Pregnancy, Abortion, and Ectopic Pregnancy

  • Tricia A. Murdock
  • Emanuela F. T. Veras
  • Robert J. Kurman
  • Michael T. Mazur


Recognition of the features of gestational endometrium, trophoblast, and villi, as well as the pathologic changes in chorionic tissues, is an important part of endometrial biopsy interpretation. The presence of intrauterine products of conception generally excludes the diagnosis of ectopic pregnancy and can help explain other pathologic states such as abnormal bleeding or chronic endometritis.


Ectopic pregnancy Gestational endometrium Intrauterine products of conception Spontaneous abortion Trophoblast and villi Endometrium associated with ectopic pregnancy 


  1. 1.
    Mishell DRJ. Spontaneous and recurrent abortion. In: Stenchever MA, Droegemueller W, Herbst AL, Mishell Jr DR, editors. Comprehensive gynecology. 2nd ed. St. Louis: Mosby; 2001. p. 413–41.Google Scholar
  2. 2.
    Kalousek DK. Pathology of abortion: chromosomal and genetic correlations. In: Kraus FT, Damjanov I, Kaufman N, editors. Pathology of reproductive failure. Baltimore: Williams & Wilkins; 1991. p. 228–56.Google Scholar
  3. 3.
    Miller JF, Williamson E, Glue J, Gordon YB, Grudzinskas JG, Sykes A. Fetal loss after implantation. A prospective study. Lancet. 1980;2:554–6.CrossRefGoogle Scholar
  4. 4.
    Benirschke K, Kaufmann P. Pathology of the human placenta. 4th ed. New York: Springer; 2000.CrossRefGoogle Scholar
  5. 5.
    Wilcox AJ, Weinberg CR, O’Conner JF, Baird DD, Schlatterer JP, Camfield RE, et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319:189–94.CrossRefGoogle Scholar
  6. 6.
    Simpson JL. Incidence and timing of pregnancy losses. Am J Med Genet. 1990;35:165–73.CrossRefGoogle Scholar
  7. 7.
    Mazur MT, Duncan DA, Younger JB. Endometrial biopsy in the cycle of conception. Histologic and lectin histochemical evaluation. Fertil Steril. 1989;51:764–7.CrossRefGoogle Scholar
  8. 8.
    Foss BA, Horne HW, Hertig AT. The endometrium and sterility. Fertil Steril. 1958;9:193–206.CrossRefGoogle Scholar
  9. 9.
    Karow WG, Gentry WC, Skeels RF, Payne SA. Endometrial biopsy in the luteal phase of the cycle of conception. Fertil Steril. 1971;22:482–95.CrossRefGoogle Scholar
  10. 10.
    Hertig AT. Gestational hyperplasia of endometrium. A morphologic correlation of ova, endometrium, and corpora lutea during early pregnancy. Lab Investig. 1964;13:1153–91.PubMedGoogle Scholar
  11. 11.
    Wentz AC, Herbert CMI, Maxson WS, Hill GA, Pittaway DE. Cycle of conception endometrial biopsy. Fertil Steril. 1986;46:196–9.CrossRefGoogle Scholar
  12. 12.
    Lichtig C, Korat A, Deutch M, Brandes JM. Decidual vascular changes in early pregnancy as a marker for intrauterine pregnancy. Am J Clin Pathol. 1988;90:284–8.CrossRefGoogle Scholar
  13. 13.
    Clement PB, Young RH, Scully RE. Nontrophoblastic pathology of the female genital tract and peritoneum associated with pregnancy. Semin Diagn Pathol. 1989;6:372–406.PubMedGoogle Scholar
  14. 14.
    Holmes EJ, Lyle WH. How early in pregnancy does the Arias–Stella reaction occur? Arch Pathol. 1973;95:302–3.PubMedGoogle Scholar
  15. 15.
    Arias-Stella J. Atypical endometrial changes produced by chorionic tissue. Hum Pathol. 1972;3:450–3.CrossRefGoogle Scholar
  16. 16.
    Arias-Stella J. Atypical endometrial changes associated with the presence of chorionic tissue. AMA Arch Pathol. 1954;58:112–28.PubMedGoogle Scholar
  17. 17.
    Arias-Stella J. The Arias-Stella reaction: facts and fancies four decades after. Adv Anat Pathol. 2002;9:12–23.CrossRefGoogle Scholar
  18. 18.
    Dardi LE, Ariano L, Ariano MC, Gould VE. Arias-Stella reaction with prominent nuclear pseudoinclusions simulating herpetic endometritis. Diagn Gynecol Obstet. 1982;4:127–32.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Beswick IP, Gregory MM. The –Arias-Stella phenomenon and the diagnosis of pregnancy. J Obstet Gynaecol. 1971;78:143–8.CrossRefGoogle Scholar
  20. 20.
    Bernhardt RN, Bruns PD, Drose VE. Atypical endometrium associated with ectopic pregnancy. The Arias-Stella phenomenon. Obstet Gynecol. 1966;23:849–53.Google Scholar
  21. 21.
    LaIuppa MA, Cavanagh D. The endometrium in ectopic pregnancy. A study based on 35 patients treated by hysterectomy. Obstet Gynecol. 1963;21:155–64.PubMedGoogle Scholar
  22. 22.
    Roach WR, Guderian AM, Brewer JI. Endometrial gland cell atypism in the presence of trophoblast. Am J Obstet Gynecol. 1960;79:680–91.CrossRefGoogle Scholar
  23. 23.
    Huettner PC, Gersell DJ. Arias-Stella reaction in nonpregnant women: a clinicopathologic study of nine cases. Int J Gynecol Pathol. 1994;13:241–7.CrossRefGoogle Scholar
  24. 24.
    Yokoyama S, Kashima K, Inoue S, Daa T, Nakayama I, Moriuchi A. Biotin-containing intranuclear inclusions in endometrial glands during gestation and puerperium. Am J Clin Pathol. 1993;99:13–7.CrossRefGoogle Scholar
  25. 25.
    Mazur MT, Hendrickson MR, Kempson RL. Optically clear nuclei. An alteration of endometrial epithelium in the presence of trophoblast. Am J Surg Pathol. 1983;7:415–23.CrossRefGoogle Scholar
  26. 26.
    Genest DR, Brodsky G, Lage JA. Localized endometrial proliferations associated with pregnancy: clinical and histopathologic features of 11 cases. Hum Pathol. 1995;26(11):1233–40.CrossRefGoogle Scholar
  27. 27.
    Schammel DP, Mittal KR, Kaplan K, Deligdisch L, Tavassoli FA. Endometrial adenocarcinoma associated with intrauterine pregnancy. A report of five cases and a review of the literature. Int J Gynecol Pathol. 1998;17:327–35.CrossRefGoogle Scholar
  28. 28.
    Kovacs AG, Cserni G. Endometrial adenocarcinoma in early pregnancy. Gynecol Obstet Investig. 1996;41:70–2.CrossRefGoogle Scholar
  29. 29.
    Nakamura Y, Moritsuka Y, Ohta Y, Itoh S, Haratake A, Kage M, et al. S-100 protein in glands within decidua and cervical glands during early pregnancy. Hum Pathol. 1989;20:1204–9.CrossRefGoogle Scholar
  30. 30.
    Agarwal S, Singh UR. Immunoreactivity with S100 protein as an indicator of pregnancy. Indian J Med Res. 1992;96:24–6.PubMedGoogle Scholar
  31. 31.
    Shih I-M, Mazur MT, Kurman RJ. Gestational trophoblastic tumors and related tumor-like lesions. In: Kurman RJ, editor. Blaustein’s pathology of the female genital tract. 6th ed. New York: Springer; 2011. p. 1075–135.CrossRefGoogle Scholar
  32. 32.
    Kurman RJ, Main CS, Chen HC. Intermediate trophoblast: a distinctive form of trophoblast with specific morphological, biochemical and functional features. Placenta. 1984;5:349–70.CrossRefGoogle Scholar
  33. 33.
    Kurman RJ, Young RH, Norris HJ, Main CS, Lawrence WD, Scully RE. Immunocytochemical localization of placental lactogen and chorionic gonadotropin in the normal placenta and trophoblastic tumors, with emphasis on intermediate trophoblast and the placental site trophoblastic tumor. Int J Gynecol Pathol. 1984;3:101–21.CrossRefGoogle Scholar
  34. 34.
    Yeh IT, O’Connor DM, Kurman RJ. Intermediate trophoblast: further immunocytochemical characterization. Mod Pathol. 1990;3:282–7.PubMedGoogle Scholar
  35. 35.
    Yeh I-T, Kurman RJ. Functional and morphologic expressions of trophoblast. Lab Investig. 1989;61:1–4.PubMedGoogle Scholar
  36. 36.
    Wells M, Bulmer JN. The human placental bed: histology, immunohistochemistry and pathology. Histopathology. 1988;13:483–98.CrossRefGoogle Scholar
  37. 37.
    Shih IM, Seidman JD, Kurman RJ. Placental site nodule and characterization of distinctive types of intermediate trophoblast. Hum Pathol. 1999;30:687–94.CrossRefGoogle Scholar
  38. 38.
    Mao T-L, Kurman RJ, Huang C-C, Lin M-C, Shih I-M. Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis. Am J Surg Pathol. 2007;31:1726–32.CrossRefGoogle Scholar
  39. 39.
    Kalhor N, Ramirez PT, Deavers MT, Malpica A, Silva EG. Immunohistochemical studies of trophoblastic tumors. Am J Surg Pathol. 2009;33:633–8.CrossRefGoogle Scholar
  40. 40.
    Singer G, Kurman RJ, McMaster MT, Shih I-M. HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis. Am J Surg Pathol. 2002;26:914–20.CrossRefGoogle Scholar
  41. 41.
    Mao TL, Kurman RJ, Jeng YM, Huang W, Shih IM. HSD3B1 as a novel trophoblast-associated marker that assists in the differential diagnosis of trophoblastic tumors and tumorlike lesions. Am J Surg Pathol. 2008;32(2):236–42.CrossRefGoogle Scholar
  42. 42.
    Chou YY, Jeng YM, Mao TL. HSD3B1 is a specific trophoblast-associated marker not expressed in a wide spectrum of tumors. Int J Gynecol Cancer. 2013;23(2):343–7.CrossRefGoogle Scholar
  43. 43.
    Mirkovic J, Elias K, Drapkin R, Barletta JA, Quade B, Hirsch MS. GATA3 expression in gestational trophoblastic tissues and tumours. Histopathology. 2015;67(5):636–44.CrossRefGoogle Scholar
  44. 44.
    Bamberger AM, Aupers S, Milde-Langosch K, Löning T. Expression pattern of the cell cycle promoter cyclin E in benign extravillous trophoblast and gestational trophoblastic lesions: correlation with expression of Ki-67. Int J Gynecol Pathol. 2003;22(2):156–61.CrossRefGoogle Scholar
  45. 45.
    Shih IM. Trophogram, an immunohistochemistry-based algorithmic approach, in the differential diagnosis of trophoblastic tumors and tumorlike lesions. Ann Diagn Pathol. 2007;11(3):228–34.CrossRefGoogle Scholar
  46. 46.
    Shih IM, Kurman RJ. Immunohistochemical localization of inhibin-alpha in the placenta and gestational trophoblastic lesions. Int J Gynecol Pathol. 1999;18:144–50.CrossRefGoogle Scholar
  47. 47.
    Shih IM, Kurman RJ. Expression of melanoma cell adhesion molecule in intermediate trophoblast. Lab Investig. 1996;75:377–88.PubMedGoogle Scholar
  48. 48.
    Silverberg SG, Kurman RJ. Tumors of the uterine corpus and gestational trophoblastic disease, Atlas of tumor pathology, 3rd series, fascicle 3. Washington, DC: Armed Forces Institute of Pathology; 1992.Google Scholar
  49. 49.
    Kurman RJ. The morphology, biology, and pathology of intermediate trophoblast—a look back to the present. Hum Pathol. 1991;22:847–55.CrossRefGoogle Scholar
  50. 50.
    Young RE, Kurman RJ, Scully RE. Proliferations and tumors of intermediate trophoblast of the placental site. Semin Diagn Pathol. 1988;5:223–37.PubMedGoogle Scholar
  51. 51.
    Wan SK, Lam PWY, Pau MY, Chan JKC. Multiclefted nuclei. A helpful feature for identification of intermediate trophoblastic cells in uterine curetting specimens. Am J Surg Pathol. 1992;16:1226–32.CrossRefGoogle Scholar
  52. 52.
    O’Connor DM, Kurman RJ. Intermediate trophoblast in uterine curettings in the diagnosis of ectopic pregnancy. Obstet Gynecol. 1988;72:665–70.PubMedGoogle Scholar
  53. 53.
    Daya D, Sabet L. The use of cytokeratin as a sensitive and reliable marker for trophoblastic tissue. Am J Clin Pathol. 1991;95:137–41.CrossRefGoogle Scholar
  54. 54.
    Angel E, Davis JR, Nagle RB. Immunohistochemical demonstration of placental hormones in the diagnosis of uterine versus ectopic pregnancy. Am J Clin Pathol. 1985;84:705–9.CrossRefGoogle Scholar
  55. 55.
    Shih IM, Kurman RJ. Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and Mel-CAM antibodies. Hum Pathol. 1998;29:27–33.CrossRefGoogle Scholar
  56. 56.
    Szulman AE. Examination of the early conceptus. Arch Pathol Lab Med. 1991;115:696–700.PubMedGoogle Scholar
  57. 57.
    Rushton DI. Examination of products of conception from previable human pregnancies. J Clin Pathol. 1981;34:819–35.CrossRefGoogle Scholar
  58. 58.
    Redline RW, Zaragoza M, Hassold T. Prevalence of developmental and inflammatory lesions in nonmolar first-trimester spontaneous abortions. Hum Pathol. 1999;30(1):93–100.CrossRefGoogle Scholar
  59. 59.
    Jurkovic I, Muzelak R. Frequency of pathologic changes in the young human chorion in therapeutic abortions of normal pregnancies: a report of 500 cases studied histologically. Am J Obstet Gynecol. 1970;108:382–6.CrossRefGoogle Scholar
  60. 60.
    Vanlijnschoten G, Arends JW, Delafuente AA, Schouten HJA, Geraedts JPM. Intra-observer and inter-observer variation in the interpretation of histological features suggesting chromosomal abnormality in early abortion specimens. Histopathology. 1993;22:25–9.CrossRefGoogle Scholar
  61. 61.
    Novak R, Agamanolis D, Dasu S, Igel H, Platt M, Robinson H, et al. Histologic analysis of placental tissue in first trimester abortions. Pediatr Pathol. 1988;8:477–82.CrossRefGoogle Scholar
  62. 62.
    Gersell DJ, Kraus FT. Diseases of the placenta. In: Ellenson LH, Ronnett BM, Kurman RJ, editors. Blaustein’s pathology of the female genital tract. 6th ed. New York: Springer; 2011. p. 999–1073.CrossRefGoogle Scholar
  63. 63.
    Genest DR. Estimating the time of death in stillborn fetuses: II. Histologic evaluation of the placenta; a study of 71 stillborns. Obstet Gynecol. 1992;80:585–92.PubMedGoogle Scholar
  64. 64.
    Ladefoged C. Hydrop degeneration: a histopathological investigation of 260 early abortions. Acta Obstet Gynecol Scand. 1980;59:509–12.CrossRefGoogle Scholar
  65. 65.
    Rehder H, Coerdt W, Eggers R, Klink F, Schwinger E. Is there a correlation between morphological and cytogenetic findings in placental tissue from early missed abortions? Hum Genet. 1989;82:377–85.CrossRefGoogle Scholar
  66. 66.
    Fox H. Morphological changes in the human placenta following fetal death. J Obstet Gynaecol Br Commonw. 1968;75:839–43.CrossRefGoogle Scholar
  67. 67.
    Hustin J, Gaspard U. Comparison of histological changes seen in placental tissue cultures and in placentae obtained after fetal death. Br J Obstet Gynaecol. 1977;84:210–5.CrossRefGoogle Scholar
  68. 68.
    Buckley CH, Fox H. Biopsy pathology of the endometrium. 2nd ed. London: Arnold; 2002.Google Scholar
  69. 69.
    Romney SL, Hertig AT, Reid DE. The endometria associated with ectopic pregnancy. A study of 115 cases. Surg Gynecol Obstet. 1950;91:605–11.PubMedGoogle Scholar
  70. 70.
    Shih I-M, Mazur M, Kurman R. Gestational trophoblastic tumors and related tumor-like lesions. Blaustein’s pathology of the female genital tract. 6th ed. New York: Springer; 2011. p. 1075–135.Google Scholar
  71. 71.
    Kaspar HG, To T, Dinh TV. Clinical use of immunoperoxidase markers in excluding ectopic gestation. Obstet Gynecol. 1991;78:433–7.PubMedGoogle Scholar
  72. 72.
    Sørensen FB, Marcussen N, Daugaard HO, Kristiansen JD, Møller J, Ingerslev HJ. Immunohistological demonstration of intermediate trophoblast in the diagnosis of uterine versus ectopic pregnancy: a retrospective survey and results of a prospective trial. Br J Obstet Gynaecol. 1991;98:463–9.CrossRefGoogle Scholar
  73. 73.
    Shih I, Wang T, Wu T, Kurman RJ, Gearhart JD. Expression of Mel-CAM in implantation site intermediate trophoblastic cell line, IST-1, limits its migration on uterine smooth muscle cells. J Cell Sci. 1998;111(Pt 17):2655–64.PubMedGoogle Scholar
  74. 74.
    Hiby SE, King A, Sharkey A, Loke YW. Molecular studies of trophoblast HLA-G: polymorphism, isoforms, imprinting and expression in preimplantation embryo. Tissue Antigens. 1999;53:1–13.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Tricia A. Murdock
    • 1
  • Emanuela F. T. Veras
    • 1
  • Robert J. Kurman
    • 1
  • Michael T. Mazur
    • 2
  1. 1.Department of PathologyThe Johns Hopkins HospitalBaltimoreUSA
  2. 2.Department of Pathology and Laboratory MedicineState University of New York Upstate Medical UniversitySyracuseUSA

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