4.6 Article

Risk-based stratification of carcinomas concurrently involving the endometrium and ovary

Journal

GYNECOLOGIC ONCOLOGY
Volume 152, Issue 1, Pages 38-45

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2018.10.033

Keywords

Synchronous carcinomas; Endometrium; Endometrioid carcinoma; Non-endometrioid carcinoma; Ovary

Funding

  1. NIH/NCI Cancer Center Support Grant [P30 CA008748]

Ask authors/readers for more resources

Objective. Determining whether carcinomas concurrently involving endometrium and ovary are independent primary tumors (IPTs) or endometrial carcinomas with ovarian metastases (at least stage IIIA endometrial cancers, IIIA-EC) using clinicopathologic criteria is often challenging. Recent genomic studies showed that most such tumors are clonally related. We sought to identify clinicopathologic features associated with clinical outcomes, and to separate women with these tumors into clinically low-risk and high-risk groups. Methods. We reviewed clinical and pathologic data from 74 women who, between 1993 and 2014, underwent primary surgery for endometrial cancer and had concurrent ovarian involvement. Results. The endometrial carcinomas were endometrioid (EECs, n = 41) or non-endometrioid (ENECs, n = 33). Nineteen (26%) cases were originally classified as IPTs using clinicopathologic criteria. Multivariate analysis revealed that lymph node involvement (hazard ratio (HR) = 2.38, 95% CI 1.13-5.02, p = 0.023) and non-endometrioid endometrial tumor histology (HR = 6.27, 95% CI 2.6-15.13, p < 0.001) were associated with poorer progression-free survival (PFS). Multivariate analysis of 65 women with known lymph node status revealed two prognostically distinct groups: a high-risk group comprising ENECs with >= 50% myometrial invasion irrespective of lymph node status (n = 21; median PFS 12.7 months, 95% CI, 9.24-19.8); and a low-risk group consisting of all EECs, as well as lymph node-negative ENECs with <50% myometrial invasion (n = 44, median PFS not reached). The risk-based classification was superior to the original classification of endometrial cancers as IPTs vs. IIIA-EC for predicting PFS (log-rank test, p < 0.001 vs. p = 0.07). Conclusion. Our proposed risk-based stratification enables categorization of women with concurrent endometrial and ovarian tumors according to their likely clinical outcomes. (C) 2018 Elsevier Inc. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Oncology

Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell-like Program Conserved in HPV-Positive Cancers

Lukas Leiendecker, Tobias Neumann, Pauline S. Jung, Shona M. Cronin, Thomas L. Steinacker, Alexander Schleiffer, Michael Schutzbier, Karl Mechtler, Thibault Kervarrec, Estelle Laurent, Kamel Bachiri, Etienne Coyaud, Rajmohan Murali, Klaus J. Busam, Babak Itzinger-Monshi, Reinhard Kirnbauer, Lorenzo Cerroni, Eduardo Calonje, Arno Rutten, Frank Stubenrauch, Klaus G. Griewank, Thomas Wiesner, Anna C. Obenauf

Summary: This study reveals the presence of human papillomavirus 42 (HPV42) in 96% of digital papillary adenocarcinoma (DPA), a cancer occurring on fingers and toes. It shows that HPV42, previously considered nononcogenic, behaves similarly to oncogenic, high-risk HPVs. Machine learning analysis indicates that HPV-driven transformation induces a germ cell-like transcriptional program conserved across all HPV-driven cancers, with implications for early detection, diagnosis, and therapy.

CANCER DISCOVERY (2023)

Article Oncology

Cytologic features of gynecologic germ cell tumors and carcinomas exhibiting germ cell tumor differentiation

Anjelica Hodgson, Veronica Kim, Rajmohan Murali

Summary: This study aimed to describe the cytologic features of primary gynecologic germ cell tumors and carcinomas exhibiting germ cell differentiation. The researchers reviewed available cytologic material and recorded morphological features, patient age at diagnosis, tumor site, and cytologic preparation type. They found that adult women with germ cell tumors and somatic neoplasms exhibiting germ cell tumor differentiation may share some cytologic features, making it difficult to distinguish between them.

CANCER CYTOPATHOLOGY (2023)

Article Oncology

Expanding the molecular spectrum of gene fusions in endometrial stromal sarcoma: Novel subunits of the chromatin remodeling complexes PRC2 and NuA4/TIP60 as alternative fusion partners

Josephine K. K. Dermawan, Nooshin Dashti, Sarah Chiang, Gulisa Turashvili, Brendan C. C. Dickson, Lora H. H. Ellenson, Martina Kirchner, Albrecht Stenzinger, Gunhild Mechtersheimer, Abbas Agaimy, Cristina R. R. Antonescu

Summary: In this study, we report a series of endometrial stromal sarcoma (ESS) cases with novel gene fusions. These cases demonstrate morphological and molecular heterogeneity. The identified fusion genes play important roles in the regulation of the PRC2 and/or NuA4/TIP60 complexes.

GENES CHROMOSOMES & CANCER (2023)

Review Urology & Nephrology

Evaluation of Women With a Positive Urine Cytology and no Demonstrable Disease in the Urinary Tract

Sherri M. Donat, Yukio Sonoda, Hikmat Al-Ahmadie, Rajmohan Murali, Dianna L. Ng, Samuel A. Funt, Kay J. Park

Summary: Urinary cytology is crucial for evaluating gross hematuria and monitoring urothelial neoplasms. A positive urine cytology typically indicates the presence of urothelial carcinoma in the urinary tract, but it may also suggest involvement of the lower gynecologic tract or rectum in women. Guidelines for evaluating women with positive cytology and normal urinary tract are lacking. This review aims to raise clinicians' awareness of this diagnostic dilemma with case scenarios. UROLOGY 173: 10-16, 2023. (c) 2023 Elsevier Inc.

UROLOGY (2023)

Article Hematology

Low toxicity and excellent outcomes in patients with DLBCL without residual lymphoma at the time of CD19 CAR T-cell therapy

Kitsada Wudhikarn, Ana Alarcon Tomas, Jessica R. Flynn, Sean M. Devlin, Jamie Brower, Veronika Bachanova, Loretta J. Nastoupil, Joseph P. McGuirk, Richard T. Maziarz, Olalekan O. Oluwole, Stephen J. Schuster, David L. Porter, Michael R. Bishop, Peter A. Riedell, Miguel-Angel Perales, Cell Therapy Consortium

Summary: CD19 CAR T-cell therapy is effective in inducing sustained remissions in patients with R/R DLBCL, but can lead to significant toxicities. Treating patients in complete remission at the time of CAR T-cell infusion is feasible, safe, and associated with favorable disease control. Further exploration in larger clinical trials is needed.

BLOOD ADVANCES (2023)

Article Hematology

Open-label pilot study of romiplostim for thrombocytopenia after autologous hematopoietic cell transplantation

Michael Scordo, Leah J. Gilbert, Danielle M. Hanley, Jessica R. Flynn, Sean M. Devlin, Linh K. Nguyen, Josel D. Ruiz, Gunjan L. Shah, Craig S. Sauter, David J. Chung, Heather J. Landau, Oscar B. Lahoud, Richard J. Lin, Parastoo B. Dahi, Miguel-Angel Perales, Sergio A. Giralt, Gerald A. Soff

Summary: There is currently no standard treatment for severe thrombocytopenia after autologous hematopoietic cell transplantation (auto-HCT). A pilot study was conducted to evaluate the use of romiplostim, a thrombopoietin receptor agonist, in enhancing platelet recovery in patients undergoing auto-HCT for multiple myeloma or lymphoma. Results showed that romiplostim-treated patients had improved platelet recovery compared to those who did not receive romiplostim. However, the improvement occurred later than expected. Overall, romiplostim demonstrated promising activity and safety in this setting. (ClinicalTrials.gov identifier: NCT04478123)

BLOOD ADVANCES (2023)

Article Pathology

Mammary Spindle Cell Proliferations on Core Needle Biopsy Is Excision Always Necessary?

Cherry Pun, Gulisa Turashvili, Anna Marie Mulligan, Elzbieta Slodkowska

Summary: Mammary spindle cell proliferations (SCPs) cover a wide range of lesions and are difficult to diagnose accurately on core needle biopsies (CNBs). Most SCPs require excision for definitive diagnosis, but in some cases, conservative follow-up may be possible. This study aimed to examine SCPs diagnosed on CNB and evaluate the necessity of excision for benign/indeterminate SCPs. Among 197 SCPs that met the inclusion criteria, 53% were classified as benign, 26% as indeterminate, and 19% as malignant on CNB. Excision was performed in 47% of benign, 87% of indeterminate, and 86% of malignant CNBs. Of the 123 excised SCPs, 63% were benign and 36% were malignant. Most benign lesions showed no suspicious radiological features, while indeterminate and malignant lesions were more likely to be suspicious. Proper ancillary tests can safely exclude some malignant entities, and accurate pathological diagnosis with correlation to imaging and clinical data can potentially spare surgery for patients with mammary SCPs.

AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2023)

Article Oncology

Landscape of chromatin remodeling gene alterations in endometrial carcinoma

Amir Momeni-Boroujeni, Chad Vanderbilt, Elham Youse, Nadeem R. Abu-Rustum, Carol Aghajanian, Robert A. Soslow, Lora H. Ellenson, Britta Weigelt, Rajmohan Murali

Summary: This study investigated the prevalence and clinicopathological associations of chromatin remodeling gene (CRG) alterations in endometrial carcinoma (EC). The results showed that about 66.4% of EC patients had CRG alterations, with ARID1A being the most commonly altered gene. These CRG alterations were associated with the clinicopathological features of EC and likely played a crucial role in its development.

GYNECOLOGIC ONCOLOGY (2023)

Article Cell Biology

Consensus based recommendations for the diagnosis of serous tubal intraepithelial carcinoma: an international Delphi study

Joep M. A. Bogaerts, Majke H. D. van Bommel, Rosella P. M. G. Hermens, Miranda P. Steenbeek, Joanne A. de Hullu, Jeroen A. W. M. van Der Laak, Michiel Simons

Summary: It is crucial to diagnose or exclude serous tubal intraepithelial carcinoma (STIC), a precursor lesion of tubo-ovarian high-grade serous carcinoma (HGSC), in a reliable and safe manner. This study aimed to optimize STIC diagnosis and increase reproducibility through a three-round Delphi study involving an international panel of expert gynecologic pathologists. The resulting consensus statements provide recommendations for more consistent STIC diagnosis.

HISTOPATHOLOGY (2023)

Article Pathology

Comprehensive Clinical-Pathologic Assessment of Malignant Phyllodes Tumors

Gulisa Turashvili, Qingqing Ding, Yi Liu, Limin Peng, Miralem Mrkonjic, Haider Mejbel, Yihong Wang, Huina Zhang, Gloria Zhang, Jigang Wang, Shi Wei, Xiaoxian Li

Summary: The latest World Health Organization classification of breast tumors recommends diagnosing malignant phyllodes tumors (MPTs) when all 5 morphologic features are present. However, a retrospective study found that the current recommendation may miss a significant number of MPTs with distant metastases, suggesting the need for refined diagnostic criteria.

AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2023)

Article Oncology

Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP

Jennifer K. Litton, Meredith M. Regan, Lajos Pusztai, Hope S. Rugo, Sara M. Tolaney, Elizabeth Garrett-Mayer, Laleh Amiri-Kordestani, Reva K. Basho, Ana F. Best, Jean-Francois Boileau, Carsten Denkert, Jared C. Foster, Nadia Harbeck, Heather A. Jacene, Tari A. King, Ginny Mason, Ciara C. O'Sullivan, Tatiana M. Prowell, Andrea L. Richardson, Karla A. Sepulveda, Mary Lou Smith, Judy A. Tjoe, Gulisa Turashvili, Wendy A. Woodward, Lynn Pearson Butler, Elena I. Schwartz, Larissa A. Korde

Summary: The STEEP criteria, updated as STEEP 2.0 in 2021, provide standardized definitions for adjuvant breast cancer end points. A working group called NeoSTEEP was established to evaluate and align neoadjuvant breast cancer trial end points.

JOURNAL OF CLINICAL ONCOLOGY (2023)

Article Pathology

Low interobserver agreement among subspecialised breast pathologists in evaluating HER2-low breast cancer

Gulisa Turashvili, Yuan Gao, Di (Andy) Ai, Abdulwahab M. Ewaz, Sandra Gjorgova Gjeorgjievski, Qun Wang, Thi T. A. Nguyen, Chao Zhang, Xiaoxian Li

Summary: This study evaluated the interobserver agreement among subspecialised breast pathologists for the assessment of HLBC and developed a practical algorithm. The results showed suboptimal agreement among the pathologists, highlighting the need for a new reliable evaluation method for HLBC.

JOURNAL OF CLINICAL PATHOLOGY (2023)

Article Pathology

DNA Methylation Signature of Synchronous Endometrioid Endometrial and Ovarian Carcinomas

Lawrence Hsu Lin, Douglas H. R. Allison, Gulisa Turashvili, Varshini Vasudevaraja, Ivy Tran, Jonathan Serrano, Britta Weigelt, Marc Ladanyi, Nadeem R. Abu-Rustum, Matija Snuderl, Sarah Chiang

Summary: This study found that co-occurring sporadic endometrioid endometrial carcinoma (EEC) and endometrioid ovarian carcinoma (EOC) are clonally related, but there is a shift in DNA methylation signatures between the ovarian and endometrial tumors. The results also indicate epigenetic overlap between ovarian and peritoneal tumors, suggesting a role for the tumor microenvironment in the epigenetic modulation of metastatic EEC.

MODERN PATHOLOGY (2023)

Article Hematology

Identifying an optimal fludarabine exposure for improved outcomes after axi-cel therapy for aggressive B-cell non-Hodgkin lymphoma

Michael Scordo, Jessica R. Flynn, Mithat Gonen, Sean M. Devlin, Allison Parascondola, Ana Alarcon Tomas, Roni Shouval, Jamie Brower, David L. Porter, Stephen J. Schuster, Veronika Bachanova, Joseph Maakaron, Richard T. Maziarz, Andy I. Chen, Loretta J. Nastoupil, Joseph P. Mcguirk, Olalekan O. Oluwole, Andrew Lp, Lori A. Leslie, Michael R. Bishop, Peter A. Riedell, Miguel-Angel Perales

Summary: Using a population pharmacokinetic model, researchers estimated the exposure of fludarabine in lymphodepleted patients before receiving CD19 chimeric antigen receptor T cells. They found that an optimal fludarabine exposure was associated with the highest progression-free survival and lowest risk of disease relapse/progression, without increasing the risk of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. On the other hand, a high fludarabine exposure was linked to a higher risk of neurotoxicity. These findings suggest that personalized dosing based on fludarabine exposure could improve outcomes for patients receiving axicel therapy.

BLOOD ADVANCES (2023)

Meeting Abstract Medicine, Research & Experimental

Methylation Profiling of High-Grade Ovarian Carcinomas and Comparison with High Grade Endometrial Carcinomas

Rofieda Alwaqfi, Gulisa Turashvili, Varshini Vasudevaraja, Ivy Tran, Jonathan Serrano, M. Herman Chui, Britta Weigelt, Robert Soslow, Lora Ellenson, Nadeem Abu-Rustum, Matija Snuderl, Sarah Chiang

LABORATORY INVESTIGATION (2023)

Article Oncology

Molecular landscape of ERBB2/HER2 gene amplification among patients with gynecologic malignancies; clinical implications and future directions

Dimitrios Nasioudis, Stefan Gysler, Nawar Latif, Lory Cory, Robert L. Giuntoli II, Sarah H. Kim, Fiona Simpkins, Lainie Martin, Emily M. Ko

Summary: The prevalence of ERBB2 gene amplification was investigated among patients with gynecologic malignancies. The study found that ERBB2 amplification is frequently encountered in uterine serous carcinoma and mucinous ovarian carcinoma, but less common in endometrioid endometrial carcinoma.

GYNECOLOGIC ONCOLOGY (2024)