{"paper_id":"b984cdcf-7d0e-4ba0-b9a2-23eef287b4be","body_text":"~ 174 ~ \nInternational Journal of Clinical and Diagnostic Pathology 2019; 2(1): 174-181 \n \nISSN (P): 2617-7226 \nISSN (E): 2617-7234 \nwww.patholjournal.com \n2019; 2(1): 174-181 \nReceived: 17-01-2019 \nAccepted: 20-02-2019 \n \nDr. Srinivas DD Gubbala \nAssociate Professor, \nDepartment of Pathology, \nKamineni Institute of Medical \nSciences, Narketpalli, \nTelangana, India \n \nDr. Sridevi Mattaparti \nAssistant Professor, \nDepartment of Pathology, \nKamineni Institute of Medical \nSciences, Narketpalli, \nTelangana, India \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nCorrespondence \nDr. Srinivas DD Gubbala \nAssociate Professor, \nDepartment of Pathology, \nKamineni Institute of Medical \nSciences, Narketpalli, \nTelangana, India \n \nClinico-pathological evaluation and etiological \nstratification of chronic AUB patients based on \nPALM-COEIN classification: A prospective study in \ntertiary care center of Nalgonda District \n \nDr. Srinivas DD Gubbala and Dr. Sridevi Mattaparti \n \nDOI: https://doi.org/10.33545/pathol.2019.v2.i1c.26 \n \nAbstract \nContext: Abnormal uterine bleeding (AUB) is a common crippling gynaecological co ndition with vast \nfinancial implications. A structured approach for establishing the cause using the FIGO defined PALM-\nCOEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulo pathy, Ovulatory \ndisorders, Endometrial, Iatrogenic and Not otherwise classified) classification system  will facilitate \naccurate diagnosis and inform treatment options.  \nAims and objectives:  1. Clinico-pathological evaluation of patients presenting with chronic AUB. 2.  \nEtiological stratification of patients with chronic AUB in accordance to PA LM-COEIN Classification. \n3. To determine frequency of various uter ine histopathological findings and their associated etiologies \nin the population of Nalgonda district. \nSettings and Design:  The present study was a cross -sectional prospective study conducted at the \nDepartment of pathology and Department of Obstetrics and Gynecology, Kamineni Institute of Medical \nSciences, Narketpalli over a period of 2 years starting from June 2016 to June 2018.  \nMethods and Material:  The study population included 188 cases of Chronic AUB.  Specimens \nanalysed were:  1. endometrial biopsy obt ained by dilatation and curettage. 2. Hysteroscopy guided \nbiopsy 3. Hysterectomy specimens. Histopathological evaluation of specimens was done and reported \nin accordance with PALM-COEIN classification.  \nResults: The commonest Age group involved was perimenopausal group (41- 50) constituting (39.4%). \nMultiparous women most commonly presented with AUB accounting fo r 44.1% of all cases. \nMenorrhagia is the most common clinical presentation in reproductive age group (50.6%) and \nperimenopausal women (39.2%). Post-menopausal bleeding (36.0%) is commonest presentation in \nPost- menopausal age-group of AUB patients. Proliferative endometriu m is the most common \nhistological finding in reproductive age group (44.9%) and perimen opausal women (33.8%). \nLeiomyomas are the most common presentation is Post-menopausal wom en (32%). 4 Patients in the \nPost-menopausal Age group presented with Endometrioid Adenocarcino ma. According to PALM-\nCOEIN classification AUB-E is the most common etiologic factor across all age groups. Non-structural \ncauses account for 54.8% of AUB cases and among 45.2% of structural causes, Simple cystic \nhyperplasia is the most common histological finding. \nConclusions: AUB is a common and debilitating condition with high direct and ind irect costs. \nHistopathological evaluation is the gold standard tool in the evalua tion of the patients with Chronic \nAUB. A structured approach to establishing the cause using the FIGO PALM-COEIN c lassification \nsystem will facilitate accurate diagnosis and inform treatment options. \n \nKeywords: Abnormal uterine bleeding (AUB), fibroids, FIGO PALM-COEIN classification of AUB \n \n1. Introduction  \nAbnormal uterine bleeding (AUB) is a common gynaecological clinical entity having a \nsignificant impact on the physical, social, emotional and materi al quality of women’s life [1]. \nAUB is defined as any type of bleeding in which the duration, frequ ency, or amount is \nexcessive for an individual patient [2]. AUB is regarded as a sign of uterine disease or \nhormonal imbalance resulting pathology of hypothalamus-pituitary -ovarian axis [3]. \nAccording to the data published by National Health Portal the prevalence of AUB v aries in \neach country fluctuating between 9-14% and in India the reported prev alence of AUB is \naround 17.9% [4]. AUB affects around 10-30% of Reproductive-aged female and up to 50% \nof perimenopausal women [5] Though there is relief from heavy menstrual bleeding during \npregnancy and lactation, and an end to the problem at menopause, affected women suffer the  \n\n\n~ 175 ~ \n \nadverse impacts of AUB over the prime years of their lives \nincurring significant financial burden, necessitating \nadequate prompt management.  \nThe management of AUB has been hindered for quite a long \ntime owing to the confusion and inconsistency in \nnomenclature, lack of research and inadequate classification \nmethods of various etiological criteria.  In 2009 FIGO \nintroduced a new nomenclature for AUB and defined \nPALM-COEIN classification (Table 1) for categorizing the \ncauses of AUB in 2011 to facilitate ease of investigation, \ncomparison of similar patient populations and improve \nevidence-based care [6]. Chronic AUB was defined as \n‘bleeding from the uterine corpus that is abnormal in \nvolume, regularity and/or timing that has been present for \nthe majority of the last 6 months’ [7]. \nIn the past many women with chronic AUB underwent \nunwarranted hysterectomy without a definite diagnosis. In \nview of increased availability of Medical options, proper \netiological stratification in accordance to PALM-COEIN \nclassification decreases the necessity of potentially \ncomplicated surgery. \n \nThe diagnosis of AUB depends on the comprehensive \nassessment of the medical history, combined with blood \ntests, ultrasound, hysteroscopic examination and \nhistopathological analysis of specimens. Histopathological \nanalysis plays a significant role in identification of structural \ncauses of AUB and Non-Structural endometrial causes \n(AUB-E) and an adequate endometrial biopsy is of \nparamount importance in the evaluation of these patients. \nWith this background we initiated a prospective study to \ndescribe the prevalence of the various causes of chronic \nAUB in women of Nalgonda District and establish \ncorrelation with histopathological findings using the PALM-\nCOIEN classification system.  \n \n2. AIMS and Objectives \n1. Clinico-pathological evaluation of patients presenting \nwith chronic AUB. \n2. Etiological stratification of p atients with chronic AUB \nin accordance to PALM-COEIN Classification.  \n3. To determine frequency of various uterine \nhistopathological findings and their associated \netiologies in the population of Nalgonda district. \n \n3. Material and Methods \nThe present study was a cross-sectional prospective study \nconducted at the Department of pathology and Department \nof Obstetrics and Gynecology, Kamineni Institute of \nMedical Sciences, Narketpalli over a \nperiod of 2 years \nstarting from June 2016 to June 2018.  Prior informed \nconsent was taken from all the patients and the study was \napproved by Institutional review board of kamineni Institute \nof medical sciences, Narketpalli. The study population \nincluded 188 cases of Chronic AUB. The causes of AUB in \naccordance with PALM -COEIN classification which can be \ncorrelated and determined by histopathological examination \nwere included in the study and cases with other causes were \nexcluded from the study.  \n \n3.1 Definitions used in the study  \nAcute AUB is defined as an episode of bleeding that is of \nsufficient quantity requiring immediate intervention to \nprevent further blood loss in a woman of reproductive age \nwho is not pregnant.  \nChronic AUB is defined as bleeding from the uterine corpus \nwhich is abnormal in duration, volume, and/or frequency \nand has been present for the majority of the last 6 months [8, 9] \n \n3.2 Inclusion Criteria \n1. Women aged 15 to 75 years \n2. Women with Chronic AUB. Definition of Chronic AUB \nin our study is based on medical terms defined by \nFIGO, as shown in Table 2.  Values out with the \naccepted 5-95 th percentile indicated abnormal uterine \nbleeding.  \n3. Signed informed consent to participate in this study. \n \n3.3 Exclusion Criteria \n1. Acute AUB \n2. Vaginal bleeding caused by pregnancy and pregnancy-\nrelated factors (Abortion, Ectopic pregnancy, \nGestational trophoblastic diseases.) \n3. Vaginal bleeding caused by cervical diseases. \n4. Bleeding Diathesis. \n5. Iatrogenic causes of AUB: Exogenous therapy leading \nto unscheduled endometrial bleeding (continuous \noestrogen or progestin therapy (systemic or intrauterine \ndelivery routes, gonadotropin-releasing hormone \n(GnRH) agonists, and Intrauterine device (IUD)) \n \nAll women who consulted Gynaecological OPD with AUB \nwere initially evaluated, Standard Menstrual index was \nprepared for all the patients which included 4 elements of \nmenstrual bleeding: the frequency and regularity of the \nmenstruation and menstrual cycle, the length of the period, \nduration of flow (days), and volume of monthly blood loss \n(millilitres) and patients with Chronic AUB are identified \n(Refer to Table 2). A structured screening for \ncoagulopathies were done (Table 3) and history of drug \nintake was elicited.\n \n \n\n\nInternational Journal of Clinical and Diagnostic Pathology \n \n~ 176 ~ \n \n \n  \nTable 2: Suggested Normal limits for Menstrual Parameters. (Adapted from Fraser et al.) [6]. \n \nClinical Parameter Descriptive term Normal limits(5–95th percentiles) \nFrequency of menses (days) Frequent <24 \n Normal 24–38 \n Infrequent >38 \nRegularity of menses, cycle to cycle Absent No bleeding \n(Variation in days over 12 months) Regular Variation ± 2–20 days \n Irregular Variation >20 days \nDuration of flow (days) Prolonged >8.0 \n Normal 4.5–8.0 \n Shortened <4.5 \nVolume of monthly blood loss (mL) Heavy >80 \n Normal 5–80 \n Light <5 \nPatient information, such as age, height, weight, menarche ag e, medical and surgical history, and the results of relevant \nimaging examination and hysteroscopic examination, were obtained. Oth er lab investigations done were: CBP, ESR, \ncoagulation studies (Bleeding time (BT), Clotting time (CT), Prothrombin Time (PT), Activated Partial Thromboplastin Time \n(APTT), liver function, renal function, sex hormone analysis. \n \nTable 3: Structured history for coagulopathy screen. (Adapted \nfrom Koudies et al.) [29]. \n \nCriteria for Evaluation of Coagulopathy \n1. Heavy bleeding since the menarche \n2. One of the following: \n Postpartum haemorrhage \n Surgical-related bleeding \n Bleeding associated with dental work \n3. Two or more of the following: \n Bruising 1–2 times/month \n Epistaxis 1–2 times per/month \n Frequent gum bleeding \n Family history of bleeding problems \n \n3.4 Specimen Analysed: From patients with CHRONIC \nAUB were: 1. Endometrial biopsy obtained by dilatation and \ncurettage. 2. Hysteroscopy guided biopsy-Endometrium and \nPolyps 3. Hysterectomy specimens of radiologically \ndiagnosed fibroids and Adenomyosis. All specimens were \nprocessed in Yorco Automated tissue processor. Paraffin \nblocks were prepared and tissue sections of 3-5 microns \nwere cut and were stained with haematoxylin and eosin \nstains (H&E) and examined by pathologist. Histo-\nmorphological findings were reported and later stratified in \naccordance with PALM-COEIN classification and the data \nwas expressed as percentage.  \n \n4. Observations/Results \n4.1 Histopathological findings in Chronic AUB \n \n \n\nInternational Journal of Clinical and Diagnostic Pathology \n \n~ 177 ~ \n \n \n4.2 Graphical representation of the data \n \n \n \n \n \n \n \n \n \n\nInternational Journal of Clinical and Diagnostic Pathology \n \n~ 178 ~ \n4.3 Statistics \n \nTable 4: Age wise distribution of AUB patients \n \nCategory Age group No. of Cases Percentage \nReproductive Age Group < 20 6 3.2% \n 21-30 20 10.6% \n 31-40 63 33.5% \nPerimenopausal 41-50 74 39.4% \nPost-menopausal 51-60 14 7.4% \n > 60 11 5.9% \nTotal Range 18-72 Yrs. 188 100% \n \nTable 5: Distribution of AUB Patients based on Parity \n \nParity No. of Cases Percentage \nNulliparity 12 6.4% \nLow Parity 69 36.7% \nMulti-Parity 83 44.1% \nGrand Multiparity 21 12.8% \nTotal 188 100% \n \nTable 6: Age wise Distribution of clinical presentation in AUB Patients. \n \nClinical Reproductive Perimenopausal Post-Menopausal Total \npresentation Age (< 40 Yrs.) Age (41-50 Yrs.) Age (> 50 Yrs.)  Menorrhagia 45 (50.6%) 29 (39.2%) 05 (20.0%) 79 (42.0%) \nPoly-menorrhoea 21 (23.6%) 12 (16.2%) 06 (24.0%) 39 (20.7%) \nMenometrorrhagia 08 (9.0%) 16 (21.6%) 05 (20.0%) 29 (15.4%) \nOligomenorrhoea 07 (7.8%) 17 (23.0%) 0 24 (12.8%) \nPost-Menopausal Bleeding 0 0 09 (36.0%) 09 (4.8%) \nMetrorrhagia 08 (9%) 0 0 08 (4.3%) \nTOTAL 89 (100%) 74 (100%) 25 (100%) 188 (100%) \n \nTable 7: Age wise Distribution of Histopathological findings in AUB Patients \n \nHistomorphology Reproductive Perimenopausal Post-Menopausal Total \n Age (< 40 Yrs.) Age (41-50 Yrs.) Age (> 50 Yrs.)  Proliferative 40 (44.9%) 25 (33.8%) 01 (4%) 66 (35.1%) \nSecretory 19 (21.3%) 07 (9.5%) 0 26 (13.8%) \nDPE** 05 (5.7%) 02 (2.7%) 0 07 (3.7%) \nAtrophic 0 02 (2.7%) 02(8%) 04 (2.1%) \nSimple cystic hyperplasia 13 (14.8%) 17 (22.9%) 03 (12%) 33 (17.6%) \nComplex Hyperplasia 0 03 (4.1%) 03 (12%) 06 (3.2%) \nEndometrioid Carcinoma 0 01 (1.3%) 03 (12%) 04 (2.1%) \nLeiomyoma 04 (4.5%) 09 (12.2%) 08 (32%) 21 (11.2%) \nEndometrial polyp 03 (3.4%) 04 (5.4%) 02 (8%) 09 (4.8%) \nAdenomyosis 05 (5.6%) 04 (5.4%) 03 (12%) 12 (6.4%) \nTOTAL 89 (100%) 74 (100%) 25 (100%) 188 (100%) \nDPE **: Disordered Proliferative Endometrium \n \nTable 8: Histopathological findings in accordance to PALM-COEIN Classification \n \nHistomorphology Palm-Coein Type Number of Cases Total \n Classification    \nProliferative Non-Structural AUB-E 66 (35.1%) 103 (54.8%) \nSecretory  AUB-E 26 (13.8%)  \nDPE**  AUB-E 07 (3.7%)  \nAtrophic  AUB-E 04 (2.1%)  \nSimple cystic hyperplasia Structural AUB-M 33 (17.6%) 85 (45.2%) \nComplex Hyperplasia  AUB-M 06 (3.2%)  \nEndometrioid Carcinoma  AUB-M 04 (2.1%)  \nLeiomyoma  AUB-L 21 (11.2%)  \nEndometrial polyp  AUB-P 09 (4.8%)  \nAdenomyosis  AUB-A 12 (6.4%)  \n  TOTAL 188 (100%) 188 (100%) \nNote: AUB-E: Abnormal Uterine bleeding -Endometrial causes, AUB-M: Abnormal Uterine \nBleeding-Malignancy including hyperplasia, AUB-L: Abnormal uterine bleeding-Leiomyoma, \nAUB-P: Abnormal uterine bleeding-Polyp, AUB-A: Abnormal uterine bleeding-Adenomyosis \nDPE **: Disordered Proliferative Endometrium \n\nInternational Journal of Clinical and Diagnostic Pathology \n \n~ 179 ~ \n4.4 Interpretation of the Results \nTable 4:  Age of the patients ranged from 18-71 yrs. The \ncommonest age group involved is the perimenopausal group \n(41-50) constituting 39.4% of total presented cases Second \ncommonest age group was Fourth decade (31-40) and the \nleast common age group was less than 20 years constituting \nonly 3.2% of total cases. \nTable 5: Multiparous women most commonly presented \nwith AUB accounting for 44.1% of all cases. There is \nlimited representation of grand multipara in our study and \nhence the lower incidence of AUB in that group of patients \n(12.8%). \nTable 6: Menorrhagia was the most common clinical \npresentation in the patients of reproductive age group \n(50.6%) and perimenopausal group (39.2%). Least common \npresentation in the reproductive age group and \nperimenopausal group were Oligomenorrhoea (7.8%) and \npoly-menorrhoea (16.2%) respectively. Post-menopausal \nbleeding was present in 36.0% of cases in post-menopausal \nage group. \nTable 7: Benign proliferative endometrium is the most \ncommon histo-morphological finding in the Reproductive \nage group (44.9%) and perimenopausal women (33.8%). \nLeiomyomas were the most common presentation in post-\nmenopausal women (32%) Secretory endometrium was \nreported in 26 cases and majority of causes were in the \nreproduction age group. Disordered proliferative \nendometrium and Atrophic Endometrium were reported in 7 \nand 4 cases respectively. Among the endometrial \nhyperplasia, Simple cystic Hyperplasia was reported in 33 \ncases and constituted 84.6%. (33/39) of total cases which \nhad microscopic evidence of endometrial hyperplasia. 4 \npatients in the post-menopausal age group presented with \nendometrioid adenocarcinoma and were associated with \npost-menopausal bleeding clinically. Leiomyomas were \nreported histologically on hysterectomy specimens and \nconstituted 11.2% of total cases and majority of the cases \nwere clustered in the perimenopausal and post-menopausal \nage group. Endometrial polyps were reported in a 9 cases \nand majority (4/9) around 44% were seen in the \nperimenopausal women. Adenomyosis was reported in 12 \ncases and the cases were distributed evenly among all age \ngroups. \nTable 8: According to PALM-COEIN classification Normal \ncyclical changes of Endometrium (AUB-E) is the most \ncommon etiologic factor across all age groups. Non-\nstructural causes of AUB account for 54.8% of cases and \namong structural causes (45.2%), Simple cystic hyperplasia \nin the most common histopathological finding and \nEndometrioid adenocarcinoma was reported in 4 cases, \nconstituting (2.1%) of all structural causes. \n \n5. Discussion \nChronic Abnormal uterine bleeding (AUB) is a common \ncrippling gynaecological condition with vast financial \nimplications [5]. AUB is excessive, erratic and abnormal \nbleeding due to intra-uterine pathology or hormonal \nimbalance resulting from pathology involving \nhypothalamus-pituitary-ovarian axis [3]. With increased \navailability of medical options and individualised treatment \nprotocols, accurate diagnosis in accordance to PALM-\nCOEIN classification will help the clinician and has also \nexpanded the choice for women and they no longer need to \nrecourse to potentially complicated surgery. \nHistopathological analysis plays a significant role in \nidentification of structural causes of AUB and Non-\nStructural endometrial causes (AUB-E) and an adequate \nendometrial biopsy is of paramount importance in the \nevaluation of these patients. Hysterectomy specimens were \nanalysed in our study in cases of endometrial hyperplasia, \nendometrial carcinomas and radiologically diagnosed cases \nof leiomyoma to rule out sarcomatous change. \nIn our study there is clustering of cases (39%) in the \nperimenopausal period probably resulting from reduction in \nthe number of ovarian follicles, gonadotropin resistance and \nresultant low levels of oestrogen. These findings correlated \nwith studies done by Abdullah et al. and Saraswathi D et al. \nwho reported similar incidence of 32.1% and 33.5% \nrespectively in the perimenopausal women [10, 11]. \nParity had significant affect and increased incidence of AUB \nwas reported in multiparous women (44.1%). These findings \nwere concordant with figures reported by Mahmoud et al . \n[12]. In our study there is limited representation of grand \nmultipara and hence the lower incidence in this group \n(12.8%). This was a major limitation of our study. Majority \nof the AUB cases in our study presented with menorrhagia \nin reproductive age group (50.6%) and perimenopausal \ngroup (39.2%) and these findings were consistent with \nreference studies done by Sajitha et al. [13].  \nPalm Coein Classification defined by FIGO was \nincorporated in our study to facilitate stratification of \netiological causes and establish corre lation with \nhistopathological findings. In our study structural and Non -\nstructural causes reported were 45.2% and 54.8% \nrespectively. These figures were concordant with studies \ndone by Mirza et al . (Non-structural: 57% and structural : \n43%) and Mahmoud et a l. (Non -structural: 61.3% and \nstructural: 38.7%) [12, 14].  \n \n5.1 AUB-E: AUB that occurs in the context of a structurally \nnormal uterus with regular menstrual cycles without \nevidence of coagulopathy is likely to have an underlying \nendometrial cause. AUB-E may be implicated in many \nwomen with AUB, but a lack of clinically available specific \ntests or biomarkers means that practical testing for such \ndisorders is not yet feasible. Diagnosis depends on careful \nhistory taking and exclusion of other contributors. \nHistopathological analysis of specimens in our study reveal \nnormal cyclical endometrium with proliferative phase being \nthe most common presentation reported in 35.1% of cases \nwith clustering of cases in reproductive age group. Secretory \nphase endometrium was present in 13.8%, These findings \nwere consistent with the study done by Abdullah LS et al . \n(10) Other reference studies revealed concordant results as a \nstudy by Riaz et al . revealed proliferative endometrium in \n33% of cases study [15]. Disordered proliferative \nendometrium was reported in 3.7% and atrophic \nendometrium in 2.1% of cases and these findings were \nconsistent with findings in study done by Jetley et al . (16) \nLower incidence was reported in study by Saraswathi et al. \n(21.78%) and discordance may be due to selection criteria s \nand timing of endometrial biopsy. (11) AUB in these cases \nwhich represent Non-Structural/Functional causes in \nPALM-COEIN Classification are a result of hormonal \nimbalance due to pathology involving hypothalamus-\npituitary-Ovarian axis leading to intermittent anovulatory \n\nInternational Journal of Clinical and Diagnostic Pathology \n \n~ 180 ~ \ncycles, progressive rise of oestrogen resulting in feed-back \ninhibition by pituitary and eventual sudden fall in oestrogen. \nAll these patients benefit form hormone-manipulation \ntechniques.  \n \n5.2 AUB-P:  Endometrial polyps which present \nstructural/Organic causes of PALM-COEIN classification \nare formed due to prolonged oestrogen stimulation resulting \nin hyperplasia of basal endometrial layer. Endometrial \npolyps were reported in 4.8% of cases in our study and \nmajority (44%) were in the perimenopausal age group. \nThese finding were consistent with reference studies (Sarwat \nAra et al.  (4.2%) and Forae and Aligbe (3.0%) [17, 18] . \nClustering of cases in perimenopausal age group was also \nconcordant with reference studies by Saraswathi D et al . \n(39.1%) and by Jairajpuri ZS et al. (54.5%) [11, 19]. \n \n5.3 Adenomyosis (AUB-A): In our study adenomyosis was \nreported in 6.4% of cases. These findings correlated with \nwork done by Yu Sun et al . which revealed figures of \n4.94%. [20] Uterine adenomyosis is one cause of AUB and \nthe incidence of AUB-A is 20% to 35% [21-23]. Previous \nstudy has rarely reported AUB caused by uterine \nadenomyosis as standard criterion for the histological \ndiagnosis of uterine adenomyosis has inevitable limitations. \nTherefore, the prevalence of AUB-A in AUB is not clear. \n5.4 AUB-L (leiomyoma):  Leiomyomas were reported in \nhysterectomy specimens of 21 cases of AUB, constituting \n11.2% of total cases. These findings were concordant with \nstudy done by Yu Sun et al. which reported an incidence of \n12.35% [20]. There is still lack of data on the proportion of \nAUB-L in AUB as many of the previous studies \nconcentrated on histopathology of endometrial biopsy alone \nin evaluation of AUB and did not adequately evaluate \nhysterectomy specimens. Few studies done had indicated \nthat incidence of AUB caused by AUB-L ranged between \n14%-25% [24, 25]. The cause of AUB in patients with fibroids \nremains incompletely understood. Previous postulated \ntheories include an increased endometrial surface area and \nthe presence of fragile and engorged vasculature in the peri-\nmyoma environment [26]. The increase in vascular flow \nobserved along with these enlarged vessels can overcome \nplatelet action [27]. There is increasing knowledge regarding \nthe complex cellular and molecular changes found in \nassociation with fibroids, with impact on angiogenesis, \nalteration in vasoactive substrates and growth factors as well \nas alteration in coagulation [27]. Our study found that the \nincidence of AUB-L increased with age and majority of \ncases are in the perimenopausal and post-menopausal age \ngroup. \n \n5.5 AUB-M (Malignancy and Hyperplasia):  In our study \nsimple cystic Hyperplasia was reported in 17.6% of cases \nwhich correlated with study done by Riaz S et al. which had \nfigures of 25.0%. [15] Complex Hyperplasia were reported in \n3.2% of cases and these figures \nwere similar to the findings \nof 2.8% reported in the study done by Khan S et al . [28] \nAmongst endometrial hyperplasia, complex hyperplasia \ncomprised 15.38% of cases  and study done by Mahmoud et \nal. reported figures of 28.7%. (12%) The minor differences \nbetween these studies may be due variation in selection of \ncases and prompt initiation of hormonal therapy.  \nEndometrial Hyperplasia is the pre -cursor of carcinoma and \nresults due to anovulatory cycles with persistent un-ripened \nfollicles e xposing endometrium to prolonged estrogenic \nstimulation. Endometrial carcinoma is the significant \nhistopathological finding in our study but with least \nincidence (2.1%) All cases were associated with \npostmenopausal bleeding. These findings were consistent \nwith results of Abdullah LS et al. (1.8%) and Riaz s et al . \n(1.0%) [10, 15]. \nThus, our study which involved histopathological evaluation \nand etiological stratification of cases with AUB based on \nPALM-COEIN classification succeeded in determining the \nprevalence in our population and provided our clinicians and \nauthorities with the data to work on and plan therapy for \nefficient management of AUB.  \n \n6. Conclusion \n1. In our study majority of cases of Abnormal Uterine \nBleeding were due to hormonal imbalance in the setting \nof Normal cyclical endometrium (AUB-E) and \npredominantly presented in the reproductive age group \nwhich represented the Non-structural causes of PALM-\nCOEIN Classification. These cases can be managed by \nhormone manipulation therapy thereby excluding the \nneed for unwanted hysterectomy. Among the structural \ncauses, simple cystic hyperplasia was the major \ncontributor and these patients also benefit from medical \nmanagement.  \n2. In view of presence of reported cases of endometrial \nhyperplasia and carcinoma in our study endometrial \nsampling/biopsy has emerged as a gold standard in the \nevaluation of patients with chronic AUB. \n3. The role of Hysterectomy in patients with Chronic AUB \nshould be restricted to endometrial hyperplasia, \nendometrial carcinoma and for ruling out Malignant \ntransformation/malignancy in Leiomyomas due to \nlimitations of Imaging techniques (MRI). \n4. With increased availability of medical options and \nindividualised treatment prot ocols, accurate diagnosis in \naccordance to PALM-COEIN classification will help the \nclinician a great deal and has also expanded the choice \nfor women as now they no longer need to recourse to \npotentially complicated surgery. \n5. Our study would provide statistical data to the \nGovernment and administrative authorities to plan \npatient education, construct robust screening programs \nfor effective management of patients with chronic AUB. \n \n7. Source of Funds: None Declared.  \n8. Conflict of Interest: None Declared. \n \n9. References \n1. NICE. Clinical Guideline 44; Heavy menstrual bleeding \nNational Institute for Health and Clinical Excellence \n(NICE), 2007. Available at: \nhttp://www.nice.org.uk/nicemedia/pdf/ CG44 \nFullGuideline.pdf.  \n2. Munro MG, Critchley HO, Fraser IS. The flexible \nFIGO classification concept for underlying causes of \nabnormal uterine bleeding. Semin Reprod Med. 2011; \n29:391-9.  \n3. Practice bulletin no. 128: diagnosis of abnormal uterine \nbleeding in reproductive aged women. Obstet Gynecol. \n2012; 120:197-206.  \n\nInternational Journal of Clinical and Diagnostic Pathology \n \n~ 181 ~ \n4. Abnormal uterine Bleeding/ National Health Portal of \nIndia. 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