Evaluation of Hysteroscopic Findings and Histopathologic Report of Endometrium in Postmenopausal Bleeding

Background: Women with postmenopausal bleeding have 10%-15% chance of having endometrial carcinoma and therefore the diagnostic work is aimed at excluding uterine malignancy. For accurate diagnosis of cause of postmenopausal bleeding, endometrial abnormalities can be assessed by hysteroscopy and hysteroscopy directed biopsy or fractional curettage. Objective: To compare the hysteroscopic findings with histopathologic report of endometrium in postmenopausal bleeding. Methods: Cross sectional study was conducted in the department of gynaecological oncology in Bangabandhu Sheikh Mujib Medical University over 1 year from June 2019 to May 2020. Thirty women with the complaints of postmenopausal bleeding were enrolled. Each women underwent hysteroscopic evaluation and endometrial tissue was obtained by hysteroscopy directed biopsy as well as fractional curettage in some cases, then sent for histopathology. Results were analyzed to find out sensitivity, specificity, accuracy, positive predictive value and negative predictive value of hysteroscopy, taking histopathological diagnosis as gold standard. Analysis was carried out by using SPSS version 26. Results: Hysteroscopic examination findings and histopathology of endometrium in 30 postmenopausal women, 11(36.6%) cases were found normal both on hysteroscopy and histopathology, among them 4(13.3%) cases were proliferative endometrium, 1(3.3%) was secretory endometrium and 5(16.6%) cases were found atrophic endometrium and 1(3.3%) tissue was insufficient. Hysteroscopic view of normal endometrium showed a sensitivity 100%, specificity 100%, positive predictive value 100%, negative predictive value 100% and accuracy 100%. For Endometrial polyp showed sensitivity , specificity , positive predictive value , negative predictive value and accuracy 100%respectively .For Hyperplasia, hysteroscopy showed sensitivity 100%, specificity 96.2%, positive predictive value 80%, negative predictive value 100% and accuracy 96.7%. Endometrial carcinoma was found in 3(10%) cases and showed sensitivity of 100%, specificity of 96.3%, positive predictive value 75.0%, negative predictive value 100% and accuracy 96.7%. For the atrophic endometrium, sensitivity (100%), specificity (96.0%), positive predictive value (83.3%), negative predictive value (100%) and accuracy (96.7%). 1(3.3%) had in situ endometrial carcinoma and 2(6.6%) had adenomyosis on histopathology. Conclusion: The study concludes that hysteroscopy and directed biopsy or fractional curettage is a highly accurate, sensitive, specific, positive predictive value and negative predictive value for diagnosis of cause of postmenopausal bleeding.


Introduction
Postmenopausal bleeding can be defined as bleeding per vagina that occurs from the genital tract in any amount, duration and frequency occurring at least one year after menopause. 1 A woman is considered menopausal, after cessation of menstruation for 1 year. The average age of menopause in Asian women is 46 years, range 45 to 58 years. 2 Any uterine bleeding irrespective of amount and duration during menopause should be considered alarming symptom and needs meticulous evaluation. It may be the sole manifestation of the underlying endometrial cancer at a stage when it can be cured completely with appropriate treatment. In 90% of carcinoma of the endometrium PMB occurs, but only 10%-15% of women with PMB will have endometrial cancer. 3 Causes of postmenopausal bleeding included-1) Atrophic endometritis, (30%), 2) Atrophic vaginitis 3) Exogenous estrogen (30%), 4) Endometrial cancer (15%), 5) Endometrial hyperplasia (5%), 6) Endometrial polyp (10%), 7) Miscellaneous cause (cervical cancer, uterine sarcoma, urethral caruncle, trauma) (10%). 4 Steps for evaluation of Postmenopausal bleeding is shown in a flow chart For evaluation of postmenopausal bleeding following steps can be follows: Step 1: History and examination For each women with PMB evaluation should be done by careful detailed history, clinical examination including general, abdominal, speculum, per vaginal and rectovaginal examination together with doing some noninvasive and invasive investigations. Step 2: Sonography:

Guideline for post-menopausal bleeding assessment 5
Following history and clinical examination, then we do Trans Vaginal Sonogram (TVS) to see endometrial thickness, to segregate of the patients for further procedure.
Step 3: Endometrial biopsy: After the segregation of the patients, endometrial biopsy will be taken by following methods: a. Fractional curettage b. Endometrial sampling c. Hysteroscopy: For evaluation of endometrium in postmenopausal bleeding hysteroscopic direct view and guided biopsy is considered as the gold standard diagnostic procedure. 1,2,3 Hysteroscopy is a procedure that allows to look inside the uterus in order to diagnosis and treatment of postmenopausal bleeding.
Hysteroscopy is done by using a thin, lighted tube with 2.9mm or 4mm 30 degree rigid telescope. 1,6 As a diagnostic procedure it is safe, less time consuming and a low incidence of complication. 6 It is also less invasive than fractional curettage.
By the use of hysteroscope we can get the panoramic view of whole endometrial cavity. Hysteroscopic findings are classified as normal if endometrium is proliferative, secretory, atrophic and hypotrophic and as abnormal when endometrial polyp, submucous fibroid, endometritis, endometrial hyperplasia or endometrial cancer is present. 3,7 The hysteroscopic criteria for suspecting endometrial hyperplasia are a focal or diffuse increase in endometrial thickness, irregular aspect of the endometrial surface, corrugated endometrial hypertrophy without vascularization, a decrease in intraglandular space, cystic formation protruding in to the uterine cavity, and increase in dilated superficial vessels on panoramic view. 3,7 Hysteroscopic criteria for endometrial cancer are: atypical vessels, irregular and shiny necrotic tissues, somewhat tissues are softened, friable consistency, irregular vascularization, necrotic area and also bleeding may be present. 3,7 Advantage: Hysteroscopy has following advantages. 6 Lee et al 9 concluded that biopsy by fractional curettage may not be reliable for the evaluation of endometrial pathology. The authors suggest that hysteroscopically guided endometrial biopsy can be considered as the gold standard for evaluation of endometrium in postmenopausal bleeding.
Since hysteroscopy alone is not sufficient to exclude endometrial neoplasia, 3 even when the endometrium appear normal on hysteroscopy, endometrium should be sampled for histopathologic evaluation. 3 So, the combination of hysteroscopy with hysteroscopy directed biopsy potentially serves a diagnostic and therapeutic purpose. 9,10,11 Several studies had been done for evaluation of endometrium in postmenopausal bleeding and most of the studies showed high sensitivity, specificity, positive predictive value, negative predictive value of hysteroscopy for diagnosis of endometrial pathology.
A study by Tandulwadkar  purpose of the study is to evaluate the endometrium in postmenopausal bleeding by comparing the hysteroscopic gross findings with histopathological report of hysteroscopy directed biopsy and or with fractional curettage as histopathology report is considered as gold standard.

Objectives
General objective: To correlate hysteroscopic findings with histopathological diagnosis in postmenopausal bleeding.
Specific objectives: • To determine the hysteroscopic findings of endometrium in postmenopausal bleeding.
• To evaluate the histopathological report of endometrial tissues obtained by hysteroscopy directed biopsy and or fractional curettage.
• To correlate the hysteroscopic findings with histopathological diagnosis in determination of accuracy.
Review of Literature: Postmenopausal bleeding: As the 90% of the carcinoma of the endometrium occurs with PMB. 10-15% of the women with PMB will have endometrial carcinoma.
Postmenopausal bleeding not only cause of endometrial carcinoma, but also due to some benign lesions like atrophic vaginitis, atrophic endometritis, endometrial hyperplasia, endometrial polyp. Endometrial hyperplasia: In broad terms, endometrial hyperplasia relates to excessive cellular proliferation leading to an increased volume endometrial tissue, where an increased endometrial gland and strauma at a ratio of >1:1.
Type of hyperplasia: • Simple hyperplasia (Cystic grandular hyperplasia)here glands show hypertrophy rather than hyperplasia.
• Atipical hyperplasia: Both simple and complex hyperplasia can be associated with cytologic atypia. Risk of hyperplasia progessing to carcinoma is related to the presence and severity of cytologic atypia. 8 Endometrial Polyp: It is found either in single or multiple. Single endometrial polyp is common, specially in the postmenopausal women. Mostly they are symptom less, they often found surprisingly on openingly excised organ.
Symptoms are more likely when the tip of the polyp becomes necrotic and ulcerative. TVS reveals a thickened endometrial shadow but certain diagnosis made by hysteroscopy. 8 Atrophic endometritis: Usually non-cancerous condition occurs due to lack of estrogen in postmenopausal women.
More than 30% PMB occurs due to atrophic endometritis. 4 Trans Vaginal Sonogram (TVS): All patients with postmenopausal bleeding will be subjected to a TVS it will be measured as the maximum distance between two myometrial interfaces on longitudinal scan. Endometrial Carcinoma typically present as the thickening of the endometrial.1 Cut off value of endometrial thickness in postmenopausal women 5mm or less . 3,17 Fractional curettage: Fractional curettage: It is a diagnostic procedure by which thorough curettage done to obtain specimen from endocervix and endometrium separately.
Fractional curettage began with the introduction of the dilatation of cervix and curettage of endometrium in the 19 th century and since than it has been considered as a gold standard diagnostic procedure for postmenopausal bleeding and abnormal uterine bleeding as well as therapeutic for removing endometrial polyp that causes abnormal bleeding and also exclude malignancy. 12 There is some drawback in fractional curettage, it is blind procedure, more invasive and sometime missing of diagnosis of intrauterine focal lesion and polyp. 1,10 It has low sensitivity and specificity than hysteroscopy. 1 Complication of fractional curettage: injury to the cervix, uterine perforation, injury to the gut and infection.
Hysteroscopy: The development of hysteroscopy is rooted in the work of Pantaleoni, who first reported uterine endoscopy in 1869. He evaluated a 60 years old lady with therapy resistant bleeding and detected a polypoid growth in the uterus on hysteroscopy.
Hysteroscopy is a minimally invasive procedure involving the direct inspection of the cervical canal and endometrial cavity through a rigid, flexible or a contact hysteroscope. 8,13 Hysteroscopic system comprises of a rigid telescope of different diameters ( Hysteroscopy: Hysteroscopy is a minimally invasive procedure, involving the direct inspection of the cervical canal and endometrial cavity through a rigid, flexible, or a contact hysteroscope. Hysteroscopic system comprises of a rigid telescope of different diameters (2-4 mm) and a variety of viewing capabilities are available (0º,12º,30º,70º) and there is an outer sheath for instillation of the distention media. 8 Fractional curettage: It is a diagnostic procedure by which thorough curettage done to obtain specimens from endocervix and from endometrium separately. For evaluation of endometrium in PMB, it is also considered as a gold standard diagnostic procedure but it is more invasive with low sensitivity and specificity. 1 • 30 women were taken in this study.
• Women were selected from outpatient department of gynecological oncology.
· Women were informed about the purpose of the study, diagnostic procedure and ethical issue. Details of the study was explained to each women and informed oral and written consent from the responded was obtained.
• Following selection, of women with postmenopausal bleeding were evaluated carefully by proper history including age, obstetrical history and duration since menopause, duration, amount and pattern of postmenopausal bleeding, history of gynecological operation.
• Thorough general and systemic examination was done including pelvic and rectal examination to exclude causes of postmenopausal bleeding like vulvar, vaginal, cervical, anal and urethral lesion.
• Women were informed that hysteroscopy and fractional curettage both are invasive procedure and general anaesthesia will be required.
• Transvaginal sonography will be done in all women with to see the endometrial thickness and exclude adnexal pathology.
• Then diagnostic procedure was done by introducing hysteroscopy by senior oncologists.
• First endocervical tissues were taken then cervix gently dilated prior to introducing the hysteroscope.
• Following introducing of hysteroscopy, directed biopsy was taken from suspicious area of endometrium or if there were any abnormalities found.
• If any polyp or submucous fibroid were found removed at the same time.
• Fractional curettage was done when hysteroscopy showed normal or atrophic endometrium.
• All the specimens immediately placed in 10% formaldehyde separately and sent to the pathology laboratory for histopathological examination.
• For each and every subject separate data collection sheet was used.
• Data were collected from the women on variable of interest using the structured designed by interviewing, observing and thorough clinical examination as well as recorded from hysteroscopic findings and histopathological diagnosis report. Ethical consideration: Prior to commencement of this study the research protocol was approved by the Institutional Review Board (IRB) of BSMMU, Dhaka. The aim and objectives of the study along with its procedure, risk and benefits of this study was explained to the women in easily understandable local language and then informed consent was taken from each women both orally and written forms. Those who refused to take part in the study were excluded.
The following ethical issues were addressed accordingly: 1. Strict confidentiality and security of data related to patient was maintained. The presentation of data and information related to patient was documented anonymously.
2. There is no additional risk or safety concerned due to research process to either patient or researcher.
3. There is no potential conflict of interest in this study and an entirely an academic research process.
Procedure of maintaining confidentiality: 1. For safeguarding confidentiality and protecting anonymity each of the patients were given a special ID no. which was followed during examination and each and every step of the procedure.

2.
A signed informed consent was taken from the women convincing that privacy of the women were maintained.
3. A data collection was enclosed for which a short interview was required.

Utilization of the study result:
This study is designed to know the actual cause of PMB and accurate diagnosis by hysteroscopy and histopathology in PMB. This study may help the clinician to take the essential steps to evaluate the endometrium for the diagnosis of cause of postmenopausal bleeding.

Results
This cross sectional observational study was conducted in the Department of gynecological oncology in BSMMU. A total 30 participants were selected following selection criteria.      Regarding educational status of women in present study, most of the women passed primary education 12(40.0%).
In present study most of women came from middle class 23(76.7%) followed by lower middle class 6(20%) only one came from upper class.

Conclusion
The study revealed that hysteroscopy and directed biopsy or fractional curettage in some cases is a highly accurate, sensitive, specific, positive predictive value and negative predictive value for diagnosis of cause of postmenopausal bleeding.
Finally concludes that hysteroscopic findings almost correlates with histopathological diagnosis of cause of postmenopausal bleeding in present study.