Mesonephric adenocarcinoma of the uterine cervix with a prominent spindle cell component

Mesonephric adenocarcinoma of the uterine cervix with a prominent spindle cell component | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Article Mesonephric adenocarcinoma of the uterine cervix with a prominent spindle cell component Yingying Fan, Ying He, Liang Sun, Tianmin Liu, Name：Yangmei Shen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3942369/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Mesonephric adenocarcinomas (MAs) with spindle cell components are rare malignant tumors of the cervix. We conducted a retrospective analysis of MAs with spindle cell components. Clinicopathological data were collected from electronic surgical pathology records, and immunohistochemistry and targeted next-generation sequencing (NGS) were performed. The study included three postmenopausal women aged 51 to 60 years. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. There were no recurrences or deaths after surgery. The NGS analysis identified KRAS mutations in two cases and a lone PIK3CA mutation in one case. Spindle cell components could be a morphological feature of MAs in the advanced stage. Spindle cell components in MAs are diagnostic pitfalls, and the use of immunohistochemical panels and molecular detection is recommended for cases with overlapping morphological features. While KRAS mutation is the most frequent molecular alteration, PIK3CA mutation can be identified independently in cases without KRAS mutation. Biological sciences/Cancer/Gastrointestinal cancer Biological sciences/Molecular biology Mesonephric adenocarcinomas Prognosis Next generation sequencing KRAS PIK3CA Figures Figure 1 Figure 2 Introduction Mesonephric adenocarcinomas (MAs) are rare malignant HPV-independent cervical tumors that arise from vestiges of the embryological male reproductive system (Wolffian/mesonephric duct) remnants located deep in the cervical wall 1 , 2 . MAs display diverse morphologic architectural patterns, including tubular, glandular, papillary, cribriform, retiform, spindle cell, and solid structures 2 . Morphologically, the tumor is characterized by eosinophilic luminal secretions, mesonephric remnants, and hyperplasia 3 . Molecularly, the majority of MAs exhibit KRAS mutations. Patients with MAs have a worse prognosis compared to those with cervical squamous cell carcinoma and other types of adenocarcinomas 4 , 5 . Spindle cell components can be observed in MAs, but current studies have paid little attention to exploring the biological behavior and prognosis of MAs with these components. We present three cases of cervical MAs with prominent spindle cell components and comprehensively review the literature to investigate whether the presence of spindle morphology indicates distinct clinicopathological and molecular features. Materials and methods The cases included in this study were all obtained from West China Second University Hospital, Sichuan University. All procedures performed in studies involving human participants were adhered to ethical standards. Clinicopathological information of patients, including age, clinical presentations, procedures, tumor size, follow-up information, and FIGO stage, was extracted from electronic medical records. Two pathologists reviewed all hematoxylin and eosin (HE) sections and immunohistochemical findings of all included cases. The institutional ethics committee of West China Second University Hospital, Sichuan University approved this study, and written informed consent was obtained from each patient. Immunohistochemical staining testing was performed on 4µm formalin-fixed paraffin-embedded (FFPE) tumor samples. All immunohistochemically stained tumor samples were evaluated using appropriate internal and external controls. The following antibodies were used in the diagnostic work-up: CK pan, EMA, PAX8, ER, PR, p16, GATA3, CD10, TTF1, p53, and Ki67 (Maxim, CHN). The genomic alteration profiling test was conducted by Precision Scientific, Inc. (Beijing, CHN) using targeted next-generation sequencing (NGS) technology. The targeted NGS panel assesses 107 genes, which are listed in the Supplemental Table. Genomic DNA was extracted from 5µm FFPE tumor tissues from all three patients after selecting a region with over 20% tumor cells. Sequencing libraries were prepared using more than 300 ng total DNA followed by paired-end sequencing by synthesis technology. NGS was conducted using the Illumina sequencing platform NovaSeq6000, and the final sequencing results were analyzed using bioinformatics. Results Clinical features The clinicopathological features of the patients are summarized in Table 1 . The study included three postmenopausal women aged 51 to 60 years (mean age, 56 years). The three patients presented with different clinical symptoms, including cervical ThinPrep cytologic test (TCT) results indicating abnormal, abdominal distension and pain, and postmenopausal vaginal bleeding. In case 1, colposcopy revealed a 1 cm × 0.5 cm ulcerated area on the cervix at 11 o'clock. Table 1 Clinicopathological features Parameters Case 1 Case 2 Case 3 Age (y) 51 60 57 Clinical presentation None Abdominal distension and pain for 1 month Postmenopausal vaginal bleeding for 5 months Surgical procedure TAHBSO + LND TAHBSO + LND + CRT TAHBSO + LND + CT Tumor size (cm) 1 7.3 3.5 FIGO stage IB IIB IIB Gross appearance Ulceration Cauliflower-like mass Cauliflower-like mass Outcomes DFS DFS DFS Follow-up (months) 2 4 9 Initial diagnosis Synovial sarcoma Mesenchymal tumor Clear cell carcinoma Imaging findings Enlarged cervix with heterogeneous enhancement A solid-cystic mass A low-density mass Serum tumor markers CA125 and CA19-9 levels elevated CA125, CA19-9, and CEA levels elevated Normal Immunohistochemical findings EMA Positive Positive Positive CK pan Positive NA Positive PAX8 Positive Positive NA GATA3 Positive Positive (focal) Heterogeneous (positive in epithelioid areas and negative in spindle cell components) CD10 Negative Positive Positive TTF1 Negative Positive Negative ER Positive (focal) Negative Negative PR Positive (focal) Negative Negative p16 Positive (focal) Positive (patchy) Positive (patchy) p53 wild type wild type wild type Ki67 20% 20% 40% CT: Chemotherapy; CRT: Chemotherapy and radiotherapy; DFS: Disease free survival; LND, lymph node dissection; LWD: Living with disease; NA: Not available; TAHBSO, Total abdominal hysterectomy and bilateral salpingo-oophorectomy. Imaging examinations revealed cervical masses in two cases. In case 2, a contrast-enhanced computed tomography (CT) scan showed a solid-cystic mass measuring 5.4 cm × 6.4 cm × 7.3 cm on the left side of the pelvic cavity, with unclear boundaries with the left adnexa and the posterior wall of the uterus. Imaging examinations revealed cervical masses in two cases. In case 2 a contrast-enhanced computed tomography (CT) scan revealed a solid-cystic mass on the left side of the pelvic cavity, measuring 5.4 cm × 6.4 cm × 7.3 cm, and the boundaries with the left adnexa and the posterior wall of the uterus were unclear. Additionally, CT imaging also showed a low-density uterine cervical mass in case 3, measuring 3.5 cm × 2.8 cm × 2.7 cm. Two cases showed slightly elevated serum tumor markers. Furthermore, both of these patients had a history of surgery for pulmonary carcinoma. The family histories of all patients were unremarkable. Treatment and follow-up All three patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection. Two patients (66.7%) were were classified as FIGO stage IIB, while the remaining patient was classified as FIGO stage IB. Patients with FIGO stage IIB received postoperative adjuvant chemotherapy using carboplatin and paclitaxel, while case 2 additionally underwent adjuvant radiation therapy. Follow-up information was obtained for all three patients, and no recurrences or deaths were observed during the 2, 4, and 9 months postoperative follow-up period. Pathological features On gross examination, two tumors presented as cauliflower-like masses in the cervix (Fig. 1 A). A total of two biopsy specimens, one frozen specimen, and three surgical specimens were reviewed from all three cases. Histologically, all surgical specimens from the three cases exhibited biphasic tumors characterized by the coexistence of epithelioid and spindle cell areas. In the spindle cell areas, tumor cells exhibited an invasive growth pattern, arranged in fascicular and storiform patterns (Fig. 1 B). These spindle cells had small amounts of indistinct cytoplasm, oval to fusiform nuclei, non-prominent nucleoli, and moderate to marked nuclear atypia. Mitotic figures were observed. In the adjacent area to the spindle cell areas, glandular, papillary, cribriform, and back-to-back tubular structures were observed, lined by cuboidal tumor cells with moderate to marked nuclear atypia, mitotic figures, and nuclear grooves. The cuboidal epithelioid cells formed glandular tubular structures with luminal eosinophilic hyaline secretions (Fig. 1 C). Additionally, benign mesonephric remnants and hyperplasia surrounding the tumor were visible (Fig. 1 D). In one of the biopsy specimens, the tumor was primarily composed of spindle cells with occasional glandular components, microscopically. The initial diagnosis was synovial sarcoma at the local hospital. In another biopsy specimen, no spindle cell component was observed, leading to the initial diagnosis of clear cell carcinoma. Prominent spindle cell components were also observed in the frozen specimen. In the frozen sections, only diffuse spindle tumor cells were observed with no evidence of epithelioid areas. Based on the above morphological features, the initial diagnosis of the intraoperative frozen initial was spindle cell tumor, tending toward mesenchymal tumor. The results of immunohistochemistry were showed in Table 1 . Immunohistochemically, tumor cells demonstrated positive staining for epithelial marker (CK pan and/or EMA) (Fig. 2 A) and PAX8 (Fig. 2 B). CD10 (Fig. 2 C) and TTF-1 (Fig. 2 D) were expressed positive in two cases and in one case respectively. Tumor cells were negative or focal positive for ER and PR. p16 was focal or patchy positive in tumor cells. p53 was wild type expressed in all three cases. The Ki67 proliferative index ranged from 20–40%. GATA3 was positive in two cases, while in case 3 GATA3 was negative in spindle cell components (Fig. 2 E) and positive in epithelioid areas (Fig. 2 F). Molecular features NGS was performed in all three cases. Microsatellite instability was not identified in any of the included cases. In case 1 only a KRAS (Q61K) mutation was identified. In case 2, the tumor had mutations of KRAS (G12D) and CHEK , along with amplifications of KRAS , MDM4 , and NTRK1 . A mutation of PIK3CA (E726K) and amplification of NTRK1 were identified in case 3. Discussion Primary cervical MAs are rare malignant tumors, representing only 1% of all cervical malignancies 2 . Currently, cervical MAs have only been reported as case reports or small series. The largest study on cervical MAs to date is the multicenter study conducted by Pors J et al 5 , which included 30 cases. In the published literature, most MAs were not clearly described regarding the presence of spindle cell components, and a few MAs with spindle cell components were diagnosed as mesonephric carcinosarcomas (previously referred to as mesonephric mixed tumors). To the best of our knowledge, only 11 cases of cervical MAs explicitly described in the published literature have been reported to have spindle cell components, including the cases we described (Table 2 ). Table 2 Mesonephric carcinoma with spindle cell components in the literature and the present cases Ref. Case Age (y) Tumor size (cm) FIGO stage Percentage of spindle cell components Outcome Follow-up (months) KRAS/NRAS mutation Mirkovic et al, 2015 8 1 76 2.2 IIB 5% NA NA Yes 2 47 NA IIB 80% NA NA Yes 3 38 NA IIIB 15% LWD 10 Yes 4 64 4.5 IB 60% DFS 36 Yes 5 67 1 NA 40% NA NA Yes 6 54 12 NA 90% NA NA Yes 7 48 NA NA 5% NA NA No 8 37 NA NA 30% NA NA No Present cases 9 51 1 IB 80% DFS 2 Yes 10 60 7.3 IIB 50% DFS 4 Yes 11 57 3.5 IIB 60% DFS 9 No DFS: Disease free survival; LWD: Living with disease; NA: Not available. The median age at diagnosis of cervical MAs with spindle cell components was 54 years (range: 37years to 76 years). The age at diagnosis was similar to that of MAs without spindle cell components (52 years to 59 years) and mesonephric carcinosarcomas (54 years) 4 – 6 . The median tumor size of cervical MAs with spindle cell components was 4.5 cm (ranging from 1 cm to 12 cm), which was larger than that of mesonephric carcinosarcomas (3.5 cm) 6 . Among the seven patients with MAs and spindle cell components, five (71%) were diagnosed at FIGO stage II-IV. A previous review of literature revealed that only 30% of patients with MAs are diagnosed at FIGO stage II-IV 4 . Contrary to the aforementioned literature review, the multicenter study of Pors J et al 5 showed that a higher percentage of patients (60%) with MAs were diagnosed at an advanced stage (FIGO stage II-IV). Moreover, approximately 40% of patients with mesonephric carcinosarcomas were diagnosed at FIGO stage II-IV 6 , 7 . This suggests that MAs with spindle cell components are more likely to be diagnosed at an advanced stage compared to MAs without spindle cell components and mesonephric carcinosarcomas. Spindle cell components could be a morphological feature of MAs in the advanced stage. Prognostic information is available for only 5 cases of MAs with spindle cell components, including the three cases presented in this study. The mean follow-up duration was 12 months (range: 2–36 months). Only one patient (20%) lived with disease at FIGO stage IIIB, and no death was observed. The sites of recurrence and metastasis were the abdominal, pelvic, and liver 8 . The recurrence rate of MAs with spindle cell components is higher than that of cervical adenocarcinomas (16%) and squamous cell carcinomas (11%) in the cervix 9 . A previous literature review revealed that approximately 30% of patients with MAs lacking spindle cell components experienced recurrence and 23% of patients died from the disease, regardless of the disease stage 4 . The recent study from Pors J et al 5 demonstrated that patients with MAs without spindle cell components had a poorer prognosis, with a 5-year overall survival rate of 74% and progression-free survival rate of 60% in cervical MAs, compared to the findings of previous literature reviews. Additionally, patients with mesonephric carcinosarcomas had a recurrence rate of 22% and a mortality rate of 25% 6, 7 . The limited follow-up data for MAs with spindle cell components makes prognostic evaluation challenging and unreliable. However, based on the available data, the recurrence rate of MAs with spindle cell components appears to be lower than that of MAs without spindle cell components and mesonephric carcinosarcomas, but higher than that of adenocarcinoma and squamous cell carcinoma in the cervix. MAs with spindle cell components seem to have an aggressive clinical behavior. All three patients we reported underwent hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. Two out of three patients received adjuvant chemotherapy with carboplatin and paclitaxel, and one patient also underwent adjuvant radiation therapy following primary surgery. Currently, there is no standardized treatment for this rare tumor. At present there is no standard treatment for this rare tumor. Treatments depend on the stage of MAs, and the treatment principles is consistent with other types of cervical adenocarcinomas 10 . The majority of patients with early-stage MAs underwent hysterectomy with bilateral salpingo-oophorectomy, while a small proportion of patients also received adjuvant radiotherapy and chemotherapy 4 . While adjuvant chemotherapy with carboplatin and paclitaxel is commonly used as first-line treatment, its role in early-stage MAs remains unclear 11 . Similarly, the efficacy of adjuvant radiotherapy is also unclear. Spindle cell components in MAs are diagnostic pitfalls. In the two cases we reported, the initial diagnoses were initially considered to be mesenchymal tumors. Therefore, MAs should be included in the differential diagnosis when obvious spindle cell components are present morphologically, particularly in biopsy specimens. An immunohistochemical panel including PAX8, GATA3, CD10, and TTF1 should be used in the differential diagnosis. MAs typically exhibit luminal CD10 staining, negative or focal positive expression of ER and PR, and positive expression of PAX8 12 . Among the immunohistochemical markers mentioned above, GATA3 is a highly sensitive and specific marker for MAs 13 , 14 . One case (case 3) from our study, GATA3 showed negative staining in the spindle cell areas and positive staining in the adenoid areas. The staining intensity of GATA3 may decrease in the solid areas, which is consistent with previous reports 13 , 14 . Therefore, it is worth noting that if a spindle cell component is recognized with GATA3 expression as negative or weakly positive in the biopsy specimen, it should also be suspected of being MA. TTF1 may be helpful in diagnosing cases where GATA3 is negatively expressed, due to the inverse staining pattern between GATA3 and TTF1 14 . Correct diagnosis is challenging since MAs usually exhibit a variety of morphologic patterns, especially in biopsy specimens. The correct diagnostic rate is only 10% in initial biopsy specimens 5 . The overlapping morphology features of MAs with prominent spindle cell components make for a broader range of differential diagnoses. The main differential diagnoses include endocervical adenocarcinoma, clear cell carcinoma, and endometrioid adenocarcinoma. Endocervical adenocarcinoma, which is often associated with HPV, exhibits mucin production or ciliation. p16 shows diffuse staining in HPV-related endocervical adenocarcinomas, but shows patchy staining pattern in MAs. In cases with overlapping morphologic features that are difficult to diagnose, a combination of immunohistochemical markers such as CEA, p16, GATA3, and CD10 can be used. Clear cell carcinoma, HPV-independent adenocarcinoma, is characterized by clear, eosinophilic, and hobnailed tumor cells. It should be noted that HNF1β, a marker commonly used in the diagnosis of clear cell carcinoma, is also positively expressed in a subset of MAs 12 . Squamous and mucinous differentiation are helpful for the diagnosis of endometrial endometrioid adenocarcinoma. Immunohistochemical staining for ER and PR is usually positive in endometrioid adenocarcinoma. Moreover, the most confusing differential diagnosis is mesonephric carcinosarcomas. Mesonephric carcinosarcomas, which are biphasic tumors, consist of distinguishable epithelial and frankly malignant spindle cell components 15 . 16% of cervical carcinosarcomas originate from mesonephric duct remnants 7 , 16 . According to Mirkovic et al 17 recommended that MAs with heterologous mesenchymal elements should be diagnosed as mesonephric carcinosarcomas. So far, reported heterologous sarcomatous components in the literature have included osteosarcoma, chondrosarcoma, and rhabdomyosarcoma, while the homologous component has been limited to endometrial stromal sarcoma 7 . The spindle cell components observed in MAs may be part of the morphologic spectrum of the tumors 17 , 18 . Epithelial immunohistochemical markers can be helpful in distinguishing between these entities. Consistent with previous studies, no specific molecular events were found to differentiate MAs with spindle cell components from those without spindle cell components 8 . The molecular alterations of MAs mainly included KRAS/NRAS mutation, microsatellite stability, and gains of chromosome 1q 8 , 19 . Alterations in the RAS/MAPK pathway may contribute to the development of MAs 8 , 15 . KRAS/NRAS mutations are the most common molecular alterations in MAs, and they are mutually exclusive. KRAS mutation is more recurrent than NRAS mutation, and it has been reported that the majority of MAs (75%-100%) harbor KRAS mutations which mainly affected the hotspot codons 12 and 13 8, 15, 19 . Common mutation sites include G12C, G12D, and G12V 15 , 19 . Other molecular changes also have been reported, which included chromatin remodeling genes of ARID1A/B and SMARCA4 8 . The PIK3CA encodes the p110α catalytic subunit of the class IA phosphatidylinositol 3-kinases (PI3Ks) 20 . Mutations in PIK3CA can result in abnormally increased catalytic activity of PI3Ks, promoting cell carcinogenesis 20 , 21 . In the female reproductive system PIK3CA mutation is more common in endometrial and other types of cervical adenocarcinomas arising from the Mullerian ducts 22 – 24 . In the study of Mirkovic et al 8 , PIK3CA mutations were not identified from 13 cervical MAs. Subsequently, Silva et al 15 reported that two cervical MAs harbored KRAS mutations and PIK3CA mutations simultaneously. As far as we know, there have been no documented cases of PIK3CA mutations without KRAS or NRAS mutations in MAs or mesonephric-like carcinomas. This study presents the first case of a cervical MA with a lone PIK3CA mutation, without KRAS or NRAS mutation. Additionally, CTNNB1 mutations are commonly found in carcinomas originating from the Mullerian ducts, and a recent report described an MA with alterations in both CTNNB1 and KRAS 25 . These observations suggest that there are shared molecular alterations between MAs and carcinomas that arise from the Mullerian ducts. NTRK genes encode tropomyosin receptor kinases (Trk) 26 . Fusion of NTRK1/2/3 genes is the most common mechanism of Trk activation in various cancers 26 . In malignant melanoma, the amplification of the NTRK1 gene is associated with poorer clinical outcomes 27 . NTRK1 amplification was detected in both two cases of MAs with FIGO stage IIB that we reported. NTRK1 amplification may promote tumor cell proliferation in MAs leading to an advanced stage. Conclusion In conclusion, MAs exhibit morphologic diversity, with those containing spindle cell components often associated with advanced stages and aggressive behavior. Prominent spindle cell components in MAs are diagnostic pitfalls especially in cervical biopsy specimens. Utilizing a panel of immunohistochemical stains may aid in the differential diagnosis. Despite KRAS being the most frequently observed molecular alteration, PIK3CA mutations can also be identified independently in MAs. Declarations Funding This work supported by Sichuan Science and Technology Program(2022NSFSC0708). CRediT authorship contribution statement Yingying Fan: conceptualization, data curation, writing – original draft. Ying He: Data curation. Liang Sun: Data curation. Tianmin Liu: Methodology. Yangmei Shen: Conceptualization, writing – review & editing, supervision, funding acquisition. Data availability statement Due to restrictions related to participant confidentiality, the data are not publicly available. The data that support the findings of this study are available from the corresponding author upon reasonable request. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. References Sajjad Y. Development of the genital ducts and external genitalia in the early human embryo. J Obstet Gynaecol Res 2010; 36: 929–937. Howitt BE and Nucci MR. Mesonephric proliferations of the female genital tract. Pathology 2018; 50: 141–150. Menon S, Kathuria K, Deodhar K, et al. Mesonephric adenocarcinoma (endometrioid type) of endocervix with diffuse mesonephric hyperplasia involving cervical wall and myometrium: an unusual case report. Indian J Pathol Microbiol 2013; 56: 51–53. Dierickx A, Goker M, Braems G, et al. 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PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer. Sci Rep 2017; 7: 10240. McIntyre JB, Wu JS, Craighead PS, et al. PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy. Gynecol Oncol 2013; 128: 409–414. Montalvo N, Redroban L and Galarza D. Mesonephric adenocarcinoma of the cervix: a case report with a three-year follow-up, lung metastases, and next-generation sequencing analysis. Diagn Pathol 2019; 14: 71. Cocco E, Scaltriti M and Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731–747. Pasini L, Re A, Tebaldi T, et al. TrkA is amplified in malignant melanoma patients and induces an anti-proliferative response in cell lines. BMC Cancer 2015; 15: 777. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3942369","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":273654013,"identity":"fee7c6ac-7cdc-48ba-a6ad-187233424900","order_by":0,"name":"Yingying Fan","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yingying","middleName":"","lastName":"Fan","suffix":""},{"id":273654014,"identity":"e74fa680-7df7-4ab0-a5e5-d445bb84b2ad","order_by":1,"name":"Ying He","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"He","suffix":""},{"id":273654015,"identity":"6c7ea266-75e8-45b1-ba20-d233f2a9c71b","order_by":2,"name":"Liang Sun","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Sun","suffix":""},{"id":273654016,"identity":"c9e2c25d-4171-48f7-b4ca-3542182c51da","order_by":3,"name":"Tianmin Liu","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tianmin","middleName":"","lastName":"Liu","suffix":""},{"id":273654017,"identity":"5fbdf36a-4a8d-4878-bdd3-3736a850d235","order_by":4,"name":"Name：Yangmei Shen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYLACCQYLHgb2xsaHH0jQIsHDwHO42ViCJHsYJNLbBHiIUSs/IzuBwbJNQoZ/5sM2oE47Od0GAloMbuRuYJBsk+CRuJ3Y9qCAIdnY7AAhLRJQLQy3E9sNJBgOJG4jpEV+BlSL/M2DII1EaGGAOczgBiORWgzOvN1wQOKcBI/hmURgIBsQ4Rf59tyNjyXKbOzljh9/+PBDhZ0cQS0MAgkMhxExaEBIOQjwH2BgJD6djIJRMApGwYgEAMaEPkeAxPsEAAAAAElFTkSuQmCC","orcid":"","institution":"Sichuan University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Name：Yangmei","middleName":"","lastName":"Shen","suffix":""}],"badges":[],"createdAt":"2024-02-09 07:59:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3942369/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3942369/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51445830,"identity":"abf6adc3-ffa7-4505-8e27-ea2e5e66c562","added_by":"auto","created_at":"2024-02-21 18:12:26","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3056252,"visible":true,"origin":"","legend":"\u003cp\u003eThe gross lesion presented as a cauliflower-like mass in the cervix (A). The spindle tumor cells were arranged in storiform and fascicular patterns (B, ×200). Glandular tubular structures containing eosinophilic and hyaline secretions (C, ×100). Mesonephric remnants and hyperplasia (left) were surrounded by epithelioid areas (D, ×400).\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3942369/v1/2c6229328cc894f16a95a09a.jpg"},{"id":51445831,"identity":"d40d0811-d49a-491f-9383-13dc99a3ee47","added_by":"auto","created_at":"2024-02-21 18:12:26","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":4765980,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemically, the tumor cells showed positive expression of EMA (A, ×40), PAX8 (B, ×100), CD10 (C, ×100), and TTF1 (D, ×100). GATA3 was negative expression in spindle cell areas (E, ×200) and positive expression in gland structures (F, ×200).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3942369/v1/c1921e302260a219bc50d924.jpg"},{"id":55707441,"identity":"b0b109c3-1380-4878-8d73-104ed9fdb17f","added_by":"auto","created_at":"2024-05-02 05:17:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1037259,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3942369/v1/ebc8a681-3707-4273-9f07-b5f73bda37ba.pdf"},{"id":51445832,"identity":"bbb249eb-8830-49c2-8a42-080b7085b2f8","added_by":"auto","created_at":"2024-02-21 18:12:26","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13953,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementTable.docx","url":"https://assets-eu.researchsquare.com/files/rs-3942369/v1/7f9ed0a13ef4db9ecb0242ce.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mesonephric adenocarcinoma of the uterine cervix with a prominent spindle cell component","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMesonephric adenocarcinomas (MAs) are rare malignant HPV-independent cervical tumors that arise from vestiges of the embryological male reproductive system (Wolffian/mesonephric duct) remnants located deep in the cervical wall\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. MAs display diverse morphologic architectural patterns, including tubular, glandular, papillary, cribriform, retiform, spindle cell, and solid structures\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Morphologically, the tumor is characterized by eosinophilic luminal secretions, mesonephric remnants, and hyperplasia\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Molecularly, the majority of MAs exhibit \u003cem\u003eKRAS\u003c/em\u003e mutations.\u003c/p\u003e \u003cp\u003ePatients with MAs have a worse prognosis compared to those with cervical squamous cell carcinoma and other types of adenocarcinomas\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Spindle cell components can be observed in MAs, but current studies have paid little attention to exploring the biological behavior and prognosis of MAs with these components. We present three cases of cervical MAs with prominent spindle cell components and comprehensively review the literature to investigate whether the presence of spindle morphology indicates distinct clinicopathological and molecular features.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e The cases included in this study were all obtained from West China Second University Hospital, Sichuan University. All procedures performed in studies involving human participants were adhered to ethical standards. Clinicopathological information of patients, including age, clinical presentations, procedures, tumor size, follow-up information, and FIGO stage, was extracted from electronic medical records. Two pathologists reviewed all hematoxylin and eosin (HE) sections and immunohistochemical findings of all included cases. The institutional ethics committee of West China Second University Hospital, Sichuan University approved this study, and written informed consent was obtained from each patient.\u003c/p\u003e \u003cp\u003eImmunohistochemical staining testing was performed on 4\u0026micro;m formalin-fixed paraffin-embedded (FFPE) tumor samples. All immunohistochemically stained tumor samples were evaluated using appropriate internal and external controls. The following antibodies were used in the diagnostic work-up: CK pan, EMA, PAX8, ER, PR, p16, GATA3, CD10, TTF1, p53, and Ki67 (Maxim, CHN).\u003c/p\u003e \u003cp\u003eThe genomic alteration profiling test was conducted by Precision Scientific, Inc. (Beijing, CHN) using targeted next-generation sequencing (NGS) technology.\u003c/p\u003e \u003cp\u003eThe targeted NGS panel assesses 107 genes, which are listed in the Supplemental Table. Genomic DNA was extracted from 5\u0026micro;m FFPE tumor tissues from all three patients after selecting a region with over 20% tumor cells. Sequencing libraries were prepared using more than 300 ng total DNA followed by paired-end sequencing by synthesis technology. NGS was conducted using the Illumina sequencing platform NovaSeq6000, and the final sequencing results were analyzed using bioinformatics.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eClinical features\u003c/h2\u003e \u003cp\u003eThe clinicopathological features of the patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The study included three postmenopausal women aged 51 to 60 years (mean age, 56 years). The three patients presented with different clinical symptoms, including cervical ThinPrep cytologic test (TCT) results indicating abnormal, abdominal distension and pain, and postmenopausal vaginal bleeding. In case 1, colposcopy revealed a 1 cm \u0026times; 0.5 cm ulcerated area on the cervix at 11 o'clock.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicopathological features\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCase 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCase 3\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbdominal distension and pain for 1 month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePostmenopausal vaginal bleeding for 5 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical procedure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAHBSO\u0026thinsp;+\u0026thinsp;LND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTAHBSO\u0026thinsp;+\u0026thinsp;LND\u0026thinsp;+\u0026thinsp;CRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTAHBSO\u0026thinsp;+\u0026thinsp;LND\u0026thinsp;+\u0026thinsp;CT\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIGO stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGross appearance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUlceration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCauliflower-like mass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCauliflower-like mass\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDFS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSynovial sarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMesenchymal tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImaging findings\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnlarged cervix with heterogeneous enhancement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA solid-cystic mass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eA low-density mass\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum tumor markers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCA125 and CA19-9 levels elevated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCA125, CA19-9, and CEA levels elevated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunohistochemical findings\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCK pan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePAX8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGATA3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive (focal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHeterogeneous (positive in epithelioid areas and negative in spindle cell components)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTTF1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive (focal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive (focal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive (focal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive (patchy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive (patchy)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ewild type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ewild type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ewild type\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKi67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCT: Chemotherapy; CRT: Chemotherapy and radiotherapy; DFS: Disease free survival; LND, lymph node dissection; LWD: Living with disease; NA: Not available; TAHBSO, Total abdominal hysterectomy and bilateral salpingo-oophorectomy.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eImaging examinations revealed cervical masses in two cases. In case 2, a contrast-enhanced computed tomography (CT) scan showed a solid-cystic mass measuring 5.4 cm \u0026times; 6.4 cm \u0026times; 7.3 cm on the left side of the pelvic cavity, with unclear boundaries with the left adnexa and the posterior wall of the uterus.\u003c/p\u003e \u003cp\u003eImaging examinations revealed cervical masses in two cases. In case 2 a contrast-enhanced computed tomography (CT) scan revealed a solid-cystic mass on the left side of the pelvic cavity, measuring 5.4 cm \u0026times; 6.4 cm \u0026times; 7.3 cm, and the boundaries with the left adnexa and the posterior wall of the uterus were unclear. Additionally, CT imaging also showed a low-density uterine cervical mass in case 3, measuring 3.5 cm \u0026times; 2.8 cm \u0026times; 2.7 cm.\u003c/p\u003e \u003cp\u003eTwo cases showed slightly elevated serum tumor markers. Furthermore, both of these patients had a history of surgery for pulmonary carcinoma. The family histories of all patients were unremarkable.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and follow-up\u003c/h2\u003e \u003cp\u003eAll three patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection. Two patients (66.7%) were were classified as FIGO stage IIB, while the remaining patient was classified as FIGO stage IB. Patients with FIGO stage IIB received postoperative adjuvant chemotherapy using carboplatin and paclitaxel, while case 2 additionally underwent adjuvant radiation therapy.\u003c/p\u003e \u003cp\u003eFollow-up information was obtained for all three patients, and no recurrences or deaths were observed during the 2, 4, and 9 months postoperative follow-up period.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePathological features\u003c/h2\u003e \u003cp\u003eOn gross examination, two tumors presented as cauliflower-like masses in the cervix (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). A total of two biopsy specimens, one frozen specimen, and three surgical specimens were reviewed from all three cases.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistologically, all surgical specimens from the three cases exhibited biphasic tumors characterized by the coexistence of epithelioid and spindle cell areas. In the spindle cell areas, tumor cells exhibited an invasive growth pattern, arranged in fascicular and storiform patterns (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). These spindle cells had small amounts of indistinct cytoplasm, oval to fusiform nuclei, non-prominent nucleoli, and moderate to marked nuclear atypia. Mitotic figures were observed.\u003c/p\u003e \u003cp\u003eIn the adjacent area to the spindle cell areas, glandular, papillary, cribriform, and back-to-back tubular structures were observed, lined by cuboidal tumor cells with moderate to marked nuclear atypia, mitotic figures, and nuclear grooves. The cuboidal epithelioid cells formed glandular tubular structures with luminal eosinophilic hyaline secretions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Additionally, benign mesonephric remnants and hyperplasia surrounding the tumor were visible (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003eIn one of the biopsy specimens, the tumor was primarily composed of spindle cells with occasional glandular components, microscopically. The initial diagnosis was synovial sarcoma at the local hospital. In another biopsy specimen, no spindle cell component was observed, leading to the initial diagnosis of clear cell carcinoma. Prominent spindle cell components were also observed in the frozen specimen. In the frozen sections, only diffuse spindle tumor cells were observed with no evidence of epithelioid areas. Based on the above morphological features, the initial diagnosis of the intraoperative frozen initial was spindle cell tumor, tending toward mesenchymal tumor.\u003c/p\u003e \u003cp\u003eThe results of immunohistochemistry were showed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Immunohistochemically, tumor cells demonstrated positive staining for epithelial marker (CK pan and/or EMA) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA) and PAX8 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). CD10 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC) and TTF-1 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD) were expressed positive in two cases and in one case respectively. Tumor cells were negative or focal positive for ER and PR. p16 was focal or patchy positive in tumor cells. p53 was wild type expressed in all three cases. The Ki67 proliferative index ranged from 20\u0026ndash;40%. GATA3 was positive in two cases, while in case 3 GATA3 was negative in spindle cell components (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE) and positive in epithelioid areas (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eMolecular features\u003c/h2\u003e \u003cp\u003eNGS was performed in all three cases. Microsatellite instability was not identified in any of the included cases. In case 1 only a \u003cem\u003eKRAS\u003c/em\u003e (Q61K) mutation was identified. In case 2, the tumor had mutations of \u003cem\u003eKRAS\u003c/em\u003e (G12D) and \u003cem\u003eCHEK\u003c/em\u003e, along with amplifications of \u003cem\u003eKRAS\u003c/em\u003e, \u003cem\u003eMDM4\u003c/em\u003e, and \u003cem\u003eNTRK1\u003c/em\u003e. A mutation of \u003cem\u003ePIK3CA\u003c/em\u003e (E726K) and amplification of \u003cem\u003eNTRK1\u003c/em\u003e were identified in case 3.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrimary cervical MAs are rare malignant tumors, representing only 1% of all cervical malignancies\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Currently, cervical MAs have only been reported as case reports or small series. The largest study on cervical MAs to date is the multicenter study conducted by Pors J et al\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, which included 30 cases.\u003c/p\u003e \u003cp\u003eIn the published literature, most MAs were not clearly described regarding the presence of spindle cell components, and a few MAs with spindle cell components were diagnosed as mesonephric carcinosarcomas (previously referred to as mesonephric mixed tumors). To the best of our knowledge, only 11 cases of cervical MAs explicitly described in the published literature have been reported to have spindle cell components, including the cases we described (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMesonephric carcinoma with spindle cell components in the literature and the present cases\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e(y)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTumor size\u003c/p\u003e \u003cp\u003e(cm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFIGO stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePercentage of spindle cell components\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eFollow-up (months)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eKRAS/NRAS\u003c/em\u003e mutation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMirkovic et al, 2015\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLWD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eDFS: Disease free survival; LWD: Living with disease; NA: Not available.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe median age at diagnosis of cervical MAs with spindle cell components was 54 years (range: 37years to 76 years). The age at diagnosis was similar to that of MAs without spindle cell components (52 years to 59 years) and mesonephric carcinosarcomas (54 years)\u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. The median tumor size of cervical MAs with spindle cell components was 4.5 cm (ranging from 1 cm to 12 cm), which was larger than that of mesonephric carcinosarcomas (3.5 cm)\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Among the seven patients with MAs and spindle cell components, five (71%) were diagnosed at FIGO stage II-IV. A previous review of literature revealed that only 30% of patients with MAs are diagnosed at FIGO stage II-IV\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Contrary to the aforementioned literature review, the multicenter study of Pors J et al\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e showed that a higher percentage of patients (60%) with MAs were diagnosed at an advanced stage (FIGO stage II-IV). Moreover, approximately 40% of patients with mesonephric carcinosarcomas were diagnosed at FIGO stage II-IV\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. This suggests that MAs with spindle cell components are more likely to be diagnosed at an advanced stage compared to MAs without spindle cell components and mesonephric carcinosarcomas. Spindle cell components could be a morphological feature of MAs in the advanced stage.\u003c/p\u003e \u003cp\u003ePrognostic information is available for only 5 cases of MAs with spindle cell components, including the three cases presented in this study. The mean follow-up duration was 12 months (range: 2\u0026ndash;36 months). Only one patient (20%) lived with disease at FIGO stage IIIB, and no death was observed. The sites of recurrence and metastasis were the abdominal, pelvic, and liver\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. The recurrence rate of MAs with spindle cell components is higher than that of cervical adenocarcinomas (16%) and squamous cell carcinomas (11%) in the cervix\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. A previous literature review revealed that approximately 30% of patients with MAs lacking spindle cell components experienced recurrence and 23% of patients died from the disease, regardless of the disease stage\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. The recent study from Pors J et al\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e demonstrated that patients with MAs without spindle cell components had a poorer prognosis, with a 5-year overall survival rate of 74% and progression-free survival rate of 60% in cervical MAs, compared to the findings of previous literature reviews. Additionally, patients with mesonephric carcinosarcomas had a recurrence rate of 22% and a mortality rate of 25%\u003csup\u003e6, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The limited follow-up data for MAs with spindle cell components makes prognostic evaluation challenging and unreliable. However, based on the available data, the recurrence rate of MAs with spindle cell components appears to be lower than that of MAs without spindle cell components and mesonephric carcinosarcomas, but higher than that of adenocarcinoma and squamous cell carcinoma in the cervix. MAs with spindle cell components seem to have an aggressive clinical behavior.\u003c/p\u003e \u003cp\u003eAll three patients we reported underwent hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. Two out of three patients received adjuvant chemotherapy with carboplatin and paclitaxel, and one patient also underwent adjuvant radiation therapy following primary surgery. Currently, there is no standardized treatment for this rare tumor. At present there is no standard treatment for this rare tumor. Treatments depend on the stage of MAs, and the treatment principles is consistent with other types of cervical adenocarcinomas\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. The majority of patients with early-stage MAs underwent hysterectomy with bilateral salpingo-oophorectomy, while a small proportion of patients also received adjuvant radiotherapy and chemotherapy\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. While adjuvant chemotherapy with carboplatin and paclitaxel is commonly used as first-line treatment, its role in early-stage MAs remains unclear\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Similarly, the efficacy of adjuvant radiotherapy is also unclear.\u003c/p\u003e \u003cp\u003eSpindle cell components in MAs are diagnostic pitfalls. In the two cases we reported, the initial diagnoses were initially considered to be mesenchymal tumors. Therefore, MAs should be included in the differential diagnosis when obvious spindle cell components are present morphologically, particularly in biopsy specimens. An immunohistochemical panel including PAX8, GATA3, CD10, and TTF1 should be used in the differential diagnosis. MAs typically exhibit luminal CD10 staining, negative or focal positive expression of ER and PR, and positive expression of PAX8\u003csup\u003e12\u003c/sup\u003e. Among the immunohistochemical markers mentioned above, GATA3 is a highly sensitive and specific marker for MAs\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. One case (case 3) from our study, GATA3 showed negative staining in the spindle cell areas and positive staining in the adenoid areas. The staining intensity of GATA3 may decrease in the solid areas, which is consistent with previous reports\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Therefore, it is worth noting that if a spindle cell component is recognized with GATA3 expression as negative or weakly positive in the biopsy specimen, it should also be suspected of being MA. TTF1 may be helpful in diagnosing cases where GATA3 is negatively expressed, due to the inverse staining pattern between GATA3 and TTF1\u003csup\u003e14\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCorrect diagnosis is challenging since MAs usually exhibit a variety of morphologic patterns, especially in biopsy specimens. The correct diagnostic rate is only 10% in initial biopsy specimens\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The overlapping morphology features of MAs with prominent spindle cell components make for a broader range of differential diagnoses. The main differential diagnoses include endocervical adenocarcinoma, clear cell carcinoma, and endometrioid adenocarcinoma. Endocervical adenocarcinoma, which is often associated with HPV, exhibits mucin production or ciliation. p16 shows diffuse staining in HPV-related endocervical adenocarcinomas, but shows patchy staining pattern in MAs. In cases with overlapping morphologic features that are difficult to diagnose, a combination of immunohistochemical markers such as CEA, p16, GATA3, and CD10 can be used. Clear cell carcinoma, HPV-independent adenocarcinoma, is characterized by clear, eosinophilic, and hobnailed tumor cells. It should be noted that HNF1β, a marker commonly used in the diagnosis of clear cell carcinoma, is also positively expressed in a subset of MAs\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Squamous and mucinous differentiation are helpful for the diagnosis of endometrial endometrioid adenocarcinoma. Immunohistochemical staining for ER and PR is usually positive in endometrioid adenocarcinoma.\u003c/p\u003e \u003cp\u003eMoreover, the most confusing differential diagnosis is mesonephric carcinosarcomas. Mesonephric carcinosarcomas, which are biphasic tumors, consist of distinguishable epithelial and frankly malignant spindle cell components\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. 16% of cervical carcinosarcomas originate from mesonephric duct remnants\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. According to Mirkovic et al\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e recommended that MAs with heterologous mesenchymal elements should be diagnosed as mesonephric carcinosarcomas. So far, reported heterologous sarcomatous components in the literature have included osteosarcoma, chondrosarcoma, and rhabdomyosarcoma, while the homologous component has been limited to endometrial stromal sarcoma\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The spindle cell components observed in MAs may be part of the morphologic spectrum of the tumors\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Epithelial immunohistochemical markers can be helpful in distinguishing between these entities.\u003c/p\u003e \u003cp\u003eConsistent with previous studies, no specific molecular events were found to differentiate MAs with spindle cell components from those without spindle cell components\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. The molecular alterations of MAs mainly included \u003cem\u003eKRAS/NRAS\u003c/em\u003e mutation, microsatellite stability, and gains of chromosome 1q\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Alterations in the RAS/MAPK pathway may contribute to the development of MAs\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. \u003cem\u003eKRAS/NRAS\u003c/em\u003e mutations are the most common molecular alterations in MAs, and they are mutually exclusive. \u003cem\u003eKRAS\u003c/em\u003e mutation is more recurrent than \u003cem\u003eNRAS\u003c/em\u003e mutation, and it has been reported that the majority of MAs (75%-100%) harbor \u003cem\u003eKRAS\u003c/em\u003e mutations which mainly affected the hotspot codons 12 and 13\u003csup\u003e8, 15, 19\u003c/sup\u003e. Common mutation sites include G12C, G12D, and G12V\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Other molecular changes also have been reported, which included chromatin remodeling genes of \u003cem\u003eARID1A/B\u003c/em\u003e and \u003cem\u003eSMARCA4\u003c/em\u003e\u003csup\u003e8\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe \u003cem\u003ePIK3CA\u003c/em\u003e encodes the p110α catalytic subunit of the class IA phosphatidylinositol 3-kinases (PI3Ks)\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Mutations in \u003cem\u003ePIK3CA\u003c/em\u003e can result in abnormally increased catalytic activity of PI3Ks, promoting cell carcinogenesis\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. In the female reproductive system \u003cem\u003ePIK3CA\u003c/em\u003e mutation is more common in endometrial and other types of cervical adenocarcinomas arising from the Mullerian ducts\u003csup\u003e\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. In the study of Mirkovic et al\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, \u003cem\u003ePIK3CA\u003c/em\u003e mutations were not identified from 13 cervical MAs. Subsequently, Silva et al\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e reported that two cervical MAs harbored \u003cem\u003eKRAS\u003c/em\u003e mutations and \u003cem\u003ePIK3CA\u003c/em\u003e mutations simultaneously. As far as we know, there have been no documented cases of \u003cem\u003ePIK3CA\u003c/em\u003e mutations without \u003cem\u003eKRAS\u003c/em\u003e or \u003cem\u003eNRAS\u003c/em\u003e mutations in MAs or mesonephric-like carcinomas. This study presents the first case of a cervical MA with a lone \u003cem\u003ePIK3CA\u003c/em\u003e mutation, without \u003cem\u003eKRAS\u003c/em\u003e or \u003cem\u003eNRAS\u003c/em\u003e mutation. Additionally, \u003cem\u003eCTNNB1\u003c/em\u003e mutations are commonly found in carcinomas originating from the Mullerian ducts, and a recent report described an MA with alterations in both \u003cem\u003eCTNNB1\u003c/em\u003e and \u003cem\u003eKRAS\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. These observations suggest that there are shared molecular alterations between MAs and carcinomas that arise from the Mullerian ducts.\u003c/p\u003e \u003cp\u003e \u003cem\u003eNTRK\u003c/em\u003e genes encode tropomyosin receptor kinases (Trk)\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Fusion of \u003cem\u003eNTRK1/2/3\u003c/em\u003e genes is the most common mechanism of Trk activation in various cancers\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. In malignant melanoma, the amplification of the \u003cem\u003eNTRK1\u003c/em\u003e gene is associated with poorer clinical outcomes\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. \u003cem\u003eNTRK1\u003c/em\u003e amplification was detected in both two cases of MAs with FIGO stage IIB that we reported. \u003cem\u003eNTRK1\u003c/em\u003e amplification may promote tumor cell proliferation in MAs leading to an advanced stage.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, MAs exhibit morphologic diversity, with those containing spindle cell components often associated with advanced stages and aggressive behavior. Prominent spindle cell components in MAs are diagnostic pitfalls especially in cervical biopsy specimens. Utilizing a panel of immunohistochemical stains may aid in the differential diagnosis. Despite \u003cem\u003eKRAS\u003c/em\u003e being the most frequently observed molecular alteration, \u003cem\u003ePIK3CA\u003c/em\u003e mutations can also be identified independently in MAs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work supported by Sichuan Science and Technology Program(2022NSFSC0708).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYingying Fan:\u003c/strong\u003e conceptualization, data curation, writing \u0026ndash; original draft. \u003cstrong\u003eYing He:\u003c/strong\u003e Data curation. \u003cstrong\u003eLiang Sun:\u003c/strong\u003e Data curation. \u003cstrong\u003eTianmin Liu:\u003c/strong\u003e Methodology. \u003cstrong\u003eYangmei Shen:\u003c/strong\u003e Conceptualization, writing \u0026ndash; review \u0026amp; editing, supervision, funding acquisition.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to restrictions related to participant confidentiality, the data are not publicly available. The data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of competing interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSajjad Y. Development of the genital ducts and external genitalia in the early human embryo. J Obstet Gynaecol Res 2010; 36: 929\u0026ndash;937.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHowitt BE and Nucci MR. Mesonephric proliferations of the female genital tract. Pathology 2018; 50: 141\u0026ndash;150.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMenon S, Kathuria K, Deodhar K, et al. 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Am J Surg Pathol 2018; 42: 227\u0026ndash;233.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamuels Y, Diaz LA, Jr., Schmidt-Kittler O, et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 2005; 7: 561\u0026ndash;573.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEngelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009; 9: 550\u0026ndash;562.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCancer Genome Atlas Research N, Kandoth C, Schultz N, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497: 67\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMjos S, Werner HMJ, Birkeland E, et al. PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer. Sci Rep 2017; 7: 10240.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcIntyre JB, Wu JS, Craighead PS, et al. PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy. Gynecol Oncol 2013; 128: 409\u0026ndash;414.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMontalvo N, Redroban L and Galarza D. Mesonephric adenocarcinoma of the cervix: a case report with a three-year follow-up, lung metastases, and next-generation sequencing analysis. Diagn Pathol 2019; 14: 71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCocco E, Scaltriti M and Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731\u0026ndash;747.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePasini L, Re A, Tebaldi T, et al. TrkA is amplified in malignant melanoma patients and induces an anti-proliferative response in cell lines. BMC Cancer 2015; 15: 777.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Mesonephric adenocarcinomas, Prognosis, Next generation sequencing, KRAS, PIK3CA","lastPublishedDoi":"10.21203/rs.3.rs-3942369/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3942369/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMesonephric adenocarcinomas (MAs) with spindle cell components are rare malignant tumors of the cervix. We conducted a retrospective analysis of MAs with spindle cell components. Clinicopathological data were collected from electronic surgical pathology records, and immunohistochemistry and targeted next-generation sequencing (NGS) were performed. The study included three postmenopausal women aged 51 to 60 years. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. There were no recurrences or deaths after surgery. The NGS analysis identified \u003cem\u003eKRAS\u003c/em\u003e mutations in two cases and a lone \u003cem\u003ePIK3CA\u003c/em\u003e mutation in one case. Spindle cell components could be a morphological feature of MAs in the advanced stage. Spindle cell components in MAs are diagnostic pitfalls, and the use of immunohistochemical panels and molecular detection is recommended for cases with overlapping morphological features. While \u003cem\u003eKRAS\u003c/em\u003e mutation is the most frequent molecular alteration, \u003cem\u003ePIK3CA\u003c/em\u003e mutation can be identified independently in cases without KRAS mutation.\u003c/p\u003e","manuscriptTitle":"Mesonephric adenocarcinoma of the uterine cervix with a prominent spindle cell component","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-21 18:12:21","doi":"10.21203/rs.3.rs-3942369/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3c0c2088-64dd-490d-888f-d2d6ce4fd6e2","owner":[],"postedDate":"February 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28837177,"name":"Biological sciences/Cancer/Gastrointestinal cancer"},{"id":28837178,"name":"Biological sciences/Molecular biology"}],"tags":[],"updatedAt":"2024-05-02T05:08:49+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-21 18:12:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3942369","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3942369","identity":"rs-3942369","version":["v1"]},"buildId":"oE6Zbj460LM0Up2FdVbMZ","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}