Lec.no.2/Female genital tract
Dr.Ro
,
aa S.Mahdi
THE UTERUS
Endometritis
*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.
Adenomyosis
This 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.
Endometriosis
This 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 features
• Endometriosis 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.
Microscopic features
• 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 Hyperplasia
This 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 features
• In simple hyperplasia the endometrium is diffusely thickened.
• In complex & atypical hyperplasia there is usually focal thickening of the
endometrium.
Microscopic features
• 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 typical and 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 Myometrium
The 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.
Microscopic features
• 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.
Gross features
• 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 features
• They 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
b. Diabetes
c. Hypertension
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.
Gross features
• EMC may be exophytic (fungating, polypoid) or infiltrative.
Microscopic features
• 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.