Pelvic Endometriosis is Rarely Associated with Ovarian Borderline Tumours, Cytologic and Architectural Atypia: A Clinicopathologic Study

  • Mohamed Ali Bedaiwy
  • Mahmoud Rezk Abd-Elwahed Hussein
  • Charles Biscotti
  • Tommaso Falcone
Original Paper


Endometriotic foci, especially ovarian ones, with epithelial cytologic atypia may be precursors of cancer. This study presents an overview of the atypical cytological and histopathological findings associated with endometriosis. Six cases of endometriosis, with atypical histological and cytological changes, were obtained from the archives of the Department of Pathology at Cleveland Clinic Foundation between year 2000 and 2003. The size of the base from which these cases were drawn was 2000 cases of endometriosis. The age range of the patients was from 29 to 52 years. The clinical presentations included infertility (three cases), pelvic pain (three cases), adenexal and pelvic masses (four cases). Stage IV endometriosis with extensive pelvic involvement was found in two patients. Intraoperatively, the endometriotic lesions involved the ovaries (all cases); Cul de sac (four cases); urinary bladder (two cases); sigmoid colon, hemidiaphragms, and uterine vessels (one case each). The endometriotic lesions were associated with uterine leiomyomas (two patients) and adenocarcinoma of the vagina (one patient). Histologically, in addition to endometrial type glands and stroma, usually found in endometriosis, we observed both cytologic and pattern atypism involving the epithelium in all cases. The features of cytologic atypia included nuclear stratification, hyperchromatism, and pleomorphism. The features of pattern atypia were complex glandular pattern, papillary formations and psammoma bodies. In two cases, these features were sufficient for diagnosis of borderline Mullerian seromucinous tumours. One patient had recurred with metastatic adenocarcinoma of the vault. She died later from disseminated metastatic disease. There is a rare association between pelvic endometriosis and borderline ovarian tumours (three cases), cytologic and pattern atypia (two cases); mesothelial hyperplasia, endosalpingiosis (two cases), and metastasis (one case). Cytologic and pattern atypia can develop in the endometriotic foci and therefore, these lesions should be thoroughly scrutinized for presence of these changes. Our findings recommend surgical excision of these foci rather than their simple cauterization.


Endometriosis Cytologic atypia Pattern atypia 


  1. 1.
    Akahane T, Sekizawa A, Purwosunu Y et al (2007) The role of p53 mutation in the carcinomas arising from endometriosis. Int J Gynecol Pathol 26:345–351PubMedCrossRefGoogle Scholar
  2. 2.
    Ali-Fehmi R, Khalifeh I, Bandyopadhyay S et al (2006) Patterns of loss of heterozygosity at 10q23.3 and microsatellite instability in endometriosis, atypical endometriosis, and ovarian carcinoma arising in association with endometriosis. Int J Gynecol Pathol 25:223–229PubMedCrossRefGoogle Scholar
  3. 3.
    Bese T, Simsek Y, Bese N et al (2003) Extensive pelvic endometriosis with malignant change in tamoxifen-treated postmenopausal women. Int J Gynecol Cancer 13:376–380PubMedCrossRefGoogle Scholar
  4. 4.
    Clement PB (2007) The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects. Adv Anat Pathol 14:241–260PubMedCrossRefGoogle Scholar
  5. 5.
    Edghill EL, Bingham C, Ellard S et al (2006) Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 43:84–90PubMedCrossRefGoogle Scholar
  6. 6.
    Friedrich M, Villena-Heinsen C, Mink D et al (1999) Carcinosarcoma, endometrial intraepithelial carcinoma and endometriosis after tamoxifen therapy in breast cancer. Eur J Obstet Gynecol Reprod Biol 82:85–87PubMedCrossRefGoogle Scholar
  7. 7.
    Groisman GM, Meir A (2003) CD10 is helpful in detecting occult or inconspicuous endometrial stromal cells in cases of presumptive endometriosis. Arch Pathol Lab Med 127:1003–1006PubMedGoogle Scholar
  8. 8.
    Guo L, Liu T, Lang J (2001) The malignant potential of ovarian atypical endometriosis. Zhonghua Bing Li Xue Za Zhi 30:169–172PubMedGoogle Scholar
  9. 9.
    Higashiguchi A, Yamada T, Susumu N et al (2007) Specific expression of hepatocyte nuclear factor-1beta in the ovarian clear cell adenocarcinoma and its application to cytological diagnosis. Cancer Sci 98:387–391PubMedCrossRefGoogle Scholar
  10. 10.
    Hutton RL, Dalton SR (2007) Primary peritoneal serous borderline tumors. Arch Pathol Lab Med 131:138–144PubMedGoogle Scholar
  11. 11.
    Jelovsek JE, Winans C, Brainard J et al (2004) Endometriosis of the liver containing Mullerian adenosarcoma: case report. Am J Obstet Gynecol 191:1725–1727PubMedCrossRefGoogle Scholar
  12. 12.
    Kato N, Sasou S, Motoyama T (2006) Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary. Mod Pathol 19:83–89PubMedCrossRefGoogle Scholar
  13. 13.
    Korner M, Burckhardt E, Mazzucchelli L (2006) Higher frequency of chromosomal aberrations in ovarian endometriosis compared to extragonadal endometriosis: A possible link to endometrioid adenocarcinoma. Mod Pathol 19:1615–1623PubMedCrossRefGoogle Scholar
  14. 14.
    Lee KR, Nucci MR (2003) Ovarian mucinous and mixed epithelial carcinomas of Mullerian (endocervical-like) type: a clinicopathologic analysis of four cases of an uncommon variant associated with endometriosis. Int J Gynecol Pathol 22:42–51PubMedCrossRefGoogle Scholar
  15. 15.
    Leiserowitz GS, Gumbs JL, Oi R et al (2003) Endometriosis-related malignancies. Int J Gynecol Cancer 13:466–471PubMedCrossRefGoogle Scholar
  16. 16.
    Leng JH, Lang JH, Zhao XY et al (2006) Visual and histologic analysis of laparoscopic diagnosis of endometriosis. Zhonghua Fu Chan Ke Za Zhi 41:111–113PubMedGoogle Scholar
  17. 17.
    Madej P, Plewka A, Madej JA et al (2006) Nucleolar organizer regions (NORs) in adenomyosis. Pathol Res Pract 202:433–437PubMedCrossRefGoogle Scholar
  18. 18.
    Marchino GL, Gennarelli G, Enria R et al (2005) Diagnosis of pelvic endometriosis with use of macroscopic versus histologic findings. Fertil Steril 84:12–15PubMedCrossRefGoogle Scholar
  19. 19.
    McCluggage WG, Bryson C, Lamki H et al (2000) Benign, borderline, and malignant endometrioid neoplasia arising in endometriosis in association with tamoxifen therapy. Int J Gynecol Pathol 19:276–279PubMedCrossRefGoogle Scholar
  20. 20.
    Mhawech P, Kinkel K, Vlastos G et al (2002) Ovarian carcinomas in endometriosis: an immunohistochemical and comparative genomic hybridization study. Int J Gynecol Pathol 21:401–406PubMedCrossRefGoogle Scholar
  21. 21.
    Minkowitz G (1996) Psammoma bodies in endometriosis: clinical, cytological, and physiopathological implications. Diagn Cytopathol 14:331–333PubMedCrossRefGoogle Scholar
  22. 22.
    Mok SC, Kwong J, Welch WR et al (2007) Etiology and pathogenesis of epithelial ovarian cancer. Dis Markers 23:367–376PubMedGoogle Scholar
  23. 23.
    Obata K, Hoshiai H (2000) Common genetic changes between endometriosis and ovarian cancer. Gynecol Obstet Invest 50(Suppl 1):39–43PubMedCrossRefGoogle Scholar
  24. 24.
    Oral E, Ilvan S, Tustas E et al (2003) Prevalence of endometriosis in malignant epithelial ovary tumours. Eur J Obstet Gynecol Reprod Biol 109:97–101PubMedCrossRefGoogle Scholar
  25. 25.
    Parker RL, Dadmanesh F, Young RH et al (2004) Polypoid endometriosis: a clinicopathologic analysis of 24 cases and a review of the literature. Am J Surg Pathol 28:285–297PubMedCrossRefGoogle Scholar
  26. 26.
    Qian J, Shi Y, Chen X (2000) Clinical analysis of 25 cases of malignant transformation of endometriosis of the ovary. Zhonghua Fu Chan Ke Za Zhi 35:667–669PubMedGoogle Scholar
  27. 27.
    Gruppo Italiano per lo Studio dell’Endometriosi (2001) Relationship between stage, site and morphological characteristics of pelvic endometriosis and pain. Hum Reprod 16:2668–2671CrossRefGoogle Scholar
  28. 28.
    Ria R, Loverro G, Vacca A et al (2002) Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 agree with progression of ovarian endometriomas. Eur J Clin Invest 32:199–206PubMedCrossRefGoogle Scholar
  29. 29.
    Santeusanio G, Ventura L, Partenzi A et al (1999) Omental endosalpingiosis with endometrial-type stroma in a woman with extensive hemorrhagic pelvic endometriosis. Am J Clin Pathol 111:248–251PubMedGoogle Scholar
  30. 30.
    Sekizawa A, Amemiya S, Otsuka J et al (2004) Malignant transformation of endometriosis: application of laser microdissection for analysis of genetic alterations according to pathological changes. Med Electron Microsc 37:97–100PubMedCrossRefGoogle Scholar
  31. 31.
    Selvaggi SM (2002) Pelvic endometriosis diagnosed on touch imprint cytology. Diagn Cytopathol 27:379–381PubMedCrossRefGoogle Scholar
  32. 32.
    Spaczynski M, Kedzia W (2001) Ovarian cancer and endometriosis. Ginekol Pol 72:268–272PubMedGoogle Scholar
  33. 33.
    Staats PN, Clement PB, Young RH (2007) Primary endometrioid adenocarcinoma of the vagina: a clinicopathologic study of 18 cases. Am J Surg Pathol 31:1490–1501PubMedCrossRefGoogle Scholar
  34. 34.
    Stratton P, Winkel CA, Sinaii N et al (2002) Location, color, size, depth, and volume may predict endometriosis in lesions resected at surgery. Fertil Steril 78:743–749PubMedCrossRefGoogle Scholar
  35. 35.
    Swiersz LM (2002) Role of endometriosis in cancer and tumor development. Ann N Y Acad Sci 955:281–292 discussion 293–285, 396–406PubMedCrossRefGoogle Scholar
  36. 36.
    Thomas EJ, Campbell IG (2000) Evidence that endometriosis behaves in a malignant manner. Gynecol Obstet Invest 50(Suppl 1):2–10PubMedCrossRefGoogle Scholar
  37. 37.
    Thomas EJ, Campbell IG (2000) Molecular genetic defects in endometriosis. Gynecol Obstet Invest 50(Suppl 1):44–50PubMedCrossRefGoogle Scholar
  38. 38.
    Ulrich U, Richter O, Wardelmann E et al (2003) Endometriosis and malignoma. Zentralbl Gynakol 125:239–242PubMedCrossRefGoogle Scholar
  39. 39.
    Uzan C, Cortez A, Dufournet C et al (2005) Endometrium from women with and without endometriosis, and peritoneal, ovarian and bowel endometriosis, show different c-kit protein expression. J Reprod Immunol 65:55–63PubMedCrossRefGoogle Scholar
  40. 40.
    Valenzuela P, Ramos P, Redondo S et al (2007) Endometrioid adenocarcinoma of the ovary and endometriosis. Eur J Obstet Gynecol Reprod Biol 134:83–86PubMedCrossRefGoogle Scholar
  41. 41.
    Walter AJ, Hentz JG, Magtibay PM et al (2001) Endometriosis: correlation between histologic and visual findings at laparoscopy. Am J Obstet Gynecol 184:1407–1411 discussion 1411–1403PubMedCrossRefGoogle Scholar
  42. 42.
    Walter I, Handler J, Reifinger M et al (2001) Association of endometriosis in horses with differentiation of periglandular myofibroblasts and changes of extracellular matrix proteins. Reproduction 121:581–586PubMedCrossRefGoogle Scholar
  43. 43.
    Yamamoto S, Tsuda H, Aida S et al (2007) Immunohistochemical detection of hepatocyte nuclear factor 1beta in ovarian and endometrial clear-cell adenocarcinomas and nonneoplastic endometrium. Hum Pathol 38:1074–1080PubMedCrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2008

Authors and Affiliations

  • Mohamed Ali Bedaiwy
    • 1
  • Mahmoud Rezk Abd-Elwahed Hussein
    • 2
    • 3
  • Charles Biscotti
    • 4
  • Tommaso Falcone
    • 5
  1. 1.Department of Obstetrics and GynaecologyThe Assuit University Hospitals and The Cleveland Clinic FoundationClevelandUSA
  2. 2.Department of PathologyAssir Central Hospital, King Khalid UniversityAbhaKingdom of Saudi Arabia
  3. 3.Pathology Department, Faculty of Medicine and Assuit University HospitalsAssuit UniversityAssuitEgypt
  4. 4.Department of PathologyThe Cleveland Clinic FoundationClevelandUSA
  5. 5.Department of Obstetrics and GynaecologyThe Cleveland Clinic FoundationClevelandUSA

Personalised recommendations