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Flídrová M, Hájková N, Hojný J, Dvořák J, Michálková R, Krkavcová E, Laco J, McCluggage WG, Giordano G, Silini EM, Michalová K, Bizoń M, Němejcová K, Dundr P, Kendall Bártů M. Unraveling the Molecular Landscape of Uterine Tumor Resembling Ovarian Sex Cord Tumor: Insights From A Clinicopathological, Morphologic, Immunohistochemical, and Molecular Analysis of 35 Cases. Mod Pathol 2024; 37:100611. [PMID: 39265954 DOI: 10.1016/j.modpat.2024.100611] [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: 06/17/2024] [Revised: 08/09/2024] [Accepted: 09/01/2024] [Indexed: 09/14/2024]
Abstract
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of uncertain lineage and low malignant potential. Most tumors behave in a benign manner, but a subset of UTROSCT exhibit an aggressive clinical course with recurrences and metastases. The recurrent molecular alterations in UTROSCT mostly represent gene fusions involving NCOA1-3. We performed a comprehensive clinicopathological, morphologic, immunohistochemical, and molecular analysis on a cohort of 35 UTROSCT. The tumors exhibited various architectural patterns (diffuse, corded/trabecular, tubular, sertoliform, fascicular, whorled, nested, microfollicular, and pseudoglandular), often in combination. The immunohistochemical analysis confirmed the polyphenotypic immunoprofile, often with coexpression of sex cord-stromal, smooth muscle, and epithelial markers, as well as hormone receptors. Next-generation sequencing RNA analysis revealed recurrent NCOA1-3 gene fusions in 22/32 analyzed cases (69%), including ESR1::NCOA3 (11/22), GREB1::NCOA2 (7/22), ESR1::NCOA2 (3/22), and GREB1::NCOA1 (1/22). Tumor mutation burden was low in all cases. The fusion-positive cases exhibited statistically significant association with whorled architecture, conversely necrosis was associated with fusion-negative status. We did not find a significant relationship between any architectural pattern and GREB1 alterations, but the NCOA2-altered tumors were associated with pseudoglandular architecture. The GREB1-altered cases occurred in older patients and tended to be more often intramural masses compared with ESR1-altered cases. On the contrary, the ESR1-altered cases presented more often like submucosal or polypoid tumors. Two tumors exhibited aggressive behavior with recurrent disease. Both of these cases harbored a GREB1::NCOA2 fusion. Unsupervised hierarchical cluster analysis of our cohort revealed 2 main clusters. The tumors with GREB1 or NCOA2 fusion cluster together, suggesting that there are underlying molecular differences between these cases and cases with ESR1::NCOA3 fusion or without fusion. Our findings contribute to the growing knowledge about a rare neoplasm with currently uncertain biological behavior.
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Affiliation(s)
- Miroslava Flídrová
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
| | - Nikola Hájková
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Jan Hojný
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Jiří Dvořák
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Romana Michálková
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Eva Krkavcová
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Jan Laco
- The Fingerland Department of Pathology, Charles University, Faculty of Medicine Hradec Králové and University Hospital Hradec Králové, Hradec Králové, Czech Republic
| | - W Glenn McCluggage
- Department of Pathology, Belfast Health and Social Care Trust, Belfast, United Kingdom
| | - Giovanna Giordano
- Department of Medicine and Surgery, Pathology Unit, University of Parma, Parma, Italy
| | - Enrico Maria Silini
- Department of Medicine and Surgery, Pathology Unit, University of Parma, Parma, Italy
| | - Květoslava Michalová
- Department of Pathology, Charles University, Faculty of Medicine in Plzeň, Bioptical Laboratory, Ltd, Plzeň, Czech Republic
| | | | - Kristýna Němejcová
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Pavel Dundr
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Michaela Kendall Bártů
- Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
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Bennett JA, Pinto A. The "Other" Uterine Mesenchymal Neoplasms: Recent Developments and Emerging Entities. Adv Anat Pathol 2024; 31:380-396. [PMID: 38623604 DOI: 10.1097/pap.0000000000000440] [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: 04/17/2024]
Abstract
Uterine mesenchymal neoplasms are a challenging group of tumors that often show overlapping morphologic features and immunohistochemical profiles. The increasing use of molecular testing in these tumors has enabled a better appreciation of their pathobiology, resulting in a wave of emerging neoplasms and improved characterization of ones previously considered exceptionally rare. Identification of specific molecular alterations has permitted targeted therapy options in tumors that were typically unresponsive to conventional therapies, as well as recognition that a subset can have a hereditary basis. This review will discuss the more "common" of the uncommon uterine mesenchymal neoplasms, including inflammatory myofibroblastic tumor, perivascular epithelioid cell tumor, uterine tumor resembling ovarian sex cord tumor, and embryonal rhabdomyosarcoma. This will be followed by an overview of emerging entities, including NTRK -rearranged uterine sarcoma, SMARCA4 -deficient uterine sarcoma, KAT6B/A::KANSL1 fusion uterine sarcoma, and MEIS1::NCOA2/1 fusion sarcoma.
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Affiliation(s)
| | - Andre Pinto
- Department of Pathology and Laboratory Medicine, University of Miami, Miami, FL
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Watrowski R, Palumbo M, Guerra S, Gallo A, Zizolfi B, Giampaolino P, Bifulco G, Di Spiezio Sardo A, De Angelis MC. Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Scoping Review of 511 Cases, Including 2 New Cases. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:179. [PMID: 38276058 PMCID: PMC10820159 DOI: 10.3390/medicina60010179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 01/10/2024] [Accepted: 01/15/2024] [Indexed: 01/27/2024]
Abstract
Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs) are rare uterine mesenchymal neoplasms with uncertain biological potential. These tumors, which affect both premenopausal and postmenopausal women, usually have a benign clinical course. Nevertheless, local recurrences and distant metastases have been described. By analyzing 511 cases retrieved from individual reports and cases series, we provide here the most comprehensive overview of UTROSCT cases available in the literature, supplemented by two new cases of UTROSCTs. Case 1 was an asymptomatic 31-year-old woman who underwent a laparoscopic resection of a presumed leiomyoma. Case 2 was a 58-year-old postmenopausal woman with abnormal vaginal bleeding who underwent an outpatient hysteroscopic biopsy of a suspicious endometrial area. In both cases, immunohistochemical positivity for Calretinin and Inhibin was noted, typical for a sex cord differentiation. In both cases, total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed. In light of the available literature, no pathognomonic clinical or imaging finding can be attributed to UTROSCT. Patients usually present with abnormal uterine bleeding or pelvic discomfort, but 20% of them are asymptomatic. In most cases, a simple hysterectomy appears to be the appropriate treatment, but for women who wish to become pregnant, uterus-preserving approaches should be discussed after excluding risk factors. Age, tumor size, lymphovascular space invasion, nuclear atypia, and cervical involvement are not reliable prognostic factors in UTROSCT. The current research suggests that aggressive cases (with extrauterine spread or recurrence) can be identified based on a distinct genetic and immunohistochemical phenotype. For instance, UTROSCTs characterized by GREB1::NCOA1-3 fusions and PD-L1 molecule expression appear to be predisposed to more aggressive behaviors and recurrence, with GREB1::NCOA2 being the most common gene fusion in recurrent tumors. Hence, redefining the criteria for UTROSCTs may allow a better selection of women suitable for fertility-sparing treatments or requiring more aggressive treatments in the future.
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Affiliation(s)
- Rafał Watrowski
- Department of Obstetrics and Gynecology, Helios Hospital Müllheim, 79379 Müllheim, Germany
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Mario Palumbo
- Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy; (M.P.); (S.G.); (A.G.); (B.Z.); (P.G.); (G.B.); (A.D.S.S.); (M.C.D.A.)
| | - Serena Guerra
- Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy; (M.P.); (S.G.); (A.G.); (B.Z.); (P.G.); (G.B.); (A.D.S.S.); (M.C.D.A.)
| | - Alessandra Gallo
- Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy; (M.P.); (S.G.); (A.G.); (B.Z.); (P.G.); (G.B.); (A.D.S.S.); (M.C.D.A.)
| | - Brunella Zizolfi
- Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy; (M.P.); (S.G.); (A.G.); (B.Z.); (P.G.); (G.B.); (A.D.S.S.); (M.C.D.A.)
| | - Pierluigi Giampaolino
- Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy; (M.P.); (S.G.); (A.G.); (B.Z.); (P.G.); (G.B.); (A.D.S.S.); (M.C.D.A.)
| | - Giuseppe Bifulco
- Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy; (M.P.); (S.G.); (A.G.); (B.Z.); (P.G.); (G.B.); (A.D.S.S.); (M.C.D.A.)
| | - Attilio Di Spiezio Sardo
- Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy; (M.P.); (S.G.); (A.G.); (B.Z.); (P.G.); (G.B.); (A.D.S.S.); (M.C.D.A.)
| | - Maria Chiara De Angelis
- Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy; (M.P.); (S.G.); (A.G.); (B.Z.); (P.G.); (G.B.); (A.D.S.S.); (M.C.D.A.)
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Ise K, Tanei ZI, Oda Y, Tanikawa S, Sugino H, Ishida Y, Tsuda M, Gotoda Y, Nishiwaki K, Yanai H, Hasegawa T, Nagashima K, Tanaka S. A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Prominent Myxoid Features. Int J Gynecol Pathol 2024; 43:41-46. [PMID: 37406360 DOI: 10.1097/pgp.0000000000000949] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/07/2023]
Abstract
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging. The uterine mass had a glistening mucinous appearance on gross examination. Microscopically, most of the tumor cells were floating in the myxoid stroma. The tumor cells formed clusters or nests with abundant cytoplasm, while some exhibited trabecular or rhabdoid appearances. Immunohistochemically, tumor cells were positive for pancytokeratin (AE1/AE3), α-smooth muscle actin, CD10, progesterone receptor, and some sex cord markers such as calretinin, inhibin, CD56, steroidogenic factor-1. Electron microscopy demonstrated epithelial and sex cord differentiation. This tumor was negative for JAZF1-JJAZ1 fusion gene that is frequently found in low-grade endometrial stromal sarcoma. Fusion genes related to UTROSCT, including NCOA2/3 , were not detected by reverse transcription polymerase chain reaction. The present case suggests that UTROSCT should be included in the differential diagnosis of myxoid uterine tumors.
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Bi R, Yao Q, Ji G, Bai Q, Li A, Liu Z, Cheng Y, Tu X, Yu L, Chang B, Huang D, Ge H, Zuo K, Li H, Chang H, Cai X, Jiang W, Zhou X, Yang W. Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior. Am J Surg Pathol 2023; 47:739-755. [PMID: 37132508 DOI: 10.1097/pas.0000000000002046] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm that mainly harbors NCOA1-3 rearrangements with partner genes ESR1 or GREB1 . Here, we explored 23 UTROSCTs by targeted RNA sequencing. The association between molecular diversity and clinicopathologic features was investigated. The mean age of our cohort was 43 years (23-65 y). Only 15 patients (65%) were originally diagnosed with UTROSCTs. Mitotic figures ranged from 1 to 7/10 high power fields, of primary tumors and increased from 1 to 9/10 high power fields in recurrent tumors. Five types of gene fusions were identified in these patients, including GREB1::NCOA2 (n=7), GREB1::NCOA1 (n=5), ESR1::NCOA2 (n=3), ESR1::NCOA3 (n=7), and GTF2A1::NCOA2 (n=1). To our knowledge, our group included the largest cohort of tumors with GREB1::NCOA2 fusions. Recurrences were most common in patients with GREB1::NCOA2 fusion (57%), followed by 40% ( GREB1::NCOA1 ), 33% ( ESR1::NCOA2 ), and 14% ( ESR1::NCOA3 ). The recurrent patient who harbored an ESR1::NCOA2 fusion was characterized by extensive rhabdoid features. Both of the recurrent patients who harbored GREB1::NCOA1 and ESR1::NCOA3 had the largest tumor sizes in their own gene alteration groups, and another recurrent GREB1::NCOA1 patient had extrauterine involvement. The GREB1 -rearranged patients were of older age, larger tumor size, and higher stage than non- GREB1 -rearranged patients ( P =0.004, 0.028, and 0.016, respectively). In addition, the GREB1 -rearranged tumors presented more commonly as intramural masses rather than non- GREB1 -rearranged tumors presenting as polypoid/submucosal masses ( P =0.021). Microscopically, nested and whorled patterns were frequently seen in GREB1- rearranged patients ( P =0.006). Of note, estrogen receptor expression was weaker than progesterone receptor in all 12 GREB1- rearranged tumors, whereas the similar staining intensity of estrogen receptor and progesterone receptor was observed in all 11 non- GREB1- rearranged tumors ( P <0.0001). This study demonstrated that UTROSCTs were present at a younger age in the Chinese population. The genetic heterogeneity of UTROSCTs was correlated with variable recurrence rate. Tumors with GREB1::NCOA2 fusions are more likely to recur compared with those with other genetic alterations.
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Affiliation(s)
- Rui Bi
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Qianlan Yao
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Gang Ji
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Qianming Bai
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Anqi Li
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zebing Liu
- Department of Pathology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yufan Cheng
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Xiaoyu Tu
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Lin Yu
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Bin Chang
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Dan Huang
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Huijuan Ge
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Ke Zuo
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Hui Li
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Heng Chang
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Xu Cai
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Wenhua Jiang
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Xiaoyan Zhou
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
| | - Wentao Yang
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
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Ye S, Wu J, Yao L, He J. Clinicopathological characteristics and genetic variations of uterine tumours resembling ovarian sex cord tumours. J Clin Pathol 2022; 75:776-781. [PMID: 34348985 PMCID: PMC9606539 DOI: 10.1136/jclinpath-2021-207441] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 07/03/2021] [Indexed: 12/29/2022]
Abstract
AIMS To investigate the clinicopathological and molecular characteristics of uterine tumours resembling ovarian sex cord tumours (UTROSCTs) and the value of molecular diversity in the clinical diagnosis and treatment. METHODS Five patients with UTROSCT were enrolled, and their clinical data, pathological morphologies, immunophenotypes and molecular features were analysed. Fluorescence in situ hybridisation for NCOA1, NCOA2, NCOA3, JAZF1 and PHF1 and next-generation sequencing for 27 homologous recombination/repair (HRR) pathway genes were performed on five and three UTROSCT specimens, respectively. RESULTS All five patients were treated for abnormal uterine bleeding and grossly presented with intrauterine polyps. Under a microscope, tumour cells grew diffusely and presented a cordlike arrangement and glandular duct-like structures, with nuclei ranging from round to oval, vesicular chromatin and visible nucleoli in some cases. The mitotic count was less than 3/10 high-power fields. Immunohistochemistry showed sex cord, epithelial cell and smooth muscle cell biomarkers and diffuse, strong staining for B cell lymphoma-2 (BCL-2). NCOA1 and NCOA3 rearrangements were identified in 80% (4/5) of the cases. JAZF1 and PHF1 rearrangements were not detected in any of five patients. HRR pathway gene mutations were detected in all three patients, including FANCE, ATR and ARID1A mutations in one case each. CONCLUSION UTROSCT is a rare mesenchymal tumour, and biopsy specimens are easily misdiagnosed. UTROSCT diagnosis requires the combined use of biomarkers and molecular detection. BCL-2 has potential diagnostic value as a marker. UTROSCT can have mutations related to the HRR pathway, suggesting that this tumour type may be sensitive to platinum/poly (ADP-ribose) polymerase inhibitors.
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Affiliation(s)
- Shan Ye
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,Department of Pathology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China
| | - Jing Wu
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,Department of Pathology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China
| | - Lingli Yao
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Jie He
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,Department of Pathology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China
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Zhou FF, He YT, Li Y, Zhang M, Chen FH. Uterine tumor resembling an ovarian sex cord tumor: A case report and review of literature. World J Clin Cases 2021; 9:6907-6915. [PMID: 34447841 PMCID: PMC8362530 DOI: 10.12998/wjcc.v9.i23.6907] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/02/2021] [Accepted: 06/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Endometrial stromal tumors originate from the endometrial stroma and account for < 2% of all uterine tumors. Uterine tumor resembling an ovarian sex cord tumor (UTROSCT) is a rare histological class of endometrial stromal and related tumors according to the latest World Health Organization classification of female genital tumors. Here, we report a case of UTROSCT in a 51-year-old woman.
CASE SUMMARY A 51-year-old woman had irregular menses for 6 mo. The patient visited a local hospital for vaginal bleeding. Pelvic computed tomography (CT) showed a mass in the pelvic cavity. Five days later, she came to our hospital for further diagnosis. The results of contrast-enhanced CT and pelvic ultrasound at our hospital suggested a malignant pelvic tumor. She then underwent total removal of the uterus with bilateral salpingectomy. Postoperative histological examination showed that the tumor cells had abundant cytoplasm, ovoid and spindle-shaped nuclei, fine chromatin, a high nucleoplasm ratio, and a lamellar distribution. The findings were consistent with UTROSCT, and the results of immunohistochemical analysis supported that diagnosis. The tumor was International Federation of Gynecology and Obstetrics stage IB. No adjuvant therapy was administered after radical surgery. The patient was followed up for 58 mo, and no recurrence was found.
CONCLUSION We report a case of UTROSCT with abnormal menstruation as a symptom, which is one of the most common symptoms. In patients with vaginal bleeding, ultrasonography can be used as a screening test because of its convenience, speed, and lack of radiation exposure. For patients with long-term tamoxifen use, routine monitoring of the endometrium is recommended. As UTROSCT may have low malignant potential, surgery remains the primary management strategy. Additionally, fertility preservation in patients of childbearing age is a vital consideration.
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Affiliation(s)
- Fang-Fang Zhou
- Department of Ultrasound, Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, Zhejiang Province, China
| | - Ying-Tao He
- Department of Ultrasound, Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, Zhejiang Province, China
| | - Ying Li
- Department of Ultrasound, Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, Zhejiang Province, China
| | - Min Zhang
- Department of Pathology, Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, Zhejiang Province, China
| | - Fang-Hong Chen
- Department of Ultrasound, Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, Zhejiang Province, China
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Kao YC, Lee JC. An update of molecular findings in uterine tumor resembling ovarian sex cord tumor and GREB1-rearranged uterine sarcoma with variable sex-cord differentiation. Genes Chromosomes Cancer 2020; 60:180-189. [PMID: 33099842 DOI: 10.1002/gcc.22909] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 10/21/2020] [Indexed: 12/26/2022] Open
Abstract
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a uterine mesenchymal tumor defined histologically by showing sex cord-like growth patterns, such as sheets, nests, trabeculae, cords, or tubules, with/without Sertoli-like or Leydig-like components, and immunohistochemically by exhibiting variable sex cord markers in addition to epithelial, myogenic, and sex hormone markers. Recent years have seen the emergence in UTROSCT of novel fusion genes that involve key genes in sex hormone pathways, including ESR1 and GREB1 as the 5' partner, and (co)activator oncogenes, particularly NCOA1-3, as the 3' partner. While the identification of similar fusions in the majority of cases serves as a strong argument for UTROSCT to be a distinct entity, there is no denying significant clinicopathologic heterogeneity within the disease spectrum, which might to some extent correlate with the different fusion types. The current review gives a summary of the recently identified fusions in UTROSCT, along with their possible clinicopathologic relevance. Also discussed are unsolved issues including the relationship between UTROSCT and so-called GREB1-rearranged uterine sarcoma as well as other uterine mesenchymal tumors harboring similar fusions.
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Affiliation(s)
- Yu-Chien Kao
- Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.,Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jen-Chieh Lee
- Department and Graduate Institute of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Abstract
CD56 is used in gynecologic pathology, typically in the context of a neuroendocrine, sex cord or sex cord-like tumor. It has never been studied in uterine smooth muscle tumors, which can potentially enter their differential diagnosis, and thus CD56 positivity could potentially be a pitfall. Thus, the aim of this study was to explore its expression in this category of tumors. Seventy-eight uterine smooth muscle tumors, including 14 leiomyosarcomas, 46 leiomyomas and their variants, 14 smooth muscle tumors of uncertain malignant potential, and 4 intravenous leiomyomatoses were studied in regard to CD56 expression. Fifty-eight nearby myometria were also analyzed. Sixty-five (83.4%) tumors showed CD56 expression. Nearby myometrium showed CD56 expression in 15 cases (25.9%). Staining ranged from 10% to 100% of tumor or myometrial cells (median 80% and 50%, respectively). Among the tumor types, leiomyoma with bizarre nuclei, had the lowest extensive expression (P=0.01). Most uterine smooth muscle neoplasms express CD56; thus, it is not useful in attempting to discriminate from endometrial stromal or sex cord-like neoplasms.
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10
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Karpathiou G, Papoudou-Bai A, Clemenson A, Chauleur C, Peoc'h M. The Uterine Plexiform Lesions Revisited. Am J Clin Pathol 2020; 154:178-189. [PMID: 32459343 DOI: 10.1093/ajcp/aqaa054] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVES Uterine lesions with plexiform morphology are uncommon lesions with debated histogenesis. Despite being an incidental and usually benign finding (plexiform tumorlet), some cases can pose diagnostic problems. Their paucity in the recent literature adds to these difficulties and often causes ambiguities. The objective of this study is to systematically review published cases to highlight the historical aspects of their recognition, reappraising their morphology, histogenesis, and differential diagnosis. METHODS English literature is reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and 32 reports are analyzed. RESULTS Most cases are reported in the fourth to sixth decades. In most cases (66.7%), plexiform lesions are incidental findings while 33.3% of cases have been the chief pathology. Size varies from 0.5 to 195 mm. Plexiform foci were solitary in 78.2% cases and multiple in 21.8%. In 67.8% of cases, the lesions are reported as myometrial, while 32.2% are arising from endometrial stroma. Immunohistochemistry shows smooth muscle and no sex cord marker expression. They are usually benign lesions, but worrisome features include plexiform morphology in disseminated peritoneal leiomyomatosis, intravenous leiomyomatosis, and diffuse uterine leiomyomatosis. CONCLUSIONS Plexiform lesions represent a diverse pathology varying from epithelioid leiomyomas to epithelioid smooth muscle metaplasia of endometrial type of stroma.
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Affiliation(s)
| | | | - Alix Clemenson
- Department of Pathology, University Hospital of Saint-Etienne, France
| | - Celine Chauleur
- Department of Pathology, University Hospital of Ioannina, Greece
| | - Michel Peoc'h
- Department of Pathology, University Hospital of Saint-Etienne, France
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Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT): A Morphologic and Molecular Study of 26 Cases Confirms Recurrent NCOA1-3 Rearrangement. Am J Surg Pathol 2020; 44:30-42. [PMID: 31464709 DOI: 10.1097/pas.0000000000001348] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain biological potential, that was recently reported to exhibit recurrent gene fusions involving NCOA2-3. The purpose of this study was to, using a larger sample size, better characterize the histopathologic and molecular diversity of UTROSCT. Twenty-six cases of UTROSCT from 5 institutions were selected for further study. Fluorescence in situ hybridization for NCOA1, NCOA2, NCOA3, ESR1 and GREB1, and targeted RNA sequencing was performed on 17 and 8 UTROSCTs, respectively. Eight cases underwent massively parallel sequencing to detect single nucleotide variants (SNV), copy number variations, and structural variants using a targeted hybrid-capture based assay. NCOA1-3 rearrangement was identified in 81.8% (18/22) of cases. The most common fusion was ESR1-NCOA3, occurring in 40.9% (9/22). GREB1-NCOA1 (n=4), ESR1-NCOA2 (n=3), and GREB1-NCOA2 (n=1) rearrangements were also identified. No recurrent SNVs were identified and no tumor had SNVs in FOXL2, DICER1, STK11, or AKT1, which can be seen in ovarian sex cord-stromal tumors. Copy number variations were infrequent. Clinical follow-up was available for 11 cases with a mean follow-up interval of 94.4 (range, 1 to 319) months. Only one case had a recurrence 66 months after the initial diagnosis and this was the single case with a GREB1-NCOA2 fusion. This study reports the morphologic spectrum of UTROSCT and confirms the recently reported recurrent NCOA2-3 gene fusions, in addition to identifying novel rearrangements involving NCOA1 in these tumors.
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Jia M, Sun PL, Gao H. Uterine lesions with sex cord-like architectures: a systematic review. Diagn Pathol 2019; 14:129. [PMID: 31739799 PMCID: PMC6862816 DOI: 10.1186/s13000-019-0909-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 11/07/2019] [Indexed: 12/14/2022] Open
Abstract
Background Sex cord-like elements are rarely observed in uterine lesions, but these morphological patterns could appear in a variety of uterine tumors and non-tumorous lesions. In this review, we collected the literatures regarding the uterine tumorous and non-tumorous lesions containing sex cord-like elements and summarized these lesions in terms of clinicopathological, immunohistochemical, and molecular features in order to further understand these lesions and provide some new ideas for differential diagnosis. Main body This section provides a comprehensive overview of the clinicopathological, immunohistochemical, and molecular features of uterine lesions with sex cord-like architectures including uterine tumors resembling ovarian sex cord tumors, endometrial stromal tumors, adenomyosis, endometrial polyps, leiomyoma, epithelioid leiomyosarcoma, adenosarcoma, sertoliform endometrioid carcinoma, corded and hyalinized endometrioid carcinoma, mesonephric adenocarcinoma, and mesonephric-like adenocarcinoma. The differential diagnosis based on morphology, immunohistochemistry, and molecular alterations has also been discussed. Conclusion The sex cord-like areas in these lesions show heterogeneous but similar morphological features. Additionally, immunohistochemical staining plays a limited role in differential diagnosis. Furthermore, it is of significance for pathologists to better understand these lesions in order to avoid confusion and mistakes during pathological diagnosis, especially in a biopsy/curettage specimen.
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Affiliation(s)
- Meng Jia
- Department of pathology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China
| | - Ping-Li Sun
- Department of pathology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China.
| | - Hongwen Gao
- Department of pathology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China.
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