|Ahead of print publication
Histopathological pattern of endometrial biopsies in patients with abnormal uterine bleeding
Sadbhawana Ranjan, Harsh Kumar, Charusheela Gore, Shirish Chandanwale, Aniket Bhide, Aishwarya Desai
Department of Pathology, Dr D Y Patil Medical College, Pimpri, Pune, Maharashtra, India
|Date of Submission||07-Aug-2021|
|Date of Decision||23-Aug-2021|
|Date of Acceptance||15-Oct-2021|
D1/1202, Mahindra Antheia, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Abnormal uterine bleeding (AUB) is bleeding from the uterus that is longer than usual or that occurs at an irregular time. Bleeding may be heavier or lighter than usual and may occur often or randomly. In most women, AUB is caused by a hormone imbalance. Any woman over the age of 40 years with menorrhagia or any other forms of abnormal vaginal bleeding should undergo a gynaecological check and an endometrial biopsy as indicated, in order to detect a potentially treatable cause as atypical endometrial hyperplasia and early endometrial carcinoma. The present study was done on women with AUB to evaluate the histopathological patterns in endometrial biopsy among different age groups. Materials and Methods: A cross-sectional study was carried out in Department of Pathology, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune. The clinical history and findings of 100 patients were collected and recorded. Histopathological study of endometrial patterns and age specific correlation was done. Results: Out of a total of 100 patients of AUB, 72 of them had a functional cause and the remaining 28 patients revealed an organic cause. The mean affected age was 40 years with youngest being 21 years old and the oldest patient was 57 years of age. Functional causes constituted 72% and organic lesions were seen in 28% out of which Proliferative phase endometrium was the most common functional lesion observed while endometrial hyperplasia was the commonest organic pathology seen. P value was calculated as <0.008 which was significant using chi square for trend seen in age. Conclusion: Histopathological examination of endometrial biopsy in patients of AUB is considered as a gold standard of patient evaluation, diagnosis and management and avoids any future complications.
Keywords: Bleeding, endometrium, uterine
|How to cite this URL:|
Ranjan S, Kumar H, Gore C, Chandanwale S, Bhide A, Desai A. Histopathological pattern of endometrial biopsies in patients with abnormal uterine bleeding. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Dec 7]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=337216
| Introduction|| |
Abnormal uterine bleeding (AUB) is one of the commonest gynaecological complaint seen in about 10%–15% of women. The female genital tract is highly responsive to sex hormones as compared to any other organ system in the body. Cyclical uterine bleeding marks an important stage of reproductive maturation. AUB includes both organic and nonorganic causes of uterine bleeding. In addition; it is also the commonest cause of iron deficiency anaemia and chronic malaise around the world. It is a disorder which is both medically and socially debilitating. Our present study is based on histopathological correlation of endometrial biopsies in patients in different age groups suffering from AUB. This study was done to evaluate the endometrial causes of AUB and to determine various histopathological patterns associated with AUB in women of different age groups.
| Materials and Methods|| |
The present study was a 2 years cross sectional study carried out in Department of Pathology, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune. The study included 100 endometrial biopsies.
All patients who presented to our hospital with a history of AUB and who underwent D and C were included in the study.
Patients with a gestational cause, hemostatic disorder, isolated cervical or vaginal pathology and leiomyoma were excluded. Also, autolysed specimens and sections not having enough material were excluded from the study.
Patients with a gestational cause, hemostatic disorder, isolated cervical or vaginal pathology and leiomyoma will be excluded. Also, autolysed specimens and sections not having enough material were excluded from the study.
Detailed clinical history, important clinical examination findings, results of relevant investigations done were obtained and recorded in a structured proforma. The data for the study was obtained from departmental files along with the clinical profile of the patient with results of the supportive investigations, slides, histopathology reports and paraffin blocks were analysed. All endometrial specimens obtained through D and C were received in 10% formal saline and were fixed overnight. Grossing of the specimens was done followed by selection of tissues for processing in an automatic tissue processor. Multiple sections of approximately 5 μm thick were prepared with the microtome and stained with routine Hematoxylin and Eosin stain. Microscopic evaluation was done by two pathologists to reduce observer bias.
| Results|| |
Out of the total of 100 patients, 46 patients were in the reproductive age group with a mean age of 40 years followed by 45 patients in perimenopausal age group. There were 9 cases in the age group of >50 years [Graph 1]. [Table 1] shows that the majority (72%) of patients with AUB had no organic lesion, thereby indicating a functional cause. The histopathological findings of endometrial biopsies thus analysed were categorized into functional and organic causes. It was observed that 72 out of the total of 100 patients had a functional cause for the AUB and the remaining 28 revealed an organic lesion. [Graph 2] depicts, out of the total 72 cases attributed to functional causes for AUB, proliferative followed by secretory endometrium were the most common pattern. They were seen in 35 (35%) and 33 (33%) of the patients, respectively. Age-related changes seen in the endometrium were seen in the age-group >50 years. Atrophic endometrium was noted in 4 patients. Out of 28 patients with organic lesions, endometrial hyperplasia was the most common finding. It was observed in 22/28 (78.5%) patients. The other organic causes of AUB observed in this study included disordered proliferative endometrium which was seen in 3/28 (10.7%) cases. Chronic endometritis seen in 2/28 (7.1%) patients and malignancy was observed in 1/28 (3.5%) patient.
Total of 7/22 (31.82%) cases showed atypical hyperplasia remaining 15/22 (68.1%) showed nonatypical hyperplasia (WHO 2014) [Graph 3]. In the present study, it was also noted that there were no organic lesions seen in the age group <30 years followed by 27.6% of incidence in 31–40 years, 29.5% and 62.5% seen in the age group of 41–50 years and >50 years [Table 2].
|Table 2: Distribution of causes of abnormal uterine bleeding in various age groups|
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In the analysis, shown in [Graph 4] there is a decreasing trend in functional lesions observed with advancing age. The highest incidence of functional lesions was seen in <30 years age group followed by 70.5% observed in age group 41–50 years and 37.5% seen in the age group more than 50 years. [Figure 1] shows disordered proliferative endometrium, [Figure 2] shows nonaypical endometrial hyperplasia, [Figure 3] shows Atypical endometrial hyperplasia, [Figure 4] shows moderately differentiated endometroid adenocarcinoma.
|Figure 1: Disordered proliferative endometrium: The photomicrograph is showing disordered proliferative endometrium with widely spaced glands that vary in size and shapes, some are cystically dilated and others show shallow budding. The glands are irregular in shape and separated by compact stroma. Gland to stroma ratio is normal. (H and E, ×100) paraffin embedded|
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|Figure 2: Nonaypical endometrial hyperplasia: The photomicrograph shows proliferating lining of the endometrial glands with no cytological atypia. (H and E, ×400) paraffin embedded|
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|Figure 3: Atypical endometrial hyperplasia: The photomicrograph shows pleomorphism of the glandular lining cells and stratification. (H and E, ×400) paraffin embedded|
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|Figure 4: Moderately differentiated endometroid adenocarcinoma: The photomicrograph shows lining cells of the neoplastic glands which exhibit severe nuclear pleomorphism, hyperchromatism and prominent nucleoli. (H and E, ×400) paraffin embedded|
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Histopathological correlation between causes of AUB with age was significantly seen. Chi-square test was calculated for trend as 7.06. Degree of freedom was calculated as 1.
P value was calculated as <0.008 which is statistically significant using Chi-square for trend (App used: WINPEPI).
| Discussion|| |
AUB is a commonly encountered gynaecological problem. It often interferes significantly with the quality of life in otherwise healthy women due to various distressing symptoms like menorrhagia, polymenorrhea and metrorrhagia. AUB includes both dysfunctional uterine bleeding (DUB) and bleeding from structural causes. DUB is defined as AUB without a demonstrable organic cause. In most instances, DUB is due to the occurrence of an anovulatory cycle. The mechanisms involved in anovulatory bleeding vary, but each reflects an abnormal pattern of steroid hormone stimulation, which may include estrogen breakthrough, estrogen withdrawal and progestin breakthrough bleeding. It is diagnosed after exclusion of structural, iatrogenic, medications, psychological and systemic disorders by various diagnostic techniques.
In our study the youngest patient was 21 years of age and the oldest was 57 years of age. The maximum cases were observed in 40-50 years followed by 31-40 years and minimum cases observed in the age group <30 years age group. Singh et al studied 300 similar cases also reported a significant occurrence of menstrual disorder in similar age group age, accounted for 48.6% (40-50 years). Doraiswamy et al studied 409 cases which also showed similar results. In our study the age group < 30 years, cases accounted for 12 %. Our study is comparable with Vaidya et al. with 16% in the age group of less than 30 years and 46.1% in 41-50 years of age. Malathi et al. noted 33% cases in 31-40 years of age groupwhich was comparable with 34% of cases in our present study. It was also observed that Goel et al. observed a higher incidence of patients (26.5%) in <30 years of age. The commonest pattern of bleeding abnormality observed in our patients was menorrhagia and post-menopausal bleeding. In an observational study done by Dhadhania B reported that menorrhagia was highest presenting complaint constituting 33% cases,the same observation was noted in similar studies. The commonest pattern of bleeding abnormality observed in the study conducted by Malathi et al. was Menorrhagia followed bypolymenorrhia. Singh et al. also observed similar pattern of bleeding with highest as Menorrhagia (42%) and lowest as intermenstrual bleeding (9.3%) which was comparable with the present study.
In the present study, histopathological examination of received endometrial biopsies revealed the commonest histological finding in this functional group was Proliferative 35 cases followed by secretory endometrium 33 cases, accounting for 35% and 33% cases, respectively. Study of Jairajpuri et al. and Vaidya et al. also showed these two as the most common functional causes of patients presenting with AUB. Singh et al. revealed 37% and 30% of Proliferative and Secretory Endometrium, respectively while Malathi et al. revealed 41.5% of Proliferative endometrium which was the commonest pattern observed. Beyna et al also observed 35.3% cases of proliferative endometrium.Secretory pattern was noted in 33% cases in our study which was comparable to study done by Singh et al and Doriswamy et al., The bleeding in proliferative endometrium could be due to ovulatory dysfunctional bleeding. There is no histopathological correlation with type of AUB and blood loss consequent to AUB.We noted atrophic endometrium in the age group of 50-60 years accounting for 4%. Malathi et al also accounted for 5.6%in the age group 41-50 years. Doraiswamy S. and authors found these cases often in the 5th and 6th decade of life. Singh et al accounted for 3 % of cases of AUB. Goel et al. reported atrophic endometrium in 6.8% cases. Studies conducted by Ara et al. reported an incidence of 7%. The cause of AUB in cases of atrophic endometrium is not clear. It can be due to diminished number and quality of ovarian follicles, abnormal local hemostatic mechanism or thin-walled veins which lie superficial to expanding cystic glands making it vulnerable to injury. Our study observed cases of chronic endometritis in 2% of patients, all fell in the reproductive age group of <40 yrs. Singh et al also noted 1.6% detection rate of chronic endometritis common in reproductive age group accounting for 2.11% cases of endometrial pathology. Chronic endometritis usually follows pregnancy, IUCD insertion and abortion. No specific infection like tuberculosis was observed in our cases. The detection rate of endometritis in study of Shah et al. and Forae et al. was 2.6% and 1.3%, respectively.
Amongst 28 organic lesions causing AUB, endometrial hyperplasia was the most common and was seen in 22/28 cases (78.5%), which was comparable with Vaidya et al. accounting for 61.11% cases. Similar data was published by Anwer et al. (62.8%). Goel et al. evaluated 61.9% of cases of endometrial hyperplasia in perimenopausal and menopausal women which was comparable with our study. The studies in the past also revealed similar results showing nonatypical hyperplasia as the highest and the commonest organic lesion amongst sub types endometrial hyerplasias. It is to be noted that atypical hyperplasias are recognized to be as the precursors of endometrial carcinomas, they are often associated with underlying risk factors like obesity, diabetes increased intake of animal fat and sedentary lifestyle. We noted endometrial adenocarcinoma in 1% (1/100) cases falling in >50 years age group. Malathi et al. also reported comparable incidence as 1.4% of endometrial carcinomas in the age group of 51–60 years. Singh et al. also reported 1% incidence among 300 cases in more than 50 years age group. Doraiswamy et al. also noted similar incidence in 51–60 years age group. In a similar study done by Dangal et al. the incidence was lower than other studies, which could be attributed to the practice of early child bearing and multiparity.
Histopathological examination of the endometrium that revealed malignant lesions as causes of AUB in our study constituted 1/28 (3.5%) cases which was comparable with Vaidya et al. with a total of 2.48% cases. Patel et al. revealed a higher incidence of carcinomas as 6.7%. Singh et al. revealed 1% cases of endometrial carcinoma as an organic cause of AUB. Malathi et al. and Goel et al. also observed similar number of cases as 1.40% and 0.76% of cases in the similar category.
| Conclusion|| |
AUB is a fairly common symptom amongst females. It may be due to functional or organic causes affecting the endometrium. The endometrial lesions vary according to the patient's age. Endometrial sampling is an effective and reliable diagnostic test. Its interpretation can be quite challenging and also may show considerable inter observer variability. Clinical information regarding age, menstrual history, parity, and imaging studies are important prerequisites in the interpretation of endometrial samples. The biopsy analysis reveals the different endometrial patterns in various forms of AUB and it also helps to exclude the presence of any organic pathology. To conclude, a histopathological evaluation of endometrium is very informative in assessing the cause of AUB. It is especially indicated in women over the age of 35 years for early detection of preneoplastic lesions and malignancies so that better treatment modalities can be offered.
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Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]