Pathology Thread

IV. Benign conditions

Objectives:

After completing this section you will be able to:

• list common benign non-neoplastic diseases of the endometrium
• discuss possible etiologic factors
• describe clinical presentation
• describe histologic features
• state possible outcome

1. Dysfunctional uterine bleeding (DUB)

This is a clinical term used to describe abnormal uterine bleeding not attributable to a pathologic lesion of the endometrium or uterus. It is due to deranged magnitude or duration of hormonal (estrogen/progesterone) effects on the endometrium. The cause is usually due to ovarian dysfunction, which may result in anovulation or in luteal phase defect.

Anovulation

This refers to the absence of ovulation during the reproductive years (in the absence of pregnancy) and is the commonest cause of DUB. Anovulation can occur at any age but more commonly occurs at menarche and at menopause. In an anovulatory cycle, the failure of ovulation leads to excessive and prolonged estrogen stimulation, with absence of the postovulatory surge in progesterone levels. This results in a disordered proliferative endometrium. The spiral arterioles do not develop properly in the absence of progesterone. When estrogen levels decline, there is loss of stromal fluid causing collapse of the poorly developed spiral arterioles, stasis, and thrombosis and "break-through bleeding" occurs. In some cases, there is no drop in estrogen levels and bleeding occurs because adequate blood supply to the proliferating endometrium cannot be maintained. The exact cause of anovulation is not really understood.

Histologic appearances reflect the effect of estrogen stimulation without subsequent progesterone stimulation. The endometrial glands are proliferative and show mild architectural changes including cystic dilatation. Breakdown of the stroma results in fragmented, isolated glands with no evidence of secretory activity.

Dysfunctional uterine bleeding. Fragmented glands and stroma.

Luteal phase defect

Luteal phase defect refers to the occurrence of inadequate corpus luteum function resulting in inadequate progesterone output and an abnormally short menstrual cycle. This dysfunction occurs when the corpus luteum does not develop properly or regresses prematurely. It manifests clinically as infertility with increased bleeding or amenorrhea.

The histologic findings are those of secretory endometrium more than 2 days out of phase with the chronologic day of the menstrual cycle.

2. Endometriosis

This is the presence of benign endometrial glands and stroma outside the uterus. The lesions are usually found on the peritoneal surfaces of the reproductive organs and adjacent pelvic organs. The most frequent location is the ovary (approx. 50%) followed by the pouch of Douglas, uterosacral ligaments, posterior surface of the uterus and the remaining pelvic peritoneum. Occasional sites include the cervix, vagina, perineum, bladder, large bowel and the umbilicus. Rare lesions are seen as far afield as small bowel, kidneys, lungs and brain.

Several theories have been used to explain the occurrence of endometriosis:

Menstrual implantation: This proposes that fragments of menstrual endometrium regurgitate through the fallopian tubes and implant on various sites in the pelvic peritoneum.

Vascular dissemination: Suggests that occurrence of endometriosis may be due to hematogenous or lymphatic spread from the endometrium.

Celomic metaplasia: The lining of the peritoneal cavity originates from the embryonic celomic epithelium, which also gives rise to the müllerian duct system from which the uterus and tubes develop. It is proposed that endometriosis arises from celomic metaplasia of the peritoneum.

Question: Can endometriosis occur in males (who do not have any endometrial tissue)?

Clinical appearances

The clinical presentation depends on the site of endometriosis. Dysmenorrhea, cyclic abdominal pain and dyspareunia are common symptoms. Infertility occurs in about a third of affected women.

Endometriosis usually appears as multiple red, purplish or brown (due to presence of hemosiderin) 1mm to 5mm nodules, but some may form larger masses or cysts. Dense fibrous adhesions may surround the foci. Repeated hemorrhage into foci in the ovary with each menstrual cycle produces cysts, which contain inspissated, chocolate-brown material, called "chocolate cysts".

Histology

Microscopic diagnosis of endometriosis is made by the presence of ectopic endometrial glands and stroma. Macrophages containing hemosiderin (siderophages) and ceroid may be present in lesions with previous hemorrhage. In others, the endometrial tissue is inactive and no evidence of past bleeding is seen. When endometriosis develops in a muscular viscus, the smooth muscle around it is often hyperplastic.

Clinical behavior

Benign with no malignant potential. May recur after surgical excision but the risk is low.

Question: What complication can arise when endometriosis involves the gut?

3. Adenomyosis

This is defined as the presence of endometrial glands and stroma in the myometrium. The condition involves the posterior wall more often than the anterior but it may affect both walls in the same uterus.

Clinical appearances

The disease is primarily a disorder of parous women and occurs infrequently in the nullipara. It is associated with menorrhagia and increasingly severe secondary dysmenorrhea. In about a third of patients there are no symptoms and the lesions are discovered accidentally.

When extensive the lesions produce myometrial thickening. On section the thickened myometrium presents a whorled and trabeculated appearance with small yellow or brown cystic spaces containing fluid or blood. Sometimes small hemorrhagic areas of endometrial islands can be seen.

Occasionally, a proliferation of smooth muscle around a focus of adenomyosis produces a tumor called adenomyoma, which resembles uterine leiomyoma.

Adenomyosis. Endometrial gland and stroma in myometrium.

Adenomyosis. Another example.

Clinical behavior.

This is a benign condition with no known malignant potential that regresses after the menopause.