of fallopian tube carcinoma with cisplatin, doxorubicin, and cyclophosphamide. Obstet Gynecol 76:1020, 1990 29. Muntz HG, Tarraza HM, Goff BA, et al: Combination chemotherapy in advanced adenocarcinoma of the fallopian tube. Gynecol Oncol 40:268, 1991 30. Navani SS, Alvarado-Cabrero I, Young RH, et al: Endometrioid carcinoma of the fallopian tube: A clinicopathologic analysis of 26 cases. Gynecol Oncol 63:371, 1996 31. Niloff JM, Klug TL, Schaetzl E, et al: Elevation of serum CA125 in carcinomas of the fallopian tube, endometrium, and endocervix. Am J Obstet Gynecol 148:1057, 1984 32. Nurnberger L: Die gutartigen und bosartugen Neubildungen der Tuben. In Stoeckel W (ed): Handbuch der Gynakologie. Miinchen, Bergmann, 1932, p 574 33. Orthmann E: Ein primares Carcinoma Papillare Tubae Dextrae, Verbunden mit Ovarialabszess. Zentralbl Gynakol 10:816, 1886 34. Orthmann E: Uber Carcinoma Tubae. Zeitschrift for Geburtshilfe und Gynakologie 15:212, 1888 35. Patton GW Jr, Goldstein DP: Gestational choriocarcinoma of the tube and ovary. Surg Gynecol Obstet 137:608, 1973 36. Perry EP, Smart JG: Hydrops tubae profluens: Not a genitourinary fistula but a diagnosis to be missed. Br J Urol 66:547, 1990 37. Peters WA III, Andersen WA, Hopkins MP, et al: Prognostic features of carcinoma of the fallopian tube. Obstet Gynecol 71:757, 1988 38. 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 28:7-11, 1989 39. Podratz KC, Podczaski ES, Gaffey TA, et al: Primary carcinoma of the fallopian tube. Am J Obstet Gynecol 154:1319, 1986 40. Puls LE, Davey DD, DePriest PD, et al: Immunohistochemical staining for CA-125 in fallopian tube carcinomas. Gynecol Oncol 48:360, 1993

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41. Roberts JA, Lifshitz S: Primary adenocarcinoma of the fallopian tube. Gynecol Oncol 13:301, 1982 42. Rose PG, Piver MS, Tsukada Y: Fallopian tube cancer. The Roswell Park experience. Cancer 66:2661, 1990 43. Rosen AC, Sevelda P, Klein M, et al: A comparative analysis of management and prognosis in stage I and II fallopian tube carcinoma and epithelial ovarian cancer. Br J Cancer 69:577, 1994 44. Schink JC, Lurain JR: Rare gynecologic malignancies. Curr Opin Obstet Gynecol 3:7890, 1991 45. Scully R, Young R, Clement P: Tumors of the ovary, maldeveloped gonads, fallopian tube and broad ligament. In Atlas of Tumor Pathology. Washington, DC, Armed Forces Institute of Pathology, in press 46. Sedlis A: Carcinoma of the fallopian tube. Surg Clin North Am 58:121, 1978 47. Tamimi HK, Figge DC: Adenocarcinoma of the uterine tube: Potential for lymph node metastases. Am JObstet Gynecol 141:132, 1981 48. Tresukosol D, Kudelka A, Edwards C, et al: Primary fallopian tube adenocarcinoma: Clinical complete response after salvage treatment with high-dose paclitaxel. Gynecol Oncol 58:258, 1995 49. Weiss PD, Mac Dougall MK, Reagan JW, et al: Primary adenosquamous carcinoma of the fallopian tube. Obstet Gynecol 55:88S-89S, 1980 50. Yoonessi M: Carcinoma of the fallopian tube. Obstet Gynecol Surv 34:257-270, 1979 51. Yoonessi M, Leberer JP, Crickard K: Primary fallopian tube carcinoma: Treatment and spread pattern. J Surg Oncol 38:97-100, 1988 52. Zheng W, Sung CJ, Cao P, et al: Early occurrence and prognostic significance of p53 alteration in primary carcinoma of the fallopian tube. Gynecol Oncol 64:38-48, 1997

Address reprint requests to Najmosama Nikrui, MD Division of Gynecologic Oncology WACC2 Massachusetts General Hospital Fruit Street Boston, MA 02114

APPENDIX A

The staging of fallopian tube carcinoma follows: Stage 0 Stage I Stage Ia Stage lb Stage le Stage II Stage Ila Stage Ilb Stage Ile Stage III

Stage Illa Stage Illb Stage Ille Stage IV

carcinoma in situ (limited to tubal mucosa) growth is limited to the fallopian tube growth is limited to one tube with extension into the submucosa and/ or muscularis but not penetrating the serosal surface; no ascites growth is limited to both tubes with extension to submucosa and/ or muscularis but not penetrating the serosal surface; no ascites. tumor either stage Ia or lb but with extension through or onto the tubal serosa or with ascites present containing malignant cells or with positive peritoneal washing growth involving one or both fallopian tubes with pelvic extension extension or metastasis to the uterus and/ or ovaries extension to other pelvic tissues tumor either stage Ila or Ilb but with extension through or onto the tubal serosa, or with ascites present containing malignant cells or with positive peritoneal washing tumor involves one or both fallopian tubes with peritoneal implants outside of the pelvis and/ or positive retroperitoneal or inguinal lymph nodes; superficial liver metastasis; tumor limited to the pelvis but with histologically proven malignant extension to the small bowel or omentum tumor is grossly limited to true pelvis with negative nodes and with histologically confirmed microscopic seeding of the abdominal peritoneal surface tumor involving one or both tubes with histologically confirmed implants of abdominal peritoneal surfaces, not exceeding 2 cm in diameter; lymph nodes are negative abdominal implants more than 2 cm in diameter and/ or positive retroperitoneal or inguinal nodes growth involving one or both tubes with distant metastases; if pleural effusion is present there must be positive cytology to be stage IV; parenchymal liver metastases equals stage IV

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