{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T04:47:11Z","timestamp":1789274831314,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro\u2014FAPERJ","award":["E-26\/201.166\/2022"],"award-info":[{"award-number":["E-26\/201.166\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Molar pregnancy (MP) is a gestational disorder resulting from abnormal fertilization, leading to atypical trophoblastic proliferation and the formation of a complete or partial hydatidiform mole. This condition represents the most common form of gestational trophoblastic disease (GTD) and carries a significant risk of progression to gestational trophoblastic neoplasia (GTN). Although rare in high-income countries, MP remains up to ten times more prevalent in low-income and developing countries, contributing to preventable maternal morbidity and mortality. This narrative review provides an updated, practical overview of the clinical presentation, diagnosis, treatment, and follow-up of MP. A key focus is the challenge of early diagnosis, particularly given the increasing frequency of first-trimester detection, where classical histopathological criteria may be subtle, leading to diagnostic errors. The review innovates by integrating advanced diagnostic methods\u2014combining histopathology, immunohistochemistry using p57Kip2, Ki-67, and p53 markers, along with cytogenetic analysis\u2014to improve diagnostic accuracy in early gestation. The central role of referral centers is also emphasized, not only in facilitating timely treatment and access to chemotherapy, but also in implementing standardized post-molar follow-up protocols that reduce progression to GTN and maternal mortality. By focusing on both advanced diagnostic strategies and the organization of care through referral centers, this review offers a comprehensive, practice-oriented perspective to optimize patient outcomes in GTD and address persistent care gaps in high-burden regions.<\/jats:p>","DOI":"10.3390\/diagnostics15151953","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T10:48:08Z","timestamp":1754304488000},"page":"1953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molar Pregnancy: Early Diagnosis, Clinical Management, and the Role of Referral Centers"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2942-6182","authenticated-orcid":false,"given":"Ant\u00f4nio","family":"Braga","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, School of Medicine, Federal University of Rio de Janeiro (UFRJ), Rua das Laranjeiras, No. 180, Laranjeiras, Rio de Janeiro 22240-003, RJ, Brazil"},{"name":"Department of Maternal and Child Health, Postgraduate Program in Medical Sciences, School of Medicine, Fluminense Federal University (UFF), Niter\u00f3i 24070-090, RJ, Brazil"},{"name":"Postgraduate Program in Applied Health Sciences, University of Vassouras, Vassouras 27700-000, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8481-5204","authenticated-orcid":false,"given":"Lohayne","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Applied Health Sciences, University of Vassouras, Vassouras 27700-000, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4455-8342","authenticated-orcid":false,"given":"Marcela","family":"Chagas","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Applied Health Sciences, University of Vassouras, Vassouras 27700-000, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-4501","authenticated-orcid":false,"given":"Juliana Pereira","family":"Soares","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Applied Health Sciences, University of Vassouras, Vassouras 27700-000, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6694-6569","authenticated-orcid":false,"given":"Gustavo Yano","family":"Callado","sequence":"additional","affiliation":[{"name":"Discipline of Woman Health, Albert Einstein Israelite College of Health Sciences (FICSAE), Albert Einstein Israelite Hospital, S\u00e3o Paulo 05653-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Alevato","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Postgraduate Program in Medical Sciences, School of Medicine, Fluminense Federal University (UFF), Niter\u00f3i 24070-090, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Lozoya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fluminense Federal University (UFF), Niter\u00f3i 24070-090, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6573-7386","authenticated-orcid":false,"given":"Sue Yazaki","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Paulista School of Medicine, Federal University of S\u00e3o Paulo (EPM-UNIFESP), Sao Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6145-2532","authenticated-orcid":false,"given":"Edward","family":"Araujo J\u00fanior","sequence":"additional","affiliation":[{"name":"Discipline of Woman Health, Albert Einstein Israelite College of Health Sciences (FICSAE), Albert Einstein Israelite Hospital, S\u00e3o Paulo 05653-000, SP, Brazil"},{"name":"Department of Obstetrics, Paulista School of Medicine, Federal University of S\u00e3o Paulo (EPM-UNIFESP), Sao Paulo 04023-062, SP, Brazil"},{"name":"Discipline of Woman Health, Municipal University of S\u00e3o Caetano do Sul (USCS), S\u00e3o Caetano do Sul 09521-160, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-3374","authenticated-orcid":false,"given":"Jorge","family":"Rezende-Filho","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, School of Medicine, Federal University of Rio de Janeiro (UFRJ), Rua das Laranjeiras, No. 180, Laranjeiras, Rio de Janeiro 22240-003, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/AOG.0000000000004240","article-title":"Gestational Trophoblastic Disease: Current Evaluation and Management","volume":"137","author":"Soper","year":"2021","journal-title":"Obstet. 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Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.hoc.2024.07.003","article-title":"Epidemiology of Gestational Trophoblastic Disease","volume":"38","author":"Joneborg","year":"2024","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.hoc.2024.08.017","article-title":"Pathology of Gestational Trophoblastic Disease (GTD)","volume":"38","author":"Kaur","year":"2024","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bpobgyn.2020.12.001","article-title":"Clinical presentation and diagnosis of Gestational Trophoblastic Disease","volume":"74","author":"Lok","year":"2021","journal-title":"Best Pr. Res. Clin. Obstet. 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