International Journal of Current Research and Review
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IJCRR - 7(22), November, 2015

Pages: 67-73

Date of Publication: 21-Nov-2015


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CLINICOPATHOLOGICAL STUDY OF ENDOMETRIUM IN PATIENTS WITH ABNORMAL UTERINE BLEEDING

Author: Humaira Bashir, Nazia Bhat, Mehnaz Sultan Khuroo, Ruby Reshi, Mir Junaid Nazeir, Mohammad Zubair Qureshi

Category: Healthcare

Abstract:Objectives: Abnormal Uterine Bleeding (AUB) is considered one of the most common and challenging problems presenting to the gynaecologist, regardless of the age the women .The present study was done with the aim of studying the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Methods: This was a prospective study conducted on endometrial curettings of 460 patients in the Department of Pathology, from January 2013 to August 2014. Results: The age of patients ranged from 18 to 70 yrs. The patients were categorized in reproductive age group (< 40yrs), perimenopausal >40yrs and post-menopausal group (>50yrs/clinical scenario). Maximum number of patients were in the perimenopausal group, 220 patients (47.8%), followed by 182 patients (39.6%) in the reproductive age group. Post-menopausal patients constituted 12.6 % ( 58) of total no of cases. Menorrhagia was the most common presenting symptom. Normal cyclic endometrium, 210 cases (45.65%), was the most common histopathological pattern seen in the reproductive and perimenopausal group, whereas in the postmenopausal group simple hyperplasia, 16 cases (27.6%), followed by complex hyperplasia, 8 cases (13.7%) was the commonest pattern seen. Malignancy was seen in 7 cases (1.52%)
Conclusion:
Histopathological examination of endometrial curetting specimens in patients with Abnormal uterine bleeding showed a wide spectrum of histopathological changes ranging from normal endometrium on one hand to malignancy on another hand thus rendering endometrial curetting an important diagnostic procedure in evaluation of Abnormal uterine bleeding. Accurate analysis of endometrial samplings is the key to effective therapy and optimal outcome

Keywords: Abnormal uterine bleeding, Endometrial hyperplasia, Histopathology

Full Text:

INTRODUCTION

Normal menstruation is defined as bleeding from secretory endometrium associated with ovulatory cycles, not exceeding a length of five days. Any bleeding not fulfilling these criteria is referred to as Abnormal Uterine Bleeding (AUB)1 . It is one of the frequently encountered gynaecological problem and is responsible for about one third of patients visiting gynaecological OPD (Out Patient Department)2. It can be caused by a wide variety of structural and functional causes. Common structural causes include fibroids, polyps, adenomyosis or neoplasia. The largest single group encompasses functional disturbances, referred to as Dysfunctional Uterine Bleeding (DUB). DUB is defined as any excessive bleeding (excessively heavy, pro longed or frequent) of uterine origin which is not due to demonstrable organic disease, complications of pregnancy or systemic disease3 . Histopathological examination of endometrial biopsy, taken by dilatation and curettage, remain the standard diagnostic procedure for the diagnosis of endometrial pathology4 . It should be considered in all women if AUB does not resolve with medical management and particularly in those above the age of 40 years, and in women who are at increased risk of endometrial cancer. An accurate histopathological diagnosis facilitates the implementation of optimal treatment strategies and unnecessary radical surgery may be avoided.The present study was undertaken to determine the histopathological pattern of the endometrium in women of various age groups presenting with Abnormal Uterine Bleeding

MATERIAL AND METHODS

The Present study was conducted in the Department of Pathology, Government medical College, Srinagar. This was a prospective study conducted on 460 specimens of endometrial curetting’s received from patients presenting with Abnormal Uterine Bleeding over a period of 20 months from January 2013 to August 2014. Patients were divided into three groups; Reproductive age group : 40 yrs and Postmenopausal age group : Patients who have had cessation of menstrual cycles for at least a period of twelve months with dating of postmenopausal period from the final menstrual period. Patients with bleeding due to pregnancy related complications such as abortions, gestational trophoblastic diseases or ectopic pregnancy were excluded from the study. Detailed clinical history was obtained. Specimens were fixed in 10% formalin followed by routine processing. The paraffin block sections were cut at 4-5μ and the sections were stained by routine Haematoxylin and Eosin (H&E) stains, and special stains were used when required. Data was analysed using the Statistical Package for Social Science (SPSS version 20) for windows.

RESULTS

A total of 460 cases of endometrial curetting’s presenting with Abnormal Uterine Bleeding were studied. Of these 51(11.08%) specimens were inadequate /inconclusive for opinion. The age of patients ranged from 18 to 70yrs. Maximum number of patients, 47.8 %( 220), were in the perimenopausal group followed by 39.6 %( 182) patients in the reproductive age group. Postmenopausal patients constituted 12.6% (58) of total number of cases. The most common presenting symptom was menorrhagia (56.73%) followed by polymennorrhea (17.82%). (Table 1) Functional causes accounted for majority of the diagnosis, 274 (59.56%). Of these secretory endometrium being the most common histological pattern (27.17% cases) followed by proliferative endometrium (18.69% cases). While secretory endometrium was the most common functional cause of AUB in reproductive and perimenopausal age groups respectively, atrophic endometrium predominated among postmenopausal patients. Among organic causes simple cystic hyperplasia accounted for majority of the diagnosis in all the three age groups. In the reproductive age group (table 2) secretory endometrium seen in 34.06% (62 cases) of cases, was the most common histopathological pattern observed followed by proliferative endometrium 24.72% (45 cases) and disordered proliferative endometrium 9.3% cases (17 cases). Among organic causes, most common histological finding was endometrial hyperplasia 10.98% cases (20 cases), out of which simple hyperplasia without atypia was seen in 16 cases , complex hyperplasia without atypia in 3 cases and complex hyperplasia with atypia in 1 case. One case of uterine malignancy (rhabdomyosarcoma) was also seen. In addition acute endometritis and endometrial polyp was also seen in 8 cases and 7 cases respectively In the perimenopausal patients (Table 2) functional causes predominated and most common pattern seen was secretory endometrium in 30% cases (66 cases) followed by proliferative endometrium in 16.8% cases (37 cases), disordered proliferative endometrium in 12.3% cases (27 cases) and hormonal effect in 4.1% cases (9 cases). Simple hyperplasia seen in 14.5% cases (32 cases), followed by complex hyperplasia without atypia in 4.5% cases (10 cases), endometrial polyp in 2.7% cases (6 cases), chronic endometritis in 2.27% cases (5 cases), complex hyperplasia with atypia in 0.5% cases (1 case) and malignancy in 0.9% cases (2 cases) were the organic lesions seen. Among malignant lesions, one case each of endometriod carcinoma and malignant mixed mullerian tumour was diagnosed. Among postmenopausal patients (Table 2) organic causes were more common than functional causes. Simple hyperplasia without atypia was seen in 27.6% cases (16 cases), complex hyperplasia without atypia in 10.3% cases (6 cases), complex hyperplasia with atypia in 3.4% cases (2 cases) and malignant lesions 6.9% in cases (4 cases). Malignant lesions in post-menopausal group included 2 cases of endometriod carcinoma and one case each of clear cell adenocarcinoma and endometrial stromal sarcoma. Endometrial polyps in 3.4 % cases (2 cases), acute endometritis in 3.4% cases (2 cases) and granulomatous endometritis in 1.7 % cases (1case) were other organic lesions diagnosed. Among functional causes most common was atrophic endometrium seen in 12.06 % cases (7 cases), followed by proliferative endometrium in 6.8% cases (4 cases), disordered proliferative endometrium in 3.4% cases (2 cases) and secretory endometrium in 3.4 % cases (2 cases).

DISCUSSION

AUB is a common gynaecological complaint accounting for one third of patients visiting outpatient clinics5 . It is caused by a wide variety of disorders represented by an aberrant physiologic status at one hand to uterine malignancy at the other. The present study was done to evaluate the histopathology of endometrium in abnormal uterine bleeding. In our study organic causes of AUB were seen in 29.34 %( 135) and functional causes in 59.56 %( 274) patients. Similar observations were made in the study done by Vaidya S et al 6 . Most patients in our study were in the perimenopausal age group (47.8%). This could be due to the fact that as menopause approaches, decreased number of ovarian follicles and their increased resistance to gonadotrophic stimulation, results in a low level of estrogen, which cannot keep the normal endometrium growing7 . Lesser number of patients were seen in the higher ages which may be due to earlier evaluation, detection as well as management of the disease. Menorrhagia was the most common presenting feature (56.73%) followed by polymennorrhea (17.82%).These findings were compatible with the study done by Muzaffar M et al 8 . The two most common histopathological pattern were normal cyclic pattern (secretory and proliferative endometrium) in the perimenopausal and reproductive age group and atrophic endometrium in the post-menopausal age group. The abnormal bleeding in the proliferative phase could be due to anovulatory cycles and in the secretory phase due to ovulatory dysfunctional uterine bleeding. Similar results were reported by Doraiswami et al 9 . Disordered proliferative serves as a bridge between normal proliferation and hyperplasia. It denotes an endometrial appearance that is hyperplastic but without an increase in endometrial volume. An essentially normal proliferative phase endometrium with a few widely scattered cystic glands would better be called “disordered proliferative” than simple hyperplasia10. Disordered proliferative endometrium was seen in 12.17% of patients in our study. Study of Vaidya et al6 showed 13.4% cases. In our study disordered proliferative endometrium was more common in perimenopausal group similar to study of Doraiswami et al9 . Endometrial hyperplasia is a precursor of endometrial cancer. The incidence of endometrial hyperplasia without and with atypia peaks in the early fifties and early sixties respectively with symptoms of irregular or prolonged bleeding due to anovulatory cycles in majority of cases, secondary to sustained level of oestrogens11. The overgrowth not only affects glands and stroma but there is also abnormal vascularisation. In our study endometrial hyperplasia was found in 18.9% of cases, which is concordant to observations made by Sheetal G P12 (20%) but higher than that observed by Doraiswami et al9 (6.11%) and Abid et al13 (5%). Most common type of hyperplasia encountered was simple hyperplasia without atypia (Fig 1) in 13.91% cases. Hyperplasia was found to be the most common cause of AUB in post-menopausal women and most common organic cause of AUB in reproductive and peri- menopausal women. However, its frequency peaked in perimenopausal age group accounting for about 50% cases. Similar observations were made by Vaidiya et al6 and Muzaffar M et al 8 . Endometrial cancer is the most common malignancy of the female genital tract with 80% patients being post menopausal14. In our study malignancy was observed in 1.52% cases (7cases). Of these there were 5 cases of endometrial carcinomas with 3 cases diagnosed as type1 (Fig 2) and 2 cases as type 2 endometrial carcinoma. Other tumours included one case each of endometrial stromal sarcoma and rhabdomyosarcoma. Most of the patients belonged to post-menopausal age group. Similar observations are seen in literature from sub contienent6, 12, 13, 15 as compared to the west16,17 where higher incidence is reported. This may be attributed to early child bearing and multiparity practised by women in our subcontinent. Polyps such as endometrial polyps and submucosal leiomyomatous polyps are common source of AUB in all age groups18. In our study 15 polyps (3.26%) were seen of which 12(2.62%) were reported as endometrial polyps and 3(0.65%) as submucosal leiomyomatous polyps. Data from other studies shows variable trends ranging from 1.2% to 14.10%8, 9, 12, 13. None of the polyps in our study showed atypical changes. Atrophic endometrium was seen predominantly in postmenopausal group accounting for 12.6% cause of AUB in this group. This is compatible to the observation made by Doraiswami et al9 (9.5%) but lower than the results observed by Abid et al13 and Gredmark et al19. Anovulatory cycles followed by ovarian failure leads to atrophic changes in the endometrium at menopause.14 Chronic endometritis was observed in 2.6% of endometrial curetting’s of which 2 were granulomatous endometritis (due to tuberculosis) positive for AFB (Fig 3). Study by Vaidya et al6 showed chronic endometritis in 3.23% cases. The diagnosis of chronic endometritis is made on the basis of presence the basis of presence of plasma cells. Chronic endometritis is often a result of intra uterine contraceptive devices (IUCD), pregnancy and incomplete abortions. Hormonal effect (exogenous administration) was noted in 2.17% cases (10cases) out of which 9 cases were seen in perimenopausal group. Muzzafar et al8 have reported 2.3% cases as pill effect similar to our observation however majority of their cases were in the 31-40 year age group were as in our study cases were in the 41-50 year age group Specimens inadequate for reporting were 51, accounting for 11.8% of the total cases. . In our study specimens were labelled unsatisfactory for reporting when there were scant glands and stroma, fragmented tissues and haemorrhage. A study by Harmanli et al20 revealed that an inadequate endometrial sample has a high negative predictive value of ruling out endometrial neoplasm. Similar views were expressed by Bakour et al21 in their study wherein they observed scant tissue in atrophic endometrium with no focal lesion on ultrasound scan has little chance of missing relevant pathology.

CONCLUSION

Histopathological examination of endometrial curetting’s in patients with AUB showed a wide spectrum of pathological changes ranging from normal endometrium on one hand to malignancy on other hand thus rendering endometrial curetting an important diagnostic procedure in evaluation of AUB. In the present study since most of the preneoplastic lesions were seen in the perimenopausal group and neoplastic in postmenopausal age group, therefore it is especially recommended in women above 40 years of age presenting with AUB, to rule out preneoplastic lesions and malignancy. Accurate analysis of endometrial samplings is the key to effective therapy and optimal outcome.

ACKNOWLEDGEMENTS

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

References:

1. Rosai J: Female reproductive system-uterus-corpus. In:Rosai and Ackerman’s Surgical Pathology. 10th Edn.;Mosby: An Imprint of Elsevier, Missouri, 2011;pp.1579- 1615.

2. Wren BG. Dysfunctional Uterine Bleeding. Aus Fam Physician 1998; 27: 371-7.

3. ACOG Practice Bulletin: Clinical Management of Anovulatory Bleeding. Int J Gynaecol Obstet 2001; 72: 263-71

4. Takreem A, Danish N, Razaq S. Incidence of endometrial hyperplasia in 100 cases presenting with polymenorrhagia/menorrhagia in perimenupausal women. J Ayub Med Coll Abbottabad. 2009 Apr-Jun;21:60-3.

5. Ely JW, Kennedy CM, Clark EC, Bowdler NC. Abnormal Uterine Bleeding: A Management Algorithm. J Amer Board Fam Med 2006; 19: 590-602.

6. Vaidya S, Lakhey M, Vaidya S, Sharma PK, Hirachand S, Lama S, KC S. Histopathological pattern of abnormal uterine bleeding in endometrial biopsies. Nepal Med Coll J. 2013 Mar;15:74-7.

7. Davey DA. Dysfunctional Uterine Bleeding. In: Whitfield CR, ed. Dewhurst’s Textbook of Obstetrics and Gynaecologyfor Postgraduates. Glasgow: Blackwell Science; 1997:590-608

8. Muzzafar M, Akhtar KAK and Yasmin S et al. Menstrual Irregularities with excessive blood loss: a clinico-pathological correlation. J Pak Med Assoc 2005;55:486-489

9. 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 Aug;61:426-30.

10. Silverberg SG. Problems in the differential diagnosis of endometrial hyperplasia and carcinoma. Mod Pathol. 2000;13:309– 27

11. Ellenson LH, Ronnett BM, Kurman RJ. Precursor Lesions of Endometrial Carcinoma. In:Kurman RJ, Ellenson LH, Ronnett BM, eds. Blaustein’s Pathology of the Female GenitalTract. 6th Ed. New York: Springer Verlag, 2011: 385-92.

12. Patil SG1 , Bhute SB, Inamdar SA, Acharya NS, Shrivastava DS. Role of diagnostic hysteroscopy in abnormal uterine bleeding and its histopathologic correlation. J Gynecol Endosc Surg. 2009 Jul;1:98-104.

13. Abid M, Hashmi AA, Malik B, Haroon S, Faridi N, Edhi MM, Khan M. Clinical pattern and spectrum of endometrial pathologies in patients with abnormal uterine bleeding in Pakistan: need to adopt a more conservative approach to treatment. BMC Womens Health. 2014 Nov 5;14:132.

14. Ellenson LH, Edyta C and Pirog. The female genital tract. Robbins and Cotran Pathologic Basis of Disease. 8th edition., Elsevier, A division of Reed Elsevier India Pvt. Ltd.,2010. Chapter 22: p. 1005-1063

15. Soleymani E, Ziari K, Rahmani O, Dadpay M, Taheri-Dolatabadi M, Alizadeh K, Ghanbarzadeh N. Histopathological findings of endometrial specimens in abnormal uterine bleeding. Arch Gynecol Obstet. 2014 Apr;289:845-9.

16. Purdie DM1 , Green AC. Epidemiology of endometrial cancer. Best Pract Res Clin Obstet Gynaecol. 2001 Jun;15:341-54.

17. Canavan TP, Doshi NR. Endometrial cancer. Am Fam Physician 1999Jun;59:3069-77

18. Davis PC1 , O’Neill MJ, Yoder IC, Lee SI, Mueller PR. Sonohysterographic findings of endometrial and subendometrial conditions. Radiographics. 2002 Jul-Aug;22:803-16.

19. Gredmark T, Kvint S, Havel G, Mattsson LA. Histopathological Findings in women with postmenopausal Bleeding. Br J Obstet Gynaecol. 1995 Feb;102:133-6.

20. Harmanli OH, Shunmugham S, Shin T, Houck KL, Chatwani A. The negative predictivevalue of inadequate endometrial biopsy in diagnosing endometrial neoplasia. J Gynecol surg 2004 ;20:13-6

21. Bakour SH1 , Khan KS, Gupta JK. Controlled analysis of factors associated with insufficient sample on outpatient endometrial biopsy. BJOG. 2000 Oct;107:1312-4.

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A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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