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- My approach to the interpretation of endometrial biopsies and curettings!
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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 appearance and the glands are often few in number. After assessing tissue that is not derived from the 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.
My approach to the interpretation of endometrial biopsies and curettings
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.
Pathology Outlines - Dating of endometrium
An atrophic endometrium, which may or may not be an indication of the postmenopausal state atrophy is also characteristic of some hormonal agents , may 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 the 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.
Clinical history
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 a 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 cause 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 degree 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.
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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 regimens , characteristically result in a weak or poorly developed secretory endometrium, 27 , 28 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.
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. The most common endometrial lesions seen in association with tamoxifen are benign polyps, which may be single or multiple.
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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.
Most epidemiological studies, however, suggest that tamoxifen is associated with an increased risk of developing endometrial cancer, which is two to three times that in patients with breast cancer who are not taking tamoxifen. As the effects of tamoxifen on the endometrium are believed to be due to oestrogenic activity, it is expected that most endometrial cancers should be endometrioid in type, as these neoplasms are hormone receptor positive. In my experience, various aspects related to endometrial hyperplasia commonly create problems for pathologists.
In the following sections, I discuss some of these problematic areas. Before diagnosing an endometrial hyperplasia, it is important to exclude the many benign mimics. The potential benign mimics of endometrial hyperplasia are listed in box 1. Most of these show an increase in the normal gland to stroma ratio, which is a defining feature of complex endometrial hyperplasia and is present in most cases of atypical hyperplasia complex atypical hyperplasia.
One of the most common lesions to be misdiagnosed as a hyperplasia is an endometrial polyp, especially when this is removed piecemeal, and when the gynaecologist is not aware of the presence of a polyp and the suggestion of this is not conveyed to the pathologist. The morphological features of endometrial polyps, as well as several of the other potential benign mimics of endometrial hyperplasia, have been discussed.
A secretory endometrium and Arias—Stella effect endometrium often shows an increase in the gland to stroma ratio and may be misdiagnosed as an endometrial hyperplasia, especially when subnuclear vacuolation is not obvious. In general, secretory activity is rare in endometrial hyperplasias, although this does occur, especially when hormone treatment has already been instigated.
Cystic atrophy is distinguished from simple hyperplasia by the atrophic appearance of the glands, including the lack of proliferative activity. In general, mitotic activity should be identified before diagnosing an endometrial hyperplasia. The term dysplasia should not be used with regard to the endometrium.