The Tubal Fimbria Is a Preferred Site for Early Adenocarcinoma in Women With Familial Ovarian Cancer Syndrome

A proportion of adenocarcinomas in prophylactic adnexectomies (bilateral salpingo-oophorectomies [BSOs]) from women with BRCA mutations (BRCA positive) occur in the fallopian tube. We analyzed a consecutive series of BSOs from BRCA-positive women following an index case of fimbrial serous carcinoma. To determine if the fimbria is a preferred site of origin, we followed a protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Immunostaining for p53 and Ki-67 was also performed. Thirteen BRCA-positive women (cases) and 13 women undergoing BSOs for other disorders (controls) were studied. Tubal carcinoma was detected in 4 cases at the initial histologic evaluation and in no controls. A fifth carcinoma was discovered following further sectioning of the fimbriae. Three were BRCA2 positive and two BRCA1 positive. Three were in the fimbria, one in both the fimbria and proximal tube, and one involved the ampulla. Four were serous carcinomas, four were confined to the tube, and three were noninvasive (intraepithelial). No ovarian carcinomas were identified. All tumors were Ki-67 positive (>75% of cell nuclei), and excluding one endometrioid carcinoma, p53 positive (>75% cell nuclei); p53 positivity in the absence of elevated Ki-67 did not correlate with morphologic neoplasia. The fimbria was the most common location for early serous carcinoma in this series of BRCA-positive women. Protocols that extensively examine the fimbria (SEE-FIM) will maximize the detection of early tubal epithelial carcinoma in patients at risk for ovarian cancer. Investigative strategies targeting the fimbriated end of the fallopian tube should further define its role in the pathogenesis of familial and sporadic ovarian serous carcinomas.

[1]  R. Vang,et al.  Immunohistochemical Staining for Ki-67 and p53 Helps Distinguish Endometrial Arias-Stella Reaction from High-Grade Carcinoma, Including Clear Cell Carcinoma , 2004, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[2]  S. Navani,et al.  Tumors of the Fimbriated End of the Fallopian Tube: A Clinicopathologic Analysis of 20 Cases, Including Nine Carcinomas , 1997, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[3]  R. Demopoulos,et al.  Clues to the Pathogenesis of Fallopian Tube Carcinoma: A Morphological and Immunohistochemical Case Control Study , 2001, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[4]  P. Kenemans,et al.  Intraperitoneal serous adenocarcinoma: a critical appraisal of three hypotheses on its cause. , 2004, American journal of obstetrics and gynecology.

[5]  S. Silverberg,et al.  Mucosal Epithelial Proliferation of the Fallopian Tube: Prevalence, Clinical Associations, and Optimal Strategy for Histopathologic Assessment , 2000, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[6]  Rochelle L. Garcia,et al.  Pathologic findings in prophylactic oophorectomy specimens in high-risk women. , 2002, Gynecologic oncology.

[7]  Rochelle L. Garcia,et al.  Unexpected Gynecologic Neoplasms in Patients With Proven or Suspected BRCA-1 or -2 Mutations: Implications for Gross Examination, Cytology, and Clinical Follow-up , 2002, The American journal of surgical pathology.

[8]  P. Bannatyne,et al.  Early adenocarcinoma of the fallopian tubes. A case for multifocal tumorigenesis. , 1981, Diagnostic gynecology and obstetrics.

[9]  P. V. van Diest,et al.  Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer , 2001, The Journal of pathology.

[10]  J. Niloff,et al.  Occult ovarian tumors in women with BRCA1 or BRCA2 mutations undergoing prophylactic oophorectomy. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  T. Colgan Challenges in the Early Diagnosis and Staging of Fallopian-Tube Carcinomas Associated with BRCA Mutations , 2003, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[12]  B. Rosen,et al.  Occult Carcinoma in Prophylactic Oophorectomy Specimens: Prevalence and Association With BRCA Germline Mutation Status , 2001, The American journal of surgical pathology.

[13]  Rochelle L. Garcia,et al.  Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis. , 2001, Gynecologic oncology.

[14]  I. Shih,et al.  Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. , 2004, The American journal of pathology.

[15]  S. Silverberg,et al.  Mucosal Epithelial Proliferation of the Fallopian Tube: A Particular Association with Ovarian Serous Tumor of Low Malignant Potential? , 1995, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[16]  M. Beattie,et al.  Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.