title: Multistep level sections to detect occult fallopian tube carcinoma in risk-reducing salpingo-oophorectomies from women with BRCA mutations: implications for defining an optimal specimen dissection protocol.
abstract: Risk-reducing salpingo-oophorectomy (RRSO) significantly lowers the incidence of ovarian, tubal, peritoneal, and breast cancer in women who carry BRCA1 or BRCA2 germline mutations. A minority of RRSO specimens from these women will contain occult early-stage carcinoma. Most occult cancer is localized in the fallopian tube fimbriae and is as small as 1 mm in size. Pathologic detection is dependent on thoroughness of tissue examination. Recommended protocols to maximize tumor detection emphasize the role of thinly slicing the tubes and ovaries and embedding the entire specimen for microscopic examination. Additional multistep level sections of tubal fimbriae tissue blocks could theoretically increase detection of occult tubal carcinoma but the value of level sections has not been formally evaluated. This study tests the diagnostic utility of multistep level sections in RRSO specimens from 102 women with BRCA germline mutations. The original diagnoses were based on a single section from each block of thinly sliced (2 to 3 mm intervals) tissues of the entire RRSO specimen. Three multistep level sections were retrospectively obtained from each block containing tubal fimbriae. Clinically occult carcinoma ranging in size from 1 to 13 mm was initially detected in 11 of 102 women (5 in tubal fimbriae only, 1 in tubal isthmus only, 2 in fimbriae and ovary, and 3 in ovary only). Diagnoses in the original fimbrial slides and their level sections were concordant in all cases. All tubal cancers were detected in both the original sections and in the multistep level sections. None of the tubal carcinomas that were noninvasive on the original slides showed invasive growth on additional level sections. No tubal carcinoma was identified in the level sections of any case originally classified as benign. Clinical follow-up among women with benign RRSO findings revealed that 2 women subsequently developed peritoneal carcinomatosis at 22 and 62 months postoperatively. Retrospective exhaustive multistep level sectioning of all remaining tubal and ovarian blocks from both these women confirmed the original benign diagnosis in 1 woman but in the other woman, the deepest levels of 1 ovarian block revealed a single 1-mm nodule of cancer at the base of an ovarian surface epithelial invagination. This specimen was one of the first RRSO cases in our experience and on review of the original report, this ovary was not dissected into multiple slices along its short axis but was only bivalved along its long axis. We propose that there does not seem to be any diagnostic value in automatically performing multistep deeper level sections of RRSO specimens if the tissue is sectioned appropriately and if the specimen is sliced at intervals that are no more than 3 mm thick. Guidelines for evaluation of RRSO specimens should emphasize the use of an optimal dissection protocol and the importance of thin tissue slice intervals.
authors.affiliation: Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. joseph.rabban@ucsf.edu
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Rabban
authors.forename: Ellen
authors.initials: E
authors.lastname: Krasik
authors.forename: Lee-May
authors.initials: LM
authors.lastname: Chen
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Powell
authors.forename: Beth
authors.initials: B
authors.lastname: Crawford
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Zaloudek
mesh_terms: D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001706:Biopsy; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004210:Dissection; D055088:Early Detection of Cancer; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008867:Microtomy; D010052:Ovariectomy; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human