The range of endometrial pathologies in patients with abnormal uterine bleeding at a tertiary care center in central India

The study analyzed 226 endometrial biopsies/specimens collected over two years from patients with AUB as the main complaint. These specimens were processed, and slides stained with hematoxylin and eosin (H&E) were examined to determine the endometrial patterns. A chi-square test assessed the relationship between age and specific endometrial pathologies. Observations and Results: Most of the 226 cases were from perimenopausal women (40–49 years), representing 57% of the total, with proliferative endometrium being the most common pattern (40.9%). About 20% of the cases were in the reproductive age group (49 years), with endometrioid carcinoma being the most frequent pattern observed. Other endometrial patterns included disordered proliferative endometrium, endometritis, endometrial polyps, Arias–Stella reaction, and progesterone effects.

Patients with AUB present with a wide range of endometrial patterns, from normal cyclic endometrium to malignancies. Histopathological examination remains the gold standard for diagnosing AUB, showing a significant association between endometrial lesions and age.

Abnormal uterine bleeding (AUB) is one of the most common complaints that prompts endometrial samples to be taken using endometrial curettage. A total of 10%–30% of women in the reproductive age group and up to 50% of the perimenopausal age group are affected by it.[1] AUB can be defined as the variation in bleeding pattern inconsistent with that seen during a typical menstrual cycle or following menopause in frequency, length, or amount.[2] AUB includes menorrhagia (regular but heavy menses), metrorrhagia (bleeding in between regular menses), polymenorrhea (regular bleeding more often than 21days), oligomenorrhea (bleeding at a frequency of greater than 35 days), and postmenopausal bleeding. It hampers the quality of life and results in iron deficiency anemia. It includes both AUB and bleeding caused by pathological lesions such as leiomyoma, endometrial polyp, or endometrial carcinoma. A new categorization system (PALM-COEIN) for the causes of AUB has been created by the working group on menstrual disorders of the International Federation of Gynecology and Obstetrics. The nine clinical categories are listed alphabetically: polyp, adenomyosis, leiomyoma, malignancy and hyperplasia coagulopathy, ovulatory dysfunction, endometritis, iatrogenic, and not yet classified.[3] The PALM group classifies the causes of AUB as structural. It can be identified visually using imaging techniques and/or histopathology, while the COEIN group classifies the causes as nonstructural and can not be defined by imaging or histopathology. Dysfunctional uterine bleeding (DUB) is defined as AUB without any demonstrable organic cause.[4] Diagnostic modalities for AUB include a urine pregnancy test (to rule out abortion, which may cause heavy bleeding), complete blood test and coagulation profile, thyroid profile, hormonal assay, hysteroscopic evaluation of the uterus, pelvic/transvaginal ultrasound, and endometrial biopsy. Endometrial biopsy and curettage are the two most important diagnostic modalities for the definitive diagnosis of the lesion.[5] The histopathological spectrum of endometrial lesions in cases of AUB includes organic causes like endometritis, hyperplasia, polyp, and carcinoma, as well as functional causes like normal cyclical endometrium (proliferative or secretory phase), abnormal physiological changes of the endometrium (atrophic, weakly proliferative, disordered), and many others. The age of patients plays a pivotal role in various histological patterns of the endometrium.[6] Atypical hyperplasia and endometrial carcinoma are quite uncommon in premenopausal women and common in postmenopausal women.[7] This study was undertaken to study the histopathological lesions of endometrium in patients presenting with complaints of AUB and the incidence of various lesions among various age groups.

Study design This study was carried out in the Department of Pathology at Pt. Jawahar Lal Nehru Memorial Medical College, Raipur, Chhattisgarh, India, over nine months (February–October 2022). Approval was obtained from the Institutional Ethics and Scientific Committee. The study design was an observational descriptive cross-sectional study. Study tools This study included endometrial biopsies and histopathological specimens from patients presenting with AUB at the Histopathology Laboratory of the Department of Pathology during the study period. Operational definition AUB: The abnormal menstrual cycle has a frequency of 24–38 days and lasts 7–9 days with 5–80 mL of blood loss. Variations in any of these three parameters constitute AUB.[8] Inclusion criteria Biopsies or histopathological specimens were received from patients of all age groups presenting with AUB who underwent dilatation and curettage (D&C) or hysterectomy for their condition. Exclusion criteria Endometrial biopsies or histopathological specimens related to pregnancy complications, including abortion, molar pregnancy, and ectopic pregnancy, as well as those that were inadequate, crushed, or partially or fully autolyzed, were excluded.

The study samples were received as endometrial curettage, endometrial biopsy, and hysterectomy specimens. All specimens were fixed in 10% formalin for 24 h. The gross morphology of a small biopsy was described in terms of amount, size, color, and consistency. Small biopsies were entirely submitted for histopathological processing.(Curettage = 1 g per cassette). Gross examination of hysterectomy specimen (non-malignant lesion)[9] Gross morphological features, including dimension, weight, and appearance, were recorded for large specimens (hysterectomy specimens) and serially sliced to ensure fixation. Representative bits were taken post-24 h fixation in 10% formalin. After weighing, the uterus was opened longitudinally from the anterior through the posterior surface. Length of uterine cavity, endocervical canal, and average endometrial and myometrial thickness were measured. The presence of polyps, cysts, and fibroids was noted in the endometrial cavity. Number, location (submucosal, intramural, subserosal), size of smallest and largest, and any change in the fibroid–hyalinization, red degeneration, calcification, cystic change, and necrosis were noted. Representative sections were taken as per Figure 1. Gross examination of hysterectomy specimen (non-malignant lesion) Gross examination of hysterectomy specimen for carcinoma endometrium[9] Gross morphological features, including size, location, the appearance of the tumor (solid, cystic, papillary) color, and the presence of ulceration, necrosis, and hemorrhage were noted. Involvement of the myometrium, cervix, isthmus, and parametrium was noted. Representative sections were taken as per Figure 2. Gross examination of hysterectomy specimen (carcinoma endometrium) Microscopic examination Tissues were processed using an automated tissue processor (Thermo Automatic Tissue Processor 120) and embedded in paraffin wax. Five microns thick sections were cut with a rotary microtome and stained with hematoxylin and eosin (H&E). The H&E-stained slides were examined under a light microscope to assess endometrial lesions [Figures 3 and 4]. H&E images of the spectrum of endometrial changes in various conditions of AUB

In this study, 226 cases of endometrial biopsies and hysterectomy specimens were analyzed from patients presenting with AUB. Of these, 130 specimens (58%) were endometrial biopsies, while 96 (42%) were hysterectomy specimens. The study population was divided into three age groups: reproductive age (49 years). Of the 226 cases, 127 cases (57%) were in the perimenopausal group, 53 cases (23%) were in the postmenopausal group, and 46 cases (20%) were in the reproductive age group [Figure 5]. The average age of the study population was 44.2 years. Age-wise distribution of study population (n = 226) The two most common histopathological patterns observed were proliferative phase endometrium and hyperplasia without atypia, each found in 28.8% of cases. Secretory phase endometrium was seen in 11.1% of cases, while endometrial carcinoma was found in 8.0%. Additionally, 13 cases (5.8%) showed benign endometrial polyps, nine cases (4.0%) had disordered proliferative endometrium, and three cases (3.1%) each showed chronic endometritis and menstrual phase endometrium. Atrophic endometrium was seen in six cases (2.7%). There were also two cases of Arias–Stella reaction, two cases of progesterone effect, one of inadequate secretory phase/luteal phase defect, and one of endometrial stromal sarcoma [Table 1]. Histopathological spectrum of endometrium in the study population (n = 226) In the 127 cases within the perimenopausal age group, the most common finding was proliferative phase endometrium, observed in 52 cases (40.9%). This was followed by hyperplasia without atypia in 34 cases (26.8%). Other findings included 15 cases of secretory phase endometrium, six cases of disordered proliferative endometrium, five cases of menstrual phase endometrium, and four cases of benign endometrial polyps. Additionally, three cases of endometrial carcinoma were identified, including two cases of type I and one case of type II [see Table 2]. Histopathological spectrum of endometrium in various age groups (n = 226) In the postmenopausal age group (53 cases, 23%), endometrial carcinoma was the most prevalent histopathological finding, observed in 13 cases (24.5%). This was followed by hyperplasia without atypia in 10 cases (18.9%) and proliferative phase endometrium in eight cases (15.1%). Additionally, there was one case of endometrial stromal sarcoma in this group [see Table 2]. In the reproductive age group (46 cases, 20%), hyperplasia without atypia was the most common lesion, found in 21 cases (45.7%). This was followed by secretory phase endometrium in three cases (15.2%) and proliferative phase endometrium in five cases (10.9%). Other findings included four cases of benign endometrial polyps, two cases of chronic endometritis, and one case each of disordered proliferative endometrium, progesterone effect, luteal phase defect, type I endometrial carcinoma, and type II endometrial carcinoma. Arias–Stella reaction and atrophic changes were not observed in this group [see Table 2]. The chi-square test found a statistically significant association between age groups and different endometrial patterns (P-value < 0.01). Out of 226 cases, 18 were diagnosed as endometrial carcinoma. Among these, 15 cases were type I endometrial carcinoma, and three were type II. The majority of type I cases (66.7%, 12 cases) were in the postmenopausal age group, two cases (11.1%) were in the perimenopausal group, and one case (5.2%) was in the reproductive age group. The type II endometrial carcinoma distribution was equal across all three age groups, with one case each [Table 3]. Distribution of cases of endometrial carcinoma (n = 18) Additionally, 67 cases (30%) showed coexisting non-endometrial pathologies. Leiomyoma was the most common finding, present in 26 cases (39%), followed by adenomyosis in 19 cases (28%) and adenomyoma in 20 cases (30%). Leiomyomatous polyps were observed in two cases (3%) [Table 4]. Non-endometrial lesions in patients presenting with AUB (n = 67)

Endometrium exhibits histological variance depending on the woman’s age, the stage of the menstrual cycle, and coexisting pathology, if any.[10] In our study, out of 226 cases, 127 (57%) were in the perimenopausal age group. Almost similar observations were also made in the study by Bhatta et al.,[11] Sanjitha et al.,[12] Mune et al.,[13] Singh et al.,[14] Bindroo et al.,[15] and Brahmaiah et al.,[16] showing 39.34%, 42.95%, 42%, 49.2%, 43.2%, and 35.71%, respectively. The incidence of AUB was higher in the perimenopausal age group than in the postmenopausal age group. The prompt and early evaluation of patients can explain this.[17] This can also be explained that as menopause approaches, the number of ovarian follicles decreases, and their susceptibility to gonadotrophic stimulation increases, which results in low levels of estrogen that are insufficient to maintain the growth of the normal endometrium in this age range.[18] Histopathological evaluation of endometrium revealed various patterns ranging from physiological to pathological lesions of endometrium. In the present study, the most common pattern was normal cyclical endometrium comprising proliferative (28.8%) and secretory (11.1%) phase endometrium, totaling 39.9%. The incidence of 28.8% of proliferative endometrium compares with that of 26.23% by Bhatta et al.,[11] 27.8% by Mune et al.,[13] 31.90% by Brahmaiah et al.,[16] 22.5% by Forae et al.,[19] and 29% by Naeem et al.[20] In the present study, the secretory phase was found in 11.1% of cases of AUB, which is comparable with that of 11.43% by Brahmaiah et al.,[16] 12.89% by Prathipaa et al.,[21] and 10% by Forae et al.[19] A slightly higher number of cases was found in a study done by Bhatta et al.[11] (16.39%), Sajitha et al.[12] (16.7%), Sharma et al.[17] (16.4%), Rajagopal et al.[22] (23.9%), and Naeem et al.[20] (16.8%). The failure of the corpus luteum to synthesize an appropriate amount of progesterone, despite being active for 12–14 days, explains why bleeding during the secretory phase is caused by ovulatory DUB.[19] In the present study, menstrual phase endometrium was seen in 3.1% of cases, which is slightly higher than that seen in the study done by Sajitha et al.[12] (1.28%) and Rajagopal et al.[22] (0.5%). The spectrum of proliferative lesions of the endometrium includes carcinoma at one end and disordered proliferative endometrium at the other end, with stages of hyperplasia in between. Disordered proliferative endometrium exaggerates the normal proliferative phase without a noticeably increased glands-to-stroma ratio.[19] The absence of uniform glandular development sets it apart from abnormal proliferative endometrium, but it is not abnormal enough to be classified as hyperplastic. Although the process is focal rather than diffuse, it resembles simple hyperplasia. In practice, gynecologists will be able to stop the progression of the disease by diagnosing patients at the earliest possible stage of this spectrum. In the present study, 4.0% (09) cases of disordered proliferative endometrium were seen which was comparable with that of 6.56% by Bhatta et al.,[11] 2.4% by Bindroo et al.,[15] 6.67% by Brahmaiah et al.,[16] 6.5% by Sharma et al.,[17] and 3.13% by Prathipaa et al.[21] The results were found comparatively lower compared with Sanjitha et al.[12] (12.2%), Mune et al.[13] (13.7%), Singh et al.[14] (16.1%), and Parmar et al.[23] (33.33%). In the present study, we found 70 cases of endometrial hyperplasia. Of 70, 65 (92.8%) were typical hyperplasia, and 05 cases (7.2%) were atypical. These results were comparable with the study done by Sharma et al.[17] (77.2% and 22.8%), Bhat et al.[24] (78.9% and 21.1%), Rajagopal et al.[22] (92.1% and 7.9%), and Prathipaa et al.[21] (90% and 10%), respectively. Endometrial polyps can also occur due to persistent estrogen stimulation.[25] In the present study, 5.8% of cases of benign endometrial polyps were found, which was similar to the results seen in a study done by Sajitha et al.[12] (5.12%), 8% by Mune et al.,[13] and 8.1% by Singh et al.[14] The findings were found higher compared with Bhatta et al.[11] (2.46%), Brahmaiah et al.[16] (0.95%), Sharma et al.[17] (2.2%), Bhat et al.[19] (1.9%), Forae et al.[22] (2.2%), and Baral et al.[25] (1.3%). Out of 226 cases, 3.1% of cases were diagnosed as chronic endometritis, which is consistent with the results found in a study done by Mune et al.[13] (2.4%), 2.4% by Singh et al.[14] 2% by Bindroo et al.,[15] and 3.3% by Sharma et al.[17] It has been reported that chronic endometritis, which is characterized by an irregular fibrotic stroma and lymphoplasmacytic cells, follows pregnancy or abortion. It may also develop from IUCD or be connected to PID and mucopurulent cervicitis. Atrophic endometrium was found in 2.7% of cases of AUB, which was comparable to 5.12% by Sajitha et al.,[12] 3.33% by Brahmaiah et al.,[16] and 4.4% by Sharma et al.[17] An atrophic endometrium is usually linked to postmenopausal bleeding. The precise reason is unknown. Theoretically, postmenopausal bleeding could be caused by a thin, atrophic endometrium that is vulnerable to small harm as a result of a protracted lack of any exogenous or endogenous estrogenic stimulation, even in the absence of a visible lesion.[11] In the present study, effects of exogenous hormones (pill endometrium) were seen in 0.9% of cases, compared to that of 7.7% of cases by Sajitha et al.,[12] 0.8% by Bindroo et al.,[15] 3.81% by Brahmaiah et al.,[16] and 2.9% by Rajagopal et al.[22] This study identified two cases (0.9%) of the Arias–Stella reaction. Additionally, one case (0.4%) of inadequate secretory phase/luteal phase defect was observed, aligning with Sajitha et al.[12] study findings (2.56%). Endometrial carcinoma can arise from either de novo with low progesterone levels or excessive estrogenic stimulation and develop against a background of endometrial hyperplasia. In the present study, 18 (8.0%)of endometrial carcinoma cases were noted. Similar results were seen in a study by Bhatta et al.[11] (5.74%) and Sajitha et al.[12] (4.5%). Of 18 cases, 15 were of type I endometrial carcinoma, and 03 were of type II endometrial carcinoma. Of 15 cases of type I endometrial carcinoma, 12 were well-differentiated classical endometrioid adenocarcinoma, 02 were reported as Villoglandular variants, and 01 showed endometrioid carcinoma with secretory changes. Of three cases of type II endometrial carcinoma, 02 were serous carcinomas, and 01 was reported as clear cell adenocarcinoma. Most cases (41%) of proliferative phase endometrium were observed in perimenopausal women. Similar results were obtained in the study done by Bhatta et al.[11] and Bindroo et al.,[15] i.e., 43.75% cases and 37.2% cases were seen in the perimenopausal age group, respectively. Bleeding during the proliferative phase is caused by an anovulatory cycle, a gradual rise in estrogen to a relatively high level, and an abrupt fall in estrogen caused by feedback suppression of pituitary or FSH release and bleeding.[24] The maximum number of disordered proliferative endometrium (66.7%) was seen in the perimenopausal age group. The results were comparable with the study done by Sanjitha et al.[12] (57.9%), Mune et al.[13] (58.6%), Singh et al.[14] (60%), and Prathipaa et al.[21] (62.5%). The results were slightly lower in a study done by Bhatta et al.[11] (50%), Bindroo et al.[15] (33.4%), Sharma et al.[17] (33.4%), and Parmar et al.[23] (29.4%). The result was slightly higher in the study done by Brahmaiah et al.[16] (78.5%). A significant contributing factor to AUB is endometrial hyperplasia, marked by an increased proliferation of endometrial glands relative to the stroma, leading to a higher gland-to-stroma ratio. Given its association with endometrial carcinoma, endometrial hyperplasia demands special attention as it is considered a precursor lesion to malignancy. Unopposed estrogen exposure to the endometrium is the primary cause of endometrial hyperplasia. According to the latest World Health Organization (WHO) classification published in 2014, endometrial hyperplasia is categorized into typical and atypical types. Atypical endometrial hyperplasia has a higher risk of progressing to carcinoma. The two categories differ in prognosis and treatment implications. However, the presence of hyperplasia alone does not necessarily warrant a hysterectomy. In the present study, maximum numbers of endometrial hyperplasia were seen in the perimenopausal age group (50%). The results were comparable with the study done by Bhatta et al.[11] (45.5%), Sanjitha et al.[12] (56.4%), Mune et al.[13] (42.5%), Singh et al.[14] (46.1%), Brahmaiah et al.[16] (54.7%), and Parmar et al.[24] (54.5%). The results were slightly lower in the study done by Prathipaa et al.[21] (36.7%). Slightly higher results were seen in the study done by Bindroo et al.[15] (67.5%) and Sharma et al.[17] (59%). In the present study, endometrial polyps were seen equally in the reproductive and perimenopausal age groups (30.7%), with a slightly higher postmenopausal age group (38.6%). The results of the study by Mune et al.,[13] Singh et al.,[14] Prathipaa et al.,[21] and Parmar et al.[23] showed a maximum number of cases in the perimenopausal age group that is 47%, 45%, 50%, and 45.4%, respectively. In a study by Sanjitha et al.,[12] the maximum number of endometrial polyp cases (50%) were in the postmenopausal age group, as in the present study. In the present study, maximum numbers of atrophic endometrium were seen in the postmenopausal age group (66.67%). The results were comparable with the study done by Bhatta et al.[11] (77.8%), Sanjitha et al.[12] (75%), Singh et al.[14] (63.7%), Brahmaiah et al.[16] (71.5%), and Sharma et al.[17] (75%). The results were slightly lower in the study by Mune et al.[13] (50%). Higher results were seen in the study done by Bindroo et al.[15] (100%) and Prathipaa et al.[21] (100%). In the present study, maximum numbers of endometrial carcinoma were seen in the postmenopausal age group (72.2%). The results were comparable with the study done by Bhatta et al.[11] (57.1%), Sanjitha et al.[12] (57.3%), and Singh et al.[14] (66.7%). The results were higher in the study done by Sharma et al.[17] (100%) and Prathipaa et al.[21] (100%). This study observed a significant age-specific correlation across various endometrial lesions. A statistically significant link between malignant and premalignant lesions and the postmenopausal and perimenopausal age groups was identified. In contrast, normal cyclical endometrium and other benign lesions were more prevalent in the reproductive age group. Endometrial biopsies play a crucial role in the early detection of premalignant and malignant lesions, potentially saving lives. Additionally, they can help prevent unnecessary hysterectomies in benign lesions or those related to hormonal imbalances. Accurate interpretation of endometrial samples is vital for effectively managing AUB across all age groups. However, variations in biopsy interpretation between observers can occur, highlighting the need for standardized reporting practices.

Histopathological examination of the endometrium in patients with AUB can reveal a wide spectrum of changes, ranging from normal endometrium at various hormonal stages to malignancies. Endometrial sampling is often the first diagnostic step for AUB, especially in postmenopausal women, who are at increased risk for malignancy. AUB necessitates thorough and prompt evaluation, as it may be the only clinical indicator of endometrial cancer. However, pathologists often face challenges in histopathological assessment due to the frequent issue of inadequate endometrial samples. Ethical policy and institutional review board statement Institutional Ethics Committee (IEC) of Pt. Jawahar Lal Nehru Memorial Medical College, Raipur, Chhattisgarh, India, reviewed the research protocol on February 16, 2022, and found it suitable for research purposes. Accordingly, the IEC approved the research proposal. Notification of the IEC’s approval was communicated via letter no. MC/Ethics/2022/86, dated 16.02.2022. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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