MINILIK II MEDICAL AND
HEALTH SCIENCE COLLEGE
Pathology assignment
Setna Besufekad
Id: MRT/R/016/14
Submitted to Dr.Bethelhem
Submission Date:july21/2023
Female Genital System pathology
(Cervical, endometrial , ovarian pathology )
Cervix
Most cervical lesions are relatively banal inflammations (cervicitis), but the cervix
also is the site of one of the most common cancers in women worldwide.
CERVICITIS
Inflammatory conditions of the cervix are extremely common and may be associated
with a purulent vaginal discharge.Most tumors of the cervix are of epithelial origin
and are caused by oncogenic strains of HPV,With the onset of puberty, the
squamocolumnar junction undergoes eversion, causing the columnar epithelium to
become visible on the exocervix. The exposed columnar cells, however, eventually
undergo squamous metaplasia, forming a region called the transformation zone, where
tumors most commonly arise.Cervicitis can be subclassified as infectious or
noninfectious, although differentiation is difficult owing to the presence of normal
vaginal flora including incidental vaginal aerobes and anaerobes, streptococci,
staphylococci, enterococci, and Escherichia coli and Candida spp. Much more
important are Chlamydia trachomatis, Urea plasma urealyticum, T. vaginalis,
Neisseria gonorrhoeae, HSV-2 (the agent of herpes genitalis), and certain types of
HPV, all of which are often sexually transmitted. C. trachomatis is by far the most
common of these pathogens.Although less common, herpetic infections are
noteworthy because maternal–infant transmission during childbirth may result in
serious, some times fatal systemic herpetic infection in the newborn.
Cervicitis commonly comes to attention on routine examination or because of
leukorrhea. It often is treated empirically with antibiotics that are active against
chlamydia and gonococcus. In some instances, nucleic acid amplification tests are
used on vaginal fluid to identify the presence of these organisms as well as
Trichomonas vaginalis.
Pathogenesis
HPV, the causative agent of cervical neoplasia, has a tropism for the immature
squamous cells of the transformation zone. Most HPV infections are transient and are
eliminated within months by the host immune response. some causesquamous
intraepithelial lesions (SILs), HPV is detectable by molecular methods in nearly all
cases of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. Important
risk factors for the development of CIN and invasive carcinoma thus are directly
related to HPV exposure and include: • Early age at first intercourse • Multiple sexual
partners • Male partner with multiple previous sexual partners • Persistent infection by
high-risk strains of papillo mavirus Like most other DNA viruses, HPV uses host cell
DNA polymerases to replicate its genome and produce virions.
High-risk HPV infection is the most important risk factor for the development of SIL
that can progress to carcinoma. Two high-risk HPV viruses, types 16 and 18, account
for approximately 70% of cases of SIL and cervical carcinoma. Low-risk HPV
variants (e.g., types 6 and 11) associated with the development of condylomas of the
lower genital tract, HPV is not sufficient to drive the neoplastic process. As
mentioned later, HPV infected high-grade precursor lesions do not invariably progress
to invasive cancer. Diverse other factors such as immune and hormonal status and
coinfection with other sexually transmitted agents are suspected to play a role
Squamous Intraepithelial Lesion (SIL, Cervical Intraepithelial Lesion)
HPV-related carcinogenesis begins with the precancerous epithelial change termed
SIL, • SIL is divided into low-grade squamous intraepithelial lesion (LSIL), still often
referred to as cervical intraepithelial neoplasia I (CIN I), and high-grade squamous
intraepithelial lesion (HSIL), encompassing cervical intraepithelial neoplasia II and III
(CIN II and III) of the previous three-tiered system. • LSIL is associated with
productive HPV infection and does not progress directly to invasive carcinoma. Actu
ally, most LSILs regress and only a small percentage progress to HSIL. LSIL is not
treated as a premalignant lesion, whereas HSIL is considered at high risk for
progression to carcinoma. Importantly, LSIL is 10 times more common than HSIL
and while HSILs are precancerous, the majority of them fail to progress to cancer and
may even regress.
SIL is asymptomatic and comes to clinical attention through an abnormal Pap smear
result. These cases are followed up by colposcopy, in which acetic acid is used to
highlight the lesions so they can be biopsied. Women with biopsy-documented LSIL
are managed conservatively with careful observation, whereas HSILs and persis tent
LSIL are treated with surgical excision (cone biopsy). Follow-up smears and clinical
examination are required in patients with HSIL, as these women remain at risk for
HPV-associated cervical, vulvar, and vaginal cancers.
Invasive Carcinoma of the Cervix The most common cervical carcinomas are
squamous cell carcinomas (75%), followed by adenocarcinomas and mixed
adenosquamous carcinomas (20%) and small cell neuroendocrine carcinomas (<5%).
Risk factors for progression include cigarette smoking and human immunodeficiency
virus (HIV) infection, the latter finding suggesting that immune surveillance plays a
role in preventing progression. .
Clinical Features
Invasive cervical cancer most often is seen in women who have never had a Pap
smear or who have not been screened for many years. In such cases, cervical cancer
often is symptomatic, with patients coming to medical attention for unexpected
vaginal bleeding, leukorrhea, painful coitus (dyspareunia), or dysuria. The primary
treatment is hysterectomy and lymph node dissection; small microinvasive
carcinomas may be treated with cone biopsy. Radiation and chemotherapy are also of
benefit in instances where surgery alone is not curative. Mortality is most strongly
predicted by tumor stage and, in the case of neuroendo crine carcinomas (which
pursue an aggressive course) to cell type.
Endocervical Polyp
Endocervical polyps are benign polypoid masses seen protruding from the
endocervical mucosa (sometimes through the exocervix). They can be as large as a
few centimeters and have a smooth, glistening surface with underlying cystically
dilated spaces filled with mucinous secretions. The surface epithelium and lining of
the underlying cysts are composed of the same mucus-secreting columnar cells that
line the endocervical canal. The stroma is edematous and may contain scattered
mononuclear cells. Superimposed chronic inflammation may lead to squamous
metaplasia of the overlying epithelium and ulcerations. These lesions may bleed,
thereby arousing concern, but they have no malignant potential.
Uterus
The body (corpus) of the uterus is composed of the endo metrium, consisting of
glands and stroma, and the myo metrium, made up of smooth muscle. The more
frequent and significant disorders of the uterus are considered here. ENDOMETRITIS
Inflammation of the endometrium is classified as acute or chronic depending on
whether a neutrophilic or a lymphoplasmacytic infiltrate predominates, respectively.
The diagnosis of chronic endometritis generally requires the presence of plasma cells,
as lymphocytes are present even in the normal endometrium. Endometritis is a
component of pelvic inflammatory disease and is frequently a result of N.
gonorrhoeae or C. trachomatis infection. Histologic examination shows a neutrophilic
infiltrate in the superficial endometrium coexisting with a stromal lymphoplasmacytic
infiltrate. Endometritis also may be a result of retained products of conception
subsequent to miscarriage or delivery or the presence of a foreign body such as an
intrauterine device. Retained tissue or foreign bodies act as a nidus for ascending
infection by vaginal or intestinal tract flora. Removal of the offending tissue or
foreign body typically results in resolution.
ADENOMYOSIS
Adenomyosis refers to the presence of endometrial tissue in the myometrium. Nests
of endometrial stroma, glands, or both are found deep in the myometrium interposed
between the muscle bundles. This endometrial tissue induces reactive hypertrophy of
the myometrium, resultingin an enlarged, globular uterus, often with a thickened
uterine wall. Extensive adenomyosis may produce menorrhagia, dysmenorrhea, and
pelvic pain, particularly just prior to menstruation, and can coexist with
endometriosis. ENDOMETRIOSIS Endometriosis is defined by the presence of
endometrial glands and stroma in a location outside the uterus. It occurs in as many as
10% of women in their reproductive years and in nearly half of women with
infertility. It fre quently is multifocal and often involves pelvic structures (ovaries,
pouch of Douglas, uterine ligaments, tubes, and rectovaginal septum). Less
frequently, distant areas of the peritoneal cavity or periumbilical tissues are involved.
Uncommonly, distant sites such as lymph nodes, lungs, and even heart, skeletal
muscle, or bone are affected.
Studies suggest that endometriotic tissue is not just misplaced but is also abnormal
increased levels of inflammatory mediators, particularly prostaglandin E2. It is
proposed that the inflammation results from the recruitment and activation of
macrophages by factors made by endometrial stromal cells. Stromal cells also make
aromatase, leading to local production of estro gen. These factors enhance the survival
and persistence of the endometriotic tissue within a foreign location (a key feature in
the pathogenesis of endometriosis) and help to explain the beneficial effects of COX-
2 inhibitors and aro matase inhibitors in the treatment of endometriosis.
Clinical Features
. Extensive scarring of the fallopian tubes and ovaries often produces discomfort in
the lower abdomen and eventual sterility. Rectal wall involvment may produce pain
on defecation, whereas involvement of the uterine or bladder serosa can cause
dyspareunia (painful intercourse) and dysuria, respectively. Almost all cases feature
severe dysmenorrhea and pelvic pain resulting from intrapelvic bleeding and
intraabdominal adhesions.
ABNORMAL UTERINE BLEEDING
Activated macrophages Women commonly seek medical attention for abnormal
uterine bleeding, such as menorrhagia (profuse or pro longed bleeding at the time of
the period), metrorrhagia (irregular bleeding between the periods), or postmeno pausal
bleeding. Common causes include dysfunctional uterine bleeding, endometrial polyps,
leiomyomas, endo metrial hyperplasia, and endometrial carcinoma. The probable
cause of uterine bleeding in any given case varies depending on the age of the patient
Abnormal bleeding from the uterus in the absence of an organic uterine lesion is
called dysfunctional uterine bleeding. The most common cause of dysfunctional
uterine bleed ing is anovulation (failure to ovulate).
PROLIFERATIVE LESIONS OF THE ENDOMETRIUM AND
MYOMETRIUM
The most common proliferative lesions of the uterine corpus are endometrial
hyperplasia, endometrial carcinomas, endometrial polyps, and smooth muscle tumors.
All tend to produce abnormal uterine bleeding as their earliest manifestation.
Endometrial Hyperplasia An excess of estrogen relative to progestin, if sufficiently
prolonged or marked, can induce exaggerated endometrial proliferation (hyperplasia),
Endometrial hyperplasia is placed in two categories based on the presence of
cytologic atypia: hyperplasia without atypia and hyperplasia with atypia. The
importance of this classification is that the presence of cytologic atypia correlates with
the development or concurrent finding of endometrial carcinoma. Hyperplasia without
cellular atypia carries a low risk (between 1% and 3%) for progression to endometrial
carcinoma, whereas hyperplasia with atypia, also called endometrial intraepithelial
neoplasia (EIN), is associated with a much higher risk (20%–50%).
Pathogenesis
Endometrioid cancers arise in association with estrogen excess in the setting of
endometrial hyperplasia in peri menopausal women, whereas serous cancers arise in
the setting of endometrial atrophy in older postmenopausal women. Risk factors for
this type of carcinoma include (1) obesity, (2) diabetes, (3) hypertension, (4)
infertility, and (5) exposure to unopposed estrogen. Many of these risk factors result
in increased estrogenic stimulation of the endometrium and are associated with
endometrial hyperplasia. In fact, it is well rec ognized that prolonged estrogen
replacement therapy and estrogen-secreting ovarian tumors increase the risk of the
endometrioid type of endometrial carcinoma. Mutations in mismatch repair genes and
the tumor suppressor gene PTEN are early events in the stepwise development of
endometrioid carcinoma.
Clinical Features
Endometrial carcinomas usually manifest with irregular or postmenopausal bleeding.
With progression, the uterus enlarges and may become affixed to surrounding struc
tures as the cancer infiltrates surrounding tissues
Endometrial Polyps
These polyps are usually sessile and range from 0.5 to 3 cm in diameter. Larger
polyps may project from the endometrial mucosa into the uterine cavity. They are
composed of endometrium resembling the basalis, frequently with small muscular
arteries. Some glands are normal architecturally, but more often they are cystically
dilated. Although endometrial polyps may occur at any age, they are most common
around the time of menopause. Their main clinical significance is that they may
produce abnormal uterine bleeding. Leiomyoma Benign tumors that arise from the
smooth muscle cells in the myometrium are properly termed leiomyomas are the most
common benign tumor in females, affecting 30% to 50% of women of reproductive
age, and are considerably more frequent in black women. These tumors are associated
with several different recurrent chromosomal abnormalities, including rearrangements
of
chromosomes 6 and 12 that also are found in a variety of other benign neoplasms,
leiomyomas
Leiomyomas of the uterus often are asymptomatic, being discovered incidentally on
routine pelvic examina tion. The most frequent presenting sign is menorrhagia, with
or without metrorrhagia. Leiomyomas rarely, if ever, transform into sarcomas, and the
presence of multiple lesions does not increase the risk of malignancy.
Leiomyosarcoma
Leiomyosarcomas of the uterus virtually always arise de novo from the mesenchymal
cells of the myometrium. They are almost always solitary and most often occur in
postmenopausal women, in contradistinction to leiomyomas, which frequently are
multiple and usually arise premenopausally. Recurrence after surgery is common with
these cancers, and many metastasize, typically to the lungs, yielding a 5-year survival
rate of about 40%. The outlook with anaplastic tumors is less favorable than with
well- differentiated tumors.
Fallopian Tubes
The most common disorder of the fallopian tubes is inflammation (salpingitis), almost
invariably occurring as a component of pelvic inflammatory disease. Less common
abnormalities are ectopic (tubal) pregnancy and endometriosis. Inflammation of the
fallopian tubes is almost always caused by infection. In addition to gonorrhea,
nongonococcal organisms, such as Chlamydia, Mycoplasma hominis, coli forms, and
(in the postpartum setting) streptococci and staphylococci are the major offenders.
Tuberculous salpingitis is far less common and is almost always encountered in
combination with tuberculous endometritis. All forms of salpingitis may produce
fever, lower abdominal or pelvic pain, and pelvic masses, which are the result of
distention of the tubes with either exudate or inflammatory debris
Ovaries
FOLLICLE AND LUTEAL CYSTS
Follicle and luteal cysts in the ovaries are so common place that they may be
considered variants of normal physiol ogy. These innocuous lesions originate from
unruptured graafian follicles or from follicles that rupture and then immediately seal.
When small, they are lined by granulosa lining cells or luteal cells, but as fluid
accumulates, pressure may cause atrophy of these cells. Sometimes these cysts
rupture, pro ducing intraperitoneal bleeding and peritoneal symptoms (acute
abdomen).
POLYCYSTIC OVARIAN SYNDROME
Polycystic ovarian syndrome (formerly called Stein-Leventhal syndrome) is a
complex endocrine disorder characterized by hyperandrogenism, menstrual
abnormalities, polycys tic ovaries, chronic anovulation, and decreased fertility. It
usually comes to attention after menarche in teenage girls or young adults who
present with oligomenorrhea, hirsutism, infertility, and sometimes with obesity. The
ovaries are usually twice the normal size, gray white with a smooth outer cortex,There
is a conspicuous absence of corpora lutea in the ovary.
TUMORS OF THE OVARY
Tumors of the ovary are remarkably varied as they may arise from any of the three
cell types in the normal ovary: the multipotent surface (coelomic) epithelium, the
totipotent germ cells, and the sex cord–stromal cells. Neoplasms of epithelial origin
account for the great majority of ovarian tumors and, in their malignant forms,
account for almost 90% of ovarian cancers. Germ cell and sex cord–stromal cell
tumors are much less frequent.Surface Epithelial Tumors The majority of ovarian
tumors arise from the fallopian tube or epithelial cysts in the cortex of the ovary. As
mentioned
Some ovarian epithelial tumors fall into an intermediate category currently referred to
as borderline tumors. Although the majority of borderline tumors behave in a benign
manner they can recur and some can progress to carcinoma. Important risk factors for
ovarian cancer include nulliparity, family history, and germline mutations in certain
tumor suppressor genes. There is a higher incidence of carcinoma in unmarried
women and married women with low parity. Of interest, prolonged use of oral
contraceptives reduces the risk
The prognosis for patients with high-grade serous carcinoma is poor, even after
surgery and chemotherapy, and depends heavily on the stage of the disease at
diagnosis.
Similar to endometrioid-type carcinoma of the endometrium, endo metrioid
carcinomas of the ovary frequently have mutations in the PTEN tumor suppressor
gene as well as mutations in other genes that also act by upregulating PI3K-AKT
signaling.
BrennerTumor
The Brenner tumor is an uncommon, solid, usually unilateral ovarian tumor consisting
of abundant stroma containing nests of transitional-type epithelium resembling that of
the urinary tract. Occasionally, the nests are cystic and are lined by columnar mucus-
secreting cells. Brenner tumors generally are smoothly encapsulated and gray-white
on cut section, ranging from a few centimeters to 20 cm in diameter. These tumors
may arise from the surface epi thelium or from urogenital epithelium trapped within
the germinal ridge. Although most are benign, both malignant and borderline tumors
have been described.
Other Ovarian Tumors
Many other types of tumors of germ cell and sex cord stromal origin also arise in the
ovary, but only the teratomas of germ cell origin are sufficiently common to merit
description.Teratomas Teratomas constitute 15% to 20% of ovarian tumors. A
distressing feature of these germ cell tumors is their predilection to arise in the first 2
decades of life; to make matters worse, the younger the person, the greater the
likelihood of malignancy. More than 90% of these germ cell neoplasms, however, are
benign mature cystic teratomas; the immature, malignant variant is rare.A rare, but
fascinating, paraneoplastic complication is limbic encephalitis, which may develop
in women with teratomas containing mature neural tissue and often remits with tumor
resection. Malignant transformation, usually to a squamous cell carcinoma, is seen in
about 1% of cases. Immature Malignant Teratomas Malignant (immature) teratomas
are found early in life, the mean age at clinical detection being 18 years.
which is composed entirely of mature thyroid tissue that may actually produce
hyperthyroidism. These tumors appear as small, solid, unilateral brown ovarian
masses. Other specialized teratomas include ovarian carcinoid, which in rare instances
produces carcinoid syndrome.
Clinical Features
Ovarian tumors of surface epithelial origin usually are asymptomatic until they
become large enough to cause local pressure symptoms (e.g., pain, gastrointestinal
complaints, urinary frequency). Indeed, about 30% of all ovarian neoplasms are
discovered incidentally on routine gynecologic examination. Larger masses,
particularly the common epithelial tumors, may cause an increase in abdominal girth.
Smaller masses, particularly dermoid cysts, sometimes twist on their pedicles
(torsion), producing severe abdominal pain that mimics an acute abdomen. Metastatic
seeding of malignant serous tumors often causes ascites, whereas functioning ovarian
tumors often come to attention because of the endocrinopathies they produce.
Unfortunately, treatment of ovarian tumors remains unsatisfactory. .
