Diag of Endometrial Biopsies and Curettings A Practical Apprch

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Choose your country's store to see books available for purchase. See if you have enough points for this item. Sign in. A logical approach to formulating a pathologic diagnosis from the diverse array of tissue received in the surgical pathology laboratory. The authors are both prominent gynaecologic pathologists, and this book is the result of their long-running Short Course presented at the International Academy of Pathology.

Illustrations show typical artefacts and distortion and explain their impact on diagnostic interpretation, and each chapter includes a section on "Clinical Queries and Reporting" that summarises the features to be discussed in the final pathology report. Here is a strongly didactic approach to one of the most frequently ordered pathological examinations. You find superb illustrations on virtually every page and fast answers to everyday questions since emphasis is placed on clinically relevant material: commonly encountered specimens, common problems and common diagnostic issues.

Warren E. James Feinstein. Ken S. Tao Le.

Langman's Medical Embryology. Tom F. Ultrasonography in Obstetrics and Gynecology E-Book. Peter W. Pathology Secrets E-Book. Ivan Damjanov. Alan DeCherney. Williams Gynecology, Third Edition. Lisa M. Derek M. Conrad Fischer. Theodore X. Kaplan Medical. Stephen A. Kevin Schwechten. Joel S. Karen L. Mims' Medical Microbiology. Mark Zuckerman. Kendall Krause. Shirish N Daftary. Johns Hopkins Manual of Gynecology and Obstetrics.

Jessica L. Phyllis Glanc. Robert Klein. Wesley Lee. Earl J. Crush Step 1 E-Book. High Risk Pregnancy E-Book. David K. Case Files High-Risk Obstetrics. Eugene C. Obstetric Imaging E-Book. Table 3. Histologic changes of the endometrium in pregnancy. 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. Early gestational endometrium with decidualized stroma. The decidualized cells have abun- dant, pale cytoplasm, distinct cell borders, and uniform round to oval nuclei. Granular lymphocytes are numerous. Spiral artery walls are thicker than in nongestational endometrium. Along with progressive decidual transformation of the stromal cells, the glands and the vessels undergo pronounced alterations. Secretory changes in the glands become more prominent with increased cytoplasmic vacuolization and augmented luminal secretions that distend the glands Fig.

In addition to this hypersecretory activity, the glands become highly coiled with prominent serrations and papillary folds of epithelium projecting into the lumen. Concurrently, spiral arteries are more prominent Fig.

Diagnosis of Endometrial Biopsies and Curettings - A Practical Approach | Michael Mazur | Springer

Decidual cell nuclei become somewhat larger and may appear vesicular, but they maintain their uniform contours. The decidua shows small foci of physiologic necrosis during pregnancy, as it remodels during growth of the fetus and placenta and as the decidua capsularis fuses with the decidua parietalis. These small foci of necrosis, with a localized neutrophilic response, are physiologic. The decidua continues to contain a sprinkling of granular lymphocytes that remain throughout gestation. The hypersecretory pattern of the glands begins to regress early in pregnancy, and with increasing decidualization the glands become atrophic Fig.

The decidualized Figure 3. Decidualized stroma. Decidual cells have prominent cell borders and uniform, round to oval nuclei. Their cytoplasm has small vacuoles. A portion of an atrophic gland is present in the left upper corner. Figure 3. Gestational endometrium. Hypersecretory pattern of endometrial glands in early pregnancy with extensive cytoplasmic vacuolization.

Decidualized stroma was present in other areas of the sections. Endometrial Glands and Stroma in Pregnancy 39 Figure 3. Endometrium from spontaneous abortion shows diffuse decidual reaction of stroma. The glands are dilated and lined by atrophic, indistinct epithelial cells. Therapy with high-dose progestins could induce a similar pattern. As pregnancy advances, the spiral arteries maintain thick walls, a feature that persists to term and is helpful in recognizing gestational changes.

Arias—Stella Reaction At 4 to 8 weeks after blastocyst implantation, the endometrium often shows at least a focal Arias—Stella reaction in the glands. The morphologic features of the Arias—Stella reaction include nuclear enlargement up to three times normal size and nuclear hyperchromasia, often accompanied by abundant vacuolated cytoplasm Figs. Arias-Stella reaction. Glands from an abortion specimen show prominent Arias-Stella reaction with hyperchromatic nuclei that bulge into the glandular lumen. The glands also show marked cytoplasmic vacuolization.

Identical changes can be seen in an ectopic pregnancy. Several nuclei show prominent cytoplasmic invaginations. Endometrial Glands and Stroma in Pregnancy 41 into the gland lumen. These large nuclei may contain prominent cytoplasmic invaginations. This process may be extensive, involving many glands, or the reaction can be focal, involving only a few glands Fig.

The change can even be limited to part of a gland, leaving the remaining nuclei unaffected. The Arias—Stella reaction has two histologic patterns Fig. This pattern is characterized by glands lined by enlarged hobnail cells with little cytoplasmic secretory activity. In fact, the two patterns are not very distinct and there is frequent overlap between them. The degree and extent of the Arias—Stella reaction are highly variable in normal and abnormal intrauterine gestation, in ectopic pregnancy, and in gestational trophoblastic disease.

There is no apparent relationship between the presence and extent of the Arias—Stella reaction and the status of the fetus. The Arias—Stella reaction is almost unique to pregnancy or gestational trophoblastic disease. Similar phenomena are rarely produced by administration of exogenous progestins. Gestational endometrium with AriasStella reaction. A dilated venule is present beneath surface epithelium on the right. Pregnancy, Abortion, and Ectopic Pregnancy changes in the presence of trophoblastic tissue. One such change is abundant clear cytoplasm.

With this change the gland cells accumulate abundant amounts of clear, glycogen-rich cytoplasm Fig. Another pregnancy-related change is optically clear nuclei of gland cells Fig. Optically clear nuclei usually are focal.

Diagnosis of Endometrial Biopsies and Curettings

A recent study indicates that the change is related to the intranuclear accu- mulation of biotin. These changes may persist until term, however. Localized atypical-appearing endometrial glandular proliferations rarely may be found during gestation. Mitotic activity is present, but nuclear cytology is bland. The few lesions studied have been Figure 3. Gestational endometrium with clear cell change. Glands in early gestational endometrium are lined by cells with abundant clear cytoplasm.

The cells lack the nuclear enlargement of the Arias-Stella reaction. Trophoblast and Villi 43 Figure 3. Gestational endometrium with optically clear nuclei. Crowded glands show prominent optically clear nuclei. This gland cell change is infrequent and usually is focal. It may be seen throughout pregnancy, however. Normal proliferative and secretory endometrium, as well as glands in patients with hyperplasia and neoplasia, do not stain for S protein. There are no other markers of the glands that are generally practical for identifying pregnancy-related changes except for the low Ki index of the Arias—Stella reaction, which helps to indicate a benign glandular change.

Trophoblast and Villi In early pregnancy trophoblastic proliferation begins with the development of the blastocyst, the outer layer of which is termed the trophoblastic shell. Villous formation does not begin until about 7 days after implantation of the blastocyst 13 days following conception. Usually these tissues are easy to recognize. Also, the presence of placental and fetal tissue in curettage samples, for all practical purposes, rules out an ectopic pregnancy.

Mazur, M. — Kurman, R.

The morpho- 44 3. Pregnancy, Abortion, and Ectopic Pregnancy logic features of these abortion specimens can be highly varied. Recognizing the full morphologic spectrum of normal trophoblastic cells is important, not only for establishing the presence of an intrauterine pregnancy, but also for distinguishing exaggerated but physiologic changes from gestational trophoblastic disease.

Trophoblastic Cells The trophoblast is extraembryonic but fetal in origin, growing in intimate association with host maternal tissues. Very early in pregnancy trophoblastic cells differentiate and invade decidua, even before villi form. The trophoblast continues to grow along this interface of maternal and placental tissue throughout pregnancy. The decidua basalis where trophoblast interfaces with the endometrium and myometrium becomes the placental implantation site. The trophoblastic cells are the epithelial component of the placenta and are divided into three cytologically and functionally distinct populations: cytotrophoblastic CT cells, syncytiotrophoblastic ST cells, and intermediate trophoblastic IT cells Table 3.

Accordingly, they are mitotically active. They are uniform cells about the size of a decidualized stroma cell, with a single nucleus, one or two nucleoli, pale to faintly granular cytoplasm, and prominent cell borders Fig. ST cells, in contrast, are larger and multinucleate with dense amphophilic to basophilic cytoplasm. The nuclei of ST cells are dark and often appear pyknotic; they do not contain mitoses.

A microvillous brush border Table 3. Trophoblast and Villi 45 Figure 3. Immature chorionic villi with trophoblast. The villi are lined by an inner layer of mononu- cleated CT cells capped by ST cells. To the right of the villus a dimorphic mixture of ST and villous IT cells proliferates toward the implanting margin of the placental tissue. CT and ST cells typically display a dimorphic growth pattern, with the two cell types growing in close proximity.

In early abortions, the CT and ST cells are quite prominent compared with the amount of villi present. In very early, unanticipated abortions, the entire products of conception consist of previllous trophoblast that can be easily confused with choriocarcinoma Fig. In curettage for suspected abortions, sometimes the only evidence of an intrauterine pregnancy is the presence of a few isolated trophoblastic cells mixed with blood, and these may be necrotic Fig.

Careful scrutiny may be necessary to identify these diagnostic cells. Trophoblast of early pregnancy. A prominent network of ST and CT encountered in inadvertent endometrial biopsy during early pregnancy. No villi are present. Despite the biopsy, the pregnancy continued to term and uneventful delivery. They have pale cytoplasm and large, round nuclei. The chorionic-type IT constitute the cells of the chorion laeve where they form a cohesive layer of epithelium. These latter IT are composed of relatively unform cells with eosinophilic to clear glycogen-rich cytoplasm. These cells are smaller than implantation site IT although an occasional cell is multinucleated Table 3.

The villous and the implantation site IT constitute the two forms of IT usually seen in biopsy specimens from early pregnancy. Implantation site IT also are the primary cell type of the placental site trophoblastic tumor discussed in Chapter 4. The chorionic-type IT constitute the cell population seen in the placental site nodule discussed later in this chapter and in the epithelioid trophoblastic tumor discussed in Chapter 4.

Immunohistochemistry of Trophoblastic Cells Trophoblastic cells express a number of proteins. Isolated ST cells in abortion specimen. Isolated ST cells such as this are often found in areas of hemorrhage. Cytokeratin is the most ubiquitous cell product. Trophoblast also is reactive for simple epithelium-type cytokeratins, and cytokeratins 7 and 18 are especially notable for their reactivity in trophoblast. Cytokeratin 20, in contrast, is variably reactive in trophoblast, and high molecular weight cytokeratin is negative in trophoblastic cells.

Other than cytokeratin, CT cells show limited immunoreactivity to commonly available antibodies. Inhibin-a is seen only in chorionic-type IT. Ki immunostaining also shows a variable proliferation index. The Ki proliferation index in villous trophoblast is high at the junction with the CT at the base of the villus but decreases progressively toward the tip distal end of the trophoblastic column. The Ki proliferation index is low 3. It can be diffuse or focal in endometrial biopsy specimens. Placental site intermediate trophoblast characteristically diffusely permeates the decidua and implantation site Figs.

Because they closely resemble decidual Figure 3. Placental implantation site. Fibrin and implantation site IT with irregular, hyperchromatic nuclei and cytoplasmic vacuoles are interspersed among decidual cells. In the right lower corner the IT cells are partially replacing the endothelial cells of a blood vessel. Chorionic villi are not seen, but the presence of intermediate trophoblast in decidua establishes the diagnosis of intrauterine pregnancy.

Placental Implantation Site Figure 3. IT cells and decidua. IT have characteristic large, irregular, hyperchromatic nuclei. Some of the IT cells have prominent nucleoli. The implantation site IT arrows have irregular, hyperchromatic nuclei that contrast with the round to oval, uniform nuclei of the surrounding decidualized stromal cells.

In fact, these IT cells have been misinterpreted as degenerating decidual cells because of their intimate association with the latter Figs. The implantation site IT cells have variable size and shape ranging from polygonal to round to spindle-shaped, with a moderate amount of eosinophilic to amphophilic cytoplasm. They may have sharply outlined cytoplasmic vacuoles. The nuclear morphology of implantation site IT, however, is the most important feature that distinguishes these cells from decidua. They are enlarged, lobated, and hyperchromatic with irregular nuclear membranes.

Sometimes they have deep clefts, and some nuclei appear smudged. The dark and irregular implantation site IT nuclei, which often contain a prominent nucleolus, contrast with the nuclei of decidualized stromal cells, which are uniform and round to oval with an even, delicate chromatin distribution. Immunohistochemical stains for keratin and human placental lactogen hPL help identify intermediate trophoblast cells and distinguish them from decidual cells which are negative see later.

The implantation site IT cells are often more conspicuous here, especially when some of them become multinucleated. Many are spindle shaped and can closely resemble smooth muscle cells. IT cells in myometrium. These cells often become multinucleated when they invade the myometrium. The presence of enlarged, hyalinized spiral arteries in the decidua of curettage specimens is a valuable adjunct in diagnosing intrauterine gestation.

IT cells. Trophoblast and Villi 53 Figure 3. Often several implantation site vessels are seen in cross section forming a prominent cluster. These vascular changes, like the presence of IT in the decidua, are characteristic of the implantation site and are not found in endometrium associated with ectopic pregnancy. Histologic recognition of the placental implantation site usually is straightforward.

In these instances, ancillary immunohistochemical techniques are useful for the detection of IT. Broad-spectrum keratin antibodies are very useful for demonstrating IT. With the keratin immunostain, the IT cells appear as intensely staining single cells or irregular clusters of cells with intervening decidua or smooth muscle that is nonreactive for keratin Fig.

Keratin immunoreactivity of intermediate trophoblast. Scattered IT in decidua show cytoplasmic staining for keratin arrows. In complete molar pregnancy the placental site is typically exaggerated, but exaggerated placental site can occur in association with a normal gestation as well. The exaggerated placental site is characterized by an increase in the number and size of individual IT cells.

A few chorionic villi may be present. In the exaggerated placental site, IT cells appear larger and more hyperchromatic than normal. Despite their apparent prominence, these IT cells show no mitotic activity, and Ki immunostaining is zero when the exaggerated implantation site is associated with an abortus.

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It is important to note that lymphocytes that typically are present in the implantation site often express Ki These lymphocytes should not be misinter- preted as IT cells. Necrosis is not a feature of the exaggerated placental site, although the surrounding decidua often shows degeneration and necrosis typical of spontaneous abortions.

PSTT is an important consideration in the differential diagnosis of this lesion.

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The distinction is largely a matter of degree, as discussed in Chapter 4. Placental Site Nodules Placental site nodules are small, circumscribed foci of hyalinized implantation site with IT cells that occasionally present in an endometrial biopsy or curettage. The nodules may be present in biopsies taken several years after tubal ligation, suggesting that they are retained in the endometrium for extended periods of time. They show a propensity for the lower uterine segment and Trophoblast and Villi 55 cervix.

The surrounding endometrium often is proliferative or secretory, and usually is not decidualized. Generally these lesions are microscopic, although hysterectomies may yield gross lesions as large as 1 or 2 cm in diameter. Occasionally, multiple nodules are present. In the past these nodules and plaques were considered hyalinized decidua, but they are now recognized as a distinctive benign lesion of IT.

The lesion itself is circumscribed, nodular, or plaque-like with densely eosinophilic, hyalinized stroma containing aggregates of IT cells Fig. The trophoblastic cells in these nodules resemble chorionic-type IT. In the placental site nodule the cells vary in size; many have small, uniform nuclei and some larger cells show irregular, hyperchromatic nuclei.

Occasional multinucleated cells are present. Mitoses are rare or absent, and the cells show a low Ki labeling index of Figure 3. Placental site nodule. Well-circumscribed fragment of placental site nodule is present in endometrial curettings. This microscopic focus is composed of hyaline material with entrapped, degenerate IT cells. Placental site nodule shows degenerate, vacuolated IT cells with smudged nuclear chromatin surrounded by dense, hyaline stroma. Immunohistochemical stain for keratin shows strong reactivity of the trophoblast.

Trophoblast and Villi 57 Villus formation in very early pregnancy depends on the existence of the embryonic disc. Villi begin to develop on the 12th to 13th day postfertilization, and by days 12 to 15 the placenta can develop for a while independently, without the presence of an embryo. In the early stages of pregnancy, villi have a loose, edematous stroma with few welldeveloped capillaries Figs. Once the yolk sac and embryo develop, vascular circulation is established in the villous stroma and these vessels contain nucleated red blood cells.

During this early period of placental development, the trophoblastic covering of the villi consists of an inner layer of CT cells and an outer layer of ST cells. The CT and IT cells also proliferate at the implanting end of the anchoring villi that grow along the basal plate of the developing placenta. A few histologic changes in the placenta help to determine the age of the developing conceptus Table 3. These developmental intervals are stated in relation to the time of fertilization, also known as the postcoital or postconception date.

As placental development proceeds, the presence of nucleated erythrocytes produced in the yolk sac helps determine the approximate Figure 3. Immature chorionic villi. Immature villi from an abortion specimen show loose, edematous stroma containing a few capillaries with nucle- ated erythrocytes.

Trophoblast emanates from one pole of several villi, which is the implanting portion of the anchoring villi. Pregnancy, Abortion, and Ectopic Pregnancy Table 3. Therapeutic abortion specimens may show pathologic changes in the villi, however. This pattern of mild villous edema and no evidence of fetal development indicates that the embryo either never developed or ceased development at a very early stage of gestation.

Hydropic change affects most villi but is minimal and microscopic; cistern formation in the villi is rare but does occur Fig. There is no associated trophoblastic hyperplasia except the normal growth at one pole of the anchoring villi. Usually these microscopic abnormalities are less impressive when the gross, quantitative aspects are considered also. Hydropic abortions usually consist of one or two cassettes of tissue with villi whereas moles typically yield multiple cassettes.

It is important to recognize the changes of the blighted ovum in order to separate an abortion with hydropic changes from a hydatidiform mole see Chapter 4. Hydropic change also may be RBCs, Red blood cells. For menstrual age add 2 weeks. By 5 to 6 weeks, nonnucleated erythrocytes from the embryonic liver also begin to appear in the villi, and from this point on there is a shift in the proportion of nucleated to non-nucleated erythrocytes.

Consequently, if the embryo dies before 4. Death of the embryo between 4. Other features also help to determine the relative length of gestation. For example, normally developing immature villi are relatively larger than those of later pregnancy. They have a loose, myxoid stroma with widely spaced capillaries.

As pregnancy progresses, the villi become smaller but more vascular and their stroma loses its edematous appearance. The morphologic features of the trophoblast covering the villi change along with growth of the placenta. The bilayered CT and ST covering of the villi persists to some extent throughout gestation, but a visible inner layer of CT cells starts to disappear at about 14 weeks of gestation.

Between week 14 and week 18, the Trophoblast and Villi 59 Figure 3. Immature chorionic villi with hydropic change. Abortion specimen shows avascular, edematous chorionic villi. This change is associated with the so-called blighted ovum and usually indicates very early demise of the embryo. Although the villi are edematous, the change is microscopic and not asso- ciated with hyperplasia of trophoblast. These features distinguish this hydropic abortus from a partial mole.

Karyotyping is necessary to determine whether a chromosomal abnormality is present. The implantation site, however, with its characteristic features, usually is present. In missed abortions the villi often are necrotic or hyalinized and the decidua is necrotic. Some or many villi may be necrotic. The villi are 60 3. This hydropic abortus shows scattered cisterns. There is no associated hyperplasia of the trophoblast, and this does not represent a hydatidiform mole. Trophoblast and Villi more numerous and become more complex.

Some abortion specimens present early in the second trimester following intrauterine fetal death. Following delivery of the term or near-term placenta, abnormal bleeding may require curettage. Failure of the implantation site to resolve quickly is called subinvolution. Immunohistochemical stains for keratin help to demonstrate the residual intermediate trophoblastic cells.

Placental Polyps Placental polyps are a form of retained product of conception that represent polypoid portions of chorionic villi from an incomplete abortion or a term gestation retained in the uterine cavity. Often these pedunculated masses of villi are found within days to weeks following abortion or delivery of a term placenta. Rarely, they persist for months or years after pregnancy. Placental polyp. Polypoid fragment of retained placental tissue removed by curettage several weeks after term delivery. The mature villi are degenerate and hyalinized. The placental tissue fails to detach from the implantation site in the myometrium and cannot be manually removed.

The usual management of extensive placenta accreta is hysterectomy, but on occasion focal placenta accreta is encountered in curettage for postpartum hemorrhage. The diagnostic feature is villi in direct apposition to myometrium without intervening decidua Fig. Placenta accreta. Implantation site 3. Pregnancy, Abortion, and Ectopic Pregnancy Some placental polyps may represent focal placenta accreta, although the latter are diagnosed only when villi are contiguous with myometrium.

Scattered IT cells without villi in the myometrium are a physiologic phenomenon and not placenta accreta. Endometrium Associated with Ectopic Pregnancy In most circumstances, the endometrium associated with an ectopic pregnancy shows the typical features of early gestation, yet trophoblastic tissue is not present. A decidualized stroma, hypersecretory to atrophic glands, and thick-walled spiral arterioles usually are present. Clinical Queries and Reporting the status of the trophoblastic tissue.

If ectopic trophoblast is actively proliferating, the endometrium continues to show the changes of pregnancy. If the trophoblast begins to regress, the endometrium can display a variety of patterns ranging from proliferative to secretory changes. The endometrium can show features seen in dysfunctional bleeding, including anovulatory bleeding patterns, abnormal secretory patterns, or progestin effects. Subtle clues, such as a focal Arias-Stella reaction or a small aggregate of gland cells with clear cytoplasm, can suggest an ectopic pregnancy.

Establishing the presence of an intrauterine pregnancy effectively rules out an ectopic pregnancy. Evidence of an intrauterine pregnancy includes chorionic villi, trophoblastic cells, or the placental implantation site. In cases where there are no villi or ST cells, an attempt should be made to identify IT cells scattered in partially necrotic decidua, often around spiral arterioles.

A panel using several of these latter immunostains can be helpful for identifying trophoblastic tissue if the keratin immunostain is inconclusive. Clearly, adequate sampling of endometrial tissue is important to ensure recognition of chorionic tissue. Clinical Queries and Reporting For most endometrial biopsies or curettings related to pregnancy, three clinical questions need to be answered by pathologic examina- 63 tion: 1 Does the endometrium show features of pregnancy?

For example, endometrial changes of pregnancy without the presence of chorionic villi or trophoblast suggest the possibility of an ectopic pregnancy. In other cases, edematous villi or proliferative trophoblast can raise the question of a hydatidiform mole, choriocarcinoma, or placental site trophoblastic tumor see Chapter 4. Most cases require only documentation of the presence of placental or fetal tissue.

The most urgent question is that of an ectopic pregnancy. If pregnancy is suspected, or if the morphology shows pregnancy-induced endometrial patterns but there is no evidence of chorionic villi, placental site trophoblast, or fetal tissue, then an ectopic pregnancy must be considered. Also, all the residual tissue should be processed. The clinician should be informed if immunohistochemical stains to identify trophoblast are pending or if residual tissue is being processed. Another call should follow as soon as the results are available. Occasional spontaneous abortion specimens show only a small amount of early placental site with intermediate trophoblast and no chorionic villi.

In spontaneous abortions, for example, mild villous edema hydropic change and absence of fetal tissues including erythrocytes in villous vessels indicates that the gestation was abnormal and may help the clinician in the counseling of a patient. If hydropic change is diagnosed, it may be useful to add a comment to indicate that this does not represent a mole. Because pregnancy can be complicated by gestational trophoblastic disease, the status of the trophoblast, especially any abnormal proliferative activity, deserves comment. A specimen containing more than a small amount of trophoblast without villi, or an exaggerated placental site without villi or unusually hydropic villi that are not clearly molar see Chapter 4 should be reported.

The placental site nodule can be a confusing diagnosis to the gynecologist. The terminology for this lesion is relatively new. Although these lesions are almost always microscopic and incidental, confusion with PSTT may arise. It is therefore important to indicate clearly the small and benign nature of the lesion. This diagnosis of placental site nodule may be perplexing to the gynecologist because the patient often has no recent history of pregnancy and may even have had a tubal ligation, so a comment regarding the fact that the gestation may have been remote helps the clinician understand the lesion.

Spontaneous and recurrent abortion. Com- 16 prehensive gynecology. Kalousek DK. Pathology of abortion: Chromosomal and genetic correlations. Pathology of reproductive failure. Fetal loss after implantation. A prospective study. Lancet ; — Benirschke K, Kaufmann P. Pathology of the human placenta, 4th ed. New York: SpringerVerlag, Incidence of early loss of pregnancy. Simpson JL. Incidence and timing of pregnancy losses.

Am J Med Genet ; — Endometrial biopsy in the cycle of conception. Histologic and lectin histochemical evaluation. The endometrium and sterility. Endometrial biopsy in the luteal phase of the cycle of conception. Hertig AT. Gestational hyperplasia of endometrium. A morphologic correlation of ova, endometrium, and corpora lutea during early pregnancy. Lab Invest ; — Cycle of conception endometrial biopsy. Endometrial dating in the conception cycle. Evaluation of endometrial biopsy in the cycle of conception. Int J Fertil ; — Endometrial biopsy during a cycle of conception. Decidual vascular changes in early pregnancy as a marker for intrauterine pregnancy.

Am J Clin Pathol ; — Nontrophoblastic pathology of the female genital tract References 17 18 19 20 21 22 23 24 25 26 27 28 29 30 and peritoneum associated with pregnancy. Semin Diagn Pathol ; — How early in pregnancy does the Arias—Stella reaction occur? Arch Pathol ; — Arias-Stella J. Atypical endometrial changes produced by chorionic tissue. Hum Pathol ; — Atypical endometrial changes associated with the presence of chorionic tissue.

AMA Arch Pathol ; — The Arias-Stella reaction: Facts and fancies four decades after. Adv Anat Pathol ; — Arias-Stella reaction with prominent nuclear pseudoinclusions simulating herpetic endometritis. Diagn Gynecol Obstet ; — The Arias-Stella phenomenon and the diagnosis of pregnancy. J Obstet Gynaecol ; — Atypical endometrium associated with ectopic pregnancy. The Arias-Stella phenomenon. The endometrium in ectopic pregnancy. A study based on 35 patients treated by hysterectomy. Endometrial gland cell atypism in the presence of trophoblast.

Arias-Stella reaction in nonpregnant women: A clinicopathologic study of nine cases. Biotin-containing intranuclear inclusions in endometrial glands during gestation and puerperium. Optically clear nuclei. An alteration of endometrial epithelium in the presence of trophoblast. Am J Surg Pathol ; — Localized endometrial proliferations associated with pregnancy: Clinical and histopathologic features of 11 cases. Hum Pathol ; 26 11 : — Endometrial adenocarcinoma 65 31 32 33 34 35 36 37 38 39 40 41 42 43 associated with intrauterine pregnancy.

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