3 Pregnancy, Abortion, and Ectopic Pregnancy Endometrial Glands and Stroma in pathologic states such as abnormal bleeding or Pregnancy . 35 chronic endometritis. Early Gestational Endometrium (1 to 3 An abortion before the 16th week of preg- Weeks Postfertilization) . 35 nancy is the usual source of endometrial tissue Endometrium in Later Pregnancy (4 or specimens that show apparent gestational More Weeks Postfertilization) . 37 changes. The different types of abortions are Arias-Stella Reaction . 39 defined as follows.“Spontaneous abortions” are Other Glandular Changes in unexpected and unplanned interruptions of Pregnancy . 41 pregnancy that present with bleeding and Trophoblast and Villi . 43 passage of tissue. Approximately 15% to 20% Trophoblastic Cells . 44 Immunohistochemistry of Trophoblastic of early pregnancies end in a spontaneous abor- 1–4 Cells . 46 tion. In addition, many other early pregnan- Placental Implantation Site . 48 cies spontaneously abort before pregnancy is Exaggerated Placental Implantation recognized by the woman and are occult.5;6 Most Site . 53 spontaneous abortions occur before 12 weeks of Placental Site Nodules . 54 pregnancy, and at least half of these are attrib- Chorionic Villi and Villous Trophoblast utable to a genetic (karyotypic) anomaly. An in the First Trimester . 57 “incomplete abortion” is a spontaneous abor- Hydropic Change and Other tion in which the conceptus and decidua are Pathologic Changes in Abortions . 58 incompletely passed, thus requiring curettage. Chorionic Villi and Villous Trophoblast A “missed abortion” refers to an abortion with After the First Trimester . 59 Placental Polyps . 61 retained products of conception but no abnor- Placenta Accreta . 62 mal bleeding for 5 to 8 weeks after death of the Endometrium Associated with Ectopic embryo or fetus. The criteria for diagnosis of a Pregnancy . 62 missed abortion vary among practitioners and Clinical Queries and Reporting . 63 institutions. “Therapeutic abortions” are those in which the pregnancy is electively terminated. Besides abortions, several other complica- Recognition of the features of gestational tions of pregnancy, such as retained placenta or endometrium, trophoblast, and villi, as well as placental implantation site, ectopic pregnancy, the pathologic changes in chorionic tissues, is an or gestational trophoblastic disease, lead to the important part of endometrial biopsy interpre- need for endometrial curettage (Table 3.1). tation. The presence of intrauterine products of Specimens from patients with these conditions conception generally excludes the diagnosis of show either trophoblastic tissue, the effects of ectopic pregnancy and can help explain other trophoblastic tissue on the endometrium, or a 34 Endometrial Glands and Stroma in Pregnancy 35 Table 3.1. Complications of pregnancy. nence with engorgement and dilation of super- 8 Spontaneous abortion ficial veins and capillaries also occurs, and the Missed abortion spiral arteries develop thicker walls. Retained placental tissue/implantation site Other reported changes in the cycle of con- Ectopic pregnancy ception include persistent basal cytoplasmic Placenta accreta, increta, and percreta vacuoles in late secretory phase glands,9 a Gestational trophoblastic disease disparity between development of the glands and stroma,11 or a histologic date earlier than combination of trophoblastic tissue and its the cycle date as determined by basal body effects. temperature or luteinizing hormone (LH) This chapter first reviews the physiologic surge.11–14 One study reported that in the cycle changes of the endometrium in pregnancy, of conception pronounced stromal edema and especially early pregnancy. This is followed by vascular engorgement of capillaries and small a discussion of normal placental implantation veins correlated better with pregnancy than did and growth, as well as benign and pathologic the glandular changes.7 Because menstruation trophoblast conditions. Chapter 4 reviews the does not occur, there is no substantial change closely related topic of gestational trophoblas- in the number of true granular lymphocytes at tic disease. this time. Practically, however, the morphologic changes during the first 1 to 2 weeks after con- Endometrial Glands and Stroma ception are subtle. It is difficult to decide in Pregnancy whether the vacuolated cytoplasm within glan- dular epithelium reflects normal persistence of Early Gestational Endometrium vacuoles in the late secretory phase or the (1 to 3 Weeks Postfertilization) changes of pregnancy. It usually is not possible to be certain of pregnancy-related changes Fertilization occurs in the fallopian tube soon until 2 weeks or more after conception, after ovulation, and implantation (nidation) of when decidua, as opposed to predecidua, is the developing blastocyst takes place on day fully developed (see later). 20 or 21 (postovulatory day 6 or 7). Implanta- Within 10 to 15 days of fertilization, the tion occurs on the surface of the endometrium, endometrium gradually begins to show more usually on the midportion of the posterior wall. characteristic changes of pregnancy as differ- The ovulatory cycle, during which fertilization entiation of stromal cells into decidua pro- and implantation take place, is called the cycle gresses (Table 3.2).As compared to predecidual of conception. Immediately after implantation, cells, decidual cells are larger and contain more subtle changes begin to appear in the glands abundant eosinophilic to amphophilic cyto- and stroma, although the tissue retains the plasm that may contain faint vacuoles (Figs. 3.2 overall characteristics of the mid- to late secre- and 3.3). These cells become more clearly tory phase for several days. An endometrial polyhedral with well-defined cell membranes. biopsy or curettage performed inadvertently at Nuclei of the decidualized stromal cells are this time, usually during infertility evaluation, round to oval and uniform, with smooth out- may not include trophoblast or disrupt the lines, finely dispersed chromatin, and indistinct early gestation, yet will show very early preg- nucleoli (compare with Fig. 3.15). Occasional nancy-related changes. These changes include decidualized stromal cells are binucleate. recrudescence or accentuation of glandular Stromal granular lymphocytes persist in early secretions, distension of the glands, edema, and pregnancy and are clearly evident among an extensive predecidual reaction.7–10 The decidual cells. The presence of granular lym- coiled glands show secretory activity and a phocytes may suggest a chronic inflammatory serrated lumen, but they appear distended or infiltrate, but the granular lymphocytes, in con- wider than those in the late secretory phase of trast to inflammatory cells, have characteristic a menstrual cycle (Fig. 3.1). Vascular promi- lobated nuclei and plasma cells are not present. 36 3. Pregnancy, Abortion, and Ectopic Pregnancy Figure 3.1. Early gestational endometrium, cycle of absence of trophoblast or chorionic villi, these fea- conception. Inadvertent endometrial biopsy in the tures are too subtle to be diagnostic of early preg- cycle of conception shows distended, coiled glands nancy until the stroma shows more advanced and engorged vessels. Early decidual reaction is decidual change. present around thickened spiral arteries. In the Table 3.2. Histologic changes of the endometrium in pregnancy.a Duration of pregnancyb Stroma Glands Vessels 1–3 weeks Edema, then progressive Hypersecretory with cytoplasmic Spiral arteries begin to thicken decidual change vacuoles, luminal secretions Superficial venules congested, Saw-toothed, tortuous, distended dilated Rare Arias-Stella reaction 4 or more weeks Marked decidual change Irregular with marked atrophy Spiral arteries thickened Variable Arias-Stella reaction, clear Superficial venules dilated cytoplasm, optically clear nuclei a Changes of endometrial glands, and stroma and vessels only. b Duration from time of fertilization (day 15–16 of menstrual cycle). Add 2 weeks for time from last menstrual period. Endometrial Glands and Stroma in Pregnancy 37 Figure 3.2. Early gestational endometrium with dant, pale cytoplasm, distinct cell borders, and decidualized stroma. Endometrial stroma from a uniform round to oval nuclei. Granular lymphocytes first-trimester abortion shows prominent decidual are numerous. Spiral artery walls are thicker than in transformation. The decidualized cells have abun- nongestational endometrium. Along with progressive decidual transforma- stromal cells are widespread and prominent, tion of the stromal cells, the glands and the especially as the cell borders become better vessels undergo pronounced alterations. Secre- defined, and they develop an epithelioid tory changes in the glands become more promi- appearance. Decidual cell nuclei become some- nent with increased cytoplasmic vacuolization what larger and may appear vesicular, but they and augmented luminal secretions that distend maintain their uniform contours. The decidua the glands (Fig. 3.4). In addition to this hyper- shows small foci of physiologic necrosis during secretory activity, the glands become highly pregnancy, as it remodels during growth of the coiled with prominent serrations and papillary fetus and placenta and as the decidua capsularis folds of epithelium projecting into the lumen. fuses with the decidua parietalis. These small The epithelial cells become stratified. Concur- foci of necrosis, with a localized neutrophilic rently, spiral arteries are more prominent