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1
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Prat J, D'Angelo E, Espinosa I. Ovarian Carcinomas: Clinicopathologic and Molecular Features With Comments on 2014 FIGO Staging. Am J Surg Pathol 2025; 49:e1-e14. [PMID: 39807827 DOI: 10.1097/pas.0000000000002352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
According to histopathology and molecular genetics, there are 5 major subtypes of ovarian carcinomas: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3% to 4%), and low-grade serous (<5%) carcinomas. These tumors, which constitute over 95% of cases, represent distinct diseases with different prognoses and therapy. This review outlines contemporary advances in molecular pathology, which have expanded our knowledge of the biology of epithelial ovarian cancer and are also important to patient management. We also comment on some controversial points of the FIGO staging classification that we proposed in 2014.
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Affiliation(s)
- Jaime Prat
- Autonomous University of Barcelona, Sant Quintin, Barcelona, Spain
| | - Emanuela D'Angelo
- Hospital de la Santa Creu i Sant Pau, Sant Quintin, Barcelona, Spain
| | - Iñigo Espinosa
- Department of Medical and Biotechnological Sciences, University "G. D'Annunzio", Via dei Vestini, Chieti-Pescara Italy
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2
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Zheng G, Liu Y, Wang Q, Mao M, Fu H, Si L, Zhang Y, Lai T, Zhao M, Chu D, Guo R. Prognosis and fertility of stage II to IV borderline ovarian tumors after fertility-sparing surgery. Int J Gynecol Cancer 2025; 35:101666. [PMID: 39984396 DOI: 10.1016/j.ijgc.2025.101666] [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: 11/14/2024] [Revised: 01/20/2025] [Accepted: 01/22/2025] [Indexed: 02/23/2025] Open
Abstract
OBJECTIVE To evaluate the prognosis and fertility of patients with stage II to IV borderline ovarian tumors who underwent fertility-sparing surgery. METHODS This retrospective single-institution study included patients aged <40 years with stage II to IV borderline ovarian tumors at the First Affiliated Hospital of Zhengzhou University between January 2007 and March 2023. The primary outcome was disease-free survival. The association of disease-free survival was assessed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS A total of 144 patients were included in this study. Based on whether fertility-sparing surgery was performed, the patients were categorized into 2 groups: a fertility-sparing surgery group with 96 patients (66.67%) and a radical surgery group with 48 patients (33.3%). There were differences between the 2 groups in terms of age (27.36 ± 6.42 vs 34.67 ± 5.43, p < .001), pregnancy history (53.1%; 51/96) vs 81.2% (39/48), p = .001), maximum tumor diameter (103.00 [76.25, 148.25] vs 88.50 [60.25, 124.75], p = .011), involvement of bilateral ovaries (45.83%; [44/96] vs 66.67% [32/48], p = .018), and whether postoperative adjuvant chemotherapy (15.6% [15/96] vs 31.2% [15/48], p = .030). The median follow-up time after primary cytoreduction was 67.0 months (interquartile range; 44.0-101.75). At the end of the observation period, 32 (22.2%) patients experienced recurrence. There were 3 (2.1%) deaths and 2 cases (1.4%) of survival with tumors. Multivariate Cox proportional hazards regression analysis showed that fertility-sparing surgery, incomplete cytoreduction, micropapillary subtype, International Federation of Gynecology and Obstetrics stage III, and invasive implants were independent risk factors for poor disease-free survival. Among the patients with fertility intentions (41 cases), 34 (82.9%) had successful pregnancies. Twenty-nine patients (70.7%) had successful births, and 3 patients were pregnant at the time of study completion. CONCLUSIONS Fertility-sparing surgery may be feasible and considered for patients lacking other significant risk factors for disease-free survival, including incomplete cytoreduction, micropapillary subtype, International Federation of Gynecology and Obstetrics stage III, and invasive implants.
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Affiliation(s)
- Guo Zheng
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Yana Liu
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Qian Wang
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Meng Mao
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Hanlin Fu
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Lulu Si
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Ye Zhang
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Tianjiao Lai
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Mengling Zhao
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Danxia Chu
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China
| | - Ruixia Guo
- The First Affiliated Hospital of Zhengzhou University, Department of Gynecology, Zhengzhou, China; Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Zhengzhou, China.
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Bašković M, Habek D, Zaninović L, Milas I, Pogorelić Z. The Evaluation, Diagnosis, and Management of Ovarian Cysts, Masses, and Their Complications in Fetuses, Infants, Children, and Adolescents. Healthcare (Basel) 2025; 13:775. [PMID: 40218072 PMCID: PMC11988711 DOI: 10.3390/healthcare13070775] [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: 03/01/2025] [Revised: 03/25/2025] [Accepted: 03/28/2025] [Indexed: 04/14/2025] Open
Abstract
The majority of abdominal masses in female children derive from the ovaries. Ovarian masses in pediatric populations can vary from simple functional cysts to malignant neoplasms. Their incidence, clinical presentation, and histological distribution vary across age groups. In the assessment of ovarian masses in children, the primary aim is to determine the probability of malignancy, as the treatment approaches for benign and malignant lesions are significantly distinct. The primary imaging tool for evaluating ovarian cysts and masses is ultrasound, which can assess the size, location, and characteristics of masses. Magnetic resonance imaging (MRI) or computed tomography (CT) may be used for further evaluation if ultrasound findings are inconclusive or if malignancy is suspected, especially in older adolescents. Serum markers may be considered in older adolescents to help assess the risk of malignancy, though it is less useful in younger populations due to normal developmental variations. Many functional ovarian cysts, especially those detected in fetuses or infants, often resolve spontaneously without intervention. Surgical intervention is indicated in cases of large cysts that cause symptoms, or if there are concerns for malignancy. Common procedures include primarily ovarian sparing laparoscopy or laparotomy. Complications like torsion, rupture, or hemorrhage may require urgent surgical intervention. Treatment should be performed in specialized centers to avoid unnecessary oophorectomies and ensure the best possible outcome for the patient. This comprehensive review aims to provide an overview of the evaluation, diagnosis, and treatment of ovarian masses in the pediatric population. Emphasis is placed on the particularities of the lesions and their management in relation to age subgroups.
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Affiliation(s)
- Marko Bašković
- Department of Pediatric Surgery, Children’s Hospital Zagreb, Ulica Vjekoslava Klaića 16, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Croatian Academy of Medical Sciences, Kaptol 15, 10000 Zagreb, Croatia
- Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
| | - Dubravko Habek
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Croatian Academy of Medical Sciences, Kaptol 15, 10000 Zagreb, Croatia
- Department of Obstetrics and Gynecology, Clinical Hospital Merkur, Zajčeva ulica 19, 10000 Zagreb, Croatia
- School of Medicine, Catholic University of Croatia, Ilica 242, 10000 Zagreb, Croatia
| | - Luca Zaninović
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Department of Obstetrics and Gynecology, University Hospital Centre Zagreb, Petrova ulica 13, 10000 Zagreb, Croatia
| | - Ivan Milas
- School of Medicine, Catholic University of Croatia, Ilica 242, 10000 Zagreb, Croatia
- Department of Surgical Oncology, University Hospital for Tumors, University Hospital Centre Sestre Milosrdnice, Ilica 197, 10000 Zagreb, Croatia
| | - Zenon Pogorelić
- Department of Pediatric Surgery, University Hospital of Split, Spinčićeva ulica 1, 21000 Split, Croatia
- School of Medicine, University of Split, Šoltanska ulica 2a, 21000 Split, Croatia
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Basarır ZO, Arslanca T, Ucar YO, Ayhan S, Ozdal B. Factors Affecting Recurrence in 165 Patients with Serous Borderline Ovarian Tumours: The Pattern of Micro-Invasion Is Main Prognostic Factor. J Clin Med 2025; 14:2050. [PMID: 40142857 PMCID: PMC11942785 DOI: 10.3390/jcm14062050] [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: 03/05/2025] [Revised: 03/12/2025] [Accepted: 03/14/2025] [Indexed: 03/28/2025] Open
Abstract
Background: The aim of this study was to evaluate the serous borderline ovarian tumours (BOTs), the recurrence rates, and the factors affecting recurrence. Methods: A total of 165 patients diagnosed with serous BOT between 2004 and 2019 were included. The patients were evaluated in respect of age, preoperative CA125 levels, FIGO stage, tumour size, stromal micro-invasion, the presence of non-invasive implants, surgical procedures, and lymphadenectomy performed, or all that affects disease-free survival. Results: Early-stage BOT (stage I-II) was determined in 149 (90.3%) patients. Conservative surgery was performed in 57 (34.5%) patients. The non-invasive implantation was detected in 19 (11.5%) patients, and micro-invasion was determined in 31 (18.8%) patients. The median follow-up was 120 months, and recurrence was observed in 8 (4.8%) patients. The 5-year disease-free survival rate was 95.2%, and the 10-year disease-free survival rate was also 95.2%. Univariate analysis showed that elevated preoperative CA125 levels and the presence of micro-invasion were associated with poor disease-free survival outcomes. In the multivariate analysis, the presence of micro-invasion was the only independent poor prognostic factor (HR: 8.944, 95%CI: 2.060-38.833; p:0.003). Conclusions: The micro-invasion was the main factor for recurrence in patients with serous BOT.
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Affiliation(s)
- Zehra Ozturk Basarır
- Department of Gynecologic Oncology, Ankara City Hospital, Ankara 06800, Turkey; (T.A.); (Y.O.U.); (S.A.); (B.O.)
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Ilenkovan N, Ryan N, Roxburgh P, Bell S, Gourley C. Controversies in the management of serous borderline tumors and low-grade serous ovarian cancer. Int J Gynecol Cancer 2025; 35:101673. [PMID: 40058134 DOI: 10.1016/j.ijgc.2025.101673] [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: 01/20/2025] [Revised: 01/26/2025] [Accepted: 01/26/2025] [Indexed: 03/18/2025] Open
Abstract
Low-grade serous ovarian cancer has been recognized as a distinct oncologic entity for the last 20 years. Over the last 10 years, treatment strategies tailored to the biological and clinical characteristics of the disease have been tested and implemented. However, several key controversies remain. Here, we articulate the uncertainties surrounding the identification of the tissues of origin of low-grade serous ovarian cancer and its precursor lesion, the serous borderline tumor, the challenges in identifying molecular drivers of low-grade serous ovarian cancer, where a driver mutation in the mitogen-activated protein kinase pathway has not been identified, and discuss the phenomenon of co-existent low- and high-grade components in a tumor. In the clinical arena, we discuss the challenges surrounding fertility preservation in young patients, difficulties encountered in patients with unresectable disease, and the controversy surrounding the recommendation of adjuvant chemotherapy. We also discuss the role of secondary debulking surgery, how to order the administration of biological therapies, and the key issues in accelerating the discovery and development of new therapies. For many of these issues, the solution lies in improved international collaboration and cooperation. For each, we allude to how this might best be achieved.
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Affiliation(s)
| | - Neil Ryan
- University of Edinburgh, Institute of Genetics and Cancer, Cancer Research UK Scotland Centre, Nicola Murray Centre for Ovarian Cancer Research, Edinburgh, United Kingdom; University of Edinburgh, Centre for Reproductive Health, Institute of Regeneration and Repair, Edinburgh, United Kingdom
| | - Patricia Roxburgh
- University of Glasgow, School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, Glasgow, United Kingdom; Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
| | - Sarah Bell
- NHS Greater Glasgow and Clyde, The Queen Elizabeth University Hospital, Department of Pathology, Glasgow, United Kingdom
| | - Charlie Gourley
- University of Edinburgh, Institute of Genetics and Cancer, Cancer Research UK Scotland Centre, Nicola Murray Centre for Ovarian Cancer Research, Edinburgh, United Kingdom.
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6
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Badlaeva AS, Tregubova AV, Udina AA, Asaturova AV. [Eosinophilic cells associated with BRAF mutation in borderline serous ovarian tumors]. Arkh Patol 2025; 87:18-23. [PMID: 40289428 DOI: 10.17116/patol20258702118] [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: 04/30/2025]
Abstract
OBJECTIVE To define the diagnostic value of eosinophilic cells for the detection of BRAF-mutated serous borderline ovarian tumors. MATERIAL AND METHODS The study included 42 cases of serous borderline ovarian tumor, each of which was analyzed by 3 pathologists for the presence of eosinophilic cells. Genetic profiling using Sanger sequencing was performed to identify the BRAFV600E mutation. Comparisons between two groups were performed using the Mann-Whitney test, Fisher's exact test. Fleiss's kappa was used to assess the interobserver agreement. To assess the diagnostic value of eosinophilic cells, sensitivity and specificity were assessed. RESULTS According to the results of a genetic study, the BRAFV600Emutation was found in 19 of 42 tumors. When analyzing interobserver agreement, the Fleiss's kappa values allowed us to determine the reliability of the test as sufficient (ϰ=0.7). The sensitivity and specificity for predicting BRAFV600Emutation for eosinophilic cells were 78.9% and 91.3%, respectively. Patients with the BRAFV600E mutation were significantly younger than patients without it. Thus, the average age of patients in the group with the BRAFV600E mutation was 33.6±15.6 years, while in the group of tumors without the mutation the average age of patients was 43.9±12.7 years (p=0.002). Non-invasive implants were less frequently found in tumors with the BRAFV600E mutation compared to tumors without the mutation: 11.76% (2/17) versus 33.3% (6/18), respectively, but these differences were not statistically significant (p=0.228). CONCLUSION Eosinophilic cells in ovarian serous borderline tumors may sufficiently reflect the BRAFV600E mutation, thereby correlating with disease prognosis (low risk of progression to low-grade serous carcinoma).
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Affiliation(s)
- A S Badlaeva
- National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Moscow, Russia
| | - A V Tregubova
- National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Moscow, Russia
| | - A A Udina
- N.I. Pirogov Russian National Research Medical University, Moscow, Russia
| | - A V Asaturova
- National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Moscow, Russia
- N.I. Pirogov Russian National Research Medical University, Moscow, Russia
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7
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Scaglione G, Travaglino A, Raffone A, Santoro A, Arciuolo D, Fulgione C, D'Alessandris N, Pannone G, Urtueta BP, Narducci N, Addante F, Casarin J, Ronchi S, Di Lauro E, La Rosa S, Maccio L, Inzani F, Zannoni GF. Micropapillary pattern in serous borderline ovarian tumor and the risk of extraovarian localization of low-grade serous carcinoma ('invasive implants'): A systematic review and meta-analysis. Pathol Res Pract 2024; 264:155714. [PMID: 39520971 DOI: 10.1016/j.prp.2024.155714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 11/02/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
In serous borderline ovarian tumor (SBOT), a micropapillary (MP) pattern has been considered analogous to intraepithelial low-grade serous carcinoma (LGSC). On this account, it is reasonable to hypothesize that MP-SBOT is more likely to be associated with extraovarian LGSC localizations (also referred to as 'invasive implants') compared to conventional SBOT. The aim of this study was to investigate the potential association between a MP pattern and invasive implants in SBOT. Three electronic databases were searched from 2000 (year of publication of histological criteria for MP-SBOT) to 2023 for all studies assessing the presence of invasive implants in conventional SBOT vs MP-SBOT. Exclusion criteria were sample size <20, overlapping patient data, reviews. The association between MP pattern and invasive implants was assessed by using odds ratio (OR), with a significant p-value<0.05. Seven studies with 1766 SBOT were included, out of which 205 (11.5 %) were MP-SBOT, 462 (26 %) had implants and 62 (3.5 %) had invasive implants. A MP pattern was significantly associated with the presence of invasive implants (OR=7.33, 95 % CI 3.61-14.86) (p<0.001), with low heterogeneity among studies (I2=28 %). In conclusion, a MP pattern in SBOT is significantly associated with extraovarian LGSC localization, supporting that it represents intraepithelial LGSC.
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Affiliation(s)
- Giulia Scaglione
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Life Sciences and Public Health, Catholic University of Sacred Heart, Rome, Italy
| | - Antonio Travaglino
- Pathology Unit, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy.
| | - Antonio Raffone
- Gynecology and Obstetrics Unit, Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples "Federico II", Naples, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Angela Santoro
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Life Sciences and Public Health, Catholic University of Sacred Heart, Rome, Italy
| | - Damiano Arciuolo
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Life Sciences and Public Health, Catholic University of Sacred Heart, Rome, Italy
| | - Caterina Fulgione
- Gynecology and Obstetrics Unit, Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples "Federico II", Naples, Italy
| | - Nicoletta D'Alessandris
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Life Sciences and Public Health, Catholic University of Sacred Heart, Rome, Italy
| | - Giuseppe Pannone
- Department of Surgical Sciences, Institute of Pathology and Cytopathology, University of Foggia, Italy
| | - Belen Padial Urtueta
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Nadine Narducci
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesca Addante
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Jvan Casarin
- Gynecology Unit, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
| | - Susanna Ronchi
- Pathology Unit, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
| | - Eleonora Di Lauro
- Pathology Unit, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
| | - Stefano La Rosa
- Pathology Unit, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
| | - Livia Maccio
- Surgical Pathology Unit, S. Chiara Hospital, Trient, Italy
| | - Frediano Inzani
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia 27100, Italy
| | - Gian Franco Zannoni
- Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Life Sciences and Public Health, Catholic University of Sacred Heart, Rome, Italy
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8
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Zhang X, Devereaux KA, Ryan E, Fei F, Kunder CA, Longacre TA. High-grade Anaplastic Transformation of Ovarian Serous Borderline Tumor: A Distinctive Morphology With Abundant Dense Eosinophilic Cytoplasm and Dismal Prognosis. Am J Surg Pathol 2024; 48:1395-1407. [PMID: 39028145 DOI: 10.1097/pas.0000000000002294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/20/2024]
Abstract
Ovarian serous borderline tumors (SBTs) have a generally favorable prognosis. Although the risk of progression to low-grade serous carcinoma is well documented, progression to high-grade carcinoma is rare. We report the clinicopathologic features of seven SBTs, each associated with the presence of a morphologically unique high-grade component with an extremely dismal prognosis. All of the SBTs exhibited typical hierarchical branching and scattered eosinophilic cells, whereas the high-grade component consisted of a profuse proliferation of epithelioid cells with abundant dense, eosinophilic cytoplasm, variable nuclear pleomorphism, and evident loss of WT1, estrogen receptor, and p16 positivity. In most cases, the SBT demonstrated an abrupt transition to the high-grade component, but one patient initially presented with the usual SBT and developed a recurrent disease that was composed entirely of the high-grade component. Targeted next-generation sequencing revealed identical driver mutations in both the SBT and high-grade components ( BRAF in 3, KRAS in 1), confirming clonality. Three cases, in addition, harbored telomerase reverse transcriptase promoter mutations in both components. One case, despite insufficient material for sequencing, was BRAF V600E-positive by immunohistochemistry. Most patients with available follow-up data died within 9 months of diagnosis. This study confirms prior reports of ovarian SBT transformation to high-grade carcinoma and further characterizes a distinct subset with abundant dense eosinophilic cytoplasm and an extremely dismal prognosis. The presence of BRAF mutations in a major subset of these tumors questions the notion that BRAF is associated with senescent eosinophilic cells and improved outcomes in SBT. The role of the additional telomerase reverse transcriptase promoter mutations merits further investigation.
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Affiliation(s)
- Xiaoming Zhang
- Department of Pathology, Stanford University School of Medicine, Stanford
| | - Kelly A Devereaux
- Department of Pathology, Stanford University School of Medicine, Stanford
- Merck Research Laboratories, Rahway, New Jersey
| | - Emily Ryan
- Department of Pathology, Stanford University School of Medicine, Stanford
- Department of Obstetrics and Gynecology, University of California San Francisco, Fresno
| | - Fei Fei
- Department of Pathology, Stanford University School of Medicine, Stanford
- Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte
| | - Christian A Kunder
- Department of Pathology, Stanford University School of Medicine, Stanford
- Calpath Medical Associates/GynePath Laboratory, Inc, Campbell, CA
| | - Teri A Longacre
- Department of Pathology, Stanford University School of Medicine, Stanford
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Moss E, Taylor A, Andreou A, Ang C, Arora R, Attygalle A, Banerjee S, Bowen R, Buckley L, Burbos N, Coleridge S, Edmondson R, El-Bahrawy M, Fotopoulou C, Frost J, Ganesan R, George A, Hanna L, Kaur B, Manchanda R, Maxwell H, Michael A, Miles T, Newton C, Nicum S, Ratnavelu N, Ryan N, Sundar S, Vroobel K, Walther A, Wong J, Morrison J. British Gynaecological Cancer Society (BGCS) ovarian, tubal and primary peritoneal cancer guidelines: Recommendations for practice update 2024. Eur J Obstet Gynecol Reprod Biol 2024; 300:69-123. [PMID: 39002401 DOI: 10.1016/j.ejogrb.2024.06.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 06/13/2024] [Indexed: 07/15/2024]
Affiliation(s)
- Esther Moss
- College of Life Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK
| | | | - Adrian Andreou
- Royal United Hospitals Bath NHS Foundation Trust, Combe Park, Bath BA1 3NG, UK
| | - Christine Ang
- Northern Gynaecological Oncology Centre, Gateshead, UK
| | - Rupali Arora
- Department of Cellular Pathology, University College London NHS Trust, 60 Whitfield Street, London W1T 4E, UK
| | | | | | - Rebecca Bowen
- Royal United Hospitals Bath NHS Foundation Trust, Combe Park, Bath BA1 3NG, UK
| | - Lynn Buckley
- Beverley Counselling & Psychotherapy, 114 Holme Church Lane, Beverley, East Yorkshire HU17 0PY, UK
| | - Nikos Burbos
- Department of Obstetrics and Gynaecology, Norfolk and Norwich University Hospital Colney Lane, Norwich NR4 7UY, UK
| | | | - Richard Edmondson
- Saint Mary's Hospital, Manchester and University of Manchester, M13 9WL, UK
| | - Mona El-Bahrawy
- Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | | | - Jonathan Frost
- Gynaecological Oncology, Royal United Hospitals Bath NHS Foundation Trust, Combe Park, Bath, Bath BA1 3NG, UK; University of Exeter, Exeter, UK
| | - Raji Ganesan
- Department of Cellular Pathology, Birmingham Women's Hospital, Birmingham B15 2TG, UK
| | | | - Louise Hanna
- Department of Oncology, Velindre Cancer Centre, Whitchurch, Cardiff CF14 2TL, UK
| | - Baljeet Kaur
- North West London Pathology (NWLP), Imperial College Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - Ranjit Manchanda
- Wolfson Institute of Population Health, Cancer Research UK Barts Centre, Queen Mary University of London and Barts Health NHS Trust, UK
| | - Hillary Maxwell
- Dorset County Hospital, Williams Avenue, Dorchester, Dorset DT1 2JY, UK
| | - Agnieszka Michael
- Royal Surrey NHS Foundation Trust, Guildford GU2 7XX and University of Surrey, School of Biosciences, GU2 7WG, UK
| | - Tracey Miles
- Royal United Hospitals Bath NHS Foundation Trust, Combe Park, Bath BA1 3NG, UK
| | - Claire Newton
- Gynaecology Oncology Department, St Michael's Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol BS1 3NU, UK
| | - Shibani Nicum
- Department of Oncology, University College London Cancer Institute, London, UK
| | | | - Neil Ryan
- The Centre for Reproductive Health, Institute for Regeneration and Repair (IRR), 4-5 Little France Drive, Edinburgh BioQuarter City, Edinburgh EH16 4UU, UK
| | - Sudha Sundar
- Institute of Cancer and Genomic Sciences, University of Birmingham and Pan Birmingham Gynaecological Cancer Centre, City Hospital, Birmingham B18 7QH, UK
| | - Katherine Vroobel
- Department of Cellular Pathology, Royal Marsden Foundation NHS Trust, London SW3 6JJ, UK
| | - Axel Walther
- Bristol Cancer Institute, University Hospitals Bristol and Weston NHS Foundation Trust, UK
| | - Jason Wong
- Department of Histopathology, East Suffolk and North Essex NHS Foundation Trust, Ipswich Hospital, Heath Road, Ipswich IP4 5PD, UK
| | - Jo Morrison
- University of Exeter, Exeter, UK; Department of Gynaecological Oncology, GRACE Centre, Musgrove Park Hospital, Somerset NHS Foundation Trust, Taunton TA1 5DA, UK.
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10
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Singh M, Cornwell S, Shaddaie A, Wachsmuth L, Ragupathi A, Salichos L, Nissel-Horowitz S, Roy R, Plummer M, Zhang D, Mehrotra B. A case of malignant transformation of a serous borderline ovarian tumor effectively treated with BRAF/MEK inhibitor combination. Gynecol Oncol Rep 2024; 54:101417. [PMID: 38808271 PMCID: PMC11131060 DOI: 10.1016/j.gore.2024.101417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 05/13/2024] [Accepted: 05/14/2024] [Indexed: 05/30/2024] Open
Abstract
We describe a patient diagnosed with a metastatic adenocarcinoma of Müllerian origin, harboring a BRAF V600E mutation, ten years after being treated for a serous borderline tumor (SBOT). While BRAF mutations in the setting of SBOTs are common, they have been typically associated with a low chance of transformation or recurrence. The therapeutic approach, which combined hormone inhibition with receptor tyrosine kinase inhibitors (dabrafenib and trametinib), has demonstrated notable and enduring efficacy. This is clinically evidenced through serial PET-CT scans with sustained responses and extended progression-free survival, and serologically confirmed by monitoring CA-125 levels. This case demonstrates the critical role of early next-generation sequencing in detecting actionable molecular changes in rare cancers and possible metastases. It provides valuable insights into treating uncommon Müllerian adenocarcinomas and underscores the importance of targeted therapies in achieving long-lasting treatment outcomes.
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Affiliation(s)
- Manrose Singh
- Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Samantha Cornwell
- Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Ariel Shaddaie
- Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Leah Wachsmuth
- Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Ashwin Ragupathi
- Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Leonidas Salichos
- Center for Cancer Research, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Sandra Nissel-Horowitz
- Catholic Health Cancer Institute at St. Francis Hospital & Heart Center, East Hills, NY 11548, USA
| | - Rajasree Roy
- Catholic Health Cancer Institute at St. Francis Hospital & Heart Center, East Hills, NY 11548, USA
| | - Maria Plummer
- Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568, USA
- Center for Cancer Research, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Dong Zhang
- Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568, USA
- Center for Cancer Research, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Bhoomi Mehrotra
- Catholic Health Cancer Institute at St. Francis Hospital & Heart Center, East Hills, NY 11548, USA
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11
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Badlaeva A, Tregubova A, Palicelli A, Asaturova A. Eosinophilic Cells in Ovarian Borderline Serous Tumors as a Predictor of BRAF Mutation. Cancers (Basel) 2024; 16:2322. [PMID: 39001384 PMCID: PMC11240704 DOI: 10.3390/cancers16132322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 06/10/2024] [Accepted: 06/18/2024] [Indexed: 07/16/2024] Open
Abstract
According to recent reports, ovarian serous borderline tumor (SBT) harboring the BRAF V600E mutation is associated with a lower risk of progression to low-grade serous carcinoma. Preliminary observations suggest that there may be an association between eosinophilic cells (ECs) and the above-mentioned mutation, so this study aimed to evaluate interobserver reproducibility for assessing ECs. Forty-two samples of SBTs were analyzed for ECs with abundant eosinophilic cytoplasm. Immunohistochemical staining and genetic pro-filing were performed in all cases to verify the BRAF V600E mutation. A BRAF V600E mutation was found in 19 of 42 (45%) cases. Inter-observer reproducibility in the assessment of ECs was substantial (κ = 0.7). The sensitivity and specificity for predicting the mutation were 79% and 91%, respectively. Patients with BRAF-mutated SBTs were significantly younger than those without mutation (p = 0.005). SBTs with BRAF mutation were less likely to be accompanied by non-invasive implants than wild-type SBT: 12% (2/17) versus 33% (6/18). Seven cases were excluded due to incomplete cytoreductive surgery. Nevertheless, Fisher's exact test showed no significant differences between the two groups (p = 0.228). Overall, this study strengthens the idea that ECs in ovarian SBTs may represent a mutation with prognostic significance, which can serve as a primary screening test for BRAF V600E mutation in this pathologic entity.
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Affiliation(s)
- Alina Badlaeva
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, 117513 Moscow, Russia; (A.B.); (A.T.)
| | - Anna Tregubova
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, 117513 Moscow, Russia; (A.B.); (A.T.)
| | - Andrea Palicelli
- Pathology Unit, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;
| | - Aleksandra Asaturova
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, 117513 Moscow, Russia; (A.B.); (A.T.)
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12
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Westermann T, Karabeg E, Heitz F, Traut A, Plett H, Moubarak M, Welz J, Heikaus S, Lax S, du Bois A, Harter P. Role of fertility-sparing surgery and further prognostic factors in borderline tumors of the ovary. Int J Gynecol Cancer 2024; 34:898-905. [PMID: 38627034 DOI: 10.1136/ijgc-2023-005214] [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: 12/16/2023] [Accepted: 04/03/2024] [Indexed: 06/05/2024] Open
Abstract
OBJECTIVE Borderline tumors of the ovary are a rare group of ovarian neoplasms with distinctive histological features. Considering their favorable prognosis and occurrence at a younger age, fertility-sparing surgery may be considered. Several risk factors have been identified as contributing to a higher recurrence rate, while the impact of pathohistological features varies in the literature. This study aimed to analyze risk factors for recurrence in patients with borderline tumors of the ovary. METHODS Analysis included patients treated with first diagnosis of a borderline tumor at our center between January 1997 and December 2022 to analyze disease-free survival and to identify the role of fertility-sparing surgery, defined as preservation of at least one ovary, pathohistological features, and other prognostic factors for relapse. All stages classified according to the International Federation of Gynecology and Obstetrics (FIGO) were included. RESULTS Among 507 patients, 26 patients (5.2%) had a recurrence, with 21 (4.1%) showing borderline histology and 5 (1%) with invasive relapses. Recurrence rate was higher following fertility-sparing surgery (p<0.0001). Median follow-up period was 49.2 (range 42.0-57.6) months. Among 153 patients (30.2%) who had fertility-sparing surgery, 21 (13.7%) experienced a recurrence (including one invasive relapse). Fertility-sparing surgery (HR 20; 95% CI 6.9 to 60; p<0.001), FIGO stage I with bilateral presence of tumor (HR 6.4; 95% CI 1.3 to 31; p=0.020), FIGO stage II (HR 15; 95% CI 3.4 to 68; p<0.001), FIGO stages III-IV (HR 38; 95% CI 10 to 140; p<0.001) in comparison with FIGO stage I with unilateral tumor, microinvasion (HR 8.6; 95% CI 2.7 to 28; p<0.001), and micropapillary growth patterns (HR 4.4; 95% CI 1.8 to 10; p=0.001) were identified as independent risk factors for recurrence in multivariate analysis. None of these factors were associated with an increased risk of disease-related death. CONCLUSIONS Our study showed that although a fertility-preserving approach is associated with increased recurrence rates of a borderline tumor, it does not affect overall survival and can therefore be regarded as oncologically safe for patients desiring to preserve fertility. Additionally, presence of micropapillary patterns and microinvasion were identified as prognostic risk factors.
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Affiliation(s)
- Timo Westermann
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
| | - Edin Karabeg
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
| | - Florian Heitz
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
- Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Alexander Traut
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
| | - Helmut Plett
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
- Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Malak Moubarak
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
| | - Julia Welz
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
| | | | - Sigurd Lax
- Pathology, General Hospital Graz II, Location West; Styrian Hospital Corporation and Medical University of Graz, Graz, Austria
| | - Andreas du Bois
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
| | - Philipp Harter
- Department of Gynecology and Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany
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13
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Kumari S, Bhatla N, Ray C, Arora B, Mathur S, Kumar S, Kumar L. Borderline tumours of ovary and fertility preservation-Outcomes from a tertiary care center in India. Curr Probl Cancer 2024; 50:101097. [PMID: 38598972 DOI: 10.1016/j.currproblcancer.2024.101097] [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: 12/09/2023] [Revised: 03/18/2024] [Accepted: 04/03/2024] [Indexed: 04/12/2024]
Abstract
OBJECTIVE Borderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. METHODS A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. RESULTS Median age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. CONCLUSION FSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.
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Affiliation(s)
- Sarita Kumari
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Neerja Bhatla
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Chandrima Ray
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Bhawna Arora
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Mathur
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Sunesh Kumar
- Department of Gynaecology, Sitaram Bhartia Institute of Science and Research, New Delhi, India
| | - Lalit Kumar
- Department of Medical Oncology, Artemis Hospitals, Gurugram, India.
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14
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Ordulu Z, Watkins J, Ritterhouse LL. Molecular Pathology of Ovarian Epithelial Neoplasms: Predictive, Prognostic, and Emerging Biomarkers. Clin Lab Med 2024; 44:199-219. [PMID: 38821641 DOI: 10.1016/j.cll.2023.08.004] [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: 06/02/2024]
Abstract
This review focuses on the diagnostic, prognostic, and predictive molecular biomarkers in ovarian epithelial neoplasms in the context of their morphologic classifications. Currently, most clinically actionable molecular findings are reported in high-grade serous carcinomas; however, the data on less common tumor types are rapidly accelerating. Overall, the advances in genomic knowledge over the last decade highlight the significance of integrating molecular findings with morphology in ovarian epithelial tumors for a wide-range of clinical applications, from assistance in diagnosis to predicting response to therapy.
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Affiliation(s)
- Zehra Ordulu
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02124, USA
| | - Jaclyn Watkins
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02124, USA
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15
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Sama S, Rosqvist S, Savage T, Lomo L, Sibbald K, Straubhar A, Werner TL. Durable response to BRAF inhibitor monotherapy in recurrent metastatic low grade serous ovarian cancer. Gynecol Oncol Rep 2024; 53:101412. [PMID: 38779189 PMCID: PMC11109349 DOI: 10.1016/j.gore.2024.101412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/05/2024] [Accepted: 05/06/2024] [Indexed: 05/25/2024] Open
Abstract
Low grade serous ovarian cancers (LGSOC) in an advanced setting have limited systemic treatment options. In this paper we report a case of metastatic LGSOC harboring a BRAF mutation, treated with dabrafenib. We discuss the clinical, pathologic and molecular characteristics as well as surgical considerations and ongoing investigations in LGSOC.
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Affiliation(s)
- Shashank Sama
- Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA
| | | | - Talicia Savage
- Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA
| | - Lesley Lomo
- Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA
| | | | | | - Theresa L. Werner
- Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA
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16
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Cosyns S, Van Moer E, De Quick I, Tournaye H, De Vos M. Reproductive outcomes in women opting for fertility preservation after fertility-sparing surgery for borderline ovarian tumors. Arch Gynecol Obstet 2024; 309:2143-2152. [PMID: 38494510 DOI: 10.1007/s00404-024-07445-x] [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: 11/04/2023] [Accepted: 02/22/2024] [Indexed: 03/19/2024]
Abstract
PURPOSE What are the reproductive outcomes of women who had fertility preservation (FP) using either oocyte or embryo vitrification after fertility-sparing surgery (FSS) for a borderline ovarian tumor (BOT)? METHODS A retrospective, single-center cohort study was conducted between January 2013 and December 2021. Patients with BOT who resorted to FP by vitrifying oocytes or embryos were included. Both clinical and reproductive parameters were reviewed. The primary outcome was live birth. RESULTS In total, thirteen patients who performed 31 FP cycles were included. Of those, six patients achieved eight live births after a mean follow-up period of 79 months. Three further pregnancies are still ongoing. All pregnancies/live births were obtained without using their cryopreserved oocytes or embryos. CONCLUSION Women who had FSS for BOT have favorable prospects of live offspring, even without the need to use their cryopreserved material. Fertility preservation in patients with BOT has to be considered as a tool to mitigate the risk of infertility that may arise in case of BOT recurrence requiring castrating surgery.
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Affiliation(s)
- S Cosyns
- Department of Gynaecology - Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090, Brussels, Belgium.
| | - E Van Moer
- Brussels IVF, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Brussels, Belgium
| | - I De Quick
- Brussels IVF, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Brussels, Belgium
| | - H Tournaye
- Brussels IVF, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Brussels, Belgium
- Research Group Biology of the Testis, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium
| | - M De Vos
- Brussels IVF, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Brussels, Belgium
- Research Group Follicle Biology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium
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17
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Ledermann JA, Matias-Guiu X, Amant F, Concin N, Davidson B, Fotopoulou C, González-Martin A, Gourley C, Leary A, Lorusso D, Banerjee S, Chiva L, Cibula D, Colombo N, Croce S, Eriksson AG, Falandry C, Fischerova D, Harter P, Joly F, Lazaro C, Lok C, Mahner S, Marmé F, Marth C, McCluggage WG, McNeish IA, Morice P, Nicum S, Oaknin A, Pérez-Fidalgo JA, Pignata S, Ramirez PT, Ray-Coquard I, Romero I, Scambia G, Sehouli J, Shapira-Frommer R, Sundar S, Tan DSP, Taskiran C, van Driel WJ, Vergote I, Planchamp F, Sessa C, Fagotti A. ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease. Ann Oncol 2024; 35:248-266. [PMID: 38307807 DOI: 10.1016/j.annonc.2023.11.015] [Citation(s) in RCA: 92] [Impact Index Per Article: 92.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 11/17/2023] [Accepted: 11/28/2023] [Indexed: 02/04/2024] Open
Abstract
The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
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Affiliation(s)
- J A Ledermann
- Department of Oncology, UCL Cancer Institute, University College London, London, UK.
| | - X Matias-Guiu
- CIBERONC, Madrid; Department of Pathology, Hospital Universitari Arnau de Vilanova, IRBLLEIDA, University of Lleida, Lleida; Department of Pathology, Hospital Universitari de Bellvitge, IDIBELL, University of Barcelona, Barcelona, Spain.
| | - F Amant
- Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Department of Gynecology, Center for Gynecological Oncology Amsterdam, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - N Concin
- Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Innsbruck, Austria; Department of Gynaecology and Gynaecologic Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany
| | - B Davidson
- Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - C Fotopoulou
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
| | - A González-Martin
- Department of Medical Oncology and Program in Solid Tumours-Cima, Cancer Center Clínica Universidad de Navarra, Madrid, Spain
| | - C Gourley
- Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
| | - A Leary
- Department of Medicine, Institut Gustave Roussy, Villejuif, France
| | - D Lorusso
- Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; Department of Woman, Child and Public Health, Catholic University of Sacred Heart, Rome, Italy
| | - S Banerjee
- The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK
| | - L Chiva
- Department of Gynaecology and Obstetrics, Cancer Center Clínica Universidad de Navarra, Navarra, Spain
| | - D Cibula
- Department of Gynecology, Obstetrics and Neonatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - N Colombo
- Department of Gynecologic Oncology, Istituto Europeo di Oncologia IRCCS, Milan; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - S Croce
- Department of Biopathology, Bergonié Institut, Bordeaux, France
| | - A G Eriksson
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Gynecologic Oncology, Division of Cancer Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - C Falandry
- Institute of Aging, Hospices Civils de Lyon, Lyon; CarMeN Laboratory, INSERM U1060/Université Lyon 1/INRAE U1397/Hospices Civils Lyon, Pierre-Bénite, France
| | - D Fischerova
- Department of Gynecology, Obstetrics and Neonatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - P Harter
- Department of Gynaecology and Gynaecologic Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany; Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Study Group, Germany
| | - F Joly
- GINECO Group, Department of Medical Oncology, Centre François-Baclesse, University of Caen Normandy, Caen, France
| | - C Lazaro
- Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL-CIBERONC), L'Hospitalet de Llobregat, Barcelona, Spain
| | - C Lok
- Department of Gynecology, Center for Gynecological Oncology Amsterdam, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - S Mahner
- Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Study Group, Germany; Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich
| | - F Marmé
- Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Study Group, Germany; Department of Obstetrics and Gynecology, University Hospital Mannheim, Mannheim; Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - C Marth
- Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Innsbruck, Austria
| | - W G McCluggage
- Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK
| | - I A McNeish
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
| | - P Morice
- Department of Gynecologic Surgery, Gustave Roussy Cancer Campus, Villejuif, France
| | - S Nicum
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - A Oaknin
- Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona
| | - J A Pérez-Fidalgo
- Department of Medical Oncology, Hospital Clínico Universitario - INCLIVA, CIBERONC, Valencia, Spain
| | - S Pignata
- Department of Urology and Gynecology, Istituto Nazionale Tumori di Napoli, IRCCS Fondazione Pascale, Napoli, Italy
| | - P T Ramirez
- Department of Obstetrics and Gynecology, Houston Methodist Hospital, Houston, USA
| | - I Ray-Coquard
- Department of Medical Oncology, Centre Léon Bérard, University Claude Bernard, Lyon, France
| | - I Romero
- Department of Medical Oncology, Instituto Valenciano Oncologia, Valencia, Spain
| | - G Scambia
- Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; Department of Woman, Child and Public Health, Catholic University of Sacred Heart, Rome, Italy
| | - J Sehouli
- North-Eastern German Society of Gynecological Oncology (NOGGO), Berlin; Department of Gynecology with Center for Oncological Surgery, Charité Berlin University of Medicine, Berlin, Germany
| | | | - S Sundar
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham; Pan Birmingham Gynaecological Cancer Centre, City Hospital, Birmingham, UK
| | - D S P Tan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; National University of Singapore (NUS) Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cancer Science Institute, National University of Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute Singapore, National University Hospital, Singapore, Singapore
| | - C Taskiran
- Department of Gynecologic Oncology, School of Medicine, Koç University, Istanbul, Turkey
| | - W J van Driel
- Department of Gynecology, Center for Gynecological Oncology Amsterdam, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - I Vergote
- Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
| | | | - C Sessa
- Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
| | - A Fagotti
- Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; Department of Woman, Child and Public Health, Catholic University of Sacred Heart, Rome, Italy.
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18
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Schweizer L, Krishnan R, Shimizu A, Metousis A, Kenny H, Mendoza R, Nordmann TM, Rauch S, Kelliher L, Heide J, Rosenberger FA, Bilecz A, Borrego SN, Strauss MT, Thielert M, Rodriguez E, Müller-Reif JB, Chen M, Yamada SD, Mund A, Lastra RR, Mann M, Lengyel E. Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.11.13.23298409. [PMID: 38014221 PMCID: PMC10680885 DOI: 10.1101/2023.11.13.23298409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
Serous borderline tumors (SBT) are epithelial neoplastic lesions of the ovaries that commonly have a good prognosis. In 10-15% of cases, however, SBT will recur as low-grade serous cancer (LGSC), which is deeply invasive and responds poorly to current standard chemotherapy1,2,3. While genetic alterations suggest a common origin, the transition from SBT to LGSC remains poorly understood4. Here, we integrate spatial proteomics5 with spatial transcriptomics to elucidate the evolution from SBT to LGSC and its corresponding metastasis at the molecular level in both the stroma and the tumor. We show that the transition of SBT to LGSC occurs in the epithelial compartment through an intermediary stage with micropapillary features (SBT-MP), which involves a gradual increase in MAPK signaling. A distinct subset of proteins and transcripts was associated with the transition to invasive tumor growth, including the neuronal splicing factor NOVA2, which was limited to expression in LGSC and its corresponding metastasis. An integrative pathway analysis exposed aberrant molecular signaling of tumor cells supported by alterations in angiogenesis and inflammation in the tumor microenvironment. Integration of spatial transcriptomics and proteomics followed by knockdown of the most altered genes or pharmaceutical inhibition of the most relevant targets confirmed their functional significance in regulating key features of invasiveness. Combining cell-type resolved spatial proteomics and transcriptomics allowed us to elucidate the sequence of tumorigenesis from SBT to LGSC. The approach presented here is a blueprint to systematically elucidate mechanisms of tumorigenesis and find novel treatment strategies.
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Affiliation(s)
- Lisa Schweizer
- Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Rahul Krishnan
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Aasa Shimizu
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Andreas Metousis
- Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Hilary Kenny
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Rachelle Mendoza
- Department of Pathology, The University of Chicago, Chicago, IL, USA
| | - Thierry M. Nordmann
- Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Sarah Rauch
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Lucy Kelliher
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Janna Heide
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Florian A. Rosenberger
- Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Agnes Bilecz
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Sanaa Nakad Borrego
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Maximillian T. Strauss
- Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Marvin Thielert
- Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Edwin Rodriguez
- Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Johannes B. Müller-Reif
- Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Mengjie Chen
- Medicine/Section of Genetic Medicine, The University of Chicago, Chicago, IL, USA
| | - S. Diane Yamada
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Andreas Mund
- Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ricardo R. Lastra
- Department of Pathology, The University of Chicago, Chicago, IL, USA
| | - Matthias Mann
- Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
- Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ernst Lengyel
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
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19
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Baba T, Koshiyama M, Kagabu M, Mikami Y, Minamiguchi S, Moritani S, Ishikawa M, Okamoto A, Terao Y, Nakanishi T, Katabuchi H, Tokunaga H, Satoh T, Konishi I, Yaegashi N. Ovarian serous borderline tumors with recurrent or extraovarian lesions: a Japanese, retrospective, multi-institutional, population-based study. Int J Clin Oncol 2023; 28:1411-1420. [PMID: 37526805 DOI: 10.1007/s10147-023-02393-z] [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: 06/16/2023] [Accepted: 07/18/2023] [Indexed: 08/02/2023]
Abstract
BACKGROUND Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging. METHODS A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists. RESULT The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40 months and 77.0% was observed in the contralateral ovary within 60 months. Patients aged ≤ 35 years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants. CONCLUSION The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT.
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Affiliation(s)
- Tsukasa Baba
- Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 2-1-1 Idaidori, Yahaba-Cho, Shiwa, Iwate, 028-3695, Japan.
- Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
| | - Masafumi Koshiyama
- Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Masahiro Kagabu
- Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 2-1-1 Idaidori, Yahaba-Cho, Shiwa, Iwate, 028-3695, Japan
| | - Yoshiki Mikami
- Department of Diagnostic Pathology, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Sachiko Minamiguchi
- Department of Diagnostic Pathology, Kyoto University Hospital, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Suzuko Moritani
- Department of Diagnostic Pathology, Shiga University of Medical Science Hospital, Setatsukinowa-Cho, Otsu, 520-2192, Japan
| | - Mitsuya Ishikawa
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Aikou Okamoto
- Department of Gynecology and Obstetrics, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Yasuhisa Terao
- Department of Gynecology and Obstetrics, Faculty of Medicine, Juntendo University, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Toru Nakanishi
- Department of Gynecologic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku, Nagoya, 464-8681, Japan
| | - Hidetaka Katabuchi
- Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hideki Tokunaga
- Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8675, Japan
| | - Toyomi Satoh
- Department of Gynecology and Obstetrics, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan
| | - Ikuo Konishi
- Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Nobuo Yaegashi
- Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8675, Japan
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20
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Grisham RN, Slomovitz BM, Andrews N, Banerjee S, Brown J, Carey MS, Chui H, Coleman RL, Fader AN, Gaillard S, Gourley C, Sood AK, Monk BJ, Moore KN, Ray-Coquard I, Shih IM, Westin SN, Wong KK, Gershenson DM. Low-grade serous ovarian cancer: expert consensus report on the state of the science. Int J Gynecol Cancer 2023; 33:1331-1344. [PMID: 37591609 PMCID: PMC10511962 DOI: 10.1136/ijgc-2023-004610] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2023] [Indexed: 08/19/2023] Open
Abstract
Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.
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Affiliation(s)
- Rachel N Grisham
- Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA
| | - Brian M Slomovitz
- Department of Gynecologic Oncology, Mount Sinai Medical Center, Miami Beach, Florida, USA
- Florida International University, Miami, Florida, USA
| | - Nicole Andrews
- STAAR Ovarian Cancer Foundation, Western Springs, Illinois, USA
| | | | - Jubilee Brown
- Department of Gynecologic Oncology, Levine Cancer Institute at Atrium Health, Wake Forest University, Charlotte, North Carolina, USA
| | - Mark S Carey
- Division of Gynecologic Oncology, Vancouver Coastal Health, Vancouver, British Columbia, Canada
| | - Herman Chui
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Robert L Coleman
- Sarah Cannon Research Institute (SCRI), Nashville, Tennessee, USA
| | - Amanda N Fader
- Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Stephanie Gaillard
- Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Charlie Gourley
- Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh, UK
| | - Anil K Sood
- Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Bradley J Monk
- Division of Gynecologic Oncology, Honor Health, University of Arizona, Creighton University, Phoenix, Arizona, USA
| | - Kathleen N Moore
- Department of Gynecologic Oncology, Stephenson Cancer Center at the University of Oklahoma Health Sciences, Oklahoma City, Oklahoma, USA
| | - Isabelle Ray-Coquard
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France
- Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Ie-Ming Shih
- Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Shannon N Westin
- Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Kwong-Kwok Wong
- Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - David M Gershenson
- Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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21
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McHenry A, Rottmann DA, Buza N, Hui P. KRAS mutation in primary ovarian serous borderline tumors correlates with tumor recurrence. Virchows Arch 2023:10.1007/s00428-023-03564-z. [PMID: 37219599 DOI: 10.1007/s00428-023-03564-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/05/2023] [Accepted: 05/16/2023] [Indexed: 05/24/2023]
Abstract
Oncogenic activation of the mitogen-activated protein kinase (MAPK) pathway due to KRAS or BRAF gain-of-function mutation is frequently found in ovarian serous borderline tumor (SBT) and their extraovarian implants. We investigated mutational status of KRAS and BRAF of the primary ovarian SBTs that had a high stage presentation in correlation with clinical outcome. Among 39 consecutive primary SBTs with either invasive implants (20 cases) or non-invasive implants (19 cases), KRAS and BRAF mutational analysis was informative in 34 cases. Sixteen cases (47%) harbored a KRAS mutation, while 5 cases (15%) had a BRAF V600E mutation. High-stage disease (IIIC) was seen in 31% (5/16) of patients with a KRAS mutation and 39% (7/18) of patients without a KRAS mutation (p = 0.64). KRAS mutations were present in 9/16 (56%) tumors with invasive implants/LGSC versus 7/18 (39%) tumors with non-invasive implants (p = 0.31). BRAF mutation was seen in 5 cases with non-invasive implants. Tumor recurrence was seen in 31% (5/16) of patients with a KRAS mutation, compared to 6% (1/18) of patients without a KRAS mutation (p = 0.04). A KRAS mutation predicted an adverse disease-free survival (31% survival at 160 months) compared to those with wild-type KRAS (94% at 160 months; log-rank test, p = 0.037; HR 4.47). In conclusion, KRAS mutation in primary ovarian SBTs is significantly associated with a worse disease-free survival, independent of the high tumor stage or histological subtypes of extraovarian implant. KRAS mutation testing of primary ovarian SBT may servce as a useful biomarker for tumor recurrence.
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Affiliation(s)
- Austin McHenry
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | | | - Natalia Buza
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Pei Hui
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
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22
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Lymph Node Involvement in Recurrent Serous Borderline Ovarian Tumors: Current Evidence, Controversies, and a Review of the Literature. Cancers (Basel) 2023; 15:cancers15030890. [PMID: 36765848 PMCID: PMC9913328 DOI: 10.3390/cancers15030890] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 01/24/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Borderline ovarian tumors (BOTs) account for 10-20% of epithelial ovarian neoplasms. They are characterized by their lack of destructive stromal invasion. In comparison to invasive ovarian cancers, BOTs occur in younger patients and have better outcome. Serous borderline ovarian tumor (SBOT) represents the most common subtype of BOT. Complete surgical staging is the current standard management but fertility-sparing surgery is an option for SBOT patients who are at reproductive age. While most cases of SBOTs have an indolent course with favorable prognosis, late recurrence and malignant transformation can occur, usually in the form of low-grade serous carcinoma (LGSC). Thus, assessment of the recurrence risk is essential for the management of those patients. SBOTs can be associated with lymph node involvement (LNI) in up to 30% of patients who undergo lymph node dissection at diagnosis, and whether LNI affects prognosis is controversial. The present review suggests that recurrent SBOTs with LNI have poorer oncological outcomes and highlights the biases due to the scarcity of reports in the literature. Preventing SBOTs from recurring and becoming invasive overtime and a more profound understanding of the underlying mechanisms at play are necessary.
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23
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Gilks CB, Selinger CI, Davidson B, Köbel M, Ledermann JA, Lim D, Malpica A, Mikami Y, Singh N, Srinivasan R, Vang R, Lax SF, McCluggage WG. Data Set for the Reporting of Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma: Recommendations From the International Collaboration on Cancer Reporting (ICCR). Int J Gynecol Pathol 2022; 41:S119-S142. [PMID: 36305537 DOI: 10.1097/pgp.0000000000000908] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The move toward consistent and comprehensive surgical pathology reports for cancer resection specimens has been a key development in supporting evidence-based patient management and consistent cancer staging. The International Collaboration on Cancer Reporting (ICCR) previously developed a data set for reporting of the ovarian, fallopian tube and primary peritoneal carcinomas which was published in 2015. In this paper, we provide an update on this data set, as a second edition, that reflects changes in the 2020 World Health Organization (WHO) Classification of Female Genital Tumours as well as some other minor modifications. The data set has been developed by a panel of internationally recognized expert pathologists and a clinician and consists of "core" and "noncore" elements to be included in surgical pathology reports, with detailed commentary to guide users, including references. This data set replaces the widely used first edition, and will facilitate consistent and accurate case reporting, data collection for quality assurance and research, and allow for comparison of epidemiological and pathologic parameters between different populations.
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24
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Prognosis and Prognostic Factors of Serous Borderline Tumor-Micropapillary Variant: Retrospective Study of 200 Patients with Long-Term Follow-Up. JOURNAL OF ONCOLOGY 2022; 2022:1655422. [PMID: 36262351 PMCID: PMC9576405 DOI: 10.1155/2022/1655422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 08/07/2022] [Accepted: 09/17/2022] [Indexed: 11/18/2022]
Abstract
Objective To determine the oncofertility outcomes and prognostic factors in a large series of serous borderline ovarian tumor-micropapillary variant (SBOT-M) with a long-term follow-up. Methods Consecutive patients with SBOT-Ms treated from two affiliated hospitals of the Chinese Academy of Medical Sciences were retrospectively reviewed. Prognostic factors on invasive recurrence, disease-free survival (DFS), and overall survival were analyzed, and outcomes of patients treated with conservative and radical surgery were compared. Results From 2000 to 2020, 200 patients were identified and followed. After a median follow-up of 68 months, 81 patients relapsed. In the multivariate analyses, younger age at diagnosis and conservative surgery that preserved fertility potential were independently associated with worse DFS (p = 0.018 and <0.001, respectively). Twenty-three patients experienced invasive recurrence, and seven died of progressive disease. Multivariate analysis showed that nulliparous and advanced FIGO stage were independently adversely associated with lethal recurrence (p = 0.022 and 0.029, respectively). Only advanced FIGO stage at diagnosis was associated with worse overall survival at univariate analysis (p = 0.02). Among 61 patients attempting conception, 37 achieved 44 pregnancies and resulted in 32 live births. Conclusions In this series, patients with SBOT-M have an acceptable oncofertility outcomes. The use of conservative surgery was independently associated with worse DFS, but without an impact on neither invasive relapse nor on overall survival. Patients with advanced FIGO stages had a significantly higher risk of lethal recurrence and worse overall survival, suggesting that adequate staging surgery and intensive postoperative surveillance should be warranted.
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25
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Di Lorenzo P, Conteduca V, Scarpi E, Adorni M, Multinu F, Garbi A, Betella I, Grassi T, Bianchi T, Di Martino G, Amadori A, Maniglio P, Strada I, Carinelli S, Jaconi M, Aletti G, Zanagnolo V, Maggioni A, Savelli L, De Giorgi U, Landoni F, Colombo N, Fruscio R. Advanced low grade serous ovarian cancer: A retrospective analysis of surgical and chemotherapeutic management in two high volume oncological centers. Front Oncol 2022; 12:970918. [PMID: 36237308 PMCID: PMC9551309 DOI: 10.3389/fonc.2022.970918] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 09/05/2022] [Indexed: 11/13/2022] Open
Abstract
Simple summaryLow-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade serous ovarian cancer, cytoreductive surgery is considered crucial for patient survival. This retrospective study aimed to analyze the outcomes of women affected by advanced stages (III–IV FIGO) of LGSOC from two high-volume oncological centers for ovarian neoplasm. In particular, we sought to evaluate the impact on survival outcomes of optimal cytoreductive surgery [i.e., residual disease (RD) <10 mm at the end of surgery]. The results of our work confirm the role of complete cytoreduction (i.e., no evidence of disease after surgery) in the survival of patients and even the positive prognostic role of a minimal RD (i.e., <10 mm), whenever complete cytoreduction cannot be achieved.BackgroundLow-grade serous ovarian cancer (LGSOC) is a rare entity with different behavior compared to high-grade serous (HGSOC). Because of its general low chemosensitivity, complete cytoreductive surgery with no residual disease is crucial in advanced stage LGSOC. We evaluated the impact of optimal cytoreduction on survival outcome both at first diagnosis and at recurrence.MethodsWe retrospectively studied consecutive patients diagnosed with advanced LGSOCs who underwent cytoreductive surgery in two oncological centers from January 1994 to December 2018. Survival curves were estimated by the Kaplan–Meier method, and 95% confidence intervals (95% CI) were estimated using the Greenwood formula.ResultsA total of 92 patients were included (median age was 47 years, IQR 35–64). The median overall survival (OS) was 142.3 months in patients with no residual disease (RD), 86.4 months for RD 1–10 mm and 35.2 months for RD >10 mm (p = 0.002). Progression-free survival (PFS) was inversely related to RD after primary cytoreductive surgery (RD = 0 vs RD = 1–10 mm vs RD >10 mm, p = 0.002). On multivariate analysis, RD 1–10 mm (HR = 2.30, 95% CI 1.30–4.06, p = 0.004), RD >10 mm (HR = 3.89, 95% CI 1.92–7.88, p = 0.0004), FIGO stage IV (p = 0.001), and neoadjuvant chemotherapy (NACT) (p = 0.010) were independent predictors of PFS. RD >10 mm (HR = 3.13, 95% CI 1.52–6.46, p = 0.004), FIGO stage IV (p <0.0001) and NACT (p = 0.030) were significantly associated with a lower OS.ConclusionsOptimal cytoreductive surgery improves survival outcomes in advanced stage LGSOCs. When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.
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Affiliation(s)
- Paolo Di Lorenzo
- Obstetrics and Gynecology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
- Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
- *Correspondence: Paolo Di Lorenzo, ; Ugo De Giorgi,
| | - Vincenza Conteduca
- Department of Medical Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS) Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”, Meldola, Italy
- Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, Foggia, Italy
| | - Emanuela Scarpi
- Biostatistics and Clinical Trials Unit, Istituto di ricovero e cura a carattere scientifico (IRCCS) Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”, Meldola, Italy
| | - Marco Adorni
- Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Francesco Multinu
- Division of Gynecologic Oncology, European Institute of Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS), Milano, Italy
| | - Annalisa Garbi
- Division of Gynecologic Oncology, European Institute of Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS), Milano, Italy
| | - Ilaria Betella
- Division of Gynecologic Oncology, European Institute of Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS), Milano, Italy
| | - Tommaso Grassi
- Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Tommaso Bianchi
- Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Giampaolo Di Martino
- Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Andrea Amadori
- Obstetrics and Gynecology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Paolo Maniglio
- Obstetrics and Gynecology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Isabella Strada
- Obstetrics and Gynecology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Silvestro Carinelli
- Department of Pathology, European Institute of Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS), Milano, Italy
| | - Marta Jaconi
- Department of Pathology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Giovanni Aletti
- Division of Gynecologic Oncology, European Institute of Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS), Milano, Italy
- Department of Hemato-Oncology, University of Milan, Milano, Italy
| | - Vanna Zanagnolo
- Division of Gynecologic Oncology, European Institute of Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS), Milano, Italy
| | - Angelo Maggioni
- Division of Gynecologic Oncology, European Institute of Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS), Milano, Italy
| | - Luca Savelli
- Obstetrics and Gynecology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Ugo De Giorgi
- Department of Medical Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS) Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”, Meldola, Italy
- *Correspondence: Paolo Di Lorenzo, ; Ugo De Giorgi,
| | - Fabio Landoni
- Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - Nicoletta Colombo
- Division of Gynecologic Oncology, European Institute of Oncology, Istituto di ricovero e cura a carattere scientifico (IRCCS), Milano, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Robert Fruscio
- Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
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Della Corte L, Mercorio A, Serafino P, Viciglione F, Palumbo M, De Angelis MC, Borgo M, Buonfantino C, Tesorone M, Bifulco G, Giampaolino P. The challenging management of borderline ovarian tumors (BOTs) in women of childbearing age. Front Surg 2022; 9:973034. [PMID: 36081590 PMCID: PMC9445208 DOI: 10.3389/fsurg.2022.973034] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 08/09/2022] [Indexed: 11/14/2022] Open
Abstract
Borderline ovarian tumors (BOTs) account for approximately 15% of all epithelial ovarian cancers. In 80% of cases the diagnosis of BOTs is done at stage I and more than a third of BOTs occurs in women younger than 40 years of age wishing to preserve their childbearing potential; the issue of conservative surgical management (fertility-sparing treatment) is thus becoming of paramount importance. At early stages, the modalities of conservative treatment could range from mono-lateral cystectomy to bilateral salpingo-oophorectomy. Although cystectomy is the preferred method to promote fertility it can lead to an elevated risk of recurrence; therefore, an appropriate counseling about the risk of relapse is mandatory before opting for this treatment. Nevertheless, relapses are often benign and can be treated by repeated conservative surgery. Besides the stage of the disease, histological subtype is another essential factor when considering the proper procedure: as most mucinous BOTs (mBOTs) are more commonly unilateral, the risk of an invasive recurrence seems to be higher, compared to serous histotype, therefore unilateral salpingo-oophorectomy is recommended. In the appraisal of current literature, this review aims to gain better insight on the current recommendations to identify the right balance between an accurate staging and an optimal fertility outcome.
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Affiliation(s)
- Luigi Della Corte
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Antonio Mercorio
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
- Correspondence: Antonio Mercorio
| | - Paolo Serafino
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Francesco Viciglione
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Mario Palumbo
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | | | - Maria Borgo
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Cira Buonfantino
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Marina Tesorone
- Department of Child and Adolescent Health, U.O.C Protection of Women's- ASL Napoli 1, Naples, Italy
| | - Giuseppe Bifulco
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
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Huang M, Lv Q, Xie J. Ovarian mucinous borderline tumor with anaplastic carcinomatous nodules in adolescents. J Ovarian Res 2022; 15:83. [PMID: 35836292 PMCID: PMC9284891 DOI: 10.1186/s13048-022-01010-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 06/12/2022] [Indexed: 11/10/2022] Open
Abstract
Bilateral ovarian epithelial neoplasms in adolescents are rare. Moreover, borderline mucinous neoplasms with local intraepithelial carcinoma with anaplastic carcinoma are even more infrequent. Herein, we presented a single case (a 17-year-old female) with regular menstrual cycles and stomach pain when eating who was diagnosed with a left ovarian tumor accompanied by mural nodules. The right ovarian cyst, the left ovary, and the fallopian tube were removed by surgery. Intraoperative diagnosis suggested a bilateral ovarian tumor with mural nodules, which include three different pathological types: sarcomatoid transformation, anaplastic carcinoma, and sarcoma. Paclitaxel combined with carboplatin was given for 6 cycles after an operation, and gonadotropin-releasing hormone agonist (GnRHa) was given at the beginning of chemotherapy for 3 cycles for ovarian function protection. Regular follow-up (the last follow-up was performed 48 months after the operation) of gynecological ultrasound and tumor indicators did not indicate recurrence. In clinical practice, it is necessary to pay attention to the symptoms such as abdominal pain in adolescent females. Routine non-invasive pelvic ultrasound is recommended to fully evaluate the nature of the tumor before surgery, and decide the operation mode. Also, intraoperative frozen pathology of the tissue should be performed as soon as possible.
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Affiliation(s)
- Mengqi Huang
- Departments of Gynecology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People's Republic of China
| | - Qian Lv
- Departments of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People's Republic of China
| | - Jingyan Xie
- Departments of Gynecology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People's Republic of China.
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28
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Shanta K, Nakayama K, Hossain MM, Razia S, Ishibashi T, Ishikawa M, Yamashita H, Kanno K, Sato S, Nakayama S, Otsuki Y, Kyo S. Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines. Curr Oncol 2022; 29:4020-4033. [PMID: 35735430 PMCID: PMC9221871 DOI: 10.3390/curroncol29060321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 05/19/2022] [Accepted: 05/25/2022] [Indexed: 11/16/2022] Open
Abstract
Few studies have reported hormonal agent use in the treatment of low-grade serous ovarian carcinomas (LGSOCs), which are chemoresistant. Considering the need for novel effective therapies, we investigated the hormone receptor expression and hormonal inhibition efficacy in LGSOCs. Using immunohistochemistry, we assessed the estrogen receptor (ER) expression status in 33 cases of histologically confirmed serous ovarian tumors, including 10, 11, and 12 cases of LGSOCs, serous borderline tumors (SBTs), and serous cystadenomas (SCAs), respectively. The genetic background reported in our previous study was used in the current study. MPSC1 cells, which were established from LGSOCs, were used in cell proliferation assays. We observed a higher ER expression in LGSOCs and SBTs than in SCAs (70%, 81%, and 50%, respectively). Thus, LGSOCs and SBTs exhibit higher ER expression than SCAs. Moreover, the PIK3CA mutation positively correlated with ER expression in LGSOCs (p = 0.0113). MPSC1 cells showed low ER expression on Western blotting. MPSC1 cell proliferation was significantly inhibited by fulvestrant (a selective ER downregulator). The activation of ER and PI3K/AKT signaling pathways may play an important role in LGSOC carcinogenesis. ER downregulation with fulvestrant or combination therapy with PI3K inhibitors is a possible novel treatment for patients with LGSOCs.
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Affiliation(s)
- Kamrunnahar Shanta
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
| | - Kentaro Nakayama
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
- Correspondence: ; Tel.: +81-853-20-2268
| | - Mohammad Mahmud Hossain
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
| | - Sultana Razia
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
| | - Tomoka Ishibashi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
| | - Masako Ishikawa
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
| | - Hitomi Yamashita
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
| | - Kosuke Kanno
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
| | - Seiya Sato
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
| | - Satoru Nakayama
- Department of Obstetrics and Gynecology, Seirei Hamamatsu Hospital, Hamamatsu 430-8558, Japan;
| | - Yoshiro Otsuki
- Department of Organ Pathology, Seirei Hamamatsu Hospital, Hamamatsu 430-8558, Japan;
| | - Satoru Kyo
- Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan; (K.S.); (M.M.H.); (S.R.); (T.I.); (M.I.); (H.Y.); (K.K.); (S.S.); (S.K.)
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29
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Rashid S, Arafah MA, Akhtar M. The Many Faces of Serous Neoplasms and Related Lesions of the Female Pelvis: A Review. Adv Anat Pathol 2022; 29:154-167. [PMID: 35180738 PMCID: PMC8989637 DOI: 10.1097/pap.0000000000000334] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Ovarian serous tumors and related lesions are one of the most common conditions of the female genital tract. While ovarian high-grade serous carcinoma carries high mortality and adverse prognosis, most other serous lesions have better clinical behavior. In recent years, significant progress has been made in understanding the nature and histogenesis of these lesions that has contributed to better and more precise clinical management. Most of the high-grade serous carcinomas involve the ovaries and/or peritoneum, although in most cases, their origin seems to be in the fallopian tube. This view is supported by the recognition of precursor lesions in the fallopian tube, such as p53 signature and serous tubular in situ carcinoma. This paper presents salient morphologic, immunohistochemical, and molecular data related to serous tumors and related lesions of the female pelvis and discusses the histogenetic interrelationship among these lesions in light of current knowledge.
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Affiliation(s)
- Sameera Rashid
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
| | - Maria A. Arafah
- Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Akhtar
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
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30
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Gong XQ, Zhang Y. Develop a nomogram to predict overall survival of patients with borderline ovarian tumors. World J Clin Cases 2022; 10:2115-2126. [PMID: 35321187 PMCID: PMC8895192 DOI: 10.12998/wjcc.v10.i7.2115] [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: 11/29/2021] [Revised: 01/17/2022] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prognosis of borderline ovarian tumors (BOTs) has been the concern of clinicians and patients. It is urgent to develop a model to predict the survival of patients with BOTs.
AIM To construct a nomogram to predict the likelihood of overall survival (OS) in patients with BOTs.
METHODS A total of 192 patients with histologically verified BOTs and 374 patients with epithelial ovarian cancer (EOC) were retrospectively investigated for clinical characteristics and survival outcomes. A 1:1 propensity score matching (PSM) analysis was performed to eliminate selection bias. Survival was analyzed by using the log-rank test and the restricted mean survival time (RMST). Next, univariate and multivariate Cox regression analyses were used to identify meaningful independent prognostic factors. In addition, a nomogram model was developed to predict the 1-, 3-, and 5-year overall survival of patients with BOTs. The predictive performance of the model was assessed by using the concordance index (C-index), calibration curves, and decision curve analysis (DCA).
RESULTS For clinical data, there was no significant difference in body mass index, preoperative CA199 concentration, or tumor localization between the BOTs group and EOC group. Women with BOTs were significantly younger than those with EOC. There was a significant difference in menopausal status, parity, preoperative serum CA125 concentration, Federation International of gynecology and obstetrics (FIGO) stage, and whether patients accepted postoperative adjuvant therapy between the BOT and EOC group. After PSM, patients with BOTs had better overall survival than patients with EOC (P value = 0.0067); more importantly, the 5-year RMST of BOTs was longer than that of EOC (P value = 0.0002, 95%CI -1.137 to -0.263). Multivariate Cox regression analysis showed that diagnosed age and surgical type were independent risk factors for BOT patient OS (P value < 0.05). A nomogram was developed based on diagnosed age, preoperative serum CA125 and CA199 Levels, surgical type, FIGO stage, and tumor size. Moreover, the c-index (0.959, 95% confidence interval 0.8708–1.0472), calibration plot of 1-, 3-, and 5-year OS, and decision curve analysis indicated the accurate predictive ability of this model.
CONCLUSION Patients with BOTs had a better prognosis than patients with EOC. The nomogram we constructed might be helpful for clinicians in personalized treatment planning and patient counseling.
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Affiliation(s)
- Xiao-Qin Gong
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Yan Zhang
- Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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31
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Low-Grade Serous Carcinoma of the Ovary: The Current Status. Diagnostics (Basel) 2022; 12:diagnostics12020458. [PMID: 35204549 PMCID: PMC8871133 DOI: 10.3390/diagnostics12020458] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/30/2022] [Accepted: 02/04/2022] [Indexed: 11/16/2022] Open
Abstract
Low-grade serous carcinoma (LGSC) of the ovary is a rare histological subtype of epithelial ovarian carcinoma. It has distinct clinical behavior and a specific molecular profile. Compared with high-grade serous carcinoma, this tumor presents at a younger age, has an indolent course, and is associated with prolonged survival. LGSC can arise de novo or originate following a serous borderline tumor (SBT). Pathological differentiation between LGSC and other ovarian carcinoma histological subtypes is fundamental. Several factors might influence the overall outcome, such as the age at diagnosis, current smoking, elevated body mass index, mutational status, hormonal receptors’ expression, and Ki-67 proliferation index. Surgery is the main treatment option in LGSC, and efforts must be maximized to achieve a microscopic residual in metastatic disease. Despite being relatively chemo-resistant, adjuvant platinum-based chemotherapy remains the standard of care in LGSC. Hormonal maintenance therapy after adjuvant chemotherapy results in improved outcomes. Treatment options for disease recurrence include secondary cytoreductive surgery, chemotherapy, hormonal therapy, targeted therapy, and clinical trials. Advancements in genomic studies and targeted therapies are expected to change the treatment landscape in LGSC.
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32
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Falcone F, Malzoni M, Carnelli M, Cormio G, De Iaco P, Di Donato V, Ferrandina G, Raspagliesi F, Sorio R, Losito NS, Greggi S. Fertility-sparing treatment for serous borderline ovarian tumors with extra-ovarian invasive implants: Analysis from the MITO14 study database. Gynecol Oncol 2022; 165:302-308. [DOI: 10.1016/j.ygyno.2022.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 02/12/2022] [Accepted: 02/21/2022] [Indexed: 11/04/2022]
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Kuji S, Harada M, Yoshioka N, Kajiyama H, Satoh T, Mikami M, Shozu M, Enomoto T, Osuga Y, Suzuki N. Survival and reproductive outcomes after fertility-sparing surgery performed for borderline epithelial ovarian tumor in Japanese adolescents and young adults: Results of a retrospective nationwide study. J Obstet Gynaecol Res 2021; 48:806-816. [PMID: 34951514 DOI: 10.1111/jog.15131] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 11/29/2021] [Accepted: 12/07/2021] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Epithelial borderline ovarian tumor (BOT) frequently occurs in young women. Because progression-free survival, overall survival, and reproductive function are important outcomes, BOT is often treated by fertility-sparing surgery (FSS). We conducted a Japan-wide study to understand post-FSS prognosis in relation to clinical characteristics and types of FSS performed. METHODS We analyzed clinical and outcome data pertaining to 531 adolescent and young adult (AYA) patients (aged 15-39 years) who underwent FSS for BOT between 2009 and 2013. RESULTS Median (range) age was 30 (15-39) years, and median observation time was 70 (2-120) months. The disease was of FIGO stage I in 492 (93%) patients. Histopathologically, tumors were of the mucinous (n = 372, 70%), serous (n = 120, 23%), seromucinous (n = 23, 4%), and other (n = 16, 3%) types. Five-year overall survival was 99.5% among patients with stage I and 100% among those with stage II-IV. Five-year progression-free survival was 96.7% and 69.3%, respectively. Multivariate analysis in cases of stage I showed a positive peritoneal cytology to be a significant risk factor for recurrence (HR, 5.199; p = 0.0188). The post-FSS pregnancy rate was relatively low for patients aged ≥30 years (OR, 0.868; 95% CI, 1.16-3.00; p = 0.0090). CONCLUSION Post-FFS outcomes in terms of overall and progression-free survival are favorable, especially for AYA patients with stage I BOT. However, the relapse rate is high for patients with FIGO stage II-IV and for those with stage I but a positive peritoneal cytology. A long-term prospective observation is needed before reproductive outcomes can be fully established.
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Affiliation(s)
- Shiho Kuji
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Miyuki Harada
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihito Yoshioka
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Hiroaki Kajiyama
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toyomi Satoh
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Mikio Mikami
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan
| | - Makio Shozu
- Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Medical School, Niigata, Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nao Suzuki
- Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kanagawa, Japan
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34
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Ordulu Z, Watkins J, Ritterhouse LL. Molecular Pathology of Ovarian Epithelial Neoplasms: Predictive, Prognostic, and Emerging Biomarkers. Surg Pathol Clin 2021; 14:415-428. [PMID: 34373093 DOI: 10.1016/j.path.2021.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This review focuses on the diagnostic, prognostic, and predictive molecular biomarkers in ovarian epithelial neoplasms in the context of their morphologic classifications. Currently, most clinically actionable molecular findings are reported in high-grade serous carcinomas; however, the data on less common tumor types are rapidly accelerating. Overall, the advances in genomic knowledge over the last decade highlight the significance of integrating molecular findings with morphology in ovarian epithelial tumors for a wide-range of clinical applications, from assistance in diagnosis to predicting response to therapy.
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Affiliation(s)
- Zehra Ordulu
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02124, USA
| | - Jaclyn Watkins
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02124, USA
| | - Lauren L Ritterhouse
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02124, USA.
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Hada T, Miyamoto M, Ishibashi H, Matsuura H, Sakamoto T, Kakimoto S, Iwahashi H, Suzuki R, Sato K, Tsuda H, Takano M. Prognostic similarity between ovarian mucinous carcinoma with expansile invasion and ovarian mucinous borderline tumor: A retrospective analysis. Medicine (Baltimore) 2021; 100:e26895. [PMID: 34397915 PMCID: PMC8360460 DOI: 10.1097/md.0000000000026895] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 07/18/2021] [Indexed: 01/04/2023] Open
Abstract
There is a similarity of histological features and survival between ovarian mucinous carcinoma (MC) with expansile invasion and ovarian mucinous borderline tumor (MBT). The aim of this study was to compare the clinical outcomes of MC with expansile invasion with those of MBT based on the 2020 World Health Organization (WHO) criteria.A pathological review was performed on patients with MC, ovarian MBT, and seromucinous borderline tumors that underwent surgery at our hospital between 1984 and 2019. Clinicopathological features were compared retrospectively between MC with expansile invasion and MBT.Among 83 cases of MC, 85 cases of MBT, and 12 cases of seromucinous borderline tumor, 25 MC cases with expansile invasion and 98 MBT cases were included through review. MC cases with expansile invasion were diagnosed with advanced International Federation of Gynecology and Obstetrics (FIGO) stages more frequently (P = .02) than that of MBT cases. In addition, patients with MC with expansile invasion received adjuvant chemotherapy more often (P < .01) than that of patients with MBT. There were no statistically significant differences in recurrence rate (P = .10) between MC with expansile invasion and MBT. Progression-free survival (PFS) was worse in MC cases with expansile invasion than that in MBT cases (P = .01). However, a multivariate analysis for PFS showed that histological subtype, FIGO stage, and adjuvant chemotherapy were not an independent prognostic factor.The prognostic outcome of MC with expansile invasion might mimic those of MBT. These results showed ovarian borderline tumor treatment could be applied to MC treatment.
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Affiliation(s)
- Taira Hada
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Morikazu Miyamoto
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Hiroki Ishibashi
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Hiroko Matsuura
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Takahiro Sakamoto
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Soichiro Kakimoto
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Hideki Iwahashi
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Rie Suzuki
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Kimiya Sato
- Department of Pathology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Hitoshi Tsuda
- Department of Pathology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
| | - Masashi Takano
- Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Tokorozawa, Japan
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36
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Fan Y, Zhang YF, Wang MY, Mu Y, Mo SP, Li JK. Influence of lymph node involvement or lymphadenectomy on prognosis of patients with borderline ovarian tumors: A systematic review and meta-analysis. Gynecol Oncol 2021; 162:797-803. [PMID: 34119365 DOI: 10.1016/j.ygyno.2021.05.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 05/27/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE Borderline ovarian tumors (BOTs) account for about 15% of all epithelial tumors of the ovary, and around 75% of patients are diagnosed in early stages. Although many of these patients have lymph node involvement (LNI), whether LNI decreases their survival is controversial, raising the question of whether lymphadenectomy should be performed. We conducted a systematic review and meta-analysis of these questions. METHODS We searched articles related to LNI and lymphadenectomy in patients with BOTs in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Data on rate of LNI, recurrence and survival were pooled and meta-analyzed using a random-effects model. Heterogeneity was evaluated using the I2 test. RESULTS A total of 25 studies with 12,503 patients were meta-analyzed. The overall pooled rate of LNI was 10% [95% confidence interval (CI) 0.07-0.13]. LNI was associated with a higher risk of recurrence [odds ratio (OR) 2.23, 95% CI 1.13-4.40]. However, LNI did not significantly affect cause-specific survival [hazard ratio (HR) 1.73, 95% CI 0.99-3.02] or disease-free survival (HR 1.48, 95% CI 0.56-3.92). Similarly, lymphadenectomy did not significantly affect risk of recurrence (OR 0.91, 95% CI 0.57-1.46), overall survival (HR 0.90, 95% CI 0.58-1.40), disease-free survival (HR 0.95, 95% CI 0.61-1.50) or progression-free survival (HR 0.60, 95% CI 0.24-1.49). CONCLUSIONS LNI appears to increase risk of recurrence in BOT patients, but neither it nor lymphadenectomy appears to influence prognosis. Therefore, lymphadenectomy should be considered only for certain BOT patients, such as those with suspected LNI based on imaging or surgical exploration.
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Affiliation(s)
- Yu Fan
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, People's Republic of China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People's Republic of China
| | - Yu-Fei Zhang
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, People's Republic of China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People's Republic of China
| | - Meng-Yao Wang
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, People's Republic of China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People's Republic of China
| | - Yi Mu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People's Republic of China
| | - Si-Ping Mo
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, People's Republic of China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People's Republic of China
| | - Jin-Ke Li
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, People's Republic of China.
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Jia SZ, Xiang Y, Yang JJ, Shi JH, Jia CW, Leng JH. Oncofertility outcomes after fertility-sparing treatment of bilateral serous borderline ovarian tumors: results of a large retrospective study. Hum Reprod 2021; 35:328-339. [PMID: 32048711 DOI: 10.1093/humrep/dez307] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 12/14/2019] [Indexed: 02/07/2023] Open
Abstract
STUDY QUESTION What are the oncofertility outcomes of young women (≤40 years old) with bilateral serous borderline ovarian tumors (SBOTs) after fertility-sparing surgery? SUMMARY ANSWER Fertility preservation with the bilateral ovarian cystectomy procedure is feasible for bilateral SBOTs, with an acceptable oncological outcome and worthwhile pregnancy rates. WHAT IS KNOWN ALREADY Fertility-sparing approaches are becoming the standard management of young patients with unilateral SBOTs and other borderline histological subtypes. However, there is a paucity of evidence to dictate the best management in bilateral SBOTs. STUDY DESIGN, SIZE, DURATION This was a retrospective observational study performed at the Peking Union Medical College Hospital in Beijing, China, between January 1999 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Ninety-four women (≤40 years old) with pathologically confirmed bilateral SBOTs were included. Following preoperative counseling, patients self-selected into one of three treatment modalities: bilateral ovarian cystectomy (n = 48), unilateral adnexectomy plus contralateral cystectomy (UAC; n = 31), and radical surgery (n = 15). Univariate and multivariate analyses were used to determine the clinical and pathological features associated with disease-free survival and reproductive outcomes. MAIN RESULTS AND THE ROLE OF CHANCE During the median follow-up of 64 months (range, 4-243 months), 61 patients (65%) developed relapse, including 3 (20%) in the radical group, 26 (84%) in the UAC group and 32 (67%) in the bilateral cystectomy group. In the multivariate analyses, preoperative CA-125>300 U/mL, fertility preservation and micropapillary pattern were independently associated with adverse disease-free survival (P = 0.001, 0.03 and 0.026, respectively). Fourteen patients (15%) experienced invasive recurrence, and three (3%) died of progressive disease. The micropapillary pattern was significantly associated with invasive evolution risk (P = 0.006). Of the 49 patients who attempted to conceive, 23 (47%) achieved 27 pregnancies (24 spontaneous and three after IVF-ET), resulting in 19 live births. There was no significant difference in disease-free survival (P = 0.13) or pregnancy rate (41 vs. 50%, P = 0.56) between the UAC and bilateral procedures. LIMITATIONS, REASONS FOR CAUTION As a retrospective study conducted in a referral center, inherent biases exist. The nonrandom allocation to treatment groups and relatively small number of patients attempt to conceive might limit the statistical power of our findings. Only 41 patients (43.6%) received complete staging during their initial surgeries, so an underestimation bias in terms of the FIGO stage and extraovarian implants might have occurred. WIDER IMPLICATIONS OF THE FINDINGS The ultraconservative bilateral ovarian cystectomy procedure should be proposed in bilateral SBOTs when technically feasible. Invasive evolution occurs frequently in these women, and intense follow-up and oncofertility counseling are warranted, especially for those with micropapillary patterns. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- Shuang-Zheng Jia
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P. R. China
| | - Yang Xiang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P. R. China
| | - Jun-Jun Yang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P. R. China
| | - Jing-Hua Shi
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P. R. China
| | - Cong-Wei Jia
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P. R. China
| | - Jin-Hua Leng
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P. R. China
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Falcone F, Breda E, Ferrandina G, Malzoni M, Perrone AM, Cormio G, Di Donato V, Frigerio L, Mangili G, Raspagliesi F, Festi A, Scibilia G, Biglia N, Sorio R, Vizza E, Losito NS, Greggi S. Fertility-sparing treatment in advanced-stage serous borderline ovarian tumors. An analysis from the MITO14 study database. Gynecol Oncol 2021; 161:825-831. [PMID: 33781554 DOI: 10.1016/j.ygyno.2021.03.023] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 03/20/2021] [Indexed: 12/01/2022]
Abstract
OBJECTIVES To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs). METHODS A multi-institutional retrospective study was conducted within the MITO Group. RESULTS A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT. CONCLUSIONS Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread.
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Affiliation(s)
- Francesca Falcone
- Department of Gynecologic Oncology, Istituto Nazionale Tumori, IRCSS, "Fondazione G. Pascale", Naples, Italy
| | - Enrico Breda
- Medical Oncology Unit, Ospedale S. Giovanni Calibita Fatebenefratelli, Rome, Italy
| | - Gabriella Ferrandina
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Mario Malzoni
- Endoscopica Malzoni, Center for Advanced Endoscopic Gynecologic Surgery, Avellino, Italy
| | - Anna M Perrone
- Division of Oncologic Gynecology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gennaro Cormio
- Department of Biomedical Sciences and Human Oncology, Unit of Obstetrics and Gynecology, University of Bari "Aldo Moro", Bari, Italy
| | - Violante Di Donato
- Department of Maternal and Child Health and Urological Sciences, Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Luigi Frigerio
- Obstetrics and Gynecology Department, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Giorgia Mangili
- Obstetrics and Gynecology Department, IRCCS Ospedale San Raffaele, Milan, Italy
| | | | - Anna Festi
- Gynecology and Obstetrics, University of Verona, Verona, Italy
| | - Giuseppe Scibilia
- Gynecology and Obstetrics, Maternal and Child Department, Cannizzaro Hospital, Catania, Italy
| | - Nicoletta Biglia
- Division of Gynecology and Obstetrics, Umberto I Hospital, Turin, Italy
| | - Roberto Sorio
- Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
| | - Enrico Vizza
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS, Regina Elena National Cancer Institute, Rome, Italy
| | - Nunzia S Losito
- Surgical Pathology Unit, Istituto Nazionale Tumori, IRCSS, "Fondazione G. Pascale", Naples, Italy
| | - Stefano Greggi
- Department of Gynecologic Oncology, Istituto Nazionale Tumori, IRCSS, "Fondazione G. Pascale", Naples, Italy.
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Kumari S, Kumar S, Bhatla N, Mathur S, Thulkar S, Kumar L. Oncologic and reproductive outcomes of borderline ovarian tumors in Indian population. Gynecol Oncol Rep 2021; 36:100756. [PMID: 33889704 PMCID: PMC8050374 DOI: 10.1016/j.gore.2021.100756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 02/26/2021] [Accepted: 03/16/2021] [Indexed: 01/10/2023] Open
Abstract
In BOT Fertility sparing surgery is a safe procedure in early stage disease and should be performed in a young patient. Recurrences are more common in the cystectomy group as compared to oophorectomy (33% vs 6.2%; p = 0.03). Overall and Recurrence free survival is favourable and recurrences are always salvaged by surgery. Spontaneous conception and live birth rates after fertility sparing surgery in patients with BOT are modest (50%). Borderline ovarian tumor (BOT) is characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed at early stages and in women of reproductive age group. A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at All India Institute of Medical Sciences New Delhi, during a five-year study period from March 2014 to March 2019 was performed. Surgical treatment was classified as radical, fertility sparing surgery (FSS) or cystectomy. Surgical staging was defined as complete, partial or unstaged. Median age of seventy-five women was 32 years. Follow up period ranged from 22 to 61 months (median 36 m). Radical surgery was done in 34 (45.3%), FSS in 32 (42.6%) and cystectomy in 9 (12.0%) women. Complete surgical staging was performed in 22 (29.3%), partial staging in 23 (30.6%) and 30 (40%) were unstaged. During the follow up period, 98.7% patients were alive and 90.7% were free of recurrence. Median time to recurrence was 35 months. Recurrence rate was 33.3% in cystectomy vs 6.2% in oophorectomy (p = 0.03). All seven recurrences were in unstaged (six) or partially staged patient (one). Six recurrences in ovary were salvaged by surgery and recurrent disease was of borderline histology. Spontaneous conception and live birth rate was 42.1%. FSS is a safe procedure and should be considered in a young patient with early stage disease and desirous of future fertility. Spontaneous conception and live birth rates after fertility sparing surgery in patients with BOT are modest.
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Affiliation(s)
- Sarita Kumari
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Sunesh Kumar
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Neerja Bhatla
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Mathur
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjay Thulkar
- Department of Radiology, Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Lalit Kumar
- Department of Medical Oncology, Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
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Zhang M, Zhou F, He Y, Tao X, Hua K, Ding J. Predicting Lymph Node Involvement in Borderline Ovarian Tumors with a Quantitative Model and Nomogram: A Retrospective Cohort Study. Cancer Manag Res 2021; 13:1529-1539. [PMID: 33623432 PMCID: PMC7896740 DOI: 10.2147/cmar.s287509] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/09/2021] [Indexed: 11/29/2022] Open
Abstract
Purpose This study aimed to establish a predictive model for lymph node involvement (LNI) in patients with borderline ovarian tumor (BOT) using clinicopathological factors. Patients and Methods We collected clinical data from consecutive patients who underwent lymphadenectomy for BOT between 2001 and 2018 and analyzed their clinicopathological features. Multivariate logistic regression was used to identify all independent risk factors associated with LNI; these were then incorporated into the prediction model. Results In total, we included 248 patients with BOT who were undergoing lymphadenectomy. These were divided into a training cohort (n=174) and a validation cohort (n=74). When considering histopathological data, 16 and 5 patients were identified to have LNI in the training and validation cohorts, respectively. Overall, 13.5% (21/156) patients with serous BOT had LNI while 0% (0/92) patients with non-serous BOT had LNI. We identified several predictors of LNI: the largest tumor being ≥ 12.2cm in diameter, the presence of lesions on the ovarian surface, and the presence of pelvic or abdominal lesions. We created a prediction model and nomogram that incorporated these three risk factors for serous BOT. The model achieved good discriminatory abilities of 0.951 and 0.848 when predicting LNI in the training and validation cohorts, respectively. The LNI-predicting nomogram had an area under curve (AUC) of 0.951 and generated well-fitted calibration curves. Conclusion Non-serous BOT may not require lymphadenectomy as part of surgical staging. The individual risk of LNI in patients with serous BOT can be accurately estimated using our prediction model and nomogram. The use of LNI criteria provides a practical way to support the clinician in making an optimal decision relating to surgical scope for patients with BOT.
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Affiliation(s)
- Menglei Zhang
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People's Republic of China.,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People's Republic of China
| | - Fangyue Zhou
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People's Republic of China
| | - Yuan He
- Public Health School of Fudan University, Shanghai, 200032, People's Republic of China
| | - Xiang Tao
- Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People's Republic of China
| | - Keqin Hua
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People's Republic of China.,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People's Republic of China
| | - Jingxin Ding
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People's Republic of China.,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People's Republic of China
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Taylor EC, Irshaid L, Mathur M. Multimodality Imaging Approach to Ovarian Neoplasms with Pathologic Correlation. Radiographics 2020; 41:289-315. [PMID: 33186060 DOI: 10.1148/rg.2021200086] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Ovarian neoplasms can be categorized on the basis of histopathologic features into epithelial surface cell tumors, germ cell tumors, sex cord-stromal tumors, and metastases. While their imaging appearance is often nonspecific, it closely parallels the gross pathologic appearance, and radiologic-pathologic correlation is helpful to aid in a deeper understanding of the subtypes. Epithelial cell neoplasms are the most common category, and they can be benign, borderline, or malignant. Specific subtypes include serous (most common), mucinous, seromucinous, endometrioid, clear cell, Brenner, and undifferentiated. High-grade serous cystadenocarcinoma accounts for the majority of malignant ovarian tumors and the most ovarian cancer deaths. While serous neoplasms are often unilocular and bilateral, mucinous neoplasms are larger, unilateral, and multilocular. Solid components, thickened septa, and papillary projections, particularly with vascularity, indicate borderline or malignant varieties. Endometrioid and clear cell carcinomas can arise within endometriomas. Fibrous tumors (cystadenofibroma, adenofibroma, fibroma or fibrothecoma, and Brenner tumors) demonstrate low T2-weighted signal intensity of their solid components, while teratomas contain lipid. The nonspecific imaging appearance of additional malignant ovarian germ cell tumors can be narrowed with tumor marker profiles. Sex cord-stromal tumors are often solid, and secondary signs from their hormonal secretion can be a clue to their diagnosis. The authors review the anatomy of the ovary and distal fallopian tube, the proposed origins of the histologic subtypes of tumors, the clinical features and epidemiology of ovarian neoplasms, and the applications of US, CT, and MRI in imaging ovarian neoplasms. The main focus is on the radiologic and pathologic features of the multiple ovarian neoplasm subtypes. An algorithmic approach to the diagnosis of ovarian neoplasms is presented. Online supplemental material is available for this article. ©RSNA, 2020.
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Affiliation(s)
- Erin C Taylor
- From the Department of Radiology and Biomedical Imaging (E.C.T., M.M.) and Department of Pathology (L.I.), Yale School of Medicine, 333 Cedar St, PO Box 208042, Room TE-2, New Haven, CT 06520
| | - Lina Irshaid
- From the Department of Radiology and Biomedical Imaging (E.C.T., M.M.) and Department of Pathology (L.I.), Yale School of Medicine, 333 Cedar St, PO Box 208042, Room TE-2, New Haven, CT 06520
| | - Mahan Mathur
- From the Department of Radiology and Biomedical Imaging (E.C.T., M.M.) and Department of Pathology (L.I.), Yale School of Medicine, 333 Cedar St, PO Box 208042, Room TE-2, New Haven, CT 06520
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Gouy S, Maria S, Faron M, Maulard A, Pautier P, Leary A, Chargari C, Genestie C, Morice P. Results After Conservative Surgery of Stage II/III Serous Borderline Ovarian Tumors. Ann Surg Oncol 2020; 28:3597-3604. [PMID: 33140251 DOI: 10.1245/s10434-020-09250-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 09/28/2020] [Indexed: 11/18/2022]
Abstract
OBJECTIVE The aim of this study was to assess the outcomes of a large series of patients treated conservatively for stage II or III serous borderline tumors of the ovary (SBOTs) with a long-term follow-up. METHODS Patients with SBOTs and peritoneal implants, treated in or referred to our institution, were retrospectively reviewed. Outcomes of patients treated conservatively (preservation of the uterus and at least a part of one ovary) to promote subsequent fertility were specifically analyzed. RESULTS Between 1971 and 2017, 212 patients were identified and followed-up. Among these patients, 65 underwent conservative treatment; eight patients had invasive implants. Among patients treated conservatively, 38 (58%) patients recurred. Twenty-eight recurrences were observed under the form of borderline tumor on the spared ovary and/or noninvasive implants, but eight patients had a recurrence under the form of invasive disease. Compared with radical surgery, the use of conservative treatment (p < 0.0001) was a prognostic factor on disease-free survival (DFS), but without an impact on overall survival (OS). Nevertheless, three deaths occurred. Twenty-four pregnancies (13 spontaneous) were observed in 20 patients (29 patients wanted to become pregnant). CONCLUSION In this series collecting the largest number of patients undergoing conservative surgery for stage II/III SBOTs, spontaneous pregnancies can be achieved after conservative treatment of advanced-stage disease, but the recurrence rate is high and three deaths were observed. These patients were spared their fertility but with a high rate of recurrence. Uncertainties regarding the safety of conservative treatment should be exposed to these patients.
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Affiliation(s)
- Sebastien Gouy
- Department of Gynaecologic Surgery, Institut Gustave-Roussy, Villejuif, France
| | - Sophie Maria
- Department of Gynaecologic Surgery, Institut Gustave-Roussy, Villejuif, France
| | - Matthieu Faron
- Department of Gynaecologic Surgery, Institut Gustave-Roussy, Villejuif, France
| | - Amandine Maulard
- Department of Gynaecologic Surgery, Institut Gustave-Roussy, Villejuif, France
| | - Patricia Pautier
- Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, France
| | - Alexandra Leary
- Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, France
| | - Cyrus Chargari
- Department of Radiation Oncology, Institut Gustave-Roussy, Villejuif, France
| | | | - Philippe Morice
- Department of Gynaecologic Surgery, Institut Gustave-Roussy, Villejuif, France. .,Paris-Sud University, Paris, France.
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Losi L, Botticelli L, Garagnani L, Fabbiani L, Panini R, Gallo G, Sabbatini R, Maiorana A, Benhattar J. TERT promoter methylation and protein expression as predictive biomarkers for recurrence risk in patients with serous borderline ovarian tumours. Pathology 2020; 53:187-192. [PMID: 33032810 DOI: 10.1016/j.pathol.2020.07.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 07/10/2020] [Accepted: 07/20/2020] [Indexed: 01/18/2023]
Abstract
Epithelial ovarian neoplasms can be divided into three distinct clinicopathological groups: benign, malignant and borderline tumours. Borderline tumours are less aggressive than epithelial carcinomas, with an indolent clinical course and delayed recurrence. However, a subset of these cases can progress to malignancy and relapse, and death from recurrent disease can occasionally occur. Telomerase activation is a critical element in cellular immortalisation and cancer. The enzyme telomerase comprises a catalytic subunit (TERT) expressed in various types of cancers and regulated by promoter methylation mainly in epithelial tumours. The aim of this study was to investigate the promoter methylation status and the expression of TERT in 50 serous borderline tumours (SBTs) and their correlation with clinicopathological features and outcome. TERT methylation was analysed by bisulfite pyrosequencing and TERT expression by immunohistochemistry. Methylation of TERT promoter was only observed in four SBTs. A good correlation with immunostochemistry was found: nuclear positivity for TERT expression was observed in the methylated cases, whereas no expression was detected in unmethylated tumours. One of these patients had a recurrence after 7 years and another patient died from the disease. SBTs with hypomethylated tumours and absence of TERT expression showed a good clinical behaviour. Our study highlights the low presence of TERT methylation in SBTs, confirming that these tumours have a different biology than serous carcinomas. Furthermore, the concordance between TERT promoter methylation and TERT expression and their association with clinical outcomes leads to consider TERT alteration as a potential predictive biomarker for recurrence risk identifying patients who should undergo a careful and prolonged follow-up.
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Affiliation(s)
- Lorena Losi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
| | - Laura Botticelli
- Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy
| | - Lorella Garagnani
- Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy; Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Luca Fabbiani
- Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy; Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Rossana Panini
- Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy; Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Graziana Gallo
- Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy; Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Roberto Sabbatini
- Division of Medical Oncology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy
| | - Antonino Maiorana
- Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy; Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Jean Benhattar
- Aurigen, Centre de Génétique et Pathologie, Lausanne, Switzerland
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Eymerit-Morin C, Brun JL, Vabret O, Devouassoux-Shisheboran M. [Borderline ovarian tumours: CNGOF Guidelines for clinical practice - Biopathology of ovarian borderline tumors]. GYNECOLOGIE, OBSTETRIQUE, FERTILITE & SENOLOGIE 2020; 48:629-645. [PMID: 32422414 DOI: 10.1016/j.gofs.2020.05.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVES Ovarian borderline tumors (OBT) represent a heterogeneous group of lesions with specific management for each histological subtype. Thus, the correct histological diagnosis is mandatory. MATERIAL AND METHODS References were searched by PubMed from January 2000 to January 2018 and original articles in French and English literature were selected. RESULTS AND CONCLUSIONS OBT should be classified according to the last WHO classification. Any micro-invasion (foci<5mm) or microcarcinoma (foci<5mm with nuclear atypia and desmoplastic stromal reaction) should be indicated in the pathology report. In case of serous OBT, variants (classical or the micropapillary/cribriform) should be indicated (grade C). The peritoneal implants associated with OBT, should be classified as invasive or noninvasive, according to the extension into the underlying adipous tissue. If no adipous tissue is seen the term undetermined should be used (grade B). In case of mucinous OBT bilateral and/or with peritoneal implants or peritoneal pseudomyxoma a search for primitive gastrointestinal, appendiceal or biliopancreatic tumor should be performed (grade C). In case of OBT, a thorough sampling of the tumor is recommended, with 1 block/cm and 2 blocks/cm in case of mucinous OBT, serous OBT micropapillary variant, OBT with intraepithelial carcinoma or/and micro-invasion. Peritoneal implants should be examined in toto. Omentum without macroscopic lesion should be sampled in 4 to 6 blocks (grade C). In case of ovarian cyst suspicious for OBT, fine needle aspiration is not recommended (grade C). In case of ovarian tumor suspicious for OBT, intraoperative examination should be performed by a gynecological pathologist (grade C).
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Affiliation(s)
- C Eymerit-Morin
- Service d'anatomie et cytologie pathologiques, hôpital Tenon, HUEP, UPMC Paris VI, Sorbonne université, 4, rue de la Chine, 75020 Paris, France; Institut de pathologie de Paris, 35, boulevard Stalingrad, 92240 Malakoff, France
| | - J L Brun
- Service de chirurgie gynécologique, centre Aliénor d'Aquitaine, hôpital Pellegrin, 33076 Bordeaux, France; Société française de gynécopathologie, 94410 Saint Maurice, France
| | - O Vabret
- Service de chirurgie gynécologique, centre Aliénor d'Aquitaine, hôpital Pellegrin, 33076 Bordeaux, France
| | - M Devouassoux-Shisheboran
- Institut de pathologie multi-sites, hospices civils de Lyon, centre hospitalier Lyon Sud, centre de biologie et pathologie Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France; Société française de gynécopathologie, 94410 Saint Maurice, France.
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Li N, Gou J, Li L, Ming X, Hu TW, Li Z. Staging procedures fail to benefit women with borderline ovarian tumours who want to preserve fertility: a retrospective analysis of 448 cases. BMC Cancer 2020; 20:769. [PMID: 32807135 PMCID: PMC7433083 DOI: 10.1186/s12885-020-07262-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 08/05/2020] [Indexed: 12/02/2022] Open
Abstract
Background To evaluate the effect of clinicopathologic factors on the prognosis and fertility outcomes of BOT patients. Methods We performed a retrospective analysis of BOT patients who underwent surgical procedures in West China Second University Hospital from 2008 to 2015. The DFS outcomes, potential prognostic factors and fertility outcomes were evaluated. Results Four hundred forty-eight patients were included; 52 recurrences were observed. Ninety-two patients undergoing FSS achieved pregnancy. No significant differences in fertility outcomes were found between the staging and unstaged surgery groups. Staging surgery was not an independent prognostic factor for DFS. Laparoscopy resulted in better prognosis than laparotomy in patients with stage I tumours and a desire for fertility preservation. Conclusion Patients with BOT fail to benefit from surgical staging. Laparoscopy is recommended for patients with stage I disease who desire to preserve fertility. Physicians should pay more attention to risk of recurrence in patients who want to preserve fertility.
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Affiliation(s)
- Na Li
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.,Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.,Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, P.R. China
| | - Jinhai Gou
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.,Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Lin Li
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.,Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Xiu Ming
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.,Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Ting Wenyi Hu
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.,Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Zhengyu Li
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China. .,Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.
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Nilforoushan N, Moatamed NA. Evaluation of MTAP immunohistochemistry loss of expression in ovarian serous borderline tumors as a potential marker for prognosis and progression. Ann Diagn Pathol 2020; 48:151582. [PMID: 32866902 DOI: 10.1016/j.anndiagpath.2020.151582] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/18/2020] [Accepted: 07/06/2020] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Serous borderline tumors (SBT) are the most common subtype of ovarian borderline tumors with excellent clinical course. However, they can recur or progress to low-grade serous carcinoma (LGSC) in a small proportion of the cases. Beside BRAF and KRAS mutations, copy number alterations (CNA), particularly loss of chromosome 9p21 locus which results in deletion of genes CDKN2A and MTAP, have been suggested to be involved in disease progression. MTAP immunohistochemistry recently has been introduced for mesothelioma as a reliable surrogate marker for the homozygous deletion of chromosome 9p21 locus. Therefore, in the current study, we aimed to evaluate the MTAP loss of expression in serous borderline tumors and low-grade serous carcinomas to identify if it can be used as a marker for prognosis and progression. METHOD Eighty-four total cases of ovarian serous lesions, including 21 cases of serous cystadenomas, 21 cases of serous borderline tumors, 12 cases of low-grade serous carcinomas and 30 cases of high-grade serous carcinomas were selected. MTAP immunohistochemistry was performed on the representative blocks and cytoplasmic staining was used for interpretation. The cases were labeled as positive (retained) if MTAP showed cytoplasmic granular staining and negative (loss of expression) if negative cytoplasmic staining was observed in the presence of positive internal control. RESULT Ten of 21 cases of serous borderline tumors showed loss of MTAP expression (48%). Among those, 7 cases were bilateral, 2 cases had micropapillary features, one case had supraclavicular and cervical lymph node involvement by serous borderline tumor and 2 cases had progression to low-grade serous carcinoma, including one of micropapillary tumors. Also 8 out of 12 cases of LGSCs showed MTAP loss of expression (66%). Only 4 of 30 cases of high-grade serous carcinomas (13%) and none of the serous cystadenoma cases showed loss of expression of MTAP. CONCLUSION To our knowledge, this is the first description of MTAP immunohistochemistry in serous borderline tumors and low-grade serous carcinomas. Our study was limited due to small sample size. However, it showed an association between MTAP loss of expression and adverse clinical behavior in ovarian serous borderline tumors. This supports the role for further investigations in larger series to evaluate the role of MTAP stain as a prognostic marker in these neoplasms.
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Affiliation(s)
- Neshat Nilforoushan
- Pathology & Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
| | - Neda A Moatamed
- Pathology & Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
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Li N, Ming X, Li Z. Unilateral cystectomy and serous histology are associated with relapse in borderline ovarian tumor patients with fertility-sparing surgery: a systematic review and meta-analysis. Arch Gynecol Obstet 2020; 302:1063-1074. [PMID: 32748055 DOI: 10.1007/s00404-020-05716-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 07/27/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE Surgical procedures, histological subtypes, and surgical approaches are involved in the recurrence of borderline ovarian tumors (BOTs), but whether those three factors affect relapse remains controversial. This study aimed to explore the effects of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates of BOT after fertility-preserving surgery (FPS) according to the patients' characteristics. METHODS A systematic search of PubMed, Embase, and the Cochrane library was conducted from their inception to November 2018. Studies that investigated the impact of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates in patients with BOT after FPS were eligible. The pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS Thirty-five studies involving a total of 2921 patients with BOT after FPS were included. The pooled ORs indicated that the risk of relapse was significantly increased in patients who underwent unilateral cystectomy or with serous BOT. There was no significant difference between laparoscopy and laparotomy on the risk of relapse. Surgical procedures, histological subtypes, and surgical approaches did not influence pregnancy rates. CONCLUSIONS Patients who underwent unilateral cystectomy or with serous BOT presented an excess risk of relapse after FPS, but the surgical approach did not affect the risk of relapse. The pregnancy rate is not affected by surgical procedures, histological subtypes, and surgical approaches.
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Affiliation(s)
- Na Li
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People's Republic of China
| | - Xiu Ming
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Zhengyu Li
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
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Long term follow-up of a large series of stage-II/III atypical proliferative serous ovarian tumors. Gynecol Oncol 2020; 158:659-665. [PMID: 32571680 DOI: 10.1016/j.ygyno.2020.06.489] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 06/10/2020] [Indexed: 11/23/2022]
Abstract
BACKGROUND The aim of this study was to assess prognostic factors and implications on further management in a large series of stage-II or III Atypical Proliferative Serous Tumors (APST) with a long-term follow-up. PATIENTS AND METHODS Patients with APSTs and peritoneal implants treated in, or referred to, our institution were retrospectively reviewed. Prognostic factors on invasive recurrence, disease-free (DFS) and overall survival (OS) were analyzed. RESULTS Between 1971 and 2017, 212 patients were identified and followed (33 having invasive implants). After a median follow-up of 115 months, 70 recurrences were observed, 28 of them under the form of invasive disease. DFS at 5 years and 10 years was 73% and 62% respectively. The use of a conservative treatment (HR = 5.5[3.33-9.08], p < .0001), the presence of ≥3 peritoneal sites with implants (HR = 1.65[1.01-2.72], p = .045) were unfavorable prognostic factors for DFS. The presence of ≥3 peritoneal sites with implants (HR = 3.02[0.96-9.53], p = .049) and the presence of stromal microinvasion (HR = 3.19[1.12-9.1], p = .022) were unfavorable prognostic factors for OS. Non-conservative surgery (HR = 7[2.35-20.87], p = .0002), invasive implants (HR = 5.37[1.29-22.26], p = .013), and ≥ 3 peritoneal sites with implants (HR = 3.56 [1.11-11.39], p = .024) were identified as predictors of recurrence in the form of an invasive disease. Invasive implants were not associated with DFS (HR = 1.39[0.77-2.51], p = .27), nor OS (HR = 1.76[0.57-5.47], p = .32). CONCLUSION After a long-term follow-up, type of peritoneal implants is no longer a prognostic factor for OS. Implants ≥3 peritoneal sites seem to impact significantly OS and then require a specific follow-up in this subgroup of patients.
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Characteristics and prognosis of borderline ovarian tumors in pre and postmenopausal patients. Arch Gynecol Obstet 2020; 302:693-698. [PMID: 32556512 DOI: 10.1007/s00404-020-05652-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 06/11/2020] [Indexed: 01/16/2023]
Abstract
OBJECTIVE To compare patient characteristics, imaging results, surgical management and prognosis of borderline ovarian tumors (BOT) between pre and postmenopausal patients. MATERIALS AND METHODS A retrospective cohort of all cases of histologically verified BOT between 1990-2018, comparing presentation, imaging, surgical procedures and recurrence. Patients were included in the postmenopausal group if they reported 12 months of amenorrhea with or without menopausal symptoms. RESULTS During this 28 year study period, 66 operations were performed in which BOT was confirmed. Postmenopausal patients were 37-89 years old and premenopausal patients 18-50 years old, with an average age of 63.9 ± 13.4 and 36.2 ± 8.4 years, respectively (p < 0.001). The majority of patients in both groups were diagnosed due to abdominal pain, followed by incidental diagnosis on routine ultrasound. Imaging and CA-125 levels upon presentation were similar. Almost sixty percent of postmenopausal and 26.3% of premenopausal patients underwent laparotomy (p = 0.01), while those who underwent laparoscopy were 35.7% and 60.5%, respectively (p = 0.03). Most postmenopausal patients underwent bilateral salpingo-oophorectomy (BSO), whereas premenopausal surgeries involved cystectomy. Nearly all study patients were diagnosed in stage one. Malignant transformation occurred in 7.1% of postmenopausal patients. No malignant transformation was found in premenopausal patients. CONCLUSION BOT's present similarly in pre and postmenopausal patients. Postmenopausal patients undergo more extensive surgery, and are diagnosed in early stage disease. Despite a tendency for a more conservative approach in premenopausal patients, prognosis is similar in both groups.
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St Laurent JD, Gockley AA, Cathcart AM, Baranov E, Kolin DL, Worley MJ. Serous borderline tumor of the ovary with isolated cardiophrenic lymph node spread at diagnosis. Gynecol Oncol Rep 2020; 33:100586. [PMID: 32529019 PMCID: PMC7276423 DOI: 10.1016/j.gore.2020.100586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 05/06/2020] [Accepted: 05/13/2020] [Indexed: 11/18/2022] Open
Abstract
Serous borderline tumor outside of the peritoneal cavity is rare. Involvement of cardiophrenic lymph nodes with serous borderline tumor can occur. Preoperative imaging may aid surgical planning even in serous borderline tumor cases. Sequencing can help confirm a diagnosis of serous borderline tumor at distant sites.
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Affiliation(s)
- J D St Laurent
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA.,Vincent Department of Obstetrics, Gynecology, and Reproductive Biology, Massachusetts General Hospital, Boston, MA, USA
| | - A A Gockley
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Dana-Farber Cancer Institute, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
| | - A M Cathcart
- Harvard Medical School, Harvard University, Boston, MA 02115, USA
| | - E Baranov
- Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - D L Kolin
- Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - M J Worley
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Dana-Farber Cancer Institute, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
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