DISEASES OF THE ENDOMETRIUM

Endometrial hyperplasia is caused by estrogenic stimulation and may be pre-neoplastic. An endogenous response may be seen with successive anovulatory cycles or estrogen-secreting tumours, and an exogenous response with estrogen-containing drugs. The importance of endometrial hyperplasia is that it is associated with an increased risk of development of adenocarcinoma of the endometrium.

There are several histological types — simple hyperplasia — being the most common pattern, diffusely affecting the whole endometrium. Proliferation of glands can be seen, with evident mitoses and stratification of cells. Glands grow in a regular tubular pattern, but are often dilated however, there is no cytological atypia of the nuclei. This type is associated with a very slightly increased risk of malignancy after a long period of time, typically over 10 years.

Complex hyperplasia is almost always seen focally within the endometrium. There is obvious proliferation of epithelium, evident by mitotic figures, but the glands grow in an irregular pattern, with branched irregular contours and little intervening stroma. The cells forming the glands do not show cytological atypia. This type is associated with a slightly increased risk of development of malignancy. Complex atypical hyperplasia is commonly seen only focally within the endometrium. Like complex hyperplasia, there is proliferation of epithelium, evident by mitotic figures, and the glands grow in an irregular pattern, with branched irregular contours However, the cells forming the glands show cytological atypia, with pleomorphism and hyperchro-matism. About 30% of cases with this pattern of hyperplasia will develop a carcinoma of the endometrium, usually within 5 years of diagnosis.

Acute endometritisis usually encountered as a complication of pregnancy.

Chronic endometritis is usually associated with recent gestation, pelvic inflammatory disease. Chronic endometritis may be associated with menstrual irregularities, but is also found in women who are being investigated for infertility. Histologically the endometrium shows lymphoid infiltration, with formation of plasma cells. The majority of cases are associated with a definite clinical risk factor for developing

inflammation. The condition has occurred after recent pregnancy, miscarriage or instrumentation in 50% of cases, in association with pelvic inflammatory disease (e.g. salpingitis) in 25% of cases. In the remaining 5% of cases without a defined risk factor, chronic endometritis may be caused by gonococcal or chlamydial infection, or tuberculosis.

In tuberculous endometritis, because granulomas form only in secretory endometrium, they may not be seen in samples taken from early in the cycle. The condition is commonly part of more widespread infection involving fallopian tubes.

Endometrial polyps are localized overgrowths of endometrial glands and stroma. Endometrial polyps are very common and are usually seen in the peri-menopausal age range. They are thought to be caused by over-proliferation of glands in response to estrogenic stimuli.

Macroscopically they vary in size but are usually 1—3 cm in diameter and are usually sited in the uterine fundus. They appear as firm smooth nodules within the endometrial cavity occasionally prolapsing through the cervical ostium.

Microscopically, they are made up of cystically dilated endometrial glands in a vascular stroma. They are clinically associated with menstrual abnormalities and dysmenorrhea, but may develop ulceration or undergo torsion.

Endometriosis. Endometriosis is a condition in which ectopic endometrium develops outside the uterine cavity. It affects 7% women of reproductive age, with associated infertility in about 30% of cases. The common sites for ectopic endometrial growth are ovaries, fallopian tubes, round ligaments, and pelvic peritoneum. Less common sites are intestinal wall, bladder, umbilicus, and laparotomy scars. Rarely, involvement of lymph nodes, lung and pleura is seen. The ectopic endome-trium still responds to cyclical hormonal stimulation, with phases of proliferation and breakdown with bleeding. The bleeding and breakdown stimulate the formation of fibrous adhesions and accumulation of hemosiderin pigment.

Macroscopically, foci of endometriosis appear as cystic and solid masses, which are characteristically dark brown from iron pigment accumulated as a result of repeated bleeding. Microscopically, endometrial glands and stroma are seen, together with fibrosis and macrophages containing iron pigment.

Complications: endometrial tissue growing in abnormal sites stimulates fibrosis and may cause fibrous adhesions between adjacent organs. When peritoneum is involved, adhesions may cause bowel obstruction. The condition usually presents with cyclical pelvic pain, dysmenorrhea, and infertility. When it affects the fallopian tubes and ovaries, the whole of the fallopian tube and ovary may be converted

to a cystic mass containing brown, semi-liquid material (chocolate cyst).

Endometrial carcinoma. Carcinoma of the endometrium has become more common than the invasive carcinoma of the cervix in women. Whereas the decline in the incidence of cervical cancer is due to early detection and cure of in situ stage, increased frequency of endometrial carcinoma may be due to longevity of women's life to develop this cancer of older females. The peak incidence at onset is 6th to 7th decades of life and is rare below the age of 40 years.

The exact etiology of endometrial cancer remains unknown. However, a few factors associated with increased frequency of its development are estrogen excess, obesity, diabetes, hypertension andnulliparous state.

Morphology. Macroscopically, endometrial carcinoma may have 2 patterns-localized polypoid tumour or a diffuse tumour, the latter being more common. The tumour protrudes into the endometrial cavity as irregular, friable and grey-tan mass. Extension of the growth into myometrium may be identified by the presence of soft, friable and granular tissue in cut section. In advanced disease, the involvement may extend beyond the physiologic limits into the cervical canal, into the peritoneum, besides

lymphatic metastases and hematogenous metastases to distant sites such as lungs, liver, bones and other organs.

Microscopically, most endometrial carcinomas are adenocarcinomas. Depending upon the pattern of glands and individual cell changes, these may be well-differentiated, moderately-differentiated or poorly-differentiated.

Uncommon histologic variants of endometrial carcinoma are: adenocarcinoma with squamous metaplasia (adenocanthoma), adenosquamous carcinoma (when both components are frankly malignant), clear cell carcinoma, mucinous adenocarcinoma and papillary serous carcinoma.

DISEASES OF THE CERVIX

The cervix is an important site of pathology, particularly in women of reproductive age. The ectocervix is covered by squamous epithelium, and the endocervical canal by mucus-secreting columnar epithelium, which shows glandular downgrowth. At various stages in a woman's reproductive life, the junction between the squamous and columnar epithelium migrates onto the convexity of the ectocervix, then back into the endocervical canal. This squamocolumnar junction is the seat of most of the epithelial diseases that occur in the cervix.

The original squamocolumnar junction is usually located in the region of the external os, but its precise location at birth is influenced by exposure to maternal hormones in utero.

Around puberty, hormonal influences cause extension of the columnar epithelium onto the ectocervix, forming an ectropion or cervical erosion. This process is augmented by a first pregnancy, particularly when it occurs shortly after menarche. Exposure of the sensitive columnar epithelium of the ectropion to the post-pubertal acidic environment of the vagina induces squamous metaplasia and a transformation zone between the endocervical columnar epithelium and the ectocervical squamous epithelium. This zone is composed of new squamous epithelium in an area previously occupied by columnar epithelium.

Thus the squamocolumnar junction is of variable size, but its site always approximates to the external os. In older women it may retreat into the endocervical canal.