Endometrial Hyperplasia and Related Cellular Changes

  • Robert J. Kurman
  • Henry J. Norris


Endometrial hyperplasia constitutes a heterogeneous group of abnormal proliferations, some of which are precursors of endometrial carcinoma. In the 1970s the role of unopposed estrogenic stimulation in the development of endometrial hyperplasia and carcinoma was firmly established on the basis of case-control studies linking these conditions with exogenous unopposed estrogen replacement therapy.26,28,54,58,72,81 Subsequently, in the 1980s various types of endometrial metaplasia were described.33,34 As the pathological features of both of these lesions became further characterized, their behavior and relationship to endometrial carcinoma have become more clearly delineated.


Endometrial Carcinoma Ciliated Cell Myometrial Invasion Endometrial Hyperplasia Atypical Hyperplasia 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Artacho-Perula E, Roldan-Villalobos R, Roldan-Villalobos A, Vaamonde-Lemos R (1993) Histomorphometry of normal and abnormal endometrial samples. Int J Gynecol Pathol 12: 173–179PubMedCrossRefGoogle Scholar
  2. 2.
    Ausems WEMA, van der Kamp J-K, Baak JAP (1985) Nuclear morphometry in the determination of the prognosis of marked atypical endometrial hyperplasia. Int J Gynecol Pathol 4: 180–185PubMedCrossRefGoogle Scholar
  3. 3.
    Baak JPA, Kurver PHJ, Diegenbach PC, Delemarre JFM, Brekelmans ECM, Nieuwlaat JE (1981) Discrimination of hyperplasia and carcinoma of the endometrium by quantitative microscopy—a feasibility study. Histopathology 5: 61–68PubMedCrossRefGoogle Scholar
  4. 4.
    Baak JPA, Nauta JJF, Wisse-Brekelmans ECM, Bezemer PD (1988) Architectural and nuclear morphometrical features together are more important prognosticators in endometrial hyperplasias than nuclear morphometrical features alone. J Pathol 154: 335–41PubMedCrossRefGoogle Scholar
  5. 5.
    Baak JPA, Wise-Brekelmans ECM, Fleege JC, van der Putten HWHM, Bezemer PD (1992) Assessment of the risk on endometrial cancer in hyperplasia, by means of morphological and morphometric features. Pathol Res Pract 188: 856–859PubMedCrossRefGoogle Scholar
  6. 5a.
    Beckner ME, Mori T, Silverberg SG (1985) Endometrial carcinoma: Non-tumor factors in prognosis. Int J Gynecol Pathol 4: 131–145PubMedCrossRefGoogle Scholar
  7. 6.
    Blaustein A (1982) Morular metaplasia misdiagnosed as adenoacanthoma in young women with polycystic ovarian disease. Am J Surg Pathol 6: 223–228PubMedCrossRefGoogle Scholar
  8. 7.
    Buehl IA, Vellios F, Carter JE, Huber CP (1964) Carcinoma in situ of the endometrium. Am J Clin Pathol 42: 594–601PubMedGoogle Scholar
  9. 8.
    Campbell PE, Barter RA (1961) The significance of atypical hyperplasia. J Obstet Gynaecol Br Commonw 68: 668–672PubMedCrossRefGoogle Scholar
  10. 9.
    Chamlian DL, Taylor HB (1970) Endometrial hyperplasia in young women. Obstet Gynecol 36: 659–666PubMedGoogle Scholar
  11. 10.
    Colgan TJ, Noms HJ, Foster W, Kurman RJ, Fox CH (1983) Predicting the outcome of endometrial hyperplasia by quantitative analysis of nuclear features using a linear discriminant function. Int J Gynecol Pathol 1: 347–352PubMedCrossRefGoogle Scholar
  12. 11.
    Crum CP, Richart RM, Fenoglio CM (1981) Adenoacanthosis of the endometrium. A clinicopathologic study in premenopausal women. Am J Surg Pathol 5: 15–20PubMedCrossRefGoogle Scholar
  13. 12.
    Demopoulos RI, Greco MA (1983) Mucinous metaplasia of the endometrium: Ultrastructural and histochemical characteristics. Int J Gynecol Pathol 1: 383–390PubMedCrossRefGoogle Scholar
  14. 13.
    Dewagne MP, Silverberg SG (1982) Foam cells in endometrial carcinoma. A clinicopathologic study. Gynecol Oncol 13: 67–75CrossRefGoogle Scholar
  15. 14.
    Fechner RE (1980) Ultrastructure of endometrial stromal foam cells. (Letter) Am J Clin Pathol 73: 731–732Google Scholar
  16. 15.
    Fechner RE, Bossart MI, Spjut HJ (1979) Ultrastructure of endometrial stromal foam cells. Am J Clin Pathol 72: 628–633PubMedGoogle Scholar
  17. 16.
    Fenoglio CM, Crum CP, Ferenczy A (1982) Endometrial hyperplasia and carcinoma. Are ultrastructural, biochemical, and immunocytochemical studies useful in distinguishing between them? Pathol Res Pract 174: 257–284Google Scholar
  18. 17.
    Ferenczy A (1979) Recent advances in endometrial neoplasia. Exp Mol Pathol 31: 226–235PubMedCrossRefGoogle Scholar
  19. 18.
    Ferenczy A (1982) Cytodynamics of endometrial hyperplasia and neoplasia. I. Histology and ultrastructure. In: Fenoglio CM, Wolff M (eds) Progress in Surgical Pathology, Vol. 4. New York, Masson Publishing USA, p 95Google Scholar
  20. 19.
    Ferenczy A (1983) Cytodynamics of endometrial hyperplasia and neoplasia. Part II: In vitro DNA histoautoradiography. Hum Pathol 14: 77–82PubMedCrossRefGoogle Scholar
  21. 20.
    Ferenczy A, Gelfand M (1989) The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol 160: 126–131PubMedGoogle Scholar
  22. 21.
    Fluhman CF (1954) Comparative studies of squamous metaplasia of the cervix uteri and endometrium. Am J Obstet Gynecol 68: 1447–1463Google Scholar
  23. 22.
    Fu YS, Ferenczy A, Huang I, Gelfand MM (1988) Digital imaging analysis of normal, hyperplastic and malignant endometrial cells in endometrial brushing samples. Anal Quant Cytol Histol 10: 139–149PubMedGoogle Scholar
  24. 23.
    Gal D (1986) Hormonal therapy for lesions of the endometrium. Semin Oncol 13: 33–36PubMedGoogle Scholar
  25. 24.
    Goldstein SR, Nachtigal M, Snyder JR, Nachtigal L (1990) Endometrial assessment by vaginal ultrasonography before endometrial sampling in patients with postmenopausal bleeding. Am J Obstet Gynecol 163: 119–123PubMedGoogle Scholar
  26. 25.
    Granberg S, Wikland M, Karlsson B, Norstrom A, Friberg L-G (1991) Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality. Am J Obstet Gynecol 164: 47–52PubMedGoogle Scholar
  27. 26.
    Gray LA, Christopherson WM, Hoover RN (1977) Estrogens and endometrial carcinoma. Obstet Gynecol 49: 385–389PubMedGoogle Scholar
  28. 27.
    Greenblatt RB, Gambrell RD Jr, Stoddard LD (1982) The protective role of progesterone in the prevention of endometrial cancer. Pathol Res Pract 174: 297–318PubMedCrossRefGoogle Scholar
  29. 28.
    Greenwald P, Caputo TA, Wolfgang PE (1977) Endometrial cancer after menopausal use of estrogens. Obstet Gynecol 50: 239–243PubMedGoogle Scholar
  30. 29.
    Grimes DA (1982) Diagnostic dilation and curettage: A reappraisal. Am J Obstet Gynecol 142: 1–6PubMedGoogle Scholar
  31. 30.
    Gusberg SB, Moore DB, Martin F (1954) Precursors of corpus cancer. II. A clinical and pathological study of adenomatous hyperplasia. Am J Obstet Gynecol 68: 1472–1481PubMedGoogle Scholar
  32. 31.
    Gusberg SB, Kaplan AL (1963) Precursors of corpus cancer. IV. Adenomatous hyperplasia as stage 0 carcinoma of the endometrium. Am J Obstet Gynecol 87: 662–678PubMedGoogle Scholar
  33. 32.
    Gusberg SB (1974) Precursors of corpus carcinoma. Estrogens and adenomatous hyperplasia. Am J Obstet Gynecol 54: 905–927Google Scholar
  34. 33.
    Hendrickson MR, Kempson RL (1980) Endometrial epithelial metaplasias—proliferations frequently misdiagnosed as adenocarcinoma: Report of 89 cases and proposed classification. Am J Surg Pathol 4: 525–542PubMedCrossRefGoogle Scholar
  35. 34.
    Hendrickson MR, Kempson RL (1980) In: Bennington JL (ed) Surgical Pathology of the Uterine Corpus. Major Problems in Pathology. Philadelphia, London, Toronto, W. B. SaundersGoogle Scholar
  36. 35.
    Herlyn M, Malkowicz SB (1991) Regulatory pathways in tumor growth and invasion. Lab Invest 65: 262–271PubMedGoogle Scholar
  37. 36.
    Hertig AT, Sommers SC (1949) Genesis of endometrial carcinoma. I. Study of prior biopsies. Cancer 2: 946–956PubMedCrossRefGoogle Scholar
  38. 37.
    Hertig AT, Sommers SC, Bengaloff H (1949) Genesis of endometrial carcinoma. III. Carcinoma in situ. Cancer 2: 964–971PubMedCrossRefGoogle Scholar
  39. 38.
    Hustin J (1976) Morphology and DNA content of endometrial cancer nuclei under progestogen treatment. Acta Cytol 20: 556–558PubMedGoogle Scholar
  40. 39.
    Iozzo RV (1984) Proteoglycans and neoplastic-mesenchymal cell interactions. Hum Pathol 15: 2–10PubMedCrossRefGoogle Scholar
  41. 40.
    Kaku T, Tsukamoto N, Tsuruchi N, Sugihara K, Kamura T, Nakano H (1992) Endometrial metaplasia associated with endometrial carcinoma. Obstet Gynecol 80: 812–816PubMedGoogle Scholar
  42. 41.
    Kaminski PF, Stevens CW (1988) The value of endometrial sampling in abnormal uterine bleeding. Am J Gynecol Health II: 33–36Google Scholar
  43. 42.
    Katayma KP, Jones HW (1967) Chromosomes of atypical (adenomatous) hyperplasia and carcinoma of the endometrium. Am J Obstet Gynecol 97: 978–983Google Scholar
  44. 43.
    King A, Seraj IM, Wagner RJ (1984) Stromal invasion in endometrial carcinoma. Am J Obstet Gynecol 149: 10–14PubMedGoogle Scholar
  45. 44.
    Klemi PJ, Gronroos M, Rauramo L, Punnonen R (1980) Ultrastructural features of endometrial atypical adenomatous hyperplasia and adenocarcinomas and the plasma levels of estrogens. Gynecol Oncol 9: 162–169PubMedCrossRefGoogle Scholar
  46. 45.
    Kraus FT (1985) High-risk and premalignant lesions of the endometrium. Am J Surg Pathol 9(3)(suppl): 31–40Google Scholar
  47. 46.
    Kurman RJ, Scully RE (1976) Clear cell carcinoma of the endometrium. An analysis of 21 cases. Cancer 37: 872–882PubMedCrossRefGoogle Scholar
  48. 47.
    Kurman RJ, Noms HJ (1982) Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well differentiated carcinoma. Cancer 49: 2547–2559PubMedCrossRefGoogle Scholar
  49. 48.
    Kurman RJ, Kaminski PF, Noms HJ (1985) The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer 56: 403–412PubMedCrossRefGoogle Scholar
  50. 49.
    Kurman RJ, Noms HJ (1986) Endometrium. In: Henson D, Albores Saavedra J (eds) The Pathology of Incipient Neoplasia. Philadelphia, W. B. Saunders, p 265Google Scholar
  51. 50.
    Lee KR, Scully RE (1989) Complex endometrial hyperplasia and carcinoma in adolescents and young women 15 to 20 years of age. Int J Gynecol Pathol 8: 201–212PubMedCrossRefGoogle Scholar
  52. 51.
    Leof EB, Wharton W, van Wyk JJ, Pledger WJ (1992) Epidermal growth factor (EGF) and somatomedin C regulate Gl progression in competent BALB/c-3T3 cells. Exp Cell Res 141: 107–115CrossRefGoogle Scholar
  53. 52.
    Lidor AB, Ismajovich B, Confino E, David MP (1986) Histopathological findings in 226 women with postmenopausal uterine bleeding. Acta Obstet Gynecol Scand 65: 41–43PubMedCrossRefGoogle Scholar
  54. 53.
    Liotta LA, Rao CN, Barsky SH (1983) Tumor invasion and the extracellular matrix. Lab Invest 49: 636–649PubMedGoogle Scholar
  55. 54.
    Mack TM, Pike MC, Henderson BE, Pfeffer RI, Gerkins VR, Arthur M, Brown SE (1976) Estrogens and endometrial cancer in a retirement community. N Engl J Med 294: 1262–1267PubMedCrossRefGoogle Scholar
  56. 55.
    Masterson R, Armstrong EM, Moore IAR (1975) The cyclical variation in the percentage of ciliated cells in the normal human endometrium. J Reprod Fertil 42: 537–540CrossRefGoogle Scholar
  57. 56.
    Mazur MT (1981) Atypical polypoid adenomyomas of the endometrium. Am J Surg Pathol 5: 473–482PubMedCrossRefGoogle Scholar
  58. 57.
    McBride JM (1959) Pre-menopausal cystic hyperplasia and endometrial carcinoma. J Obstet Gynaecol Br Emp 66: 288–296PubMedCrossRefGoogle Scholar
  59. 58.
    McDonald TW, Annegers JF, O’Fallon WM, Dockerty MB, Malkasian GD, Kurland LT (1977) Exogenous estrogen and endometrial carcinoma: Case-control and incidence study. Am J Obstet Gynecol 127: 572–580PubMedGoogle Scholar
  60. 59.
    Noms HJ, Tavassoli FA, Kurman RJ (1983) Endometrial hyperplasia and carcinoma. Diagnostic considerations. Am J Surg Pathol 7: 839–846Google Scholar
  61. 60.
    Noms HJ, Becker RL, Mikel UV (1989) A comparative morphometric and cytophotometric study of endometrial hyperplasia, atypical hyperplasia, and endometrial carcinoma. Hum Pathol 20: 219–223CrossRefGoogle Scholar
  62. 61.
    Novak E, Rutledge F (1948) Atypical endometrial hyperplasia simulating adenocarcinoma. Am J Obstet Gynecol 55: 46–63PubMedGoogle Scholar
  63. 62.
    Richart RM, Ludwig AS (1969) Alterations in chromosomes and DNA content in gynecologic neoplasms. Am J Obstet Gynecol 104: 463–471PubMedGoogle Scholar
  64. 63.
    Richart RM, Ferenczy A (1974) Endometrial morphologic response to hormonal environment. Gynecol Oncol 2: 180–197PubMedCrossRefGoogle Scholar
  65. 64.
    Rorat E, Wallach RC (1984) Papillary metaplasia of the endometrium: Clinical and histopathologic considerations. Obstet Gynecol 64: 90S–92SPubMedCrossRefGoogle Scholar
  66. 65.
    Rozengurt E, Sinnett-Smith J, Taylor-Papadimitriou J (1985) Production of PDGF-like growth factor by breast cancer cell lines. Int J Cancer 36: 247–252PubMedCrossRefGoogle Scholar
  67. 66.
    Salm R (1962) Macrophages in endometrial lesions. J Pathol Bacteriol 83: 405–409PubMedCrossRefGoogle Scholar
  68. 67.
    Sawhney N, Garrahan N, Douglas-Jones AG, Williams ED (1992) Epithelial-tromal interactions in tumors. A morphologic study of fibroepithelial tumors of the breast. Cancer 70: 2115–2120PubMedCrossRefGoogle Scholar
  69. 68.
    Scully RE, Poulson H, Sobin L (in press) World Health Organization—Histologic Typing of Tumors of the Female Genital Tract. Heidelberg, Springer-VerlagGoogle Scholar
  70. 69.
    Seemayer TA, Schurch W, Lagace R, Tremblay G (1979) Myofibroblasts in the stroma of invasive and metastatic carcinoma. Am J Surg Pathol 3: 525–533PubMedCrossRefGoogle Scholar
  71. 70.
    Silver MM, Miles P, Rosa C (1991) Comparison of Novak and Pipelle endometrial biopsy instruments. Obstet Gynecol 78: 828–830PubMedGoogle Scholar
  72. 71.
    Silverberg SG, Kurman RJ (1992) Atlas of Tumor Pathology. Tumors of the Uterine Corpus and Gestational Trophoblastic Disease, Third Series, Fascicle 3, Armed Forces Institute of Pathology, Washington, D.C.Google Scholar
  73. 72.
    Smith DC, Prentice R, Thompson DJ, Hermann WL (1975) Association of exogenous estrogen and endometrial carcinoma. N Engl J Med 293: 1164–1167PubMedCrossRefGoogle Scholar
  74. 73.
    Smith P, Bakos O, Heimer G, Ulmsten U (1991) Transvaginal ultrasound for identifying endometrial abnormality. Acta Obstet Gynecol Scand 70: 591–594PubMedCrossRefGoogle Scholar
  75. 74.
    Stock RJ, Kanbour A (1975) A prehysterectomy curettage. Obstet Gynecol 45: 537–541PubMedGoogle Scholar
  76. 75.
    Stovall TG, Ling FW, Morgan PL (1991) A prospective, randomized comparison of the Pipelle endometrial sampling device with the Novak curette. Am J Obstet Gynecol 165: 1287–1289PubMedGoogle Scholar
  77. 76.
    Tavassoli FA, Kraus FT (1978) Endometrial lesions in uteri resected for atypical endometrial hyperplasia. Am J Clin Pathol 70: 770–779PubMedGoogle Scholar
  78. 77.
    Tobon H, Watkins GJ (1985) Secretory adenocarcinoma of the endometrium. Int J Gynecol Pathol 4: 328–335PubMedCrossRefGoogle Scholar
  79. 78.
    Wagner D, Richart RM, Temer JY (1967) Deoxyribonucleic acid content of presumed precursors of endometrial carcinoma. Cancer 20: 2067–2077PubMedCrossRefGoogle Scholar
  80. 79.
    Welch WR, Scully RE (1977) Precancerous lesions of the endometrium. Hum Pathol 8: 503–512PubMedCrossRefGoogle Scholar
  81. 80.
    Zaman SS, Mazur MT (1993) Endometrial papillary syncytial change. A nonspecific alteration associated with active breakdown. Am J Clin Pathol 99: 741–745PubMedGoogle Scholar
  82. 81.
    Ziel HK, Finkle WD (1975) Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 293: 1167–1170PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Robert J. Kurman
  • Henry J. Norris

There are no affiliations available

Personalised recommendations