Mehmet ZENGIN, Merva AYDEMİR AKKAYA, Merve ERYOL, Tuba DEVRİM, Selim YALÇIN, Zehra Sema ÖZKAN

Did the terminology of endometrial intraepithelial neoplasia resolve the chaos in the classification of endometrial hyperplasia? a 8-year retrospective study

ABSTRACT Aim: Endometrial intraepithelial neoplasia (EIN) is a monoclonal glandular lesion defined in the new WHO classification (2014), which is the precursor of the development of endometrioid type endometrial adenocarcinoma (EEA). We retrospectively analyzed the role of this new entity on the diagnosis of EEA. Methods: 60 cases diagnosed with EEA between 2007 and 2015 were included in this retrospective study. The cases were reevaluated for EIN using sections stained with hematoxylin and eosin. Results: EIN was significantly associated with age (p = 0.022), EEA (p = 0.010) and CEH (with atypia) (p = 0.038). When the univariate analysis was examined, 5-year relapse-free survival was poor (p = 0.035) for EIN patients. When the multivariate analysis was examined, it was seen that EIN was an independent predictor of poor survival for relapse-free survival (HR=2.77 [1.22-4.78], p=0.046). Conclusions: According to our study, EIN played an important role in the development of EEA, but no significant superiority over the old classification was observed. For this reason, we recommend that the old and new classifications are noted together for a healthier decision. Keywords: Endometrial intraepithelial neoplasia, endometrial adenocarcinoma, endometrial hyperplasia. ÖZ Amaç: Endometrial intraepitelyal neoplazi (EIN), endometrioid tip endometrial adenokarsinomun (EEA) gelişiminin öncüsü olan, yeni WHO sınıflandırmasında (2014) tanımlanan, monoklonal glandüler bir lezyondur. Bu yeni antitenin endometriyal karsinom tanısı üzerindeki rolünü retrospektif olarak inceledik. Yöntemler: Bu retrospektif çalışmaya 2007-2015 yılları arasında EEA tanısı konan 60 olgu dahil edildi. Vakalar, hematoksilin ve eozin ile boyanmış bölümler kullanılarak EIN açısından yeniden değerlendirildi. Bulgular: EIN, yaş (p = 0.022), EEA (p = 0.010) ve CEA (atipili) (p = 0.038) ile anlamlı derecede ilişkiliydi. Tek değişkenli analiz incelendiğinde, EIN hastaları için 5 yıllık nükssüz sağkalım daha kötüydü (p = 0.035). Çok değişkenli analiz incelendiğinde, EIN'nin nükssüz sağkalım için kötü sağkalımın bağımsız bir öngörücüsü olduğu görüldü (HR=2.77 [1.22-4.78], p=0.046). Sonuçlar: Çalışmamıza göre EIN, EEA'nın gelişiminde önemli bir rol oynamaktadır, ancak eski sınıflandırmaya göre önemli bir üstünlük gözlenmemiştir. Bu nedenle, daha sağlıklı bir karar için eski ve yeni sınıflandırmaların birlikte not edilmesini öneririz. Anahtar Kelimeler: Endometrial intraepitelyal neoplazi, endometrial adenokarsinom, endometrioid tip, endometrial hiperplazi.

Keywords:

Endometrial intraepithelial neoplasia, endometrial adenocarcinoma, endometrial hyperplasia,

PDF

___

1. Jemal A, Siegel R, and Xu J. Cancer statistics. CA Cancer J Clin 2010;60:277-300 2. Zaino RJ. Endometrial hyperplasia: Is it time for a quantum leap to a new classification? Int J Gynecol Pathol 2000;19:314-321. 3. Bergeron C, Nogales FF, Masseroli M, et al. A multicentric European study testing the reproducibility of the WHO classification of endometrial hyperplasia with a proposal of a simplified working classification for biopsy and curettage specimens. Am J Surg Pathol 1999;23:1102-1108 4. Usubutun A, Mutter GL, Saglam A, et al. Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists. Mod Pathol. 2012;25(6):877–884. 5. Baak JP, Mutter GL, Robboy S, et al. The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system Cancer 2005;103:2304-2312 6. Mutter GL, Baak JP, Crum CP, et al. Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry. J Pathol 2000;190:462-469 7. Hecht JL, Mutter GL. Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol. 2006;24(29):4783–4791. 8. Zheng W, Baker HE, and Mutter GL. Involution of PTEN-null endometrial glands with progestin therapy. Gynecol Oncol 2004; 92:1008-1013 9. Lacey JV, Mutter GL, Nucci MR, et al. Risk of subsequent endometrial carcinoma associated with endometrial intraepithelial neoplasia classification of endometrial biopsies. Cancer. 2008;113(8):2073–2081. 10. Gultekin, M, Diribas K, Dursan P, et al. Current management of endometrial hyperplasia and endometrial intraepithelial neoplasia (EIN). Eur J Gynaecol Oncol. 2009;30(4):396–401. 11. Salman MC, Usubutun A, Boynukalin K, et al. Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia. J Gynecol Oncol. 2010;21(2):97–101. 12. Mutter GL. Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? Gynecol Oncol 2000;76:287-290 13. Lin MC, Lomo L, Baak JP, et al. Squamous morules are functionally inert elements of premalignant endometrial neoplasia. Mod Pathol 2009;22:167-174 14. Trimbel CL, Kaudener J, Zaino R, et al. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a gynecologic oncology group study. Cancer. 2006;106(4):812–819. 15. Wheeler DT, Bristow RE, and Kurman RJ: Histologic alterations in endometrial hyperplasia and well-differentiated carcinoma treated with progestins. Am J Surg Pathol 2007;31:988-998 16. Carlson JW, and Mutter GL. Endometrial intraepithelial neoplasia is associated with polyps and frequently has metaplastic change. Histopathology 2008;53:325-332 17. Kane SE, and Hecht JL. Endometrial intraepithelial neoplasia terminology in practice: 4-year experience at a single institution. Int J Gynecol Pathol. 2012;31(2):160–165 18. Allison KH, Reed SD, Voigt LF, et al. Diagnosing endometrial hyperplasia: why is it so difficult to agree? Am J Surg Pathol. 2008; 32(5):691–698. 19. Zaino RJ, Kauderer J, Trimble CL, et al. Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer. 2006;106(4):804–811. 20. Signorelli M, Caspani G, Bonazzi C, et al. Fertility-sparing treatment in young women with endometrial cancer or atypical complex hyperplasia: a prospective single-institution experience of 21 cases. Br J Obstet Gynaecol 2009;116:114-118 21. Boruban MC, Altundag K, Kilic GS, et al. From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures. Eur J Cancer Prev. 2008;17(2):133–138.