Endometrial hyperplasias is a pathological condition characterized with hyperplastic changes in the endometrial glandular and stromal structures lining the uterine cavity
7. The disorder is generally seen in the 50-54 age group of women and rare under the age of 30. Although its etiology has not been fully clarified, it is implicated that most cases of EH result from high levels of estrogens, combined with insufficient levels of progesterone
8,9. EH is more frequently seen in women with a body mass index of over 30
5. In postmenopausal women, it frequently manifests itself with abnormal uterine bleeding
8. It was diagnosed by histopathological examination of biopsy, curettage or hysterectomy material
5.
According to the classification of the WHO, EHs are divided into 4 groups as simple hyperplasias without atypia, complex hyperplasias without atypia, simple atypical hyperplasias and complex atypical hyperplasias10. Since they are precancerous and require treatments different than other diseases causing menometrorrhagia, they should be differentiated from adenocarcinomas and other endometrial disorders, as well as their types to be differentiated from other types of EH3.
Simple hyperplasia can be confused with proliferative endometrium by its pseudostratified epithelium, increased mitosis and active stroma. The cystic glands in senile cystic atrophy, cohesive endometrial glands in endometrial polyp, and focal hyperplastic changes in irregular proliferation may cause confusion in the diagnosis. However, the presence of stromal structure in senile atrophy and thick-walled vessels in endometrial polyp can be helpful in the differential diagnosis3,11. Complex hyperplasias should be differentiated from simple hyperplasia, atypical polypoid adenomyoma and endometrial adenocarcinoma3.
When it is the case that glands are demonstrating disintegration and stromal collapse in the curretage material and menstrual bleeding, this is evaluated as glandular irregularity and congestion, which may be misdiagnosed as hyperplasia. Furthermore, due to the fact that disintegrated proliferative and late secretory glands are observed as close to each other, this may be evaluated as glandular congestion. We think that this is the source of disagreement in the majority of cases diagnosed as dysfunctional uterine bleeding, secretory endometrium and irregular proliferation on the re-evaluation of cases already diagnosed with hyperplasia. Irregular proliferative endometrium may particularly be misdiagnosed as simple hyperplasia because of the demonstration of focal glandular irregularity due to estrogen stimulation. Another lesion that may be mixed up with hyperplasia is endometrial polyp. Some polyps demonstrate focal hyperplasia areas. The presence ofdense stroma and vessels with thick walls is helpful in the differential diagnosis6. In our study we observed that, the main number of endometrial polyps have been diagnosed as hyperplasia due to comprised fixation problems, mistakes in sections, and excessively bleeding curettages. The new sections applied to the cases were quite helpful. In the new sections, the thick-walled vessels belonging to the polyp and the stromal characteristics of the stroma could be visualized with more easily, and the diagnosis of endometrial polyp was made
Endometrial hyperplasias are quite often misdiagnosed lesions in surgical pathology3. Consequently, the criteria for the differential diagnosis of these lesions should be determined, and inhibiting factors for correct diagnosis should be eliminated. In a study by Winkler et al.12 100 cases formerly diagnosed as EH were re-evaluated by a reference pathologist, and only 24 cases received the diagnosis of EH in this second examination. Of the remaining cases, 25 were diagnosed as polyp, 17 as normal cyclic endometrium, and the rest as metaplastic changes and endometritis. In the study of Allison et al.5 2601 cases thought to be EH were evaluated by three academic pathologists. Although the diagnoses of the first two pathologists were consistent with each other, the diagnoses of the third pathologist were 27.7% and 43.9% consistent with the diagnoses of the first and second pathologist, respectively. The highest consistency in the diagnosis was obtained in cases without hyperplasia and the lowest consistency in cases with simple hyperplasia. When the cause of diagnostic inconsistency was assessed, it was seen that specimens smaller and larger than 0.5 cc yielded a diagnostic inconsistency of 64.6% and 56.5%, respectively. In determining the focus of hyperplasia, specimens smaller and larger than 0.5 cc yielded a diagnostic inconsistency of 61.9% and 38.8%, respectively. Furthermore, the diagnostic inconsistency related to endometrial polyp and metaplastic changes was reported, but this was insiginificant. In the present study, Of the 439 cases formerly diagnosed as simple EH without atypia, %31 (n=136) were evaluated as proliferative endometrium, %32 (n=140) as irregular proliferation, %0.7 (n=3) as metaplastic changes, %6.3 (n=28) as endometrial polyp %25(n=110) as simple EH and %5 (n=22) as insufficient. Of the 467 cases formerly diagnosed as complex hyperplasia without atypia, %37.7 (n=176) were evaluated as secretory endometrium, %6.6 (n=31) as proliferative endometrium, %8.6 (n=40) as endometrial polyp, %4.9 (n=23) as dysfunctional uterine bleeding, %2.4 (n=11) as Areas-Stella reaction, %4.5 (n=21) as metaplastic changes, %0.2 (n=1) as adenocarcinoma, %33 (n=154) as complex EH and %2.1 (n=10) as insufficient.
The criteria for atypia in EHs include loss of cellular polarity, increased irregular lining, anisocytosis, nucleomegaly, hyperchromatism, chromatin coarsening, and prominent nucleolus3,13. Moreover, an eosinophilic cytoplasm may be seen in some cases. Although cytoplasmic eosinophilia may be an alert for pathologist, it is not absolutely the necessarycriteria for the diagnosis ofatypia. These changes in cells can be confused with metaplastic changes3. Formerly, 94 cases out of a total of 1000 cases had been found to have atypia, whereas in the re-evaluation of cases, atypia was confirmed in only 18 cases. The diagnostic consistency for atypia was 38% in the study of Zaino et al.4 and 16.1% in the study of Allison et al.11 According to the WHO, many of the diagnostic criteria for atypia (nuclear irregularity, loss of polarity, prominent nucleolus, chromatin coarsening) can also be observed in hormonal irregularities, regeneration and metaplastic changes14. However, in our study, most of the diagnostic inconsistencies for atypia were associated with technical problems, such as insuitable fixation and insufficient staining quality.
There are some factors limiting the diagnosis in endometrial curettage material. Some of these factors comprise insufficient clinical data, curettage performed in the wrong cycle phase, insuitable fixation of the specimen, mistakes in histopathological sampling, sectioning and insufficient experience15. Since the diagnoses were confirmed in 23.2% of simple hyperplasia and in 34.2 % of complex hyperplasia cases, we assessed the factors limiting a correct diagnosis. The main causes of misdiagnosis were determined to be insufficient or moderately sufficient in sampling, not sampling the whole of the material, mistakes in fixation and subsequent procedures, improper sectioning and staining, and lack of experience. Some studies have reported that insufficient material is the foremost cause of misdiagnosis5. However, there is a serious inconsequence between pathologists with regard to the decision of sufficiency. In a study performed on 1280 cases, a diagnosis of insufficiency had been made by the general pathologists in 62 of the cases. These cases that had received insufficient diagnoses, were re-evaluated by the reference group who were Gynaecopathologists and an insufficient diagnosis was made in only 33 of the cases16. A total of 32 cases we had integrated into our study were evaluated as insufficient. A diagnosis of hyperplasia had been made for these cases. The majority of these cases comprised disintegrated endometrial glands. However, there were cervical epithelium demonstrating immature dysplasia in 2 cases.
In conclusion, for the diagnosis of endometrial specimens from women with the clinical prediagnosis of EH, continuous in-service training should be provided to avoid all deficiencies in the pre-analytic processes (sampling sufficient matherial, matherial fixation, etc.) and analytic processes (proper processing of the matherial, sectioning, staining-cover, diagnosis) to provide clinicopathological correlation and to increasingexperience.
)
)
)