TFE3 Associated Perivascular Epithelioid Cell Tumor with Complete Response to mTOR Inhibitor Therapy: Report of First Case and Literature Review

TFE3 Associated Perivascular Epithelioid Cell Tumor with Complete Response to mTOR Inhibitor Therapy: Report of First Case and Literature Review | 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 Research Article TFE3 Associated Perivascular Epithelioid Cell Tumor with Complete Response to mTOR Inhibitor Therapy: Report of First Case and Literature Review ROLI PURWAR, Kishan Soni, Mridula Shukla, Ashish Verma, Tarun Kumar, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-915540/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Mar, 2022 Read the published version in World Journal of Surgical Oncology → Version 1 posted 15 You are reading this latest preprint version Abstract Background : Perivascular epitheloid cell tumor (PEComas) are characterised by expression of both muscles, most often smooth muscle actin (in ~80% of cases) and melanocytic markers (mainly HMB-45 and Melan A). TFE 3 associated PEComas are new variant which are poorly defined due to their limited reports in literature. These tumors lack response to targeted mTOR inhibitor therapy due to lack of mutation in TSC gene. Hereby we are reporting a case of TFE3 associated pelvic PEComa showing excellent response to Everolimus. Case presentation : A 45-year-old female presented with complaint of abdominal mass and bleeding per vaginum for 4 months. She had a history of total abdominal hysterectomy 3 years back in view of abnormal uterine bleeding and exploratory laprotomy 7 months back to remove some pelvic mass. Imaging suggested of ill-defined heterogenous mass of 9.3 x 9.2 x 16 cm involving uterus, cervix and upper 1/3 vagina. Multiple omental and peritoneal deposits were also seen, making probable diagnosis of carcinoma endometrium. USG guided biopsy showed cores of fibrous tissue with presence of cells in sheets with granular eosinophillic cytoplasm, IHC showed positivity for TFE -3, H Caldesmon, GATA-3, Melan A-and HMB-45, Ki 67 index was 35%. On the basis of above diagnosis of PEComa was made and she was started on Everolimus, repeat imaging after 3 months of therapy, showed complete response. Conclusion : We are reporting first case of malignant pelvic TFE 3 PEComa showing response to mTOR therapy. Identification of TFE 3 PEComa is important because they showed different biologic behaviour then their conventional PEComa. Oncology Perivascular epitheliod cell tumor Mtor Therapy TFE3 PEComa uterus Gynecological Figures Figure 1 Figure 2 Figure 3 Figure 4 Background WHO defines perivascular epitheloid cell tumor (PEComas) as "mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells", including angiomyolipoma, clear cell sugar tumors of the lungs, lymphagioleiomyomatosis, hepatic falciform ligament clear cell myomelanocytic tumor and other unusual clear cell tumors at various locations.[ 1 ] PEComa tumors are characterised by expression of both muscles, most often smooth muscle actin (in ~ 80% of cases) and melanocytic markers (mainly HMB-45 and Melan A), which is one of the main characteristic feature [ 2 ]. These tumors usually show female preponderance with mean age of presentation around 45 years. Anatomically these have a ubiquitous appearance, with most common site of origin being kidney, lung and liver. Uterus is the most common site for genitourinary tract PEComa [ 3 ]. PEComas are initially divided into three categories by Folpe et al., as benign (no atypical features), uncertain malignant potential (nuclear atypia or size > 5cm) and malignant by any 2 morphological and pathological criteria such as gross size (> 5cm), high nuclear grade, necrosis, vascular invasion, or a mitotic rate higher than or one per 50 HPF [ 4 ]. Schoolmeester later classified these lesions as malignant when these lesions meet four out of the five above mentioned criteria [ 5 ]. In a largest case series reported till now by Bennet et al., of 32 uterine PEComas, most common clinical presentation were non-specific like menstrual complaints (33%), pelvic mass/adnexal mass/ uterine mass (17%), presumed fibroids (17%), metastasis from uterine primary (7%), cervical polyp (3%). At the time of disease reporting, metastasis was found in 17% cases with most common site being the lung [ 6 ]. Commonly, pre-operative diagnosis of PEComa is rare due to the presence of nonspecific imaging features. These lesions are usually confused with leiomyomas and leiomyosarcomas [ 6 ]. PEComas are usually sporadic, but 6% of cases are associated with tuberous sclerosis with mutation in TSC1 and TSC 2 gene [ 7 ]. TFE 3 or transcription factor binding to IGHM enhancer 3, associated PEComa, are newly defined verities of PEComa. Around 20% of PEComas were found to be positive for TFE3 nuclear staining, among which many of them harbour TFE3 gene rearrangement. TFE-3 is a member of microphthalmia associated transcription (MiT) family of transcription factors, which includes MITF, TFE-3, TFE B and TFEC gene located at chromosome Xp11.2. MiTF-TFE family assist in development of melanocytic cells. These tumors strongly express diffuse positiveness for HMB-45 and TFE-3, whereas it is weakly positive or negative for SMA and negative for melan A. TFE 3 associated PEComas can be associated with prior history of chemotherapy [ 8 ]. Other tumors which similarly expresses TFE 3 gene are melanoma, clear cell sarcoma, alveolar soft part sarcoma and translocation-associated renal cell carcinoma. These tumors are considered as microphthalmia associated transcription factor family of tumors [ 9 ]. In this article, we report a case of TFE 3 positive uterine PEComa, with a mixed cell pattern of both epitheliod and spindle cells, which strongly express HMB-45, Melan A, SMA and surprisingly responds to everolimus (mTOR inhibitor). Case Report A 45-year-old female presented to surgical oncology outpatient with a chief complaint of abdominal mass and per vaginal bleed for four months. As stated by the patient, she had undergone an abdominal surgical exploration before 7 months to remove pelvic mass. The patient also gave history of total abdominal hysterectomy before 3 years in view of abnormal uterine bleeding. However, the patient did not have any documentation regarding the above-mentioned surgeries. The patient did not have any significant personal and family history. On clinical examination general condition was fair, vitals were stable, pallor was present, on per abdominal examination, a large, soft abdominopelvic mass of 15x 15 cm in size was found, which was fixed, non-tender, not moving with respiration and was more deviated towards the left side. On per speculum examination, the vault was found replaced by a big smooth growth occupying upper 2/3rd of vagina, but no vaginal invasion was present. On per vaginum, a smooth lobular abdominopelvic mass of around 15x 15 cm was felt arising from vault. Routine biochemical investigations were within normal limit, except for haemoglobin level, which was 9gm%. An MRI was done which showed ill-defined heterogeneously enhancing mass lesion noted involving uterus and cervix, measuring 9.3 x 9.2 x 16 cm (AP X TR X CC). The lesion was invading adjacent myometrium, reaching up to serosa in the fundal region. It was also infiltrating the bilateral adnexa, but bilateral ovaries were not separately visualised. Inferiorly involvement extended till the upper 1/3 of vagina. Anteriorly the lesion was closely abutting the urinary bladder with suspicious loss of fat planes at places. Enlarged and necrotic common iliac lymph nodes were noted, largest measuring 1.1 cm. Multiple omental and peritoneal deposits were noted, largest measuring 4.2 x 2.9 cm. MRI suggested a probable diagnosis of endometrial carcinoma with extensions (Fig. 1A). An USG guided biopsy was taken from the pelvic mass, which on histopathological examination, showed cores of fibrous tissue along with presence of cells in sheets, micro papillae, perivascularly arranged and were polygonal with well-defined cytoplasmic borders, granular eosinophilic cytoplasm, central to eccentric round nuclei( Fig. 3 a, 3 b, 3 c). Few cells showed nuclear inclusion, occasional psammomatous calcification which suggest of neoplastic etiology. An immunohistochemistry (IHC) panel was requested which revealed TFE − 3 score 3+, H Caldesmon score 1+, GATA-3 score 1+, Melan A-score 4+, and HMB-45, score 4 +. Ki 67- positivity was seen in 30–35% of tumor cells( Fig. 4a, 4b, 4c, 4d). On the basis of histopathological and IHC analysis, the diagnosis of perivascular tumor with melanocytic differentiation was made and the possibility of TFE associated with PEComa was favoured. On considering this diagnosis, the patient was started on everolimus 10 mg OD. She was kept on monthly follow-up, in every visit she was symptomatically improved. After 3 months of therapy, she was again examined, and there was no mass/ lump palpable, on per abdomen and per vaginum examination. Repeat MRI pelvis was done which showed nearly resolution of pre-existing mass with decreased signal intensity showing nonviable remnants (Fig. 1B).As per RECIST(Response Evaluation Criteria in Solid Tumors) criteria, tumor shows partial response with mTOR inhibitors within 3 months of therapy. She was again followed after 6 months of therapy, there was again no mass /lump palpable on examination, MRI was repeated again showing no evidence of any solid mass lesion or altered enhancement noted, urinary bladder( straight long arrow) and rectum(straight short arrow) can now be clearly seen without compression in pelvis( Fig. 2 ), suggesting complete response as per RECIST criteria. Discussion And Conclusions Uterine PEComas is a rare entity, on which around 150 cases have been reported in English literature till now. There are two distinct pattern of identified in PEComas- first with epithelioid pattern (100% cases)-these are polygonal cells with clear to granular cytoplasm, and positive for melanocytic markers HMB45, Melan-A and MITF. The second being the spindle cell pattern (37% of cases), which consists of cells with less cytoplasm, arranged in fascicles like smooth muscle and are positive for SMA, desmin, caldesmon. HMB-45 is the most sensitive marker being positive in 100% cases. The diagnosis should always be differentiated from smooth muscle tumors of uterus and especially tumors which showed similar IHC like epithelioid smooth muscle tumor of uterus, high grade endometrial stromal sarcoma (HGESS), GIST, melanoma involving the uterus [ 10 ]. CD10, is diffuse and shows strong immunoreactivity in endometrial stromal tumors, GIST shows strong CD34 staining, as well as c-Kit positivity and negative for melanocytic marker. Metastatic melanoma and/or clear cell sarcoma shows strong S-100 protein immunoreactivity of the former and their muscle marker negativity. PEComas with TFE3 gene rearrangement have predominant epithelioid morphology with clear cells and have strongly positive staining for melanocytic markers like HMB-45 and Cathepsin K and weak or negative expression of myoid markers. Their rare variant is TFE 3 gene mixed cell PEComa with both epitheliod and spindle cell pattern. Morphologically these showed clear to granular cytoplasm with eosinophilic cells and showed marked immune expression for HMB-45, TFE-3, Melan A and also positive for myoid markers [ 5 ]. These lesions either represent collision between PEComa and smooth muscle tumor or PEComa with smooth muscle differentiation, which can be answered only by molecular analysis (Bennet 2018). This rearrangement can be explained by TFE3 fusing with other genes or undergoing breakage at different points along the gene [ 5 ]. In general, PEComa shows favourable prognosis, [ 4 ] but TFE3 associated PEComas show aggressive behaviour (52%of cases) and poor prognosis during follow up [ 9 , 11 , 12 ]. Folpe et al., showed that TFE3 fusion PEComa has an invasive behaviour, local recurrence and metastasis rates of 8.7% and 20.3%, respectively [ 4 ]. Careful review of English literature revealed only 10 cases of uterine and cervix pecoma with TFE3 rearrangement. Table-1 shows its clinical profile, treatment and follow up status. Table-2 shows the immunohistochemical profile of uterine PEComas. Table 1 Features of uterine TFE3 translocation associated PEComa Year Age(years) Site Clinical features Past h/o Size(cm) Pathology Treatment Follow up Outcome 1 Cho 2008 [ 13 ] 9 Uterus, lower uterine segment Vaginal spotting, metastases to pelvic lymph nodes at presentation None 5 Alveolar, epitheliod TAH + pelvic LN dissection ALL occured at 25 months Died at 33 months because of ALL, no e/o recurrence of pecoma at time of death 2 Liu 2014 [ 14 ] 34 Cervix AUB None 9 Sheets/ alveolus/nests Resection of cervical mass 5 months Alive 3 Schoolmester 2015 [ 5 ] 53 Uterine corpus AUB None 17 Sheet like nested Supracervical hysterectomy, RSO 2 months: cervix and metastases to omentum treated by radical trachelectomy, upper vaginectomy, omentectomy and adjuvant chemotherapy 11 months: small and large intestine and intraabomdinal cavity treated by debulking and adjuvant chemotherapy Alive; intraabdominal recurrence led to diagnosis revision from high grade LMS to pecoma; recently started sirolimus regimen 4 Schoolmester 2015 [ 5 ] 49 Uterine corpus Uterine mass Hodgkin lymphoma treated with ABVD chemotherapy (6 years prior) 33 Nested TAH-BSO 25 months Recurrence -none Alive, ned 5 Schoolmester 2015 [ 5 ] 47 Pelvis, site not identified Pelvic pain Morcellated supracervical hysterectomy with cellular leiomyomata (1 year prior) 8 Nested Local excision of pelvic mass, radical trachelectomy, bso, pelvic and paraaortic lymphadenopathy, omentectomy, staging biopsies 57 months Recurrence-urinary bladder treated by excision Alive, ned 6 Schoolmester 2015 [ 5 ] 46 Uterine corpus Unknown None 1 Nested Hysterectomy 1 month Recurrence- none Alive, ned 7 Choi 2016 [ 15 ] 67 Uterus AUB Ns 6 Spindle cells TAH + BSO Ns Multiple metastasis in lung and liver Ns 8 Bennet 2018 [ 6 ] Ns Uterus Ns Ns Ns Nested Ns 19 months Alive 9 Gianella 2020 [ 11 ] 45 Uterus Cyclic abdominopelvic pain and chronic constipation K/c/o breast cancer, treated with quadrantectomy, axillary dissection, and radiotherapy, Followed by tamoxifen therapy for five years 4 Nested architecture with thin-walled vascular spaces and was Composed of large cells with a clear to granular eosinophilic cytoplasm, round to ovoid nucleus, and Prominent nucleoli TLH with a bilateral salpingectomy. 2 years, no recurrence Alive 10 Hu 2020 [ 16 ] 53 Uterine endom etrial polyp Irregular menstruation K/c/o ca breast, h/o MRM f/b tamoxifen x 4 years 2 Epitheliod cells with nested architecture TLH 5months Alive Note- TAH- Total abdominal hysterectomy, TLH-Total laproscopic hysterectomy, RSO- right salpingoopherectomy, AUB- abnormal uterine bleeding, ALL- acute lymphocytic leukemia, LMS- liomyosarcoma, NS-not specified, MRM-modified radical mastectomy, BSO-bilateral salphingoophorectomy, NED-no evidence of disease Table 2 Immunohistochemical and Molecular Profile of Uterine PEComas Case no HMB 45 MELAN A CATHEPSIN K TFE 3 SMA DESMIN Caldesmon Ki 67 FISH 1 positive 0 positive positive 0 0 ns - Not done 2 3+ 3+ - 3+ 0 - - 2+ + 3 4+ 2+ 4+ 4+ 0 0 0 + 4 4+ 0 4+ 4+ 0 0 0 + 5 4+ 1+ 4+ 4+ 0 1+ 0 + 6 4+ 0 4+ 4+ - 0 0 + 7 3+ + - 3+ + + - 5% Not done 8 4+ - 4+ 4+ 4+ - - PSF-TFE3 9 positive ns positive positive Focal positive - - Not done 10 positive positive positive positive - - - 5% + Present case 4+ 4+ - 3+ - - 1+ 30% Not done In all the above cases reported in literature, the pelvic tumors were managed by primary surgical resection. In maximum of the above mentioned cases, diagnosis was confirmed postoperatively. Most of the cases does not contain any information regarding follow-up and further management. No effective therapy with TFE 3 rearranged PEComa in advanced extrarenal cases have been mentioned in the literature. Chemotherapy (CT) and radiotherapy (RT) have also been reported in literature with advanced PEComa cases. Since there is paucity of cases, poor results reported with variety of treatment modalities and no randomised trial conducted, no uniform consensus has been achieved in this regard. Both neoadjuvant and adjuvant CT (dacarbazine, ifosfamide, doxorubicin, vincristine), has been reported, but heterogenous results were achieved regarding disease progression and survival free interval. Regarding targeted therapy, the use of mTOR inhibitors in conventional metastatic PEComas with TSC1 and TSC2 mutation has been reported in very few cases at other extrarenal sites with promising results, however, further prospective studies are needed [17]. TFE 3 rearranged PEComas do not involve TSC2 gene, thus biologically these tumors behave distinctly with conventional PEComa and do not respond to mTOR inhibitors[5]. Xu et al., has reported a case of gastrointestinal PEComa with TFE3 rearrangement which did not responded to Everolimus, hence they switched to anti-VEGFR2 and Apatinib, for which the tumor remained stable and the progression free survival lasted for about 7 months [18]. Another case of ovarian TFE3 reactive PEComa was reported, which did not responded to sirolimus and develop liver recurrence [19]. Although our case showed strong nuclear positivity for TFE3, due to non affordability, the patient refused for FISH analysis to look for genetic rearrangements. In spite of TFE3 reactivity, our patient responded very well with Everolimus, in contrast to other cases reported in the literature. Prompt identification of TFE-3 PEComa is recommended before starting their management, since these tumors show different biological behaviour as compared to the conventional counterpart, which can lead to important insight into their management and the targeted therapies. Since very few cases have been reported in literature, further studies are needed to clearly define their clinical characteristics, prognosis and management. We have reported the first case of TFE 3 reactive PEComa which showed an appreciable response to Everolimus. List Of Abbreveations Perivascular epitheloid cell tumor (PEComas) Chemotherapy (CT) Radiotherapy (RT) Immunohistochemistry (IHC) RECIST(Response Evaluation Criteria in Solid Tumors) Declarations Ethics approval and consent to participate Ethical approval is not required as patient consent for publication was obtained. Consent for publication The written consent for publication of case report and accompanied images was obtained from the patient. Competing interests The authors declare that there are no competing interests. Acknowledgement None. Funding None. Availability of data and materials Not applicable as all information and data is presented in the manuscript. Authors contribution RP and KS did the literature search and prepared the draft manuscript. MS, TK and AV helped in preparation of manuscript and edited the manuscript for scientific content. MP conceived and designed the study and edited the final manuscript. All authors read and approved the final manuscript. References Fletcher CDM, Unni KK, Mertens F, et al. International Academy of Pathology: Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press; 2002. Tan Y, Zhang H, Xiao EH. Perivascular epithelioid cell tumour: dynamic CT, MRI and clinicopathological characteristics analysis of 32 cases and review of the literature. Clin Radiol. 2013;68:555–61. Bao L, Shi Y, Zhong J, Zhao M, Wu J, Hai L, Xu X, Du H, Shi Y. Histopathologic characteristics and immunotypes of perivascular epithelioid cell tumors (PEComa). Int J Clin Exp Pathol. 2019 Dec 1;12(12):4380–4389. PMID: 31933841; PMCID: PMC6949869. Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol. 2005;29:1558–75. Schoolmeester JK, Dao LN, Sukov WR, Wang L, ParkKJ, Murali R, Hameed MR, Soslow RA. TFE3 translocation-associated perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: morphology, immunophenotype, differential diagnosis. Am J Surg Pathol. 2015;39:394–404. Bennett JA, Braga AC, Pinto A, Van de Vijver K, Cornejo K, Pesci A, Zhang L, Morales-Oyarvide V, Kiyokawa T, Zannoni GF, Carlson J, Slavik T, Tornos C, Antonescu CR, Oliva E. Uterine PEComas: A Morphologic, Immunohistochemical, and Molecular Analysis of 32 Tumors. Am J Surg Pathol. 2018 Oct;42(10):1370–83. doi: 10.1097/PAS.0000000000001119 . PMID: 30001237; PMCID: PMC6133752. Shan W, Shi Y, Zhu Q, Yang B, Xie L, Li B, Ning C, Lv Q, Cheng Y, Xie B, Bai M, Xu Y, Chen X, Luo X. Five cases of uterine perivascular epithelioid cell tumors (PEComas) and review of literature. Arch Gynecol Obstet. 2019 Jan;299(1):185–190. doi: 10.1007/s00404-018-4920-4 . Epub 2018 Oct 13. PMID: 30317387. Vannucchi M, Minervini A, Salvi M, Montironi R, Raspollini MR. TFE3 Gene Rearrangement in Perivascular Epithelioid Cell Neoplasm (PEComa) of the Genitourinary Tract. Clin Genitourin Cancer. 2020 Dec;18(6):e692–7. doi: 10.1016/j.clgc.2020.04.004 . Epub 2020 May 15. PMID: 32576448. Shen Q, Rao Q, Xia QY, Yu B, Shi QL, Zhang RS, Zhou XJ. Perivascular epithelioid cell tumor (PEComa) with TFE3 gene rearrangement: clinicopathological, immunohistochemical, and molecular features. Virchows Arch. 2014 Nov;465(5):607–13. doi: 10.1007/s00428-014-1655-x . Epub 2014 Sep 20. PMID: 25239799. Parra-Herran C, Howitt BE. Uterine Mesenchymal Tumors: Update on Classification, Staging, and Molecular Features. Surg Pathol Clin. 2019 Jun;12(2):363–396. doi: 10.1016/j.path.2019.01.004 . PMID: 31097109. Giannella L, Delli Carpini G, Montik N, Verdecchia V, Puccio F, Di Giuseppe J, Tsiroglou D, Goteri G, Ciavattini A. Ultrasound Features of a Uterine Perivascular Epithelioid Cell Tumor (PEComa): Case Report and Literature Review. Diagnostics (Basel). 2020 Aug 3;10(8):553. doi: 10.3390/diagnostics10080553 . PMID: 32756336; PMCID: PMC7459969. Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S. etal. Integrative Genomic Analyses Identify Mitf as a Lineage Survival Oncogene Amplified in Malignant Melanoma. Nature. 2005;436:117–22. Cho HY, Chung DH, Khurana H, et al. The role of TFE3 in PEComa. Histopathology. 2008;53:236–49. [PubMed: 18510571]. Liu F, Zhang R, Wang ZY, et al. Malignant perivascular epithelioid cell tumor (PEComa) of cervix with TFE3 gene rearrangement: a case report. Int J Clin Exp Pathol. 2014;7:6409–14. [PubMed: 25337301]. Choi YJ, Hong JH, Kim A, et al. A Case of Malignant PEComa of the Uterus Associated with Intramural Leiomyoma and Endometrial Carcinoma. J Pathol Transl Med. 2016;50:469–73. [PubMed: 27452081]. Hu Y, Wang L, Shi H, Hu B. Endometrial polyp-like perivascular epithelioid cell neoplasm associated with TFE3 translocation: report of one case. Int J Clin Exp Pathol. 2020 Mar 1;13(3):543–549. PMID: 32269693; PMCID: PMC7137019. Musella A, De Felice F, Kyriacou AK, Barletta F, Di Matteo FM, Marchetti C, Izzo L, Monti M, Benedetti Panici P, Redler A, D'Andrea V. Perivascular epithelioid cell neoplasm (PEComa) of the uterus: A systematic review. Int J Surg. 2015 Jul;19:1–5. doi: 10.1016/j.ijsu.2015.05.002. Epub 2015 May 14. PMID: 25981307. Xu J, Gong XL, Wu H, Zhao L. Case Report: Gastrointestinal PEComa With TFE3 Rearrangement Treated With Anti-VEGFR TKI Apatinib. Front Oncol. 2020 Nov;23:10:582087. doi: 10.3389/fonc.2020.582087 . PMID: 33330059; PMCID: PMC7719820. Lin RJ, Melamed J, Wu J. PEComa with Transcription Factor E3 Overexpression: A Diagnostic and Therapeutic Challenge. Case Rep Oncol. 2017 Jun 14;10(2):531–533. doi: 10.1159/000477434 . PMID: 28690528; PMCID: PMC5498957. Cite Share Download PDF Status: Published Journal Publication published 01 Mar, 2022 Read the published version in World Journal of Surgical Oncology → Version 1 posted Editorial decision: Minor Revision 21 Oct, 2021 Review # 3 received at journal 17 Oct, 2021 Review # 1 received at journal 13 Oct, 2021 Review # 2 received at journal 11 Oct, 2021 Reviewer # 5 agreed at journal 02 Oct, 2021 Reviewer # 4 agreed at journal 01 Oct, 2021 Reviews received at journal 01 Oct, 2021 Reviewer # 3 agreed at journal 30 Sep, 2021 Reviewer # 2 agreed at journal 29 Sep, 2021 Reviewer # 1 agreed at journal 29 Sep, 2021 Reviewers invited by journal 21 Sep, 2021 Editor assigned by journal 20 Sep, 2021 Submission checks completed at journal 19 Sep, 2021 Editor invited by journal 19 Sep, 2021 First submitted to journal 16 Sep, 2021 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-915540","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":53419759,"identity":"805abb08-2199-4429-bb80-650467ed58c3","order_by":0,"name":"ROLI PURWAR","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYDADPmbmA0BKQoZ4LWzMbAkgLTwkaGHgMQDRhLWYS+Q+k/i5554cGzvP51c3aix4GNgPH92AT4vljHQzyZ5nxcZszLzbrHOOAR3Gk5Z2A58WgxtpbDd4DiQktgG1GOewAbVI8JgR1HLzD1gLzzPjnH9EarkNsYWH+XFuGxFaLHuesf+WOZAA9AubGXNunwQPGyG/mLOnMRu+OZAgx89/+PHnnG91cvzsh4/hdxgSm00CTOJTjq6F+QMh1aNgFIyCUTAyAQCgKj6kdvLLwAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-1245-239X","institution":"Banaras Hindu University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"ROLI","middleName":"","lastName":"PURWAR","suffix":""},{"id":53419760,"identity":"ce5206ea-07a4-4322-809f-e7e84afbd39b","order_by":1,"name":"Kishan Soni","email":"","orcid":"","institution":"Banaras Hindu University Institute of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kishan","middleName":"","lastName":"Soni","suffix":""},{"id":53419761,"identity":"e7245591-cece-41df-afa1-9db0250a6d8e","order_by":2,"name":"Mridula Shukla","email":"","orcid":"","institution":"lal path labs","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mridula","middleName":"","lastName":"Shukla","suffix":""},{"id":53419762,"identity":"d1e00e42-5f88-4cfb-a7ea-d97d67a13b03","order_by":3,"name":"Ashish Verma","email":"","orcid":"","institution":"Banaras Hindu University Institute of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ashish","middleName":"","lastName":"Verma","suffix":""},{"id":53419763,"identity":"7b94bbce-0ff4-4bb1-9f22-947a9bc510a0","order_by":4,"name":"Tarun Kumar","email":"","orcid":"","institution":"Banaras Hindu University Institute of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tarun","middleName":"","lastName":"Kumar","suffix":""},{"id":53419764,"identity":"37073c0a-f385-4d9c-9d1f-f754ee2232d2","order_by":5,"name":"Manoj Pandey","email":"","orcid":"","institution":"Banaras Hindu University Institute of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Manoj","middleName":"","lastName":"Pandey","suffix":""}],"badges":[],"createdAt":"2021-09-17 10:14:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-915540/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-915540/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12957-021-02462-5","type":"published","date":"2022-03-01T06:58:26+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":13914202,"identity":"d817ae61-d1bf-4cbb-bb63-a48dfa982b3c","added_by":"auto","created_at":"2021-09-23 15:07:43","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":134959,"visible":true,"origin":"","legend":"Pre-chemotherapy (A) and post-chemotherapy (B) axial MRI sections of pelvis at the level of the third sacral vertebrae. Sequences have been taken with high TE and TR values (viz. T2 weighting). The pretherapy scan (A) shows the bulky multilobulated mass (straight white arrow) with multiple satellite lesions (straight black arrow). On post therapy scan after 3 months (B) the main lesion shows near complete regression (straight white arrow) while the satellite lesions which were showing cystic degeneration (straight black arrow) have converted to much smaller hemorrhagic cysts (note the fluid-fluid level within the cyst). Also note that the urinary bladder (curved white arrow) and the rectum (curved black arrow) which were grossly compressed by the mass in the pre-therapy scan could be well visualized in the post therapy scan, confirming the regression of the tumor. Also note the reduction of signal intensity in after treatment signifying that the remaining tissue may just be the non-viable fibrotic tumoral remnant. ","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-915540/v1/c332485583d7e1b15db95fac.jpg"},{"id":13913592,"identity":"15bbc05e-5355-4af5-bddc-3f14bd4a3db9","added_by":"auto","created_at":"2021-09-23 15:04:43","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":60276,"visible":true,"origin":"","legend":"On post therapy scan after 6 months, there was no evidence of any solid mass lesion or altered enhancement noted, urinary bladder( straight long arrow) and rectum(straight short arrow) can now be clearly seen without compression.","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-915540/v1/a1dd9a099e821660a47c2ddb.jpg"},{"id":13913593,"identity":"46e44d91-1eee-49b9-9259-99cc6e0e2751","added_by":"auto","created_at":"2021-09-23 15:04:43","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":120299,"visible":true,"origin":"","legend":"On histopathological examination- A showing -cores of fibrous tissue along with presence of cells in sheets; 3 B – polygonal cells with well-defined cytoplasmic borders, granular eosinophilic cytoplasm, central to eccentric round nuclei; 3 C-- presence of cells in sheets, micro papillae, perivascularly arrangement ","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-915540/v1/4aa85c01d6d2f859145d2c7a.jpg"},{"id":13913595,"identity":"ef3bfe47-5296-4878-b3c5-c5b4e4571adb","added_by":"auto","created_at":"2021-09-23 15:04:43","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":115899,"visible":true,"origin":"","legend":"A –strong expression of HMB -45, Score 4+ ( 40 x ); B - strong expression of MELAN A Score 4 + ( 40 x ) ;C- strong expression of TFE -3, Score 3 + ( 40 x ); D -Ki -67 positivity seen in 30-35 percent of tumour cells \n\n","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-915540/v1/d11002ccafdf8887738d02b2.jpg"},{"id":18719668,"identity":"e5b0d2e6-bff6-4f37-8749-220d4c7543e2","added_by":"auto","created_at":"2022-03-01 06:58:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":638186,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-915540/v1/f74784ce-8225-4a6b-bd43-228da8bfc39a.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eTFE3 Associated Perivascular Epithelioid Cell Tumor with Complete Response to mTOR Inhibitor Therapy: Report of First Case and Literature Review\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eWHO defines perivascular epitheloid cell tumor (PEComas) as \"mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells\", including angiomyolipoma, clear cell sugar tumors of the lungs, lymphagioleiomyomatosis, hepatic falciform ligament clear cell myomelanocytic tumor and other unusual clear cell tumors at various locations.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] PEComa tumors are characterised by expression of both muscles, most often smooth muscle actin (in ~\u0026thinsp;80% of cases) and melanocytic markers (mainly HMB-45 and Melan A), which is one of the main characteristic feature [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. These tumors usually show female preponderance with mean age of presentation around 45 years. Anatomically these have a ubiquitous appearance, with most common site of origin being kidney, lung and liver. Uterus is the most common site for genitourinary tract PEComa [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePEComas are initially divided into three categories by Folpe et al., as benign (no atypical features), uncertain malignant potential (nuclear atypia or size\u0026thinsp;\u0026gt;\u0026thinsp;5cm) and malignant by any 2 morphological and pathological criteria such as gross size (\u0026gt;\u0026thinsp;5cm), high nuclear grade, necrosis, vascular invasion, or a mitotic rate higher than or one per 50 HPF [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Schoolmeester later classified these lesions as malignant when these lesions meet four out of the five above mentioned criteria [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn a largest case series reported till now by Bennet et al., of 32 uterine PEComas, most common clinical presentation were non-specific like menstrual complaints (33%), pelvic mass/adnexal mass/ uterine mass (17%), presumed fibroids (17%), metastasis from uterine primary (7%), cervical polyp (3%). At the time of disease reporting, metastasis was found in 17% cases with most common site being the lung [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Commonly, pre-operative diagnosis of PEComa is rare due to the presence of nonspecific imaging features. These lesions are usually confused with leiomyomas and leiomyosarcomas [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. PEComas are usually sporadic, but 6% of cases are associated with tuberous sclerosis with mutation in TSC1 and TSC 2 gene [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTFE 3 or transcription factor binding to IGHM enhancer 3, associated PEComa, are newly defined verities of PEComa. Around 20% of PEComas were found to be positive for TFE3 nuclear staining, among which many of them harbour TFE3 gene rearrangement. TFE-3 is a member of microphthalmia associated transcription (MiT) family of transcription factors, which includes MITF, TFE-3, TFE B and TFEC gene located at chromosome Xp11.2. MiTF-TFE family assist in development of melanocytic cells. These tumors strongly express diffuse positiveness for HMB-45 and TFE-3, whereas it is weakly positive or negative for SMA and negative for melan A. TFE 3 associated PEComas can be associated with prior history of chemotherapy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOther tumors which similarly expresses TFE 3 gene are melanoma, clear cell sarcoma, alveolar soft part sarcoma and translocation-associated renal cell carcinoma. These tumors are considered as microphthalmia associated transcription factor family of tumors [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this article, we report a case of TFE 3 positive uterine PEComa, with a mixed cell pattern of both epitheliod and spindle cells, which strongly express HMB-45, Melan A, SMA and surprisingly responds to everolimus (mTOR inhibitor).\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 45-year-old female presented to surgical oncology outpatient with a chief complaint of abdominal mass and per vaginal bleed for four months. As stated by the patient, she had undergone an abdominal surgical exploration before 7 months to remove pelvic mass. The patient also gave history of total abdominal hysterectomy before 3 years in view of abnormal uterine bleeding. However, the patient did not have any documentation regarding the above-mentioned surgeries. The patient did not have any significant personal and family history. On clinical examination general condition was fair, vitals were stable, pallor was present, on per abdominal examination, a large, soft abdominopelvic mass of 15x 15 cm in size was found, which was fixed, non-tender, not moving with respiration and was more deviated towards the left side. On per speculum examination, the vault was found replaced by a big smooth growth occupying upper 2/3rd of vagina, but no vaginal invasion was present. On per vaginum, a smooth lobular abdominopelvic mass of around 15x 15 cm was felt arising from vault. Routine biochemical investigations were within normal limit, except for haemoglobin level, which was 9gm%. An MRI was done which showed ill-defined heterogeneously enhancing mass lesion noted involving uterus and cervix, measuring 9.3 x 9.2 x 16 cm (AP X TR X CC). The lesion was invading adjacent myometrium, reaching up to serosa in the fundal region. It was also infiltrating the bilateral adnexa, but bilateral ovaries were not separately visualised. Inferiorly involvement extended till the upper 1/3 of vagina. Anteriorly the lesion was closely abutting the urinary bladder with suspicious loss of fat planes at places. Enlarged and necrotic common iliac lymph nodes were noted, largest measuring 1.1 cm. Multiple omental and peritoneal deposits were noted, largest measuring 4.2 x 2.9 cm. MRI suggested a probable diagnosis of endometrial carcinoma with extensions (Fig.\u0026nbsp;1A). An USG guided biopsy was taken from the pelvic mass, which on histopathological examination, showed cores of fibrous tissue along with presence of cells in sheets, micro papillae, perivascularly arranged and were polygonal with well-defined cytoplasmic borders, granular eosinophilic cytoplasm, central to eccentric round nuclei( Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003eb, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). Few cells showed nuclear inclusion, occasional psammomatous calcification which suggest of neoplastic etiology. An immunohistochemistry (IHC) panel was requested which revealed TFE \u0026minus;\u0026thinsp;3 score 3+, H Caldesmon score 1+, GATA-3 score 1+, Melan A-score 4+, and HMB-45, score 4 +. Ki 67- positivity was seen in 30\u0026ndash;35% of tumor cells( Fig.\u0026nbsp;4a, 4b, 4c, 4d). On the basis of histopathological and IHC analysis, the diagnosis of perivascular tumor with melanocytic differentiation was made and the possibility of TFE associated with PEComa was favoured. On considering this diagnosis, the patient was started on everolimus 10 mg OD. She was kept on monthly follow-up, in every visit she was symptomatically improved. After 3 months of therapy, she was again examined, and there was no mass/ lump palpable, on per abdomen and per vaginum examination. Repeat MRI pelvis was done which showed nearly resolution of pre-existing mass with decreased signal intensity showing nonviable remnants (Fig.\u0026nbsp;1B).As per RECIST(Response Evaluation Criteria in Solid Tumors) criteria, tumor shows partial response with mTOR inhibitors within 3 months of therapy. She was again followed after 6 months of therapy, there was again no mass /lump palpable on examination, MRI was repeated again showing no evidence of any solid mass lesion or altered enhancement noted, urinary bladder( straight long arrow) and rectum(straight short arrow) can now be clearly seen without compression in pelvis( Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e), suggesting complete response as per RECIST criteria.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion And Conclusions","content":"\u003cp\u003eUterine PEComas is a rare entity, on which around 150 cases have been reported in English literature till now. There are two distinct pattern of identified in PEComas- first with epithelioid pattern (100% cases)-these are polygonal cells with clear to granular cytoplasm, and positive for melanocytic markers HMB45, Melan-A and MITF. The second being the spindle cell pattern (37% of cases), which consists of cells with less cytoplasm, arranged in fascicles like smooth muscle and are positive for SMA, desmin, caldesmon. HMB-45 is the most sensitive marker being positive in 100% cases. The diagnosis should always be differentiated from smooth muscle tumors of uterus and especially tumors which showed similar IHC like epithelioid smooth muscle tumor of uterus, high grade endometrial stromal sarcoma (HGESS), GIST, melanoma involving the uterus [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. CD10, is diffuse and shows strong immunoreactivity in endometrial stromal tumors, GIST shows strong CD34 staining, as well as c-Kit positivity and negative for melanocytic marker. Metastatic melanoma and/or clear cell sarcoma shows strong S-100 protein immunoreactivity of the former and their muscle marker negativity.\u003c/p\u003e\n\u003cp\u003ePEComas with TFE3 gene rearrangement have predominant epithelioid morphology with clear cells and have strongly positive staining for melanocytic markers like HMB-45 and Cathepsin K and weak or negative expression of myoid markers. Their rare variant is TFE 3 gene mixed cell PEComa with both epitheliod and spindle cell pattern. Morphologically these showed clear to granular cytoplasm with eosinophilic cells and showed marked immune expression for HMB-45, TFE-3, Melan A and also positive for myoid markers [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThese lesions either represent collision between PEComa and smooth muscle tumor or PEComa with smooth muscle differentiation, which can be answered only by molecular analysis (Bennet 2018). This rearrangement can be explained by TFE3 fusing with other genes or undergoing breakage at different points along the gene [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eIn general, PEComa shows favourable prognosis, [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e] but TFE3 associated PEComas show aggressive behaviour (52%of cases) and poor prognosis during follow up [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. Folpe et al., showed that TFE3 fusion PEComa has an invasive behaviour, local recurrence and metastasis rates of 8.7% and 20.3%, respectively [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. Careful review of English literature revealed only 10 cases of uterine and cervix pecoma with TFE3 rearrangement. Table-1 shows its clinical profile, treatment and follow up status. Table-2 shows the immunohistochemical profile of uterine PEComas.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eFeatures of uterine TFE3 translocation associated PEComa\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eYear\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAge(years)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSite\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eClinical features\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePast h/o\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSize(cm)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePathology\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTreatment\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFollow up\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOutcome\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCho 2008\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterus, lower uterine segment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVaginal spotting, metastases to pelvic lymph nodes at presentation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlveolar, epitheliod\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTAH\u0026thinsp;+\u0026thinsp;pelvic LN dissection\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALL occured at 25 months\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDied at 33 months because of ALL, no e/o recurrence of pecoma at time of death\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLiu 2014\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCervix\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAUB\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSheets/ alveolus/nests\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eResection of cervical mass\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 months\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSchoolmester 2015\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterine corpus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAUB\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSheet like nested\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSupracervical hysterectomy, RSO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003e2 months: cervix and metastases to omentum treated by radical trachelectomy, upper vaginectomy, omentectomy and adjuvant chemotherapy 11 months: small and large intestine and intraabomdinal cavity treated by debulking and adjuvant chemotherapy\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eAlive; intraabdominal recurrence led to diagnosis revision from high grade LMS to pecoma; recently started sirolimus regimen\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSchoolmester 2015\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterine corpus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterine mass\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eHodgkin lymphoma treated with ABVD chemotherapy (6 years prior)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eNested\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTAH-BSO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e25 months\u003c/div\u003e\n\u003cdiv class=\"SimplePara\"\u003eRecurrence -none\u003c/div\u003e\n\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eAlive, ned\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSchoolmester 2015 [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePelvis, site not identified\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePelvic pain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMorcellated supracervical hysterectomy with cellular leiomyomata (1 year prior)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eNested\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eLocal excision of pelvic mass, radical trachelectomy, bso, pelvic and paraaortic lymphadenopathy, omentectomy, staging biopsies\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e57 months\u003c/div\u003e\n\u003cdiv class=\"SimplePara\"\u003eRecurrence-urinary bladder treated by excision\u003c/div\u003e\n\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive, ned\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSchoolmester 2015\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterine corpus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnknown\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eNested\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eHysterectomy\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 month\u003c/p\u003e\n\u003cp\u003eRecurrence- none\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"gridtable\"\u003eAlive, ned\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChoi 2016\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAUB\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpindle cells\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTAH\u0026thinsp;+\u0026thinsp;BSO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNs\u003c/p\u003e\n\u003cp\u003eMultiple metastasis in lung and liver\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNs\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBennet 2018\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNested\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 months\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGianella 2020\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCyclic abdominopelvic pain and chronic constipation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eK/c/o breast cancer, treated with quadrantectomy, axillary dissection, and radiotherapy,\u003c/p\u003e\n\u003cp\u003eFollowed by tamoxifen therapy for five years\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNested architecture with thin-walled vascular spaces and was\u003c/p\u003e\n\u003cp\u003eComposed of large cells with a clear to granular eosinophilic cytoplasm, round to ovoid nucleus, and\u003c/p\u003e\n\u003cp\u003eProminent nucleoli\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTLH with a bilateral salpingectomy.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 years, no recurrence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHu 2020\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUterine endom etrial polyp\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIrregular menstruation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eK/c/o ca breast, h/o MRM f/b tamoxifen x 4 years\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEpitheliod cells with nested architecture\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTLH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5months\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003e\u003cem\u003eNote- TAH- Total abdominal hysterectomy, TLH-Total laproscopic hysterectomy, RSO- right salpingoopherectomy, AUB- abnormal uterine bleeding, ALL- acute lymphocytic leukemia, LMS- liomyosarcoma, NS-not specified, MRM-modified radical mastectomy, BSO-bilateral salphingoophorectomy, NED-no evidence of disease\u003c/em\u003e\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eImmunohistochemical and Molecular Profile of Uterine PEComas\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eCase no\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eHMB 45\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eMELAN A\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eCATHEPSIN K\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eTFE 3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eSMA\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eDESMIN\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eCaldesmon\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eKi 67\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eFISH\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eNot done\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e3+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e3+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e3+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e2+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e2+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e1+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e1+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e3+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e3+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e5%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eNot done\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003ePSF-TFE3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eFocal positive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eNot done\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003epositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e5%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003ePresent case\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e3+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e1+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e30%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eNot done\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIn all the above cases reported in literature, the pelvic tumors were managed by primary surgical resection. In maximum of the above mentioned cases, diagnosis was confirmed postoperatively. Most of the cases does not contain any information regarding follow-up and further management.\u003c/p\u003e\n\u003cp\u003eNo effective therapy with TFE 3 rearranged PEComa in advanced extrarenal cases have been mentioned in the literature. Chemotherapy (CT) and radiotherapy (RT) have also been reported in literature with advanced PEComa cases. Since there is paucity of cases, poor results reported with variety of treatment modalities and no randomised trial conducted, no uniform consensus has been achieved in this regard.\u003c/p\u003e\n\u003cp\u003eBoth neoadjuvant and adjuvant CT (dacarbazine, ifosfamide, doxorubicin, vincristine), has been reported, but heterogenous results were achieved regarding disease progression and survival free interval. Regarding targeted therapy, the use of mTOR inhibitors in conventional metastatic PEComas with TSC1 and TSC2 mutation has been reported in very few cases at other extrarenal sites with promising results, however, further prospective studies are needed [17]. TFE 3 rearranged PEComas do not involve TSC2 gene, thus biologically these tumors behave distinctly with conventional PEComa and do not respond to mTOR inhibitors[5].\u003c/p\u003e\n\u003cp\u003eXu et al., has reported a case of gastrointestinal PEComa with TFE3 rearrangement which did not responded to Everolimus, hence they switched to anti-VEGFR2 and Apatinib, for which the tumor remained stable and the progression free survival lasted for about 7 months [18]. Another case of ovarian TFE3 reactive PEComa was reported, which did not responded to sirolimus and develop liver recurrence [19].\u003c/p\u003e\n\u003cp\u003eAlthough our case showed strong nuclear positivity for TFE3, due to non affordability, the patient refused for FISH analysis to look for genetic rearrangements. In spite of TFE3 reactivity, our patient responded very well with Everolimus, in contrast to other cases reported in the literature.\u003c/p\u003e\n\u003cp\u003ePrompt identification of TFE-3 PEComa is recommended before starting their management, since these tumors show different biological behaviour as compared to the conventional counterpart, which can lead to important insight into their management and the targeted therapies. Since very few cases have been reported in literature, further studies are needed to clearly define their clinical characteristics, prognosis and management. We have reported the first case of TFE 3 reactive PEComa which showed an appreciable response to Everolimus.\u003c/p\u003e"},{"header":"List Of Abbreveations","content":"\u003cp\u003ePerivascular epitheloid cell tumor (PEComas)\u003c/p\u003e \u003cp\u003eChemotherapy (CT)\u003c/p\u003e \u003cp\u003eRadiotherapy (RT)\u003c/p\u003e \u003cp\u003eImmunohistochemistry (IHC)\u003c/p\u003e \u003cp\u003eRECIST(Response Evaluation Criteria in Solid Tumors)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval is not required as patient consent for publication was obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe written consent for publication of case report and accompanied images was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003ch4\u003eAvailability of data and materials\u003c/h4\u003e\n\u003cp\u003eNot applicable as all information and data is presented in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRP and KS did the literature search and prepared the draft manuscript. MS, TK and AV helped in preparation of manuscript and edited the manuscript for scientific content. MP conceived and designed the study and edited the final manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFletcher CDM, Unni KK, Mertens F, et al. International Academy of Pathology: Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press; 2002.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan Y, Zhang H, Xiao EH. Perivascular epithelioid cell tumour: dynamic CT, MRI and clinicopathological characteristics analysis of 32 cases and review of the literature. Clin Radiol. 2013;68:555\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBao L, Shi Y, Zhong J, Zhao M, Wu J, Hai L, Xu X, Du H, Shi Y. Histopathologic characteristics and immunotypes of perivascular epithelioid cell tumors (PEComa). Int J Clin Exp Pathol. 2019 Dec 1;12(12):4380\u0026ndash;4389. PMID: 31933841; PMCID: PMC6949869.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFolpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol. 2005;29:1558\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoolmeester JK, Dao LN, Sukov WR, Wang L, ParkKJ, Murali R, Hameed MR, Soslow RA. TFE3 translocation-associated perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: morphology, immunophenotype, differential diagnosis. Am J Surg Pathol. 2015;39:394\u0026ndash;404.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBennett JA, Braga AC, Pinto A, Van de Vijver K, Cornejo K, Pesci A, Zhang L, Morales-Oyarvide V, Kiyokawa T, Zannoni GF, Carlson J, Slavik T, Tornos C, Antonescu CR, Oliva E. Uterine PEComas: A Morphologic, Immunohistochemical, and Molecular Analysis of 32 Tumors. Am J Surg Pathol. 2018 Oct;42(10):1370\u0026ndash;83. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PAS.0000000000001119\u003c/span\u003e\u003c/span\u003e. PMID: 30001237; PMCID: PMC6133752.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShan W, Shi Y, Zhu Q, Yang B, Xie L, Li B, Ning C, Lv Q, Cheng Y, Xie B, Bai M, Xu Y, Chen X, Luo X. Five cases of uterine perivascular epithelioid cell tumors (PEComas) and review of literature. Arch Gynecol Obstet. 2019 Jan;299(1):185\u0026ndash;190. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00404-018-4920-4\u003c/span\u003e\u003c/span\u003e. Epub 2018 Oct 13. PMID: 30317387.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVannucchi M, Minervini A, Salvi M, Montironi R, Raspollini MR. TFE3 Gene Rearrangement in Perivascular Epithelioid Cell Neoplasm (PEComa) of the Genitourinary Tract. Clin Genitourin Cancer. 2020 Dec;18(6):e692\u0026ndash;7. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clgc.2020.04.004\u003c/span\u003e\u003c/span\u003e. Epub 2020 May 15. PMID: 32576448.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShen Q, Rao Q, Xia QY, Yu B, Shi QL, Zhang RS, Zhou XJ. Perivascular epithelioid cell tumor (PEComa) with TFE3 gene rearrangement: clinicopathological, immunohistochemical, and molecular features. Virchows Arch. 2014 Nov;465(5):607\u0026ndash;13. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00428-014-1655-x\u003c/span\u003e\u003c/span\u003e. Epub 2014 Sep 20. PMID: 25239799.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParra-Herran C, Howitt BE. Uterine Mesenchymal Tumors: Update on Classification, Staging, and Molecular Features. Surg Pathol Clin. 2019 Jun;12(2):363\u0026ndash;396. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.path.2019.01.004\u003c/span\u003e\u003c/span\u003e. PMID: 31097109.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGiannella L, Delli Carpini G, Montik N, Verdecchia V, Puccio F, Di Giuseppe J, Tsiroglou D, Goteri G, Ciavattini A. Ultrasound Features of a Uterine Perivascular Epithelioid Cell Tumor (PEComa): Case Report and Literature Review. Diagnostics (Basel). 2020 Aug 3;10(8):553. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/diagnostics10080553\u003c/span\u003e\u003c/span\u003e. PMID: 32756336; PMCID: PMC7459969.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S. etal. Integrative Genomic Analyses Identify Mitf as a Lineage Survival Oncogene Amplified in Malignant Melanoma. Nature. 2005;436:117\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho HY, Chung DH, Khurana H, et al. The role of TFE3 in PEComa. Histopathology. 2008;53:236\u0026ndash;49. [PubMed: 18510571].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu F, Zhang R, Wang ZY, et al. Malignant perivascular epithelioid cell tumor (PEComa) of cervix with TFE3 gene rearrangement: a case report. Int J Clin Exp Pathol. 2014;7:6409\u0026ndash;14. [PubMed: 25337301].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi YJ, Hong JH, Kim A, et al. A Case of Malignant PEComa of the Uterus Associated with Intramural Leiomyoma and Endometrial Carcinoma. J Pathol Transl Med. 2016;50:469\u0026ndash;73. [PubMed: 27452081].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu Y, Wang L, Shi H, Hu B. Endometrial polyp-like perivascular epithelioid cell neoplasm associated with TFE3 translocation: report of one case. Int J Clin Exp Pathol. 2020 Mar 1;13(3):543\u0026ndash;549. PMID: 32269693; PMCID: PMC7137019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMusella A, De Felice F, Kyriacou AK, Barletta F, Di Matteo FM, Marchetti C, Izzo L, Monti M, Benedetti Panici P, Redler A, D'Andrea V. Perivascular epithelioid cell neoplasm (PEComa) of the uterus: A systematic review. Int J Surg. 2015 Jul;19:1\u0026ndash;5. doi: 10.1016/j.ijsu.2015.05.002. Epub 2015 May 14. PMID: 25981307.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu J, Gong XL, Wu H, Zhao L. Case Report: Gastrointestinal PEComa With \u003cem\u003eTFE3\u003c/em\u003e Rearrangement Treated With Anti-VEGFR TKI Apatinib. Front Oncol. 2020 Nov;23:10:582087. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fonc.2020.582087\u003c/span\u003e\u003c/span\u003e. PMID: 33330059; PMCID: PMC7719820.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin RJ, Melamed J, Wu J. PEComa with Transcription Factor E3 Overexpression: A Diagnostic and Therapeutic Challenge. Case Rep Oncol. 2017 Jun 14;10(2):531\u0026ndash;533. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000477434\u003c/span\u003e\u003c/span\u003e. PMID: 28690528; PMCID: PMC5498957.\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":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Perivascular epitheliod cell tumor, Mtor Therapy, TFE3 , PEComa, uterus, Gynecological","lastPublishedDoi":"10.21203/rs.3.rs-915540/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-915540/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Perivascular epitheloid cell tumor (PEComas) are characterised by expression of both muscles, most often smooth muscle actin\u0026nbsp;(in ~80% of cases) and melanocytic markers (mainly HMB-45 and Melan A). TFE 3 associated PEComas are new variant which are poorly defined due to their limited reports in literature. These tumors lack response to targeted mTOR inhibitor therapy due to lack of mutation in TSC gene. Hereby we are reporting a case of TFE3 associated pelvic PEComa showing excellent response to Everolimus. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e: A 45-year-old female presented with complaint of abdominal mass and bleeding per vaginum for 4 months. She had a history of total abdominal hysterectomy 3 years back in view of abnormal uterine bleeding and exploratory laprotomy 7 months back to remove some pelvic mass. Imaging suggested of ill-defined heterogenous mass of 9.3 x 9.2 x 16 cm involving uterus, cervix and upper 1/3 vagina. Multiple omental and peritoneal deposits were also seen, making probable diagnosis of carcinoma endometrium. USG guided biopsy showed cores of fibrous tissue with presence of cells in sheets with granular eosinophillic cytoplasm, IHC showed positivity for TFE -3, H Caldesmon, GATA-3, Melan A-and HMB-45, Ki 67 index was 35%. On the basis of above diagnosis of PEComa was made and she was started on Everolimus, repeat imaging after 3 months of therapy, showed complete response.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e:\u0026nbsp;We are reporting first case of malignant pelvic TFE 3 PEComa showing response to mTOR therapy. Identification of TFE 3 PEComa is important because they showed different biologic behaviour then their conventional PEComa.\u003c/p\u003e","manuscriptTitle":"TFE3 Associated Perivascular Epithelioid Cell Tumor with Complete Response to mTOR Inhibitor Therapy: Report of First Case and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-09-23 15:04:41","doi":"10.21203/rs.3.rs-915540/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor Revision","date":"2021-10-21T22:16:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-10-18T00:00:00+00:00","index":3,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"editorInvitedReview","content":"","date":"2021-10-14T00:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"editorInvitedReview","content":"","date":"2021-10-12T00:00:00+00:00","index":2,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"reviewerAgreed","content":"","date":"2021-10-03T00:00:00+00:00","index":5,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-10-02T00:00:00+00:00","index":4,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-10-01T23:35:36+00:00","index":0,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-10-01T00:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-09-30T01:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-09-30T00:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-09-21T04:47:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-09-20T21:52:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-09-19T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-09-19T23:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Surgical Oncology","date":"2021-09-17T00:14:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cabfc13b-f7cb-45c1-89f9-3685f1ea5a50","owner":[],"postedDate":"September 23rd, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":7385405,"name":"Oncology"}],"tags":[],"updatedAt":"2022-03-01T06:58:26+00:00","versionOfRecord":{"articleIdentity":"rs-915540","link":"https://doi.org/10.1186/s12957-021-02462-5","journal":{"identity":"world-journal-of-surgical-oncology","isVorOnly":false,"title":"World Journal of Surgical Oncology"},"publishedOn":"2022-03-01 06:58:26","publishedOnDateReadable":"March 1st, 2022"},"versionCreatedAt":"2021-09-23 15:04:41","video":"","vorDoi":"10.1186/s12957-021-02462-5","vorDoiUrl":"https://doi.org/10.1186/s12957-021-02462-5","workflowStages":[]},"version":"v1","identity":"rs-915540","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-915540","identity":"rs-915540","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}