Perivascular epithelioid cell tumor of the uterine cervix identified on the liquid-based cytology: a case report

Perivascular epithelioid cell tumor of the uterine cervix identified on the liquid-based cytology: a case report | 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 Case Report Perivascular epithelioid cell tumor of the uterine cervix identified on the liquid-based cytology: a case report Xiao Tang, Min Feng, Yangmei Shen, Qijun Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2063779/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Jan, 2023 Read the published version in Diagnostic Pathology → Version 1 posted 7 You are reading this latest preprint version Abstract Background: Perivascular epithelioid cell tumours (PEComa) occurring in the female genital tract are rare, typically found in the uterine corpus. PEComa occurring in the cervix are extremely rare, and very few cases have been reported till now.Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported. Case presentation: A 55-year-old postmenopausal women presented with abnormal vagina discharges for three months. Then, a liquid-based cytology test was performed. Microscopically, some loosely cohesive epithelioid cells were uniform with abundant clear cytoplasm, showed predominantly round or oval nuclei with finely stippled chromatin, and distinct round nucleoli were visible in some cells, notably with numerous melanin pigments in the cytoplasm. The cytopathological features were well correlated with cell blocks and histopathological findings. Upon immunohistochemistry, the tumor cells were positive for HMB45, TFE3, focally positive for MelanA, while negative for muscle marker. Fluorescence in situ hybridization (FISH) confirmed TFE3 gene rearrangement. The final pathological diagnosis was PEComa identified by the liquid-based cytology, cell blocks, immunohistochemistry and FISH. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for two years with no evidence of disease. Conclusion: The cytologic characteristics of the tumor may provide sufficient clues for diagnosing a PEComa, including loosely cohesive, epithelioid morphology with abundant clear cytoplasm or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigment. That will help cytopathologists recognize this rare tumor that occurred in the cervix, combined with results of other detection methods, can achieve the definitive diagnosis of PEComa. Perivascular epithelioid cell tumor Uterine cervix Liquid-based cytology Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Perivascular epithelioid cell tumours (PEComas) are a rare group of mesenchymal neoplasms characterized by the presence of histologically and immunohistochemically distinctive perivascular epithelioid cells [ 1 ], which can occur in any part of the body. PEComa of the gynecological tract is very rare. It is most commonly encountered on the uterus corpus and very occasionally in the cervix, and only a few cases have been reported till now [ 2 ]. Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported in the available English literature [ 3 – 4 ]. We report a case of cervix PEComa identified by the liquid-based cytology test, cell blocks, and immunohistochemistry in a 55-year-old postmenopausal woman. Our finding indicated that a definitive diagnosis of PEComa can be rendered based on cytologic examination alone. Case Presentation A 55-year-old woman presented with abnormal vagina discharges for three months after four years of menopause. Then, a liquid-based cytology test (BD Prep) was performed. Microscopically, we observed some loosely cohesive atypical cells that arranged in single or clusters and sheets, which exhibited epithelioid morphology with abundant clear cytoplasm. The epithelioid cells were uniform and approximately the same size as parabasal cells (Fig. 1 A& 1 B), showed predominantly round or oval nuclei with finely stippled chromatin, and distinct round nucleoli were visible in some cells (Fig. 1 C), notably with numerous melanin pigments in the cytoplasm (Fig. 1 D). The initial diagnosis was atypical cells which were considered to be a malignant melanoma (MM). Then we made cell blocks from the remaining specimens. Cell blocks showed single or clusters of medium-sized epithelioid cells in a background of fibrinoid fluid, with abundant clear or granular eosinophilic cytoplasm. Prominent nucleoli can be observed in some cells. A few spindled nuclei and melanin pigment were also observed (Fig. 2 A). Immunocytochemical staining demonstrated that the epithelioid cells were positive for HMB45, TFE3 (Fig. 2 B& 2 C), focally positive for Melan-A, while negative for S-100, AE1/AE3, EMA, Desmin, SMA, H-caldesmon. Finally, combined with cell block and immunohistochemistry, a tentative diagnosis of PEComa was made, and with the statement that the final diagnosis will require more representative material. Subsequently, Transvaginal ultrasound examination showed an echogenic mass measuring 3 cm×2.6 cm×2.7cm in the cervix with increased vascularity (Fig. 3 ), the patient underwent a colposcopic biopsy, which further confirmed our diagnosis. The epithelioid cells demonstrated clear or granular eosinophilic cytoplasm with a central round to oval nuclei (Fig. 4 A), typically radial arrangements around blood vessels, and displayed no nuclear atypia and sparse mitotic activity. Numerous melanin pigments were observed (Fig. 4 B). Immunohistochemical expression was also consistent with previous cell blocks. Additionally, Fluorescence in situ hybridization (FISH) confirmed TFE3 gene rearrangement with the finding of split signal in tumor cell nuclei. The final pathological diagnosis was PEComa. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for two years with no evidence of disease. Discussion PEComas have been defined by the World Health Organization as “a member of a family of mesenchymal neoplasms composed of perivascular epithelioid cells (PECs) that express melanocytic and smooth muscle markers” [ 5 ]. PEComas arise most frequently in the uterine corpus and less commonly in the cervix. However, the diagnosis of PEcoma by cervical cytology is much rarer. So far, only two cases of cervix PEComa diagnosed by conventional cervical smear have been reported. Our case was the first reported cervix PEComa diagnosed by a liquid-based cytology test. Compared with conventional cervical smear, liquid-based cytology test has the characteristics of clear background, distinct cell structure, and uniform distribution. It is difficult to diagnose based on a conventional smear alone. Since the characteristic perivascular arrangement cannot be discerned in cytologic smears, the application of a panel of immunocytochemical markers on cell blocks is likely to suggest a diagnosis of PEComa [ 6 ], especially in unusual sites like the cervix. Fortunately, in our case, the cytological features were consistent with the later biopsies. The cytologic features of this patient were similar to those reported in the previous studies, but there are also some differences. The similarities are the tumor cells had an epithelioid morphology, appeared relatively uniform and discohesive, with characteristically abundant clear or granular eosinophilic cytoplasm, spindle cells or multinucleated giant cells in previously reported cases are not found in our case. Instead, our case contains a large number of melanin pigments in the cytoplasm, which is easy to be confused with MM. The tumor in the previously reported cases was initially diagnosed as a possible high-grade glandular lesion with a more specific diagnosis of clear cell carcinoma, and the other was reported as a tentative diagnosis of low-grade sarcoma. The final diagnosis of all cervix PEComa is based on the results of the biopsy. In our case, the tumor was initially considered as a MM because of the infrequent presence of spindle cells and a large number of melanin pigments in the cytoplasm. We did not include uterine sarcomas in the differential diagnosis. Combined with the results of cell blocks, IHC, subsequent colposcopic biopsy, and FISH, we finally diagnosed PEComa. The differential diagnoses by cytology include: 1. Malignant melanoma (MM): Tumor cells are typically pleomorphic, with discrete distribution ranging from round, oval, spindle-shaped, contained large nuclei, coarsely clumped, irregularly distributed chromatin prominent nucleoli. Additionally, binucleation and intranuclear pseudoinclusions may be identified. The cytoplasm is well defined with or without cytoplasmic melanin pigment. The background is dirty, necrotic, inflammatory, or hemorrhagic because of tumor diathesis [ 7 ]. IHC can be useful for differentiating these lesions. PEComa is positive for myoid markers and negative for S-100 protein expression in contrast to MM. Controversial cases can be identified by FISH. 2. Reactive endocervical cells: The nuclei of reactive cervical glandular cells show a variable increase in nuclear size, with prominent nucleoli and uniform finely stippled chromatin, and rare intracytoplasmic polymorphonuclear leukocytes are seen; Moreover, they are not as loosely cohesive as PEComa cells and are columnar in appearance. 3. Clear cell carcinoma (CCC): Although cytologically, there are some overlaps between CCC and PEComa, the nuclear pleomorphism of CCC is striking. It often contains prominent nuclei that can be hyperchromatic and pleomorphic and project into the glandular lumen to form hobnail cells. On IHC, CCC expresses epithelial markers (AE1/AE3 and EMA), and does not show the “myomelanocytic” phenotype of PEComa. 4. Endometrial or ovarian adenocarcinoma: Three-dimensional groups and clusters or papillary configurations are more common in endometrial or ovarian adenocarcinoma cells, and the nuclear atypia is more obvious, including nuclear hyperchromasia and pleomorphism. These features are uncommon in PEComa. 5. Alveolar soft part sarcoma (ASPS): ASPS is also rare in the cervix, but the cytological morphology and immunohistochemical features of PEComa and ASPS can sometimes be similar. Similar with PEComa, some ASPS also express TFE3 [ 8 ]. However, ASPS exhibits smooth muscle markers, such as SMA but is invariably negative for melanocytes marekers [ 9 ]. Although most PEComas harbor loss-of-function TSC1/TSC2 mutations, a small subset of PEComas shows rearrangement of the TFE3 gene [ 10 ]. Recently, it was suggested that TFE3 translocation-associated PEComas of the gynecologic tract represent a distinct form of this tumor. Morphological features of these tumors include alveolar or nested growth, predominant epithelioid component, low nuclear atypia, and rare mitoses, showing Strong expression of HMB-45 and TFE3, focal or absent for melanA and smooth muscle markers [ 8 ]. In our case, FISH confirmed TFE3 gene rearrangement. Both morphology and immunophenotype of the tumor were also consistent with those TFE3 translocation-associated PEComas described previously. Immunocytochemical staining were positive for HMB45, TFE3, focally positive for Melan-A, while negative for muscle markers. Because of the rarity of cervix PEComa, there are no standardized guidelines for treatment. Complete surgical resection with a tumor-free margin is usually considered to be the standard treatment [ 11 ]. Chemotherapy and radiotherapy have not yielded conclusive results [ 10 ]. Some histologic features associated with the aggressive behaviour of uterine PEComa, including Tumor size＞5cm, high nuclear grade, ＞1 mitosis/50 HPF, necrosis, and vascular invasion were absent in our case. The tumor displayed no evidence of malignancy. She underwent total hysterectomy with bilateral salpingo-oophorectomy and was followed up for two years without any evidence disease progression. In conclusion, this is the third such case of PEComa of the cervix reported in English literature. The cytologic characteristics of the tumor may provide sufficient clues for diagnosing a PEComa, including loosely cohesive, epithelioid morphology with abundant clear cytoplasm or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigment. The pathologist should be familiar with these cytological features, combined with results of other detection methods, can achieve the definitive diagnosis of PEComa. Abbreviations PEComas: Perivascular epithelioid cell tumours; FISH: fluorescence in situ hybridization; MM: malignant melanoma; CCC: Clear cell carcinoma; ASPS: Alveolar soft part sarcoma Declarations Ethics approval and consent to participate The need for ethics approval and consent was waived since consent for publication was obtained from the patient. Consent for publication We have obtained the patients’ consent for publication and there is no personal information of the patients in our case report. Availability of data and materials All data generated or analyzed during this case are included within the article. Competing interests The authors declare that they have no conflicts of interest. Funding Not applicable. Authors’ contributions Xiao Tang drafted the manuscript and assisted with the clinical data collection and interpretation. Qijun Chen participated in revising the manuscript. Min Feng and Yangmei Shen contributed to pathological examination and diagnoses. All the authors read and approved the final manuscript. Acknowledgments Not applicable. References Fadare O, Parkash V, Yilmaz Y, et al. Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal “PEComatosis”: a clinicopathological study with comparative genomic hybridization analysis. World J Surg Oncol. 2004;2(1):35. Papoutsis D, Sahu B, Kelly J, et al. Perivascular epithelioid cell tumour and mesonephric adenocarcinoma of the uterine cervix: an unknown co-existence. Oxf Med Case Reports. 2019;1:omy115. Stone JL, Batty T, Nicklin J. Cervical perivascular epithelioid cell tumour (PEComa) of the uterine cervix: Cytological findings in a cervical smear. Cytopathology. 2013;24(4):272–3. Tajima S, Koda K. Perivascular epithelioid cell tumor of the uterine cervix identified on a conventional cervical smear. Diagn Cytopathol. 2015;43(12):1011–6. WHO Classification of Tumours Editorial Board. WHO Classification of Female Genital Tumours. 5th ed. Lyon: IARC Press; 2020. Liu S, Li Z, Shen R. Metastatic malignant perivascular epithelioid cell tumor (PEComa) in parotid gland diagnosed by fine needle aspiration biopsy- a case report and literature review. Cytol Histol Rep. 2019: CHR–104. DOI:10.29011/ CHR-104. 100004. Deshpande AH, Munshi MM. Primary malignant melanoma of the uterine cervix: Report of a case diagnosed by cervical scrape cytology and review of the literature. Diagn Cytopathol. 2001;25(2):108–11. Schoolmeester JK, Dao LN, Sukov WR, et al. TFE3 translocationassociated perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: morphology, immunophenotype, differential diagnosis. Am J Surg Pathol. 2015;39(3):394–404. Jaber OI, Kirby PA. Alveolar soft part sarcoma. Arch Pathol Lab Med. 2015;139(11):1459–62. Kovac O, Babal P, Kajo K, et al. Perivascular Epithelioid Cell Tumor (PEComa) of the Uterine Cervix: A Case Report of a 43-Yr-Old Woman With Abnormal Uterine Bleeding Treated With Hysterectomy. Int J Gynecol Pathol. 2018;37(5):492–6. Liu CH, Chao WT, Lin SC, et al. Malignant perivascular epithelioid cell tumor in the female genital tract: preferred reporting items for systematic reviews and meta-analyses. Med (Baltim). 2019;98(2):e14072. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 16 Jan, 2023 Read the published version in Diagnostic Pathology → Version 1 posted Editorial decision: Major revision 05 Nov, 2022 Reviews received at journal 19 Oct, 2022 Reviewers agreed at journal 17 Oct, 2022 Reviewers invited by journal 16 Oct, 2022 Editor assigned by journal 14 Sep, 2022 Submission checks completed at journal 14 Sep, 2022 First submitted to journal 14 Sep, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-2063779","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":136780339,"identity":"3fcb1dbe-a22e-4e8d-a9e2-3283a84739ac","order_by":0,"name":"Xiao Tang","email":"","orcid":"","institution":"Department of Pathology, West China Second University Hospital, Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"","lastName":"Tang","suffix":""},{"id":136780340,"identity":"85cc6a6c-4ec2-4c9a-9d8d-7ee0e586144d","order_by":1,"name":"Min Feng","email":"","orcid":"","institution":"Department of 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Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtklEQVRIiWNgGAWjYDACCQYGAyCUY2NvPkCaFmM+nmMJxGsBgcR5EjkKxOngn928ofBHwZ30NoYcBoYfFduIsOTOsQJjHoNnuW0MZw8w9py5TViLgUSOgTGDweHcNsa+BGbGNiK1GP4wOJzOxsxjQLwWAx6DwwlsbMRqkbiRBvLLYcM2HraEg0T5hX9G8jbDH38Oy8vPf3zwwY8KIrQAgZkBjHWAKPVAYPyAWJWjYBSMglEwQgEAPGI39aF7o+YAAAAASUVORK5CYII=","orcid":"","institution":"Department of Pathology, West China Second University Hospital, Sichuan University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Qijun","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2022-09-14 07:59:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2063779/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2063779/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13000-023-01290-3","type":"published","date":"2023-01-16T18:25:25+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":26580127,"identity":"7c7b4cbe-4b76-4b6d-945c-a449a8daf626","added_by":"auto","created_at":"2022-09-16 20:49:27","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2921873,"visible":true,"origin":"","legend":"\u003cp\u003eThe epithelioid cells were uniform and approximately the same size as parabasal cells, which with abundant clear cytoplasm (\u003cstrong\u003eA\u0026amp;B\u003c/strong\u003e, Papanicolaou stain, ×400), showed predominantly round or oval nuclei with finely stippled chromatin, distinct round nucleoli were visible (\u003cstrong\u003eC\u003c/strong\u003e, Papanicolaou stain, ×400), numerous melanin pigments were observed in the cytoplasm (\u003cstrong\u003eD\u003c/strong\u003e, Papanicolaou stain, ×400).\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2063779/v1/6f279d0b4a79f6ac9e4b31c2.jpg"},{"id":26580128,"identity":"c10b041f-d471-4321-ab4c-e51ea5c4788e","added_by":"auto","created_at":"2022-09-16 20:49:27","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1151700,"visible":true,"origin":"","legend":"\u003cp\u003eCell blocks showed the epithelioid cells in a background of fibrinoid fluid, with abundant clear or granular eosinophilic cytoplasm (\u003cstrong\u003eA\u003c/strong\u003e, H\u0026amp;E, ×400).Immunocytochemical staining demonstrated that the epithelioid cells were positive for HMB45, TFE3 (\u003cstrong\u003eB\u0026amp;C\u003c/strong\u003e)\u003c/p\u003e","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2063779/v1/cd308468cc80ecd6ed477b85.jpg"},{"id":26580125,"identity":"011582e3-b1bb-4a6e-83c2-6e92699d1824","added_by":"auto","created_at":"2022-09-16 20:49:27","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":4333814,"visible":true,"origin":"","legend":"\u003cp\u003eTransvaginal ultrasound examination showedan echogenic mass measuring 3 cm×2.6 cm×2.7cm in the cervix with increased vascularity.\u003c/p\u003e","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2063779/v1/1eae76bcc483f3229deea16a.jpg"},{"id":26581295,"identity":"212e950c-b628-4f81-95fb-c74dd8e503f0","added_by":"auto","created_at":"2022-09-16 20:54:27","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1269736,"visible":true,"origin":"","legend":"\u003cp\u003eThe epithelioid cells revealed clear or granular eosinophilic cytoplasm with central round to oval nuclei (\u003cstrong\u003eA\u003c/strong\u003e, H\u0026amp;E, ×200), numerous melanin pigments were seen (\u003cstrong\u003eB\u003c/strong\u003e, H\u0026amp;E, ×200).\u003c/p\u003e","description":"","filename":"figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2063779/v1/f3ac207fa249ea5f5710e1b6.jpg"},{"id":44717209,"identity":"59e8579d-4395-478f-97ac-d705433b8e95","added_by":"auto","created_at":"2023-10-16 18:33:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1885580,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2063779/v1/c6efa0a9-6cef-49a9-83e7-7f3334dc54c3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Perivascular epithelioid cell tumor of the uterine cervix identified on the liquid-based cytology: a case report","fulltext":[{"header":"Background","content":"\u003cp\u003ePerivascular epithelioid cell tumours (PEComas) are a rare group of mesenchymal neoplasms characterized by the presence of histologically and immunohistochemically distinctive perivascular epithelioid cells [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], which can occur in any part of the body. PEComa of the gynecological tract is very rare. It is most commonly encountered on the uterus corpus and very occasionally in the cervix, and only a few cases have been reported till now [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported in the available English literature [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. We report a case of cervix PEComa identified by the liquid-based cytology test, cell blocks, and immunohistochemistry in a 55-year-old postmenopausal woman. Our finding indicated that a definitive diagnosis of PEComa can be rendered based on cytologic examination alone.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 55-year-old woman presented with abnormal vagina discharges for three months after four years of menopause. Then, a liquid-based cytology test (BD Prep) was performed. Microscopically, we observed some loosely cohesive atypical cells that arranged in single or clusters and sheets, which exhibited epithelioid morphology with abundant clear cytoplasm. The epithelioid cells were uniform and approximately the same size as parabasal cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA\u0026amp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB), showed predominantly round or oval nuclei with finely stippled chromatin, and distinct round nucleoli were visible in some cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC), notably with numerous melanin pigments in the cytoplasm (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD). The initial diagnosis was atypical cells which were considered to be a malignant melanoma (MM). Then we made cell blocks from the remaining specimens. Cell blocks showed single or clusters of medium-sized epithelioid cells in a background of fibrinoid fluid, with abundant clear or granular eosinophilic cytoplasm. Prominent nucleoli can be observed in some cells. A few spindled nuclei and melanin pigment were also observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Immunocytochemical staining demonstrated that the epithelioid cells were positive for HMB45, TFE3 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB\u0026amp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC), focally positive for Melan-A, while negative for S-100, AE1/AE3, EMA, Desmin, SMA, H-caldesmon. Finally, combined with cell block and immunohistochemistry, a tentative diagnosis of PEComa was made, and with the statement that the final diagnosis will require more representative material. Subsequently, Transvaginal ultrasound examination showed an echogenic mass measuring 3 cm\u0026times;2.6 cm\u0026times;2.7cm in the cervix with increased vascularity (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), the patient underwent a colposcopic biopsy, which further confirmed our diagnosis. The epithelioid cells demonstrated clear or granular eosinophilic cytoplasm with a central round to oval nuclei (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA), typically radial arrangements around blood vessels, and displayed no nuclear atypia and sparse mitotic activity. Numerous melanin pigments were observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). Immunohistochemical expression was also consistent with previous cell blocks. Additionally, Fluorescence in situ hybridization (FISH) confirmed \u003cem\u003eTFE3\u003c/em\u003e gene rearrangement with the finding of split signal in tumor cell nuclei. The final pathological diagnosis was PEComa. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for two years with no evidence of disease.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePEComas have been defined by the World Health Organization as \u0026ldquo;a member of a family of mesenchymal neoplasms composed of perivascular epithelioid cells (PECs) that express melanocytic and smooth muscle markers\u0026rdquo; [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]. PEComas arise most frequently in the uterine corpus and less commonly in the cervix. However, the diagnosis of PEcoma by cervical cytology is much rarer. So far, only two cases of cervix PEComa diagnosed by conventional cervical smear have been reported. Our case was the first reported cervix PEComa diagnosed by a liquid-based cytology test. Compared with conventional cervical smear, liquid-based cytology test has the characteristics of clear background, distinct cell structure, and uniform distribution. It is difficult to diagnose based on a conventional smear alone. Since the characteristic perivascular arrangement cannot be discerned in cytologic smears, the application of a panel of immunocytochemical markers on cell blocks is likely to suggest a diagnosis of PEComa [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e], especially in unusual sites like the cervix. Fortunately, in our case, the cytological features were consistent with the later biopsies.\u003c/p\u003e\n\u003cp\u003eThe cytologic features of this patient were similar to those reported in the previous studies, but there are also some differences. The similarities are the tumor cells had an epithelioid morphology, appeared relatively uniform and discohesive, with characteristically abundant clear or granular eosinophilic cytoplasm, spindle cells or multinucleated giant cells in previously reported cases are not found in our case. Instead, our case contains a large number of melanin pigments in the cytoplasm, which is easy to be confused with MM. The tumor in the previously reported cases was initially diagnosed as a possible high-grade glandular lesion with a more specific diagnosis of clear cell carcinoma, and the other was reported as a tentative diagnosis of low-grade sarcoma. The final diagnosis of all cervix PEComa is based on the results of the biopsy. In our case, the tumor was initially considered as a MM because of the infrequent presence of spindle cells and a large number of melanin pigments in the cytoplasm. We did not include uterine sarcomas in the differential diagnosis. Combined with the results of cell blocks, IHC, subsequent colposcopic biopsy, and FISH, we finally diagnosed PEComa.\u003c/p\u003e\n\u003cp\u003eThe differential diagnoses by cytology include: 1. Malignant melanoma (MM): Tumor cells are typically pleomorphic, with discrete distribution ranging from round, oval, spindle-shaped, contained large nuclei, coarsely clumped, irregularly distributed chromatin prominent nucleoli. Additionally, binucleation and intranuclear pseudoinclusions may be identified. The cytoplasm is well defined with or without cytoplasmic melanin pigment. The background is dirty, necrotic, inflammatory, or hemorrhagic because of tumor diathesis [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. IHC can be useful for differentiating these lesions. PEComa is positive for myoid markers and negative for S-100 protein expression in contrast to MM. Controversial cases can be identified by FISH. 2. Reactive endocervical cells: The nuclei of reactive cervical glandular cells show a variable increase in nuclear size, with prominent nucleoli and uniform finely stippled chromatin, and rare intracytoplasmic polymorphonuclear leukocytes are seen; Moreover, they are not as loosely cohesive as PEComa cells and are columnar in appearance. 3. Clear cell carcinoma (CCC): Although cytologically, there are some overlaps between CCC and PEComa, the nuclear pleomorphism of CCC is striking. It often contains prominent nuclei that can be hyperchromatic and pleomorphic and project into the glandular lumen to form hobnail cells. On IHC, CCC expresses epithelial markers (AE1/AE3 and EMA), and does not show the \u0026ldquo;myomelanocytic\u0026rdquo; phenotype of PEComa. 4. Endometrial or ovarian adenocarcinoma: Three-dimensional groups and clusters or papillary configurations are more common in endometrial or ovarian adenocarcinoma cells, and the nuclear atypia is more obvious, including nuclear hyperchromasia and pleomorphism. These features are uncommon in PEComa. 5. Alveolar soft part sarcoma (ASPS): ASPS is also rare in the cervix, but the cytological morphology and immunohistochemical features of PEComa and ASPS can sometimes be similar. Similar with PEComa, some ASPS also express TFE3 [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, ASPS exhibits smooth muscle markers, such as SMA but is invariably negative for melanocytes marekers [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eAlthough most PEComas harbor loss-of-function TSC1/TSC2 mutations, a small subset of PEComas shows rearrangement of the \u003cem\u003eTFE3\u003c/em\u003e gene [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Recently, it was suggested that \u003cem\u003eTFE3\u003c/em\u003e translocation-associated PEComas of the gynecologic tract represent a distinct form of this tumor. Morphological features of these tumors include alveolar or nested growth, predominant epithelioid component, low nuclear atypia, and rare mitoses, showing Strong expression of HMB-45 and TFE3, focal or absent for melanA and smooth muscle markers [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. In our case, FISH confirmed \u003cem\u003eTFE3\u003c/em\u003e gene rearrangement. Both morphology and immunophenotype of the tumor were also consistent with those \u003cem\u003eTFE3\u003c/em\u003e translocation-associated PEComas described previously. Immunocytochemical staining were positive for HMB45, TFE3, focally positive for Melan-A, while negative for muscle markers.\u003c/p\u003e\n\u003cp\u003eBecause of the rarity of cervix PEComa, there are no standardized guidelines for treatment. Complete surgical resection with a tumor-free margin is usually considered to be the standard treatment [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. Chemotherapy and radiotherapy have not yielded conclusive results [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Some histologic features associated with the aggressive behaviour of uterine PEComa, including Tumor size＞5cm, high nuclear grade, ＞1 mitosis/50 HPF, necrosis, and vascular invasion were absent in our case. The tumor displayed no evidence of malignancy. She underwent total hysterectomy with bilateral salpingo-oophorectomy and was followed up for two years without any evidence disease progression.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this is the third such case of PEComa of the cervix reported in English literature. The cytologic characteristics of the tumor may provide sufficient clues for diagnosing a PEComa, including loosely cohesive, epithelioid morphology with abundant clear cytoplasm or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigment. The pathologist should be familiar with these cytological features, combined with results of other detection methods, can achieve the definitive diagnosis of PEComa.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePEComas: Perivascular epithelioid cell tumours; FISH: fluorescence in situ hybridization; MM: malignant melanoma; CCC: Clear cell carcinoma; ASPS: Alveolar soft part sarcoma\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe need for ethics approval and consent was waived since consent for publication was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have obtained the patients\u0026rsquo; consent for publication and there is no personal information of the patients in our case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this case are included within the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXiao Tang drafted the manuscript and assisted with the clinical data collection and interpretation. Qijun Chen participated in revising the manuscript. Min Feng and Yangmei Shen contributed to pathological examination and diagnoses. All the authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFadare O, Parkash V, Yilmaz Y, et al. Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal \u0026ldquo;PEComatosis\u0026rdquo;: a clinicopathological study with comparative genomic hybridization analysis. World J Surg Oncol. 2004;2(1):35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapoutsis D, Sahu B, Kelly J, et al. Perivascular epithelioid cell tumour and mesonephric adenocarcinoma of the uterine cervix: an unknown co-existence. Oxf Med Case Reports. 2019;1:omy115.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStone JL, Batty T, Nicklin J. Cervical perivascular epithelioid cell tumour (PEComa) of the uterine cervix: Cytological findings in a cervical smear. Cytopathology. 2013;24(4):272\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTajima S, Koda K. Perivascular epithelioid cell tumor of the uterine cervix identified on a conventional cervical smear. Diagn Cytopathol. 2015;43(12):1011\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWHO Classification of Tumours Editorial Board. WHO Classification of Female Genital Tumours. 5th ed. Lyon: IARC Press; 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu S, Li Z, Shen R. Metastatic malignant perivascular epithelioid cell tumor (PEComa) in parotid gland diagnosed by fine needle aspiration biopsy- a case report and literature review. Cytol Histol Rep. 2019: CHR\u0026ndash;104. DOI:10.29011/ CHR-104. 100004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeshpande AH, Munshi MM. Primary malignant melanoma of the uterine cervix: Report of a case diagnosed by cervical scrape cytology and review of the literature. Diagn Cytopathol. 2001;25(2):108\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoolmeester JK, Dao LN, Sukov WR, et al. TFE3 translocationassociated perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: morphology, immunophenotype, differential diagnosis. Am J Surg Pathol. 2015;39(3):394\u0026ndash;404.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaber OI, Kirby PA. Alveolar soft part sarcoma. Arch Pathol Lab Med. 2015;139(11):1459\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKovac O, Babal P, Kajo K, et al. Perivascular Epithelioid Cell Tumor (PEComa) of the Uterine Cervix: A Case Report of a 43-Yr-Old Woman With Abnormal Uterine Bleeding Treated With Hysterectomy. Int J Gynecol Pathol. 2018;37(5):492\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu CH, Chao WT, Lin SC, et al. Malignant perivascular epithelioid cell tumor in the female genital tract: preferred reporting items for systematic reviews and meta-analyses. Med (Baltim). 2019;98(2):e14072.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"diagnostic-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dpat","sideBox":"Learn more about [Diagnostic Pathology](http://diagnosticpathology.biomedcentral.com)","snPcode":"13000","submissionUrl":"https://submission.nature.com/new-submission/13000/3","title":"Diagnostic Pathology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Perivascular epithelioid cell tumor, Uterine cervix, Liquid-based cytology","lastPublishedDoi":"10.21203/rs.3.rs-2063779/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2063779/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePerivascular epithelioid cell tumours (PEComa) occurring in the female genital tract are rare, typically found in the uterine corpus. PEComa occurring in the cervix are extremely rare, and very few cases have been reported till now.Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e A 55-year-old postmenopausal women presented with abnormal vagina discharges for three months. Then, a liquid-based cytology test was performed. Microscopically, some loosely cohesive epithelioid cells were uniform with abundant clear cytoplasm, showed predominantly round or oval nuclei with finely stippled chromatin, and distinct round nucleoli were visible in some cells, notably with numerous melanin pigments in the cytoplasm. The cytopathological features were well correlated with cell blocks and histopathological findings. Upon immunohistochemistry, the tumor cells were positive for HMB45, TFE3, focally positive for MelanA, while negative for muscle marker. Fluorescence in situ hybridization (FISH) confirmed \u003cem\u003eTFE3 \u003c/em\u003egene rearrangement. The final pathological diagnosis was PEComa identified by the liquid-based cytology, cell blocks, immunohistochemistry and FISH. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for two years with no evidence of disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The cytologic characteristics of the tumor may provide sufficient clues for diagnosing a PEComa, including loosely cohesive, epithelioid morphology with abundant clear cytoplasm or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigment. That will help cytopathologists recognize this rare tumor that occurred in the cervix, combined with results of other detection methods, can achieve the definitive diagnosis of PEComa.\u003c/p\u003e","manuscriptTitle":"Perivascular epithelioid cell tumor of the uterine cervix identified on the liquid-based cytology: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-16 20:49:25","doi":"10.21203/rs.3.rs-2063779/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-11-05T23:34:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-10-19T11:12:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"9abbbb4c-965e-4566-9675-d7a0087030fc","date":"2022-10-17T05:38:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-10-17T00:33:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-09-15T01:42:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-09-15T00:59:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Diagnostic Pathology","date":"2022-09-14T07:57:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"diagnostic-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dpat","sideBox":"Learn more about [Diagnostic Pathology](http://diagnosticpathology.biomedcentral.com)","snPcode":"13000","submissionUrl":"https://submission.nature.com/new-submission/13000/3","title":"Diagnostic Pathology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8e255c65-6da5-4eb9-a0d4-c6c1a2959101","owner":[],"postedDate":"September 16th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T18:29:13+00:00","versionOfRecord":{"articleIdentity":"rs-2063779","link":"https://doi.org/10.1186/s13000-023-01290-3","journal":{"identity":"diagnostic-pathology","isVorOnly":false,"title":"Diagnostic Pathology"},"publishedOn":"2023-01-16 18:25:25","publishedOnDateReadable":"January 16th, 2023"},"versionCreatedAt":"2022-09-16 20:49:25","video":"","vorDoi":"10.1186/s13000-023-01290-3","vorDoiUrl":"https://doi.org/10.1186/s13000-023-01290-3","workflowStages":[]},"version":"v1","identity":"rs-2063779","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2063779","identity":"rs-2063779","version":["v1"]},"buildId":"MNcDy3x_fV0tqtF8t3uB_","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}