Abstract
Perivascular epithelioid cell neoplasms (PEComas) are rare mesenchymal lesions, with gynecological PEComas accounting for just over a quarter of cases. Limited reports exist on gynecological PEComa, primarily treated with surgery; adjuvant therapy is considered in high-risk cases. This systematic review aims to summarize the origin and clinical, pathological and molecular characteristics of uterine PEComa, focusing on treatment options for gynecological PEComa. A comprehensive PubMed review of gynecological PEComa reports was conducted. A detailed examination of the literature ensured a thorough understanding. Gynecological PEComa diagnosis relies on histology and immunology. Despite therapy controversies, surgery remains the mainstay. Adjuvant therapy efficacy in high-risk cases is uncertain. mTOR inhibitors are the first line; alternative treatments, including angiogenesis and aromatase inhibitors, should be considered.
Papers of special note have been highlighted as: • of interest
References
- 1. . PEC and sugar. Am. J. Surg. Pathol. 16(3), 307–308 (1992).
- 2. . Perivascular epithelioid cell. Am. J. Surg. Pathol. 20(9), 1149–1153 (1996).
- 3. . HMB-45 reactivity in conventional uterine leiomyosarcomas. Am. J. Surg. Pathol. 31(1), 95–98 (2007).
- 4. Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum. Arch. Pathol. Lab. Med. 125(6), 751–758 (2001).
- 5. . PEComa: what do we know so far? Histopathology 48(1), 75–82 (2006).
- 6. . Evidence on the neural crest origin of PEComas. Rom. J. Morphol. Embryol. 52(1), 7–13 (2011).
- 7. . Telocytes are the common cell of origin of both PEComas and GISTs: an evidence-supported hypothesis. J. Cell. Mol. Med. 15(12), 2569–2574 (2011).
- 8. Expression of CD44 and CD29 by PEComa cells suggests their possible origin of mesenchymal stem cells. Int. J. Clin. Exp. Pathol. 8(10), 13023–13033 (2015).
- 9. Alveolar soft part sarcoma of the female genital tract: a morphologic, immunohistochemical, and molecular cytogenetic study of 10 cases with emphasis on its distinction from morphologic mimics. Am. J. Surg. Pathol. 41(5), 622–632 (2017).
- 10. . 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. 29(12), 1558–1575 (2005).
- 11. Sclerosing variant of perivascular epithelioid cell tumor in the female genital organs. Pathol. Int. 61(12), 768–772 (2011).
- 12. Uterine PEComas: a morphologic, immunohistochemical, and molecular analysis of 32 tumors. Am. J. Surg. Pathol. 42(10), 1370–1383 (2018).
- 13. . Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum. Am. J. Surg. Pathol. 32(4), 493–501 (2008).
- 14. Perivascular epithelioid cell tumors (PEComa) in pregnancy with uterine rupture and ongoing abdominal gestation: a case report. Case Rep. Womens Health 25, e00172 (2020). • The authors recommend this paper for clinicians interested in navigating perivascular epithelioid cell neoplasm complexities during pregnancy.
- 15. . Uterine rupture: an unusual presentation of a uterine perivascular epithelioid cell tumor (PEComa). Int. J. Gynecol. Cancer 30(12), 2008–2011 (2020).
- 16. Epithelioid lymphangioleiomyomatosis-like tumour of the uterus in a patient without tuberous sclerosis: a lesion mimicking epithelioid leiomyosarcoma. Histopathology 33(1), 91–93 (1998).
- 17. Perivascular epithelioid cell (PEC) tumors of the uterus: a clinicopathologic study of two cases with aggressive features. Mod. Pathol. 18(10), 1336–1342 (2005).
- 18. . Perivascular epithelioid cell tumor of the uterus: report of two cases and mini-review of the literature. Int. J. Surg. Case Rep. 28, 85–87 (2016).
- 19. . An unusual case of uterine PEComa presenting with disseminated intravascular coagulation. Gynecol. Oncol. Rep. 29, 76–78 (2019).
- 20. Uterine PEComa with aggressive behavior: a review with an additional case of spontaneous vaginal expulsion. Pathol. Res. Pract. 216(6), 152991 (2020). • The authors recommend this paper for clinicians interested in aiming to refine diagnostic approaches and optimize surgical interventions in cases of uterine perivascular epithelioid cell neoplasm with aggressive behavior.
- 21. Ultrasound features of a uterine perivascular epithelioid cell tumor (PEComa): case report and literature review. Diagnostics (Basel) 10(8), (2020). • The authors recommend this paper for clinicians interested in enhancing diagnostic strategies and surgical management.
- 22. . A case of HMB45-negative perivascular epithelioid cell tumor (PEComa) of the uterine corpus: a possible diagnostic application of molecular-cytogenetic analysis. Eur. J. Gynaecol. Oncol. 30(2), 216–219 (2009).
- 23. . Caesarean section unmasking perivascular epithelioid cell tumour of the uterus. J. Obstet. Gynaecol. 34(5), 441–442 (2014).
- 24. . Rupture of perivascular epithelioid cell neoplasm at 34 weeks' gestation: a nonendometriosis case of spontaneous hemoperitoneum in pregnancy. J. Obstet. Gynaecol. Res. 45(3), 709–713 (2019).
- 25. . Perivascular epithelioid cell tumor masquerading as retained placenta. J. Ultrasound Med. 34(8), 1515–1517 (2015).
- 26. . Perivascular epithelioid cell tumor (PEComa) of the uterus: an outcome-based clinicopathologic analysis of 41 reported cases. Adv. Anat. Pathol. 15(2), 63–75 (2008).
- 27. . Malignant perivascular epithelioid cell tumor of the uterus. Rare Tumors 4(1), e14 (2012).
- 28. . Perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: clinicopathologic and immunohistochemical characterization of 16 cases. Am. J. Surg. Pathol. 38(2), 176–188 (2014).
- 29. . Perivascular epithelioid tumours (PEComas) of the gynaecological tract. J. Clin. Pathol. 68(6), 418–426 (2015).
- 30. . Perivascular epithelioid cell tumor (‘PEComa’) of the uterus: a subset of HMB-45-positive epithelioid mesenchymal neoplasms with an uncertain relationship to pure smooth muscle tumors. Am. J. Surg. Pathol. 26(1), 1–13 (2002).
- 31. . [Perivascular epithelioid cell tumor of uterus: report of 5 cases and literature review]. Zhonghua Bing Li Xue Za Zhi 36(5), 302–306 (2007).
- 32. 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. 2, 35 (2004).
- 33. Five cases of uterine perivascular epithelioid cell tumors (PEComas) and review of literature. Arch. Gynecol. Obstet. 299(1), 185–190 (2019).
- 34. . A retrospective case study of 13 uterine perivascular epithelioid cell neoplasm (PEComa) patients. Onco Targets Ther. 14, 1783–1790 (2021). • The authors recommend this paper for clinicians interested in enhancing diagnostic accuracy and treatment strategies for uterine perivascular epithelioid cell neoplasm.
- 35. . Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor. Diagn. Pathol. 7, 117 (2012).
- 36. . Perivascular epithelioid cell neoplasms: pathology and pathogenesis. Hum. Pathol. 41(1), 1–15 (2010).
- 37. . Uterine PEComa: appraisal of a controversial and increasingly reported mesenchymal neoplasm. Int. Semin. Surg. Oncol. 5, 7 (2008).
- 38. . Malignant perivascular epithelioid cell tumor in the female genital tract: preferred reporting items for systematic reviews and meta-analyses. Medicine (Baltimore) 98(2), e14072 (2019).
- 39. . PNL2: an adjunctive biomarker for renal angiomyolipomas and perivascular epithelioid cell tumours. Histopathology 72(3), 441–448 (2018).
- 40. . PNL2: a useful adjunct biomarker to HMB45 in the diagnosis of uterine perivascular epithelioid cell tumor (PEComa). Int. J. Gynecol. Pathol. 39(6), 529–536 (2020).
- 41. . Uterine perivascular epitheloid cell tumor (PEComa) with CD117 and PNL2 positivity and entrapped endometriotic glands, mimicking sex-cordlike differentiation. Ann. Diagn. Pathol. 15(3), 216–218 (2011).
- 42. CD1a expression in PEComas. Pathol. Int. 58(3), 169–173 (2008).
- 43. . Epithelioid smooth muscle tumors of the uterus do not express CD1a: a potential immunohistochemical adjunct in their distinction from uterine perivascular epithelioid cell tumors. Ann. Diagn. Pathol. 12(6), 401–405 (2008).
- 44. . CD1a immunopositivity in perivascular epithelioid cell neoplasms: true expression or technical artifact? A streptavidin-biotin and polymer-based detection system immunohistochemical study of perivascular epithelioid cell neoplasms and their morphologic mimics. Hum. Pathol. 42(3), 369–374 (2011).
- 45. . Perivascular epithelioid cell tumor of the uterus: immunohistochemical, ultrastructural and molecular study. Pathol. Int. 53(11), 800–805 (2003).
- 46. . Perivascular epithelioid cell tumour (PEComa) of the uterus associated with malignant neoplasm of the female genital tract. J. Obstet. Gynaecol. 24(5), 600–604 (2004).
- 47. Ang-1 and Ang-2 expression in angiomyolipoma and PEComa family tumors. J Orthop. 14(1), 154–160 (2017).
- 48. . Perivascular epithelioid cell tumors (PEComa) of the gynecologic tract. Genes Chromosomes Cancer 60(3), 168–179 (2021).
- 49. Perivascular epithelioid cell neoplasm (PEComa) of the uterus: a systematic review. Int. J. Surg. 19, 1–5 (2015).
- 50. Characterization of clinical cases of malignant PEComa via comprehensive genomic profiling of DNA and RNA. Oncology 98(12), 905–912 (2020).
- 51. Malignant perivascular epithelioid cell tumor (PEComa) of cervix with TFE3 gene rearrangement: a case report. Int. J. Clin. Exp. Pathol. 7(9), 6409–6414 (2014).
- 52. Dichotomy of genetic abnormalities in PEComas with therapeutic implications. Am. J. Surg. Pathol. 39(6), 813–825 (2015).
- 53. TFE3 translocation-associated perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: morphology, immunophenotype, differential diagnosis. Am. J. Surg. Pathol. 39(3), 394–404 (2015).
- 54. . Perivascular epithelioid cell tumour: dynamic CT, MRI and clinicopathological characteristics – analysis of 32 cases and review of the literature. Clin. Radiol. 68(6), 555–561 (2013).
- 55. Imaging features of primary and metastatic malignant perivascular epithelioid cell tumors. AJR Am. J. Roentgenol. 202(2), 252–258 (2014).
- 56. . Malignant perivascular epithelioid cell tumour of the round ligament mimics leiomyoma on computed tomography. Singapore Med. J. 50(7), e239–e242 (2009).
- 57. . Ultrasound appearance of perivascular epithelioid cell tumor (PEComa). Ultrasound Obstet. Gynecol. 57(5), 844–845 (2021).
- 58. MR findings of uterine PEComa in patients with tuberous sclerosis: report of two cases. Abdom. Radiol. (NY) 44(4), 1256–1260 (2019).
- 59. . A case of uterine lymphangioleiomyomatosis in a young woman that was identified via peritonitis. J. Obstet. Gynaecol. Res. 45(2), 482–486 (2019).
- 60. . HMB45+ hyalinized epithelioid tumor of the uterus is linked to epithelioid leiomyoma rather than to PEC-omas. Int. J. Surg. Pathol. 9(4), 341–343 (2001).
- 61. . Uterine epithelioid leiomyosarcomas with clear cells: reactivity with HMB-45 and the concept of PEComa. Am. J. Surg. Pathol. 28(2), 244–249 (2004).
- 62. . Uterine leiomyosarcoma with HMB45+ clear cell areas: report of two cases. Histopathology 47(5), 540–542 (2005).
- 63. . Uterine perivascular epithelioid cell tumor coexisting with pulmonary lymphangioleiomyomatosis and renal angiomyolipoma: a case report. Appl. Immunohistochem. Mol. Morphol. 16(4), 405–409 (2008).
- 64. . [Endometrial stromal sarcoma complicating uterine perivascular epithelioid cell tumor: report of a case]. Zhonghua Bing Li Xue Za Zhi 42(5), 345–346 (2013).
- 65. . Late pulmonary metastasis in uterine PEComa. J. Clin. Pathol. 56(8), 627–628 (2003).
- 66. . Recurrent perivascular epithelioid cell tumor of the uterus (PEComa): an immunohistochemical study and review of the literature. Gynecol. Oncol. 90(3), 677–681 (2003).
- 67. . Malignant perivascular epithelioid cell tumor (PEComa) of the uterus with late renal and pulmonary metastases: a case report with review of the literature. Diagn. Pathol. 2, 45 (2007).
- 68. . Perivascular epithelioid cell tumors (PEComa) of the female genital tract: a challenging question for gynaecologic oncologist and pathologist. Gynecol. Oncol. Rep. 33, 100603 (2020).
- 69. . Malignant perivascular epithelioid cell tumor (PEComa) of the uterus: serial imaging with F-18 FDG PET/CT for surveillance of recurrence and evaluation of response to therapy. Clin. Nucl. Med. 36(4), e16–e19 (2011).
- 70. . Laparoscopic radical excision of primary round ligament perivascular epithelioid cell tumor mimicking leiomyoma. J. Minim. Invasive Gynecol. 16(5), 626–629 (2009).
- 71. . Fertility-sparing operation for recurrence of uterine cervical perivascular epithelioid cell tumor. Rare Tumors 2(2), e26 (2010).
- 72. . Multimodal treatment using surgery, radiotherapy, and chemotherapy in a patient with a perivascular epithelioid cell tumor of the uterus. J. Pediatr. Hematol. Oncol. 27(12), 681–684 (2005).
- 73. . Perivascular epithelioid cell tumor (PEComa) of the uterus with aggressive behavior at presentation. Hematol. Oncol. Stem Cell Ther. 2(3), 426–430 (2009).
- 74. Treatment with the mTOR inhibitor temsirolimus in patients with malignant PEComa. Ann. Oncol. 21(5), 1135–1137 (2010).
- 75. . Treatment of advanced malignant uterine perivascular epithelioid cell tumor with mTOR Inhibitors: single-institution experience and review of the literature. Anticancer Res. 36(11), 6161–6164 (2016).
- 76. . A patient presenting with a perivascular epithelioid cell tumor in the broad ligament: a case report. J. Med. Case Rep. 5, 383 (2011).
- 77. . Fertility sparing treatment of a malignant uterine perivascular epithelioid cell tumor: a case report. Gynecol. Oncol. Case Rep. 8, 14–16 (2014).
- 78. Combination targeted therapy of VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus induced a remakable response of rapid progressive uterine PEComa. Cancer Biol. Ther. 17(6), 595–598 (2016).
- 79. . Rapid and durable response with nab-sirolimus after everolimus failure in a patient with perivascular epithelioid cell tumors (PEComas) of the uterus. Cureus 13(5), e14951 (2021).
- 80. . VEGFR inhibitors for uterine metastatic perivascular epithelioid tumors (PEComa) resistant to mTOR inhibitors. A case report and review of literature. Front. Oncol. 11, 641376 (2021).
- 81. Estrogen maintains myometrial tumors in a lymphangioleiomyomatosis model. Endocr. Relat. Cancer 23(4), 265–280 (2016).