Does It Matter How Ovaries Removed Prophylactically Are Processed Pathologically?

Abstract & Commentary

Robert L. Coleman, MD, Associate Professor, University of Texas; M.D., Anderson Cancer Center, Houston Texas, is Associate Editor for OB/Gyn Clinical Alert

Synopsis: 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.

Source: Powell B, et al. J Clin Oncol. 2005;23:127-132.

It has been consistently demonstrated that women with deleterious BRCA1 and BRCA2 mutations have an increased lifetime risk for ovarian cancer, prompting some to consider prophylactic adnexectomy after childbearing. While not completely protective, the procedure appears to reduce incident risk significantly. In addition, it has been documented that a small proportion of these removed ovaries harbor occult malignancy, a finding that provoked Powell and colleagues to institute a specific specimen processing protocol for ovaries removed under the indication of prophylactic adnexectomy. The principal deviation from standard protocol was 2-mm serial sectioning in the removed adnexal structures (tube and ovary) combined with random biopsies and cytology. From 118 probands and female relatives, 67 patients (57%) had pathological material and operative records for analysis. In 41 of these cases (61%) the protocol was followed fully or partially. In total, 7 cancers were identified—all within the group for whom the protocol was followed (17% of protocol patients). None were identified among the 26 cases processed by standard methods. This strong effect of the protocol in cancer identification was independent of other variables such as age, BRCA1 or BRCA2 mutation, or type of surgery. Powell et al concluded that rigorous pathological sampling will identify more patients with occult malignancy, and suggested the reported detection rate among high-risk women is likely underestimated.

Comment by Robert L. Coleman, MD

"The more you look, the more you find. . ."—a phrase true to the dictum of sampling. It should not come as a surprise that more thorough investigation would identify more disease, particularly if these lesions were typically occult. However, time, cost, and resource constraints limit our ability to follow this practice on all specimens removed at the time of surgery. In the case of genetically high-risk women undergoing prophylactic surgery, prevalence of disease would support the resource allocation. There are other examples where extended sampling, as well as other procedures, now accompanies the evaluation of a high-profile specimen. One good example is the evaluation of a sentinel node. This specimen is characterized and identified intraoperatively as the first and highest at-risk node draining a primary tumor. Prevalence of disease is by definition highest here. Validation of this hypothesis has now mandated serial sectioning in most cases as well as adjuvant immunohistochemistry and PCR-based analysis in some situations searching for the earliest evidence of metastatic spread. The difficulty in practice is what to do with the information when it is found.

It is likely that most of the women with occult primary disease identified by serial sampling in the current study will be salvaged by surgery with or without indicated adjuvant chemotherapy. The question remains as to what degree adjunctive procedures should be performed in the absence of gross tumor. Should all patients undergo peritoneal sampling with an omentectomy? Should a lymphadenectomy be performed given that 10%-20% of the patients in this cohort will have a malignancy? Currently, justification for formal staging of borderline ovarian tumors is supported on a similar incidence of up-classifying the disease to invasive malignancy. Validation of these additional and potentially invasive procedures is necessary prior to formal guidelines.

Previous studies have suggested that both the ovary and fallopian tubes are tissues of increased risk in patients with BRCA mutations. This trial adds to the growing body of data in this regard as 4 of the 7 identified abnormalities were fallopian tube in origin. Concern for complete tubal resection in these patients has prompted some to also recommend hysterectomy in order to insure the cornual section of the tube is removed as well. The addition of this procedure will likely increase the potential for morbidity, necessitating the conduct of future prospective trials to clearly demonstrate its benefit in the care of these patients. Currently, hysterectomy is more strongly advocated among women undergoing risk-reducing surgery because of family or personal history of hereditary non-polyposis colorectal cancer.

Additional Reading

  • Paley PJ, et al. Gynecol Oncol. 2001;80:176-180.
  • Watson P, et al. Am J Med. 1994;96:516-520.