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Objective: Prophylactic surgical removal of the ovaries has been offered for many years as a potential preventative of ovarian cancer in women deemed to be at increased hereditary risk for this disease. Now, it is possible to test for specific mutations of the BRCA1 and BRCA2 genes that render members of hereditary breast ovarian cancer (HBOC) syndrome families susceptible to cancer. Widespread intra-abdominal carcinomatosis, which mimics metastatic ovarian serous carcinoma, has been reported following oophorectomy in individuals at increased hereditary risk. This study was undertaken to examine and report particularly the occurrence of intra-abdominal carcinomatosis, as well as other cancers, following prophylactic oophorectomy in patients who carry cancer susceptibility mutations of BRCA1 and BRCA2 and to assess the cumulative risks for this disease in order to assist in developing appropriate surgical interventions, based on currently available information, and to counsel patients who choose prophylactic surgery, concerning the potential prognosis, thereafter., Methods: The Creighton University Hereditary Cancer Institute registry was searched for members of HBOC syndrome families who had undergone prophylactic oophorectomy. The histories and results of DNA testing for the BRCA1 and BRCA2 mutations carried in their families were recorded, tabulated and examined, and the aggregate data are reported along with pertinent details of those individuals who developed neoplastic diseases after prophylactic oophorectomy. All available histologic and cytologic materials of patients who were diagnosed with intra-abdominal carcinomatosis were reviewed, and life-table calculations were performed to assess cumulative risks for this disease following prophylactic oophorectomy., Results: From 72 HBOC syndrome families that carried either BRCA1 or BRCA2 cancer-associated mutations, 238 individuals who had undergone prophylactic oophorectomy were recorded in our registry between January 1985 and December 2002. During a mean follow-up of 9.3 years, cancers were diagnosed in 27 subjects, including 16 individuals with breast cancer and five patients with intra-abdominal carcinomatosis. Breast cancers were stage I in 10 of 12 proven carriers of cancer-associated mutations. All five cases of intra-abdominal carcinomatosis were serous carcinomas, and all occurred in BRCA1 mutation carriers. Histologic review of the prophylactically removed ovaries found borderline lesions in two cases, one with possible early stromal invasion. Two of the five patients who developed intra-abdominal carcinomatosis were among 78 patients in this series who were diagnosed and treated for breast cancer before prophylactic oophorectomy. A 3.5% cumulative risk for all mutation carriers and a 3.9% cumulative risk for BRCA1 mutation carriers were calculated through 20 years of follow-up after prophylactic oophorectomy., Conclusions: Intra-abdominal carcinomatosis in our series was diagnosed only in BRCA1 mutation carriers. The calculated cumulative risks of developing intra-abdominal carcinomatosis after prophylactic oophorectomy in members of HBOC syndrome families, specifically those who carry deleterious mutations, are well below the estimated risks of ovarian cancer published in the literature for similar patients. Breast cancers, which tended to be small and localized, were the most common malignancy in BRCA1 and BRCA2 mutation carriers after prophylactic oophorectomy.

Objective: The literature reports conflicting studies claiming premalignant histological features in benign ovaries from women who may have hereditary predilections for ovarian carcinoma. To test the veracity of these claims, this investigation studied ovaries prophylactically removed from members of hereditary breast ovarian cancer (HBOC) syndrome families who carry BRCA1 and BRCA2 mutations and compared these with the ovaries of mutation-negative women from the same HBOC syndrome kindred., Methods: Sixty cases of women from HBOC syndrome families who had undergone prophylactic oophorectomies and whose BRCA1 and BRCA2 mutation status had been tested were selected from our database. Thirty had tested positive for BRCA1 mutations, 3 carried BRCA2 mutations, and 27 were negative for both BRCA1 and BRCA2 germline mutations. Histologic material from each case was examined by light microscopy blinded to the mutation status. Histologic features, previously reported to be possible precursor lesions for ovarian cancer, were quantified. Data from BRCA1 and BRCA2 mutation carriers were compared with those from mutation-negative cases in the direct line of genetic inheritance from the same HBOC syndrome families., Results: Statistical analysis found that a more frequent occurrence of ovarian surface micropapillae in 87% of mutation carriers compared with just 55% of mutation-negative cases was the only histologic feature which was significantly different between the two groups (P = 0.39). Cortical clefts tended to be deeper in the ovaries of mutation carriers, but this did not reach significance (P = 0.051). There were no other significant histologic differences between the ovaries removed from mutation carriers and those from noncarriers., Conclusions: The results of our large and prospectively controlled, blinded study contrast with those reported from smaller, unblinded investigations. Except for the possible biological significance of surface micropapillae on ovaries from BRCA1 and BRCA2 mutation carriers, we found no histologic evidence for a genetically determined ovarian carcinoma precursor lesion., (Copyright 2000 Academic Press.)

Our first year of experience in the use of PET scanning in the management of nine patients with ovarian cancer leads us to conclude that this promising new technique may be more sensitive than either serum CA-125 determinations or computed tomography for the detection and demonstration of residual or recurrent abdominal and pelvic tumor. Seven of these patients underwent second-look laparotomy which confirmed our impressions from preoperative PET scans in six patients, and the one other scan showed a focus of metabolic uptake coinciding with residual tumor in our retrospective review. The clinical courses of two other patients who did not undergo laparotomy confirmed the impressions gained from PET scans.

Lynch syndrome II was diagnosed when two sisters manifested early-onset synchronous carcinomas of the ovary and endometrium and a third sister was found to have Duke's A carcinoma of the cecum. A detailed cancer family history indicated paternal transmission of the deleterious genotype. The pattern of carcinoma of the colorectum and extracolonic sites throughout the extended family was then found to be consonant with this hereditary cancer-prone disorder. Lynch syndrome II may be exceedingly difficult to diagnose due to an absence of premonitory clinical signs or biomarkers of genotypic susceptibility. Its recognition is therefore dependent on a detailed cancer family history (all anatomic sites), coupled with knowledge of the pattern of the cancer spectrum, distribution, and natural history, as manifested in this hereditary disorder. We describe the decision logic that was involved in the diagnosis of Lynch syndrome II in this family and indicate the important role of the gynecologists in this process.