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Yamagata T, Watanabe K, Yamanoi K, Kakiuchi N, Ogura J, Taki M, Murakami R, Yamaguchi K, Hamanishi J, Minamiguchi S, Ogawa S, Mandai M. Origin of Peritoneal Cancer With Features of High-grade Serous Carcinoma: A Detailed Molecular Analysis. Int J Gynecol Pathol 2025; 44:280-285. [PMID: 39254218 DOI: 10.1097/pgp.0000000000001069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Abstract
Primary peritoneal cancer has characteristics similar to high-grade serous carcinomas of ovarian and fallopian tube origin. However, the relationship between endometriosis and primary peritoneal cancer is not well understood. This study focuses on a case of peritoneal cancer in a patient who had undergone hysterectomy and bilateral salpingo-oophorectomy 5 yr before. In addition to morphology, there was a positive for TP53 in immunohistochemistry and homologous recombination deficiency test, which were similar to high-grade serous carcinomas. However, WT1 was negative in the tumor, and extensive endometriosis coexisted. To reveal the clonal relationship between tumor and endometriosis, we dissected 3 sites each from the tumor and endometriosis and performed whole-exome sequencing analysis. As a result, we found that the tumors were of identical origin. Contrarily, no shared mutations were found in the 3 endometriosis sites. Furthermore, several shared mutations were found between the tumor and 1 endometriosis tissue, showing that the tumor and 1 ectopic endometrial gland originated from the same clone. This study indicates that several peritoneal cancers may be derived from endometriosis. We should consider the possibility of more diverse origins of peritoneal cancer than we speculated before.
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Affiliation(s)
- Tomo Yamagata
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
| | - Koichi Watanabe
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
- Department of Pathology and Tumor Biology, Graduate School of Medicine
| | - Koji Yamanoi
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
| | - Nobuyuki Kakiuchi
- Department of Pathology and Tumor Biology, Graduate School of Medicine
- The Hakubi Center for Advanced Research
| | - Jumpei Ogura
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
| | - Mana Taki
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
| | - Ryusuke Murakami
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
| | - Ken Yamaguchi
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
| | - Junzo Hamanishi
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
| | | | - Seishi Ogawa
- Department of Pathology and Tumor Biology, Graduate School of Medicine
- Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University
| | - Masaki Mandai
- Department of Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine
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Antoci F, Colella T, Biletta E, Travaglino E, De Lisi G, Quaquarini E, Arpa G, Pisacane AM, Paris MK, Corallo S, Di Sabatino A, Leone F, Vanoli A. BRCA2-Related Hereditary Cancer Syndrome-Associated Small Bowel Adenocarcinoma With Multiple BRCA2 Mutations: A Case Report and Review of the Literature. Cancer Rep (Hoboken) 2025; 8:e70200. [PMID: 40205657 PMCID: PMC11981949 DOI: 10.1002/cnr2.70200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 02/25/2025] [Accepted: 03/28/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Small bowel adenocarcinomas (SBAs) are rare and aggressive cancers. About one-fifth of SBA patients have predisposing conditions; among them, there are also genetic tumor syndromes, including Lynch syndrome, familial adenomatous polyposis, and Peutz-Jeghers syndrome. Although BRCA2 mutations, both somatic and germline, have been recently described in SBAs, direct evidence of BRCA2 inactivation in SBA tumor tissue of patients with BRCA2-related hereditary cancer syndrome is still very limited. CASE PRESENTATION Herein, we described a case of a 51-year-old woman with a history of breast cancer who developed an adenocarcinoma of the duodeno-jejunal flexure causing persistent vomiting. After clinical staging, the patient underwent surgical resection, and histologic examination of the specimen confirmed a poorly differentiated adenocarcinoma infiltrating the visceral peritoneum and showing lymph node metastases (stage III, pT4N1). Two years later, the SBA relapsed, and next generation sequencing was performed in matched tumor and normal tissues. In addition to KRAS and TP53 mutations in the tumor, both somatic and germline BRCA2 mutations were identified, indicating biallelic BRCA2 alterations. CONCLUSION BRCA2-associated hereditary tumor syndrome could have an etio-pathogenetic role in SBA development; thus, we suggest that this syndrome should be considered in patients with an SBA diagnosis below the age of 50 years, especially when a personal or family history of breast cancer is present.
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Affiliation(s)
- Francesca Antoci
- Anatomic Pathology UnitIRCCS San Matteo Hospital FoundationPaviaItaly
| | | | - Elena Biletta
- Unit of Pathology, Department of Surgery ASL BINuovo Ospedale Degli InfermiPonderanoItaly
| | - Erica Travaglino
- Anatomic Pathology UnitIRCCS San Matteo Hospital FoundationPaviaItaly
| | - Giuseppe De Lisi
- Anatomic Pathology Unit, Department of Molecular MedicineUniversity of PaviaPaviaItaly
| | - Erica Quaquarini
- Medical Oncology UnitFondazione IRCCS Policlinico San MatteoPaviaItaly
| | - Giovanni Arpa
- Unit of PathologyIstituti Clinici Scientifici Maugeri IRCCSPaviaItaly
| | - Alberto Maria Pisacane
- Unit of Pathology, Department of Surgery ASL BINuovo Ospedale Degli InfermiPonderanoItaly
| | - Myriam Katja Paris
- Unit of Oncology, Department of OncologyOspedale Degli InfermiPonderanoItaly
| | - Salvatore Corallo
- Medical Oncology UnitFondazione IRCCS Policlinico San MatteoPaviaItaly
| | - Antonio Di Sabatino
- First Department of Internal MedicineIRCCS San Matteo Hospital Foundation, University of PaviaPaviaItaly
| | - Francesco Leone
- Unit of Oncology, Department of OncologyOspedale Degli InfermiPonderanoItaly
| | - Alessandro Vanoli
- Anatomic Pathology UnitIRCCS San Matteo Hospital FoundationPaviaItaly
- Anatomic Pathology Unit, Department of Molecular MedicineUniversity of PaviaPaviaItaly
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Masuda K, Kobayashi Y, Seki T, Yoshihama T, Nakamura K, Goto Y, Yamada M, Nagayama A, Uchida S, Ono I, Misu K, Yokota M, Yamagami W. Current Situation and Future Directions of Risk-reducing Salpingo-oophorectomy. Keio J Med 2025:2024-0024-RE. [PMID: 40128982 DOI: 10.2302/kjm.2024-0024-re] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
High-grade serous carcinoma (HGSC), the most aggressive subtype of epithelial ovarian cancer, is strongly associated with hereditary breast and ovarian cancer (HBOC) syndrome and is primarily linked to germline BRCA1/2 pathogenic variants (PVs). The cumulative risks of ovarian cancer by the age of 70 years are 40% and 18% for carriers of BRCA1 and BRCA2 PVs, respectively. Risk-reducing salpingo-oophorectomy (RRSO) is a recommended preventive strategy that reduces the risk of ovarian cancer by more than 80% and may improve overall survival. However, surgical menopause after RRSO poses several challenges, including infertility and hormonal deficiency. Although the use of hormone replacement therapy may alleviate symptoms, it requires careful consideration of breast cancer risk. Emerging strategies, such as prophylactic salpingectomy with delayed oophorectomy, are being investigated to balance cancer prevention and patient quality of life. Further research is required to refine personalized prevention and management approaches for HBOC-associated ovarian cancer.
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Affiliation(s)
- Kenta Masuda
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
| | - Yusuke Kobayashi
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
| | - Tomoko Seki
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Tomoko Yoshihama
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
| | - Kohei Nakamura
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
- Center for Cancer Genomics, Keio University School of Medicine, Tokyo, Japan
| | - Yumiko Goto
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
- Center for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Mamiko Yamada
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
| | - Aiko Nagayama
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Sayaka Uchida
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
| | - Ikumi Ono
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
| | - Kumiko Misu
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
- Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
| | - Megumi Yokota
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
| | - Wataru Yamagami
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
- Center for Hereditary Breast and Ovarian Cancer Syndrome, Keio University Hospital, Tokyo, Japan
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Lee YJ, Kim JH, Kim YJ, Chang YJ, Kong SY, Yoo CW, Lee DO, Seo SS, Kang S, Park SY, Lim MC. The pathologic and clinical outcomes of risk-reducing salpingo-oophorectomy in asymptomatic carriers of homologous recombination repair gene mutation. J Gynecol Oncol 2025; 36:e15. [PMID: 39028150 PMCID: PMC11964960 DOI: 10.3802/jgo.2025.36.e15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/16/2024] [Accepted: 06/25/2024] [Indexed: 07/20/2024] Open
Abstract
OBJECTIVE To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). METHODS This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. RESULTS Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9-71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. CONCLUSION Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.
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Affiliation(s)
- Yeon Jee Lee
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
- Department of Obstetrics and Gynecology, Myongji Hospital, Goyang, Korea
| | - Ji Hyun Kim
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Youn Jee Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jung Chang
- Department of Family Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Sun-Young Kong
- Department of Laboratory Medicine and Genetic Counseling Clinic, Hospital, National Cancer Center, Goyang, Korea
| | - Chong Woo Yoo
- Center for Gynecologic Cancer and Department of Pathology, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Dong Ock Lee
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Sang-Soo Seo
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Sokbom Kang
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Sang-Yoon Park
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Myong Cheol Lim
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
- Rare and Pediatric Cancer Branch and Immuno-Oncology Branch, Division of Rare and Refractory Cancer, Research Institute and Center for Clinical Trial, Hospital, National Cancer Center, Goyang, Korea
- Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
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Le Saux O, McNeish I, D'Incalci M, Narducci F, Ray-Coquard I. Controversies in the management of serous tubal intra-epithelial carcinoma lesions of the fallopian tube. Int J Gynecol Cancer 2025; 35:101667. [PMID: 39987717 DOI: 10.1016/j.ijgc.2025.101667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/25/2025] Open
Abstract
High-grade serous carcinoma is the most lethal gynecological malignancy. Although serous tubal intra-epithelial carcinoma is increasingly recognized as a precursor to high-grade serous carcinoma, its optimal management remains controversial. This review examines the controversies in serous tubal intra-epithelial carcinoma pathogenesis, diagnosis, management, and follow-up, highlighting the need for collaboration, standardized guidelines, and further research to improve patient outcomes.
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Affiliation(s)
- Olivia Le Saux
- Department of Medical Oncology, Center Léon Bérard, Lyon, France; Université Claude Bernard Lyon 1, Université de Lyon, Centre Léon Bérard, INSERM 1052-CNRS 5286, Cancer Research Center of Lyon, "Cancer Immune Surveillance and Therapeutic Targeting" Laboratory, Lyon, France.
| | - Iain McNeish
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Maurizio D'Incalci
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Laboratory of Cancer Pharmacology, Rozzano, Milan, Italy
| | | | - Isabelle Ray-Coquard
- Department of Medical Oncology, Center Léon Bérard, Lyon, France; University Claude Bernard Lyon I Laboratoire RESHAPE U1290, Lyon, France
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Mor-Hadar D, McNally O, Grant A, Rajadevan N, McBain R, Naaman Y, Chan F, Vicario E, Wrede CD. Outcomes of risk-reducing surgeries in women at high risk for gynaecological cancers: A tertiary center experience. Surg Oncol 2025; 58:102193. [PMID: 39970568 DOI: 10.1016/j.suronc.2025.102193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 01/29/2025] [Accepted: 02/04/2025] [Indexed: 02/21/2025]
Abstract
OBJECTIVE Ovarian and endometrial carcinomas are the most common gynecologic malignancies, with general population risks of 1.4 % and 2.5 % respectively. Certain genetic factors can raise these risks to 44 % and 60 % respectively. The most effective risk-reduction (RR) method is the removal of the fallopian tubes, ovaries, and/or uterus. This study investigates surgical outcomes and occult cancer rates following RR surgery in high-risk women. METHODS This is a retrospective cohort study of all women identified as high-risk for gynaecologic cancer who were referred to a high-volume tertiary centre and underwent RR surgery. All pathology specimens were assessed by sectioning and extensively examining the fimbriated end (SEE-FIM) protocol. The analysis included patients' demographics, peri- and post-operative evaluation, and final histopathological reports. RESULTS Between 2008 and 2024, 576 women completed RR surgery in our centre. The rates of intra- and post-operative complications were 3.1 % and 4.5 %, respectively. The overall occult cancer rate was 3.4 % (n = 20). Of these, 11 (55 %) patients had high-grade serous carcinoma of the ovary/fallopian tube, and seven (35 %) patients were found to have endometrial cancer. Two cases had unexpected metastasis in the ovaries (10 %). Of the whole cohort, 12 (2.1 %) patients were found to have premalignant disease; eight serous tubal intraepithelial carcinoma; two atypical endometrial hyperplasia and two dysplasia of the cervix. CONCLUSION RR surgeries are safe with a low complication rate. The incidence of occult cancer at the time of RR surgery is low but significant. Endometrial sampling is to be considered, and all fallopian tubes should be examined with the SEE-FIM protocol.
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Affiliation(s)
| | - Orla McNally
- The Royal Women's Hospital Oncology & Dysplasia Unit, Australia; Department of Obstetrics and Gynaecology at the University of Melbourne, Australia
| | - Abby Grant
- The Royal Women's Hospital Oncology & Dysplasia Unit, Australia
| | | | - Rosemary McBain
- The Royal Women's Hospital Oncology & Dysplasia Unit, Australia
| | - Yael Naaman
- The Royal Women's Hospital Oncology & Dysplasia Unit, Australia
| | - Fiona Chan
- A Division of Royal Children's Hospital Laboratory Services, Australia
| | | | - C David Wrede
- The Royal Women's Hospital Oncology & Dysplasia Unit, Australia
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7
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Aoun E, Lawson B, Awujo C, Nebgen D, Soletsky BR, Chisholm GB, Lu KH, Nitecki Wilke R. Oncologic outcomes of incidental serous tubal intraepithelial carcinoma and associated high-grade serous carcinoma in high-risk patients undergoing risk-reducing surgery. Int J Gynecol Cancer 2025:ijgc-2024-005964. [PMID: 39496390 DOI: 10.1136/ijgc-2024-005964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2024] Open
Abstract
OBJECTIVE We sought to describe the oncologic outcomes of isolated serous tubal intraepithelial carcinomas compared to an intraepithelial carcinoma found concurrently with microscopic high-grade serous carcinoma among patients with hereditary predisposition to ovarian cancer who underwent risk-reducing surgery. METHODS We conducted a retrospective analysis of 32 high-risk patients with BRCA1, BRCA2, RAD51C/D, BRIP1, or PALB2 pathogenic variants who were diagnosed with either isolated serous tubal intraepithelial carcinoma or concurrent serous tubal intraepithelial carcinoma and microscopic high-grade serous carcinoma following risk-reducing surgery between January 2006 and December 2023. Our population included patients who underwent surgery at our institution as well as those who had surgery elsewhere, but sought second opinions, follow-up care, or treatment at our institution. Data were gathered from medical and pathologic records, and pathologic specimens were re-reviewed by a gynecologic pathologist. Standard statistical methods were used to describe oncologic outcomes per group. RESULTS Among 32 patients in the cohort, we found that 68.7% had a pathologic diagnosis of an incidental serous tubal intraepithelial carcinoma, while 31.3% had a pathologic diagnosis of microscopic high-grade serous carcinoma with associated serous tubal intraepithelial carcinoma. Notably, two patients (9%) with isolated serous tubal intraepithelial carcinoma developed primary peritoneal carcinoma within a median of 29 months after surgery. One-third of patients with microscopic cancer experienced recurrence despite receiving standard staging surgery and chemotherapy for early-stage disease. Most of the patients in the cohort were older at the time of risk-reducing surgery than recommended for their pathologic variant. CONCLUSIONS The study supports the critical need for timely risk-reducing surgery in high-risk populations, as well as a comprehensive pathologic examination along with vigilant post-operative surveillance. Consensus guidelines for management of serous tubal intraepithelial carcinoma are necessary to identify a group of patients at higher risk of progression to primary peritoneal carcinoma and optimize patient care.
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Affiliation(s)
- Eliane Aoun
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Barrett Lawson
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Chika Awujo
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Denise Nebgen
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Beth R Soletsky
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Gary B Chisholm
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Karen H Lu
- Department of Gynecologic Oncology, Moffitt Cancer Center & Research Institute, Tampa, Florida, USA
| | - Roni Nitecki Wilke
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Luvero D, Angioli R, Notaro E, Plotti F, Terranova C, Angioli AM, Festa A, Stermasi A, Manco S, Diserio M, Montera R. Serous Tubal Intraepithelial Carcinoma (STIC): A Review of the Literature on the Incidence at the Time of Prophylactic Surgery. Diagnostics (Basel) 2024; 14:2577. [PMID: 39594243 PMCID: PMC11592719 DOI: 10.3390/diagnostics14222577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/10/2024] [Accepted: 11/14/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Serous tubal intraepithelial carcinoma (STIC) is an early-stage cancerous lesion found in the fallopian tubes, often at the fimbrial end. It is strongly associated with high-grade serous carcinoma (HGSC), a highly aggressive type of ovarian cancer. STIC is considered a precursor to many HGSC cases, originating in the fallopian tubes. Its development is frequently linked to mutations in the TP53 gene, leading to the formation of a p53 signature, an early abnormality that may progress to HGSC. This signature is more common in BRCA mutation carriers, explaining the higher incidence of STIC in this group. The aim of this review is to evaluate the literature on the incidence of serous tubal intraepithelial carcinoma in patients (both BRCA-positive and BRCA-negative) undergoing preventive salpingo-oophorectomy, analysing the available data and identifying associations between specific characteristics and the onset of STIC. METHODS A comprehensive review of the literature from 2016 to 2023 was conducted using PubMed, focusing on studies analysing the incidence of STIC in BRCA-positive patients undergoing preventive salpingo-oophorectomy. Data on patient characteristics, interventions, outcomes, and incidence of STIC were extracted and analysed. RESULTS Nine international studies were included in the review, reporting varying incidences of STIC among patients undergoing salpingo-oophorectomy. The overall incidence of STIC in all the women included in the studies was 7.31%, while that in the BRCA-mutated women was approximately 6.08%. Notably, the presence of the TP53 signature was significantly associated with the occurrence of STIC. CONCLUSIONS The etiopathogenesis of STIC involves complex interactions between genetic, environmental, and molecular factors. Further research is needed to fully understand its mechanisms and identify additional risk factors beyond BRCA mutations. Establishing a national database of STIC cases could facilitate future research and improve patient outcomes.
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Affiliation(s)
- Daniela Luvero
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Roberto Angioli
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
- Research Unit of Gynecology, Department of Medicine and Surgery, Università Campus Bio Medico, Via Alvaro del Portillo 21, 00128 Roma, Italy
| | - Erika Notaro
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Francesco Plotti
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
- Research Unit of Gynecology, Department of Medicine and Surgery, Università Campus Bio Medico, Via Alvaro del Portillo 21, 00128 Roma, Italy
| | - Corrado Terranova
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
- Research Unit of Gynecology, Department of Medicine and Surgery, Università Campus Bio Medico, Via Alvaro del Portillo 21, 00128 Roma, Italy
| | - Anna Maria Angioli
- Research Unit of Gynecology, Department of Medicine and Surgery, Università Campus Bio Medico, Via Alvaro del Portillo 21, 00128 Roma, Italy
| | - Asia Festa
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Andi Stermasi
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Serena Manco
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Miriana Diserio
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Roberto Montera
- Department of Gynecology, Fondazione Policlinico Universitario Campus Bio Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
- Research Unit of Gynecology, Department of Medicine and Surgery, Università Campus Bio Medico, Via Alvaro del Portillo 21, 00128 Roma, Italy
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9
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Kim J, Choi CH. Basic knowledge for counseling patients undergoing risk-reducing salpingo-oophorectomy. Obstet Gynecol Sci 2024; 67:343-355. [PMID: 38817104 PMCID: PMC11266848 DOI: 10.5468/ogs.24054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/09/2024] [Accepted: 05/23/2024] [Indexed: 06/01/2024] Open
Abstract
Significant progress has been made in the molecular diagnosis of cancer. It provides personalized medicine, including cancer diagnosis, prognosis, targeted therapy, and risk detection. These advances allow physicians to identify patients at risk for cancer before it develops and offer them an opportunity to prevent its development. Mutations in breast cancer susceptibility genes 1 and 2 (BRCA1 and 2) are one of the most well-known cancer-related gene mutations since actor Angelina Jolie shared her experience with genetic mutations and risk-reducing surgery in the media. In Korea, tests for germline BRCA1/2 mutations have been covered by insurance since May 2012 and the number of women of BRCA1/2 mutations has continued to increase over the past decade. Most carriers of BRCA1/2 mutations consider risk-reducing salpingo-oophorectomy (RRSO) resulting in early menopause and want to know the lifetime risks and benefits of RRSO. However, despite the increasing number of carriers of BRCA1/2 mutations, the counseling and management of patients requiring RRSO varies among physicians. This article provides basic knowledge on RRSO to help physicians comprehensively assess its risks and benefits and manage at-risk women.
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Affiliation(s)
- Jihye Kim
- Department of Obstetrics and Gynecology, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea
| | - Chel Hun Choi
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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KARLAN BETHY. Improving the Lives of Women With Ovarian Cancer. Clin Obstet Gynecol 2024; 67:347-351. [PMID: 38230704 PMCID: PMC11047303 DOI: 10.1097/grf.0000000000000851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Being a gynecologic oncologist is a privilege. Women with cancer address their challenges with grit and resilience. Their most basic questions motivated my career-long search for scientific answers hidden in genetics, novel therapeutics, and cancer prevention. But medicine is a team sport. Working alongside gifted colleagues and mentoring trainees to assume starring roles on the team has sustained and enriched my career. Advocating for patients and the specialty of gynecologic oncology provided another means to advance research and cancer awareness to improve patient outcomes. The author believe the most exciting times are yet to come.
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Kang OJ, Lee SW, Kim JH, Park JY, Suh DS, Kim DY, Kim JH, Kim YM, Kim YT. Pathological findings and long-term prognosis in Korean BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy. Int J Gynecol Cancer 2023; 33:1743-1749. [PMID: 37541685 DOI: 10.1136/ijgc-2023-004618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/06/2023] Open
Abstract
OBJECTIVE Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.
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Affiliation(s)
- Ok-Ju Kang
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Shin-Wha Lee
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ju-Hyun Kim
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jeong-Yeol Park
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dae-Shik Suh
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dae-Yeon Kim
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jong-Hyeok Kim
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yong-Man Kim
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Young-Tak Kim
- Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea
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Abstract
The risk of death from ovarian cancer is highly associated with the clinical stage at diagnosis. Efforts to implement screening for ovarian cancer have been largely unsuccessful, due to the low prevalence of the disease in the general population and the heterogeneity of the various cancer types that fall under the ovarian cancer designation. A practical test for early detection will require both high sensitivity and high specificity to balance reducing the number of cancer deaths with minimizing surgical interventions for false positive screens. The technology must be cost-effective to deliver at scale, widely accessible, and relatively noninvasive. Most importantly, a successful early detection test must be effective not only at diagnosing ovarian cancer but also in reducing ovarian cancer deaths. Stepwise or multimodal approaches among the various areas under investigation will likely be required to make early detection a reality.
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Affiliation(s)
- Naoko Sasamoto
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
| | - Kevin M Elias
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
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13
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Abay M, Ozgen L, Yalcin Y, Ozerkan K. Clinical significance of risk-reducing salpingo-oophorectomy in patients with BRCA1/2 mutation. J Gynecol Obstet Hum Reprod 2023; 52:102642. [PMID: 37573025 DOI: 10.1016/j.jogoh.2023.102642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 08/06/2023] [Indexed: 08/14/2023]
Abstract
OBJECTIVE Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion which is located in the distal fallopian tube and causes high grade serous ovarian carcinoma (HGSOC). The incidence of STIC for women underwent risk reducing salpingo-oophorectomy for BRCA mutation varies from 0.6 to 7% and its clinical outcomes are still unclear. The aim of this study was to demonstrate the incidence of STIC and HGSOC in BRCA1/2 mutation carriers after risk reducing salpingo-oophorectomy (RRSO) and the clinical outcomes of these patients. MATERIAL AND METHODS We retrospectively reviewed the records of 48 BRCA1 and/or 2 mutation carriers who underwent prophylactic salpingo-oophorectomy with or without hysterectomy at the Department of Obstetrics and Gynecology, Bursa Uludag University between January 2000 and January 2022. INCLUSION CRITERIA BRCA 1 and/or 2 mutation carriers diagnosed by genetic testing, asymptomatic patients with no abnormal findings on pelvic examination. EXCLUSION CRITERIA patients with no abnormal findings on pelvic examination and a presence of a personal history of ovarian, fallopian tube or peritoneal cancer. RESULTS A total of 48 BRCA 1 and/or 2 mutation carriers underwent RRSO. STIC was diagnosed in 1 (2,0%) patient and restaging surgery was not performed. Primary peritoneal carcinoma (PPC) did not develop during the 20 months follow-up period. One (2.0%) patient was diagnosed with occult ovarian cancer. Restaging surgery was performed and chemotherapy treatments were given after surgery. A pelvic recurrence developed 25 months after the occult cancer diagnosis in the follow up period. One (2.0%) patient with normal histopathological findings after RRSO was diagnosed with peritoneal cancer 57 months after the operation. CONCLUSION The risk of PPC continues after RRSO. Therefore, close follow-up procedure is very important for early diagnosis and effective treatment of patients with PPC after RRSO.
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Affiliation(s)
- Merve Abay
- Faculty of Medicine Gynecological Oncology Surgery, Uludag University, Bursa 16059, Turkey
| | - Levent Ozgen
- Faculty of Medicine Gynecological Oncology Surgery, Uludag University, Bursa 16059, Turkey.
| | - Yakup Yalcin
- Faculty of Medicine Gynecological Oncology Surgery, Uludag University, Bursa 16059, Turkey
| | - Kemal Ozerkan
- Faculty of Medicine Gynecological Oncology Surgery, Uludag University, Bursa 16059, Turkey
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14
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Schwartz ZP, Li AJ, Walsh CS, Rimel BJ, Alvarado MM, Lentz SE, Cass I. Patterns of care and outcomes of risk reducing surgery in women with pathogenic variants in non-BRCA and Lynch syndrome ovarian cancer susceptibility genes. Gynecol Oncol 2023; 173:1-7. [PMID: 37030072 DOI: 10.1016/j.ygyno.2023.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 03/22/2023] [Accepted: 03/23/2023] [Indexed: 04/10/2023]
Abstract
OBJECTIVES Guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) for women with pathogenic variants of non-BRCA and Lynch syndrome-associated ovarian cancer susceptibility genes. Optimal timing and findings at the time of RRSO for these women remains unclear. We sought to characterize practice patterns and frequency of occult gynecologic cancers for these women at our two institutions. METHODS Women with germline ovarian cancer susceptibility gene pathogenic variants who underwent RRSO between 1/2000-9/2019 were reviewed in an IRB-approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. RESULTS 26 Non-BRCA (9 BRIP1, 9 RAD51C, and 8 RAD51D) and 75 Lynch (36 MLH1, 18 MSH2, 21 MSH6) pathogenic variants carriers were identified. Median age at time of RRSO was 47. There were no occurrences of occult ovarian or fallopian tube cancer in either group. Two patients (3%) in the Lynch group had occult endometrial cancer. Median follow up was 18 and 35 months for non-BRCA and Lynch patients, respectively. No patient developed primary peritoneal cancer upon follow up. Post-surgical complications occurred in 9/101 (9%) of patients. Hormone replacement therapy (HRT) was rarely used despite reported post-menopausal symptoms in 6/25 (23%) and 7/75 (37%) patients, respectively. CONCLUSIONS No occult ovarian or tubal cancers were observed in either group. No recurrent or primary gynecologic-related cancers occurred upon follow-up. Despite frequent menopausal symptoms, HRT use was rare. Both groups experienced surgical complications when hysterectomy and/or concurrent colon surgery was performed suggesting concurrent surgeries should only be performed when indicated.
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Affiliation(s)
- Zachary P Schwartz
- Kaiser Permanente Panorama City Medical Center, Division of Gynecologic Oncology, 13640 Roscoe Blvd., Panorama City, CA 91402, USA.
| | - Andrew J Li
- Cedars-Sinai Medical Center, Samuel Oschin Cancer Center, 127 S. San Vicente Blvd., 7th Floor, Los Angeles, CA 90048, USA.
| | - Christine S Walsh
- University of Colorado Cancer Center, 1665 Aurora Court, Aurora, CO 80045, USA.
| | - B J Rimel
- Cedars-Sinai Medical Center, Samuel Oschin Cancer Center, 127 S. San Vicente Blvd., 7th Floor, Los Angeles, CA 90048, USA.
| | - Monica M Alvarado
- Kaiser Permanente Southern California Regional Genetic Services, 393 E. Walnut St. 6 SW, Pasadena, CA 91188, USA.
| | - Scott E Lentz
- Kaiser Permanente Los Angeles Medical Center, Gynecology Oncology Department, 4950 W., Sunset Blvd., Los Angeles, CA 90027, USA.
| | - Ilana Cass
- Dartmouth Hitchcock Medical Center, Department of Obstetrics and Gynecology, 1 Medical, Center Drive, Lebanon, NH 03756, USA.
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Manley K, Ryan N, Jenner A, Newton C, Hillard T. Counselling of path_ BRCA carriers who are considering risk-reducing oophorectomy. Post Reprod Health 2023; 29:42-52. [PMID: 36757900 DOI: 10.1177/20533691231156640] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
path_BRCA 1/2 increases a woman's lifetime risk of breast and ovarian cancer. Interventions can be offered which manage cancer risk; annual breast screening from age 30, chemoprevention and, once a woman's family is complete, risk-reducing surgery. The latter is the most effective method of reducing cancer in path_BRCA carriers; salpingo-oophorectomy reduces breast and ovarian cancer, respectively, by up to 50% and 95%. Factors affecting a woman's decision to undergo risk-reducing surgery are complex; dominant factors include risks of surgery, effect on cancer outcomes and menopausal sequelae. Specific information relating to hormone replacement and non-hormonal alternatives are an important consideration for women but, are often overlooked. Informative counselling is required to enable satisfaction with the chosen intervention whilst improving survival outcomes. This review paper outlines the current data pertaining to these decision-making factors and provides a proforma to enable effective counselling.
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Affiliation(s)
- Kristyn Manley
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
| | - Neil Ryan
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
- Department of Gynaecology Oncology, Royal Infirmary of Edinburgh, Edinburgh
| | - Abigail Jenner
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- Department of Oncology, 1556Royal United Hospitals Bath, Bath, UK
| | - Claire Newton
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
| | - Timothy Hillard
- Department of Gynaecology, 6655University Hospitals Dorset, Poole, UK
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16
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Amuzu S, Fu L, Demko N, Rivera B, Domecq C, de Kock L, Hamel N, Gilbert L, Polak P, Ragoussis J, Foulkes WD. Long-term tumour dormancy in a BRCA1 heterozygote. J Med Genet 2023; 60:33-35. [PMID: 35039446 DOI: 10.1136/jmedgenet-2021-108269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/10/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Setor Amuzu
- Genome Sciences, McGill Genome Centre, Montreal, Quebec, Canada.,Department of Human Genetics, McGill University, Montreal, Quebec, Canada
| | - Lili Fu
- Department of Pathology, McGill University, Montreal, Quebec, Canada
| | - Nadine Demko
- Department of Pathology, McGill University, Montreal, Quebec, Canada
| | - Barbara Rivera
- Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.,Program in Molecular Mechanisms and Experimental Therapy in Oncology (ONCOBELL), and Hereditary Cancer Program at ICO-IDIBELL, Bellvitge Biomedical Research Institut (IDIBELL), Barcelona, Spain
| | - Celine Domecq
- Cancer Research Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Leanne de Kock
- Department of Human Genetics, McGill University, Montreal, Quebec, Canada.,Department of Pediatrics, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
| | - Nancy Hamel
- Cancer Research Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Lucy Gilbert
- Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.,Cancer Research Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.,Departments of Obstetrics & Gynaecology, McGill University, Montreal, Quebec, Canada
| | - Paz Polak
- Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.,Department of Oncological Sciences, and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jiannis Ragoussis
- Genome Sciences, McGill Genome Centre, Montreal, Quebec, Canada.,Department of Human Genetics, McGill University, Montreal, Quebec, Canada
| | - William D Foulkes
- Department of Human Genetics, McGill University, Montreal, Quebec, Canada .,Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.,Cancer Research Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.,Department of Medicine, McGill University, Montreal, Quebec, Canada
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17
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Cassani C, Rossi C, Camnasio CA, Urtis M, Fiandrino G, Grasso M, Zanellini F, Lucioni M, D’Ambrosio G, Di Toro A, Rossi M, Roccio M, Ferrari A, Secondino S, Nappi RE, Arbustini E, Paulli M, Spinillo A, Cesari S. Pathologic Findings at Risk Reducing Surgery in BRCA and Non- BRCA Mutation Carriers: A Single-Center Experience. Diagnostics (Basel) 2022; 12:diagnostics12123054. [PMID: 36553061 PMCID: PMC9776991 DOI: 10.3390/diagnostics12123054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022] Open
Abstract
Risk-reducing surgery (RRS) is recommended in BRCA-mutated carriers because of their increased risk of developing ovarian cancer, while its role is still discussed for women harboring mutations in non-BRCA homologous repair genes. The aim of this study was to retrospectively evaluate the occurrence of pathological findings in a high-risk population undergoing RRS in San Matteo Hospital, Pavia between 2012 and 2022, and correlate their genetic and clinical outcomes, comparing them with a control group. The final cohort of 190 patients included 85 BRCA1, 63 BRCA2, 11 CHEK2, 7 PALB2, 4 ATM, 1 ERCC5, 1 RAD51C, 1 CDH1, 1 MEN1, 1 MLH1 gene mutation carriers and 15 patients with no known mutation but with strong familial risk. Occult invasive serous carcinoma (HGSC) and serous tubal intraepithelial carcinoma (STIC) were diagnosed in 12 (6.3%) women, all of them BRCA carriers. No neoplastic lesion was diagnosed in the non-BRCA group, in women with familial risk, or in the control group. Oral contraceptive use and age ≤45 at surgery were both found to be favorable factors. While p53 signature and serous tubal intraepithelial lesion (STIL) were also seen in the control group and in non-BRCA carriers, STIC and HGSC were only found in BRCA1/2 mutation carriers.
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Affiliation(s)
- Chiara Cassani
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Unit of Obstetrics and Gynecology, University of Pavia, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Chiara Rossi
- Department of Molecular Medicine, Unit of Anatomic Pathology, University of Pavia, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Cristina Angela Camnasio
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Unit of Obstetrics and Gynecology, University of Pavia, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Mario Urtis
- Transplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Giacomo Fiandrino
- Unit of Anatomic Pathology, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Maurizia Grasso
- Transplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Francesca Zanellini
- Unit of Obstetrics and Gynecology, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Marco Lucioni
- Department of Molecular Medicine, Unit of Anatomic Pathology, University of Pavia, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Gioacchino D’Ambrosio
- Unit of Anatomic Pathology, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Alessandro Di Toro
- Transplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Margherita Rossi
- Unit of Obstetrics and Gynecology, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Marianna Roccio
- Unit of Obstetrics and Gynecology, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Alberta Ferrari
- General Surgery III—Breast Surgery, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Simona Secondino
- Unit of Medical Oncology, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Rossella Elena Nappi
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, University of Pavia, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Eloisa Arbustini
- Transplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Marco Paulli
- Department of Molecular Medicine, Unit of Anatomic Pathology, University of Pavia, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Arsenio Spinillo
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Unit of Obstetrics and Gynecology, University of Pavia, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
| | - Stefania Cesari
- Unit of Anatomic Pathology, IRCCS San Matteo Hospital Foundation, 27100 Pavia, Italy
- Correspondence:
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18
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Marchetti C, Arcieri M, Vertechy L, Ergasti R, Russo G, Zannoni GF, Minucci A, Ercoli A, Scambia G, Fagotti A. Risk reducing surgery with peritoneal staging in BRCA1-2 mutation carriers. A prospective study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2539-2544. [PMID: 35871032 DOI: 10.1016/j.ejso.2022.07.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 06/23/2022] [Accepted: 07/05/2022] [Indexed: 01/07/2023]
Abstract
INTRODUCTION International guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) in BRCA1-2 mutations carriers to decrease ovarian cancer occurrence. In this prospective study, we describe the incidence of occult malignancies and the surgical outcomes in asymptomatic BRCA mutation carriers submitted to RRSO. METHODS Data on BRCA1-2 carriers undergoing RRSO with peritoneal washing and peritoneal/omental biopsies (PeS), between January 2019 until March 2021, were prospectively collected. RESULTS A total of 132 patients were enrolled: 74 BRCA1 and 58 BRCA2 mutation carriers. 31.1% women underwent RRSO and PeS (16.2% of BRCA1 and 50% of BRCA2 carriers), while 68.9% patients were submitted also to concomitant hysterectomy. Almost all the procedures (99.2%) were performed by minimally invasive surgery. Postoperative complications occurred in twelve patients (9.1%): 10 in the concomitant hysterectomy group and two complications in the RRSO group. At the final pathological examination, 6 (4.5%) occult carcinomas were diagnosed: 3 fallopian tube carcinomas, one ovarian carcinoma and two serous tubal intraepithelial carcinomas (STICs), with negative PeS. Median age of occult carcinomas patients at RRSO was 54 (range: 48-79) years. The mean follow up was 20 (range: 7-34) months. During the follow up, no primary peritoneal cancer has been diagnosed. CONCLUSIONS Occult pathologic findings in RRSO occurred in 4.5% (3% invasive carcinomas, STIC 1.5%) among our patients. The routine use of peritoneal biopsies does not improve the detection of occult malignancies. Our data confirm the importance of timely performing RRSO in BRCA1-2 carriers.
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Affiliation(s)
- Claudia Marchetti
- Department of Women, Child and Public Health, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy; Catholic University of Sacred Heart, Rome, Italy
| | - Martina Arcieri
- Department of Biomedical, Dental, Morphological and Functional Imaging Science, University of Messina, Messina, Italy
| | - Laura Vertechy
- Department of Women, Child and Public Health, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
| | - Raffaella Ergasti
- Department of Women, Child and Public Health, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
| | - Giorgia Russo
- Department of Women, Child and Public Health, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
| | - Gian Franco Zannoni
- Department of Women, Child and Public Health, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
| | - Angelo Minucci
- Molecular and Genomic Diagnostics Unit (MGDUnit), Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
| | - Alfredo Ercoli
- Department of Human Pathology in Adult and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Giovanni Scambia
- Department of Women, Child and Public Health, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy; Catholic University of Sacred Heart, Rome, Italy.
| | - Anna Fagotti
- Department of Women, Child and Public Health, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy; Catholic University of Sacred Heart, Rome, Italy
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19
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Ruel-Laliberté J, Kasasni SM, Oprea D, Viau M. Outcome and Management of Serous Tubal Intraepithelial Carcinoma Following Opportunistic Salpingectomy: Systematic Review and Meta-Analysis. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2022; 44:1174-1180. [PMID: 36099965 DOI: 10.1016/j.jogc.2022.08.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/24/2022] [Accepted: 08/25/2022] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Serous ovarian cancer is the most common subtype of epithelial ovarian carcinoma-the most prevalent type of ovarian cancer. High-grade serous ovarian carcinoma (HGSOC) is thought to arise from the distal fallopian tube, with a precursor lesion known as serous tubal intraepithelial carcinoma (STIC). STICs are found in the final pathology of a salpingectomy specimen in 10%-20% of women with a BRCA gene mutation and 1%-7% of women without a mutation. However, there is currently no official guideline and a paucity of data on the management of STICs. DATA SOURCES We performed a systematic review following PRISMA guidelines. Five databases were searched for relevant studies on STICs. STUDY SELECTION Two independent reviewers performed the abstract and full-text screening and data extraction, with conflicts resolved through discussion with the third reviewer. The risk of bias of each study was assessed using the Newcastle-Ottawa scale. DATA EXTRACTION AND SYNTHESIS Fourteen articles were included. Ninety-nine patients who were diagnosed with STIC and subsequently followed for a mean period of 55.5 months were included in this analysis. Eighty-three patients (83.9%) were BRCA mutation carriers. After the diagnosis of isolated STIC, 7 patients (7.3%) received chemotherapy and 25 (26%) underwent surgical staging. Three of the 25 patients were diagnosed with HGSOC based on the staging surgery. Nine patients were later diagnosed with HGSOC during follow-up, with an average duration of follow-up of 58.5 months between the diagnosis of STIC and the diagnosis of HGSOC. CONCLUSION Based on our review of the literature, there is a 10.7% risk of having concurrent HGSOC at the time of STIC diagnosis, and the risk of developing a subsequent HGSOC is 14.5%. BRCA mutation status should be determined in cases of isolated STIC, as 83.9% of patients included in this study were found to carry BRCA mutations. We believe it is necessary to further investigate the role of surgical staging following the diagnosis of STIC.
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Affiliation(s)
- Jessica Ruel-Laliberté
- Department of Obstetrics & Gynecology, Division of Gynaecologic Oncology, Université de Sherbrooke, Sherbrooke, QC.
| | | | - Diana Oprea
- Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC
| | - Mathieu Viau
- Department of Obstetrics & Gynecology, Division of Gynaecologic Oncology, Université de Sherbrooke, Sherbrooke, QC
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20
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Smallwood KG, Crockett S, Huang V, Cullimore V, Davies J, Satti G, Phillips A. Changing patterns of referral into a family history clinic and detection of ovarian cancer: a retrospective 10-year review. J OBSTET GYNAECOL 2022; 42:2652-2658. [PMID: 35980980 DOI: 10.1080/01443615.2022.2111253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
This study examines whether a change in the criteria for genetic testing for ovarian cancer risk changed the nature of referrals into our Familial Cancer service. This is a retrospective review of 273 women who underwent risk reducing surgery (RRS). The primary outcome was to establish whether there was an increase in women having RRS with a confirmed genetic mutation. Secondary outcomes included the incidence of occult cancer and of subsequent primary peritoneal cancer. The results showed an increase in women being offered RRS based on genetic diagnosis; 91% versus 32% before the criteria change. Four occult malignancies (1.5%) and two peritoneal cancers (0.7%) were noted.We have demonstrated a change in the nature of referrals to the familial cancer service from perceived risk to genetic diagnosis. We can now counsel women more accurately. With a defined risk we are enabling them to make an informed decision regarding risk reduction.
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Affiliation(s)
- K G Smallwood
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
| | - S Crockett
- Department of Familial Cancer, University Hospitals of Derby and Burton, Derby, UK
| | - V Huang
- Medical School, University of Nottingham, Nottingham, UK
| | - V Cullimore
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
| | - J Davies
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
| | - G Satti
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
| | - A Phillips
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
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21
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Chandanwale SS, Lad YP, Bardapurkar PR, Buch AC. Coexistence of Ectopic Tubal Pregnancy with Serous Tubal Intraepithelial Carcinoma: A Rare Case Report with Review of Literature. J Hum Reprod Sci 2022; 15:399-401. [PMID: 37033139 PMCID: PMC10077741 DOI: 10.4103/jhrs.jhrs_134_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/01/2022] [Accepted: 11/15/2022] [Indexed: 12/15/2022] Open
Abstract
Serous tubal intraepithelial carcinoma is a precursor lesion for high-grade pelvic serous carcinoma. The incidence is 0.6%-6% in tubectomy specimens of women who are BRCA-1,2 positive or have a strong family history of breast or ovarian cancer. STIC in women who do not have BRCA-1,2 mutations or concomitant high-grade serous carcinoma is exceedingly rare. Ectopic tubal gestation coexisting with serous tubal intraepithelial carcinoma is very rarely reported. These lesions pose considerable difficulty in the diagnosis. A combination of histology and immunohistochemical expression p53 and ki67 substantially improves the reproducibility of the diagnosis. Diagnosing these lesions will help identify potential at risk patients and their families for carcinoma. Adequate prolonged follow-up for incidental serous tubal intraepithelial carcinoma is the mainstay. We report one such case of a 31-year-old female who was operated for the right tubal gestation and found to have serous tubal intraepithelial carcinoma.
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Affiliation(s)
| | | | | | - Archana Chirag Buch
- Department of Pathology, Dr. D Y Patil Medical College, Pune, Maharashtra, India
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22
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Linz VC, Löwe A, van der Ven J, Hasenburg A, Battista MJ. Incidence of pelvic high-grade serous carcinoma after isolated STIC diagnosis: A systematic review of the literature. Front Oncol 2022; 12:951292. [PMID: 36119503 PMCID: PMC9472545 DOI: 10.3389/fonc.2022.951292] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/09/2022] [Indexed: 11/29/2022] Open
Abstract
Objective Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion of pelvic high-grade serous carcinoma (HGSC). Information on treatment and outcome of isolated STIC is rare. Therefore, we reviewed systematically the published literature to determine the incidence of subsequent HGSC in the high- and low-risk population and to summarize the current diagnostic and therapeutic options. Methods A systematic review of the literature was conducted in MEDLINE-Ovid, Cochrane Library and Web of Science of articles published from February 2006 to July 2021. Patients with an isolated STIC diagnosis and clinical follow-up were included. Study exclusion criteria for review were the presence of synchronous gynaecological cancer and/or concurrent non-gynaecological malignancies. Results 3031 abstracts were screened. 112 isolated STIC patients out of 21 publications were included in our analysis with a pooled median follow-up of 36 (interquartile range (IQR): 25.3-84) months. 71.4% of the patients had peritoneal washings (negative: 62.5%, positive: 8%, atypic cells: 0.9%). Surgical staging was performed in 28.6% of all STICs and did not show any malignancies. 14 out of 112 (12.5%) patients received adjuvant chemotherapy with Carboplatin and Paclitaxel. Eight (7.1%) patients developed a recurrence 42.5 (IQR: 33-72) months after isolated STIC diagnosis. Cumulative incidence of HGSC after five (ten) years was 10.5% (21.6%). Recurrence occurred only in BRCA1 carriers (seven out of eight patients, one patient with unknown BRCA status). Conclusion The rate of HGSC after an isolated STIC diagnosis was 7.1% with a cumulative incidence of 10.5% (21.6%) after five (ten) years. HGSC was only observed in BRCA1 carriers. The role of adjuvant therapy and routine surveillance remains unclear, however, intense surveillance up to ten years is necessary. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42021278340.
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23
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Vang R, Shih IM. Serous tubal intraepithelial carcinoma: What Do We Really Know at this Point? Histopathology 2022; 81:542-555. [PMID: 35859323 DOI: 10.1111/his.14722] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 06/18/2022] [Accepted: 06/23/2022] [Indexed: 11/27/2022]
Abstract
Serous tubal intraepithelial carcinoma (STIC) is the earliest morphologically recognizable step in the development of invasive high-grade serous carcinoma of the fallopian tube. Lesions occurring prior to STIC within the carcinogenic sequence for the pathogenesis of invasive high-grade serous carcinoma include the p53 signature and secretory cell outgrowth (SCOUT). Variable histologic criteria have been used for diagnosing STIC, but a combination of morphology and immunohistochemistry for p53/Ki-67 improves interobserver agreement. Half of all carcinomas identified in risk-reducing salpingo-oophorectomy specimens are in the form of STIC; however, STIC also may be incidentally found on occasion in specimens from women at low or average risk of ovarian/tubal/peritoneal carcinoma. TP53 mutation is the earliest known DNA sequence alteration in STIC and almost all invasive high-grade serous carcinomas of the ovary and peritoneum. Data on the clinical behavior of STIC are limited. While the short-term follow-up in the prior literature suggests a low risk of malignant progression, a more recent meta-analysis indicates a 10-year risk of 28%. STIC probably should be best regarded as a lesion with uncertain malignant potential at present, and future molecular analysis will help classify those with higher risk of dissemination. This review article provides an update on the current knowledge of STIC and related issues.
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Affiliation(s)
- Russell Vang
- Departments of Pathology (Division of Gynecologic Pathology), The Johns Hopkins University School of Medicine; Baltimore, MD, USA.,Gynecology & Obstetrics, The Johns Hopkins University School of Medicine; Baltimore, MD, USA
| | - Ie-Ming Shih
- Departments of Pathology (Division of Gynecologic Pathology), The Johns Hopkins University School of Medicine; Baltimore, MD, USA.,Gynecology & Obstetrics, The Johns Hopkins University School of Medicine; Baltimore, MD, USA.,Oncology, The Johns Hopkins University School of Medicine; Baltimore, MD, USA
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24
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Steenbeek MP, van Bommel MH, Bulten J, Hulsmann JA, Bogaerts J, Garcia C, Cun HT, Lu KH, van Beekhuizen HJ, Minig L, Gaarenstroom KN, Nobbenhuis M, Krajc M, Rudaitis V, Norquist BM, Swisher EM, Mourits MJ, Massuger LF, Hoogerbrugge N, Hermens RP, IntHout J, de Hullu JA. Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis. J Clin Oncol 2022; 40:1879-1891. [PMID: 35302882 PMCID: PMC9851686 DOI: 10.1200/jco.21.02016] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
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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Affiliation(s)
- Miranda P. Steenbeek
- Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Obstetrics and Gynaecology, Nijmegen, the Netherlands,Miranda P. Steenbeek, MD, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, the Netherlands; e-mail:
| | - Majke H.D. van Bommel
- Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Obstetrics and Gynaecology, Nijmegen, the Netherlands
| | - Johan Bulten
- Radboud University Medical Center, Department of Pathology, Nijmegen, the Netherlands
| | - Julia A. Hulsmann
- Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Obstetrics and Gynaecology, Nijmegen, the Netherlands
| | - Joep Bogaerts
- Radboud University Medical Center, Department of Pathology, Nijmegen, the Netherlands
| | - Christine Garcia
- Kaiser Permanente Northern California, Division of Gynecologic Oncology San Francisco, San Francisco CA
| | - Han T. Cun
- Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Karen H. Lu
- Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Heleen J. van Beekhuizen
- Erasmus MC Cancer Center, University Medical Center Rotterdam, Department of Gynecological Oncology, Rotterdam, the Netherlands
| | - Lucas Minig
- Gynecologic Oncology Unit, IMED Hospitales, Valencia, Spain
| | - Katja N. Gaarenstroom
- Leiden University Medical Center, Department of Obstetrics and Gynecology, Leiden, the Netherlands
| | - Marielle Nobbenhuis
- The Royal Marsden NHS Foundation Trust, Department of Gynaecology, London, England
| | - Mateja Krajc
- Institute of Oncology Ljubljana, Department of Clinical Genetics, Ljubljana, Slovenia
| | - Vilius Rudaitis
- Vilnius University Faculty of Medicine, Clinic of Obstetrics and Gynecology, Vilnius, Lithuania
| | | | | | - Marian J.E. Mourits
- University Medical Center Groningen, University of Groningen, Department of Gynecologic Oncology, Groningen, the Netherlands
| | - Leon F.A.G. Massuger
- Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Obstetrics and Gynaecology, Nijmegen, the Netherlands
| | - Nicoline Hoogerbrugge
- Radboud University Medical Center, Department of Human Genetics, Nijmegen, the Netherlands
| | - Rosella P.M.G. Hermens
- Radboud University Medical Center, Radboud Institute for Health Sciences, Scientific Institute for Quality of Healthcare, Nijmegen, the Netherlands
| | - Joanna IntHout
- Radboud University Medical Center, Radboud Institute for Health Sciences, Department for Health Evidence, Nijmegen, the Netherlands
| | - Joanne A. de Hullu
- Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Obstetrics and Gynaecology, Nijmegen, the Netherlands
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25
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Endometrial Cancer and BRCA Mutations: A Systematic Review. J Clin Med 2022; 11:jcm11113114. [PMID: 35683509 PMCID: PMC9181458 DOI: 10.3390/jcm11113114] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/25/2022] [Accepted: 05/28/2022] [Indexed: 11/16/2022] Open
Abstract
This systematic review identifies, evaluates, and summarises the findings of all relevant individual studies on the prevalence of BRCA mutation (BRCAm) in endometrial cancer patients and the incidence of endometrial cancer in BRCAm women patients. Consequently, the benefits and limits of a prophylactic hysterectomy at the time of the risk-reducing salpingo-oophorectomy are analysed and discussed. A systematic literature search was performed in the databases of PubMed, Cochrane, and Web of Science until May 2022; 13 studies met the eligibility criteria. Overall, 1613 endometrial cancer patients from 11 cohorts were tested for BRCA1/2 mutation. BRCA1/2m were identified in 4.3% of women with endometrial cancer (70/1613). BRCA1m was the most represented (71.4%) pathogenic variant. Alongside, a total of 209 BRCAm carriers from 14 studies were diagnosed with endometrial cancer. Only 5 out of 14 studies found a correlation between BRCAm and an increased risk of endometrial cancer. Nevertheless, two studies found a statistical difference only for BRCA1m women. The present systematic review does not provide strong evidence in favour of performing routine hysterectomy at the time of risk-reducing salpingo-oophorectomy; however, it provides epidemiological data that can be useful for counselling patients in order to offer a tailored approach.
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26
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Bogaerts JMA, Steenbeek MP, van Bommel MHD, Bulten J, van der Laak JAWM, de Hullu JA, Simons M. Recommendations for diagnosing STIC: a systematic review and meta-analysis. Virchows Arch 2022; 480:725-737. [PMID: 34850262 PMCID: PMC9023413 DOI: 10.1007/s00428-021-03244-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 10/27/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022]
Abstract
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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Affiliation(s)
- Joep M A Bogaerts
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
| | - Miranda P Steenbeek
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Majke H D van Bommel
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Johan Bulten
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands
| | | | - Joanne A de Hullu
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Michiel Simons
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands
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27
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Sina F, Cassani C, Comerio C, De Ponti E, Zanellini F, Delle Marchette M, Roversi G, Jaconi M, Arbustini E, Urtis M, Dell'Oro C, Zambetti B, Paniga C, Acampora E, Negri S, Lazzarin S, Cesari S, Spinillo A, Kotsopoulos J, Fruscio R. Tubal histopathological abnormalities in BRCA1/2 mutation carriers undergoing prophylactic salpingo-oophorectomy: a case-control study. Int J Gynecol Cancer 2022; 32:41-47. [PMID: 34845040 DOI: 10.1136/ijgc-2021-003153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/15/2021] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE To describe tubal histopathological abnormalities in women with germline BRCA1/2 mutations and in controls. METHODS Consecutive women with BRCA1/2 mutations undergoing bilateral salpingo-oophorectomy between 2010 and 2020 in two centers (San Gerardo Hospital, Monza and San Matteo Hospital, Pavia) were considered in this analysis and compared with controls who had the same surgical procedure for benign conditions. Frequency of p53 signature, serous tubal intraepithelial carcinoma, and high-grade serous ovarian cancer were compared between the two groups. RESULTS A total of 194 women with pathogenic BRCA1/2 mutations underwent prophylactic salpingo-oophorectomy. Of these, 138 women (71%) had a completely negative histological examination, while in 56 (29%) patients an ovarian or tubal alteration was reported. Among controls, 84% of patients had a p53wt signature, while 16% had a p53 signature. There was no difference in the frequency of a p53 signature between cases and controls; however, women with BRCA1/2 mutations were more likely to have pre-malignant or invasive alterations of tubal or ovarian epithelium (p=0.015). Among mutation carriers, older age both at genetic testing and at surgery was associated with an increased risk of having malignancies (OR=1.07, p=0.006 and OR=1.08, p=0.004, respectively). The risk of malignancy seems to be increased in patients with a familial history of high-grade serous ovarian cancer. Previous therapy with tamoxifen was significantly more frequent in patients with malignant lesions (40.0% vs 21.3%, p=0.006). CONCLUSION We found that a p53 signature is a frequent finding both in BRCA1/2 mutation carriers and in controls, while pre-invasive and invasive lesions are more frequent in BRCA1/2 mutation carriers. Genetic and clinical characteristics are likely to affect the progression to malignancy.
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Affiliation(s)
- Federica Sina
- Department of Surgery, Gynecological Surgery Unit, San Gerardo Hospital, Monza, Lombardia, Italy
| | - Chiara Cassani
- Gynecology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
| | - Chiara Comerio
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
| | - Elena De Ponti
- Department of Physical Medicine, San Gerardo Hospital, Monza, Italy
| | - Francesca Zanellini
- Gynecology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
| | | | - Gaia Roversi
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
- Department of Pathology, Unit of Genetics, San Gerardo Hospital, Monza, Italy
| | - Marta Jaconi
- Department of Pathology, San Gerardo Hospital, Monza, Lombardia, Italy
| | - Eloisa Arbustini
- Center for Inherited Cardiovascular Disease, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
| | - Mario Urtis
- Center for Inherited Cardiovascular Disease, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
- Department of Industrial and Information Engineering, University of Pavia, Pavia, Italy
| | - Cristina Dell'Oro
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
| | - Benedetta Zambetti
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
| | - Cristiana Paniga
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
| | - Eleonora Acampora
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
| | - Serena Negri
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
| | - Sara Lazzarin
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
| | - Stefania Cesari
- Pathology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
| | - Arsenio Spinillo
- Gynecology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
| | - Joanne Kotsopoulos
- Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Robert Fruscio
- Department of Surgery, Gynecological Surgery Unit, San Gerardo Hospital, Monza, Lombardia, Italy
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
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28
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Pross T, Karsten MM, Blohmer JU, Speiser D. Role of Routine Peritoneal Biopsies During Risk Reducing Salpingo-Oophorectomy (RRSO). Geburtshilfe Frauenheilkd 2021; 81:1031-1038. [PMID: 34531609 PMCID: PMC8437580 DOI: 10.1055/a-1395-7715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 02/17/2021] [Indexed: 11/23/2022] Open
Abstract
Objective
The objective of this retrospective study was to assess the role of routine peritoneal biopsies during risk reducing salpingo-oophorectomy (RRSO).
Methods
Data of 204 women who underwent RRSO between January 1, 2014 and February 20, 2020 at Charité – Universitätsmedizin Berlin, Campus Mitte were retrospectively analyzed. RRSO was done according to the standard operating procedures of the German Consortium Hereditary Breast and Ovarian Cancer (GC-HBOC) with peritoneal washing and several peritoneal biopsies. Specimen collected during RRSO were analyzed using the protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Perioperative complications were classified using the Clavien-Dindo-Classification.
Results
147 women who underwent RRSO had peritoneal biopsies and pelvic washing, 44 women had none of that. 123 patients (64.4%) carried a pathologic variant in
gBRCA1
, 53 (27.7%) carried a pathologic variant in
gBRCA2
. Histopathological evaluation identified four patients (2.1%) with pathological findings. Neither peritoneal biopsies nor pelvic washings revealed additional information after histological examination. There was no statistically significant difference in complication rate between the two groups. The mean surgery time for RRSO without peritoneal biopsies was 64.3 minutes compared to 77.8 minutes with peritoneal biopsies. That shows a statistically significant prolongation of 16% (13.5 minutes, p = 0.0383).
Conclusions
The routine use of peritoneal biopsies during RRSO does not improve detection of occult ovarian cancer or STIC but prolongs the operation time significantly. By omitting peritoneal biopsies in RRSO not only perioperative risks are diminished but also costs could be reduced by shortening of surgery time as well as decreased number of pathological samples.
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Affiliation(s)
- Therese Pross
- Charité - Universitätsmedizin Berlin, Department of Gynecology and breast center, Berlin, Germany
| | - Maria Margarete Karsten
- Charité - Universitätsmedizin Berlin, Department of Gynecology and breast center, Berlin, Germany
| | - Jens-Uwe Blohmer
- Charité - Universitätsmedizin Berlin, Department of Gynecology and breast center, Berlin, Germany
| | - Dorothee Speiser
- Charité - Universitätsmedizin Berlin, Department of Gynecology and breast center, Berlin, Germany.,Charité - Universitätsmedizin Berlin, Hereditary Breast and Ovarian Cancer Center, Berlin, Germany
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Efficacy of risk-reducing salpingo-oophorectomy in BRCA1-2 variants and clinical outcomes of follow-up in patients with isolated serous tubal intraepithelial carcinoma (STIC). Gynecol Oncol 2021; 163:364-370. [PMID: 34465478 DOI: 10.1016/j.ygyno.2021.08.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/20/2021] [Accepted: 08/23/2021] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic high-grade serous carcinoma. The management of STIC diagnosed after risk-reducing salpingo-oophorectomy (RRSO) in women with BRCA1-2 variants remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and occult invasive cancer (OC) and to determine the long-term outcomes of these patients. METHODS We conducted a retrospective study of patients with BRCA 1-2 variants who underwent RRSO between January-2010 and Dicember-2020 at the Clinic of Gynaecology of University of Padova. INCLUSION CRITERIA women with a negative pelvic examination at the last screening prior to RRSO, patients with fallopian tubes analysed using the SEE-FIM protocol. EXCLUSION CRITERIA patients with a positive gynaecologic screening or with ovarian/tubal cancer prior to RRSO. RESULTS We included 153 patients. STICs were diagnosed in 4 patients (2.6%) and STILs in 6 patients (3.9%). None of the patients with STIC underwent restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months. None of the patients developed primary peritoneal carcinomas (PPCs) with a median FUP of 54.5 months (15-106). OC was diagnosed in 3 patients (2%). All patients with OC underwent staging surgery, and one patient developed a peritoneal carcinoma (PC) after 18 months by staging surgery. CONCLUSION(S) The incidence of STIC, STIL and OC after RRSO in BRCA1-2 variants was low. Our results demonstrated that long-term close surveillance in patients diagnosed with STIC should be considered a possible management strategy.
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Kuji S, Kondo H, Ohara T, Deura I, Tozawa-Ono A, Migita O, Kawamoto H, Tsugawa K, Chosokabe M, Koike J, Maeda I, Suzuki N. Value of adjuvant chemotherapy and informed microscopic examination for occult gynecologic cancer detected upon risk-reducing salpingo-oophorectomy after chemotherapy for BRCA1/2-associated breast cancer: a case report. Jpn J Clin Oncol 2021; 51:492-497. [PMID: 33377156 DOI: 10.1093/jjco/hyaa239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 11/16/2020] [Indexed: 11/13/2022] Open
Abstract
BRCA1/2 mutation carriers are at high risk for type II ovarian, fallopian tube or peritoneal cancer. Although risk-reducing salpingo-oophorectomy plays an important role in the prevention of these BRCA1/2-associated gynecological cancers, occult ovarian, fallopian tube, or peritoneal cancer is discovered upon risk-reducing salpingo-oophorectomy in 1-4% of BRCA1/2 mutation carriers. Notably, around 30% of BRCA1/2 mutation carriers who undergo risk-reducing salpingo-oophorectomy have undergone adjuvant chemotherapy for breast cancer. We describe the discovery and treatment of occult cancer at the edge of the left fimbria in a BRCA1 mutation carrier who had, just a short time previously, undergone neoadjuvant paclitaxel plus carboplatin (TC) chemotherapy for triple-negative breast cancer. During subsequent risk-reducing salpingo-oophorectomy, a 5.5-mm nodule was observed at the edge of the left fimbria. Microscopic examination of the tumour tissue revealed high-grade serous carcinoma with degenerate tumour cells and fibrosis. Peritoneal fluid was negative for cancer cells. Two months later, hysterectomy, omentectomy and retroperitoneal lymphadenectomy were performed. The final diagnosis was stage FIGO IA fallopian tube cancer. Adjuvant chemotherapy (TC administered every 3 weeks) was applied, and there has been no evidence of recurrence for 5 years. In applying gynecologic surgery and adjuvant chemotherapy, we followed the general recommendation for stage IA fallopian tube cancer. There is no standard strategy for the treatment of occult fallopian tube cancer detected after chemotherapy for BRCA1-associated triple-negative breast cancer. According to our experience in this case, we believe the clinical value of staging laparotomy in cases of a small occult BRCA1/2-associated gynecological cancer should be further investigated.
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Affiliation(s)
- Shiho Kuji
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Haruhiro Kondo
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Tatsuru Ohara
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Imari Deura
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Akiko Tozawa-Ono
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Ohsuke Migita
- Department of Clinical Genetics, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Hisanori Kawamoto
- Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine, Kawasaki-shi, Japan.,St. Marianna University Breast & Imaging Center, Kawasaki-shi, Japan
| | - Koichiro Tsugawa
- Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Motohiro Chosokabe
- Department of Pathology, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Junki Koike
- Department of Pathology, St. Marianna University School of Medicine, Kawasaki-shi, Japan
| | - Ichiro Maeda
- Department of Diagnostic Pathology, Kitasato University Kitasato Institute Hospital, Tokyo Japan.,Department of Pathology, Kitasato University School of Medicine, Sagamihara-shi, Japan
| | - Nao Suzuki
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki-shi, Japan
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Cowan R, Nobre SP, Pradhan N, Yasukawa M, Zhou QC, Iasonos A, Soslow RA, Arnold AG, Trottier M, Catchings A, Roche KL, Gardner G, Robson M, Abu Rustum NR, Aghajanian C, Cadoo K. Outcomes of incidentally detected ovarian cancers diagnosed at time of risk-reducing salpingo-oophorectomy in BRCA mutation carriers. Gynecol Oncol 2021; 161:521-526. [PMID: 33712278 DOI: 10.1016/j.ygyno.2021.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 02/03/2021] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Prior data suggested that women with incidentally detected occult invasive ovarian cancer (OIOC) at the time of risk-reducing salpingo-oophorectomy (RRSO) for BRCA mutation may have poorer prognoses than would be expected based on disease stage. We sought to evaluate prevalence and outcomes of patients with OIOC in a tertiary referral center. METHODS Patients with BRCA mutation undergoing RRSO from 01/2005 to 05/2017 were identified, and their records reviewed. Women with incidentally detected OIOC were included; those with clinical features raising preoperative suspicion for malignancy were excluded. RESULTS 548 patients with BRCA mutation who underwent RRSO were identified. 26 (4.7%) had an OIOC (median age 55 years; range 42-75); 15(58%) patients, BRCA1; 9(34%), BRCA2; 2(8%) had a mutation in both genes. All OIOCs were high-grade serous: 10 (38%) Stage I; 8 (31%) Stage II; 8(31%) Stage III. 24(92%) patients received adjuvant platinum/taxane therapy. Of Stage III patients, 4 (50%) were identified intraoperatively; the remaining 4 (50%) had microscopic nodal disease on final pathology only. At median follow-up of 67.3 months (28-166) no Stage I patients have recurred; 2 Stage II and 6 Stage III patients recurred. 5-year progression-free survival (PFS) was 72% (95%CI, 50.2-85.7%); median PFS for the cohort was 129 months (95%CI, 75.3-not estimable). 5-year disease-specific survival (DSS) was 96% (95%CI, 76-99%); median DSS not reached. CONCLUSION Consistent with prior reports, almost 5% of patients had an OIOC at RRSO. The majority with early-stage disease had excellent PFS and DSS outcomes, as would be expected based on disease stage.
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Affiliation(s)
- Renee Cowan
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Silvana Pedra Nobre
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nisha Pradhan
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maya Yasukawa
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Qin C Zhou
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alexia Iasonos
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Robert A Soslow
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA
| | - Angela G Arnold
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Magan Trottier
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Amanda Catchings
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kara Long Roche
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA
| | - Ginger Gardner
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA
| | - Mark Robson
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA; Robert and Kate Niehaus Center for Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nadeem R Abu Rustum
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA
| | - Carol Aghajanian
- Weill Medical College of Cornell University, New York, NY, USA; Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Karen Cadoo
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA; Robert and Kate Niehaus Center for Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; HOPe Directorate, St. James's Hospital, Dublin, Ireland.
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Kobayashi Y, Hirasawa A, Chiyoda T, Ueki A, Masuda K, Misu K, Kawaida M, Hayashi S, Kataoka F, Banno K, Kosaki K, Aoki D. Retrospective evaluation of risk-reducing salpingo-oophorectomy for BRCA1/2 pathogenic variant carriers among a cohort study in a single institution. Jpn J Clin Oncol 2021; 51:213-217. [PMID: 33037428 DOI: 10.1093/jjco/hyaa173] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/27/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast-ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast-ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. METHODS To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. RESULTS The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38-58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. CONCLUSIONS Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.
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Affiliation(s)
- Yusuke Kobayashi
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo.,Center for Medical Genetics, Keio University School of Medicine, Tokyo
| | - Akira Hirasawa
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo.,Center for Medical Genetics, Keio University School of Medicine, Tokyo.,Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama
| | - Tatsuyuki Chiyoda
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo
| | - Arisa Ueki
- Center for Medical Genetics, Keio University School of Medicine, Tokyo
| | - Kenta Masuda
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo
| | - Kumiko Misu
- Center for Medical Genetics, Keio University School of Medicine, Tokyo
| | - Miho Kawaida
- Division of Diagnostic Pathology, Keio University Hospital, Tokyo
| | - Shigenori Hayashi
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo
| | - Fumio Kataoka
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo.,Department of Obstetrics and Gynecology, International University of Health and Welfare School of Medicine, Chiba, Japan
| | - Kouji Banno
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo
| | - Kenjiro Kosaki
- Center for Medical Genetics, Keio University School of Medicine, Tokyo
| | - Daisuke Aoki
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo
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Abstract
OBJECTIVE To perform a systematic review of the literature to estimate the prevalence and outcomes of occult tubal carcinoma in BRCA mutation carriers and high-risk patients undergoing risk-reducing salpingo-oophorectomy. DATA SOURCE A search was done using OVID MEDLINE, EMBASE, and ClinicalTrials.gov between 1946 and March 2019 with keywords and MeSH terms selected by an expert medical librarian and coauthors. METHODS OF STUDY SELECTION Two independent reviewers performed study selection with an initial screen on abstracts and a second on full articles. Articles were rejected if they were irrelevant to the study question, pertained to a different population or did not report occult tubal neoplasia. Quality was assessed using methodologic index for nonrandomized studies criteria. TABULATION, INTEGRATION, AND RESULTS Data were extracted and recorded in an Excel database. Forest plots for the prevalence of occult carcinoma were done using STATA. Among 2,402 studies assessed, 27 met the inclusion criteria for qualitative and quantitative analysis. A total of 6,283 patients underwent risk-reducing salpingo-oophorectomy between 2002 and 2019: 2,894 cases were BRCA1, 1,579 BRCA2, and 1,810 high-risk based on family history. Among these, 75 patients were diagnosed with occult tubal carcinoma at the time of surgery. The pooled prevalence was 1.2% (I=7.1%, P=.363) occurring at a median age of 53.2 years (range 42.4-67). In a subanalysis of 18 studies reporting follow-up data, 10 recurrences (18.7%, 95% CI 7.5-53%) and 24 cases of post-risk-reducing salpingo-oophorectomy peritoneal cancer (0.54%, 95% CI 0.4-1.9%) were reported after a median follow-up of 52.5 months. BRCA1, older age, and previous breast cancer were more often associated with occult malignancy. CONCLUSION Occult tubal carcinomas found at risk-reducing salpingo-oophorectomy in high-risk patients and BRCA mutation carriers have significant potential for recurrence despite the frequent administration of postoperative chemotherapy.
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Incidence and Risk Factors of Ovarian Cancer and Breast Cancer Following Prophylactic Surgery: A Retrospective Cohort Study. J Gynecol Surg 2020. [DOI: 10.1089/gyn.2019.0135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Kotsopoulos J, Karlan B, Gronwald J, Hall E, Moller P, Tung N, Zakalik D, Foulkes WD, Rosen B, Neuhausen SL, Sun P, Lubinksi J, Narod SA. Long-term outcomes following a diagnosis of ovarian cancer at the time of preventive oophorectomy among BRCA1 and BRCA2 mutation carriers. Int J Gynecol Cancer 2020; 30:825-830. [PMID: 32354794 DOI: 10.1136/ijgc-2019-001141] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/24/2020] [Accepted: 03/05/2020] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION Preventive bilateral salpingo-oophorectomy is the most effective means of reducing the risk of ovarian cancer among women with an inherited BRCA1 or BRCA2 mutation. Some women are diagnosed with an invasive cancer (ovarian or fallopian tube) at the time of preventive surgery, referred to as an 'occult' cancer. The survival experience of these women is not known. METHODS We estimated the 10-year survival for 52 BRCA mutation carriers diagnosed with an occult ovarian or fallopian tube cancer at the time of preventive bilateral salpingo-oophorectomy. RESULTS The mean age at diagnosis was 51.6 (range 33-69) years. All were serous cancers (although 14 were missing information on histologic subtype). Of the 20 cases with information available on stage at diagnosis, 10 were stage I, 1 was stage II, and 9 were stage III (n=32 missing). After a mean of 6.8 years, 12 women died (23%). The 10-year all-cause survival was 74%. CONCLUSION Although based on only 52 cases, these findings suggest a more favorable prognosis for BRCA mutation carriers diagnosed with an occult rather than incident disease.
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Affiliation(s)
- Joanne Kotsopoulos
- Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Beth Karlan
- David Geffen School of Medicine, UCLA, Los Angeles, California, USA
| | - Jacek Gronwald
- International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian, Pomeranian Medical University in Szczecin, Szczecin, Zachodniopomorskie, Poland
| | - Elizabeth Hall
- Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
| | - Pal Moller
- Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Nadine Tung
- Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Dana Zakalik
- Beaumont Hospital, Royal Oak, Troy, Michigan, USA
| | - William D Foulkes
- Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada
| | - Barry Rosen
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
| | - Susan L Neuhausen
- Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, Beckman Research Institute City of Hope, Duarte, California, USA
| | - Ping Sun
- Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
| | - Jan Lubinksi
- International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian, Pomeranian Medical University in Szczecin, Szczecin, Zachodniopomorskie, Poland
| | - Steven A Narod
- Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
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The prevalence of occult ovarian cancer in the series of 155 consequently operated high risk asymptomatic patients - Slovenian population based study. Radiol Oncol 2020; 54:180-186. [PMID: 32463390 PMCID: PMC7276639 DOI: 10.2478/raon-2020-0020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 03/22/2020] [Indexed: 12/16/2022] Open
Abstract
Background We assessed the prevalence, localization, type and outcome of occult cancer at risk-reducing salpingo-oophorectomy or salpingectomy (RRSO) in asymptomatic carriers of pathogenic or likely pathogenic BRCA1/2 variants and high-risk BRCA1/2 negative women. Patients and methods A retrospective analysis of all consecutive gynaecologic preventive surgeries from January 2009 to December 2015 was performed. Participants underwent genetic counselling and BRCA1/2 testing before the procedure. Data on clinical parameters, adjuvant treatment and follow-up were collected and analysed. Results One hundred and fifty-five RRSO were performed in 110 BRCA1, 35 BRCA2 carriers of pathogenic or likely pathogenic variants and 10 high-risk BRCA1/2 negative women, at the mean age of 48.3 years. Nine occult cancers (9/155, 5.8%) were identified; eight in BRCA1 positive women and one in high-risk BRCA1/2 negative woman. We identified four non-invasive serous intraepithelial tubal carcinomas (3 in BRCA1 carriers and 1 in a high-risk BRCA1/2 negative woman) and five invasive tubo-ovarian high grade serous cancers (all detected in BRCA1 carriers). Only one out of nine patients (11.1%) with occult cancer had a slightly elevated CA-125 value preoperatively. Conclusions A 5.8% prevalence of occult invasive and noninvasive tubo-ovarian serous cancer after RRSO was found in high risk asymptomatic and screen negative women. We conclude that RRSO should be performed in BRCA1/2 carriers and in high-risk BRCA1/2 negative women. Age of preventive gynaecologic surgery should be carefully planned, taking into account the completion of childbearing age and type of mutation. The results favour the tubal hypothesis of tubal origin of high grade serous ovarian and peritoneal cancer. Cytology result of peritoneal cavity washing was important for the decision making process in determining treatment. Cytology examination should be performed in all cases of RRSO. CA-125 assay did not prove to be an effective screening tool for early cancer detection in our patients.
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Rush SK, Swisher EM, Garcia RL, Pennington KP, Agnew KJ, Kilgore MR, Norquist BM. Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience. Gynecol Oncol 2020; 157:514-520. [PMID: 32199636 DOI: 10.1016/j.ygyno.2020.02.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 02/01/2020] [Accepted: 02/02/2020] [Indexed: 12/19/2022]
Abstract
OBJECTIVES Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of ovarian, fallopian tube (FT), and peritoneal carcinoma (collectively OC). We describe rates of occult neoplasia in the largest single-institution prospective cohort of women undergoing RRSO, including those with mutations in non-BRCA homologous repair (HRR) genes. METHODS Participants undergoing RRSO enrolled in a prospective tissue bank between 1999 and 2017. Ovaries and FTs were serially sectioned in all cases. Participants had OC susceptibility gene mutations or a family history suggesting OC risk. Analyses were completed in Stata IC 15.1. RESULTS Of 644 women, 194 (30.1%) had mutations in BRCA1, 177 (27.5%) BRCA2, 27 (4.2%) other HRR genes, and 15 (2.3%) Lynch Syndrome-associated genes. Seventeen (2.6%) had occult neoplasms at RRSO, 15/17 (88.2%) in the FT. Of BRCA1 carriers, 14/194 (7.2%) had occult neoplasia, 8/194 (4.1%) invasive. One PALB2 and two BRCA2 carriers had intraepithelial FT neoplasms. Occult neoplasm occurred more frequently in BRCA1/2 carriers ≥45 years of age (6.5% vs 2.2%, chi square, p = .04), and 211/371 (56.9%) BRCA1/2 carriers had surgery after guideline-recommended ages. Four in 8 (50%) invasive and 2/9 (22%) intraepithelial neoplasms had positive pelvic washings. None with intraepithelial neoplasms developed recurrence or peritoneal carcinoma. CONCLUSIONS BRCA1 carriers have the highest risk of occult neoplasia at RRSO, and the frequency increased with age. Women with BRCA1/2 mutations often have RRSO beyond recommended ages. One PALB2 carrier had FT intraepithelial neoplasia, a novel finding. Serial sectioning is critical to identifying occult neoplasia and should be performed for all risk-reducing surgeries.
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Affiliation(s)
- Shannon K Rush
- Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
| | - Elizabeth M Swisher
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
| | - Rochelle L Garcia
- Department of Pathology, University of Washington Medical Center, United States of America
| | - Kathryn P Pennington
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
| | - Kathy J Agnew
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
| | - Mark R Kilgore
- Department of Pathology, University of Washington Medical Center, United States of America
| | - Barbara M Norquist
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America.
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Chong GO, Park JY, Lee HJ. Incidental Serous Tubal Intraepithelial Carcinoma that Developed into Primary Peritoneal Serous Carcinoma in a Patient without BRCA Mutation. AMERICAN JOURNAL OF CASE REPORTS 2020; 21:e921146. [PMID: 32034117 PMCID: PMC7032530 DOI: 10.12659/ajcr.921146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Patient: Female, 62-year-old Final Diagnosis: Peritoneal high grade serous carcinoma Symptoms: Serous tubal intraepithelial carcinoma Medication: — Clinical Procedure: Total laparoscopic hysterectomy and both salpingo-oophorectomy Specialty: Obstetrics and Gynecology
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Affiliation(s)
- Gun Oh Chong
- Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Ji Young Park
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Hyun Jung Lee
- Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Daegu, South Korea
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When Should Prophylactic Oophorectomy Be Recommended at the Time of Elective Hysterectomy? Clin Obstet Gynecol 2019; 63:337-348. [DOI: 10.1097/grf.0000000000000521] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Ma YN, Bu HL, Jin CJ, Wang X, Zhang YZ, Zhang H. Peritoneal cancer after bilateral mastectomy, hysterectomy, and bilateral salpingo-oophorectomy with a poor prognosis: A case report and review of the literature. World J Clin Cases 2019; 7:3872-3880. [PMID: 31799317 PMCID: PMC6887594 DOI: 10.12998/wjcc.v7.i22.3872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 09/19/2019] [Accepted: 10/05/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Primary peritoneal cancer (PPC) patients with BRCA mutations have a good prognosis; however, for patients with BRCA mutations who are diagnosed with PPC after prophylactic salpingo-oophorectomy (PSO), the prognosis is poor, and survival information is scarce.
CASE SUMMARY We treated a 56-year-old woman with PPC after bilateral mastectomy, hysterectomy, and bilateral salpingo-oophorectomy. This patient had primary drug resistance and died 12 mo after the diagnosis of PPC. The genetic test performed on this patient indicated the presence of a germline BRCA1 mutation. We searched the PubMed, Scopus, and Cochrane databases and extracted studies of patients with BRCA mutations who developed PPC after PSO. After a detailed literature search, we found 30 cases, 7 of which had a history of breast cancer, 14 of which had no history of breast cancer, and 9 of which had an unknown history. The average age of PSO patients was 48.86 years old (range, 31-64 years). The average time interval between the diagnosis of PPC and preventive surgery was 61.03 mo (range, 12-292 mo). The 2-year survival rate for this patient population was 78.26% (18/23), the 3-year survival rate was 50.00% (9/18), and the 5-year survival rate was 6.25% (1/16).
CONCLUSION Patients with BRCA mutations who are diagnosed with PPC after preventative surgery have a poor prognosis. Prevention measures and treatments for these patients need more attention.
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Affiliation(s)
- Ya-Na Ma
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - Hua-Lei Bu
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - Cheng-Juan Jin
- Department of Obstetrics and Gynecology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China
| | - Xia Wang
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - You-Zhong Zhang
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - Hui Zhang
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
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Kyo S, Ishikawa N, Nakamura K, Nakayama K. The fallopian tube as origin of ovarian cancer: Change of diagnostic and preventive strategies. Cancer Med 2019; 9:421-431. [PMID: 31769234 PMCID: PMC6970023 DOI: 10.1002/cam4.2725] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 11/06/2019] [Accepted: 11/08/2019] [Indexed: 01/20/2023] Open
Abstract
Ovarian cancer is the leading cause of gynecologic cancer death in the world, and its prevention and early diagnosis remain the key to its treatment, especially for high‐grade serous carcinoma (HGSC). Accumulating epidemiological and molecular evidence has shown that HGSC originates from fallopian tube secretory cells through serous tubal intraepithelial carcinoma. Comprehensive molecular analyses and mouse studies have uncovered the key driver events for serous carcinogenesis, providing novel molecular targets. Risk‐reducing bilateral salpingo‐oophorectomy (RRSO) has been proposed to reduce the subsequent occurrence of serous carcinoma in high‐risk patients with BRCA mutations. However, there is no management strategy for isolated precursors detected at RRSO, and the role of subsequent surgery or chemotherapy in preventing serous carcinoma remains unclear. Surgical menopause due to RRSO provides a variety of problems related to patients’ quality of life, and the risks and benefits of hormone replacement are under investigation, especially for women without a previous history of breast cancer. An additional surgical option, salpingectomy with delayed oophorectomy, has been proposed to prevent surgical menopause. The number of opportunistic salpingectomies at the time of surgery for benign disease to prevent the future occurrence of HGSC has increased worldwide. Thus, the changing concept of the origin of serous carcinoma has provided us a great opportunity to develop novel diagnostic and therapeutic approaches.
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Affiliation(s)
- Satoru Kyo
- Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Noriyoshi Ishikawa
- Department of Pathology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Kohei Nakamura
- Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Kentaro Nakayama
- Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
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Cheng A, Li L, Wu M, Lang J. Pathological findings following risk-reducing salpingo-oophorectomy in BRCA mutation carriers: A systematic review and meta-analysis. Eur J Surg Oncol 2019; 46:139-147. [PMID: 31521389 DOI: 10.1016/j.ejso.2019.09.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 08/23/2019] [Accepted: 09/04/2019] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE To evaluate the benefit of risk-reducing salpingo-oophorectomy (RRSO) by estimating the pathological positive rate of occult lesions, including serous tubal intraepithelial carcinoma (STIC) and occult cancers (OCCs). METHODS BRCA1/2 mutation carriers who underwent RRSO in a Chinese study center between 2014 and 2018 were included. A literature review was performed, followed by a meta-analysis of the literature to further validate the findings. RESULTS Twenty-four BRCA1/2 mutation carriers who underwent RRSO were identified; one patient (4.2%) had STIC, and one patient (4.2%) had occult fallopian tube cancer complicated by STIC. Thirty-four articles were ultimately included in the meta-analysis. Of the reported cases of OCC, 61.3% occurred in the fallopian tubes and 32.3% in the ovaries, and 81.5% were in the early stages. The estimated rate of overall pathological positive events was 5%. The estimated rates of overall STIC events and OCC were 1% and 3%, respectively. The rates of STIC and OCC were 1% and 3%, respectively, for BRCA1 mutation carriers and 1% and 1%, respectively, for BRCA2 mutation carriers. No significant difference was observed between the results of a routine examination of pathological sections and those of the Sectioning and Extensively Examining the Fimbriae (SEE-FIM) protocol. CONCLUSIONS This study is the first report of RRSO results in China. In this systematic review, the positive rates of STIC or OCC after RRSO were no more than 3%, which are 200-fold higher than the risk of the general population. The use of a strict SEE-FIM protocol would likely increase positive results.
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Affiliation(s)
- Aoshuang Cheng
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
| | - Lei Li
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
| | - Ming Wu
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
| | - Jinghe Lang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
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Petelin L, Hossack L, Mitchell G, Liew D, Trainer AH, James PA. A Microsimulation Model for Evaluating the Effectiveness of Cancer Risk Management for BRCA Pathogenic Variant Carriers: miBRovaCAre. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2019; 22:854-862. [PMID: 31426925 DOI: 10.1016/j.jval.2019.03.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 02/20/2019] [Accepted: 03/05/2019] [Indexed: 06/10/2023]
Abstract
OBJECTIVES To develop a validated model for evaluating the real-world effectiveness of long-term clinical management strategies for women with germline BRCA1 or BRCA2 pathogenic variants. METHODS A microsimulation model was developed that included a BRCA-specific natural history for breast and ovarian cancer, a clinical framework for carrier follow-up, and cancer risk management strategies (breast screening, risk-reducing mastectomy, and bilateral salpingo-oophorectomy). Adherence rates and outcomes for breast screening and risk-reducing surgery were obtained from BRCA carriers seen through a familial cancer service in Melbourne, Australia. The model was assessed for internal and external validity. The model was used to compare women perfectly adhering to screening recommendations versus actual adherence of the clinical cohort. RESULTS The model accurately predicted cancer incidence, pathology, and mortality. Using actual adherence for breast screening resulted in additional breast cancer deaths (per 1000 women: BRCA1, 2.7; BRCA2, 1.6) compared with perfect screening adherence. This decreased average life expectancy by 0.30 life-years for BRCA1 and 0.07 life-years for BRCA2. When carriers had access to risk-reducing mastectomy, the benefit from improved screening adherence was not significant. CONCLUSIONS The developed model is a good descriptor of BRCA carriers' lifetime trajectory and its modification by use of risk management strategies alone or in combination. Evaluations of breast screening in BRCA carriers may overestimate the benefits of screening programs unless adherence is considered. By incorporating real-world clinical practice and patient behavior, this model can assist in developing clinical services and improving clinical outcomes for carriers.
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Affiliation(s)
- Lara Petelin
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
| | - Lucinda Hossack
- Clinical Genetics, Austin Health, Austin Hospital, Melbourne, Victoria, Australia
| | - Gillian Mitchell
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia; Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Danny Liew
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Alison H Trainer
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia; Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Paul A James
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia; Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Royal Melbourne Hospital, Melbourne, Victoria, Australia
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Toss A, Molinaro E, Sammarini M, Del Savio MC, Cortesi L, Facchinetti F, Grandi G. Hereditary ovarian cancers: state of the art. Minerva Med 2019; 110:301-319. [DOI: 10.23736/s0026-4806.19.06091-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Hoskins P, Eccleston A, Hurry M, Dyer M. Targeted surgical prevention of epithelial ovarian cancer is cost effective and saves money in BRCA mutation carrying family members of women with epithelial ovarian cancer. A Canadian model. Gynecol Oncol 2019; 153:87-91. [PMID: 30704745 DOI: 10.1016/j.ygyno.2019.01.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 01/18/2019] [Accepted: 01/20/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Survival but not cure rates have improved for epithelial ovarian cancer (EOC), demonstrating the need for effective prevention. Targeted prevention in BRCA carriers by risk reducing surgery (RRS) prevents 80% of cases but incurs additional up-front costs, compensated for by the potential for long term savings from treatment avoidance. Does prevention represent value for money? In the absence of long-term data from prospective trials, determining the cost effectiveness of a prevention strategy requires economic modelling. METHODS A patient level simulation was developed comparing outcomes between two groups, using Canadian data. Group 1: no mutation testing with treatment if EOC developed. Group 2: cascade testing (index patient BRCA tested and the first and second-degree relatives tested if index patient or first-degree relative respectively were positive) with RRS in carriers. End points were Incremental Cost-Effectiveness Ratio (ICER) and budget impact. RESULTS 2786 women with EOC (1 year incidence) had 766 first and 207 second-degree female relatives. BRCA mutations were present in 390 index cases, 366 first and 49 second-degree relatives. With 100% RRS uptake, 59 EOC were prevented and testing dominated no testing (more effective and less costly; ICER -$8919). The total cost saving over 50 years was $2,904,486 (cost saving of $9,660,381 in treatment costs versus increased cost from cascade testing/RRS of $6,755,895). At a threshold of $100,000 per QALY, prevention was cost effective in all modelled scenarios. CONCLUSIONS Targeted prevention in BRCA mutation carriers not only prevents EOC but is cost-effective compared to treating EOC if it develops.
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Affiliation(s)
- Paul Hoskins
- BC Cancer, Department of Medical Oncology, Vancouver, Canada.
| | | | - Manjusha Hurry
- AstraZeneca, Health Economics, Mississauga, Ontario, Canada
| | - Matthew Dyer
- AstraZeneca, Health Economics, Cambridge, United Kingdom
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46
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Stewart ME, Knisely AT, Sullivan MW, Ring KL, Modesitt SC. Evaluation of screening and risk-reducing surgery for women followed in a high-risk breast/ovarian cancer clinic: it is all about the tubes in BRCA mutation carriers. Gynecol Oncol Rep 2019; 28:18-22. [PMID: 30775416 PMCID: PMC6365389 DOI: 10.1016/j.gore.2019.01.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 01/20/2019] [Accepted: 01/27/2019] [Indexed: 12/14/2022] Open
Abstract
The objectives of this study were to determine both surgical and subsequent cancer outcomes for high-risk women from the University of Virginia's High-Risk Breast/Ovarian Cancer clinic undergoing ovarian cancer risk-reducing surgery. Retrospective review identified high risk women who had ovarian risk reducing surgery over the past decade and surgical outcomes, pathology, pre-operative screening results, and pre-/post-operative cancer diagnoses were evaluated. One hundred and eighty-three high-risk women had risk reducing surgery at a mean age of 50.1 years and with a mean BMI of 28.9 kg/m2 at the time of surgery. Most women (103; 56.3%) had a strong family history of cancer concerning for a hereditary syndrome without an identified mutation, 35.5% of women carried a known deleterious mutation and 7.7% of women had a personal history of breast or ovarian cancer. The most common procedure was a risk-reducing bilateral salpingo-oophorectomy with or without hysterectomy (RRBSO, 89.1%). All women underwent the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) pathology protocol which found two (1.1%) invasive ovarian cancers (one ovarian/tubal carcinosarcoma, one granulosa cell ovarian cancer), three (1.6%) serous tubal intraepithelial carcinomas (STIC), and one (1.1%) invasive fallopian tube cancer. Subsequent cancer diagnoses included one (0.5%) primary peritoneal cancer, four (2.2%) DCIS, and seven (3.8%) invasive breast cancers. Ultimately, among all high-risk women undergoing RR surgery, about 3.3% were diagnosed with a STIC or an ovarian cancer none of which were identified on screening. All STIC and tubal cancers were diagnosed in women with BRCA mutations (6.6% rate for this group).
Ovarian risk reducing surgery improves outcomes. Women with BRCA 1 mutations have a higher risk of occult tubal pathology. Subsequent cancers, particularly breast cancer, occur in these women.
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Affiliation(s)
- Martha E Stewart
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Virginia Health System, Charlottesville, VA, USA
| | - Anne T Knisely
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Virginia Health System, Charlottesville, VA, USA.,Department of Obstetrics & Gynecology, Columbia University Medical Center, New York, NY, USA
| | - Mackenzie W Sullivan
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Virginia Health System, Charlottesville, VA, USA
| | - Kari L Ring
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Virginia Health System, Charlottesville, VA, USA
| | - Susan C Modesitt
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Virginia Health System, Charlottesville, VA, USA
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Perioperative Management of Women Undergoing Risk-reducing Surgery for Hereditary Breast and Ovarian Cancer. J Minim Invasive Gynecol 2019; 26:253-265. [DOI: 10.1016/j.jmig.2018.09.767] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 09/04/2018] [Accepted: 09/06/2018] [Indexed: 01/01/2023]
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An Unusual Adenomatoid Tumor of Fimbria with Pronounced Psammoma Bodies in a BRCA Positive Patient as a Pitfall for Carcinoma on Frozen Section. Case Rep Pathol 2018; 2018:8148147. [PMID: 30538879 PMCID: PMC6280236 DOI: 10.1155/2018/8148147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Accepted: 11/13/2018] [Indexed: 11/17/2022] Open
Abstract
Background BRCA gene mutations significantly increase the risk of breast and ovarian cancers where the lifetime risk of the ovarian cancer is about 40%. Therefore, many women with such mutations undergo prophylactic bilateral mastectomy and salpingo-oophorectomy. About 5-6% of these individuals display occult carcinomas in tubo-ovarian locations of which over 85% are tubal in origin. The objective of this case study was to emphasize emergence of benign lesions mimicking cancer under these circumstances. Case Report We present a case with positive BRCA1 mutation who underwent the prophylactic procedure where a small mass was identified in her fallopian tube. Our initial encounter with this tumor was during intraoperative consultation. The tumor was associated with extensive psammoma bodies arranged in closely packed small tubules, mimicking serous carcinoma. Frozen section limitations including artifact, time constraint, and lack of ancillary studies as well as the clinical history further complicated our diagnostic assessment, which was deferred. A diagnosis of adenomatoid tumor was rendered on permanent sections. Conclusion It is important to be familiar with this morphologic presentation of adenomatoid tumor as it is a pitfall for carcinoma, particularly on frozen section, and inaccurate diagnosis could lead to further unnecessary extensive procedures.
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Hormone replacement therapy after prophylactic risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A meta-analysis. Crit Rev Oncol Hematol 2018; 132:111-115. [DOI: 10.1016/j.critrevonc.2018.09.018] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 09/29/2018] [Indexed: 12/12/2022] Open
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Soong TR, Howitt BE, Horowitz N, Nucci MR, Crum CP. The fallopian tube, "precursor escape" and narrowing the knowledge gap to the origins of high-grade serous carcinoma. Gynecol Oncol 2018; 152:426-433. [PMID: 30503267 DOI: 10.1016/j.ygyno.2018.11.033] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Revised: 11/20/2018] [Accepted: 11/26/2018] [Indexed: 12/28/2022]
Abstract
Most ovarian carcinomas are high-grade serous carcinomas (HGSC) that contain TP53 mutations, present at advanced stage, and eventually become resistant to chemotherapy. The rapid evolution of this disease has been attributed to an origin in the distal fallopian tube, in the form of serous tubal intraepithelial carcinomas (STICs). This has led to a disease model where malignancy develops first in the tube and spreads to the peritoneum or regional lymph nodes. However, although most early or incidentally discovered HGSCs manifest in the tube with STICs, many advanced HGSCs are not accompanied by a malignancy in the fimbria. To resolve this paradox, the focus has shifted to earlier, premalignant serous proliferations (ESPs) in the tubes, which lack the cytomorphologic features of malignancy but contain TP53 mutations. These have been termed p53 signatures or serous tubal intraepithelial lesions (STILs). Although they have not been presumed to have cancer-causing potential by themselves, some ESPs have recently been shown to share identical TP53 mutations with concurrent HGSCs, indicating a shared lineage between these early mucosal changes and metastatic malignancy. This discovery supports a paradigm by which HGSCs can emerge not only from STICs but also from exfoliated precursor cells (precursor escape) that eventually undergo malignant transformation within the peritoneal cavity. This paradigm unifies both localized and widespread HGSCs to a visible pre-existing cellular alteration in the tubal epithelium, and highlights a consistent and necessary biologic event (TP53 mutation) rarely encountered in the ovary or secondary Mullerian system. This dual pathway to HGSCs underscores the subtle nature of many serous cancer origins in the tube, explains contrasting clinico-pathologic presentations, and explains why, until recently, the fallopian tube was unappreciated as the principal origin of HGSCs. Moreover, it highlights additional challenges faced in preventing or intercepting HGSCs at a curable stage.
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Affiliation(s)
- Thing Rinda Soong
- Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, United States of America
| | - Brooke E Howitt
- Department of Pathology, Stanford University Medical Center, Palo Alto, CA 94305, United States of America
| | - Neil Horowitz
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, United States of America
| | - Marisa R Nucci
- Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, MA 02115, United States of America
| | - Christopher P Crum
- Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, MA 02115, United States of America.
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