|Year : 2014 | Volume
| Issue : 2 | Page : 76-81
Study of histopathological patterns of endometrium in abnormal uterine bleeding
K Sajitha, Shetty K Padma, K Jayaprakash Shetty, HL KishanPrasad, Harish S Permi, Panna Hegde
Department of Pathology, KS Hegde Medical Academy of Nitte University, Mangalore, Karnataka, India
|Date of Web Publication||11-Jun-2014|
Assistant Professor, Department of Pathology, KS Hegde Medical Academy of Nitte University, Deralakatte, Mangalore 575 018, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Abnormal uterine bleeding (AUB) is a common gynecological complaint associated with considerable morbidity and significantly affects the patient's family, personal and social life. The aim of the study was to analyze the histomorphological patterns of endometrium in patients presenting with AUB and also to determine the incidence of AUB in various age groups. Materials and Methods: This is a prospective study, conducted in the Department of Pathology, in a tertiary care teaching hospital, Mangalore from October 2011 till date. All cases of AUB with a probable endometrial cause were included in the study. Data was entered in Microsoft Excel and managed in Statistical Package for the Social Sciences (SPSS) version 16. Analysis was done in the form of percentages and proportions and represented as tables where necessary. Results: A total of 156 cases were analyzed. Patients' age ranged from 23-78 years. AUB was most prevalent in the perimenopausal age group. The most common presenting complaint was menorrhagia (47%). Endometrial hyperplasia was the most common histopathological finding and was seen in 25% patients, followed by secretory endometrium in 16.7% patients, and proliferative phase pattern and disordered proliferative endometrium were seen in 12.2% patients each. Malignancy was detected in 6.4% of cases and endometrial carcinoma was the most common lesion (4.5%). Conclusions: Histopathological evaluation of endometrial samples is especially indicated in women over the age of 35 years to rule out malignancy and preneoplasia. Among the patients with no organic pathology, normal physiological patterns with proliferative, secretory, and menstrual changes were observed. The most common endometrial pathology in this series was endometrial hyperplasia.
Keywords: Abnormal uterine bleeding, dilatation and curettage, dysfunctional uterine bleeding, endometrium
|How to cite this article:|
Sajitha K, Padma SK, Shetty K J, KishanPrasad H L, Permi HS, Hegde P. Study of histopathological patterns of endometrium in abnormal uterine bleeding. CHRISMED J Health Res 2014;1:76-81
|How to cite this URL:|
Sajitha K, Padma SK, Shetty K J, KishanPrasad H L, Permi HS, Hegde P. Study of histopathological patterns of endometrium in abnormal uterine bleeding. CHRISMED J Health Res [serial online] 2014 [cited 2017 Mar 27];1:76-81. Available from: http://www.cjhr.org/text.asp?2014/1/2/76/134265
| Introduction|| |
Abnormal Uterine Bleeding (AUB)-a term used to describe any type of bleeding that does not fall within the normal ranges for amount, frequency, duration, or cyclicity.  The most common presentations are menorrhagia, polymenorrhoea, metrorrhagia, and intermenstrual bleeding. Dilatation and Curettage (D and C) is the mainstay of endometrial sampling since a long time. D and C also allows for a fractional curettage with separate sampling of both the endometrial and endocervical tissue. Hysteroscopy has almost replaced blind curettage as the uterine cavity can be observed and the area in question can be curetted. Transvaginal/transabdominal ultrasonography is another useful adjunctive technique for examining the endometrium in the evaluation of AUB. ,,
The underlying disease can be detected by histological variations of endometrium taking into account the age of the woman, the phase of her menstrual cycle, and use of any exogenous hormones. Pregnancy-related and dysfunctional uterine bleeding are more common in younger patients, whereas atrophy and organic lesions become more frequent in older individuals. Hyperplasia is found in up to 16% and endometrial carcinoma in fewer than 10% of postmenopausal patients undergoing biopsy.  Patients with a history of anovulation, obesity, hypertension, diabetes, and exogenous estrogen use are at an increased risk for hyperplasia and adenocarcinoma.  Early evaluation in the perimenopausal and postmenopausal women is essential to confirm the exact nature of the lesion and to rule out malignancy.
| Materials and Methods|| |
All patients who presented in this hospital with a history of AUB between October 2011 till date and who underwent D&C or hysterectomy were included in the study. Patients with a gestational cause, hemostatic disorders, isolated cervical or vaginal pathology, and leiomyoma excluded. Relevant clinical data regarding age, pattern and duration of abnormal bleeding, menstrual history, obstetric history, use of exogenous hormones, physical and gynecological examination findings, lab investigation results, and sonological and hysteroscopic findings were obtained from case records from Medical Records Department. All data were recorded in a carefully structured proforma.
All the specimens were fixed in 10% formalin, processed and embedded in paraffin, and 3-4 μ thick sections were made. Sections were stained with hematoxylin and eosin stain. A total of 156 cases were analyzed and histological diagnosis was made. Data were entered in Microsoft Excel and managed in SPSS version 16. Analysis was done in the form of percentages and proportions and represented as tables and figures where necessary.
| Results|| |
A total of 156 endometrial specimens submitted with a clinical diagnosis of AUB were studied.
Patients' age ranged from 23-78 years and most of them were seen in the age group of 46-55 years, followed by 36-45 years [Table 1].
|Table 1: Distribution of patients with abnormal uterine bleeding in different age groups: (n=156)|
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The commonest complaint was menorrhagia in 73 patients (47%).
Parity in the present study ranged from para 1 to para 8. Seventy five (48.4%) of them were in the low parity group (para 1-2) followed by para 3-4 (32.4%).
In our study, 75.6% of the patients were of normal weight, 18.6% patients were overweight, and 3.8% were obese [Table 2].
The commonest pathology observed in the study was endometrial hyperplasia in 39 (25%) patients. Secretory endometrium was the next commonly observed pattern seen in 26 (16.7%) patients, followed by proliferative and disordered proliferative endometrium in 19 (12.2%) patients each. Endometrial carcinoma was seen in 7 (4.5%) cases [Table 3].
|Table 3: Distribution of endometrial patterns in abnormal uterine bleeding patients|
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Endometrial hyperplasia and polyps the most common patterns seen in the age group ≤35 years. Between 36-45 years, secretory pattern was the most common followed by proliferative change. In the 46-55 age group, endometrial hyperplasia was the most common pattern followed by disordered proliferative pattern. Most of the endometrial and other carcinomas were presented after age 55 years [Table 4].
| Discussion|| |
AUB accounts for almost 25% of gynecological operations and 20% of outpatient visits.  In this study, we have studied the histopathology of endometrium to identify the endometrial causes and also observe the incidence of various pathologies in different age groups and their relation to parity.
In the present study, the maximum incidence of AUB was in the 46-55 years age range (67 patients), followed by 36-45 years age group (62 patients). Our study and other studies have found a maximum incidence of AUB in the perimenopausal age group. ,,,,,, Perimenopause is defined by the World Health Organization as the 2-8 years preceding menopause and the 1 year after the final menses.  As women approach menopause, cycles shorten and often become intermittently anovulatory due to a decline in the number of ovarian follicles and fluctuations in the estradiol level leading to various patterns of abnormal bleeding. 
Our study and other studies found menorrhagia as the most common complaint. ,,, Most of our patients were in the low parity category. Other studies reported a higher incidence of AUB with increase in parity. ,, However, this pattern was not noted in our study and majority of our patients were para 1-2.
Endometrial hyperplasia was the most common histological pattern observed in our study and was seen in 39 cases (25%). A few studies have reported a similar incidence with 24.7% and 26%, respectively. , However, most other studies have observed a lower incidence with 12.6%, 15%, and 4.33%. ,,
In the present study, the maximum incidence of hyperplasia was noted in the 46-55-year age group and was seen in 22 of 39 patients (56.4%). This was consistent with the findings in other studies. ,,,,
In our study, there was a fair correlation between a finding of increased endometrial thickness (ET) by ultrasonography (USG) and histopathological diagnosis of endometrial hyperplasia, but there was a poor correlation between hysteroscopic and histopathological diagnosis of endometrial hyperplasia [Table 5] as calculated by Spearman Correlation Test.
|Table 5: Correlation of ultrasonography, hysteroscopy and hypersensitivity pneumonitis in diagnosis of endometrial|
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Identification of endometrial hyperplasia is important because they are thought to be precursors of endometrial carcinoma.  The overall risk of progression of hyperplasia to cancer is 5-10%.  Simple (SH) [Figure 1]a], complex (CH) [Figure 1]b], simple atypical (SAH), and complex atypical hyperplasia (CAH) have different progression risks of 1%, 3%, 8%, and 29%, respectively, to carcinoma.  The different types of hyperplasias observed in this study were SH-20 (12.8%), SAH-6 (3.85%), CH-2 (1.28%), and CAH-11 (7.05%).
|Figure 1: (a) Simple hyperplasia without atypia, showing mildly irregular, variably sized glands in abundant stroma with squamousmetaplasia. H and E ×400 (b) Complex hyperplasia without atypia, highly irregular glands with scant stroma and inset showing regular, uniform nuclei. H and E ×400 (c) Proliferative endometrium, glands are tubular and regularly spaced in abundant stroma. H and E ×100 (d) Disordered proliferative endometrium, showing disorganized proliferative phase glands with focal glandular dilatation. H and E ×100|
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In the present study, body mass index (BMI) was found to be significantly higher in women with endometrial hyperplasia. Of the 39 patients with hyperplasia, 10.2% were found to be obese and 30.76% were overweight. In obese women, there is an increased risk of endometrial hyperplasia (EH) and endometrial carcinoma which can be explained by the increased availability of peripheral estrogens as a result of aromatization of androgens to estrogens in adipose tissue and lower concentrations of sex hormone-binding globulins.  Also the occurrence of other concurrent risk factors like diabetes mellitus and increased dietary fat intake probably contribute to the pathology in this group.
In our study, predominant number of patients in the age group 36-45 years showed normal physiological changes like proliferative and secretory phase patterns. Secretory endometrium was the second most common pattern observed in this study and was seen in 26 (16.7%) patients. A similar incidence of secretory pattern (16.6%) was noted in another study.  The bleeding in secretory phase is due to ovulatory dysfunctional uterine bleeding and is characterized by regular episodes of heavy menstrual blood loss. The main defect is in the control of processes regulating the volume of blood lost during the menstrual breakdown of endometrium. 
In the present study, a proliferative pattern of endometrium [Figure 1]c] was observed in 12.2% patients. Other studies reported incidences of 17.8%, 33%, 32.6%, and 32%. ,,, This pattern was commonly observed in the late reproductive and perimenopausal women in our study and other studies and may be due to the hormonal imbalance in this group leading to intermittent anovulatory cycles.
Disordered proliferative endometrium [Figure 1]d] is an exaggeration of the normal proliferative phase without significant increase in the overall ratio of glands to stroma and is due to persistent oestrogen stimulation. , This pattern is particularly seen in perimenopausal women. The disordered proliferative endometrium resembles normal proliferative tissue in consisting of glands lined by cytologically bland, pseudostratified, proliferative, mitotically active epithelium and in having a normal ratio of glands to stroma. It differs from the normal proliferative endometrium in the absence of uniform glandular development. Disordered proliferative pattern lies at one end of the spectrum of proliferative lesions of the endometrium that includes carcinoma at the other end with intervening stages of hyperplasias.  This pattern was seen in 19 (12.2%) of our cases. Another study reported a similar incidence of 10%. 
Atrophic endometrium is the most common cause of bleeding in postmenopausal stage.  Thin walled veins, superficial to the expanding cystic glands, make the vessels vulnerable to injury and lead to excessive uterine bleeding.  Atrophic endometrium was seen in 5.13% of the patients in this study and they presented as postmenopausal bleed. A similar incidence was reported in other studies with incidences of 4.34% and 7%, respectively. ,
In our study, pill endometrium was seen in 12 (7.69%) cases. Other studies reported a lower incidence. ,, In this pattern, the endometrium shows a combination of inactive glands, abortive secretions, decidual reaction, and thin blood vessels.  This pattern was predominantly seen in the perimenopausal age group. This was probably due to increased number of patients in this age resorting to early medical management for bleeding.
The other benign patterns included endometrial polyps (5.12%), irregular shedding (3.84%), luteal phase defect (2.56%), endometritis (0.64%), and menstrual pattern (1.28%).
The malignant conditions observed in this study included seven cases of endometrial carcinoma, two cases of squamous cell carcinoma of the cervix infiltrating into endometrium, and one case of low-grade endometrial stromal sarcoma [Figure 2]a and b].
|Figure 2: (a) Endometrial stromal sarcoma, gross: Tumour presenting as a fleshy mass in the parametrium (b) Endometrial stromal sarcoma, composed of cells with uniform round to oval nuclei, fi nely granular chromatin, small nucleoli, and scanty cytoplasmwith ill-defi ned cell borders. H and E ×100 (c) Endometrial carcinoma, gross: Hysterectomy specimen, showing exophytic irregular growth involving the endometrial cavity and extending up to the lower uterine segment (d) Endometrioid adenocarcinoma, International Federation of Gynecology and Obstetrics (FIGO) grade 2, showing well-defi ned glands with confl uent pattern, nuclei are enlarged, irregular to rounded, vesicular with prominent nucleoli. H and E ×400|
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The predominant type of endometrial carcinoma was endometrioid type which constituted five cases. One each of classical endometrioid adenocarcinoma [Figure 2]c and d] and villoglandular variants and three were endometrioid carcinoma with squamous differentiation. We had one case each of serous carcinoma and clear cell carcinoma. The most common presentation in these patients was postmenopausal bleeding and incidence of endometrial carcinoma was 21.73% in the postmenopausal group. This was similar to that reported by Baral R et al. with an incidence of 21%.  Nulliparity, increased BMI, and chronic anovulation have been implicated as risk factors for endometrial carcinoma. Out of the total seven cases of endometrial carcinomas in our study, two (28.6%) were nulliparous and two (28.6%) were overweight (BMI 25-30 kg/m2). Similar pattern was reported in another study with an incidence of 20% in nulliparous women and 60% in patients with a BMI of >30 kg/m2. 
Primary cancer of cervix extending to the endomerium was observed in two cases (1.28%) and they presented with postmenopausal bleed. This was consistent with the findings of Ara S who reported an incidence of 1.24%.  The patient with low-grade Endometrial Stromal Sarcomas (ESS) was 47-years old and presented with menorrhagia and mass in the pelvis. In a previously reported study of 14 cases of low grade ESS, the most common presentation was vaginal bleed (86%), followed by pelvic mass (7%) and pelvic pain (7%). 
| Conclusion|| |
Endometrial lesions vary according to the patient's age. Endometrial sampling by dilatation and curettage is an effective and reliable diagnostic test. Its interpretation can be quite challenging and also may show considerable interobserver variability. Clinical information regarding age, menstrual history, parity, and imaging studies are important prerequisites in the interpretation of endometrial samples. Dilatation and curettage reveals the endometrial patterns in various forms of AUB and also helps to exclude the presence of any organic pathology. Thus, histopathological evaluation of endometrium is especially indicated in women over the age of 35 years to rule out preneoplastic lesions and malignancies.
| References|| |
|1.||Munro MG, Critchley HO, Fraser IS, FIGO Menstrual Disorders Working Group. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertil Steril 2011;95:2204-8. |
|2.||Mazur MT, Kurman RJ. Normal endometrium and infertility evaluation. In: Mazur MT, Kurman RJ, editors. Diagnosis of endometrial biopsies and curettings: A practical approach. 2 nd ed. New York: Springer Verlag; 2005. p. 7-33. |
|3.||Goldstein SR. Menorrhagia and abnormal bleeding before the menopause. Best Pract Res Clin Obstet Gynaecol 2004;18:59-69. |
|4.||Jyotsana, Manhas K, Sharma S. Role of hysteroscopy and laparoscopy in evaluation of abnormal uterine bleeding. JK Sci 2004;6:23-7. |
|5.||Muzaffar M, Akhtar KA, Yasmin S, Mahmood-Ur-Rehman, Iqbal W, Khan MA. Menstrual irregularities with excessive blood loss: A clinicopathological correlation. J Pak Med Assoc 2005;55:486-9. |
|6.||Doraiswami S, Johnson T, Rao S, Rajkumar A, Vijayaraghavan J, Panicker VK. Study of Endometrial pathology in abnormal uterine bleeding. J Obstet Gynaecol India 2011;61:426-30. |
|7.||Bhosle A, Fonseca M. Evaluation and histopathological correlation of abnormal uterine bleeding in perimenopausal women. Bombay Hosp J 2010;52:69-72. |
|8.||Khan S, Hameed S, Umber A. Histopathological pattern of endometrium on diagnostic D and C in patients with abnormal uterine bleeding. Annals 2011;17:166-70. |
|9.||Sinha P, Rekha PR, Konapur PG, Thamilsevi R, Subramaniam PM. Pearls and pitfalls of endometrial curettage with that of hysterectomy in DUB. J Clin Diagn Res 2011;5:1199-202. |
|10.||Azim P, Khan MM, Sharif N, Khattak EG. Evaluation of abnormal uterine bleeding on endometrial biopsies. Isra Med J 2011;3:84-8. |
|11.||Patil SG, Bhute SB, Inamdar SA, Acharya NS, Shrivastava DS. Role of diagnostic hysteroscopy in abnormal uterine bleeding and its histopathological correlation. J Gynecol Endosc Surg 2009;1:98-104. |
|12.||Cornitescu FI, Tãnase F, Simionescu C, Iliescu D. Clinical, histopathological and therapeutic considerations in non-neoplastic abnormal uterine bleeding in menopause transition. Rom J Morphol Embryol 2011;52:759-65. |
|13.||Riaz S, Ibrar F, Dawood NS, Jabeen A. Endometrial pathology by endometrial curettage in menorrhagia in premenopausal age group. J Ayub Med Coll Abbottabad 2010;22:161-4. |
|14.||Takreem A, Danish N, Razaq S. Incidence of endometrial hyperplasia in 100 cases which presented with polymenorrhagia/menorrhagia in peri-menupausal women. J Ayub Med Coll Abbottabad 2009;21:60-3. |
|15.||Farquhar CM, Lethaby A, Sowter M, Verry J, Baranyai J. An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding. Am J Obstet Gynaecol 1999;181:525-9. |
|16.||Baral R, Pudasini S. Histopathological pattern of endometrial samples in abnormal uterine bleeding. J Path Nepal 2011;1:13-6. |
|17.||Jesadapatrakul S, Tangjitgamol S, Mausirivitaya S. Histopathologic consistency between endometrial hyperplasia diagnosis from endometrial curettage and pathologic diagnoses from hysterectomy specimens. J Med Assoc Thai 2005;88:S16-21. |
|18.||Baak JP, Mutter GL. EIN and WHO94. J Clin Pathol 2005;58:1-6. |
|19.||McCluggage WG. Benign diseases of the endometrium. In: Kurman RJ, editor. Blaustein's Pathology of the Female Genital Tract. 6 th ed. New York: Springer-Verlag; 2011. p. 305-58. |
|20.||Livingstone M, Fraser IS. Mechanisms of abnormal uterine bleeding. Hum Reprod Update 2002;8:60-7. |
|21.||Dangal G. A study of endometrium of patients with abnormal uterine bleeding at Chitwan valley. Kathmandu Univ Med J (KUMJ) 2003;1:110-2. |
|22.||Perveen S, Perveen S. Endometrium histology in abnormal uterine bleeding. MC 2011;17:68-70. |
|23.||Mutter GL. Diagnosis of premalignant endometrial disease. J Clin Pathol 2002;55:326-31. |
|24.||Saadia A, Mubarik A, Zubair A, Jamal S, Zafar A. Diagnostic accuracy of endometrial curettage in endometrial pathology. J Ayub Med Coll Abbottabad 2011;23:129-31. |
|25.||Ara S, Roohi M. Abnormal uterine bleeding: Histopathological diagnosis by conventional dilatation and curettage. Prof Med J 2011;18:587-91. |
|26.||Deligdisch L. Hormonal pathology of the endometrium. Mod Pathol 2000;13:285-94. |
|27.||Yousaf S, Shaheen M, Rana T. Frequency of endometrial carcinoma in patients with postmenopausal bleeding. Annals 2010;16:290-4. |
|28.||Ashraf-Ganjoei T, Behtash N, Shariat M, Mosavi A. Low grade endometrial stromal sarcoma of uterine corpus, a clinic-pathological and survey study in 14 cases. World J Surg Oncol 2006;4:50. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]