Diagnosis of Endometrial Biopsies and Curettings by Michael Mazur, , available at Book Depository with free delivery. Diagnosis of Endometrial Biopsies and Curettings: A Practical Approach. Veli Marjoniemi. x. Veli Marjoniemi. Search for articles by this author. Department of. Generally, this should comprise a formal curetting rather than an outpatient biopsy. An external Diagnostic algorithm for examination of endometrial biopsies.

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A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy specimens.

The increasing use of pipelle and other methods of biopsy not necessitating general anaesthesia has resulted in greater numbers of specimens with scant tissue, resulting in problems in assessing adequacy and in interpreting artefactual changes, some of which appear more common with outpatient biopsies.

In this review, the criteria for adequacy and common artefacts in endometrial biopsies, as well as the interpretation of endometrial biopsies in general, are discussed, concentrating on areas that cause problems for pathologists. An adequate clinical history, including knowledge of the age, menstrual history and menopausal status, and information on the use of exogenous hormones and tamoxifen, is necessary for the pathologist to critically evaluate endometrial biopsies.

Topics such as endometritis, endometrial polyps, changes that are induced by hormones and tamoxifen within the endometrium, endometrial metaplasias and hyperplasias, atypical polypoid adenomyoma, adenofibroma, adenosarcoma, histological types of endometrial carcinoma and grading of endometrial carcinomas are discussed with regard to endometrial biopsy specimens rather than hysterectomy specimens.

The value of ancillary techniques, especially immunohistochemistry, is discussed where appropriate.

In many histopathology laboratories, endometrial specimens account for a major proportion of the workload. Most specimens are taken because of abnormal uterine bleeding or other related symptoms, and the pathologist is expected to exclude an endometrial cancer or a precancerous lesion.

Diagnosis of Endometrial Biopsies and Curettings : A Practical Approach

In some cases, a benign cause for abnormal uterine bleeding is identified, such as endometritis or endometrial diafnosis. In this review, I will outline my approach to the interpretation of endometrial biopsy specimens, especially concentrating on areas which, in my experience, create difficulties for pathologists.

Endometrial biopsy specimens are now rarely taken to date the endometrium and to assess whether ovulation has occurred, as serum measurements of various hormones give equivalent or more information.

In this review, dating of the endometrium will not be discussed, as this has been o with in detail recently. In evaluating an endometrial biopsy specimen, an adequate clinical history is important, including the age of the patient and the reason for the biopsy. The menopausal status as well as the date of onset of the last menstrual period and the length of the menstrual cycle in premenopausal women should be provided. In many cases of postmenopausal bleeding, the patient is not actually postmenopausal but rather is perimenopausal, with a prolonged interval between periods.

This results in the clinician and the patient assuming that the woman is postmenopausal. Before biopsy, many women with abnormal uterine bleeding are already taking exogenous hormones, especially progestogenic compounds, to control the bleeding, and this information is not always conveyed to the pathologist. Other women may be taking hormone replacement therapy or contraceptives. These hormonal compounds may alter the morphological appearance of the endometrium and a knowledge that these, and other relevant drugs such as cufettings, are being taken is of paramount importance to the pathologist.

Previously, endometrial biopsy specimens were largely obtained by dilatation and curettage carried out under general anaesthesia. Most endometrial specimens are now taken at outpatients by pipelle or other techniques, with the result that many biopsy specimens contain scant, or even no, endometrial tissue.

Paradoxically, superficial endometrial biopsy specimens with scant tissue often take longer to assess than intact biopsy specimens with an appreciable amount of tissue. The pathologist is faced with making a decision on whether the biopsy specimen is adequate. A recent study showed that there is considerable disagreement among specialist endometriao pathologists about what constitutes an adequate endometrial biopsy specimen.

For example, some clinicians routinely conduct a repeat biopsy when an endometrial specimen has been classified as inadequate. It is my policy in reporting endometrial specimens that a biopsy specimen from either outpatient clinic or curettage is classified as inadequate only if no endometrial tissue is present.

If there is any endometrial tissue, no matter how little, I do not categorise the specimen as inadequate. If intact tissue, comprising glands and stroma, is present then this can be typed, although with a comment that only a limited amount of tissue is available for examination.


The interpretation of the relevance of an unassessable specimen biopssies scant specimen rests with the clinician. As discussed, this is the norm with an atrophic endometrium and no focal lesion on ultrasound scan, blopsies not a reason for repeating the biopsy. With a thickened endometrium, a focal lesion or a strong clinical suspicion of major pathology, however, a scant specimen may be an indication of the need for repeat biopsy.

Generally, this should comprise a formal curetting rather than an outpatient biopsy. Tissues not derived from the endometrium are commonly represented in endometrial biopsies. These should be identified, evaluated and mentioned in the pathology report. Cervical tissue, either cervical glandular or squamous epithelium with or without stroma, may be present and should be examined to exclude major pathology.

The presence of adipose tissue or even intestinal mucosa may indicate uterine perforation, which should be conveyed to the clinician. In cases of uterine perforation, mesothelial cells or inflammatory cells may be mixed in with the adipose tissue.

Adipose tissue in an endometrial biopsy specimen may rarely be derived from a uterine lipoleiomyoma or currttings. Other tissues that may be present in an endometrial biopsy specimen include myometrial smooth muscle and tissue derived from the lower uterine segment or isthmus.

Tissue from the lower uterine segment may morphologically be confused with an endometrial polyp, as the stroma has a fibrous ejdometrial and the glands are often few in number. After assessing tissue that is not derived from endometriaal endometrium, the endometrial tissue present if any should be examined. It is useful to give some indication of the amount of endometrial tissue represented and the criteria for adequacy have already been discussed. Next, the endometrium should be typed with reference to the age of the patient, the date of onset of the last menstrual period and any hormonal treatment.

The morphological features of a cyclical and atrophic endometrium will not be detailed, but a few salient points are mentioned in the following sentences.

Caution should be exercised in diagnosing a proliferative endometrium in the absence of mitoses, although these may be few in number. Stromal and glandular mitoses are commonly found in a proliferative endometrium.

An atrophic endometrium, which may or may not be an indication of the postmenopausal state atrophy is also characteristic of some hormonal agentsmay be confused with a proliferative endometrium, as the glands commonly have a tubular appearance and there may be apparent nuclear stratification. A further point of confusion is that not all areas of endometria endometrium respond at the same rate to endogenous or exogenous hormones—for example, some areas may show proliferative features but others exhibit early secretory activity.

Difficulty arises when an endometrium from a truly postmenopausal woman as stated previously, some women with postmenopausal bleeding are not truly postmenopausal, but rather are perimenopausal, with irregular cycles shows proliferative activity without features of hyperplasia. My approach is to state in the report that there is continuing proliferative activity suggesting ongoing oestrogenic stimulation, although there are no features of hyperplasia or malignancy.

Endometrial proliferative activity may occur with uterine prolapse and in endometrial polyps in postmenopausal women. Several common artefacts are observed in endometrial biopsy specimens, which have received scant attention in the literature. Some of these may be misinterpreted as endometrial hyperplasia or even as carcinoma if not appreciated to be artefactual.

With this artefact, the glands become moulded together and often there is tearing of the tissue around the glands, which is a clue to the artefactual nature. This may result in consideration of enfometrial wide range of papillary lesions, benign and malignant, which occur in the endometrium. Such superficial strips of papillary endometrium, which are generally atrophic, should be examined under high power to look for proliferative activity and nuclear atypia.

Crushed endometrial glands and stroma may be extremely cellular and can biospies concern. As with other tissues, crushed areas should not be viewed in isolation. Tearing of the tissue is seen around the glands. Endometritis may result in symptoms of abnormal uterine bleeding and the pathologist should always exclude this. Lymphocytes, including natural killer cells and lymphoid aggregates, are a normal component of the endometrium, and polymorphs are characteristic of the premenstrual and menstrual phases.

The presence of plasma cells is widely regarded as the most useful criterion for a diagnosis of endometritis, although these are often admixed with other inflammatory cells, both acute and chronic, and may be a minor component of the inflammatory cell infiltrate.

Other morphological features that alert the pathologist to a possible endometritis may also exist. A ov of architectural complexity and cytological atypia may also be seen if the inflammatory cell infiltrate is marked, resulting in potential overdiagnosis of a hyperplasia or carcinoma.


Problems in recognising plasma cells may occur, especially on histological sections that are less than optimal. Endometrial stromal cells may have a plasmacytoid appearance with eccentric nuclei, and the pathologist should be certain that classic plasma cells are present.

It is emphasised that in the absence of the other morphological features of endometritis described earlier, an exhaustive search for plasma cells is not justified. Occasional stromal plasma cells may be identified in an otherwise normal endometrium, and in these circumstances a diagnosis of endometritis should not be made. Plasma cells may be present in the stroma of endometrial polyps and also in association with an endometrial malignancy.

Ancillary studies may aid in the diagnosis of endometritis, although they are not generally necessary. Antibodies against B and T lymphoid cells may also be of value. A recent study showed that in cases of endometritis, the number of T lymphocytes and natural killer cells did not differ from controls. This may be of value in diagnosing endometritis on small biopsy specimens in which the superficial endometrium is preferentially sampled.

The endometrial glands are positive but the stroma is negative. Polyps are a common cause of abnormal bleeding in premenopausal and postmenopausal women. The pathological diagnosis is generally straightforward if the gynaecologist is aware of the presence of a polyp, has conveyed this information to the pathologist and has removed the polyp intact.

The gynaecologist may believe that a polyp is present, but histological examination shows a cyclical endometrium, often secretory in type, reflecting the fact that an abundant secretory endometrium may have a polypoid appearance.

Often, the gynaecologist is not aware of the presence of a polyp. When a biopsy is carried out for abnormal uterine bleeding, the pathologist should always consider the possibility of a polyp. On examination under low power, the initial clue to the presence of a polyp is often the admixture of fragments of a normal cyclical endometrium and fragments that are morphologically different. The glands within a polyp often show proliferative activity, even when the surrounding endometrium does not.

The following points on endometrial polyps are worthy of mention:. It is useful to have a checklist of benign lesions other than those listed earlier, including granulomas, placental site nodules and the various forms of epithelial and stromal metaplasias. These metaplasias will not be discussed in detail, as they have been reviewed recently. Assessing the underlying glandular architecture is problematic.

This may result in consideration of a serous carcinoma or endometrial intraepithelial carcinoma. Hormones have varying effects on the endometrium and it is essential that the clinician supplies details to the pathologist regarding any hormone treatment.

Such information is not always provided. Some hormone preparations, especially those that contain both oestrogen and progestogen most modern hormone replacement treatment regimenscharacteristically result in a weak or poorly developed secretory endometrium, 2728 whereas with other preparations the endometrium is atrophic.

This pseudodecidualisation is often most prominent just beneath the surface glands and is usually accompanied by an inflammatory cell infiltrate, largely comprising natural killer cells.

Diagnosis of Endometrial Biopsies and Curettings : Michael Mazur :

Similar appearances occur with the Mirena coil, an intrauterine device containing progestogen, which is widely used. Tamoxifen is widely used as adjuvant therapy in the management of breast cancer.

The use of tamoxifen as a prophylactic agent in patients with a family history of breast cancer is now being investigated. The effects of tamoxifen on the endometrium has been the subject of several reviews. Endometrial samples from women taking tamoxifen tend to be scanty, as tamoxifen may result in fibrosis of the endometrial stroma, making evaluation by biopsy difficult.

The fibrosis can result in cystic dilatation of endometrial glands on an obstructive basis and this can be seen on hysteroscopy.

My approach to the interpretation of endometrial biopsies and curettings

The most common endometrial lesions seen in association with tamoxifen are benign polyps, which may be single or multiple. Indeed, as discussed previously, there is a peculiar tendency for serous carcinoma and EIC to arise within endometrial polyps, whether sporadic or associated with tamoxifen. As women with breast cancer are more likely to develop endometrial carcinoma due to common risk factors, such as high socioeconomic status, low parity or hyperoestrogenic states, it is difficult to ascertain whether a true association exists between tamoxifen and the development of endometrial cancer.