Study on endometrial histopathology of women with postmenopausal bleeding and its clinical correlation

(1)

A Dissertation on

STUDY ON ENDOMETRIAL HISTOPATHOLOGY OF WOMEN WITH POSTMENOPAUSAL BLEEDING AND ITS CLINICAL

CORRELATION Dissertation submitted to

THE TAMIL NADU Dr.M.G.R.MEDICAL UNIVERSITY CHENNAI.

in partial fulfillment of the regulations for the Award of the degree of

M.S., (Obstetrics &Gynecology)Branch – II INSTITUTE OF SOCIAL OBSTETRICS AND

GOVT. KASTURBA GANDHI HOSPITAL FOR WOMEN AND CHILDREN

(2)

BONAFIDE CERTIFICATE

Certified that this dissertation is the bonafide work of

Dr. T . KAVITHA on

“STUDY ON ENDOMETRIAL HISTOPATHOLOGY OF WOMEN

WITH POSTMENOPAUSAL BLEEDING AND ITS CLINICAL CORRELATION” during her M.S., (Obstetrics &Gynecology)

course from 2012 to 2015 at the Institute of Social

Obstetrics, Government Kasturba Gandhi Hospital for Women and

Children, Madras Medical College, Chennai.

Prof.Dr.M.Padmini Prof. Dr.S.Baby vasumathi, M.D., D.G.O. M.D. D.G.O.

Dept. of Obstetrics &Gynecology Director, ISO-KGH Madras Medical College Dept. of Obstetrics ISO-KGH &Gynecology,

Madras Medical College Madras Medical College Chennai. Chennai.

Prof. Dr.R. VIMALA, M.D., DEAN,

Madras Medical College &

Rajiv Gandhi Government General Hospital,

(3)

DECLARATION

I solemnly declare that the dissertation titled

“STUDY ON ENDOMETRIAL HISTOPATHOLOGY OF WOMEN WITH POSTMENOPAUSAL BLEEDING AND ITS CLINICAL

CORRELATION” is

done by me at INSTITUTE OF SOCIAL OBSTETRICS AND

GOVT. KASTURBA GANDHI HOSPITAL FOR

WOMEN AND CHILDREN,Madras Medical College under the guidance and supervision of

Prof. Dr.M.PADMINI M.D.,D.G.O.,

Professor of Obstetrics and Gynecology,

Madras Medical College,

Chennai.

This dissertation is submitted to the Tamilnadu Dr. M.G.R

Medical University towards the partial fulfillment of requirements for

the award of M.S. Degree (Branch II) in Obstetrics and Gynecology

(4)

ACKNOWLEDGEMENT

I Thank our prof. Dr.R. VIMALA, M.D., Dean Madras Medical

College for permitting me to conduct this study in Institute of Social

Obstetrics and Government Kasturba Gandhi Hospital for Women and

Children, Chennai.

I owe my sincere thanks to Prof. Dr. S.Baby Vasumathi, M.D. D.G.O. Director, ISO – KGH for her valuable guidance, during the study.

I express my profound gratitude to my guide

Prof.Dr.M.PADMINI, M.D. D.G.O., Professor of Obstetrics and Gynecology and my

co-guide prof. Dr.RAMA, M.D., Professor of PATHOLOGY for their unwavering support and encouragement.

My gratitude to my Assistant Professors, Statistician Mr.Ravanan

my colleagues, my brother , Hospital Staff and patients for enabling me to

(5)

CONTENTS

S.NO

TOPICS

PAGE NO

1. INTRODUCTION 6

2.

AIM & OBJECTIVES OF THE STUDY

9

3. REVIEW OF LITERATURE 10

4. METHODOLOGY 42

5. RESULTS 43

6. DISCUSSION 84

7. CONCLUSIONS 107

8 SUMMARY 109

9. BIBLOGRAPHY 113

10. ANNEXURES

PROFORMA 119

MASTER CHART 122

LIST OF ABBREVATIONS 132

INFORMATION SHEET 133

CONSENT FORM 134

TURNITIN SCREEN SHOT 136

ETHICAL COMMITTEE APPROVAL FORM

(6)

INTRODUCTION

Menopause is defined retrospectively as the time of final menstrual

period followed by 12 months of amenorrhea.1

Average age of menopause for Indian women is 47years.

Postmenopausal bleeding is bleeding from the reproductive system that

occurs one year or more after menstrual periods have stopped. Bleeding

from the genital tract occurring after the menopause is much more sinister

than premenopausal bleeding. In defining postmenopausal bleeding, the

question arises as to when the menopause can be regarded as established.

Even without amenorrhea or irregularity, menstruation continuing after

the age of 55 years should beinvestigated.2

The main objective in the diagnostic workup in postmenopausal women

presenting with uterine bleeding is to detect or rule out endometrial

cancer or atypical hyperplasia, further referred to as (pre) malignancy of

the endometrium. As most cases are found to be benign, the goal of

clinical management is to achieve an accurate diagnosis without

(7)

Organic pathology, causing uterine bleeding in postmenopausal women

include endometrial polyps, endometrial hyperplasia and endometrial

carcinoma. More often an organic cause is not identifiable, and the

histopathology may show atrophic endometrium, proliferative

endometrium and rarely secretoryendometrium.4

At least 20 - 25%of postmenopausal women with bleeding is said to have

a neoplastic lesion; approximately 10-15% of which is having

endometrialcarcinoma1.

The carcinoma of endometrium is one of the most common female

pelvic malignancy and ranks fifth most common cancer in females after

cervix, breast, oral cavity and ovarian malignancies5. The relatively low

mortality for this cancer is probably due to the fact that most of these

patients turn up for consultation at an early stage with symptoms of

postmenopausal bleeding. The recent rise in the incidence of endometrial

carcinoma may be related to the decreased incidence of cervical

carcinoma , prolonged life expectancy and earlier diagnosis.

Both endometrial thickness and the risk of endometrial

carcinoma are found to be associated with Various other individual risk

(8)

diabetes mellitus and parity. These risk indicators might be used for

(9)

AIM & OBJECTIVES OF THE STUDY

1. To establish the various endometrial causes of

postmenopausal bleeding, through histopathological evaluation.

2. To correlate the clinical and histopathological

findings.

3.This study also evaluates the relation between age

(10)

REVIEW OF LITERATURE

ANATOMY OF ENDOMETRIUM

Endometrium, the lining mucosa of the uterus is a labile tissue

hormonally, responsive to sex steroids secreted in the ovary. In the first

half of the menstrual cycle, endometrium undergo proliferation under the

influence of estrogens, and in the later half it responds to progesterone so

that it leads to stromal alterations necessary for implantation of a

fertilized ovum.

The adult uterus measures 50-80 grams. It measures 7-9 cm in length,4.5

– 6 cm in width and antero posterior thickness of 4 cm. The endometrium

varies from 1-8 mm thickness and the myometrium averages 1.5 – 2.5

cmthickness.6

During menopause ,the endometrium becomes thin and inactive, because

of the failure of the ovary to respond to gonadotrophic hormones. Inactive

endometrium becomes thin and may measure 1mm in thickness.

BLOOD SUPPLY :

Main blood supply to the endometrium, is by branches of uterine artery

(11)

Two types of arteries supply the endometrium , one of these is limited to

the basal third and consists of small straight and short arteries. The

superficial two thirds of the endometrium is being supplied by coiled

arteries. The veins follow the arteries, and drain into the pelvic plexus of

veins.

LYMPHATICS :

The lymphatic’s from basal layer of endometrium run through

myometrium in close relation to the blood vessels to reach the

subserosalplexus.Through the parametrium and ovarian ligament, they

communicate with the ovarian lymphatics to terminate in the pre aortic

lymph nodes. The lymphatic’s from the lower uterine segment drains to

the obturator, iliac, hypogastric and sacral nodes.6

HISTOLOGY OF ENDOMETRIUM :

The endometrium of the uterus is composed of 2 layers :

1) The basalis is the layer from which the endometrium, regenerates after

menstrual shedding.

2) The overlying functionalis layer , may be differentiated into the

superficial compactum and the underlying spongiosa, which extends to

(12)

During menstrual cycle, the endometrium varies from 1 mm

(postmenstrual) to 8mm , at the end of the 3rd week. Every layer consists

of 2major components, the epithelial component, either as glands or as

superficial epithelium and the mesenchymal component of stromal cells,

with pleuri potential properties.

1) The glandular epithelium :

It is a single layer of , columnar epithelial cells. Their height varies

depending on the functional (hormonal) state from 6mm postmenstrual,

to20mm at the end of the proliferative phase. During ,the proliferative

phase, the nuclei of the glandular cells are elongated and have a dense

chromatin. During the secretory phase, the nuclei become round,

vesicular and gradually lose their DNA.The apical surface of the

epithelial cells is the proliferative phase, possess elongated delicate

microvilli which contain alkaline phosphatases.During the secretory

phase, as these microvilli draw back and disappear, the activity of

alkaline phosphates diminishes. It is sometimes, possible to find ciliated

cells among the glandular epithelial cells. Each cell always has just 11

cilia. The number of ciliated cells , fluctuates considerably , from patient

to patient depending on the functional state of the endometrium. The

(13)

2) The superficial epithelium:

It contains, greater number of ciliated cells than does, the glandular

epithelium during the proliferative phase.

3) The stromal cells :

The endometrial stroma consists of pleuripotential

mesenchymal cells, which at the beginning of the menstrual cycle, are

uniformly spindle shaped, poorly differentiated and joined to one another

by cytoplasmic processes. The cells lie firmly anchored within a delicate

network of reticulum fibres. Characteristically, it is spindle shaped with

scant cytoplasm surrounding a bursiform nucleus. In addition, to

fibroblasts, leucocytes, mast cells and plasma cells are frequently found

in the stroma.

4) The reticulum fibers :

The reticulum fibers, in contrast to collagen fibers may be reformed

within a few days ,giving rise to a dense reticular network. While the

stroma of the basalis and isthmus mucosa remains uniformly dense, the

content of fibres in the stratum functionalis, fluctuates considerably

(14)

made out during the first 8 days of the proliferative phase. As ovulation

approaches, these fibers became smaller and thicker. During the secretory

phase, they are temporarily pulled apart, by the transistory edema that

develops. By 4th week of the cycle, they surround each predecidual cell

and form a dense network around the glands and spiral arterioles. With

the decrease in progesterone level the reticulum fibres disintegrate.

5)The vessels :

The vessels of the stratum functionalis of the endometrium , are very

much sensitive to hormones where as the vessels of the basalis are not

influenced by hormonal changes of the cycle. There is an irregular

network of venous channels with the veins frequently intersecting

forming venous lakes.6

ENDOCRINE CHANGES AT MENOPAUSE

The basic feature of menopause is that the

primordial follicle, and its derivatives, the granulosa cells and the

surrounding theca cells degenerate, or fail to react to endogenous

gonadotrophins. The stromal cells produce the androgens,

androstenedione, testosterone and deydroepiandrosterone in thenormal

premenopausal ovary, and this process continues in the postmenopausal

(15)

Thus in the postmenopausal women, about 40 g/day of estrone, is

excreted and virtually none of it is secreted by the ovary, almost all of it

is, derived from androstenedione. The androstenedione is secreted

largely from adrenal gland, and conversion occurs peripherally; that is

outside ovary, which is the adipose tissue and this suggests why

carcinoma of corpus uteri is common in obese women.7

Plasma estradiol levels decrease, gradually over the first year or so of

menopausal amenorrhea. With eventual loss of all follicular activity, the

ovary ceases, to be an estrogen secreting organ. The hormonal status of

postmenopausal women has been studied. The most important feature of

menopause is that estradiol ceases to be the major circulating estrogen

and is present at levels of 20-25 pg/ml or less.

The adrenal glands are the major site of sex hormone, production, in

postmenopausal women. Estrogens in postmenopausal women originate

almost completely from the so called peripheral conversion of androgens

to estrogens.

ENDOMETRIUM AFTER MENOPAUSE :

Once the ovaries cease their cyclic production of estrogen and

progesterone, the endometrium is no longer subject to its normal

stimulation and it undergoes atrophy. The endometrium after the

(16)

thickness and becoming quite atrophic in the elderly. The glands are

typically small and sparse, and are often not evenly distributed

throughout the tissue. They exhibit an epithelium composed of cuboidal

or flattened cells. The stroma becomes fibrous and the stromal cells, lose

virtually all their cytoplasm, the stroma of the postmenopausal

endometrium may appear remarkably cellular. Commonly the

endometrium is so thin, and meager in amount that biopsy specimens

yield only strips of atrophic surface endometrial epithelium. Exposure to

low levels of estrogen, either exogenous or endogenous, can result in a

mildly expanded endometrium in which rare mitoses can be seen. This is

quaintly referred to as 'weakly proliferative endometrium’.

The presence of a proliferative endometrium in a woman past the age of

60 years is abnormal and in the absence of a history of exogenous

estrogen usage, is regarded by many as hyperplasia.9

ETIOLOGY OF POSTMENOPAUSAL BLEEDING10

1) Vulva :Vulvitis, trauma, benign and malignant lesions.

2) Vagina : Foreign body such as ring pessary for prolapse, senile

vaginitis, vaginal tumors, vaginal cancer, post radiation Vaginitis.

3) Cervix :Benign cervical erosion, polyp, cervicitis, decubitus ulcer

(17)

4) Uterus : Senile endometritis, tuberculous endometritis, endometrial

polyp, endometrial hyperplasia and endometrial carcinoma.

5) Fallopian tube malignancy.

6) Ovary : Benign ovarian tumors such as Brenner tumour, hormone

secreting granulosa cell tumor and theca cell tumor, malignant ovarian

tumor.

7) Blood dyscrasias

8) Bowel & Urinary tract : : Urethral caruncle, papilloma , carcinoma of

bladder, Bleeding from hemorrhoids and fissures & Rectal cancer may be

misinterpreted by the patient as vaginal bleeding.

9) Indiscriminate or prolonged use of estrogens.10

ENDOMETRIAL CAUSES OF POSTMENOPAUSAL BLEEDING8

Factor (%)

Atrophic endometritis 60-80

Endometrial cancer 10

Endometrial / Endocervical polyps 2-12

Endometrial hyperplasia 5-10

Estrogen replacement therapy 15-25

(18)

1) ENDOMETRIAL ATROPHY :

Bleeding associated with endometrial atrophy, related to

insufficient estrogen stimulation may develop in women taking "oral

contraceptives", in postmenopausal women with naturally occurring

atrophy, in young women with premature ovarian failure or following

radiation for cervical cancer.

Atrophy and weakly proliferative patterns, are normal in menopausal and

peri-menopausal women as well as in pre-pubertal girls. Atrophic

endometrial, are most commonly recovered in the endometrial biopsy

sample, from patients with postmenopausal bleeding. Atrophy may

account for upto82% of postmenopausal vaginal spotting or bleeding. The microscopic appearance of atrophic endometrium is different in

hysterectomy and biopsy specimens.

In hysterectomy specimens, the endometrium is thin, and composed of variably sized glands that are often cystic and surrounded by a diminished

amount of compact stroma, compared with endometrial from

(19)

Biopsy or curettage specimens of atrophic endometrium, typically

consists of scant mucus with rare fragments and strips of cuboidal or

columnar cells. Intact glands may be absent and only small clusters of

stromal cells with dark ovoid nuclei resembling those seen in anovulatory

bleeding are observed.11

The epithelium tends to be mitotically inactive, and bland in terms of cytologic appearance. The glands are embedded in a similarly

“inactive”spindled stroma that exhibits varying degrees of collagenation

and practically no mitotic activity. The ratio of glands to stroma is near unity, although pattern uniformity is variable. The glandular architecture may be cystic, or budded, and the buds may even be closely packed; as

in hyperplastic endometrium typically; however the glands are tubular.

Occasionally, the epithelium may be metaplastic.Weakly proliferative

endometrium, differ from those that are atrophic by virtue of cells with

pseudostratified, elongated, densely basophilic nuclei, rather than the

cuboidal or flattened nuclei characteristic of the cells that ,populate an atrophic endometrium.

Cystic atrophy is the term applied to endometrium composed predominantly of cystically dilated glands lined by cuboidal to flattened

(20)

2) ENDOMETRIAL POLYPS :

Endometrial polyps are benign, localized overgrowths of endometrial glands and stroma, that are covered by epithelium, and project above the adjacent surface epithelium. Polyps arise as monoclonal overgrowths,

of genetically altered endometrial stromal cells, with secondary induction

of polyclonal benign glands, through as yet undefined' stromal – epithelial interactive mechanisms'. Chromosomal analysis of polyp stroma shows in the majority of cases clonal translocations, involving,

6p21-22, 12q13-15 or 7q22 ,regions.

Endometrial polyps variably respond to circulating estrogens, and

progesterone. The glands in the polyp may, sometimes be

indistinguishable , from those in the rest of the endometrium , but this is

unusual. If the stroma is

made up predominantly of smooth muscle but the glands are not atypical,

the term adenomyoma is employed.

MORPHOLOGICAL FEATURES :

Endometrial polyps range in size from a slightly rounded, to a large broad

based or pedunculated, oval structure filling the uterine cavity. Many

polyps are sessile, and have a broad base of attachment. 20%polyps, are

multiple. The surface may be smooth and shiny, often, hemorrhagic

(21)

Microscopy :The diagnosis of a polyp in a curetting depends upon the finding of at least two , of three particular histologic features and

exclusion of mimics.

These are: (I) irregularly shaped and positioned glands,

(ii) stroma altered by fibrosis or excessive collagen,

(iii) thick walled blood vessels.

The prevalence of polyps in general population is about 24%. Polyps are

common in women over 40 years of age and extremely rare, before

menarche. The most common presentation is postmenopausal bleeding,

infolder patients and intermenstrual bleeding, in younger patients. A

polyp should always be considered if abnormal bleeding persists after

curettage, because polyps that contain a delicate, pliable stalk may elude

the curette. Polyps are believed commonly to be a risk factor for endometrial cancer ,because hyperplastic and neoplastic lesions, can be found in their context.

In studies, fragmentation of the polyp, incompleteness of the specimen,

and the presence of adjacent endometrium hamper the diagnosis, as to

whether an endometrial cancer has originated in an antecedent benign

polyp or in the surrounding endometrium.11

Glands in polyps often fail to cycle normally, secretory changes may be

weak or absent in contrast to the surrounding endometrium, or the glands

(22)

The mesenchymal component of polyps may consist of endometrial

stroma, fibrous tissue, as smooth muscle, but generally the stroma

appears more fibrous, than normal fundus endometrium. Polyps are

morphologically diverse lesions that are difficult to sub classify; but most

can be categorized as; hyperplastic, atrophic or functional.

Hyperplastic polyps contain proliferating, irregularly shaped glands, resembling diffuse, nonpolypoid endometrial hyperplasia probably

etiologically related to hormone imbalances.

Atrophic polyps, consist of low columnar or cuboidal cells lining cystically dilated glands. These polyps are typically found in

postmenopausal patients and may represent regression of hyperplastic or

functional polyps.

Functional polyps, containing glands resembling normally cycling endometrium, are relatively uncommon.

Polyps, may be difficult to recognize in curettage specimens, ideally they

appear as polypoid shaped fragments of tissue with epithelium on three

sides. These criteria may be difficult to apply if lesions are fragmented, or

partially removed. In addition, normal endometrium has an irregular

surface, that may appear as a polypoid fragment with epithelium on three

sides, when sectioned tangentially. Identification of tissue fragments

(23)

vessels, that contrast with the appearance of the surrounding

endometrium suggest a polyp.11

Robboy, et al., studied 151 endometrial polyps, and described a new

feature useful in the diagnosis of polyps, namely endometrial glands that grow parallel to each other, with their long axis, parallel to the elongate sides of a pedunculated polyp. Endometrial glands, in their

normal physiological stage, grow with their long axis perpendicular to

the mucosal surface, that lines the endometrial cavity. The parallel

arrangement was more prominentin pedunculated polyps than in sessile polyps, in premenopausal, than in postmenopausal women and in

functional and hyperplastic polyps, than in fibrous polyps.

Savelli, L. et al., studied 358 endometrial polyps, and divided them into

(group A : benign) and ( group B : atypical hyperplastic and cancerous).

Age, menopause status, and hypertension were associated significantly

with group B.

EFFECTS OF TAMOXIFEN ON ENDOMETRIUM :

Tamoxifen, acts as a partial estrogen receptor (ER) antagonist neoplastic

breast tissue and as an agonist for the endometrium. The latter , is widely believed to be responsible for a wide range of glandular and

(24)

to carcinosarcoma. Tamoxifen, has also been consistently associated with

an increased incidence of endometrial polyps.

3) ENDOMETRIAL HYPERPLASIA :

Endometrial hyperplasia is defined as a proliferation of glands of

irregular size and shape with an increase in the gland/stroma ratio,

compared with proliferative endometrium. Endometrial hyperplasia,

usually occurs in the perimenopausal or postmenopausal years. It

represents a spectrum of morphologic and biologic alterations of the

endometrial glands and stroma, ranging from an exaggerated physiologic

state to carcinoma in situ.In the past, both generalized hormone

responses and localized premalignant lesions have been dumped under

the term endometrial hyperplasia, subdivided by architectural complexity

and cytologic atypia.

Benign endometrial hyperplasia, as it has been recently termed for those

lesions occurring as a result of hormonal effects of unopposed estrogens, are most frequently encountered around the time of menopause , or postmenopause, when the normal cycle of sequentially

(25)

Ovulation does not occur in a postmenopausal women, the estrogen

remains unopposed and proliferation continues. This prolonged

proliferation as a result of anovulation, first gives rise to disordered

proliferative endometrium after a period of about 3 weeks. The serum

level of estrogen is not necessarily raised, although in some

circumstances it may be.

Longer intervals of estrogen stimulation ,cause an even greater

exaggeration of the proliferative phase, with an increasingly irregular

distribution of individually variable endometrial glands, which are

known as benign hyperplasia. Micro infarcts, and estrogen withdrawal are

responsible for symptomatic bleeding. Both mechanisms may be effective

at different times in patients with benign hyperplasia. Patchy stromal

breakdown secondary to estrogen induced micro thrombi can produce

intermittent spotting.

Benign endometrial hyperplasia, is encountered most frequently around

the time of the menopause or post menopause, when the normal cycle of

sequentially regulated estrogen and progesterone is perturbed in tempo

and amount. As the endometrial bulk, increases through proliferation as a

result of unopposed estrogenic stimulation, the bleeding may become

more frequent and almost continuous. The causes of excessive bleeding

(26)

thrombosis and this contributes to intermittent bleeding. As the condition

depends upon estrogen stimulation for its development, the fluctuation of

estrogenic support results in irregular episodes of extensive apoptotic

endometrial stromal cells death, and breakdown of the tissue.

Most hyperplasias that occur in menopausal women are associated with

chronic anovulation. Typically postmenopausal women with hyperplasia or carcinoma have moderate or heavy vaginal bleeding ,compared with

atrophic endometrium where there will be only spotting per vaginum.

Most reports provided evidence that 20% - 30% of women with

endometrial hyperplasia characterized by glands , with marked

architectural complexity and crowding, in addition to cytologic atypia, progressed to a pattern that the investigators deemed morphologic

adenocarcinoma.

Once a patient had atypical hyperplasia, no further insight into risk,

was provided by grading the degree of atypia; that is, varying degrees of

cytologic atypia were not reflected in a greater or lesser risk of

adenocarcioma once it was determined that the endometrium was

architecturally complex, and the glands were lined by cytologically

atypical cells. In summary, climacteric and menopausal women with

atypical hyperplasia are usually treated by hysterectomy if they are

(27)

GROSS FEATURES :

Hyperplastic endometrium, is not distinctive grossly usually. In

hysterectomy specimens, hyperplasia usually presents a velvety, knobby,

surface of pale, spongy tissue with vague borders. Diffuse thickening is

typical but focal overgrowth may occur and simulate a polyp. There may

be 'foci of hemorrhage' in the areas of breakdown. The volume of tissue

obtained in curetting is usually increased, but it may be quite variable.

HYPERPLASIA WITHOUT CYTOLOGIC ATYPIA : I) Simple hyperplasia :

There is an increased glands/stroma ratio and the glands typically vary in size and shape. The glands are cystically dilated ,with occasional out pouching, surrounded by an abundant cellular stroma; at other times, the

glands are only minimally dilated but focally crowded. The cells lining

the glands are pseudostratified, and columnar with amphophilic

cytoplasm mitotic activity is variable. Cells of hyperplasia lacking

nuclear atypia contain oval, basally oriented bland nuclei with smooth,

uniform contours resembling those in normal proliferative glands. The stromal cells are more densely packed than in proliferative endometrium. The cells retain their spindle shape but are plump with

enlarged nuclei and indistinct cytoplasm. Mitosis in endometrial stromal

cells may be variable but sometimes increased.

(28)

With increasing degrees of architectural abnormality, glands become complex and branched with irregular outlines and 'papillary enfolding' into the lumen. In addition, glands becomes crowded with increased

proliferation, compressing the intervening stroma, resulting in

“back-to-back” glandular crowding. Thus complex hyperplasia is composed of

'crowded glands with little intervening stroma';. Usually the glandular outlines are highly complex but at times are tubular. Epithelial

stratification and mitotic activity generally, parallel the architectural

complexity but sometimes they are discordant. Epithelial stratification

,may range from two to four layers, mitotic activity invariable and is

usually less than five mitotic figures per 10 high power fields. The

stromal cells are spindle and become compressed by the glandular

proliferation. In addition to densely packed stromal cells, clusters of

'foamy lipid laden cells' can occur in the stroma of simple and complex

hyperplasias; atypical hyperplasias and well differentiated

adenocarcinoma. Foam cells have small pyknotic nuclei and cytoplasm

that contain lipid droplets but nomucin. The foam cells have been shown

to be histiocytes by immunohistochemistry. These histiocystic cells may

also be observed in atrophic and non neoplastic endometria.The isolated

finding of histiocytes, alone is in postmenopausal women with abnormal

(29)

ofhistiocytes containing phagocytosed acute inflammatory cells, or normal endometrial cells in postmenopausal women with abnormal uterine bleeding, has been associated with a three to four fold greater likelihood of coexistent, endometrial carcinoma or hyperplasia.12

ATYPICAL HYPERPLASIAS :

The main feature which differentiates this category, from the previous

one is the atypical cytology of the glandular lining as represented by loss of axial polarity, unusual nuclear shapes that are often rounded, irregularity in the nuclear membranes, prominent nucleoli and cleared or dense chromatin.

Atypia occurs nearly always focally.

1) Simple atypical hyperplasia :

This entity features atypical glandular cytology, superimposed on the

architecture of simple hyperplasia. This pattern is extremely unusual. The

glandular outlines may be relatively simple with minimal complexity or

they may be more irregular with interglandular tufting. They are

separated by abundant stroma; back to back glands are absent.

2) Complex atypical hyperplasia :

The frequently found complex atypical hyperplasia, is a lesion

(30)

outgrowths, and cytological atypia. Irregular glandular outlines, back to

back crowding, are seen along with epithelial stratification and variable

mitotic activity, papillary infoldings are also seen. There may be

associated foci of non endometroid differentiation such as squamous

morules. Due to the expansion, and crowding of glands the inter

glandular stroma is diminished, but remains present. Characteristic

features of adenocarcinoma are absent.

CLASSIFICAION OF ENDOMETRIAL HYPERPLASIAS:

TYPE OF HYPERPLASIA PROGRESSION TO CANCER

(%)

Simple hyperplasia without atypia

1

Complex hyperplasia without atypia

3

Simple hyperplasia with atypia 8 Complex hyperplasia with atypia 29

(31)

Carcinoma of the endometrium, is the most common gynecologic

malignancy in developed countries. It typically occurs in elderly

individuals, 80% of the patients being postmenopausal, at the time of

diagnosis. Given uterine bleeding the probability of carcinoma, is a strong

function of the patients age. The rate is 9% for women in their 50’s; 16%

for those in their60s; 28% for those in their 70s and 60% for those in their

80s.

Patients with endometrial adenocarcinoma fall into two loose

clinicopathologic clusters. Patients in the first group (type I) tend to be between 40 and 60 years of age. These patients may have a history of chronic anovulation or estrogen hormone replacement therapy and the

carcinomas are usually well differentiated, Stage I, non myoinvasive

tumors associated with endometrial hyperplasia. Most of the tumors are

ER and PR positive and p53negative and express low levels of the

proliferation antigen Ki-67. Patients in the first group have a very

favorable prognosis after hysterectomy.

In contrast, patients in the second group (type II) tend to be elderly and ,typically have no history of hyperestrogenism. In these cases the

surrounding on neoplastic endometrium is almost always atrophic and there is often an insitu component with high grade cytologic features. The

carcinomas, that develop in this group of patients are usually of the

(32)

neoplasms that are first found with deep myoinvasion. The tumors tend to

be ER/PR negative, strongly expressp53, and show high Ki-67 labelling.1

The most common type, of endometrial carcinomas,

endometroidadenocarcinoma, may be manifested by such clinical

findings as obesity, infertility and late menopause. In particular high

estrone and albumin bound estradiol levels were associated with

increased risk in postmenopausal women than in premenopausal women.

Diabetes has been repeatedly associated with an increased risk of

endometrial cancer ranging from 1.2 to 2.1.14

CLASSIFICATION OF ENDOMETRIAL CARCINOMAS

The current International Society of Gynecological Pathologists and

World Health Organization classification of endometrial carcinoma.

I) Endometrial adenocarcinoma Variants

A. With squamous differentiation

I. Adenocarcinoma with squamous metaplasia

(adenocanthoma)

(33)

C. Secretory

D. Ciliated cells

II) Serous adenocarcinoma III) Clear cell adenocarcinoma IV) Mucinous adenocarcinoma V) Squamous cell carcinoma VI) Undifferentiated carcinoma VII) Others

VIII) Mixed

ENDOMETROID ADENOCARCINOMA :

Endometrioid adenocarcinoma, is defined as a cancer in which the

glandular pattern, when well differentiated, has cytologic features most

like abnormal proliferative endometrium. The most common sub type of

endometrial cancer is endometroid, its pure form constituting about 60%

of all endometrial carcinoma. Most neoplasms develop slowly in the

setting of hyperestrogenism against a background of benign endometrial hyperplasia and, EIN, although some arise in atrophic endometrium. It is

predominantly a disease of sixth and seventh decades and 75% of cases occur after the menopause. Until recent years, the diagnosis has been

(34)

play a part. Outpatient endometrial sampling techniques generally have a

good diagnostic rate for endometrial carcinoma.

Morphology :

Endometroid carcinoma can present variously, the uterus may be slightly

or grossly enlarged, but it may be of normal size or even small and

atrophic, particularly in a postmenopausal women. Most of them arise in

the corpus,

presenting either as single mass, or two or three separate masses or a

diffuse thickening of the endometrium. More frequently carcinomas are situated on the posterior wall. The most common appearance is of a raised, rough, perhaps papillary area of the endometrium, with a shaggy

surface and ulceration, frequently occupying at least half of the surface

area of the endometrium. Sometimes the tumor is polypoid with a fairly

narrow base.Myometrial invasion may be obvious to the naked eye, with

either pushing or infiltrating borders, but frequently it is difficult to

appreciate the degree ofmyometrial invasion grossly. A tumor diameter of

more than 2 cm generally, is associated with a poorer prognosis and a

higher frequency of distant failure.

Microscopically, the glandular pattern, and cellular features generally resemble that of the proliferative phase endometrium. Multilayered

(35)

Solid growth may vary widely in extent a feature of importance in tumor

grading. Individual epithelial cells are larger than would be expected in

the proliferative phase. The carcinoma cells have a distinctly altered

cytology that varies between patients, and even within areas of a single

tumor, but may include rounded nuclei, clumped chromatin, and

prominent nucleoli. Individual tumors frequently demonstrate patchy

changes, in differentiation to Mucinous, squamous, tubal or other

cytology, and in these cases ,cytoplasmic as well as nuclear features stand

out from the normal background. Some endometroid adenocarcinoma

secrete abundant extracellular mucin but lack much intracytoplasmic

mucin a feature that distinguishes them from mucinous adenocarcinoma.

Mitotic figures are ,usually present but may be scant in well differentiated

tumors.

The endometrial stroma, adjacent to the newly forming well differentiated

neoplastic glands responds by remodeling, rarely demonstrating classic

desmoplastic change. For this reason, qualitatively assessing the character

of the endometrial stroma is non contributory.

Presumptive identification of the earliest stages of endometroid

endometrial (type I) precancers has now been accomplished using a

variety of molecular marker systems, derived from this model. These

include lineage continuity (forward carry over) of mutations of genes

(36)

carcinogenesis phases in individual patients, and demonstration of

monoclonal growth of premalignant tissues.15

OTHER VARIANTS OF ENDOMETIROID ADENOCARCINOMA :

Four histologic variants of endometrioid adenocarcinoma ,are recognized

which are –

I. Endometrioid adenocarcinoma, with squamous differentiation.

ii. Endometrioid adenocarcinoma, with secretory differentiation.

iii. Endometrioid adenocarcinoma, with ciliated cell differentiation.

iv. Endometrioid adenocarcinoma, with villoglandular variant.

Endometrioid adenocarcinoma with squamous differentiation :

One fourth of endometrial adenocarcinoma display focal

squamousdifferentiation. In the late 1960s the distinction was made

between tumors where the squamous component was ‘well’ or ‘poorly’,

differentiated. The former tumors, were called ‘adenocanthoma’ and the

latter ‘adenosquamous’carcinoma. Numerous studies have confirmed the

significantly better prognosis associated with adenocanthoma, and

endometrial carcinoma without squamous differentiation (about 90%

survival at 5 years) as compared to ,adenosquamous carcinoma (65%), a

distinction related largely to the grade of the glandular component.

(37)

so that a solid focus of adenocarcinoma will not be mistaken for

squamous differentiation.

Squamous differentiation is suggested by the presence of any of the following:

o Keratin or Keratin pearls demonstrated without special stains

o Inter cellular bridges

o At least three of the following

Sheet like growth without gland formation or pallisading

Distinct cell margins

Deeply eosinophilic or ‘glassy’ cytoplasm

Decreased nuclear : cytoplasmic ratio compared with the rest

of the tumor.

In large studies where the glandular and squamous components were

graded independently, differentiation of the squamous component was

shown to parallel that of the glandular component closely. Thus, the

prognosis can be predicted by the glandular grade alone. Grading of the

glandular component is also superior in predicting lymph node metastasis

and 5 year survival.

(38)

Secretory adenocarcinoma’ are an uncommon variant of endometrioid adenocarcinoma, composed of well differentiated glands resembling the

early or mid-secretory endometrium. The most common changes are sub

nuclear and/or supranuclear vacuolation. In addition, there may be solid

areas, consisting of small polygonal cells with clear cytoplasm. Secretory

adenocarcinomas are associated with a good prognosis. The distinction of

secretory carcinoma from atypical hyperplasia, with secretory effect can

be difficult and is based on the presence of stromal invasion in the

carcinoma.

Endometrial adenocarcinoma, endometrioid type with ciliated cell differentiation :

Ciliated cell carcinoma is a rare form of differentiation in low grade endometrioid carcinoma. It does not need to be classified separately from

endometrioid carcinoma. Patients range in age from 42 to 79 years, are

often, postmenopausal and present with bleeding. Microscopically,

ciliated carcinoma is almost always well-differentiated and often displays

a cribriform pattern. The gland lumens in the cribriform areas ,are lined

by cells with prominent eosinophilic cytoplasm and cilia.

(39)

Villoglandular carcinoma is a variant of endometrioid carcinoma that

displays a papillary architecture, in which the papillary fronds are

composed of delicate fibro vascular core, covered by columnar cells that

generally contain bland nuclei. The median age is 61 years, similar to that of women with typical endometrioid carcinoma. The microscopic

appearance of villoglandular carcinoma is, characterized by thin, delicate

fronds covered by stratified columnar epithelial cells with oval nuclei that

generally display mild to moderate ,(grade 1 or 2) atypia. Mitotic activity

is variable. Myometrial invasion is usually superficial. The main

consideration in the differential diagnosis is serous carcinoma, because

both villoglandular and serous carcinoma have a prominent papillary

pattern.

PAPILLARY SEROUS CARCINOMA

Serous adenocarcinoma, is an aggressive form of endometrial cancer

exhibiting a predominantly papillary architecture composed of exfoliative

bullous hobnail like cells with marked nuclear atypia. Serous

adenocarcinoma, is a poor prognostic form of endometrial cancer. It

accounts for 1-10% of all endometrial cancers. Majority of cases have

lymphovascular invasion and deep myometrial invasion and, a higher

incidence of cervical and lower uterine segment involvement. It is

(40)

MODIFIED FIGO SURGICAL STAGING AND GRADING SYSTEM

FOR ENDOMETRIAL CARCINOMA :

Stage I : Confined to the uterine corpus

IA : No or less than half of myometrium

IB : Invasion equal to or more than half of the myometrium.

(End cervical glandular involvement under stage 1)

Stage II : Uterine cervix involved

Cervical stromal invasion , but does not extend beyond uterus

Stage III : Pelvic extension

IIIA : Tumor invasion of serosa and/or adnexa .

IIIB : Vaginal / parametrial involvement.

IIIC : Metastases to pelvic and/or para-aortic lymph nodes.

c1- positive pelvic nodes

c2-positive para - aortic lymphnodes with or without positive

pelvic nodes

Stage IV :Extra pelvic extension

IVA : Tumor invasion of bladder and/or bowel mucosa.

(41)

HISTOLOGIC GRADING SYSTEM :1

Degree of architectural differentiation

Grade 1 : 5% or less of a non squamous or non morular solid growth

pattern.

Grade 2 : 6% - 50% of a nonsquamous or non morular solid growth

pattern.

Grade 3 :>50% of a non squamous or non morular solid growth pattern.

NUCLEAR GRADING :

The nuclear grade is determined by the variation in nuclear size, and

shape, chromatin distribution, and size of the nucleoli.

Grade 1 nuclei are oval mildly enlarged and have evenly dispersed

chromatin

Grade 3 nuclei are markedly enlarged and pleomorphic with irregular,

coarse chromatin and prominent esoinophilic nucleoli.

Grade 2 nuclei have features intermediate to grades 1 and 3.

Mitotic activity is an independent histologic variable, but it is generally

(42)

METHODOLOGY

This is a study, on histopathology of endometrium in postmenopausal

bleeding women and its clinical correlation, undertaken in the department

of obstetrics& gynecology over a period of 1 year .

For the purpose of this study , materials were collected from women

& children hospital , kgh during 2013 & 2014.

All women presenting with h/o postmenopausal bleeding were admitted

Detailed history taken

BMI &Clinical examination done.

USG pelvis with endometrial thickness done.

Endometrium sampling taken during hysteroscopy, or curettage OR Pipelle biopsy.

Inclusion criteria :

• Patients with c/o postmenopausal bleeding attending kgh op

• Those patients were subjected for endometrial biopsy by

hysteroscopy guided or dilatation and curettage or pipelle biopsy .

Exclusion criteria :

(43)

RESULTS

In this study, spanning from September 2013 – september2014;

104 cases of postmenopausal bleeding were collected from kasturba

Gandhi hospital for women &children ,triplicane, chennai and were

subjected to endometrial sampling by either hysteroscopy guided biopsy,

fractional curettage or pipelle biopsy. The data thus collected was

analyzed as follows:

ENDOMETRIAL HISTOPATHOLOGY IN RELATION TO POSTMENOPAUSAL BLEEDING

Histopathological Examination

No of

cases Percentage CA Endometrium

Endometrioid type (11)

Papillary Serous carcinoma (2)

Squamous cell carcinoma (1) 14 13.5

Simple Hyperplasia without Atypia 21 20.2

Simple Hyperplasia with Atypia 3 2.9

Complex Hyperplasia without

Atypia 5 4.8

Complex Hyperplasia with Atypia 4 3.8

Proliferative Phase 11 10.6

Secretory Phase 9 8.7

Atrophic Endometrium 27 26.0

Blood Clot / No Viable Tissue 10 9.6

(44)

The different endometrial patterns, presenting as postmenopausal

bleeding in women were studied. Out of the 104 cases studied; the most

common cause of bleeding in the postmenopausal age group was

endometrial Hyperplasia, 33 out of 104 (31.7%) followed by atrophic endometrium, 27 of 104 (26%). Proliferative endometrium were11 cases

of 104 each; (10.6%).

0 5 10 15 20 25 30

11

21

3 5 ₄

11

9

27

10

ENDOMETRIAL HISTOPATHOLOGY IN

POSTMENOPAUSAL BLEEDING WOMEN

(45)

Among the malignant causes of postmenopausal bleeding the incidence

was 14 of 104 cases (13.5%). Out of which, 11 of 104 cases were

ofendometrioid type of endometrial adenocarcinoma; 1 case of poorly

differentiated carcinoma, 1 case of Papillary serous carcinoma; 1 case of

squamous cell carcinoma.

In 10 patients (9.6%); the curetting received were not representative of

the lesion and hence no diagnosis was made.

Among the causes of postmenopausal bleeding, benign causes had an

incidence of 70.2%(73 cases) and pre(malignancy) lesions had an

(46)

INCIDENCE OF VARIOUS ENDOMETRIAL CAUSES OF POSTMENOPAUSAL BLEEDING

INCIDENCE OF VARIOUS ENDOMETRIAL CAUSES OFPOSTMENOPAUSAL BLEEDING benign lesions, 70.2 pre(malignant), 20.2 cause not found, 9.6 benign lesions pre(malignant) cause not found

CAUSES NO OF

CASES PERCENTAGE Benign Hyperplasia without atypia Proliferative endometrium Secretory endometrium Atrophic endometrium Total 26 11 9 27 73 25% 10.6% 8.7% 26% 70.2% Malignant & premalignant

lesions

Hyperplasia with atypia Cancer endometrium Total 7 14 21 6.7% 13.5% 20.2% Cause no found

(47)

AGE DISRIBUTION OF ENDOMETRIAL LESIONS IN POSTMENOPAUSAL BLEEDING

<40YEARS 41 -50 YEAR S 51-60 YEAR S >60 YEAR S CA Endometrium

0 2 5 7

Simple Hyperplasia without Atypia

1 4 16 0

Simple Hyperplasia with Atypia

0 1 2 0

Complex Hyperplasia without Atypia

0 1 3 1

Complex Hyperplasia with Atypia

0 1 3 0

Proliferative Phase

0 5 6 0

Secretory Phase

1 6 2 0

Atrophic Endometrium

0 5 11 11

Blood Clot / No Viable Tissue

1 4 5 0

Total

3 29 53 19

2.8% 27.8% 51% 18.2%

(48)

Age of patients ranged from 40 years to 75 years.

IN the age group of 41-50 years, the commonest endometrial lesion presenting with postmenopausal bleeding was secretory phase 6

cases ( 20.6%) , followed b equal number of proliferative phase &

endometrial atrophy 5 cases each(17.2%) and 2 cases of malignancy (6%)

both were endometrial adenocarcinoma.

IN the age group of 50-60 years; the commonest endometrial lesion presenting with postmenopausal bleeding was endometrial

hyperplasia-24 cases (45.2%); followed by endometrial atrophy 11 cases

(20.7%)&proliferative endometrium6 cases (11.3%) . There were 5 cases

with malignancy (9.4%); 4 were endometrial adenocarcinoma.& 1 was

(49)

In the age group of >60 years- 75yrs; the highest incidence was of endometrial atrophy; 11 cases (61.1%); followed by malignancy7 cases

(33.3%). Majority of the malignancies in this study belonged to this age

range which included 5 cases of endometrial adenocarcinoma , 1 case of

(50)

SOCIOECONOMIC STATUS OF POSTMENOPAUSAL BLEEDING

Majority of cases belonged to class 5 socioeconomic status

Socio economi c status

No of cases Percent

Class III ₄ _3.8

Class IV ₁₅ _14.4

Class V ₈₅ _81.7

Total ₁₀₄ _100.0

(51)

RELATION OF AGE AT MENOPAUSE TO ENDOMETRIALHISTOPATHOLOGY

Majority of women attained menopause at the age of 46-50 yrs.

(52)

RELATION OF AGE AT MENOPAUSE TO ENDOMETRIALHISTOPATHOLOGY

RELATIONOF PARITY TO ENDOMETRIAL HISTOPATHOLOGY

Majority of cases (64.4%) were seen in the parity range of (1-3).Out of

which 21 patients(34.4%), had endometrial hyperplasia, 17cases

(29%)had atrophy, 7 cases (10.3%) had malignancy, and 9 cases (12.6%)

had proliferative endometrium.

In the parity > 4; there were 33 cases (31.7%). Majority had endometrial

hyperplasia 11cases(35.3%).

9cases(27.3%) had endometrial atrophy,6 cases had malignancy (18.2%)

(53)

There were 3 nulliparous women (2.9%) 1case had malignancy, 1 had complex hyperplasia with atypia& 1 had atrophic endometrium.

Parity Frequency Percent Nulligravida 3 2.9

P1 9 8.7

P2 26 25

P3 33 31.7

>= p4 33 31.7

(54)

RELAIONSHIP BETWEEN TIME SINCE MENOPAUSE AND HISTOPAHOLOGY OF POSTMENOPAUSAL BLEEDING

TIME SINCE MENOPAUSE

HPE <5YRS 6-10YRS 11-15YRS 16-20YRS >20YRS CA Endometrium

4 1 3 4

2

13 5 3 0 0

2 0 1 0 0

1 3 1 0 0

1 1 1 1 0

Proliferative

Phase 7 1 2 1 0

Secretory

Phase 7 1 0 1 0

Atrophic

Endometrium 7 8 4 5 3

6 1 3 0 0

Total 48 21 18 12 5

(55)

In This study the duration of menopause, or the period of

amenorrhea after menopause ranged from 1year to 20 years.

In the clear span of 1-5 years there were maximum number of 48 cases(46.2%).Majority of 17 cases (35.5%) were of endometrial

hyperplasia followed by 7 cases (14.6%) of proliferative endometrium&

secretory phase each. Malignancy was found in 4 cases (8.3%) and all are

endometroid carcinoma.

In the duration of 6-10yrs there were 9 cases(42.9%) of endometrial

hyperplasia. There were 8 cases (38.1%) of endometrial atrophy and 1

case (4.8%) of proliferative endometrium and of endometrial

(56)

In the clear span of 11-15 years; there were 18 cases; of

which 6 (33.5%)showed endometrial hyperplasia;4 (22.2%) had

endometrial atrophy; 3 (16.7%) had malignancy. All 3 cases were

endometrial adenocarcinoma.

After a 15 years duration of menopause there were 17 cases in this study

out of which majority 8 (47.3%) showed endometrial atrophy followed by

6 (35.2%) cases of malignancies. Majority of malignant cases (64.2%) were found after a duration of menopause of 10 years. This indicates that endometrial malignancies were more likely to occur with prolonged

duration of menopause and increasing age. Majority of Endometrial

adenocarcinoma of endometrioid type were seen within shorter duration

of menopause and lesser age; whereas the variants of endometrial

carcinomas like, serous carcinoma, squamous cell carcinoma were seen

after 14, & 20 years after menopause respectively.1 case of moderately

differentiated endometroid adenocarcinoma occurred after 26 years of

(57)

RELATION OF SIZE OF UTERUS (ON PELVIC EXAMINATION) TO ENDOMETRIAL HISTOPATHOLOGY

HPE UTERINE SIZE

NORMAL BULKY 6 - 8 Weeks

CA

Endometrium

6 8 0

10 7 4

2 1 0

3 2 0

2 2 0

Proliferative Phase

5 5 1

Secretory Phase

7 0 2

21 3 3

10 0 0

Total

66 28 10

% 63.5% 26.9% 9.6%

(58)

In this study, 66 cases (63.5%) had normal sized uterus; out of which

17cases (51%) hadhyperplasia,6 cases(42%) had malignancy,21 cases

(77.7%) had atrophic endometrium .

Bulky uterus was observed in 28 cases (26.9%) where the predominating

pathology was hyperplasia 12 cases( 36.3%) , 8cases (57%) had

malignancy, and 3cases had atrophic endometrium.

Uterus of 6-8 weeks size was present in 10 cases (10.6%) where the

pathology was 4 cases(12%) with hyperplasia, 1case each with

(59)

RELATIONSHIP OF POSTMENOPAUSAL BLEEDING DURATION AND HISTOPATHOLOGY

HISTOPATHOLOGY POSTMENOPAUSAL BLEEDING DURATION IN MONTHS

< 1MON 1-2 MONS 2-3 MONS 3-4 MONS >4MONS

PRE ( MALIGNANT LESIONS) CA Endometrium Simple Hyperplasia with Atypia Complex Hyperplasia with Atypia

6 1 4 5 5

BENINGN LESIONS (hyperplasia without atypia& non - organic lesions)

34

20 11 8 10

TOTAL CASES

40 21 15 13 15

PERCENTAGE

38.5% 20.2% 14.4% 12.5% 14.4%

PMB duration ranged from 2days to 3yrs.

From this study, it showed that 76% of pre ( malignant) cases & 88 % of

benign lesions got admitted in hospital within 4 months of duration of

(60)

(61)

RELATIONSHIP OF BMI OF POSTMENOPAUSAL BLEEDING WOMEN WITH HISTOPATHOLOGY

From this study majority of malignancy ( 57%) occurred in patients with

BMI >30: followed by 45% of women with hyperplasia had BMI >30:

Where as 75% of women with atrophic endometrium had BMI <30.

BMI

HPE 21-30 31-35 36-40

CA Endometrium

6 5 3

18 6 9

Proliferative Phase

7 3 1

Secretory Phase

2 6 1

20 5 2

7 3 0

Total 60 28 16

(62)

(63)

RELATIONSHIP OF COLPOSCOPY OF POSTMENOPAUSAL BLEEDING WOMEN WITH HISTOPATHOLOGY

Colposcopy

HPE No

Lesions

Ectopy /

Infection CIN1 CIN2

Metaplasia

CA

Endometrium 10 4 0 0 0

14 3 2 0 2

2 0 1 0 0

4 1 0 0 0

3 0 0 0 1

Proliferative Phase

7 2 0 2 0

Secretory Phase

6 2 1 0 0

10 7 5 3 2

6 1 1 1 1

Total

62 20 10 6 6

(64)

From this study majority of cases (71%) malignancy have normal

(65)

RELATIONSHIP OF DIABETES MELLITUS WITH HISTOPATHOLOGY OF POSTMENOPAUSAL BLEEDING

DIABETES ABSENT DIABETES PRESENT

CA Endometrium 7 7

13 8

1 2

Complex

Hyperplasia without Atypia

2 3

Complex

Hyperplasia with Atypia

2 2

Proliferative Phase 5 6

Secretory Phase 8 1

15 12

5 5

Total 58 46

% 55.8% 44.2%

(66)

(67)

RELATIONSHIP OF HYPERTENSION AND

HISTOPATHOLOGY OF POSTMENOPAUSAL BLEEDING

Histopathological Examination HYPERTENSION ABSENT HYPERTENSION PRESENT CA Endometrium 7 7 Simple Hyperplasia without Atypia 19 2 Simple Hyperplasia with Atypia 2 1 Complex Hyperplasia without Atypia 4 1 Complex Hyperplasia with Atypia 1 3 Proliferative Phase 9 2 Secretory Phase 8 1 Atrophic Endometrium 18 9

(68)

From this study.,29 cases had hypertension: out of which 9cases (34%)

were atrophic endometrium, 7 cases (24%)) each were malignancy

&hyperplasia.

(69)

RELATIONSHIP OF HYPOTHYROIDISMAND

HISTOPATHOLOGY OF POSTMENOPAUSAL BLEEDING

In this study, only 8 cases (7%) had hypothyroidism: of which 3 cases had malignancy , 1 case each had atrophic , proliferative & secretory endometrium.

3

0 2 1 2 0

0 5 10 15 20 25 30 35

(70)

RELATIONSHIP OF TRANSVAGINAL ENDOMETRIAL THICKNESS AND HISTOPATHOLOGY OF POSMENOPAUSAL

BLEEDING

Trans Vaginal USG Endometrial Thickness

HPE <= 4 5-10 11-15 > 15

CA

Endometrium

0 4 5 5

5 10 5 1

1 1 1 0

0 4 1 0

0 3 1 0

Proliferative Phase

0 10 1 0

Secretory Phase

0 7 2 0

16 9 2 0

9 0 1 0

Total

31 48 19 6

29.8% 46.2% 18.3% 5.8%

(71)

From this study, 39 ( 29.8%) cases were < 4mm endometrial thickness;

out of which 16 cases ( 51%) are atrophic endometrium, 6 cases (19%)

were hyperplasia , no tissue seen in 29% of cases;

In this study majority of cases (46.2%) presented with endometrial thickness were

between 5 and 10mm; out of which 18 cases (37.5%) were hyperplasia, 10 cases(21%)

were proliferative phase: and 4 cases (8%) were malignancy.

In this study 71% of cancer endometrium presented with endometrial thickness

(72)

RELATIONSHIP BETWEEN H/O PREVIOUS MENSTRUAL CYCLESAND HISTOPATHOLOG OF POSTMENOPAUSAL

BLEEDING

From this study, majority of cases(50%) of post menopausal

bleeding had normal previous menstrual cycles; Histopathological

Examination Previous Menstrual Cycles

Regular Menorrhagia Hypo/ Oligo Menorrhea CA Endometrium

7 3 4

10 7 4

2 0 1

2 2 1

2 0 2

Proliferative Phase

8 3 0

Secretory Phase

4 1 4

10 10 7

7 1 2

Total

52 27 25

(73)

In this study, 7cases of malignancy(50%) had normal menstrual cycles;

among hyperplasia 16cases(48%) had normal menstrual cycles;37% 0f

atrophic endometrium had normal menstrual cycles; majority of

proliferative phases also had previous normal menstrual cycles;

(74)

RELATIONSHIP OF POSTMENOPAUSAL BLEEDING WITH ASSOCIATED PATHOLOGY

ASSOCIATED CONDITIONS

Histopathologica

l Examination Nil

Fibroi d Prolaps e Adnexa l Mass Polyp Endocer vical Endometria l CA Endometrium

11 0 0 1 1 1

14 3 1 0 1 2

3 0 0 0 0 0

4 0 0 0 1 0

3 0 0 0 0 1

Proliferative Phase

9 1 0 0 1 0

Secretory Phase

5 2 1 0 0 1

14 3 5 1 0 4

4 0 2 0 0 4

Total

67 9 9 0 17

PERCENTAG E

64.4

(75)

In this study 64% of postmenopausal bleeding patients had no

associations;

Among the associated conditions, polyp is being identified in

48%(17) of cases. In that one endometrial polyp had been diagnosed as

squamous cell carcinoma;

In this study, 1 Case of PMB was associated with the fibroid uterus

on hysteroscopy curettage revealed atrophic endometrium; Hysterectomy

specimen revealed leio myosarcoma confined to with atrophic endometrium.

In this study., 2cases had been associated with ovarian tumors;

(76)

(synchronous tumor of carcinoma endometrium & ovary).other one was cyst adenoma of ovary.

In this study, leiomyoma and prolapse are associated with 9cases each

(8.7%)of postmenopausal bleeding.

(77)

(78)

HISTORY OF MALIGNANCY ELSEWHERE ( OTHER THAN CA ENDOMETRIUM) IN POSTMENOPAUSAL BLEEDING

In this study, Only 2 cases of cancer breast seen associated with cancer endometrium; In that both cases were operated for ductal carcinoma of

breast and were undergoing tamoxifene chemotherapy. In that one case

turned out to be tamoxifene induced synchronous tumour of cancer endometrium & ovary .No family history of cancer endometrium / breast/ ovary noted in our study group.

H/O

MALIGNANCY ELSEWHERE

Frequency Percent

None 102 98.1

CA Breast

2 1.9

Total

(79)

SAMPLING METHOD

No significant comparison between sampling method, could be made out in his study.

Sampling Method Freque ncy

Perce nt Hysteroscopy

Guided Biopsy

61 58.7

Fractional Curettage

35 33.7

Pipelle Biopsy

8 7.7

Total

(80)

ENDOMETRIAL HYPERPLASIA

GRAPHICAL REPRESENATATION OF ENDOMETRIAL HYPERPLASIA 0 5 10 15 20 25 Simple Hyperplasia without Atypia Simple Hyperplasia with Atypia Complex Hyperplasia without Atypia Complex Hyperplasia with Atypia 21

3 5 4

HYPERPLASIA NO OF CASES PERCENTAGE

Simple Hyperplasia

without Atypia 21 63.3

Simple Hyperplasia

with Atypia 3 9

(81)

(82)

CLINICAL CHARRACTERISTICS OF PATIENTS WITH HYPERPLASIA

CLINICAL CHARRACTERISTICS OF PATIENTS WITH ATROPHIC ENDOMETRIUM

CLINICAL CHARACTERISTICS MEAN RANGE

AGE( mean) 63 years

AGE AT MENOPAUSE(mean) 47years

MEAN DURATION OF MENOPAUSE

6-10years

POSTMENOPAUSAL BLEEDING DURATION IN MONTHS

1 - 2 MONTHS

PARITY >3

BMI 21 -30

TRANSVAGINAL ENDOMETRIAL

THICKNESS < 4MM

PREVIOUS MENSTRUAL CYCLES REGULAR /

CLINICAL CHARACTERISICS MEAN RANGE

AGE at presentation (mean) 55 years

AGE AT MENOPAUSE(mean) 48 years

MEAN DURATION OF MENOPAUSE

<5years

POSTMENOPAUSAL BLEEDING DURATION IN MONTHS

<1MONTH

PARITY(mean) 4

BMI(mean) 26

TRANSVAGINAL ENDOMETRIAL

THICKNESS 5-10MM

PREVIOUS MENSTRUAL CYCLES REGULAR

(83)

CLINICAL CHARRACTERISTICS OF PATIENTS WITH CANCER ENDOMETRIUM

The incidence of endometrial carcinoma in this study was 13.5% (14 out

of 104 cases). It was higher in the age range of 60-70 years, mean age of

61.3yrs. The incidence was higher when the duration of menopause was

greater than 10 years; mean duration of menopause was 10 years. Mean

parity of patients with endometrial carcinoma was 4.

HISTOLOGICAL SUBTYPES OF ENDOMETRIAL CARCINOMA :

0 1 2 3 4 5 6 7 8

endometroid carcinoma with

squamous differentiation

endometroid carcinoma with

villoglandular variety

endometroid carcinoma other

varieties

papillary serous

carinoma squamous cell carcinoma

1 2

8

2