Detailed Pathological Assessment of Fallopian Tube Paramount in Women Undergoing Prophylactic BSO for BRCA Mutation

Abstract & Commentary

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

Dr. Coleman reports no financial responsibility to this field of study.

Synopsis: Adnexal tissues removed during surgery for risk-reduction in women with BRCA mutations should have thorough and directed evaluation of the ampulla and fimbrial sections for occult malignancy.

Source: Callahan MJ, et al. J Clin Oncol. 2007;25:3985-3990.

The performance of risk-reducing surgery in women with BRCA mutation has a profound effect on the potential for subsequent cancer development. While gross tumor is occasionally identified in these specimens, it is more common that pathological processing identifies occult cancer. This has led to the recommendation of serial step sectioning of the ovaries and tubes in these cases. Callahan and colleagues sought to determine the frequency and location of malignancies detected after prophylactic salpingo-oophorectomy in women with BRCA mutations. Over an eight-year period, 122 women (median age 46.5 years) with BRCA mutations undergoing risk-reducing surgery were evaluated for cancer in the resected adnexa. The group used two techniques of serialized pathologic sectioning: a standard cross-sectional method and a newer technique, which in addition to cross-sectional sectioning of the proximal tube, sagittally sectioned the amputated fimbrial portion. The majority of the procedures were done laparoscopically (70%) and included cytology in all but 3 cases. Concomitant hysterectomy was performed in 25%. In total, 7 cancers (5.7%) were identified; 6 were microscopic and discovered on pathological analysis. All patients were older than 44 years and all involved the fallopian tube. Two also had microscopic foci in the ovary and two were associated with malignant cytology. There was no difference in identification by technique; however, fewer rounds of sectioning were required to identify occult malignancies. The authors conclude that the distal fallopian tube appears to be the dominant site for early, occult malignancies identified in the adnexa of women undergoing prophylactic risk-reducing surgery. They implore aggressive sectioning to accurately identify these cases given their potential for metastatic spread.

Commentary

Concomitant with an increased awareness of and sought-after professional counseling for women with potential genetic risk of gynecologic malignancy has been a wider acceptance of risk-reducing prophylactic surgery. The net impact of these procedures appears to have a beneficial effect on lifetime cancer risk. In addition, recognition of the potential for occult cancer has ushered in recommendations for a more careful inspection of the resected tissues. Reports to date have suggested that occult malignancy may be found in 2.3% to 17% of patients with BRCA mutation. What is being more clearly defined, and is one of the stated objectives of the current report, is that the fallopian tube is "ground zero" for these occult malignancies. Further, it appears that the ampulla and fimbrial sections of the distal tube are the most common sites for primary involvement. While the entire fallopian tube is still recommended to undergo serial sectioning, the authors recommend sagittal sectioning of this higher-risk locale in order to clearly find these tumors. This is being emphasized as many of the occult lesions represent tubal in-situ carcinomas, which have been additionally associated with malignant cytology despite the absence of an invasive component. While the impact of adjuvant chemotherapy is not known in these patients, recurrences have been documented. In addition, some patients develop cancer subsequently despite prophylactic surgery. It is not known if these cases are a result of sampling error or peritoneal transformation.

The Society of Gynecologic Oncologists has published guidelines in the care of these women including a recommendation to perform risk-reducing surgery at the completion of childbearing or by age 44. Given the age at diagnosis in the current and previous studies, this recommendation appears sound. Further follow-up and continued reporting of improved sectioning techniques will refine the care of these women.