Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers: Role of Serial Sectioning in the Detection of Occult Malignancy

University of California, San Francisco, San Francisco, California, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2005; 23(1):127-32. DOI: 10.1200/JCO.2005.04.109
Source: PubMed


Women who carry deleterious mutations of BRCA1 or BRCA2 genes have up to a 54% lifetime risk of developing ovarian cancer. After childbearing, women at high risk increasingly choose bilateral risk-reducing salpingo-oophorectomy (RRSO). Two recent studies of BRCA mutation carriers reported occult malignancy in 2.5% of women undergoing RRSO. This study aimed to increase this detection rate using a protocol.
In 1996, the University of California San Francisco Gynecologic Oncology Program instituted a surgical-pathologic RRSO protocol that was composed of complete removal and serial sectioning of both ovaries and fallopian tubes, peritoneal and omental biopsies, and collection of peritoneal washings for cytology. We report the pathologic findings in 67 BRCA mutation carriers according to the degree of adherence to this protocol.
Of the 67 procedures, the protocol was followed completely or partially in 41 (61%). Seven occult malignancies were discovered, four in the fallopian tube and three in the ovaries. Six of these were microscopic, and all seven (17%) were found in specimens from complete or partial protocol procedures as opposed to standard procedures (P = .026). Other variables such as age, parity, BRCA1 or BRCA2 mutation, or type of surgery did not alter the strong effect of protocol procedure on the cancer detection rate.
A rigorous operative and pathologic protocol for RRSO increases the detection rate of occult ovarian malignancy in BRCA mutation carriers nearly seven-fold. If confirmed, this finding will alter postoperative management because additional staging, chemotherapy, and follow-up may be necessary in affected women.

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    • "Both had preoperative negative transvaginal ultrasounds. In 2006, Powell et al.[18]detected seven malignancies (10.4%) in 67 patients, six of which were microscopic. In the GOP -199[28]fourteen of 25 neoplasms were stage 0 to II, including five ovarian and nine tubal malignancies (four were STICs). "
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    ABSTRACT: At present, there is no effective screening of ovarian cancer. Primary prevention may be the only strategy to decrease the mortality from ovarian cancer, not only in women at high risk but also at low risk. Several recent studies have identified the distal fimbriae end of the fallopian tubes as primary precursor of High-grade serous carcinoma. Serous tubal intraepithelial carcinomas and occult invasive serous carcinomas have been identified in 2-17% of the fallopian tubes of BRCA 1/2 positive women undergoing risk-reducing salpingooophorectomy. Removal of the fallopian tubes with ovarian preservation has been suggested as a reasonable strategy that could reduce the risk of developing ovarian carcinoma in both low and high-risk women. It has been proposed after childbearing in women at high risk to be followed by bilateral oophorectomy at a later date. Bilateral salpingectomy is also suggested for low risk women, at the time of other benign gynaecologic surgery as a primary preventive strategy. Some studies have shown a risk reduction of ovarian cancer in women with bilateral prophylactic salpingectomy. Current research regarding bilateral salpingoophorectomy as primary prevention approach of ovarian cancer is reviewed here. In addition, the potential use of bilateral salpingectomy as prevention approach of ovarian cancer is discussed Key Words: High grade serous carcinoma, Serous tubal intraepithelial carcinomas, BRCA 1 /2 mutation carriers, Salpingectomy and ovarian cancer.
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    • "During systematic histopathological examination of tissues from prophylactic adnexectomies for a genetic risk, the revelation of occult tubal cancer designed as STIC (about 10%, and between 50 and nearly 100% of these cases have exhibited involvement of the fimbriated end of the fallopian tube) gave rise to the postulate of a tubal origin for ovarian cancer, and encouraged comprehensive analysis of the tubes [18] [19]. Serous Tubal Intraepithelial Lesions (STILs) or Tubal Intraepithelial Lesions in Transition (TILT) described a spectrum of epithelial changes from normal appearing tubal epithelium to cytological atypia and tubal dysplasia, expressing p53 [3] [20]. "
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    • "Since PSC can originate as an occult mullerian neoplasm that commonly proliferates at other peritoneal sites (Colgan et al., 2001, 2002; Cass et al., 2005; Powell et al., 2005; Finch et al., 2006; Chand et al., 2007), the pathological (histology and staining) evaluation of PSC often does not identify the original tumor site and should be augmented with detailed analysis of the patient's clinical and family history and BRCA phenotype in order to assign the final diagnosis with reasonable medical certainty (Risch et al., 2001; Piek et al., 2004; Kindelberger et al., 2007; Gilks et al., 2008). BRCA-positive families are noted to have higher cancer rates affecting the colon, prostate, pancreas and peritoneum, as well as melanoma (Struewing et al., 1997; Frank, 2001; Paley et al., 2001; Al-Hussaini et al., 2004). "
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