Lec.no.2/Female genital tractDr.Ro,aa S.Mahdi
*This may be associated with retained products of conception subsequent to miscarriage or delivery, or a foreign body such as an intrauterine device. Retained tissues or foreign bodies act as a nidus for infection, frequently by flora ascending from the vaginal or anal region.
* Endometritis is either acute or chronic depending on whether there is a predominant neutrophilic or lymphoplasmacytic response; however, components of both may be present in otherwise normal endometrium. Generally the diagnosis of chronic endometritis requires the presence of plasma cells . Acute endometritis is frequently due to N. gonorrhoeae or C. trachomatis. Microscopically, neutrophilic infiltrate in the superficial endometrium and glands coexists with a stromal lymphoplasmacytic infiltrate.
*All forms of endometritis may present with menstrual abnormalities, infertility and ectopic pregnancy due to extension of the damaging inflammation to the fallopian tubes. Occasionally tuberculosis may present as granulomatous endometritis, frequently with tuberculous salpingitis and peritonitis.
AdenomyosisThis refers to the “invagination of the stratum basalis of endometrium down into the myometrium.” Nests of endometrial stroma, glands, or both, are found well down in the myometrium between the muscle bundles. The latter become hypertrophied. Accordingly, the uterine wall often becomes thickened and the uterus is enlarged and globular. Because these glands derive from the stratum basalis, they do not undergo cyclical bleeding. Nevertheless, marked adenomyosis may produce menorrhagia, dysmenorrhea, and pelvic pain before the onset of menstruation.
EndometriosisThis is characterized by “the presence of endometrial glands and stroma in a location outside the endomyometrium.” It occurs in as many as 10% of women in their reproductive years and in nearly half of women with infertility. It may present as a pelvic mass filled with degenerating blood (chocolate cyst). It is frequently multifocal and may involve any tissue in the pelvis (ovaries, pouch of Douglas, uterine ligaments, tubes, and rectovaginal septum), less frequently in more remote sites of the peritoneal cavity and about the umbilicus. Three possibilities have been suugested to explain the origin of these lesions.
1. The regurgitation theory, currently the most accepted, proposes menstrual backflow through the fallopian tubes with subsequent implantation.
2. The metaplastic theory proposes endometrial differentiation of coelomic epithelium.
3. The vascular or lymphatic dissemination theory has been raised to explain extrapelvic endometriosis.
Gross featuresEndometriosis almost always contains functioning endometrium, which undergoes cyclic bleeding. Because blood collects in these ectopic foci, they usually appear grossly as red-blue to yellow-brown nodules.
They vary in size from microscopic up to 2 cm in diameter and lie on or just under the affected serosal surface. Often individual lesions coalesce to form larger masses.
When the ovaries are involved, the lesions may form large, blood-filled cysts that are transformed into so-called chocolate cysts as the blood ages .
hemorrhage and organization of the blood leads to widespread fibrosis, adherence of pelvic structures, sealing of the tubal fimbriated ends, and distortion of the oviducts and ovaries.
The histologic diagnosis depends on finding two of the following three features within the lesions:
1. Endometrial glands
2. Endometrial stroma, or
3. Hemosiderin pigment.
Endometrial HyperplasiaThis is an exaggerated endometrial proliferation induced by sufficiently prolonged excess of estrogen relative to progestin. The severity of hyperplasia is classified according to two parameters
a. architectural crowding of the glands &
b. cytologic atypia.
Accordingly there are three categories
1. Simple hyperplasia
2. Complex hyperplasia
3. Atypical hyperplasia
These three categories represent a spectrum based on the level and duration of the estrogen excess. The risk of developing carcinoma depends on the severity of the hyperplastic changes and associated cellular atypia. Simple hyperplasia carries a negligible risk, while a woman with atypical hyperplasia has a 20% risk of developing endometrial carcinoma. Thus When atypical hyperplasia is discovered, it must be carefully evaluated for the presence of cancer and must be monitored by repeated endometrial biopsy.
Any estrogen excess may lead to hyperplasia.
Potential contributors include
1. Failure of ovulation, e.g. around the menopause
2. Prolonged administration of estrogenic steroids
3. Estrogen-producing ovarian lesions such as
a. polycystic ovaries (Stein-Leventhal syndrome)
b. cortical stromal hyperplasia
c. granulosa-theca cell tumors of the ovary
4. Obesity, because adipose tissue processes steroid precursors into estrogens.
Gross featuresIn simple hyperplasia the endometrium is diffusely thickened.
In complex & atypical hyperplasia there is usually focal thickening of the endometrium.
Simple hyperplasia involves both the glands & stroma; the normal gland to stroma ratio is maintained. The glands are proliferative and some are cystically dilated.
Complex hyperplasia: there is glandular crowding with little stroma separating the proliferative glands. Typically, this is a focal process.
Simple and complex hyperplasias are further divided into atypical and non-atypical
Atypical hyperplasia: characterized by atypical nuclei of the proliferative glands as evidenced by nuclear stratification, nuclear crowding and the presence of nucleoli
Tumors of the Endometrium and MyometriumThe most common neoplasms of the body of the uterus are
1. Endometrial polyps,
2. Smooth muscle tumors, and
3. Endometrial carcinomas.
All tend to produce bleeding from the uterus as the earliest manifestation.
Endometrial Polyps are usually sessile, hemispheric lesions up to 3 cm in diameter. Larger polyps tend to be pedunculated & may project from the endometrial mucosa into the uterine cavity & sometimes through the cervix into the vagina. Microscopically, they are composed of basalis-type, often cystically dilated glands with a rather fibroblastic stroma. Small muscular arteries are often prominent. The stromal cells have been found to be monoclonal. This signifies that they are the neoplastic component. The clinical significance of these polyps lies in the production of abnormal uterine bleeding and, more important, the risk (however rare) of giving rise to a cancer.
Leiomyomas are benign tumors that arise from the smooth muscle cells in the myometrium. Because of their firmness they are also called fibroids. They are the most common benign tumor in females and are found in 30% to 50% of women during reproductive life. Estrogens and possibly oral contraceptives stimulate their growth; conversely, they shrink postmenopausally.
Gross features:They are sharply circumscribed, firm gray-white masses with a characteristic whorled cut surface.
They may occur singly, but are often multiple tumors scattered within the uterus, ranging in size from small seedlings to massive neoplasms that dwarf the size of the uterus.
Some are embedded within the myometrium (intramural), whereas others may lie directly beneath the endometrium (submucosal) or directly beneath the serosa (subserosal).
Larger neoplasms may show foci of ischemic necrosis with areas of hemorrhage and cystic softening (red degeneration)
After menopause they may become densely collagenous and even calcified.
There are whorling bundles of smooth muscle cells.
Foci of fibrosis, calcification, ischemic necrosis, cystic degeneration, and hemorrhage may be present.
Leiomyomas of the uterus may be entirely asymptomatic and be discovered only on routine pelvic examination or imaging studies. The most frequent manifestation, when present, is menorrhagia. Large masses in the pelvic region may become palpable or may produce a dragging sensation. Benign leiomyomas rarely transform into sarcomas.
Leiomyosarcomas typically arise de novo from the mesenchymal cells of the myometrium. They are almost always solitary tumors, in contradistinction to the frequently multiple leiomyomas.
The tumor is typically bulky
It infiltrates the uterine wall.
Some times it projects into the endometrial cavity.
They are frequently soft, hemorrhagic, and necrotic.
Microscopic featuresThey show a wide range of differentiation, from those that closely resemble leiomyoma to wildly anaplastic tumors.
The diagnostic features of leiomyosarcoma include tumor necrosis, cytologic atypia, and mitotic activity. Since increased mitotic activity alone is sometimes seen in benign smooth muscle tumors in young women, an assessment of all three features is necessary to make a diagnosis of malignancy.
Recurrence after removal is common with these cancers, and many metastasize, typically to the lungs.
Endometrial Carcinoma (EMC)After the dramatic drop in the incidence of cervical carcinoma, EMC is currently the most frequent cancer occurring in the female genital tract.
Epidemiology and Pathogenesis
EMC appears most frequently around the age of 60 years. There are two clinico-pathological settings in which endometrial carcinomas arise:
1. In perimenopausal women with estrogen excess; these are of endometrioid type
2. In older women with endometrial atrophy; these are of serous type.
Well-defined risk factors for endometrioid carcinoma include
a. Obesity: associated with increased synthesis of estrogens in fat depots
d. Infertility: women tend to be nulliparous, often with anovulatory cycles.
At least some of these risk factors point to increased estrogen stimulation, and indeed it is well recognized that prolonged estrogen replacement therapy and estrogen-secreting ovarian tumors increase the risk of this form of cancer. Many of these risk factors are the same as those for endometrial hyperplasia, and endometrial carcinoma frequently arises on a background of endometrial hyperplasia. Mutations in DNA mismatch repair genes and PTEN have been demonstrated. Serous carcinoma of the endometrium typically arises in a background of atrophy. Nearly all cases have mutations in the p53 tumor suppressor gene.
EMC may be exophytic (fungating, polypoid) or infiltrative.
The endometrioid carcinoma consists of malignant endometrial-like tubular glands of varying grades. Squamous metaplasia is frequent. Sometimes, the tumor is adeno-squamous carcinoma.
Tumors originate in the mucosa and may infiltrate the myometrium and enter vascular spaces, with metastases to regional lymph nodes.
Serous carcinoma forms small tufts and papillary arrangements rather than the glands seen in endometrioid carcinoma, and has much greater cytologic atypia. They are particularly aggressive .
Patients with EMC presents with leukorrhea and irregular bleeding. With progression, the uterus may become palpable, and in time it becomes fixed to surrounding structures by extension of the cancer beyond the uterus. EMCs are usually late-metastasizing neoplasms, but dissemination eventually occurs, with involvement of regional nodes and more distant sites. The prognosis depends heavily on the stage of the disease.