Pathological findings following risk-reducing salpingo-oophorectomy in BRCA mutation carriers: A systematic review and meta-analysis

Cheng, Aoshuang; Li, Lei; Wu, Ming; Lang, Jinghe

doi:10.1016/j.ejso.2019.09.002

Cited by 12 publications

(11 citation statements)

References 94 publications

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“…As STIC is found in approximately 3% of BRCA -PV carriers at RRSO, the finding by Harmsen et al is notably higher than expected, which suggests an association between STIC and PC later on. 17,18 Moreover, the same TP53 mutation was identified in PC and STIC from the same patient, 19 suggesting that an isolated STIC at RRSO increases the risk for developing PC. As STIC lesions are rather rare, only small series describing the follow-up of BRCA -PV carriers with STIC have been published.…”

Section: Introductionmentioning

confidence: 85%

“…The IPDMA method is most suitable for investigating this issue because of the infrequent prevalence of STIC, which is about 3% in the BRCA -PV population. 18 Moreover, the usage of IPD enables the adjustment for potential confounders and duration of follow-up. Our results are robust as results of individual studies were highly consistent and strengthened by the fact that a similar effect was found with a different analysis method (two-stage analysis), when aggregated data of studies without IPD were used, and when studies with IPD only on women with STIC were excluded.…”

Section: Discussionmentioning

confidence: 99%

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Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis

Steenbeek¹,

Bommel²,

Bulten

et al. 2022

JCO

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PURPOSE After risk-reducing salpingo-oophorectomy (RRSO), BRCA1/ 2 pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO. METHODS Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a BRCA-PV with and without STIC at RRSO until September 2020. Primary outcome was the hazard ratio for the risk of PC between BRCA-PV carriers with and without STIC at RRSO, and the corresponding 5- and 10-year risks. Primary analysis was based on a one-stage Cox proportional-hazards regression with a frailty term for study. RESULTS From 17 studies, individual patient data were available for 3,121 women, of whom 115 had a STIC at RRSO. The estimated hazard ratio to develop PC during follow-up in women with STIC was 33.9 (95% CI, 15.6 to 73.9), P < .001) compared with women without STIC. For women with STIC, the five- and ten-year risks to develop PC were 10.5% (95% CI, 6.2 to 17.2) and 27.5% (95% CI, 15.6 to 43.9), respectively, whereas the corresponding risks were 0.3% (95% CI, 0.2 to 0.6) and 0.9% (95% CI, 0.6 to 1.4) for women without STIC at RRSO. CONCLUSION BRCA-PV carriers with STIC at RRSO have a strongly increased risk to develop PC which increases over time, although current data are limited by small numbers of events.

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Section: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis

Steenbeek¹,

Bommel²,

Bulten

et al. 2022

JCO

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“…Stratification with epithelial atypia, loss of cilia, hyperchromasia, presence of nucleolus, increased nucleocytoplasmic ratio and loss of polarity were considered significant for STIC. Sectioning and Extensively Examining the Fimbriated End protocol was used for sampling fallopian tubes of all cases including the control group [18][19][20]. The best representative formalin-fixed paraffin-embedded tissue section (for tumor group; ovarian tumor and concomitant invasive tumor in FEs, for control group; normal appearing FEs) was chosen in each case.…”

Section: Methodsmentioning

confidence: 99%

“…The name of the study Tumor at the fimbrial end (%) Mehra et al 2011 [19] 80 Medeiros et al 2006 [18] 38 Salvador et al 2009 [20] 58 Our study 71…”

Section: Table V Comparison Of the Presence Of Tumors At The Fimbrial...mentioning

confidence: 98%

Are histomorphologic changes in the fimbrial ends more to blame for primary epithelial ovarian carcinomas than initially thought?

Askan¹,

Seven

Özkan

et al. 2022

Marmara Medical Journal

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Objective: To investigate the relationship between primary epithelial ovarian tumors and histomorphologic changes in the fimbrial ends (FEs) of the fallopian tubes.Materials and Methods: Twenty-eight serous carcinomas (SCs) and 12 non-serous carcinomas (NSC) were studied. Ovarian and concomitant invasive tumors in FEs were labeled with PAX8, WT-1 and Calretinin.Results: Eighty-six percent of SCs were high grade (HG), 14% of were low grade (LG). 71% of SCs (85% HG, 15% LG) had concomitant invasive tumors in FEs. Serous tubal intraepithelial carcinoma (STIC) was seen in 29% (75% HG, 25% LG), all had concomitant invasive tumors in FEs. The presence of tumors in FEs was statistically significant in SCs (p=0.03). 33% of NSCs had concomitantly invasive tumors in FEs. 67% of endometrioid tumors, 33% of clear cell carcinomas had endometriosis. 50% of mucinous tumors, 67% of endometrioid tumors, 50% of benign Brenner tumors had Walthard nest. Except for mucinous carcinomas, ovarian and concomitant invasive tumors in FEs displayed tubal phenotype (Calretinin-/PAX8+). Conclusion:The results of our study suggest that, invasive tumors and STIC in FEs are not only limited to HGSCs, but can also be seen in LGs. FEs could also be a site of origin for NSCs, however, future studies with more cases are needed.

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“…P53 signatures are reported on by six studies, with an estimated incidence of 16.2% (95% CI, 2.2-39.7) [16,20,25,27,40,47]. Finally, STIL was reported on by six studies and has an estimated incidence of 1.6% (95% CI, 0.3-3.8) [16,26,27,44,47,55].…”

Section: Study Characteristicsmentioning

confidence: 98%

Recommendations for diagnosing STIC: a systematic review and meta-analysis

et al. 2021

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Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has significantly increased over the last decades. Adequate and reproducible diagnosis of these precursor lesions is important. Diagnosing STIC can have prognostic consequences and is an absolute requirement for safely offering alternative risk reducing strategies, such as risk reducing salpingectomy with delayed oophorectomy. However, diagnosing STIC is a challenging task, possessing only moderate reproducibility. In this review and meta-analysis, we look at how pathologists come to a diagnosis of STIC. We performed a literature search identifying 39 studies on risk reducing salpingo-oophorectomy in women with a known BRCA1/2 PV, collectively reporting on 6833 patients. We found a pooled estimated proportion of STIC of 2.8% (95% CI, 2.0–3.7). We focused on reported grossing protocols, morphological criteria, level of pathologist training, and the use of immunohistochemistry. The most commonly mentioned morphological characteristics of STIC are (1) loss of cell polarity, (2) nuclear pleomorphism, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. The difference in reported incidence of STIC between studies who totally embedded all specimens and those who did not was 3.2% (95% CI, 2.3–4.2) versus 1.7% (95% CI, 0.0–6.2) (p 0.24). We provide an overview of diagnostic features and present a framework for arriving at an adequate diagnosis, consisting of the use of the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague.

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Pathological findings following risk-reducing salpingo-oophorectomy in BRCA mutation carriers: A systematic review and meta-analysis

Cited by 12 publications

References 94 publications

Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis

Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis

Are histomorphologic changes in the fimbrial ends more to blame for primary epithelial ovarian carcinomas than initially thought?

Recommendations for diagnosing STIC: a systematic review and meta-analysis

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