Shilpa m d

I

“STUDY OF ENDOMETRIAL PATHOLOGY IN ABNORMAL

UTERINE BLEEDING”

By

Dr. SHILPA M D

Dissertation Submitted to the Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka

In partial fulfilment of the requirements for the degree of

DOCTOR OF MEDICINE

IN

PATHOLOGY

Under the guidance of

DR. SUBRAMANYA.H Professor of Pathology

DEPARTMENT OF PATHOLOGY M.V.J. MEDICAL COLLEGE AND RESEARCH HOSPITAL, HOSKOTE,

BANGALORE 2014

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ACKNOWLEDGEMENT

I Dr. Shilpa. M. D bow my head in gratitude to Almighty god, without whose

blessings I could not have reached so far in my life.

It gives me pleasure to express my sincere and heartfelt gratitude to my

respected guide Dr. Subramanya.H, Professor, Department of Pathology MVJ

Medical College, Research Hospital Hoskote Bangalore, for all the support, help,

guidance and care.

I would like to express my deepest gratitude and respect to our Principal,

Dr.T.S. Raghuraman for his constructive guidance, generous support and inspired

suggestions which have greatly helped to improve my work. I have always benefited

from his timely advice and encouragement.

I am grateful to Dr. Shammem shariff., Professor and Head, Department of

Pathology MVJ Medical College, Research Hospital Hoskote Bangalore, for her co-

operation, timely help, motivation and effective advice during the study. My special

thanks to her for the enormous amount of time given in the department towards the

preparation of dissertation.

I express my thanks to the Management for their encouragement for providing

the necessary facilities during my study without which this task could not be

accomplished.

I thank my respected madam Dr. Madhusmita Jena and respected sir Dr. Raja

Parthiban, Professor Department of Pathology MVJ Medical College, Research

Hospital Hoskote Bangalore for their constant guidance and support .

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LIST OF ABBREVIATIONS

AUB Abnormal Uterine bleeding

D&C Dilatation and curettage

DUB Dysfunctional uterine bleeding

FSH Follicular stimulating hormone

GnRH Gonadotropin releasing hormone

H&E Haematoxylin and eosin

HCG Human chorionic gonadotropin

WHO World Health Organization

FIGO International Federation of Gynecology & Obstretics

HMB Heavy menstrual bleeding

IMB Inter menstrual bleeding

HPMB Heavy and prolonged menstrual bleeding

FMB Frequent menstrual bleeding

PMB Post menopausal bleeding

PP Proliferative phase

SP Secretory phase

SHWOA Simple hyperplasia without atypia

CHWA Complex hyperplasia with atypia

EP Endometrial polyp

DP Disordered proliferative

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ME Mixed endometrium

AE Atrophic endometrium

EAC Endometrial adenocarcinoma

ESS Endometrial stromal sarcoma

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ABSTRACT

Background & Objectives The study was a prospective study done from October 2011 to May 2013. The

specimens received from dilatation & curettage & hysterectomy were included in the

study. The main objective was to evaluate histopathology of endometrium for

identifying the causes of abnormal uterine bleeding & to observe the incidence of

various pathology in different age groups.

Results

A total no. of 200 cases were studied. Out of these, 70 cases were of Proliferative

endometrium, 53 cases of Secretory endometrium, 48 cases of simple hyperplasia

without atypia, 03 cases of complex hyperplasia with atypia, 04 cases of Endometrial

polyp, 06 cases of Mixed endometrium , 06 cases of Disordered proliferative, 07 cases

of Atrophic endometrium, 01 case of Endometrial stromal sarcoma and 02 cases of

Endometrial adenocarcinoma were seen. Maximum cases Abnormal uterine bleeding

were seen between 31-40 years of age. Most of the cases presented with heavy

menstrual bleeding.

Interpretation and conclusion

In conclusion, abnormal uterine bleeding is one of the commonest condition for which

patients seek advice in the gynecological outpatient department. Analysis of

histopathology of endometrium in abnormal uterine bleeding helps in management of

patients and to know the pathological incidence of structural causes in AUB prior to

surgery.

Keywords- Abnormal uterine bleeding ; Proliferative endometrium; Secretory endometrium; Endometrial hyperplasia; Complex hyperplasia

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CONTENTS

SI. NO PARTICULARS PAGE NO

1 INTRODUCTION 1

2 AIMS & OBJECTIVES 3

3 REVIEW OF LITERATURE 4

4 CLINICO-PATHOLOGICAL CORRELATION 42

5 MATERIAL & METHODS 46

6 RESULTS AND OBSERVATIONS 47

7 DISCUSSION 70

8 CONCLUSION 77

9 SUMMARY 79

10 BIBLIOGRAPHY 82

11 ANNEXURES (i) PROFORMA (ii) KEY TO MASTER CHART (iii) MASTER CHART

89

92

93

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LIST OF TABLES

Table No

Title

Page No

1 Existing menstrual terminologies that in consence with the current ' PALM - COEIN' system should be discarded

22

2 Acceptable Abbreviations Describing Menstrual Symptoms Established by Popular Usage

23

3 Suggested "Normal" Limits for Menstrual Parameters in the Mid- Reproductive Years

28

4 Age distribution pattern of AUB patients in the present study 48

5 Relationship of AUB with parity 49

6 Bleeding patterns in AUB patients in the present study

50

7 Histopathological findings in the present study 51

8 Patterns of distribution of histopathological findings in patients of reproductive age group (21-40yrs)

52

9 Patterns of distribution of histopathological findings in patients of peri-menopausal age group

53

10 Patterns of distribution of histopathological findings in patients of post-menopausal age group

54

11 Age group wise distribution of histopathological findings in the present study

55

12 Study of histopathological findings in correlation with HMB 56

13 Study of histopathological findings in correlation with IMB 57

14 Study of histopathological findings in correlation with HPMB 58

15 Study of histopathological findings in correlation with FMB

59

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16 Study of histopathological findings in correlation with

oligomenorrhea

59

17 Comparative study of age incidence by different authors 70

18 Comparative study of parity and AUB 71

19 Comparative study of types of bleeding and AUB 72

20 Comparative study of histopathological pattern in AUB

73

21 Comparative study of incidence of endometrial hyperplasia in AUB

74

22 Comparative study of incidence of atrophic endometrium in

AUB

75

23 Comparative study of incidence of mixed endometrium in AUB

75

24 Comparative study of incidence of disordered proliferative endometrium in AUB

76

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LIST OF BAR / PIE DIAGRAM CHARTS

GRAPH

NO

TITLE

PAGE NO

1 Age distribution pattern 48

2 Relationship of AUB with parity 49

3 Distribution of bleeding patterns 50

4 Distribution of histopathological patterns 51

5 Distribution of histopathological pattern in reproductive

age (21-40 yrs)

52

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LIST OF FIGURES

FIGURE NO TITLE

PAGE NO

1 Proliferative phase (6a & 6b) 60

2 Secretory phase (7a & 7b) 61

3 Simple hyperplasia witout atypia (8a & 8b) 62

4 Disordered proliferative endometrium (9a & 9b) 63

5 Mixed endometrium (10a & 10b) 64

6 Atrophic endometrium (11a & 11b) 65

7 Endometrial polyp (12a & 12b) 66

8 Complex hyperplasia with atypia (13a & 13b) 67

9 Endometrial adenocarcinoma (14a & 14b) 68

10 Endometrial stromal sarcoma (15a & 15b) 69

INTRODUCTION

The endometrium which lines the uterine cavity is one of the most dynamic tissues

in the human body; an interesting tissue for histopathologic study. It is characterized

by cyclic processes of cell proliferation, differentiation and death in response to sex

steroids elaborated

in the ovary.1

Abnormal uterine bleeding is the commonest presenting symptom and major

gynecological problem responsible for as many as one-third of all out patient

gynecologic visit.2,3

Menorrhagia affects 10-30% of menstruating women at any one time, and may

occur at some time during the perimenopause in upto 50% of women.4

Abnormal uterine bleeding is defined as any bleeding pattern that differs in the

frequency, duration and amount from a pattern observed during a normal menstrual

cycle or menopause. It is a common problem having a long list of causes in different

age groups.5

The endometrial sampling is chosen to evaluate abnormal uterine bleeding

because it has several advantages over other diagnostic methods. The hormonal assay

is very expensive and laboratories with hormonal assay are not available in rural areas.

Ultrasonography clearly depicts the uterine contour and the status of the ovary,

but fails to provide adequate information regarding the endometrium , except in

atrophy and hyperplasia. Other investigations like hysteroscopy and

hysterosalpingography are mainly helpful in diagnosing organic pathology. 6

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Endometrial curettage is relatively inexpensive and accurate as an outpatient

procedure. The only disadvantage of endometrial biopsy is that, it is an invasive

procedure.

An understanding of the varieties in the normal morphological appearance of the

endometrium provides an essential background for the evaluation of endometrial

pathology.1

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AIMS AND OBJECTIVES

1. To evaluate histopathology of endometrium for identifying the causes of

abnormal uterine bleeding.

2. To observe the incidence of various pathology in different age groups.

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REVIEW OF LITERATURE HISTORICAL REVIEW: The term “menstruation” is derived from the Latin word “menstruus” meaning

“monthly”.7

Sir John Williams stated that menstruation is a cyclical process, which begins at

cessation of menstrual flow, passes through the developmental changes of mucus

membrane of the uterus and ends with the cessation of the next following

menstruation”. 8

The fact that menstruation is a normal physiological process of female

reproductive system is obvious, but in the earlier centuries it was considered

to be an impure phase of every woman's life. Pliny the elder, back in the first

century AD, represented the way menstruation was viewed. It was then considered as

an unpleasant event of a women's life.9

Indeed, over 1500 years later, seventeenth-century descriptions of

menstruation continued to reflect the perception of normal menstruation as a disorder

and included terms such as “the monthly disease, the monthly infirmity, the

sickness, monthly evacuations, natural purgations,” or even, the “time of your

unwonted grief,” or, perhaps even worse, “the monthly flux of excrementitious and

unprofitable blood.9

It is of interest that primitive societies quite independently usually have negative

terms for menstruation, such as the “sik bilong mun” of the Pidgin language of

Papua New Guinea. The phrase, “at those monthly periods”, was used for the

first time in the early seventeenth century.9

However, this thought has changed to a modernised one by nineteenth century AD.

H.Beckwith White House described menstruation in academic context as- "one of the

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sacrifices to be offered by woman at the altar of evolution and civilization".9

There were very few medical textbooks that dealt with the disorders of

menstruation process. It was Hippocrates who described abnormal uterine bleeding

for the first time around 460 BC. Until 1800 s the description mostly reflected

abnormal bleeding symptoms as excessive bleeding described as heavy evacuations of

the menses, inordinate flowing, immoderate flux, an overflowing of "courses",

menstruation to be too profuse, excessive flooding, and uterine haemorrhage.10

The medical text books of Hippocrates were later translated and quoted by

Aristotle as- "in quantity, bleeding is excessive saith Hippocrates, when

they flow about eighteen ounce". But the fact that eighteen ounce is about 540ml. is

quite shocking to know since it is about seven times the maximum limit.9

In the middle part of the seventeenth century, William Heberlen, a

gynecologist and successful physician provided earliest and best description of

abnormal uterine bleeding available till then . None of the early writers used terms

like menorrhagia or metrorrhagia until the later parts of seventeenth century.9

The term menorrhagia was used for the first time by William Cullen,

professor at the university of Edinburg . According to Cullen, menorrhagia was a

disease involving deviations from normal which are too high in degree and causes a

state of disability. 10

The term menorrhagia rubra was used for non puerperal women and

menorrhagia abortus was used for pregnant women . The term menorrhagia

was first found in treatise by a postgraduate student of Cullen which was

attributed to him. Exact spelling used by Cullen was maetrorrhagia .

Fleetwood Churchill, a specialist in gynaecology described the abnormalities

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associated with uterine bleeding as metrorrhagia in his medical books

which later came to be known as menorrhagia.9

The word menorrhagia, is derived from Greek word " mene" meaning moon and

"regnumi" meaning to burst forth. Graves used the term dysfunctional uterine

bleeding for the first time which according to him meant impairment of endocrine

factors which is similar to regular or irregular menorrhagia or disturbances that were

caused during ovulation state.9

EMBRYOLOGY 11,12,13

The uterus arises from the paramesonephric ducts. They appear in the embryo at

around the 40th day. In the female embryo, as soon as the paramesonephric ducts

come in deposition within the urorectal septum, they begin to fuse and the

uterus is formed. The endometrium and myometrium are of mesodermal origin

and both structures are formed secondary to fusion of the mullerian ducts . Until

the 20th week of gestation, the endometrium is composed of a single layer

of columnar epithelium supported by a thick layer of fibroblastic stroma.

By the 20th gestational week, the surface epithelium invaginated into

the underlying stroma, forming glandular structures that extends towards the

underlying myometrium.

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ANATOMY 12

The adult uterus is a hollow, pear shaped organ that weighs 40- 80 grams and

measures 7-8 cm long in the non-pregnant state. The uterine cavity has a

mucosal lining, the endometrium which provides the environment for foetal

development ; the myometrium, which expands greatly during pregnancy

and provides protection for the foetus and a mechanism for the expulsion of

the foetus at parturition.

The endometrium is variable in thickness measuring between 1-5 mm at different

stages of the menstrual cycle. The myometrium makes up the bulk of the uterus

measuring up to 13-20 mm in a woman of reproductive age.

HISTOLOGY 14,15

The endometrium is divided into three distinct layers histologically

and functionally. The deepest or the basal layer, the stratum basalis is

adjacent to the myometrium, undergoes little changes during the menstrual

cycle and is not shed during menstruation. It is made up of weakly

proliferative glands and spindled stroma. The broad intermediate layer is

characterized by stroma with a spongy appearance and is called the

stratum spongiosum. The thinner superficial layer which has a compact stromal

appearance is known as the stratum compactum. The compact and spongy

layers exhibit dramatic changes throughout the cycle and are shed during

menstruation, hence they are together referred to as stratum functionalis.

The stroma is mainly composed of endometrial stromal cells and vessels,

of which the spiral arterioles are most distinctive. Other components include

the stromal granulocytes ( made up of either the T- lymphocytes or

macrophages) and an inconstant stromal foamy cells.

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Normal Menstrual Cycle

Normal menstruation is defined as bleeding from secretory endometrium

associated with ovulatory cycles, not exceeding a length of 5 days.3

In women who menstruate, the endometrium thickens every month in preparation

for pregnancy. If the woman does not become pregnant, the endometrial lining is shed

during the menstrual period. After menopause, the lining normally stops growing and

shedding.

Under normal circumstances, a woman's uterus sheds a limited amount of blood

during each menstrual period (less than 5 tablespoons or 80 mL). Bleeding that occurs

between menstrual periods or excessive menstrual bleeding is considered to be

abnormal uterine bleeding. Once a woman who is not taking hormone therapy enters

menopause and the menstrual cycles have ended, any uterine bleeding is considered

abnormal.16

In the normal menstrual cycle, there is an orderly cyclic hormone production and

parallel proliferation of the uterine lining in preparation for implantation of the

embryo. Disorders of the menstrual cycle and, likewise, disorders of menstrual

physiology may lead to various pathologic states, including infertility, recurrent

miscarriage, and malignancy.

The normal human menstrual cycle can be divided into two segments:

1) Ovarian cycle and

2) Uterine cycle

The ovarian cycle may be further divided into

1) Follicular

2) Luteal phases

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The uterine cycle is divided into

1) Proliferative phase and

2) Secretory phase

The four major hormones are involved in the control of menstrual cycle and can be

measured in peripheral blood are:

1) Follicular stimulating hormone (FSH)

2) Luteinizing hormone (LH)

3) Estrogen, and

4) Progesterone

The menstrual cycle is regulated by pituitary- hypothalamic axis.

OVARIAN CYCLE : 17,18

1. The follicular phase:

During the follicular phase an orderly sequence of events takes place that ensures

that proper number of follicles is ready for ovulation. In the human ovary the end

result of this follicular development is (usually) one surviving mature follicle. This

process, which occurs over the space of 10-14 days, features a series of sequential

actions of hormones and autocrine / paracrine peptides on the follicle, leading the

follicle destined to ovulate through a period of initial growth from a primordial follicle

through the stages of the preantral, antral and preovulatory follicles. Variability in

length of follicular phase is responsible for most variations in total cycle length.

(Normal 10-14 days).17

The primordial Follicle 18

The primordial germ cells originate in the endoderm of the yolk sac, allantois, and

hindgut of the embryo, and by 5 to 6 weeks of gestation they migrate to genital ridge.

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Multiplication of germ cells begin at 6 to 8 weeks of pregnancy and by 16 to 20 weeks

maximum number of oocyte is reached (6 to 7 million in both ovaries). The primordial

follicle is non growing which consists of an oocyte surrounded by a single layer of

spindle shaped granulosa cells. The first visible signs of follicular development are an

increase in the size of the oocyte and the granulosa cells becoming cuboidal.

a) Events in the preantral follicle 18

Initially development of follicles occurs independently of hormonal influence.

This is followed by FSH stimulation which propels follicles to the preantral stage.

FSH induces aromatization of androgen in the granulosa resulting in the production of

estrogen. And together, FSH and estrogen causes increase in the FSH receptor content

of the follicle.

b) Events in the antral follicle 18

During days 5 to 7 dominant follicle selection is established and peripheral levels

of estradiol begin to rise significantly by cycle day 7 consequently and estradiol

levels, which are derived from the dominant follicle, increase steadily and, through

negative feedback effects, exert a progressively greater suppressive influence on FSH

release. Due to a decline in FSH levels, the midfollicular rise in estradiol exerts a

positive feedback influence on LH secretion. The positive action of estrogen also

modifies the gonadotropin molecules, by increasing the quality as well as the quantity

of FSH and LH at midcycle.

LH levels rise steadily during the late follicular phase and stimulate androgen

production in the theca. The dominant follicle utilizes the androgen as substrate and

further accelerates estrogen production. LH receptors start appearing on granulosa

cells by the action of FSH. Granulosa cells secrete inhibin B in response to

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FSH. This can suppress pituitary FSH secretions directly. FSH secretion and

action is further augmented by activin (originating in pituitary and granulosa).

c) Events in the Pre ovulatory follicle 18

Estrogen production is sufficient to achieve and maintain peripheral threshold

concentration of estradiol which is required in order to induce the LH surge.

Luteinization and progesterone production in the granulosa layer is initiated by LH

through its receptors. This pre ovulatory rise in progesterone facilitates the positive

feedback action of estrogen and induces the mid cycle FSH peak.

2. Ovulation 18

The pre ovulatory follicle, through the elaboration of estradiol, provides its

own ovulatory stimulus. Considerable variation in ovulation timing exists

from cycle to cycle, even in the same woman.

A reasonable and accurate estimate places ovulation approximately

10-12 hours after the LH peak and 24-36 hours after peak estradiol levels

are attained. The onset of the LH surge appears to be the most reliable

indicator of LH concentration must be maintained for 14-27 hours in

order for full maturation of the oocyte to occur. Usually LH surge lasts 48-50 hours.

Ovulatory events 18

The LH surge is responsible for continuous reduction division in the oocyte,

luteinization of the granulosa, and for the synthesis of progesterone and prostaglandins

within the follicle. This progesterone and prostaglandins together enhance the activity

of proteolytic enzymes which is responsible for digestion and rupture of the follicular

wall. The progesterone influence mid cycle rise in FSH is responsible to free the

oocyte from follicular attachments and, to convert plasminogen to the proteolytic

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enzyme, plasmin, and to ensure that sufficient LH receptors are present to allow an

adequate normal luteal phase.

3. Luteal phase 18

Before rupture of the follicle and release of the ovum, the granulosa cells begin to

increase in size and assume a characteristic vacuolated appearance associated with the

accumulation of a yellow pigment, Lutein, which lends its name to the process of

luteinization and the anatomical subunit the corpus luteum. Angiogenesis is an

important feature of the luteinization process. Luteal phase - the time from ovulation to

the onset of menses, with an average length of 14 days.

Events in the luteal phase 18

Adequate FSH stimulation and continued tonic LH support is required for

normal luteal function. New follicular growth is suppressed by progesterone which is

acting centrally and within the ovary. Corpus luteum regression involves the luteolytic

action of its own estrogen production, mediated by an alteration in local prostaglandin

and endothelin- I concentrations. In early pregnancy, the corpus luteum is rescued by

human chorionic gonadotropin (HCG) which maintains luteal function until placental

functions develop.

The luteal- follicular transition 18

The interval extending from the late luteal decline of estradiol and progesterone

production to the selection of the dominant follicle is a critical and decisive time,

marked by the appearance of menses, very important are the hormone changes that

initiate the next cycle. The critical factors include GnRH (Gonadotropin releasing

hormone), FSH, LH, estradiol, progesterone, and inhibin.

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Events in the luteal follicular transition 18

• The demise of the corpus luteum results in a nadir in the circulating levels of

estradiol, progesterone, and inhibin.

• FSH secretion suppressing influence in the pituitary is removed by the decreasing

levels of inhibin A.

• Also the decrease in estradiol and progesterone will allow a progressive and rapid

increase in the frequency of GnRH pulsatile secretion and removal of the pituitary

from negative feedback suppression.

UTERINE CYCLE 17,19,20,21

The mucosal lining of the uterus is composed of the glands and the stroma. The

endometrium of the corpus is composed of two layers,

1. The basalis: is the deepest region of the endometrium and does not undergo

significant monthly proliferation Instead, it is the layer from which the endometrium

regenerates after shedding.

2. Overlying Functionalis: It is the superficial two thirds of the endometrium that

proliferates and is ultimately shed with each cycle if pregnancy does not occur. In the

second half of the menstrual cycle, the functionalism may be differentiated into

superficial compacta and the underlying spongiosa, which extends to the basalis.

The endometrium varies in thickness over the cycles.

• At menstruation - 0.5mm thick

• Immediate post menstrual phase -1-2mm

• Proliferative phase - 2- 4mm

• Mid secretory phase - 7-8mm

There is some reduction to 5-6mm in the immediate premenstrual phase. Customarily

the normal menstrual cycle (in uterus) is divided into two main phases.

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1. The proliferative phase

2. The secretory phase

To which can be added the menstrual phase.

Estrogen predominates in the proliferative phase, the progesterone effects prevails in

the secretory phase.

ENDOMETRIAL DATING 22,23

A normal endometrial cycle is associated with changes in both endometrial

glands and stroma that allow the pathologist to diagnose microscopically the phase

of menstrual cycle.

Proliferative phase

This phase lasts 2 weeks, but under physiological conditions, may fluctuate

between 10 and 20 days. It is subdivided into early, middle and late stages. It is

under the control of oestrogen. In this phase, growth of the glands outstrips that

of the stroma, resulting in increasing coiling or tortuosity.

Early proliferative stage (4th - 7th day of a 28 day cycle)

Thin regenerating surface epithelium; straight, short and narrow glands;

compact stroma, with some mitotic activity and large nuclei.

Mid-proliferative stage (8th-10th day of a 28 day cycle)

Columnar surface epithelium; longer curved glands; variable amount of

stromal oedema; numerous mitoses in stroma.

Late-proliferative (11-14th day)

Undulant surface; tortuous glands showing active growth and

pseudostratification; moderately dense, actively growing stroma.

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Early secretory phase (Upto 48 hrs after ovulation)

36-48 hrs after ovulation – No microscopic changes apparent.

Sixteenth day – Subnuclear vacuolation of epithelium appears.

Seventeenth day – Orderly row of nuclei with homogeneous

cytoplasm above them and large vacuoles below.

Eighteenth day – Vacuoles decrease in size; nuclei approach base

of cell.

Nineteenth day – Few vacuoles; appearance of intraluminal secretion.

Mid secretory phase

Twentieth day – Peak of acidophilic intraluminal secretion.

Twenty-first day – Tissue oedema appears abruptly.

Twenty-second day – Oedema reaches peak.

Late secretory phase

Twenty-third day – Spiral arterioles become prominent.

Twenty-fourth day – Collections of predecidual cells appear

around arterioles.

Twenty-fifth day – Predecidua appears under surface epithelium.

Twenty-sixth day – Predecidua appears as solid sheet of well-

Developed cells; polymorphonuclear cell infiltration

appear.

Twenty-seventh day – Polymorphonuclear cell infiltration becomes

prominent; areas of focal necrosis and

haemorrhage begin to appear.

Twenty-eighth day – Necrosis and haemorrhage prominent.

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The menstrual phase 21

If pregnancy has not occurred, the late secretory phase leads inevitably to

menstrual phase, starts 14 days after ovulation. This phase is recognized histologically

by crumbling of the stroma and glandular collapse and haemorrhage in the superficial

stroma. On the second day of menstruation- scattered stromal cells and remnants of

glandular epithelium lying amidst fresh blood and aggregates of neutrophils are present

Regeneration:

Immediately after menstrual shedding ceases and before proliferation begin,

regenerative phase sets in, lasting one to two days, during which the denuded

endometrium becomes epithelized.

THE MORPHOMETRIC APPROACH 14

A variety of light microscopic morphometric methods have

provided greater precision in histological dating of the endometrial biopsy

and given insight into the complex cellular changes. Four parameters were

found to be important for dating the endometrial biopsy during the luteal phase.

These include:

i. Number of mitoses/ 1000 gland cells

ii. Amount of secretion in gland lumen

iii. Proportion of gland occupied by gland cell

iv. Amount of predecidual reaction .

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MECHANISM OF NORMAL MENSTRUATION 4, 24

Menstruation occurs as a universal endometrial event following the withdrawal of

estrogen and progesterone subsequent to normal menstrual cycle.

In normal menstruation, one half to three quarters of the menstrual

discharge is blood with the rest being fragments of endometrial tissue and mucus.

Menstrual blood does not clot normally and consists of aggregation of

endometrial tissue, red cells and degenerated platelets and fibrin. The

following are the changes seen in normal menstruation.

1. Changes in the endometrium

The unique feature is the existence of spiral arteries or arterioles in

the endometrium. In the proliferative phase, the spiral arterioles grow

upward from basal to more superficial layers of the endometrium. In the luteal phase,

there is marked increase in length and coiling of the arteriole with

dilatation. In premenstrual phase, the endometrium shrinks and spiral

arterioles become more coiled. At the same time gaps start appearing between

endothelial cells of spiral arterioles and the associated thin walled veins.

Leukocytes migrate through the gaps into the stroma. Immediately before

menstruation, the spiral arteriole starts constricting intensely for a period of

24 hrs and then dilates with a massive extravasation of erythrocytes into

the stroma of the endometrium. According to Markee, the key event in

menstruation is the vasoconstriction of the spiral arterioles due to the

liberation of an unknown substance in the endometrium which produces

vasoconstriction, resulting in damage to the wall of the spiral arterioles and necrosis of

the superficial layers of the endometrium. Matrix metalloproteases are upregulated by

falling progesterone levels. These molecules are active in degrading the extracellular

- 18 -

matrix, leading to breakdown of endometrial architecture and basement membranes

independently from the vasoconstrictive mechanisms This is one of the primary

mechanism in tissue breakdown

2. Haemostasis and endometrial regeneration

Primary haemostasis in the spiral arterioles is achieved by the formation of

plugs of aggregated platelets and fibrin. After 24 hours, the main

mechanism ensuring haemostasis is, constriction of the spiral arterioles, with swelling

of the endothelial cells which completely occlude the spiral arterioles. On the second

day of bleeding, re-epithelialization commences from the basal glands and usually gets

completed by third or fourth day. Rate of re-epithelialization depends

upon the amount of estrogen stimulation which is dependent on the rate of growth

of the follicles developing in the ovary

.

3. Fibrinolysis and liquefaction of menstrual blood

Liquefaction of menstrual blood is an important part of the mechanism of

menstruation, not only in facilitating the passage of the menstrual

products through the cervix, but also in ensuring easy and rapid discharge and

preventing infection and adhesions of the endometrium. The endometrium and the

cervix are sites of marked fibrinolytic activity. Plasminogen activators are

demonstrated in the myometrium, endometrium and menstrual blood.

The concentration of plasminogen activators in menstrual blood is maximal on the

first day of bleeding and also higher in samples taken from the uterus than from

vagina. It suggests that, the activators are rapidly consumed and clot rarely forms in the

uterus than in the vagina.

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4. Angiogenic factors

Angiogenic factors such as vascular endothelial growth factor (VEGF) and

fibroblast growth factor (FGF) have potential role in endometrial angiogenesis. It

appears probable that a precise series of interaction between VEGFs, FGFs, their

receptors and other molecular systems occurs during angiogenesis in the normal

endometrial cycle, and that disruption of part of this system can lead to disordered

angiogenesis, abnormally small vessels and clinically important disturbances of

bleeding.

Definition and Classification of causes AUB

Goldstein et al defined abnormal uterine bleeding as “Patients having either

metrorrhagia defined as vaginal bleeding separated from expected menses or

menorrhagia defined as patients’ subjective complaints of either increased duration or

increased volume of flow or both". 25

Until the eighteenth century reason for menorrhagia was guessed by Aristotle. It

was thought that excessive uterine bleeding was due to heating of blood,

trauma, or due to breaking of veins. 9

Later, by the middle of eighteenth century several interesting hypothesis

came into existence. Dewees, from his observations described the cause for heavy

menstrual bleeding in women with some imbalance in daily activities like little or no

exercise, intemperate nature, irregular dancing, having several child bearings, who

were affected by some infections in the past, who were at their advancement of

non menstrual period, who yielded to passions or emotions easily.9

In the book The Married Woman s Private Medical Companion, written by

Mauriceau some other causes as per his observations were stated .

Women who had miscarriages in the past, weak women, women who underwent

- 20 -

heavy exercise, highly obese women are prone to have fair chances of suffering from

menorrhagia.9

Terms used to describe abnormal uterine bleeding 26,27

Oligomenorrhea - Bleeding occurs at intervals of > 35 days and usually is

caused by a prolonged follicular phase.

Polymenorrhea - Bleeding occurs at intervals of < 21 days and may be caused

by a luteal-phase defect.

Menorrhagia - Bleeding occurs at normal intervals (21 to 35 days) but with

heavy flow ( ≥80 mL) or duration ( ≥7 days).

Menometrorrhagia - Bleeding occurs at irregular, noncyclic intervals and with

heavy flow ( ≥80 mL) or duration ( ≥7 days).

Amenorrhea - Bleeding is absent for 6 months or more in a nonmenopausal

woman.

Metrorrhagia/ - Irregular bleeding occurs between ovulatory cycles causes to

intermenstrual consider include cervical disease intrauterine device,

bleeding endometritis, polyps, submucous myoma,

endometrial hyperplasia, and cancer.

Midcycle spotting - Spotting occurs just before ovulation, usually because of a

decline in the estrogen level.

Postmenopausal - Bleeding recurs in a menopausal woman at least 1year after

bleeding cessation of cycles.

Dysfunctional uterine - This ovulatory or anovulatory bleeding is diagnosed after the

bleeding exclusion of pregnancy, pregnancy- related disorders,

medications, iatrogenic causes obvious genital tract

pathology, and systemic conditions.

- 21 -

Over the past decade it has become abundantly clear that many terms used to

describe menstrual symptoms and causes of abnormal menstrual bleeding are ill

defined and confusing. 28

A formal initiative was established with an international workshop in

Washington, D.C., in 2005 which primarily addressed the most obvious and

confusing of issues around terminologies, definitions, and classifications of abnormal

uterine bleeding but also addressed issues that were less prominent at that time. These

additional issues included quality of life and obvious patient-based considerations;

cultural issues, and controversies around investigations and management.28

It was strongly recommended that poorly defined and confusing terminologies

such as menorrhagia, metrorrhagia, and dysfunctional uterine bleeding be abandoned.

In their place should be substituted clear and simple terms that women and men in the

general community could understand and could be easily translated into other

languages. These terms should be defined, and ideally the definitions should be based

on statistics derived from population studies. Extensive international discussions have

strongly recommended that certain terminologies be abandoned because of their

controversial, confusing, and poorly defined usage . These terminologies particularly

include several english language terms with Latin and Greek origins:

- 22 -

Table 1. Existing menstrual terminologies that in conscience with the current

PALM-COEIN system should be discarded 28

Menorrhagia (all usages, including "essential menorrhagia," "idiopathic

menorrhagia," "primary menorrhagia," "functional menorrhagia," "ovulatory or

anovulatory menorrhagia")

Metrorrhagia

Hypermenorrhea

Hypomenorrhea

Menometrorrhagia

Polymenorrhea

Polymenorrhagia

Epimenorrhea

Epimenorrhagia

Metropathica hemorrhagica

Uterine hemorrhage

Dysfunctional uterine bleeding

Functional uterine bleeding

A further term strongly recommended to be abandoned is dysfunctional uterine

bleeding (DUB), which was first used in 1935, never clearly defined, and is variably

used as a symptom and a diagnosis. It has mostly been used as a diagnosis of

exclusion where the underlying pathology has not been defined, but these underlying

mechanisms are being increasingly researched and defined.

- 23 -

Recommended terminology, definition, classification of symptoms of AUB 28

Disturbances of menstrual bleeding manifest in a wide range of presentations .

AUB is the overarching term used to describe any departure from normal

menstruation or from anormal menstrual cycle pattern. The key characteristics are

regularity, frequency, heaviness of flow, and duration of flow, but each of these may

exhibit considerable variability . Several abbreviations for these terminologies are

established or becoming established by increasing popular usage.

Table 2. Acceptable Abbreviations Describing Menstrual Symptoms Established

by Popular Usage28

AUB: Abnormal uterine bleeding (the overarching symptom)

HMB: Heavy menstrual bleeding

HPMB: Heavy and prolonged menstrual bleeding

IMB: Inter menstrual bleeding

PMB: Postmenopausal bleeding

Disturbances of Regularity 28

Irregular Menstrual Bleeding (IrregMB): "a range of varying lengths of bleeding-free

intervals exceeding 17 days within one 90-day reference period." These data include

women of varying ages but with no known pathology or hormonal therapy.

- 24 -

Absent Menstrual Bleeding (Amenorrhea): No bleeding in a 90-day period (some

authorities prefer to use a longer denominator). It is recommended that the term

amenorrhea be retained because there is little controversy in its use or definition.

Disturbances of Frequency28

Infrequent Menstrual Bleeding (Oligomenorrhea): One or two episodes in a 90-day

period. It is recommended that the term oligomenorrhea be abolished.

Frequent menstrual bleeding: More than four episodes in a 90-day period (this term

only includes frequent menstruation and not erratic intermenstrual bleeding; it is very

uncommon).

Disturbances of Heaviness of Flow28

Heavy Menstrual Bleeding (HMB): This is the most common clinical presentation of

AUB. The term was first used in New Zealand National Guidelines on HMB. It has

been well defined in the routine clinical context on the basis of the patient's presenting

complaint in the NICE Guidelines of the National Institute of Health and Clinical

Excellence of the United Kingdom: "HMB should be defined as excessive menstrual

blood loss which interferes with the woman's physical, emotional, social and material

quality of life, and which can occur alone or in combination with other symptoms." A

corollary of this definition is that any interventions should aim to improve quality of

life measures.

HMB also needs to be defined more objectively on a research basis as the

measurement of actual blood loss per menstrual period, using the extraction of

hemoglobin (alkaline hematin method) from menstrual sanitary supplies (pads and

tampons, carefully collected after detailed counseling). Clinicians and researchers also

- 25 -

need to be aware that >50% of the total menstrual loss is an endometrial transudate

and the whole blood component usually varies between 30% and 50%. HMB is

typically associated with a symptom complex, including variable pelvic pain and

somatic symptoms.

Heavy and Prolonged Menstrual Bleeding (HPMB): This complaint is much less

common than HMB on its own. The distinction from HMB is worth making because

these two symptomatic components may have different etiologies and may respond

differently to therapies.

Light Menstrual Bleeding: This is based on complaint by the patient, is only rarely

related to pathology, and is usually a cultural complaint in those communities where a

heavy, "red" bleed is valued as a perceived sign of health.

Disturbances of the Duration of Flow28

Prolonged Menstrual Bleeding: Recommended to be used to describe menstrual

periods that exceed 8 days in duration on a regular basis. This phenomenon is

commonly associated with heavy menstrual bleeding ("heavy and prolonged

menstrual bleeding" [HPMB]). This is much less common than HMB of normal

duration.

Shortened Menstrual Bleeding: A very uncommon complaint and defined as

menstrual bleeding of no longer than 2 days in duration. The bleeding is also usually

light in volume and is uncommonly associated with serious pathology (such as

intrauterine adhesions and endometrial tuberculosis)

- 26 -

Irregular Nonmenstrual Bleeding28

Nonmenstrual bleeding is common and usually consists of the occasional episode

of intermenstrual or postcoital bleeding associated with minor surface lesions of the

genital tract, but such bleeding may herald more serious lesions such as cervical or

endometrial cancer.

Intermenstrual bleeding is defined as irregular episodes of bleeding, often light

and short, occurring between otherwise fairly normal menstrual periods. This bleeding

may occasionally be prolonged or heavy, and it may occur on a regular basis around

ovulation as a physiological event in 1–2% of cycles. Women with surface lesions of

the genital tract may typically experience bleeding during or immediately after sexual

intercourse ( postcoital bleeding).

The term acyclic bleeding is rarely used but encompasses those few women who

present with totally erratic bleeding, with no discernable cyclic pattern, usually

associated with fairly advanced cervical or endometrial cancer. Premenstrual and

postmenstrual spotting (or staining) are descriptions of very light bleeding that may

occur regularly for ≥1 days before or after the recognized menstrual period. These

symptoms may be indicative of endometriosis or endometrial polyps or other

structural lesions of the genital tract.

Bleeding Outside Reproductive Age28

Precocious menstruation (occurring before 9 years of age) is uncommon and

usually associated with other signs of precocious puberty. Postmenopausal bleeding

(PMB) is common and usually defined as bleeding occurring >1 year after the

acknowledged menopause. "The menopause" is the last natural menstrual period that

a woman will experience and can only be determined in retrospect when a year of

- 27 -

amenorrhea has followed it. PMB is an important symptom because of its common

association with structural uterine pathology, including malignancy.

Acute or Chronic Abnormal Uterine Bleeding28

It is proposed that acute AUB is "an episode of bleeding in a woman of

reproductive age, who is not pregnant, that is of sufficient quantity to require

immediate intervention to prevent further blood loss." Chronic AUB is "bleeding from

the uterine corpus that is abnormal in duration, volume, and/or frequency and has

been present for the majority of the last 6 months."

Patterns of Bleeding28

In general, in the normal cycle, it is recognized that ~90% of the total menstrual

flow is lost within the first 3 days of menstruation, with day 1 or 2 the heaviest and

day 4 and 5 very light . However, in women with AUB, daily patterns of loss may be

highly variable.

Definitions of normal menstruation, menstrual cycle, and AUB28

Normal menstruation and the normal menstrual cycle should be defined according

to the following parameters : (1) regularity of menses, (2) frequency of menses, (3)

heaviness of menstrual flow, and (4) duration of menstrual flow.

- 28 -

Table 3. Suggested "Normal" Limits for Menstrual Parameters in the Mid-

Reproductive Years

Adapted from Fraser et al. It is recommended that these parameters be defined on the

basis of published population data, using medians and confidence intervals. Anything

outside these limits should be regarded as AUB. Different population studies provide

different data, and little is really known about cultural, ethnic, or geographic

Clinical Dimensions of

Menstruation

Cycle Descriptive

Terms Normal Limits

Menstruation and menstrual

Cycle (5–95th

percentiles)

Frequency of menses (days) Frequent <24

Normal 24–38

Infrequent >38

Regularity of menses, cycle to

cycle Variation over 12 months

(days)

Absent No bleeding

Regular Variation ±2 – 20

days

Irregular Variation >20

days

Duration of flow (days) Prolonged >8.0

Normal 4.5–8.0

Shortened <4.5

Volume of monthly blood loss

(mL) Heavy >80

Normal 5–80

Light <5

- 29 -

variations. Also, there is an apparent large variation within the normal population in

the regularity and frequency of menstrual periods when 5th to 95th centiles are used,

and this may need to be considered in situations where minor irregularities may gain

greater importance, such as infertility.

New Classification System 29

• The new system classifies uterine bleeding abnormalities by bleeding pattern as

well as by etiology.

• Other changes- heavy menstrual bleeding (HMB) (instead of menorrhagia) and

inter menstrual bleeding (IMB)(instead of metrorrhagia / menometrorrhagia).

• “The term dysfunctional uterine bleeding––often used synonymously with AUB in

the literature to indicate AUB for which there was no systemic or locally definable

structural cause––is not part of the PALM–COEIN system, and discontinuation of

its use is recommended.”

Classification System 29, 30 , 31

PALM –COEIN

• Polyp

• Adenomyosis

• Leiomyoma

• Malignancy and hyperplasia

• Coagulopathy

• Ovulatory dysfunction

• Endometrial

• Iatrogenic, and

• Not yet classified

- 30 -

PALM: Structural Causes

•Polyp (AUB-P)

•Adenomyosis (AUB-A)

•Leiomyoma (AUB-L)

– Submucosal myoma (AUB-LSM)

– Other myoma (AUB-LO)

•Malignancy & hyperplasia (AUB-M)

Polyp (AUB-P) 14,29,32

Endometrial polyps are benign and represent circumscribed foci of hyperplasia,

possibly due to decreased expression of hormone receptors in the stromal component.

Endometrial polyps are found in up to 50% of women presenting with abnormal

uterine bleeding. There is no precise etiology for the formation of these polyps but

they clearly originate from the endometrium.33

Grossly, they are pedunculated / sessile lesions with a fibrous stroma in

which characteristic thick-walled, tortuous and dilated blood vessels are found. The

glandular component is patchily distributed and shows cystically dilated and

occasionally crowded glands lined by an inactive, atrophic to weakly

proliferative endometrium. The glands and stroma of the polyp are unresponsive to

progesterone stimulation and retain their integrity throughout the cycle. Bleeding,

when it occurs is due to a fragile and friable vascular structure.

Polyps containing cyclic endometrium are called as functional polyp.

Polyps having smooth muscle fibres in addition to customary glands and

stroma are designated as adenomyomatous polyp. They have a characteristic

hard consistency. Polyps with glands occurring between the endometrial stroma and

smooth muscle exhibit varying degrees of hyperplasia and atypia are designated as

- 31 -

atypical polypoid adenomyoma. These are more common in premenopausal women

and present with abnormal uterine bleeding.

All types of endometrium including those showing signs of

hyperplasia can be found in polyps. Occasionally malignant transformation can

occur in the form of in- situ and invasive serous carcinomas.

Polyps should be differentiated from endometrial hyperplasias. The latter will

have active stromal cells, large vesicular nuclei and occasional mitotic figures

whereas the former will have stroma composed of spindle cells and large blood

vessels with thick walls.

Adenomyosis (AUB-A)

The term adenomyosis was initially used by Frankl who was the first to describe the

entity in detail.9

It refers to the presence of islands of endometrial glands and stroma

within the myometrium. It is made up of the non-functional (basal) layer of

the endometrium. The prevalence of adenomyosis vary widely ranging from 5% to

70%. 29

Grossly, the uterus is enlarged and globular in shape, due to the accompanying

myometrial hypertrophy. Cross section shows the presence of depressed

small cystic lesions in ill defined bulging zones of the muscle hypertrophy. 13

Microscopically, the diagnosis requires demonstrating the presence of

endometrial glands and stroma in the myometrium at a distance of at

least one low power field from the endo-myometrial junction. The

endometrium usually has a proliferative appearance.

- 32 -

Occasionally, adenomyosis may be only composed of endometrial

stroma and is known as stromal adenomyosis.

Histological criteria for diagnosis 34

Two of the following 3 components should be present to make the diagnosis.

1) Endometrial glands

2) Stroma

3) Haemosidirin laden macrophages

Leiomyoma (AUB-L)

Leiomyomas are extremely common benign fibro muscular tumors of the

myometrium.14 They are known by several names like leiomyoma, myoma and

fibroid. Fibroids are localized, benign proliferations of uterine smooth muscle tumors.

Occurs in women during childbearing age and then regress in menopause. 29

Uterine leiomyomas are usually diagnosed on physical examination. The overall

incidence is between 4% and 11%, but it rises to nearly 40% in women over the age

of 50 years. Clinically apparent lesions are less common in parous than nulliparous

women and premenopausal than postmenopausal women. They may occur singly but

often are multiple.14

They may cause a range of symptoms, from abnormal bleeding to pelvic pressure,

which may lead to the diagnosis. Fewer than one-half of uterine leiomyomas are

estimated to produce symptoms. The cause of uterine leiomyomas is unknown.

Several studies have suggested that each leiomyoma arises from a single neoplastic

cell within the smooth muscle of the myometrium . There appears to be an increased

familial incidence . Fibroids have the potential to enlarge during pregnancy as well as

to regress after menopause.

- 33 -

Classification of leiomyoma includes the relationship of the leiomyoma of the

endometrium and the serosa; the uterine location of the leiomyoma; the size of the

lesions; the number of the lesions.

The primary classification system reflects only the presence or absence of 1 or

more leiomyomas, regardless of the location, number and size.29

In the secondary classification system, the clinician is required to distinguish

leiomyomas involving the endometrial cavity (submucosal[SM]) from others because

it is generally submucosal lesions are most likely to contribute to AUB.29

Tertiary system is a design for subendometrial or submucosal leiomyomas that was

originally submitted by Wamsteker et al. and subsequently adopted by European

Society for Human Reproduction and Embryology (ESHRE). This system

has been in use worldwide for more than 15 years and was considered important

when designing the present system. As a result, the PALM-COEIN system includes

the categorization of intramural and subserosal leiomyomas, in addition to a

category that includes types such as the parasitic lesions that become detached

from the uterus after establishing blood supply from another source. When a

leiomyoma abuts or distorts both the endometrium and the serosa, it is categorized

initially via the submucosal classification, then by the subserosal location.29

The usual leiomyoma occurs within the myometrium as a well

circumscribed, solid white tumour, which may be single or multiple. They

bulge above the surrounding myometrium from which they are easily

shelled out. Cut surface are white to tan with a whorled trabecular

pattern and may show various patterns of degeneration. Although

they do not have a true capsule, the margins of the tumor are blunt, noninfiltrating,

- 34 -

and pushing, and are usually separated from the myometrium by a pseudo capsule of

connective tissue, which allows easy enucleation at the time of surgery. 11, 14

Microscopy:

Leiomyomas are typically composed of smooth muscle cells with bland,

uniform, cigar shaped nuclei arranged in interlacing bundles, showing little

or no mitotic activity. Nuclear chromatin is finely dispersed. The smooth

muscle cells are separated by viable amounts of collagen, which increases in

amount with age. Most leiomyomas are more cellular than surrounding

myometrium. The borders are usually sharply defined from surrounding

myometirum. Increased mitotic activity is associated with secretory phase of the

menstrual cycle.14

Malignancy & hyperplasia (AUB-M)

Endometrial hyperplasia is defined as a proliferation of glands of irregular size

and shape with an increase in the glands/stroma ratio.35

Endometrial hyperplasia is linked to the prolonged stimulation by

estrogen in anovulation or increased estrogen production. Conditions

promoting hyperplasia include obesity, polycystic ovarian disease, functioning

granulosa cell tumours of ovary and excessive cortical function.36

The classification that is currently preferred and sanctioned by WHO, originally

proposed by Kurman and Norris, divides hyperplasia into simple and complex on

the basis of architecture and subdivides each into typical and atypical on the

basis of cytology. 14

1. Hyperplasia without cytologic atypia (non atypical hyperplasia)

a) Simple

b) Complex

- 35 -

2. Hyperplasia with cytologic atypia (atypical hyperplasia)

a) Simple

b) Complex

1. Simple hyperplasia: is also known as cystic or simple hyperplasia and is

characterized by architectural changes in glands of various sizes,

producing irregularity in gland shape with cystic alterations. The glands,

although not increased in number, proliferate intensely and undergo cystic

dilatation; producing the characteristic Swiss cheese appearance in the endometrium.

The epithelial growth pattern and cytology are similar to those of

proliferative endometrium, and may uncommonly progress to

adenocarcinoma.

2. Complex hyperplasia: Is also known as adenomatous

hyperplasia. It exhibits an increase in the number and size of endometrial

glands, with glandular crowding and a disparity in budding with finger-like

outpouchings into the adjacent endometrial stroma and also into the

glandular lumina. The lining epithelium may appear more stratified

than simple hyperplasia but is regular in contour and devoid of conspicuous cytologic

atypia. Less than 5% of these lesions evolve into carcinoma.

3. Atypical hyperplasia: Is also termed as adenomatous hyperplasia with atypia.

In addition to glandular crowding and complexity, the epithelial lining

is irregular and characterized by stratification, scalloping and

tufting with cellular atypia, cytomegaly, loss of polarity, hyperchromasia,

prominent and altered nucleocytoplasmic ratio.

- 36 -

Endometrial carcinoma 32, 36

A primary malignant epithelial tumor, usually with glandular differentiation arising

in the endometrium that has the potential to invade into the myometrium and to spread

to distant sites.

Endometrial cancer is made up of a biologically and histologically diverse group of

neoplasm. “Estrogen dependent tumors Type I” are low grade and frequently

associated with endometrial hyperplasia, in particular atypical hyperplasia. Unopposed

estrogenic stimulation is the driving force behind this group of tumors. It may be the

result of anovulatory cycles that occur in young women with polycystic ovary

syndrome or due to normally occurring anovulatory cycles at the time of menopause.

The iatrogenic use of unopposed estrogens as hormone replacement therapy in older

women also is a predisposing factor for the development of the endometrial cancer.

The second type ‘‘ (Type II)” of endometrial cancer appears less related to sustained

estrogen stimulation.

Clinical Features:

Endometrial carcinoma can be incidental finding in the specimens, but majority of

the cases present with AUB (postmenopausal bleeding or menometrorrhagia).

Endometriod adenocarcinoma:

A primary endometrial adenocarcinoma containing glands resembling those of the

normal endometrium.

All but a few rare endometrial carcinomas are adenocarcinomas, and the most

common of these is the endometrioid type. Endometrioid adenocarcinoma represents a

spectrum of histological differentiation from a very well differentiated carcinoma

difficult to distinguish from atypical complex hyperplasia to minimally differentiated

- 37 -

tumors that can be confused not only with the undifferentiated carcinoma but with the

various sarcomas as well.

A highly characteristic features of endometrioid adenocarcinoma is the presence of

atleast some glandular or villoglandular structures lined by simple to pseudostratified

columnar cells that have their long axis arranged perpendicular to the basement

membrane with atleast somewhat elongated nuclei that are also polarized in the same

directions. As the glandular differentiation decreases and is replaced by solid nests and

sheets of cells, the tumor is classified as less well differentiated (higher grade).

Deep myometrial invasion and lymph node metastases are both more frequent in

higher grade carcinomas, and survival rates are correspondingly lower.

The distinction of very well differentiated endometrioid adenocarcinoma from atypical

hyperplasia is best provided by stromal disappearance between adjacent glands, i.e.

confluent, cribriform or villoglandular patterns. Other features that may be helpful

include a stromal foam cells may be associated with adenocarcinoma or its precursors.

COEIN: Nonstructural Causes

•Coagulopathy (AUB-C)

•Ovulatory dysfunction (AUB-O)

•Endometrial (AUB-E)

•Iatrogenic (AUB-I)

•Not yet classified (AUB-N)

Coagulopathy (AUB-C) 29

The term coagulopathy encompasses the spectrum of systemic disorders of hemostasis

that may be associated with AUB. Disorders are:

– von Willebrands Disease

- 38 -

– Coagulopathies

– Advanced Renal Disease

In 13% of the women with HMB most common cause is von Willebrands disease 29

Ovulatory dysfunction (AUB-O)

Formerly it was called anovulatory DUB. It can contribute to the genesis of AUB,

generally manifesting as a combination of bleeding and variable amount of flow

It is a disturbance of hypothalamic-pitutary-ovarian axis that results in heavy,

irregular, prolonged bleeding. Corpus luteum is not produced ovary fails to secrete

progesterone, although estrogen production continues and result is continuous,

unopposed estrogen stimulation of endometrium. 27

Persistent follicle PCO- prolonged cycle ( High estrogen level) hyperplastic or

proliferative endometrium 24

Insufficient follicles short cycle (low level of estrogen) Inadequate proliferative or

atrophic endometrium

The etiology are: 29

- Endocrinopathies ( Polycystic ovary syndrome, hypothyroidism,

hyperprolactinemia, mental stress, obesity, anorexia, weight

loss)

- Iatrogenic due to gonadal steroids

- Drugs ( Phenothiazines and tricyclic antidepressants)

Endometrial (AUB-E)

Formerly called as ovulatory DUB. It leads to heavy and regular bleeding.

Corpus luteum insufficiency- Insufficiency short luteal phase - Irregular ripening of

endometrium or deficient secretory endometrium. 24

- 39 -

Persistent Corpus luteum (Halban’s disease) - Irregular shedding of endometrium

Also leads to short cycle (short proliferative phase) and long cycle (long proliferative

phase)

Reduced levels29 :

1) Vasoconstrictors: PG F2α, Endothelin‐1

2) Clotting Mechanisms

– Tissue factor pathway

Increased levels:

• Vasodilator

– PG E2, PG I2

• Fibrinolytic Activity

Iatrogenic (AUB-I) 29

Include medicated or intrauterine systems and pharmacologic agents that directly

impact the endometrium, interfere with blood coagulation mechanisms, or influence

the systemic control of ovulation.

Bleeding that occurs during the use of gonadal steroid therapy is termed

" breakthrough bleeding"

Levonorgestrel- releasing intrauterine system

Tricyclic antidepressents

Phenothiazines

Anticoagulant drugs ( warfarin, heparin, low molecular weight heparin)

Not yet classified (AUB-N) 29

The conditions not been demonstrated are chronic endometritis, arteriovenous

malformation, myometrial hypertrophy.

In addition there are many disorders not yet identified, that could be defined only by

- 40 -

biochemical or molecular biology assays.

Causes of AUB by Age Group 38

• Neonates .

– Estrogen Withdrawal

• Premenarchal

– Foreign Body

– Adenomyosis

– Trauma, Abuse

– Vulvovaginitis

– Cancer (Sarcoma Botryoides)

– Precocious puberty Precocious Puberty

• Traditional: Thelarche before 8 years, pubarche before 9

years

Reproductive Age

– Anovulation

– Pregnancy

– Endocrine Disorder

– Polyps/fibroids/Adenomyosis

– Medication related (oral contraceptives)

– Infection

– Sarcoma, ovarian

– Coagulation disorder

Perimenopausal

– Anovulation leading to unopposed estrogen and

hyperplasia

- 41 -

– Polyp/Fibroid/Adenomyosis

– Cancer

• Postmenopausal

– Atrophy

– Cancer/polyp

– Estrogen therapy

– Selective Estrogen Receptor Modulators

- 42 -

CLINICO-PATHOLOGICAL CORRELATION STUDIES

In a clinico-pathological study of endometrium by Sanyal MK et al in different

gynaecological abnormalities, it was observed that proliferative endometrium

outnumbered all the other patterns in abnormal uterine bleeding. Abnormal uterine

bleeding comprised a large group (32%) of which functional uterine bleeding was

14% and bleeding due to structural causes was 18%.39

Devi PK et al did a clinical and histological study of 357 cases of

functional uterine haemorrhage, patients admitted for functional bleeding constituted

15-20% of all gynecological admissions. The type of menstrual disorder

according to various age groups was studied.40

In a review of 150 cases done by Kanakadurgamba K et al the maximum number

of patients was seen among the age group of 21-30 years, in contrast to the popular

teaching that, AUB occurs more frequently at either end of the child-bearing period.41

Ghosh BK et al did a correlative study of the endometrium and cyto-

hormonal pattern in functional uterine bleeding, histology of the endometrium

and vaginal cytology demonstrated hyperplasia and moderately high

maturation index, respectively in the majority of cases. Organic lesions were

detected in 66% of the cases, the main causes being fibroid and adenomyosis.42

In a review of 150 cases by Mehrotra VG et al an incidence of 8.32%

of functional uterine bleeding amongst total gynaecological cases was obtained,

which was lower when compared with other studies. 48% of cases fell in the age

group of 21-30 years.43

In a clinico-pathological correlation of abnormal uterine bleeding by

Sagar S in patients at or above the age of 45 years, non-secretory

- 43 -

endometrium was the commonest type in the premenopausal as well as

the post-menopausal group.12.2% of the post-menopausal women had malignancy

of the uterine body. 44

Histopathological finding of endometrial adenomatous hyperplasia

or cancer in about 15% of the post-menopausal women with bleeding was obtained in

a study done by Gredmark T et al, thereby justifying a thorough examination.

Trans-vaginal ultrasound examination should be included in the evaluation of post-

menopausal bleeding as endometrial biopsies of atrophic endometrium could

be avoided and ovarian pathology detected.45

Maheshwari V et al did a study of 104 cases of abnormal uterine

bleeding & it was found that proliferative (30.8%) type of endometrium

was the commonest, followed by secretory (25.8%), hyperplastic (20.2%),

irregular shedding (7.7%), malignancy (5.8%) and tuberculosis (3.8%).46

In a study of 260 cases of AUB by Muhammad et al , heavy menstrual bleeding

(51.9%) was the commonest symptom, common age was 41-50 years (48%),

with endometrial hyperplasia (24.7%) being the commonest pattern. The

study revealed that 40% of the curettings detected endometrial pathology

rendering D&C as an important diagnostic procedure.47

A study by Ayesha et al on types and frequencies of pathology in endometrial

curettings of 50 cases revealed clustering of cases around peri-

menopausal age with frequent menstrual bleeding as common symptom and

estrogen dominance being the commonest pattern.48

Shazia et al did a study of 100 cases of heavy menstrual bleeding in pre-

menopausal age group, proliferative endometrium (33%) was the commonest

followed secretory phase (26%), simple cystic hyperplasia (25%) and one case of

- 44 -

carcinoma endometrium. The fact that patients with heavy menstrual bleeding

above 40 years should be screened for any endometrial pathology was

emphasized.49

Sadia et al study showed that histopathological pattern of endometrium in patients

with abnormal uterine bleeding is variable regardless of age, parity, and ethnicity.

The most common pathological pattern identified was proliferative endometrium

(46.4%). Secretary phase endometrium was second most common pathology followed

by cystic, adenomatous and atypical hyperplasia.50

In a study done by Baral R et al, normal physiological changes were seen

predominantly under 40 years. Abnormal physiological changes and benign

conditions including hyperplasia’s were common in peri-menopausal age group

in a study of 300 cases. The importance of knowing the pattern of

endometrium in different age groups for correct patient management was

stressed up on.51

In another study of 128 cases of endometrial biopsies done by Parveen et al,

revealed frequent menstrual bleeding (35%) to be the commonest symptom,

hormonal disorder (18%) to be the commonest cause of AUB in <40

years. The most common finding was products of conception (67%). The second

predominant finding was related to hormonal balance (21%) which included

disordered proliferative, weakly proliferative, inactive endometrium, weakly

secretory, simple hyperplasia. The frequency of endometrial malignancy was

remarkable (07%).52

Layla et al did a study of 2295 cases, secretory endometrium (24.9%)

was found to be most common histologic pattern followed by proliferative

- 45 -

endometrium (21.7%). Uterine malignancies and complex hyperplasia with

atypia were common in the age group of 52 years and above. 53

In a study of 1000 cases by Talat et al, 57% showed non structural and

the rest 43% had structural causes for AUB. Proliferative endometrium (35%) was

the commonest pattern followed by secretory endometrium and disordered

proliferative endometrium. Hyperplasia (30%) was the commonest structural cause

followed by chronic endometritis (13%) and polyps ( 12%). Maximum cases were in

the perimenopausal age group. 5

In a study of 84 AUB cases by Dangal G, majority (53.5%) of them were

postmenopausal ladies ranging from 45-81 years. Malignant diseases were found

most commonly in postmenopausal ladies (24.3%) when compared to perimenopausal

age group (7.7%). 2

Another study conducted by Doraiswami et al, on 620 patients with AUB, it was

most commonly seen in 41 to 50 years age group. The predominant pattern noted was

normal cycling endometrium closely followed by disordered proliferative pattern. In

perimenopausal women dysfunctional uterine bleeding was the most common cause

for abnormal uterine bleeding. The incidence of proliferative pattern was significantly

high in this study.54

In a study of 152 cases of AUB by Ghani NA et al most common histological

pattern was proliferative phase endometrium (45.1%) followed by secretory pattern

(21.6%). Low grade endometrial hyperplasia was the most frequent structural cause.55

- 46 -

MATERIAL AND METHODS

SOURCE OF DATA

The present study was conducted in the Department of Pathology, MVJ Medical

College and Research Institute, Hoskote over a period 2 years from 2011 to

2013. Detailed clinical history was collected from the patients along with relevant

investigations as per the proforma.

INCLUSION CRITERIA

Reproductive women in all age groups attending department of OBG with

abnormal uterine bleeding.

EXCLUSION CRITERIA

Women with pregnancy complications, acute pelvic inflammatory disease,

abnormal cervical pap smear, previous abnormal endometrial biopsy, leiomyoma,

hemostatic disorders and women on hormonal treatment for abnormal uterine

bleeding were excluded.

METHODS OF COLLECTION OF DATA

The endometrial samples (endometrial curettage/ biopsy and hysterectomy

specimens) sent to pathology laboratory were analyzed.

These specimens are fixed in 10% formalin and gross morphology were recorded.

Endometrial samples were totally embedded and representative bits are taken

from hysterectomy specimens. These bits were placed in cassettes and kept in fixative

and processed in the automatic tissue processor.

Paraffin tissue blocks were prepared and 3-4 micrometer thick sections were cut

and stained with routine haematoxylin and eosin. A detailed histological study was

carried out and the findings were noted. Statistical analysis was done.

- 47 -

RESULTS

The present study comprises of evaluation of histopathological findings of

200 clinically diagnosed cases of AUB which were received at the

department of pathology, MVJ Medical and Research institute, Hoskote. The study

was conducted over a period of 24 months and the data was analysed under the

following headings:

1. Age distribution pattern (Table 4)

2. Relationship of AUB with Parity (Table 5)

3. Bleeding patterns in AUB patients (Table 6)

4. Histopathological findings in the present study (Table 7)

5. Patterns of distribution of histopathological findings among various age groups.

Reproductive age group (21-40 years) (Table 8)

Perimenopausal age group (Table 9)

Postmenopausal age group (Table 10)

6. The histopathological diagnosis among various age groups (Table 11)

7. Study of histopathological findings:

In correlation with Heavy menstrual bleeding (Menorrhagia) (Table 12)

In correlation with Inter menstrual bleeding ( Metrorrhagia) (Table 13)

In correlation with Heavy & prolonged bleeding ( Menometrorrhagia) (Table 14)

In correlation with Frequent menstrual bleeding ( Polymenorrhagia) (Table 15)

In correlation with Oligomenorrhea (Table 16)

- 48 -

Table 4: Age distribution pattern

Age group (years)

Number Percentage

<20 4 2%

21-25

18 9%

26-30 27 13.5%

31-35 24 12%

36-40 52 26%

41-45 28 14%

46-50

35 17.5%

>50 12 6%

Total 200 100%

The age of patients in the present study ranged from 17 to 65 years. The maximum

number of cases were seen in the age group of 36-40 years (26%) and minimum

number were seen in the age group of <20 years (02%).

Figure 1: Graph depicting age distribution pattern

0

10

20

30

40

50

60

<20 21‐25 26‐30 31‐35 36‐40 41‐45 46‐50 >50

No

of c

ases

Age in years

- 49 -

Table 5: Relationship of AUB with parity

Parity Number Percentage

Nulliparous 25 12.5%

Multiparous (1-3)

116 58%

Grand-multiparous (>3)

59 29.5%

Total 200 100%

The parity ranged from 0 to 4 in the present study. The incidence of AUB was

found to be highest in multiparous (58%) women followed by (29.5%) in

grandmultiparous and least in nulliparous women (12.5%).

Figure 2: Graph showing relationship of AUB with parity

- 50 -

Table 6: Distribution of bleeding patterns

Bleeding patterns Number Percentage

Heavy bleeding (Menorrhagia)

121 60.5%

Intermenstrual Bleeding(Metrorrhagia)

25 12.5%

Heavy & prolonged bleeding

(Menometrorrhagia)

16 8%

Frequent menstrual bleeding

(Polymenorrhagia)

12 6%

Oligomenorrhea 06 3%

Post menopausal Bleeding

20 10%

Total 200 100%

Heavy menstrual bleeding was the most common symptom accounting

for 60.5% of patients followed by intermenstrual bleeding accounting for

12.5% with the least being oligomenorrhea (3%).

Figure 3: Graph showing distribution of bleeding patterns

0

50

100

150 121

2516 12 6

20No

of c

ases

Patterns of bleeding

- 51 -

Table 7: Analysis of histopathological findings

Histological findings Number Percentage Proliferative Phase 70 35%

Secretory Phase 53 26.5% Simple hyperplasia

without atypia 48 24%

Complex hyperplasia with atypia

03 1.5%

Endometrial Polyp 04 2% Disordered Proliferative

endometrium 06 3%

Mixed endometrium 06 3% Atrophic

endometrium 07 3.5%

Endometrial adenocarcinoma

02 1%

Endometrial stromal sarcoma

01 0.5%

Total 200 100 Proliferative phase was the most common histopathological finding accounting

for 35% followed by secretory phase accounting for 26.5% , simple hyperplasia

without atypia accounting for 24% and the least commonly seen were

endometrial polyp 2% ,complex hyperplasia with atypia 1.5% , endometrial

adenocarcinoma 1% & endometrial stromal sarcoma 0.5%.

Figure 4: Graph showing distribution of histopathological patterns

0

20

40

60

80

No of cases

Histological patterns

- 52 -

Table 8: Pattern of distribution of histopathological findings in patients of the

reproductive age group (21-40 years)

There were 121 patients belonging to the reproductive age group

(21-40 years). Proliferative endometrium was the dominant histopathological finding

in this age group accounting for 41.3% followed by 33% of secretory

phase, 18.2% of simple hyperplasia without atypia, 4.2% of mixed endometrium ,

1.7% of complex hyperplasia with atypia and 0.8% each of polyp &endometrial

stromal sarcoma.

Figure 5: Graph showing distribution of histopathological pattern in reproductive age

Histopathological Findings

Number Percentage

Proliferative phase 50 41.3%

Secretory phase

40 33%

Simple hyperplasia without atypia

22 18.2%


02 1.7%

Mixed endometrium 05 4.2%

Endometrial Polyp 01 0.8%


01 0.8%

Total 121 100%

0

10

20

30

40

50

Histological patterns

- 53 -


peri-menopausal age group

Histopathological findings Number Percentage


Secretory phase 10 18.2%

Simple hyperplasia

without atypia

20 36.4%

Complex hyperplasia

with atypia

01 1.8%

Disordered proliferative

endometrium

04 7.3%


Endometrial Polyp 02 3.4%

Atrophic endometrium 03 5.6%

Endometrial

adenocarcinoma

01 1.8%

Total 55 100%

There were 55 patients belonging to the perimenopausal age group. Simple

hyperplasia without atypia was the dominant histopathological finding in

this age group accounting for 36.4% followed by 23.7% of proliferative phase,10%

of secretory phase, 7.3% of disordered proliferative, 5.6% of atrophic

endometrium, 3.4% of endometrial polyp, 1.8% each of mixed endometrium &

endometrial adenocarcinoma.

- 54 -


postmenopausal age group

Histopathological findings Number Percentage

Proliferative phase 04 20%

Secretory phase

02 10%

Simple hyperplasia

without atypia

06 30%

Atrophic endometrium 04 20%

Disordered proliferative

endometrium

02 10%

Endometrial Polyp 01 05%

Endometrial adenocarcinoma 01 05%

Total 20 100%

There were 20 patients belonging to the postmenopausal age group. Simple

hyperplasia without atypia was the dominant histopathological finding in

this age group accounting for 30% followed by 20% each of proliferative phase &

atrophic endometrium.10% each of secretory phase & disordered proliferative

endometrium. 5% each of endometrial polyp & endometrial adenocarcinoma.

Table 11: Histopathological diagnosis among various age groups

Age in yrs

Number

Proliferative phase

Secretory phase

SH with out atypia

Complex hyperplasia With atypia

Mixed endometrium

Endometrial polyp

Disordered proliferative endometrium

Atrophic endometrium

Endometrial adenocarcinoma


No % No

% No

% No % No % No % No % No % N % N %

<20 04 03 75 01 25 - - - - - - - - - - - - - - - -

21-30

45 17 37.8 21 46.7

05 11.1

01 2.2 01 2.2 - - - - - - - -

31-40

76 33 43.5 19 25 17 22.4

01 1.3 04 5.2 01 1.3 - - - - - - 01 1.3

41-50

63 16 25.4 12 19 21 33.3

01 1.6 01 1.6 02 3.2 06 9.5 03 4.8 01 1.6 - -

>50 12 01 8.3 - - 05 41.7

- - - - 01 8.3 - - 04 33.4 01 8.3 - -

Total

200 70 70 53 53 48 48 03 03 06 06 04 04 06 06 07 07 02 02 01 01

- 56 -

Table 12: Study of histopathological findings in correlation with heavy menstrual

bleeding

Histopathologic pattern Number Percentage




27 22.3%


01 0.9%


Disordered proliferative 03 2.4%

Atrophic endometrium 03 2.4%

Endometrial polyp 01 0.9%

Endometrial Adenocarcinoma

01 0.9%


01 0.9%

Total 121 100%

Proliferative phase of endometrium was the most common

histopathological finding in the patients who had presented with heavy

menstrual bleeding accounting for 38.8% followed by secretory phase 28.9%, Simple

endometrial hyperplasia without atypia 27%, disordered proliferative 2.4%, atrophic

endometrium 2.4%, 1.6% of mixed endometrium, 0.9% each of complex hyperplasia

with atypia, endometrial polyp, endometrial adenocarcinoma & endometrial stromal

sarcoma.

- 57 -

Table 13: Study of histopathological findings in correlation with intermenstrual

bleeding

Out of the 25 patients who presented with intermenstrual bleeding, proliferative phase

of endometrium was the most common histopathological finding accounting for 28%

followed by secretory phase 20%, simple hyperplasia without atypia 20% , mixed

endometrium 12%, complex hyperplasia without atypia 8%, endometrial polyp 8% &

disordered proliferative endometrium 4%.

Histopathologic pattern Number Percentage

Proliferative phase 07 28%

Secretory phase 05 20%

Simple hyperplasia

without atypia

05 20%

Complex hyperplasia

with atypia

02 08%

Mixed endometrium 03 12%

Disordered proliferative 01 04%

Endometrial polyp 02 08%

Total 25 100%

- 58 -

Table 14: Study of histopathological findings in correlation with heavy &

prolonged bleeding

Histopathological

findings

Number Percentage



Simple hyperplasia

without atypia

03 18.7%


Total 16 100%

Proliferative phase of endometrium 43.8% was the most common

histopathological finding in patients who presented with heavy & prolonged

bleeding followed by 31.3% of secretory phase 18.7% of simple hyperplasia without

atypia and 6.2% of mixed endometrium .

- 59 -

Table 15: Study of histopathological findings in correlation with Frequent

menstrual bleeding

Histopathological

findings

Number Percentage




03 25%

Total 12 100%

In patients who presented with frequent menstrual bleeding, proliferative phase was

the commonest histopathological finding in 41.6%, followed by secretory phase

33.4% & simple hyperplasia without atypia 25%.

Table 16: Study of histopathological findings in correlation with oligomennorhea

Histopathological findings

Number Percentage

Secretory phase 02 33%


04 67%

Total 06 100%

In patients who presented with oligomenorrhea, simple hyperplasia without atypia

was the commonest histopathological finding in 67%, followed by secretory

phase 33% .

- 60 -

Figure 6a: H&E (10x)

Figure 6b: H&E (40x) Figure 6: Proliferative phase with round to tubular glands lined by

pseudostratified epithelium ( as showed by arrow), surrounded by

cellular stroma

- 61 -


Figure 7b: H&E (40x) Figure 7: Secretory phase with tortuous glands showing subnuclear

vacuolation and oedematous stroma (as shown by arrow)

- 62 -


Figure 8b: H&E (10x) Figure 8: Simple hyperplasia without atypia with large cystically dilated

glands (as shown by arrow) against compact stroma

- 63 -


Figure 9b: H&E (40x)

Figure 9: Disordered proliferative endometrium showing glands with

stratification and edematous stroma

- 64 -


Figure 10b: H&E (10x) Figure 10: Mixed endometrium showing round, tourtuos glands and

with compact to edematous stroma

- 65 -


Figure 11b: H&E (40x) Figure 11: Atrpohic endometrium showing atrophic glands and increased

stroma

- 66 -


Figure 12b: H&E (40x) Figure 12: Endometrial polyp showing glands of varying sizes with

blood vessels of varying sizes in the fibrovascular core

- 67 -



Figure 13: Complex hyperplasia with atypia with overcrowding of glands,

complex glandular architecture with nuclear atypia

- 68 -



Figure 14: Endometrial adenocarcinoma showing overcrowding of

glands, intraglandular bridging, papillary projections with

nuclear atypia & mitosis (as shown by arrow)

- 69 -

Figure 15a: H & E (10X) Endometrial stromal tumor with infiltrating margin

Figure 15b :H & E (40X) Figure 15 : Endometrial Stromal Sarcoma showing minimal atypia

with tongue like protrusions of the stromal tumor into the

myometrium

- 70 -

DISCUSSION Abnormal uterine bleeding continues to be one of the most common and

perplexing problems in Gynaecological practice. It may present at any age between

puberty and menopause. It may be associated with various kinds of histopathological

findings in the endometrium.

Table 17: Comparative study of age incidence

The highest incidence of AUB was noted in the 31-40 years age group in the present

study which is in concordance with the results of the studies by Anusuya Das 57

(1964) and Bhattacharji 58 (1964) whereas Sutherland 54 (1950), Muhammed

Muzaffar 47 (2005), Doraiswami Saraswathi 54 (2011) reported maximum incidence in

41-50 years age group and Mehrotra et al 43 (1972), Wagh and Swamy59 (1964) and

Dawn 60 (1964) reported maximum incidence in 21-30 years age group.

Authors

No

<20

21-30

31-40

41-50

51 and above

Total % Total % Total % Total % Total % Sutherland56

(1950) 1000 36 3.6 242 24.2 343 34.3 362 36.2 17 1.7

Anusuya

Das 57

(1964)

117 17 14.5 24 20.5 33 28.2 38 32.5 5 4.3

Bhattacharji 58

(1964)

164 14 8.5 50 30.5 56 34.2 44 26.8 - -

Wagh and Swamy59

(1964)

552 97 17.6 215 39 143 25.9 94 17 3 0.5

Mehrotra 43

(1972) 150 15 10 72 48 35 23.3 25 16.7 3 2

Muzaffar47

(2005) 260 0 0 33 12.7 102 39.2 125 48.1 - -

Saraswathi 54

(2011)

409 6 1.5 85 20.8 116 28.4 137 33.5 65 15.8

Present Study(2013)

200 4 2 45 22.5 76 38 63 31.5 12 6

- 71 -

Considering these discrepant observations, one may conclude that, any age after

menarche is not exempt from AUB .The highest incidence of AUB was seen in the

reproductive age group(21-40 years) in the present study (60.5%) which is in

concordance with the results of the studies by Sutherland 56 (58.5%) and Mehrotra VG

et al 43 (71.3%) .

Table 18: Parity and Abnormal uterine bleeding

In the present study, the highest incidence of AUB was seen in multiparous (58%),

which is in concordance with the results of the studies by Bhattacharji 58 (46%),

Devi PK 39 (48.6%), Pillai 61(87%), Joshi and Deshpande 62 (61.5%) , Mehrotra

VG et al43 (46%) and Sadia K50 (54%). The lowest incidence was seen in nulliparous

women in the present study which is in concordance with the results of the studies by

Mehrotra et al43 (20%), Anusuya Das57 (18%), Joshi and Deshpande62 (21.2%) ,

Bhattacharji58 ( 18.8%) and Sadia K50 (5.4%). By these observations, it may be

implied that incidence of AUB is highest in parous women in general 87.5% and

multipara in particular 58%.

Parity

Sadia Khan 50 Present study

Number Percentage Number Percentage

Nullipara 27 5.4 25 12.5%

Multipara 270 54 116 58%

Grandmultipara 203 35.6 59 29.5%

Total 500 100 200 100%

- 72 -

Table 19: Comparative study of types of bleeding and AUB

Type of bleeding Mehrotra VG 43 Present study Number Percentage Number Percentage

Heavy menstrual bleeding

(Menorrhagia)

78 52 121 60.5%

Inter menstrual Bleeding

(Metrorrhagia)

29 19.33 25 12.5%

Heavy & prolonged bleeding

(Menometrorrhagia)

0 0 16 8%

Frequent menstrual bleeding

(Polymenorrhea)

39 26 12 6%

Oligomenorrhea 0 0 06 3% Post menopausal

Bleeding 4 2.67 20 10%

Total

150

100

200

100%

In the present study, heavy menstrual bleeding was the commonest type of

bleeding (60.5%) followed by intermenstrual bleeding (12.5%), post

menopausal bleeding(10%) , heavy and prolonged bleeding (8%), frequent menstrual

bleeding (6%) and oligomennorhea (3%) in that order, whereas in the study by

Mehrotra VG 43 showed heavy menstrual bleeding was the commonest type of

bleeding followed by frequent menstrual bleeding , inter menstrual bleeding and

postmenopausal bleeding in that order.

- 73 -

Table 20: Analysis of histopathological findings

In the present study proliferative phase(35%) was found to be most common

histologic pattern followed by secretory phase (26.5%), simple hyperplasia without

atypia (24%), atrophic endometrium (3.5%), disordered proliferative (3%), mixed

endometrium (3%), endometrial polyp(2%), endometrial adenocarcinoma (1%) and

endometrial stromal sarcoma (0.5%). In the study done by Sadia Khan 50 ,

proliferative phase was most common histological pattern followed by secretory

phase, simple hyperplasia without atypia, complex hyperplasia without atypia,

atrophic endometrium, endometrial polyp, endometritis and endometrial

adenocarcinoma in that order.

Histological findings

Sadia Khan50 Present study Number Percentage Number Percentage

Proliferative Phase 233 46.6 70 35% Secretory Phase 192 38.4 53 26.5%


32 6.4 48 24%

Simple hyperplasia with atypia

12 2.4 0 0

Complex hyperplasia without atypia

14 2.8 0 0


0 0 03 1.5%

Endometrial polyp 3 0.6 04 2% Disordered Proliferative

endometrium 0 0 06 3%

Mixed endometrium 0 0 06 3% Endometritis 2 0.4 0 0

Atrophic endometrium 5 1 07 3.5% Endometrial Adenocarcinoma 2 0.4 02 1% Endometrial stromal sarcoma 0 0 01 0.5%

Total 500 100 200 100

- 74 -

Table 21: Comparative study of incidence of endometrial hyperplasia in AUB

Majority of the studies including the present study indicate that, the

incidence of hyperplasia in AUB ranges from 19.4% to 31.25% whereas,

a few other studies reported a higher incidence at 52 % to 62% range

while the lowest incidence 7% was reported by Sanyal 39.

In the present study, the two important observations were made

regarding endometrial hyperplasia in AUB and they are:

1) Endometrial hyperplasia was highest in the age group of 41-50 years (Table 11).

2) It was highest in patients with history of heavy menstrual bleeding (Table 12).

Authors Year Number Percentage with Endometrial hyperplasia

Traut et al63 1935 - 58% Sutherland 56 1950 1000 15.5%

Devi and Sutaria40 1964 357 23.5% Joshi and

Deshpande62 1964 208 19%

Kanakadurgamba41 1964 150 62% Bhattacharji58 1964 164 29.2%

Anusuya Dass57 1964 117 30.6% Mehrotra43 1972 150 19.4% Sanyal39 1980 3920 07% Pillai61 2002 100 44%

Talat Mirza5 2012 1000 13% Present study 2013 200 25.5%

- 75 -

Table22: Comparative study of incidence of atrophic endometrium in AUB

Dangal G 2 study noted maximum cases of atrophic endometrium accounting for

64.4% which was most common in post menopausal age group, whereas

Jairapuri ZS 65 noted minimum incidence of 1.10%. In the present study incidence of

atrophic endometrium was noted in 3.5%.

Table 23: Comparative study of incidence of mixed endometrium in AUB

Al-Neaimy WMT66 noted maximum number of cases of mixed endometrium

accounting for 8.3% whereas, Sutherland56 noted minimum incidence of mixed

endometrium (1.3%). In the present study, the incidence of mixed endometrium was

03% .

Authors Year Number Percentage

Dangal G 2 2003 84 64.4%

Bhatta S 64 2012 122 7.38%

Jairapuri ZS 65 2013 638 1.10%

Present study 2013 200 3.5%


Sutherland56 1950 1000 1.3%

Al-Neaimy WMT66 2010 363 8.3%

Present study 2013 200 3%

- 76 -

Table 24: Comparative study of incidence of disordered proliferative

endometrium in AUB

Mirza T5 noted maximum number of disordered proliferative endometrium accounting

for the 23%. In the present study , the incidence of disordered proliferative

endometrium was 3% which was close to the findings observed by Azim P 52.

Incidence of structural causes detected histopathologically in clinically

diagnosed AUB cases

In the present study, there were 07 (3.5%) cases of structural causes

detected on histopathological examination of endometrial biopsies from

clinically diagnosed AUB cases, out of which 04 cases (2%) were endometrial

polyp, 02 cases (1%) of endometrial adenocarcinomas and 01 case (0.5%) of

endometrial stromal sarcoma.


Azim P 52 2011 128 5.4%

Mirza T 5 2012 1000 23%

Bhatta S 64 2012 122 6.56%

Present study 2013 200 3%

- 77 -

CONCLUSION AUB is one of the most common problem in women of all age groups in

reproductive period. It is challenging gynecological problem caused by various

endometrial pathologies.

Endometrium is the mirror of hormonal status in women. Histological variations

can be seen in the endometrium according to age of women and phase of her

menstrual cycle and any other specific pathology.

Endometrial sampling could be effectively used as the first diagnostic step in

abnormal uterine bleeding although at times its interpretation could be quite

challenging to the practicing pathologist. It is a simple, cost-effective and appropriate

method that provides accurate diagnostic yield. The present study highlights the

importance of endometrial biopsy and its interpretation which plays a pivotal role in

the management of AUB.

Histopathological examination of endometrial biopsies in patients of abnormal

uterine bleeding shows a wide spectrum of changes ranging from normal

endometrium in various hormonal cycles to malignancy. In present study, the most

frequent finding seen in patients with AUB in there productive age group was

proliferative phase. In peri and postmenopausal women simple hyperplasia without

atypia was most frequently noted.

Cases of endometrial polyp, endometrial adenocarcinomas and endometrial

stromal sarcoma which are rare findings in clinically diagnosed cases of AUB were

seen in the present study.

- 78 -

Accurate diagnosis of the causative factor of abnormal uterine bleeding in any age

group is of importance so that appropriate management can be initiated. Therefore

histological characteristics of endometrial samples as assessed by light microscopy

remains the gold standard for clinical diagnosis of endometrial pathology.

- 79 -

SUMMARY A study of 200 patients in clinically diagnosed with abnormal uterine

bleeding was carried out from December 2011 to May 2013. Endometrial biopsy

specimens which were received at the Pathology Department of MVJ Medical

College and Research Hospital, Hoskote were studied by routine

histopathological examination.

Outcome of the Clinical and Histopathological findings were as follows:-

1. Patients belonging to various age groups were taken up for the study. The

maximum incidence of AUB was in the 36-40 years age group. The minimum

incidence of AUB was in 17-20 years age group (Table 4).

2. With respect to parity of subjects, maximum incidence of abnormal uterine

bleeding was seen in the parity of 1-3 (58%) and minimum incidence in

nulliparous women 12.5% (Table 5).

3. Histopathology of endometrium showed Proliferative endometrium in

30%, Secretory endometrium in 26.5%, Simple hyperplasia without atypia

in 24%, Complex hyperplasia with atypia in 1.5%, Atrophic endometrium

in 3.5%, Mixed endometrium in 3%, Disordered proliferative endometrium in 3%,

Endometrial polyp in 2%, Endometrial adenocarcinoma in 01%,

Endometrial stromal sarcoma in 0.5% (Table 7).

4. Histopathology of endometrium in the age group of 17-20 years showed 75%

of Proliferative endometrium, 25% of secretory endometrium (Table11).

5. Histopathology of endometrium in the age group of 21-30 years

showed Proliferative phase in 37.8%, Secretory phase in 46.7%, Simple

hyperplasia without atypia in 5%, Complex hyperplasia with atypia in 2.2% and

Mixed endometrium in 2.2% (Table11).

- 80 -


showed Proliferative phase in 43.5%, Secretory phase in 25%, Simple

hyperplasia without atypia in 22.4%, Complex hyperplasia with atypia in

1.3% , Mixed endometrium in 5.2% , 1.3% each of Endometrial polyp and

Endometrial stromal sarcoma(Table11).


showed Proliferative endometrium in 25.4%, Secretory endometrium in 19%, Simple

hyperplasia without atypia in 33.3%, Disordered proliferative endometrium in

9.5%, 4.8% of atrophic endometrium, 3.2% of Endometrial polyp and 1.6% each of

Complex hyperplasia with atypia, Mixed endometrium and Endometrial

adenocarcinoma(Table 11).

8 Histopathology of endometrium in the age group of >50 years showed

Proliferative endometrium in 8.3%, Simple hyperplasia without atypia in 41.7%,

atrophic endometrium in 33.4%, 8.3% each of Endometrial polyp and Endometrial

adenocarcinoma(Table11).

9. Incidence of underlying structural causes was 3.5% which included 04 cases of

Endometrial polyp, 02 cases of Endometrial adenocarcinomas and 01 case

of Endometrial stromal sarcoma.

10. The most common type of bleeding pattern observed was Heavy

menstrual bleeding in 60.5%, followed by intermenstrual bleeding in 12.5% of

patients (Table 6).

11. The new classification system approved for the causes of AUB by International

Federation of Gynecology and Obstetrics (FIGO) is PALM-COIEN : Polyp,

adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory

dysfunction, iatrogenic, endometrial causes and not yet classified.

- 81 -

12. The new terminologies have been approved by FIGO and they are :-

a) Heavy menstrual bleeding (HMB) should replace menorrhagia to describe excess

of bleeding.

b) Inter menstrual bleeding (IMB) that occurs between clearly defined cyclic and

predictable menses should replace the term metrorrhagia

c) Heavy and prolonged bleeding (HPB) should replace menometrorrhagia and

frequent menstrual bleeding should replace polymennorhea

13. In view of the recommendation by FIGO, it is proposed to incorporate the new

classification in future. However in the present study we have adopted new

terminologies for various bleeding conditions as recommended by FIGO.

- 82 -

BIBILOGRAPHY

1. Demopoulous RL. Normal endometrium. Ch.9. In : Kurman RJ editor. Blaustein’s Pathology of Female Genital tract. 5th ed. New York: Springer Verlag; 2002. 235-227.

2. Dangal G. A study of endometrium of patients with abnormal uterine bleeding at Chitwan valley. Kathmandu University Medical Journal. 2003; 1(2): 110-112. 3. Khare A, Bansal.R, Sharma.S et al. Morphological spectrum of endometrium in patients presenting with dysfunctional uterine bleeding. People's Journal of Scientific Research.2012; 5(2): 13-16. 4. Livingstone M, Fraser IS. Mechanisms of Abnormal uterine bleeding. Human Reproduction Update. 2002; 8(1): 60-7. 5. Mirza T, Akram S, Mirza A, Aziz S, Mirza T, Mustansar T. Histopathological Pattern of Abnormal Uterine Bleeding in Endometrial Biopsies. J Basic and Applied Sciences. 2012; 8: 114-7. 6. Hunter DC, McClure N. Abnormal uterine bleeding: an evaluation endometrial biopsy, vaginal ultrasound and outpatient hysteroscopy. The Ulster Medical Journal. 2001; 70(1): 25-30. 7. Fleihmann C.F. Text book of menstrual disorder and treatment, 1956. 8. William B.J and Roberston, The abnormal menstrual cycle. Text book of endometrium, Butterworth 1981: 45-72. 9. Malcolm G. Munro. Historical context. Abnormal Uterine Bleeding. Cambridge University Press: 2010: 1-7. 10. Ian S. Frasera, Hilary O.D. Critchleyb and Malcolm G. Munroc; Abnormal uterine bleeding: getting our terminology straight. Curr Opin Obstet Gynecol 2007 ; 19: 591-595.

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11. Hendrickson MR, Kempson RL. Pure Mesenchymal Tumours of the Uterine Corpus In: Fox H, Wells M, editors. Obstetrical and Gynaecological Pathology. 5th ed, vol.2. New York: Churchill Livingstone, 2003: 538-545. 12. Uterus. In: Standring S, editor. Gray’s Anatomy, The Anatomical Basis of Clinical Practice. 39th ed. Spain: Elsevier, 2005: 1331-9. 13. Zalovdek C, Hendrickson M. Mesenchymal Tumours of the Uterus. In: Kurman RJ, editor. Blaustein’s Pathology of the Female Genital Tract . 5th ed. Baltimore: Springer-Verlag, 2002: 564-74. 14. Rosai J. Female reproductive system- Uterus: corpus. Rosai and Ackerman’s Surgical Pathology. 10th ed. Vol 2. India: Elsevier; 2012: 1487-92. 15. Female Reproductive tract. In: Young B, Lowe JS, Stevens A, Heath JW, editors. Wheater’s Functional Histology. A Text and Color Atlas. 5th ed. India: Elsevier, 2006: 369-75. 16. Fraser I S, Critchley H O, Munro M G, et al. A process designed to lead to international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril 2007; 87:466. . 17. Palter SF, David L Olive. Reproductive physiology. In: Jonathan S Berek editor. Novak’s Gynecology. 12th ed. Maryland: Lippincott William and Wilkins, 1996: 149-74. 18. Speroff L, Robert H Glass, Nathan G Kase. Regulation of the Menstrual cycle. In: Charles Mitchell, editor. Clinical Gynecologic Endocrinology and Infertility. 6th ed. Maryland: Lippincott Williams and Wilkins, 1999: 201-46. 19. More Ian AR. The normal human endometrium. In: Fox H, editor. Haines and Taylor Obstetrical and Gynaecological Pathology. 4th ed. Philadelphia: Churchill Livingstone, 1995: 365-82.

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20. Dallenbach-Hellweg G. Histopathology of the endometrium. 4th ed. Berlin: Springer-Verlag, 1987: 55-165. 21. Anderson MC. The normal uterus. In: Symmers WStC, editor. Female reproductive system: Systemic Pathology. 5th ed . Edinburgh: Churchill Livingstone, 1991: 129-145. 22. Noyes RW, Haman JO. Accuracy of endometrial dating. Fertil Steril . 1954; 4: 504-17. 23. Merrill JA. The Interpretation of Endometrial Biopsies. Cl Obs Gynaec. 1991 Mar; 34(1): 211-21. 24. Davey DA. Dysfunctional uterinal bleeding.In: Charles R Whitefield, editor. Dewhurst’s Text book of Obstetrics and Gynaecology for post graduates. 5 ed. Oxford: Blackwell Science, 1995: 590-608. 25. Subhankar D, Barunoday C, Relaul K, Kanti AR, Kumar MP, Kumar GT. Abnormal uterine bleeding in peimenopausal age: Diagnostic options and accuracy. J of obstetrics and gynaecology of India. 2011 April: 189-194. 26. Albers JR, Hull SK , Wesley RM. Abnormal uterine bleeding. American family physician. 2004 April; 69(8): 1915-26. 27. Fazio SB, Ship AN. Abnormal uterine bleeding. Southern medical journal. 2007 April; 100(4): 376-82. 28. Fraser IS, Critchley HOD, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011; 29(5): 383-390. 29. Munro GM, Critchley HOD, Broder MS, Fraser IS. FIGO classification system (PALM - COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. International Journal of Gyne and Obste. 2011;113: 3-13.

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30. Munro GM, Critchley HOD, Broder MS, Fraser IS. The FIGO systems for nomenclature and classification of causes of abnormal uterine bleeding in the reproductive years: who needs them?. American Journal of Obst & Gyne. 2012: 259-65. 31. Qureshi FU, Yusuf AW. Distribution of causes of abnormal uterine bleeding using the new FIGO classification system. J Pak Med Assoc. 2013; 63(8): 973-75. 32 .Silverberg SG, Kurman RJ, Nogales F, Mutter GL, Kubik-Huch RA, Tavassoli FA. Epithelial Tumors and Related Lesions. Tumours of the Uterine Corpus. In: Tavassoli FA, Devilee P, editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC Press, 2003: 228-30. 33. David ND. Abnormal uterine bleeding. In: James R., Md. Scott, Ronald S., Md. Gibbs, Beth Y., Md. Karlan, Arthur F., Md. Haney, editors. Danforth's Obstetrics and Gynecology. 9th ed. Lippincott Williams & Wilkins Publishers, August 2003: 355. 34. Shariff S. Female genital system. Fundamentals of surgical pathology. New Delhi, India: Jaypee Brothers Medical Publisher (P) Ltd, 2010: 28. 35. Montgomery BE, Daum GS, Dunton CJ. Endometrial hyperplasia: A Review. Obstetrical and Gynecological Survey. 2004; 59(5): 368-378. 36. Menorrhagia and Dysfunctional Uterine Bleeding. In: Padubidri VG, Daftary SN, editors. Howkins and Bourne Shaw’s Textbook of Gynecology. 13th ed. India: Elsevier, 2004: 291-99. 37. Hendrickson MR, Longacre TA, Kempson RL. The Uterine Corpus. In: Mills SE, Carter D, Greenson JK, Oberman HA, Reuter V, Stoler MH, editors. Sternberg’s Diagnostic Surgical Pathology. 4th ed. Noida, India: Jaypee

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Brothers Medical Publisher (P) Ltd, 2004: 2435-525. 38. Daniels RV, McCuskey C. Abnormal vaginal bleeding in a non pregnant patient. Emerg Med Clin N Am.2003; 21: 751-772. 39. Sanyal MK, Sanyal S, Bhattacherjee KK, Roy Choudhuri NN. Clinicopathological study of endometrium: A review of three thousand nine hundred twenty cases in different gynaecological abnormalities. J Obstet Gynaecol India. 1981; 31(5): 816-21. 40. Devi, PK, Sutaria UD. Functional uterine Bleeding (A clinical and histological Study of 357 Cases. J Obstet and Gynecol India. 1964; 14(2): 355-9. 41. Kanakadurgamba K, Srinivasa Rao K. A clinical and histopathological review of Dysfunctional Uterine Bleeding, One hundred and fifty cases. J Obstet and Gynecol India. 1964; 14: 380-6. 42. Ghosh BK, Sengupta KP. A study of the endometrium and cytohormonal pattern in functional uterine bleeding. J Obstet Gynaecol India. 1968; 18: 310-6. 43. Mehrotra VG, Mukerjee K, Pandey M, Samanth V. Functional uterine bleeding (A review of 150 cases). J Obstet Gynaecol India. 1972; 22: 684-9. 44. Sagar S. Clinicopathological correlation of abnormal uterine bleeding in patients at the age of 45 years and above. J Obstet Gynaecol India. 1980; 30:165-9. 45. Gredmark T, Kvint S, Havel G, Mattssom L. Histopatological findings in women with postmenopausal bleeding. Br J Obstet Gynaecol. 1995; 102: 133-6. 46. Maheshwari V, Chakrabarti AK, Tyagi SP, Sharma R, Alam K, Mohsin S.Endometrial changes in abnormal uterine bleeding. J Obstet

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Gynaecol India. 1996; 46(3): 389-94. 47. Muzaffar M, Akhtar KAK, Yasmin S, Mahmood-ur-Rehman, Iqbal W, Khan MA. Menstrual Irregularities with excessive blood loss: a Clinico-Pathological Correlation. J Pak Med Assoc. 2005; 55(11): 486-9. 48. Ayesha S, Anwar UH. Types and Frequencies of Pathologies in Endometrial Curettings of Abnormal Uterine Bleeding. International J Path. 2005; 3(2): 65-70. 49. Riaz S, Ibrar F, Dawood NS, Jabeen A. Endometrial Pathology by Endometrial Curettage in Menorrhagia in Premenopausal age group. J Ayub Med Coll Abbottabad. 2010; 22(3): 161-4. 50. Khan S, Hameed Sadia, Umber A. Histopathological Pattern of Endometrium on Diagnostic D&C in patients with Abnormal Uterine Bleeding. Annals 2011; 17(2): 166-70. 51. Baral R, Pudasaini S. Histopathological pattern of endometrial samples in abnormal uterine bleeding. J Path Nepal .2011; 1: 13-6. 52. Azim P, Khan MM, Sharif N, Khattak EG. Evaluation of abnormal uterine bleeding on endometrial biopsies. Isra Medical J. 2011; 3(3): 84-8. 53. Abdullah LS, Bondagji NS. Histopathological pattern of Endometrial Sampling Performed for Abnormal uterine bleeding. Bahrain Medical Bulletin. 2011; 33(4): 1-5. 54. Saraswathi D, Thanka J, Shalinee R, Aarathi R, Jaya V, Kumar PV. Study of Endometrial Pathology in Abnormal Uterine Bleeding. Journal of Obstetrics and Gynecology of India. 2011 July-August; 61(4): 426-430. 55. Ghani NA, Abdulrazak AA, Abdullah EM. Abnormal uterine bleeding: A histopathological study. World reasearch journal of pathology. 2012; 1(1): 06-08.

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56. Sutherland AM. Recent Advances in Obstetrics and Gynecology. Bourne A William JA. 1962;365-81. 57. Dass Anusuya, Chugh S. Dysfunctional uterine Bleeding – A Clinico- pathological Study. J Obstet and Gynecol India. 1964; 14(2): 343-7. 58. Bhattacharji SK. Dysfunctional Uterine bleeding Correlation of endometrial pattern with clinical behavior. J. Obstet and Gynecol India. 1964; 14(2): 372-9. 59. Wagh KV, Swamy V. Functional uterine Haemorrhage. J Obstet and Gynecol India. 1964; 14: 87-392. 60. Dawn CS. Environment and dysfunctional uterine haemorrhage. J Obstet Gynaecol India. 1964; 14: 408-12. 61. Pillai GS, Sethi B, Dhaded AV, Mathur PR. Dysfunctional Uterine Bleeding (Study of 100 cases). J Obstet Gynaecol India. 2002; 52(3): 87-9. 62. Joshi SK, Deshpande DH Clinico-pathological study in 274 cases of Dysfunctional Uterine Haemorrhage. J Obstet and Gynecol India. 1964; 14(2): 360-71. 63. Traut HF, Kuder A. Irregular shedding & irregular ripening of the endometrium. Surg- Gynecol & Obstet. 1935; 61(2): 145-154. 64. Bhatta S, Sinha AK. Histopathological study of endometrium in abnormal uterine bleeding. Journal of pathology of Nepal. 2012; 2: 297-300. 65. Jairapuri ZS, Rana S, Jetley S. Atypical uterine bleeding-Histopathological audit of endometrium A study of 638 cases. Al Ameen J Med Sci. 2013; 6(1): 21-28. 66. Al-Neaimy WMT, Ahmed MT, Al-Jawadi SI. Histopathological Interpretation of Abnormal uterine bleeding after the age of 40 year. The Iraqi postgraduate medical journal. 2010; 9(3): 274-282.

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PROFORMA

Name: Age: Occupation:

Address: IP/OP no: Date:

Histopathology no: Case no:

Clinical details

1) H/O

□ Heavy menstrual bleeding

□ Intermenstrual bleeding

□ Heavy and prolonged bleeding

□ Frequent menstrual bleeding

□ Oligomennorhea

□ Post menopausal bleeding

2) Amount: Duration: Interval:

Obstetric history

1) Married life: 2) No. of children: 3)Last delivery

4) Tubectomised □ Yes □ No

Menstrual history

1) Age of menarche:

2) Menstrual cycle: □ Regular □ Irregular

3) Perimenopausal: □ Yes □ No

4) Postmenopausal: □ Yes □ No

5) Age of menopause:

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Past history

H/o TB, DM, hypertension, any previous surgeries: □ Yes □ No

General physical examination

Pulse: BP:

Pallor: □ Yes □ No Icterus: □ Yes □ No

Lympadenopathy: □ Yes □ No

Oedema: □ Yes □ No

Systemic examination:

CVS:

Perabdomen:

RS:

CNS:

Pervagina:

Provisional Clinical diagnosis:

Investigations:

Hb%: TC:

DC: Platelet count:

Blood picture:

BT/ CT:

Urine- Albumin: Sugar:

Microscopy:

Thyroid function tests: Hormonal profile:

USG done: □ Yes □ No

Findings:

Procedure done:

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□ D&C □ Endometrial biopsy □ Hysterectomy

Histopathological Examination:

Gross:

Microscopy:

Final Histopathological diagnosis:

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KEY TO MASTER CHART AUB Abnormal uterine bleeding

Para Parity

PP Proliferative phase

SH Simple hyperplasia without atypia

SP Secretory phase

CH Complex hyperplasia

Endometrial Ca Endometrial adenocarcinoma

Polyp Endometrial polyp

ESS Endometrial Stromal Sarcoma

HMB Heavy menstrual bleeding

IMB Intermenstrual bleeding

HPMB Heavy and prolonged menstrual bleeding

FMB Frequent menstrual bleeding

PMB Post menopausal bleeding

UM Unmarried

MASTER CHART Sl

.No

IP.N

o

Nam

e of

the

patie

nt

Age

(Yea

rs)

Para

Clin

ical

Dia

gnos

is

His

topa

thol

ogic

D

iagn

osis

HM

B

IMB

H&

PB

FMB

Olig

pmen

norh

ea

PMB

1 207414 Sakamma 22 1 AUB Proliferative + 2 210186 Gayathri 29 UM AUB Proliferative + 3 214181 Jayalakshmamma 25 2 AUB Secretory + 4 218897 Gowramma 23 1 AUB Secretory + 5 221146 Gowramma 33 2 AUB Proliferative + 6 224385 Sharadamma 35 3 AUB Proliferative + 7 226921 Manjula 38 3 AUB Proliferative + 8 172513 Kamala 40 2 AUB Secretory + 9 177039 Radha 39 3 AUB Secretory + 10 179342 Varalakshmi 38 2 AUB SH + 11 185492 Mousina 40 3 AUB Mixed + 12 190308 Samjeen Taj 44 4 AUB Proliferative + 13 193987 Vijayalakshmi 41 3 AUB Secretory + 14 198622 Uma 47 4 AUB SH + 15 200216 Lakshmamma 46 4 AUB SH + 16 203088 Rajeshwari 48 4 AUB En polyp + 17 153195 Dyawamma 49 3 AUB Endometrial Ca + 18 229424 Venkatamma 60 4 AUB Atrophic + 19 207650 Shilpa 20 1 AUB Secretory + 20 210612 Shyamala 30 UM AUB Proliferative + 21 213723 Nagaveni 22 1 AUB Secretory + 22 220071 Rathnamma 25 1 AUB Secretory + 23 210112 Gowramma 32 UM AUB Proliferative + 24 225155 Manjula 32 UM AUB Proliferative + 25 228037 Manjula 37 2 AUB Proliferative + 26 172762 Rathnamma 40 3 AUB Secretory + 27 177490 Yashodamma 40 3 AUB Secretory + 28 179342 Radhamma 39 2 AUB SH + 29 184006 Gowramma 39 2 AUB Mixed + 30 189917 Manjula 44 4 AUB Proliferative + 31 192466 Lakshmamma 42 2 AUB Secretory + 32 199020 Mamatha 46 4 AUB SH + 33 201266 Geetha 48 4 AUB SH + 34 203968 Rathna 47 2 AUB En.polyp + 35 153484 Rudramma 59 4 AUB Proliferative + 36 230151 Sampangiyamma 58 4 AUB Endometrial Ca + 37 208626 Anjinamma 25 UM AUB Proliferative + 38 209916 Yashodamma 24 1 AUB Proliferative + 39 215826 Venkatamma 27 2 AUB Secretory + 40 220838 Shameem 24 1 AUB Secretory +

Sl.N

o

IP.N

o

Nam

e of

the

patie

nt

Age

(Yea

rs)

Para

Clin

ical

D

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osis

His

topa

thol

ogic

D

iagn

osis

HM

B

IMB

H&

PB

FMB

Olig

pmen

norh

ea

PMB

41 223055 Sushala 33 3 AUB Proliferative + 42 225155 Mohsina Taj 35 UM AUB Proliferative + 43 227403 Lakshmamma 37 2 AUB Proliferative + 44 172766 Vinoda 38 3 AUB Secretory + 45 178894 Saraswathamma 38 2 AUB SH + 46 181067 Vimalamma 40 3 AUB SH + 47 186293 Amaravathi 38 3 AUB Mixed + 48 191553 Myrumunnisa 44 4 AUB Proliferative + 49 194210 Rajamma 45 3 AUB Secretory + 50 198769 Bhagyamma 48 4 AUB SH + 51 201796 Munivenkatamma 48 4 AUB SH + 52 205431 Bhagyamma 48 4 AUB Disordered

Proliferative +

53 160552 Nagamma 58 4 AUB Secretory + 54 207623 Shanthamma 19 1 AUB Proliferative + 55 209655 Rajamma 28 UM AUB Proliferative + 56 216326 Vimalamma 28 2 AUB Secretory + 57 221171 Rathnamma 26 1 AUB Secretory + 58 223176 Anjanamma 34 2 AUB Proliferative + 59 225505 Farheen Taj 32 UM AUB Proliferative + 60 226921 Manjula 39 3 AUB Proliferative + 61 172537 Muniyamma 40 2 AUB Secretory + 62 179333 Jayanthi 39 2 AUB SH + 63 182913 Rukminiyamma 40 3 AUB SH + 64 187089 Susheelamma 37 2 AUB Mixed + 65 191147 Anitha 43 4 AUB Proliferative + 66 195854 Rathnamma 43 4 AUB Secretory + 67 198613 Shivamma 49 4 AUB SH + 68 201603 Lakshmamma 47 2 AUB SH + 69 155401 Sulochana 49 4 AUB Disordered

proliferative +

70 161177 Munirathnamma 51 4 AUB Secretory + 71 208783 Sarojamma 30 UM AUB Proliferative + 72 210325 Shivamma 30 UM AUB Proliferative + 73 217375 Anandamma 22 1 AUB Secretory + 74 218898 Gowramma 23 1 AUB SH + 75 222562 Kanaka 35 2 AUB Proliferative + + 76 225154 Sujatha 31 UM AUB Proliferative + 77 228724 Ramadevi 40 3 AUB Proliferative + 78 172897 Mahadevamma 40 4 AUB Secretory + 79 179342 Varalakshmi 40 2 AUB SH + 80 182773 Poojamma 39 3 AUB SH + 81 186132 Puttamma 35 2 AUB En.polyp + 82 191262 Eshwaramma 45 4 AUB Proliferative + 83 196281 Narayanamma 44 4 AUB Secretory + 84 199703 Lakshmamma 48 4 AUB SH +

Sl.N

o

IP.N

o

Nam

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the

patie

nt

Age

(Yea

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Para

Clin

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D

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His

topa

thol

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D

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HM

B

IMB

H&

PB

FMB

Olig

pmen

norh

ea

PMB

85 201588 Muniyamma 46 4 AUB SH + 86 169309 Ashwini 50 4 AUB Disordered

Proliferative +

87 169296 Jayamma 55 4 AUB Secretory + 88 199234 Sudha 28 UM AUB Proliferative + 89 211092 Rathnamma 26 UM AUB Proliferative + 90 217718 Krishnadevamma 26 2 AUB Secretory + 91 213345 Shashikala 21 1 AUB SH + + 92 222279 Rathnamma 31 UM AUB Proliferative + 93 225155 Manjula 32 UM AUB Proliferative + 94 228417 Shobha 38 3 AUB Proliferative + 95 173344 Narayanamma 39 4 AUB Secretory + 96 179054 Sujathamma 39 2 AUB SH + 97 183508 Sarojamma 38 2 AUB SH + 98 187414 Munindramma 38 2 AUB ESS + 99 223176 Anjanamma 42 4 AUB Proliferative + 100 196665 Shanthamma 45 4 AUB Secretory + 101 198660 Lakshmamma 48 4 AUB SH + 102 200921 Triveni 48 4 AUB SH + 103 169061 Munirathnamma 46 4 AUB Disordered

Proliferative +

104 169417 Bhagyamma 56 4 AUB Secretory + 105 213043 Uma 19 1 AUB Proliferative + 106 210949 Papalidevi 29 UM AUB Proliferative + 107 217325 Anandamma 23 1 AUB Secretory + 108 219161 Venkatalakshmi 26 2 AUB SH + 109 223298 Narayanamma 32 2 AUB Proliferative + 110 225745 Vinoda 31 UM AUB Proliferative + 111 213777 Jayalakshmi 36 2 AUB Proliferative + 112 174676 Sunitha 38 2 AUB Secretory + 113 179745 Bhagyamma 36 2 AUB SH + 114 180855 Deviramma 37 3 AUB SH + 115 191775 Bharathi 38 2 AUB SH + 116 187946 Sukanya 42 4 AUB Proliferative + 117 222562 Kanaka 42 3 AUB Proliferative + 118 196841 Sushelamma 43 3 AUB Secretory + 119 199670 Narasamma 49 4 AUB SH + 120 201613 Lakshmamma 49 5 AUB SH + 121 169293 Anjinamma 49 4 AUB Atrophic + 122 171069 Sharadamma 60 5 AUB Secretory + 123 208627 Lakshmamma 24 UM AUB Proliferative + 124 216848 Narayanamma 26 UM AUB Proliferative + 125 216854 Shylaja 28 2 AUB Secretory + 126 219969 Gowramma 28 1 AUB SH + 127 223284 Kantamma 31 UM AUB Proliferative + 128 225351 Lalitha 35 2 AUB Proliferative +

Sl.N

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IP.N

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Age

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Clin

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D

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H&

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129 170250 Rathnamma 38 3 AUB Secretory + 130 175392 Chinamma 36 2 AUB Secretory + 131 184287 Narayanamma 40 2 AUB SH + 132 187667 Venkatamma 43 3 AUB Proliferative + 133 192465 Sharadha 44 3 AUB Proliferative + 134 196840 Kanaka 44 2 AUB Secretory + 135 202703 Venkatamma 46 4 AUB SH + 136 199673 Rathnamma 48 4 AUB SH + 137 169414 Bhagyamma 48 4 AUB Disordered

Proliferative +

138 157777 Nasima 59 4 AUB En.polyp + 139 209655 Rajamma 23 1 AUB Proliferative + 140 210252 Rathnamma 25 1 AUB Secretory + 141 193585 Pushpa 27 2 AUB Secretory + 142 221532 Chikamma 29 2 AUB SH + 143 223158 Bhagyamma 35 2 AUB Proliferative + 144 224760 Sunandamma 31 UM AUB Proliferative + 145 171452 Ashwathamma 36 2 AUB Secretory + 146 175712 Rathnamma 38 2 AUB Secretory + 147 184006 Gowramma 36 2 AUB SH + 148 187824 Mariyamma 42 4 AUB Proliferative + 149 193169 Saraswathamma 41 3 AUB Proliferative + 150 197207 Minabiswass 42 3 AUB Secretory + 151 199222 Vinodamma 42 4 AUB SH + 152 201796 Munivenkatamma 48 4 AUB SH + 153 170639 Narayanamma 50 2 AUB Atrophic + 154 170250 Rathnamma 65 4 AUB Atrophic + 155 209638 Padmamma 26 UM AUB Proliferative + 156 212063 Rajamma 30 2 AUB Secretory + 157 218061 Rathnamma 23 1 AUB Secretory + 158 220838 Shameem 28 1 AUB CH with atypia + 159 221345 Shaheena 34 2 AUB Proliferative + 160 226171 Rathnamma 32 UM AUB Proliferative + 161 171439 Sunandamma 37 2 AUB Secretory + 162 175128 Shashikala 39 3 AUB Secretory + 163 183322 Radhamma 37 2 AUB SH + 164 189914 Mary 41 3 AUB Proliferative + 165 189502 Sujatha 45 4 AUB Proliferative + 166 193394 Papamma 44 4 AUB Proliferative + 167 196873 Laxmamma 41 2 AUB Secretory + 168 200349 Munirathnamma 50 4 AUB SH + 169 200612 Sunithamma 49 4 AUB SH + 170 203312 Padma 46 4 AUB CH with atypia + 171 202703 Venkatalakshmi 46 4 AUB Mixed + 172 153052 Rathnamma 48 4 AUB Atrophic +

Sl.N

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D

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HM

B

IMB

H&

PB

FMB

Olig

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PMB

173 170275 Jersy 52 4 AUB Atrophic + 174 168702 Lakshmamma 55 4 AUB Atrophic + 175 208763 Saroja 20 1 AUB Proliferative + 176 212611 Shivamma 22 1 AUB Secretory + 177 213971 Rathnamma 23 1 AUB Secretory + 178 218535 Jayamma 22 1 AUB Secretory + 179 219042 Bharathamma 30 2 AUB Secretory + 180 221186 Nageena 29 2 AUB Mixed + 181 224409 Shanthamma 32 2 AUB Proliferative + 182 224901 Muniyamma 36 2 AUB Proliferative + 183 170635 Bhagyamma 38 2 AUB Secretory + 184 177135 Sarojamma 40 3 AUB Secretory + 185 171450 Savitha 39 2 AUB Secretory + 186 176772 Bhagyamma 36 2 AUB Secretory + 187 184287 Narayanamma 38 2 AUB SH + 188 184688 Rathnamma 39 3 AUB CH with atypia + 189 193545 Tashin Taj 43 2 AUB Proliferative + 190 193997 Vinoda 45 4 AUB Secretory + 191 197743 Lakshmamma 45 4 AUB Secretory + 192 198660 Lakamma 49 4 AUB SH + 193 209533 Ashwathamma 30 UM AUB Proliferative + 194 210174 Kamalamma 28 UM AUB Proliferative + 195 222143 Renuka 31 2 AUB Proliferative + 196 219969 Gowramma 35 2 AUB Proliferative + 197 224385 Sharadamma 33 2 AUB Proliferative + 198 177952 Archana 28 1 AUB Secretory + 199 179868 Savitha 48 4 AUB Proliferative + 200 212143 Ramakka 35 2 AUB Secretory +

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