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Background
This rare cancer affecting the fallopian tubes must be properly diagnosed by the surgical pathologist. It is important to exclude primary tumors arising from the ovary, uterus, or metastatic tumors from other organs.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Very rare, rarest of all primary gynecological malignancies
DISEASE ASSOCIATIONS CHARACTERIZATION BRCA1 AND BRCA2 MUTATIONS
*Departments of Pathology daggerExperimental Oncology-Medical Genetics Service section signGynecological Unit parallelExperimental Oncology, Istituto Nazionale Tumori, FIRC Institute of Molecular Oncology Foundation, Milan, Italy double daggerDepartment of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy.
The identification of germ-line mutations in 2 genes (BRCA1 and BRCA2) responsible for the majority of hereditary ovarian cancers has led an increasing number of women carriers of these mutations to undergo prophylactic oophorectomy (PO) to reduce their risk of subsequent ovarian carcinoma. A large number of unexpected, clinically occult neoplasms are thus being discovered.
Up to December 2004, the Medical Genetics Service of the National Cancer Institute in Milan, Italy, has tested 756 probands from breast and/or ovarian cancer families for BRCA1 and BRCA2 germ-line mutations. Molecular screening of family members led to the identification of 344 female carriers of BRCA1 (239) or BRCA2 (105) germ-line mutations. Of the 186 potentially eligible women (37 of whom had tested positive for BRCA1 and 13 for BRCA2 mutation), 50 (26.8%) chose to undergo PO. Six clinically occult primary gynecologic malignancies (2 stage IIIC serous carcinomas of the ovary, 3 in situ serous carcinomas of the fallopian tube, and 1 stage IIB invasive serous carcinoma of the fallopian tube) and 1 occult ovarian metastasis from breast carcinoma were identified in the PO specimens of 7 women (all BRCA1 mutated). Four of the patients with occult primary gynecologic cancers are alive without disease 129, 87, 38, and 7 months after PO, respectively. One of the 2 patients with primary ovarian cancer and the single patient with tubal invasive carcinoma are alive with recurrent disease 83 and 20 months after PO, respectively. In addition, one of the patients whose PO specimen did not show any malignancy presented with stage IIIC tubal carcinoma 77 months after PO.
The relatively high number of tubal neoplasms found at PO in this group of patients underlines the linkage between mutation and the risk of developing tubal cancer, and stresses the need to include removal of the entire tubes at the time of PO and of thoroughly evaluating the specimens at the microscopic level.
The upstaging of all 3 invasive carcinomas after staging surgery, and the late recurrence and persistence of 2 of them despite treatment indicate that small size of the tumors should not preclude therapy.UTERINE CARCINOMA
- Endometrioid Carcinoma Simultaneously Involving the Uterus and the Fallopian Tube: A Clinicopathologic Study of 13 Cases.
Culton LK, Deavers MT, Silva EG, Liu J, Malpica A.
*Department of Pathology, The University of Texas Medical School at Houston, Houston, TX daggerDepartment of Pathology and Laboratory Medicine, M.D. Anderson Cancer Center, The University of Texas, Houston, TX.
Am J Surg Pathol. 2006 Jul;30(7):844-849. Abstract quote
Although the simultaneous presentation of endometrial and ovarian carcinomas of the endometrioid type is well described, little is known about a similar phenomenon involving the endometrium and fallopian tube (FT).
We present the clinicopathologic features of 13 such cases seen in the Department of Pathology at The University of Texas M.D. Anderson Cancer Center over an 8 year period (1995 to 2002). FT tumors that could have represented luminal extension of the endometrial carcinoma or that represented an unequivocal metastasis to the FT were excluded. The patients' ages ranged from 34 to 77 years (median 54). The most common symptom was abnormal uterine/vaginal bleeding (11) and all of the patients were considered overweight or obese (mean body mass index was 41). The size of the endometrial carcinomas ranged from 0.3 to 8 cm. According to the FIGO grading of the endometrial endometrioid carcinomas, the cases were distributed as follows: Grade 1 (3) and Grade 2 (10). In 2 cases, there were also small areas of other histologic types, papillary serous carcinoma (1 case), and papillary endometrial carcinoma of intermediate grade (another case). The size of the fallopian tube carcinomas ranged from 0.2 to 17.5 cm. Seven of these tumors were located in the distal/fimbriated end of the FT. There was bilateral involvement in 2 cases. Three of the FT tumors were in situ. The grades of the fallopian tube carcinomas were as follows: Grade 1 (2), Grade 2 (6), and Grade 3 (2). In situ components were seen in all cases. One fallopian tube carcinoma was mixed with serous carcinoma. In 4 cases, there was also an endometrioid carcinoma involving the ovary, all of them with an intact ovarian capsule.
Patients were treated as follows: total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) (4), TAH/BSO/chemotherapy (chemo) (4), TAH/BSO/radiation (3), and TAH/BSO/chemo/radiation (2). Follow-up ranging from 6 to 54 months was available in 10 patients: 1 patient died of disease (at 38 mo), 1 patient is alive with disease (at 9 mo), 7 patients have no evidence of disease (6 to 54 mo), and 1 patient died of metastatic endometrial carcinoma (at 9 mo). Simultaneous endometrioid carcinomas of the uterus and FT are unusual and occur primarily in obese perimenopausal women.
The tumors are predominantly well or moderately differentiated with dissimilar endometrial and FT grades. The FT carcinoma is usually unilateral and located at the distal end of the tube.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC
Imaging of fallopian tube tumors.Slanetz PJ, Whitman GJ, Halpern EF, Hall DA, McCarthy KA, Simeone JF.
Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
AJR Am J Roentgenol 1997 Nov;169(5):1321-4 Abstract quote OBJECTIVE: The purposes of this study were to investigate the imaging findings in patients with primary fallopian tube neoplasms and to determine whether specific imaging features favor the preoperative diagnosis of fallopian tube tumors (FTT).
MATERIALS AND METHODS: Computerized search of medical records from 1984 to 1994 identified 20 patients with a discharge diagnosis of primary fallopian tube carcinoma. Medical records, imaging studies, and pathology findings were reviewed. Eleven patients had available preoperative imaging.
RESULTS: Seventeen of 20 patients with primary FTT had unilateral disease. Of these 17, preoperative imaging was available in nine, showing four solid adnexal masses, four complex cystic adnexal masses, and one normal adnexa. The preoperative imaging of these nine patients included six sonographic and five CT studies. Three patients with primary FTT had bilateral tumors, and preoperative imaging was available for two patients: Two sonographic studies and one CT study showed one complex cystic adnexal mass and three normal adnexa.
CONCLUSION: Primary FTT commonly presents as an adnexal mass on preoperative imaging and mimics other pelvic malignancies, especially ovarian carcinoma. Making a specific preoperative diagnosis is difficult; however, because primary FTT is unlikely to be confused with a benign process, delay in diagnosis is rare.
Preoperative diagnosis of the primary fallopian tube carcinoma by three-dimensional static and power Doppler sonography.Kurjak A, Kupesic S, Jacobs I.
Department of Obstetrics and Gynecology, Medical School, University of Zagreb, Sveti Duh Hospital, Croatia.
Ultrasound Obstet Gynecol 2000 Mar;15(3):246-51 Abstract quote OBJECTIVE: To investigate whether three-dimensional static and power Doppler ultrasound improves the diagnosis of primary Fallopian tube carcinoma.
METHODS: During a 2-year period five cases of primary Fallopian tube carcinoma were selected from a cohort of 520 patients with a previous scan suggestive of an adnexal tumor.
RESULTS: Tubal malignancy occurred in patients between 49 and 64 years, with presenting symptoms such as pain, vaginal bleeding and leukorrhea. CA 125 was elevated in three cases of tubal carcinoma with stages II and III, while in two patients with stage I, CA 125 was within the normal limits. Two-dimensional ultrasound demonstrated sausage shaped cystic masses with papillary projections in two patients and a complex adnexal mass in one patient. Three-dimensional ultrasound revealed sausage shaped cystic and/or complex masses with papillary projections in all five cases of tubal malignancy. In one patient preoperative 3-D ultrasound correctly predicted bilateral tumors, while 2-D transvaginal sonography found only unilateral changes. Additional 3-D power Doppler examination depicted vascular geometry typical for malignant tumor vessels such as arteriovenous shunts, microaneurysms, tumoral lakes, blind ends and dichotomous branching in each of the cases with Fallopian tube carcinoma.
CONCLUSIONS: Three-dimensional ultrasound allows precise depiction of tubal wall irregularities such as papillary protrusions and pseudosepta. Improved understanding of anatomical relationships may aid in distinguishing ovarian from tubal pathology. Multiple sections of the tubal sausage like structures enable determination of local tumor spread and capsule infiltration. Study of the vascular architecture in cases of Fallopian tube malignancy is further enhanced using 3-D power Doppler imaging.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS FIMBRIAL TUMORS
Tumors of the fimbriated end of the fallopian tube: a clinicopathologic analysis of 20 cases, including nine carcinomas.Alvarado-Cabrero I, Navani SS, Young RH, Scully RE.
Massachusetts General Hospital, Department of Pathology, Harvard Medical School, Boston 02114, USA.
Int J Gynecol Pathol 1997 Jul;16(3):189-96 Abstract quote Twenty tumors that were primary in the tubal fimbriae are reported. They were found in patients aged 17 to 83 (average 57) years. All were of mullerian type. Nine tumors were benign (eight adenofibromas, one cystadenoma), of which seven were serous and two, endometrioid. Two tumors were borderline, a serous papillary cystic tumor of borderline malignancy and an endometrioid adenofibroma of borderline malignancy. Nine tumors were carcinomas, of which four were serous, three endometrioid, and two undifferentiated.
Follow-up information was available for six patients with carcinoma. One with serous carcinoma was well at 1 year; a second had ascites with malignant cytologic features nine years postoperatively and is currently on chemotherapy. One patient with endometrioid carcinoma was alive without disease after 8 years, and the other died of tumor at 6.5 years. One patient with undifferentiated carcinoma was alive without disease at 5 years and the other died of disease at eight months. The occurrence of fallopian tube tumors that arise in the fimbriae has received scanty attention in the literature. A fimbrial origin for the tumors is often overlooked initially. Carcinomas confined to the fimbriae cannot be adequately staged according to the current staging system of the International Federation of Gynecology and Obstetrics.
It is proposed that they be placed in a new category, Stage I(F), because the tumor cells are exposed directly to the peritoneal cavity even though they do not invade the tubal wall. Although experience is limited it appears that they may have a worse prognosis than Stage I tubal tumors that are nonfimbrial.
Anaplastic carcinoma of the fimbriated end of the fallopian tube as an incidental finding.Gerson R, Serrano A, Dolengevich H, De Leon B, Villalobos A, Kavanagh JJ, Kudelka AP.
Chemotherapy Unit, Hospital General de Mexico.
Eur J Gynaecol Oncol 1998;19(5):431-3 Abstract quote Carcinoma of the fallopian tube is an uncommon gynecologic tumor that is usually diagnosed in an advanced stage. The majority are tubal in origin, and rarely arise in the fimbriae. It appears that the latter may have a worse prognosis than the equivalent stage of tubal tumors that do not arise from fimbriae.
We present a case of a 53-year-old white woman with FIGO stage 1 primary anaplastic carcinoma of the fimbriated end of the fallopian tube that was incidentally found in a specimen resected during a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The patient underwent surgery because of findings of severe cervical dysplasia, atypia and dyskaryosis on a routine Papanicolau smear. Postoperative recovery was uneventful, and follow-up abdominal and pelvic CT scans showed no evidence of disease. However, because of the poor degree of differentiation, focal serosal infiltration and fimbrial end tube site of the carcinoma she was considered to have a high risk of recurrence.
Thus, it was recommended that she undergo adjuvant chemotherapy with cyclophosphamide and carboplatin. Eighteen months after diagnosis, the patient is alive and well with no evidence of disease.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Histologic patterns of primary malignant tumors of the fallopian tube.Schmid C, Boeri R, Berti E, Contini V, Pasquinucci C.
Department of Pathology, S. Carlo Borromeo Hospital, Milan.
Pathologica 1994 Dec;86(6):617-22 Abstract quote From 1978 through 1993 four patients underwent surgical treatment of primary fallopian tube rumors. Mean age was 62.5 years. A different histologic pattern was found in each cases: transitional, endometrioid, serous papillary and malignant mixed mesodermal tumor.
Prognostic significance of histologic patterns is underlined together with grade and stage; all our cases were included in stage IA. Surgical treatment was, in all cases, hysterectomy with bilateral salpingo-oophorectomy; in two cases an adjunctive chemotherapy followed. A second look was performed in two cases.
All patients are alive and free of disease with a follow-up varying from 15 to 84 months.
INTRAEPITHELIAL CARCINOMA
- Kindelberger DW,
- Lee Y,
- Miron A,
- Hirsch MS,
- Feltmate C,
- Medeiros F,
- Callahan MJ,
- Garner EO,
- Gordon RW,
- Birch C,
- Berkowitz RS,
- Muto MG,
- Crum CP.
*Division of Women's and Perinatal Pathology, Department of Pathology daggerBrigham and Women's Hospital, Division of Cancer Biology, Dana Farber Cancer Institute double daggerDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA.
Proposed origins of pelvic serous carcinoma include the ovary, fallopian tube, and peritoneum. Prophylactic salpingo-oophorectomies in BRCA+ women have recently identified the fimbria as a site of origin for early serous carcinoma (tubal intraepithelial carcinoma or TIC).
We explored the relationship of TIC to pelvic serous carcinomas in consecutive cases with complete adnexal exam (SEE-FIM protocol). Cases positive (group A) or negative (group B) for endosalpinx (including fimbria) involvement, were subclassified as tubal, ovarian, or primary peritoneal in origin. Coexisting TIC was recorded in group A when present and p53 mutation status was determined in 5 cases. Of 55 evaluable cases, 41 (75%) were in group A; including tubal (n=5), peritoneal (n=6), and ovarian (n=30) carcinomas. Foci of TIC were identified in 5 of 5, 4 of 6, and 20 of 30, respectively. Ninety-three percent of TICs involved the fimbriae. Five of 5 TICs and concurrent ovarian carcinomas contained identical p53 mutations. Thirteen of 14 cases in group B were classified as primary ovarian carcinomas, 10 with features supporting an origin in the ovary.
Overall, 71% and 48% of "ovarian" serous carcinomas had endosalpinx involvement or TIC. TIC coexists with all forms of pelvic serous carcinoma and is a plausible origin for many of these tumors.
Further studies are needed to elucidate the etiologic significance of TIC in pelvic serous carcinoma, reevaluate the criteria for tubal, peritoneal, and ovarian serous carcinoma, and define the role of the distal tube in pelvic serous carcinogenesis.
- Advances in the Recognition of Tubal Intraepithelial Carcinoma: Applications to Cancer Screening and the Pathogenesis of Ovarian Cancer.
Lee Y, Medeiros F, Kindelberger D, Callahan MJ, Muto MG, Crum CP.
From the Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Boston.
Adv Anat Pathol. 2006 Jan;13(1):1-7 Abstract quote.
Prophylactic salpingo-oophorectomies from women with BRCA mutations (BRCA+) have identified the tube as a frequent site of early pelvic serous carcinoma (tubal intraepithelial carcinoma [TIC]).
These observations have implications for both the early recognition of pelvic serous carcinoma in susceptible women and determining the ultimate site of origin for pelvic serous carcinomas. Moreover, the unique pathology of TIC has shifted attention from the more exuberant proliferations mentioned in prior studies to a spectrum of neoplastic atypias that can be morphologically subtle.
This review addresses a multitude of epithelial changes; benign, malignant, and an intriguing third group, which we term "p53 signatures," is found in benign, nonciliated epithelium and stain intensely positive for p53. Understanding all 3 is important for the proper management of women undergoing prophylactic salpingo-oophorectomy and possibly formulating an integrated model for the pathogenesis of serous carcinoma in the reproductive tract.
A protocol for sectioning and extensively examining the fimbriated end (SEE-FIM), and its rationale, is described.VARIANTS ENDOMETRIOID
Endometrioid carcinoma of the fallopian tube resembling an adnexal tumor of probable wolffian origin: a report of six cases.Daya D, Young RH, Scully RE.
Department of Pathology, Henderson General Division, Hamilton Civic Hospitals, Ontario, Canada
Int J Gynecol Pathol 1992;11(2):122-30 Abstract quote Six adenocarcinomas of the fallopian tube that resembled the female adnexal tumor of probable wolffian origin are described. The tumors, which occurred in patients from 38 to 66 (average 55) years of age, typically formed intraluminal masses. One was an incidental finding on microscopic examination.
On microscopic examination, the tumors were characterized by a predominant pattern of small, closely packed cells punctured by numerous glandular spaces, which were typically small but occasionally were cystically dilated. Many of the glands contained a dense colloid-like secretion that was positive with the periodic acid-Schiff stain. Small amounts of intracellular mucin were present in all cases. In the solid areas of three cases, spindle cells that focally formed concentric whorls were present. In all cases, small numbers of tubular glands typical of endometrioid adenocarcinoma were identified. The cytologic atypia and mitotic activity of the tumors were variable, but they exceeded that usually seen in wolffian duct tumors.
The evidence indicates that this neoplasm represents an unusual form of endometrioid adenocarcinoma. It is important that it is distinguished from a tumor of wolffian duct origin.
Endometrioid carcinoma of the fallopian tube: a clinicopathologic analysis of 26 cases.Navani SS, Alvarado-Cabrero I, Young RH, Scully RE.
James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Department of Pathology, Harvard Medical School, Boston 02114, USA.
Gynecol Oncol 1996 Dec;63(3):371-8 Abstract quote Twenty-six endometrioid adenocarcinomas of the fallopian tube that occurred in patients 37 to 85 (average 57) years of age are described. Most of the patients presented with symptoms related to a pelvic mass but nine tumors were incidental findings at the time of operation.
All the neoplasms were unilateral. Eighteen tumors were Stage I, four Stage II, two Stage III, and two Stage IV. Two tumors were primary in the fimbriated end of the tube. On gross examination the typical appearance was that of a fusiform swelling of the tube which contained a predominantly intraluminal neoplasm up to 6 cm in greatest dimension. Six separate tumors were present in one case. Microscopic examination revealed that 14 tumors were typical endometrioid carcinomas with foci of squamous differentiation in 7 cases, spindle cells interpreted as epithelial cells in 4 cases, and a trabecular pattern in 1 case. One of these 14 tumors was composed almost exclusively of oxyphilic cells lining glands. Twelve tumors were characterized by a mostly solid proliferation of small closely packed cells punctured by numerous glands that varied from small to cystic, imparting a superficial resemblance to an adnexal tumor of probable Wolffian origin. Benign stromal osseous metaplasia was noted in two Wolffian-like and one typical endometrioid carcinoma.
Five tumors were grade 1, 11 were grade 2, and 10 were grade 3. Follow-up information was available for 18 patients. Five with noninvasive Stage Ia-0 tumors (intraluminal, noninvasive masses) were without disease at 2 to 5 (average 3) years postoperatively. Two of three patients with Stage Ia1 tumors were alive without recurrence at 2 and 3 years postoperatively. One of two patients with Stage Ia2 disease for whom follow-up is available was alive without disease 1.5 years postoperatively and one died of other causes 11.2 years postoperatively. One patient with Stage Ic disease had recurrence of tumor at 2 years; four with Stage II disease were without disease at 1.5, 2, 3, and 8 years; one with Stage IIIa disease died with disease at 4 years; and one with Stage IV disease died with disease after 5 years. Two additional patients had fimbrial tumors [Stage I(f)]; one of them died with disease at 7 years, and the other was alive without disease at 8 years.
This small series indicates that endometrioid carcinomas of the fallopian tube are characteristically noninvasive or only superficially invasive and have a generally favorable prognosis. This subtype of tubal carcinoma should be distinguished from the more common neoplasms of serous type and from those of various other cell types.
GLASSY CELL
Glassy cell carcinoma of the fallopian tube. A case report.Herbold DR, Axelrod JH, Bobowski SJ, Freel JH.
Department of Pathology, St. Louis University Medical Center, Missouri.
Int J Gynecol Pathol 1988;7(4):384-90 Abstract quote A 31-year-old woman, 10 weeks postpartum, presented with a right adnexal mass. The neoplasm was found to originate from the right fallopian tube and a right salpingoophorectomy was performed.
Pathological examination found an adenosquamous carcinoma with features characteristic of a glassy cell carcinoma as described in the uterine cervix. The finding of this neoplasm in the fallopian tube suggests that it may be a tumor type common to the entire mullerian system.
MALIGNANT MIXED MULLERIAN TUMOR
Malignant mixed Mullerian tumor of the fallopian tube: report of two cases and review of literature.Imachi M, Tsukamoto N, Shigematsu T, Watanabe T, Uehira K, Amada S, Umezu T, Nakano H.
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Gynecol Oncol 1992 Oct;47(1):114-24 Abstract quote Malignant mixed Mullerian tumors are usually found in the endometrium, vagina, cervix, and ovary. It is extremely rare for this tumor to arise in the fallopian tube, and to date only 37 tubal cases have been reported.
We recently experienced 2 such cases. The clinical features, pathologic findings, diagnosis, therapy, and outcome of these 39 cases were reviewed. The clinical features and diagnosis were similar to those of primary carcinoma of the fallopian tube. Correct preoperative diagnosis was difficult. Histologically, 18 patients had homologous elements and 21 had heterologous elements in the sarcomatous components. The most common type of heterologous element was cartilage, followed by striated muscle and bone. The clinical stage (FIGO staging of ovarian carcinoma) was stage I in 15 cases, stage II in 11 cases, stage III in 8 cases, stage IV in 3 cases, and unknown in 2 cases. In all the patients except 1, the tumor was surgically removed. Postoperatively, radiotherapy was given to 9 patients, chemotherapy to 9 patients, and both to 2 patients.
Sixteen patients died of the disease, after a mean period of 16.1 months. Of the 15 stage I patients, 10 survived more than 12 months. The most important prognostic factor was spread of the tumor at diagnosis.
SQUAMOUS CELL CARCINOMA
Primary squamous cell carcinoma of the ovary. Report of 37 cases.Pins MR, Young RH, Daly WJ, Scully RE.
James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, USA.
Am J Surg Pathol 1996 Jul;20(7):823-33 Abstract quote A total of 37 cases of ovarian primary squamous cell carcinoma (SCC)-19 associated with a dermoid cyst (SCCD), seven associated with endometriosis (SCCE), and 11 pure (SCCP)-are described.
The last 18 cases belong within the new World Health Organization category of SCC in the surface epithelial-stromal category. The 19 patients with SCCD were 21-75 (mean, 52) years old; three of the carcinomas were in situ and seven, six, and three tumors were stages I, II, and III, respectively. The tumors and associated dermoid cysts were 6-35 cm in greatest dimension, usually forming mural nodules with intracavitary protrusion and focal necrosis and hemorrhage; two, seven, and seven tumors were grades 1, 2, and 3, respectively. SCCD was focally associated with a columnar epithelial cyst lining in 13 cases, suggesting an origin therein. One patient with stage I, grade 1 SCCD also had squamous cell carcinoma in situ (CIS) of the cervix. The seven patients with SCCE were 29-70 (mean, 49) years old, and one, three, one, and two tumors were stages I, II, III, and IV, respectively; all of the tumors were grade 3. One was associated with squamous cell carcinoma in situ of the cervix. The 11 patients with SCCP were 27-73 (mean, 56) years old, and one, four, five, and one tumors were stages I, II, III, and IV, respectively.
The tumors were 6-26 cm in greatest diameter, usually solid with focal necrosis; one and 10 tumors were grades 2 and 3, respectively. Three patients with SCCP also had cervical squamous cell carcinoma in situ. The patients with SCCE had a poorer overall survival than those with SCCD. Five of the six patients with SCCE for whom adequate follow-up information was available died of their disease (mean survival, 5 months); also, in all five cases of SCCE reported in the literature, the patients died of their disease (mean survival, 4 months). The stage of the tumor and its grade correlated best with overall survival for all three types of SCC.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES OVARIAN CANCER
Primary carcinoma of the fallopian tube. A report of 19 cases with literature review.Schneider C, Wight E, Perucchini D, Haller U, Fink D.
Department of Obstetrics and Gynecology, University Hospital of Zurich, Switzerland.
Eur J Gynaecol Oncol 2000;21(6):578-82 Abstract quote Primary carcinoma of the fallopian tube is the rarest cancer of the female genital tract with an incidence of 0.5% of all gynecologic tumors. Since the first report in 1847 about 1,500 cases have been published. Due to similarity of the clinical presentation the staging and therapeutic management have been adapted to that of ovarian cancer.
We retrospectively evaluated all the 19 patients who had been diagnosed with primary carcinoma of the fallopian tube at the Department of Obstetrics and Gynecology of the University of Zurich between 1977 and 1998. All lesions were staged according to the rules of FIGO adopted in 1991. At the time of diagnosis the median age was 62 (46-87) years. Twelve (63%) women revealed FIGO stage III-IV, whereas four (21%) and three (16%) patients were diagnosed in stage I and stage II, respectively. Eight (42%) women were nullipara. Histology showed serous-papillary carcinoma, in ten (53%) cases. The 5-year survival rate was 22% for all FIGO stages and 80% for stage I. None of the patients with stage III and IV survived 5 years. Ovarian cancer and primary carcinoma of the fallopian tube are similar in many aspects.
Both carcinomas have a similar age distribution, show an increase among nulliparous women, are often of serous papillary histology, have a poor prognosis with stage and residual tumor size as important prognostic factors, and respond initially well to platinum-based chemotherapy. Nevertheless, there appears to be a difference between the two diseases: primary carcinoma of the fallopian tube is more often diagnosed in an earlier stage. This many be due to lower abdominal pain resulting from tubal dilatation and to abnormal bloody-watery discharge.
PSEUDOCARCINOMATOUS HYPERPLASIA
Pseudocarcinomatous hyperplasia of the fallopian tube associated with salpingitis. A report of 14 cases.Cheung AN, Young RH, Scully RE.
Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Am J Surg Pathol 1994 Nov;18(11):1125-30 Abstract quote We describe 14 cases of pseudocarcinomatous changes in the fallopian tube characterized by florid epithelial hyperplasia and in half the cases mesothelial hyperplasia and associated with chronic salpingitis. The patients' ages ranged from 17 to 40 years. Seven had clinical evidence of pelvic inflammatory disease. Tubal enlargement or thickening were observed in 12 cases and pyosalpinx, tubo-ovarian abscesses, or hydrosalpinx, in six cases. A
ll cases showed no gross evidence of tumor. The reactive atypical hyperplasia mimicked carcinoma microscopically because of a cribriform pattern, penetration of the tubal wall by hyperplastic epithelium, florid mesothelial hyperplasia, or a combination of these findings; epithelial papillae were present in the lymphatics in two cases. In five cases, an erroneous microscopic diagnosis of carcinoma had been made or seriously entertained initially, and one patient underwent a radical hysterectomy as a result.
The typically young age of the patients, absence of a gross tumor, presence of severe chronic inflammation, lack of solid epithelial proliferation, mildness of nuclear atypia, and paucity of mitotic figures facilitated the differential diagnosis. Nine patients for whom follow-up information was available had no recurrence of tubal disease.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS
Fallopian tube carcinoma: a clinicopathological study of 17 cases.King A, Seraj IM, Thrasher T, Slater J, Wagner RJ.
Department of Obstetrics and Gynecology, Loma Linda University Medical Center, California 92354.
Gynecol Oncol 1989 Jun;33(3):351-5 Abstract quote From 1969 through 1986, 17 patients with primary adenocarcinoma 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 carcinosarcoma, 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 5-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 define 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.
Primary carcinoma of the fallopian tube--a retrospective analysis of 115 patients. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.Rosen A, Klein M, Lahousen M, Graf AH, Rainer A, Vavra N.
Department of Obstetrics and Gynecology, SMZ-Ost Vienna, Austria.
Br J Cancer 1993 Sep;68(3):605-9 Abstract quote Incidence and prognostic factors of primary carcinoma of the Fallopian tube were studied in a retrospective multi-centre analysis of 115 women during the period 1980 to 1990. Data of 28 departments (university as well as general hospitals) were included in the present study which was designed to evaluate the current diagnosis and treatment of carcinoma of the Fallopian tube in Austria, and to compare the results with those from the literature.
Stages were classified according to the modified FIGO-system for ovarian cancer; grading followed the criteria of Hu et al. (1950). The mean age of the patients was 62.5 years. Forty-seven (40.9%) tumours were found to be in stage I, 20 (17.4%) in stage II, 34 (29.6%) in stage III, and 14 (12.1%) in stage IV. In 82 patients, the tumour could be completely removed. The surgical method applied in 95 cases was removal of the uterus, the adnexa, and/or the omentum, or lymph nodes. Postoperatively patients underwent adjuvant therapy which was either irradiation (n = 40; 34.8%), or chemotherapy (n = 49; 42.6%); 26 women (22.6%) had no therapy after operation.
The 5-year survival rate for all stages was 36.5%. In stages I and II the 5-year survival was 50.8% compared to 13.6% in stages III and IV. FIGO-stage I and II and a residual tumour less than 2 cm in advanced disease had a prognostically favourable impact, which was proven in univariate as well as multivariate analysis.
Primary carcinoma of the fallopian tube. A retrospective analysis of 47 patients.Cormio G, Maneo A, Gabriele A, Rota SM, Lissoni A, Zanetta G.
III Department Obstetrics and Gynecology, University of Milan, Ospedale S. Gerardo, Monza, Italy.
Ann Oncol 1996 Mar;7(3):271-5 Abstract quote BACKGROUND: Fallopian tube carcinoma is a rare disease, and few data about prognostic factors are available in the literature.
PATIENTS AND METHODS: The medical charts of 47 patients with primary carcinoma of the fallopian tube treated at our institution between 1982 and 1994 were reviewed. Age, stage, histologic grade, residual disease after surgery, peritoneal cytology and lymph-node involvement were evaluated for their prognostic impact in a univariate analysis.
RESULTS: The mean age of the patients was 57.5 years and 19 of them (40%) had early-stage disease. Poorly differentiated tumors were diagnosed in 64% of the patients. Eleven of 20 patients (55%) submitted to surgical evaluation of lymph nodes had retroperitoneal involvement. Thirty-three patients received CAP chemotherapy following surgery, and the overall clinical response rate was 80%. Sixteen patients (34%) had recurrences within 8 to 50 months from diagnosis. Twenty patients (42.6%) are alive without disease, one patient is alive with tumor, and 26 patients (55.3%) died of the disease. The median survival for the group as a whole was 44 months, and the actuarial 5-year survival was 29%. In univariate analysis stage (I + II vs. III + IV), grade (G1 + G2 vs. G3) residual disease after surgery (less than 2 cm vs. greater than 2 cm). peritoneal cytology (negative vs. positive) and lymph-node metastases were all factors significantly affecting survival.
CONCLUSIONS: Aggressive cytoreductive surgery followed by platin-based chemotherapy offer the possibility of long-term control of primary tubal carcinoma.
Carcinoma of the fallopian tube: a clinicopathological study of 105 cases with observations on staging and prognostic factors.Alvarado-Cabrero I, Young RH, Vamvakas EC, Scully RE.
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Gynecol Oncol 1999 Mar;72(3):367-79 Abstract quote One hundred five cases of carcinoma of the fallopian tube were subjected to a clinicopathological study to investigate the validity of various prognostic factors. A higher stage of tumor, an absence of closure of the fimbriated end of the tube, and an age of 66 years or older were the major predictors of a shorter length of recurrence-free postoperative survival in a univariate analysis.
In a multivariate analysis, however, stage was a highly significant prognostic factor, absence of fimbriated-end closure, marginally significant, and older age, not significant. Within Stage I cases the presence or absence of invasion of the tubal wall, the depth of invasion when present, and the location of the tumor within the tube (fimbrial or nonfimbrial) appeared to be prognostically important.
These findings strongly suggest that the FIGO staging system should be expanded to permit staging of noninvasive tubal carcinomas and fimbrial carcinomas, which cannot be staged according to the current system, and that depth of invasion of the tubal wall merits future investigation as an additional prognostic factor.
Management and prognosis of primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.Rosen AC, Klein M, Hafner E, Lahousen M, Graf AH, Reiner A.
Department of Obstetrics and Gynecology at SMZ-Ost, Vienna, Austria.
Gynecol Obstet Invest 1999;47(1):45-51 Abstract quote We retrospectively analyzed 143 women treated in 28 departments from 1980 to 1995, to study the impact of prognostic factors in primary carcinoma of the fallopian tube. Further aims of the study were to evaluate the treatment of fallopian tube carcinoma in Austria. Staging of disease was done according to the modified FIGO system, and grading according to the criteria suggested by Hu et al.
The mean age of the patients was 62.5 years. Sixty (42%) tumors were found to be in stage I, 28 (19%) in stage II, 38 (27%) in stage III, and 17 (12%) in stage IV. Radical resection was achieved in 102 (71%) patients. In 122 (85%) women surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperatively patients underwent adjuvant therapy consisting of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all stages of disease was 43%.
The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV. FIGO stage, histologic grading and residual tumor showed an independent prognostic impact in multivariate analysis.
Primary fallopian tube carcinoma: the Queensland experience.Obermair A, Taylor KH, Janda M, Nicklin JL, Crandon AJ, Perrin L.
Queensland Center for Gynaecological Cancer, Ned Hanlon Building, Royal Women's Hospital, Herston, Queensland, Australia.
Int J Gynecol Cancer 2001 Jan-Feb;11(1):69-72 Abstract quote The purpose of this study was to review the experience with fallopian tube carcinoma in Queensland and to compare it with previously published data. Thirty-six patients with primary fallopian tube carcinoma treated at the Queensland Gynaecological Cancer Center from 1988 to 1999 were reviewed in a retrospective clinicopathologic study.
All patients had primary surgery and 31/36 received chemotherapy postoperatively. Abnormal vaginal bleeding (15/36) and abdominal pain (14/36) were the most common presenting symptoms at the time of diagnosis. Median follow-up was 70.3 months and the median overall survival was 68.1 months. Surgical stage I disease (P = 0.02) and the absence of residual tumor after operation (P = 0.03) were the only factors associated with improved survival. Twenty of the 36 patients (55%) presented with stage I disease and survival was 62.7% at 5 years. No patient with postoperative residual tumor survived.
The majority of the patients with fallopian tube carcinoma present with stage I disease at diagnosis, but their survival probability is low compared with that of other early stage gynecological malignancies. If primary surgical debulking cannot achieve macroscopic tumor clearence, the chance of survival is extremely low.
Analysis of treatment failures and survival of patients with fallopian tube carcinoma: a cooperation task force (CTF) study.Gadducci A, Landoni F, Sartori E, Maggino T, Zola P, Gabriele A, Rossi R, Cosio S, Fanucchi A, Tisi G.
Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Via Roma 56, Pisa, 56127, Italy.
Gynecol Oncol 2001 May;81(2):150-9 Abstract quote OBJECTIVE: The objective of this retrospective multicenter study was to assess the pattern of failures and survival of patients with primary carcinoma of the fallopian tube.
METHODS: The hospital records of 88 patients with primary carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43 (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 55 months (range, 7-182).
RESULTS: Of the 21 patients with stage I disease, 10 had no postoperative treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred after a median of 29 months (range, 8-93) from initial surgery. Of the 21 patients with stage II disease, 2 had no postoperative treatment, 2 underwent external pelvic irradiation, 16 received platinum-based chemotherapy, and 1 patient had oral melphalan. Eight (38.1%) patients recurred after a median of 25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1 patient refused chemotherapy and died after 19 months and 45 patients received platinum-based chemotherapy. A clinical complete response was obtained in 29 (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy was performed in 14 of the 29 clinically complete responders: 12 patients were found to be in pathological complete response and 2 had persistent disease. Six (50.0%) of the former recurred after a median of 22 months (range, 13-101) from initial surgery. The two patients with persistent disease developed tumor progression after 15 and 11 months, respectively. Fifteen clinically complete responders did not undergo second-look, and 7 (46.7%) of them had a recurrence after a median of 18 months (range, 9-41). For the whole series, 5-year survival was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P = 0.0001), tumor grade (G3 vs G1 + G2, P = 0.0038), and patient age (>58.5 years vs <58.5 years, P = 0.0069), but not to histological type. The Cox model showed that FIGO stage (P = 0.0018) and patient age (P = 0.0290) were independent prognostic variables for survival. Among the patients with stage III-IV disease, 5-year survival was 55% for the patients who had residual tumor <1 cm compared with 21% for those who had larger residuum (P = 0.0169).
CONCLUSIONS: Primary carcinoma of the fallopian tube shares several biological and clinical features with ovarian carcinoma. However, when compared with the latter, fallopian tube carcinoma 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 represent important prognostic variables for survival.
TREATMENT
Combination chemotherapy in advanced adenocarcinoma of the fallopian tube.Muntz HG, Tarraza HM, Goff BA, Granai GO, Rice LW, Nikrui N, Fuller AF Jr.
Department of Gynecology, Massachusetts General Hospital, Boston 02114.
Gynecol Oncol 1991 Mar;40(3):268-73 Abstract quote Advanced adenocarcinoma of the fallopian tube has a poor prognosis, with 5-year survival rates commonly less than 20%. Since 1980, we have managed 12 patients with disseminated tumor with combination chemotherapy following surgical cytoreduction. Analogous to the International Federation of Gynecology and Obstetrics staging of ovarian carcinoma, 3 patients were classified in Stage II, 8 in Stage III, and 1 in Stage IV. Ten patients received cisplatin-containing regimens.
The 3 Stage II patients, without measurable disease after primary surgery, had an indeterminate response to chemotherapy. In Stages III-IV there were 4 complete responses (3 confirmed by second-look laparotomy) and 2 partial responses, for an overall response rate of 67%. Disease progressed in 2 patients and was stable in 1 patient.
After median follow-up of 3.5 years, 4 of the Stage III-IV patients have no evidence of disease, 1 is alive with disease, and 4 are dead.
Adenocarcinoma of the fallopian tube: results of a multi-institutional retrospective analysis of 72 patients.Wolfson AH, Tralins KS, Greven KM, Kim RY, Corn BW, Kuettel MR, Philippart C, Raub WA Jr, Randall ME.
Department of Radiation Oncology at the University of Miami School of Medicine, FL, USA.
Int J Radiat Oncol Biol Phys 1998 Jan 1;40(1):71-6 Abstract quote PURPOSE/OBJECTIVE: To determine the prognostic factors for predicting outcome of patients with adenocarcinoma of the fallopian tube and to evaluate the impact of treatment modalities in managing this uncommon disease.
MATERIALS AND METHODS: A retrospective analysis of the tumor registries from 6 major medical centers from January 1, 1960 up to March 31, 1995 yielded 72 patients with primary adenocarcinoma of the fallopian tube. The Dodson modification of the FIGO surgical staging as it applies to carcinoma of the fallopian tube was utilized. Endpoints for outcome included overall and disease-free survival. Univariate analysis of host, tumor, and treatment factors was performed to determine prognostic significance, and patterns of failure were reviewed.
RESULTS: The median age of the study cohort was 61 years (range 30-79 years). Stage distribution was 24 (33%) Stage I; 20 (28%) Stage II; 24 (33%) Stage III; and 4 (6%) Stage IV. Adjuvant chemotherapy was administered to 54 (75%) patients, and postoperative radiotherapy was employed in 22 (31%). In the latter treatment group, 14 (64%) had whole pelvic external beam irradiation, 5 (23%) whole abdominal radiotherapy, 2 (9%) P-32 instillation, and 1 (4%) vaginal brachytherapy alone. Chemotherapy was used in 67% of Stage I and in 79% of Stages II/III/IV disease (not significant); radiotherapy was more commonly employed in Stage I than in Stages II/III/IV (46% vs. 23%, p = 0.05). The 5-, 8-, 15-year overall and disease-free survival for the study patients were 44.7%, 23.8%, 18.8% and 27.3%, 17%, 14%, respectively. Significant prognostic factors of overall survival included Stage I vs. II/III/IV (p = 0.04) and age < or = 60 years vs. > 60 years at diagnosis (p = 0.03). Only Stage I vs. II/III/IV (p = 0.05) was predictive of disease-free survival. Patterns of failure included 18% pelvic, 36% upper abdominal, and 19% distant. For all patients, upper abdominal failures were more frequently found in Stages II/III/IV (29%) than in Stage I (7%) (p = 0.03). Relapses solely outside of what would be included in standard whole abdominal radiotherapy portals occurred for only 15% of patients (6 of 40) with failures. Furthermore, patients having any recurrence, including the upper abdomen, were more likely (p = 0.001) to die (45%) than those without any type of relapse (18%).
CONCLUSION: This retrospective, multi-institutional study demonstrated the importance of FIGO stage in predicting the overall and disease-free survival of patients with carcinoma of the fallopian tube. Future investigations should consider exploring whole abdominal irradiation as adjunctive therapy, particularly in Stage II and higher.
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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
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