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FEMALE GENITALIA II

CORPUS UTERI

Student-learning Objectives:At the end of this lecture the student should be able to:

Discuss endometrial hyperplasia in terms of its aetiology, classification, and

predisposition to endometrial carcinoma.

Classify endometrial carcinoma and describe its pathological features and staging.

Discuss the factors that are important in the aetiology and prognosis of endometrial

carcinoma.

Classify endometrial sarcomas and describe their pathological features and behaviour.

Discuss uterine leiomyomata in terms of their aetiology and clinico-pathological

features.

ENDOMETRIUM

Clinical Considerations

Perhaps the commonest reason why women visit doctors worldwide is abnormal uterine bleeding,whether this is in the form of excessive or prolonged bleeding at the time of the periodmenorrhagia!, irregular periods or intermenstrual bleeding. "he conditions described in thislecture may all cause these problems to a lesser or greater extent.

#n the investigation of abnormal uterine bleeding, the endometrial biopsy or curettage is a common

diagnostic procedure, and $uite often will yield the specimen that is seen by the pathologist anddiagnosed as one of the diseases discussed below.

#t must be noted, however, that $uite often patients will have uterine bleeding that does not have anorganic cause, %nown as dysfunctional uterine leedin! "DU#$% &ost often, this is due toendocrine abnormalities some disturbance of the hypothalamic-pituitary-ovarian axis!, leading toirregularities of the proliferative and'or secretory phases of the endometrial cycle, which causesirregular bleeding.

D() will not be discussed in this lecture, and the endometrial diseases that will be discussed willfall under the following headings:

#nflammation

Polyps

*yperplasia

+eoplasms

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Inflammation

Endo&etritis

Acute usually caused by bacterial infection with a variety of organisms including strep,

staph, .Coli or pseudomonas. #t most commonly follows an abortion or delivery especially whenfragments of placenta or membranes are retained in the uterus. "he pathological picture is one oftypical acute inflammation.

C'ronic ( may be specific or non-specific. #t is defined as the presence of plasma cells in

chronically inflamed endometrial tissue. #t may follow abortion, delivery, instrumentation of theendometrial cavity, or may be associated with an intrauterine contraceptive device.*owever, no cause is demonstrated in up to /0 of cases.1pecific inflammation is uncommon and is nearly always secondary to tuberculosis. #t usually is acomplication of tuberculous salpingitis. 2ther specific inflammatory diseases includeactinomycosis, toxoplasmosis and cytomegalovirus. "hese diseases are relatively rare.

Polyps

"hese are polypoid, non-neoplastic lesions that arise from the endometrium and protrude into theendometrial cavity, and that may cause abnormal uterine bleeding. "hey form as a result of focalovergrowth of the endometrium."hey are relatively common, tend to occur in peri and post-menopausal women, are composed of avariable admixture of endometrial glands sometimes cystic! and stroma, and are readily removedby curettage. &alignancy arising in endometrial polyps is rare.ndometrial polyp, grossndometrial polyp, histology 3

ndometrial polyp, histology 4

Hyperplasia

"his comprises excessive endometrial proliferation and is caused by prolonged, unopposed,relative or absolute hyperoestrogenism such as is found with:

Persistent failure of ovulation

Polycystic ovaries including 1tein-5eventhal syndrome!

"herapy with exogenous oestrogenic agents

2estrogen-secreting ovarian tumours

ndometrial hyperplasia is classified as follows:

1imple hyperplasia formerly called 67landular cystic hyperplasia8!

Complex hyperplasia formerly called 6Adenomatous hyperplasia8!

Atypical hyperplasia formerly called 6Atypical Adenomatous hyperplasia8!

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A simple explanation of these processes is as follows. 2estrogen stimulation causes proliferation ofendometrial glands and stroma.7landular proliferation tends to dominate the picture and the glands become elongated andcystically dilated, but are still separated by relatively abundant stroma."here is NO cellular atypia. "his type of hyperplasia is %nown as si&)le 'y)er)lasia*istology!and carries a very low ris% "*+$of progression to endometrial adenocarcinoma%

"he next phase of hyperplasia is called co&)le, 'y)er)lasia- in which the glands becomemar%edly tortuous, bud and branch, and become crowded to the point where they almost toucheach. "he lining epithelium of these glands is mar%edly hyperplastic. Again there is NOsignificantcellular atypia. "his category of hyperplasia is said to carry a ris% of progression to endometrialcarcinoma of about ./*0+%

"he final stage of hyperplasia is %nown as aty)ical 'y)er)lasia in which there are features ofcomplex hyperplasia with superimposed cytolo!ical aty)iain the glandular cells. "here is a highris% of progression to endometrial carcinoma, in the order of about 10 to .0+%"he ris% increaseswith the degree of cellular atypia whether mild, moderate or severe, as well as with the duration of

the disease. Progression of atypical hyperplasia to carcinoma is a slow and unpredictable processestimated to ta%e about 3/ years in some studies!.

"reatment depends on the type of hyperplasia and the age of the woman. #n younger women sayless than 9/ years! who desire preservation of fertility, treatment options for simple and complexhyperplasia include

progestin administration to combat the unopposed oestrogen stimulation!

repeated endometrial curettage

induction of ovulation e.g. wedge biopsy of the ovary in 1tein-5eventhal

syndrome.1ometimes, however, young women with atypical hyperplasia may opt for, or be advised to have a

hysterectomy.

2lder women may be managed in the same way as the younger ones, but as preservation offertility is not usually a consideration, sometimes they may come to hysterectomy more often. #nall cases of atypical hyperplasia, close follow up, usually by endometrial biopsy every or ;months, is advocated.

Neoplasms

Endo&etrial Carcino&a

A simple classification of endometrial carcinomas is as follows:3! Adenocarcinoma 4! Adenocarcinoma with s$uamous metaplasia

Adenoacanthoma

Adenos$uamous carcinoma

! 1$uamous cell carcinoma 9! (ndifferentiated ! &etastatic

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"he vast maamaica, cervical cancer greatly outnumbers endometrial cancer seefigures for cervix uteri given in those lecture notes!.

Aetiolo!y

As endometrial carcinoma almost invariably follows on endometrial hyperplasia, it is notsurprising to find that the aetiological factor for hyperplasia is that for carcinoma, i.e. unopposed,prolonged oestrogenic stimulation. "he underlying pathological causes are as previously

mentioned under hyperplasia.Nulli)arityand oesityare associated ris% factors but are not independent variables@nulliparitymay be a function of the high oestrogen levels, while obesity is thought to act by increasing theoestrogen levels via conversion of certain adrenal hormones peripherally in body fat stores.Diabetes and hypertension are also epidemiologically related. #t must be noted, however, that inmany women who develop endometrial carcinoma, no obvious precursor pathological conditionsare identified.

Pat'olo!y

Adenocarcinoma of the endometrium occurs most commonly in the postmenopausal age group

especially over /-;/ years of age. "he tumour most commonly grows as an exophytic, polypoidlesion protruding into the endometrial cavity, but is sometimes nodular or pla$ue-li%e. "hey oftenhave a prominent papillary configuration.ndometrial carcinoma, gross ndometrial carcinoma,gross 4 ndometrial carcinoma, gross

*istological grade may be well, moderate or poorly differentiated. &ost commonly, the neoplasticglands resemble the endometrial glands from which they came, and are therefore referred to asendometrioid carcinomas.ndometrial carcinoma, histology 3 ndometrial carcinoma, histology 4 ndometrial carcinoma,histology

Adenocarcinomas may show foci of s$uamous differentiation: the adenoacanthoma is an adenocarcinoma in which t'e s7ua&ous ele&ent is

eni!n the adenos$uamous carcinoma the s7ua&ous co&)onent is &ali!nant%

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A ;)ure

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+eoplasms

o 5eiomyoma benign!

o 5eiomyosarcoma malignant!.

Adeno&yosis"his is defined as the presence of ectopic endometrial glands and stroma within the myometrium.#t is a disease that predominantly affects perimenopausal women, and it may cause abnormaluterine bleeding and'or dysmenorrhoea. "he uterus is enlarged and the myometrium has atrabeculated appearance. Adenomyosis gross Adenomyosis, microscopic

Leio&yo&a5eiomyomata leiomyomas! are benign neoplasms commonly %nown as 6fibroids8. "hey areextremely common, are usually multiple and are more common in blac%s over whites. "hey maybe found in any of three locations in the uterus:

1ubmucosal i.e.