Kotebe University of Education

Department of Medical Radiology Technology

Pathology Individual assignment

Submitted to: Dr, Betelhem

Tume Guyo
MRT\R\020\1
Submission date: Jul 21
 Cervix
lesions are often minor inflammations, but they are also the site of one of the most common
cancers in women worldwide. Cervicitis can be classified as infectious or noninfectious, but
differentiation is difficult due to the presence of normal vaginal flora. Pathogens that are more
important include Chlamydia trachomatis, Urea plasma urealyticum, T. vaginalis, Neisseria
gonorrhoeae, HSV-2, and certain types of HPV. C. trachomatis is the most common, accounting
for up to 40% of cases. Cervicitis is often diagnosed during routine examinations or due to
leukorrhea. It is often treated with antibiotics against Chlamydia and gonococcus, and nucleic
acid amplification tests are used to identify the presence of these organisms.

Most cervix tumors are epithelial and caused by HPV strains. During development, the
columnar mucus-secreting epithelium joins the exocervix's squamous epithelial covering. As
puberty approaches, the squamocolumnar junction everts, revealing the columnar epithelium.
Exposed columnar cells eventually undergo squamous metaplasia, forming the transformation
zone, where tumors most commonly arise

Pathogenesis
HPV, the causative agent of cervical neoplasia, has a tropism for immature squamous cells in
the Trans formation zone. Most HPV infections are transient and are eliminated within months
by the host immune response. However, some infections persist and cause squamous
intraepithelial lesions (SILs), which are precursors to most invasive cervical carcinomas. HPV is
detectable by molecular methods in nearly all cases of cervical intraepithelial neoplasia (CIN)
and cervical carcinoma. Risk factors for CIN and invasive carcinoma development are directly
related to HPV exposure, including early age at first intercourse, multiple sexual partners, male
partners with multiple previous sexual partners, and persistent infection by high-risk strains of
papillo mavirus.
HPV solves this problem through the action of two viral oncoproteins, E6 and E7. E6 and E7
proteins of "high risk" HPV variants inhibit p53 and RB, two potent tumor suppressors that
suppress the division of squamous cells as they mature. These proteins play a central role in the
life cycle of HPV and explain its carcinogenic activity in the cervix and other sites prone to HPV
infection. HPV variants are classified as high-risk or low-risk types based on their propensity to
induce carcinogenesis.
High-risk HPV infection is the primary risk factor for the development of squamous intraepithelial lesion
(SIL) that can progress to cervical carcinoma. Two high-risk HPV viruses, types 16 and 18, account for
around 70% of cases of SIL and cervical carcinoma. These HPV types are more likely to persist and
integrate into the host cell genome, which is linked to progression. Low-risk HPV variants, such as types
6 and 11, express E6 and E7 variants with different or weaker activities and do not integrate into the
host genome. However, HPV is not sufficient to drive the neoplastic process. Factors such as immune
and hormonal status, coinfection with other sexually transmitted agents, and viral integration contribute
to the transformation. Viral integration disrupts an HPV gene that negatively regulates E6 and E7,
leading to increased expression. Additionally, HPV integrates near a host cell oncogene, such as MYC,
leading to its overexpression.

Squamous intraepithelial lesion (SIL) is a precancerous epithelial change that usually precedes the
development of an overt cancer by many years, sometimes decades. The classification of cervical
precursor lesions has evolved over time, with the current terminology being a two-tiered system that
reflects the biology of the disease and patient management. LSILThe decision to treat cervical
precancerous lesions (HSI) and observe cervical cancer (LSIL) is based on differences in their natural
histories. Cervical precancerous lesions are associated with abnormal malities in cytologic preparations,
which can be detected long before any abnormality is visible on gross inspection.

Early detection of SIL is the rationale for the Papanicolaou (Pap) test, which is the most successful
cancer-screening test ever developed. In the United States, Pap screening has dramatically lowered the
incidence of invasive cervical tumors to about 13,000 cases annually with a mortality of about 4000 per
year. However, the incidence of SIL has increased to over 50,000 cases annually, and increased detection
has contributed to this. The U.S. Food and Drug Administration has approved testing for HPV DNA in
cervical scrapings, which is highly sensitive but has lower specificity than the Pap smear. HPV DNA
screening is only recommended for women aged 30 or older, as a positive test at this age is more likely
to identify an individual with a persistent infection that may lead to cervical neoplasia. The quadrivalent
HPV vaccine for types 6, 11, 16, and 18, and the 9-valent vaccine are effective in preventing HPV
infections and are expected to greatly lower the frequency of genital warts and cervical cancers
associated with these HPV genotypes.

However, vaccination does not replace the need for routine cervical cancer screening, as many at-risk
women are already infected, and current vaccines protect against only some of the many oncogenic HPV
genotypes. SIL is asymptomatic and comes to clinical attention through an abnormal Pap smear result.
Women with biopsy-documented LSIL are managed conservatively with careful observation, while HSILs
and persistent LSIL are treated with surgical excision (cone biopsy). Follow-up smears and clinical
examination are required in patients with HSI. is associated with productive HPV infection and does not
progress directly to invasive carcinoma, while HSIL demonstrates increased proliferation, arrested
epithelial maturation, and lower viral replication. LSIL is not treated as a premalignant lesion, while HSIL
is considered at high risk for progression to carcinoma. Patient management relies on histopathologic
diagnosis.

Women are at risk for HPV-associated cervical, vulvar, and vaginal cancers. The most common
cervical carcinomas are squamous cell carcinomas (75%), followed by adenocarcinomas, mixed
adenosquamous carcinomas (20%), and small cell neuroendocrine carcinomas (<5%). The
proportion of adenocarcinomas has increased in recent decades due to the decreasing
incidence of invasive squamous carcinoma and suboptimal detection of glandular lesions by Pap
smear.
Squamous cell carcinoma has a peak incidence at age 45 years, some 10 to 15 years after
detecting precursor SIL. The progression of SIL to invasive carcinoma is variable and
unpredictable, requiring HPV infection and mutations in tumor suppressor genes and
oncogenes. Risk factors for progression include cigarette smoking and HIV infection, suggesting
that immune surveillance plays a role in preventing progression. Regular physical examinations,
Pap smears, and biopsy of suspicious lesions are the only reliable ways to monitor the disease
course.

Clinical feature
Invasive cervical cancer is common in women who have not had a Pap smear or have not been
screened for years. Symptoms include vaginal bleeding, leukorrhea, painful coitus, or dysuria.
Primary treatment is cystectomy and lymph node dissection, with small micro invasive
carcinomas treated with cone biopsy. Radiation and chemotherapy may be beneficial in cases
where surgery is not curative. Mortality is strongly predicted by tumor stage and cell type, with
neuroendo crine carcinomas having an aggressive course.

Endocervical polyps
They benign polyploidy masses protruding from the endocervcal mucosa, with a smooth
surface and underlying cystic spaces filled with mucinous secretions. The surface epithelium
and lining of the cysts are composed of mucus-secreting columnar cells, while the stroma is
edematous and may contain scattered mononuclear cells. Chronic inflammation may lead to
squamous metaplasia and ulcerations, which may bleed but have no malignant potential.

The uterus
It is composed of the endo metrium, consisting of glands and stroma, and the myo metrium,
made of smooth muscle. The most common and significant disorders of the uterus are
endometritis, which is classified as acute or chronic depending on whether a neutrophilic or lym
phoplasmacytic infiltrate predominates. Chronic endometritis typically requires the presence of
plasma cells, as lymphocytes are present even in the normal endometrium. Endometritis is a
component of pelvic inflammation disease and is often caused by N.gonorrhoeae or C.
trachomatis infection.
Histologic examination shows a neutrophilic infiltrate in the superficial endometrium coexisting
with a stromal lymphoplasmacytic infiltrate. Tuberculous endometritis causes granulo matous
endometritis, often with associated tuberculous salpingitis and peritonitis. Endometritis may
also result from retained products of conception, foreign bodies, or retained products of
conception. Retained tissue or foreign bodies act as a nidus for infection by vaginal or intestinal
tract flora, and removal typically results in resolution.

Adenomyosis
 is the presence of endometrial tissue in the myometrium, causing reactive hypertrophy and
resulting in an enlarged, globular uterus. Extensive adenomyosis can cause menorrhagia,
dysmenorrhea, and pelvic pain, especially just before menstruation. Endometriosis, on the
other hand, is defined by the presence of endometrial glands and stroma outside the uterus. It
occurs in 10% of women and nearly half of women with infertility. Endometriosis often involves
pelvic structures, distant areas of the peritoneal cavity, or distant sites like lymph nodes, lungs,
and heart, skeletal muscle, or bone. Four hypotheses have been proposed to explain the origin
of dispersed endometriosis lesions: regurgitation theory, benign metastases theory, metaplastic
theory, and extra uterine stem/progenitor cell theory.
Studies suggest that endometriosis tissue is not just misplaced but also abnormal. It exhibits
increased levels of inflammatory mediators, particularly prostaglandin E2, which is believed to
result from recruitment and activation of macrophages by endometrial stromal cells. Stromal
cells also produce aromatase, leading to local production of estrogen. These factors enhance
the survival and persistence of endometriotic tissue within a foreign location, which is a key
feature in the pathogenesis of endometriosis. The beneficial effects of COX-2 inhibitors and
aromatase inhibitors in treating endometriosis are explained by these factors.

Clinical feature
Endometriosis causes discomfort in the lower abdomen and eventual sterility due to extensive
scarring of the follicles and ovaries. Rectal wall involvement can cause pain during defecation,
while uterine or bladder serosa involvement can cause dyspareunia and dysuria. Most cases
result in severe dysmenorrhea and pelvic pain due to intrapelvic bleeding and intraabdominal
adhesions.

Abnormal uterine bleeding

is a common issue for women, causing menorrhagia, metrorrhagia, or postmeno pausal
bleeding. Common causes include dysfunctional uterine bleeding, endometrial polyps,
leiomyomas, endometrial hyperplasia, and endometrial carcinoma. The probable cause varies
depending on the patient's age. Dysfunctional uterine bleeding is the most common cause, with
anovulation being the most common cause. Anovulatory cycles result from hormonal
imbalances and are common during menarche and the menopausal period. Less common
causes include endocrine disorders, ovarian lesions, and generalized metabolic disturbances.
Dysfunctional uterine bleeding may also result from an inadequate luteal phase, which is
thought to stem from insufficient progesterone production by the corpus luteum.

PROLIFERATIVE LESIONS OF THE ENDOMETRIUM AND

MYOMETRIUM
Endometrial hyperplasia
Endometrial carcinomas, endometrial polyps, and smooth muscle tumors are common
proliferative lesions of the uterine corpus, causing abnormal uterine bleeding as their earliest
manifestation. Hyperplasia is an important precursor of endometrial carcinoma, which is
caused by an excess of estrogen relative to progestin. Other potential causes include obesity,
failure of ovulation, prolonged administration of estrogenic steroids without counterbalancing
progestin, and estrogen-producing ovarian lesions. Endometrial hyperplasia is classified into
two categories based on the presence of cytologic atypia: hyperplasia without atypia and
hyperplasia with atypia.
The presence of cytologic atypia correlates with the development or concurrent finding of
endometrial carcinoma. Hyperplasia without cellular atypia has a low risk (between 1% and 3%)
for progression to endometrial carcinoma, while hyperplasia with atypia, also called
endometrial intraepithelial neoplasia (EIN), is associated with a much higher risk (20%–50%).
Unopposed estrogen is also a risk factor for endometrial carcinoma, and inactivation of the
PTEN tumor suppressor gene has been identified at a substantial frequency in hyperplasia with
atypia (approximately 50%) and endometrioid carcinoma (>70%). Clinic pathologic and
epidemiologic studies indicate that hyperplasia with atypia is a precursor lesion for
endometrioid endometrial carcinoma.
Endometrial carcinoma
The most common cancer in the female genital tract in the US and Western countries, typically
occurring between 55 and 65 years old. It can be divided into two categories: endometrioid and
serous carcinoma. Other less common types include clear cell carcinoma and mixed Mullerian
tumor (carci nosarcoma).

Pathogenesis
Endometrioid cancers are caused by estrogen excess in the context of endometrial hyperplasia
in perimenopausal women, while serous cancers arise in the setting of endometrial atrophy in
older postmenopausal women. Endometrioid cancers account for 80% of cases, and risk factors
include obesity, diabetes, hypertension, infertility, and exposure to unopposed estrogen. These
factors increase estrogenic stimulation of the endometrium and are associated with
endometrial hyperplasia. Prolonged estrogen replacement therapy and estrogen-secreting
ovarian tumors increase the risk of endometrioid type endometrial carcinoma. Mutations in
mismatch repair genes and the tumor suppressor gene PTEN are early events in the
development of endometrioid carcinoma.
Women with germline mutations in PTEN and DNA mismatch repair genes are at high risk for
this cancer. TP53 mutations occur but are relatively uncommon and late events in the genesis
of this tumor type. Serous endometrial carcinoma is less common but more aggressive,
accounting for roughly 15% of tumors and not associated with unopposed estrogen or
endometrial hyperplasia.
Most cases of serous carcinoma have mutations in the TP53 tumor suppressor gene, while
mutations in DNA mismatch repair genes and PTEN are rare. Serous tumors are preceded by a
lesion called serous endometrial intraepithelial carcinoma (SEIC), suggesting an early role for
these mutations in the development of this form of endometrial carcinoma.

Clinical feature
Endometrial carcinomas typically show irregular or postmenopausal bleeding and progress to
uterus enlargement and tissue attachment. They are slow to metastasize but can spread to
distant sites if left untreated. Early-stage endometrioid carcinomas have a 90% 5-year survival
rate, while higher-stage tumors have a precipitous drop. Serous carcinomas have a poor
prognosis due to aggressive behavior and operative staging.

Endometrial polyps
They are sessile, 0.5-3 cm in diameter, and are composed of endometrium resembling the
basalis. They are often found during menopause and can cause abnormal uterine bleeding.
Leiomyomas, benign tumors arising from smooth muscle cells in the myometrium, are the most
common benign tumor in females, affecting 30% to 50% of reproductive-age women. They are
associated with recurrent chromosomal abnormalities, including rearrangements of
chromosomes 6 and 12. Mutations in the MED12 gene have been identified in up to 70% of
leiomyomas, but the mechanism by which they contribute to their development is not yet
understood.
Estrogens and oral contraceptives can stimulate the growth of leiomyomas, while they shrink
postmenopausally. Leiomyomas are often asymptomatic and are discovered incidentally during
routine pelvic examination. The most common presenting sign is menorrhagia, with or without
metrorrhagia. Leiomyomas rarely transform into sarcomas, and the presence of multiple lesions
does not increase the risk of malignancy.

Leiomyosarcomas
Leiomyosarcomas of the uterus are solitary, arising from mesenchymal cells of the myome
trium, and are most common in postmenopausal women. They often recur after surgery and
metastasize to the lungs, with a 5-year survival rate of 40%. Anaplastic tumors have a less
favorable outlook than well-differentiated ones.

Fallopian tubes
 They are a common disorder causing inflammation (salpingitis) as a component of pelvic
inflammatory disease. Infections, such as gonorrhea and nononococcal organisms like
Chlamydia, Mycoplasma hominis, coli forms, and streptococci and staphylococci, are the major
offenders. Gonococci produce similar morphologic changes to those in the male genital tract.
Infections with coliforms, streptococci, and staphylococci can penetrate the tubes, leading to
blood-borne infections that seed distant sites.
Tuberculous salpingitis is less common and often occurs in combination with tuberculous
endometritis. All forms of salpingitis may cause fever, lower abdominal or pelvic pain, and
pelvic masses. Adherence of the inflamed tube to the ovary and adjacent ligamentous tissues
may result in tuboovarian abscess, adhesions between the ovary and tubes, and even more
serious adhesions of the tubal plicae, which increase the risk of tubal ectopic pregnancy.

Ovaries
Follicle and luteal cysts are common lesions in the ovaries, often developing adjacent to the
serosa. These cysts are typically small (1-1.5 cm in diameter) filled with clear serous fluid. They
can become large (4-5 cm) and produce palpable masses and pelvic pain. They are lined by
granulosa lining cells or luteal cells, but pressure may cause atrophy. Sometimes, cysts rupture,
causing intraperitoneal bleeding and peritoneal symptoms, such as acute abdomen.

Polycystic ovarian syndrome

a complex endocrine disorder characterized by hyperandrogenism, menstrual abnormalities,
polycystic ovaries, chronic anovulation, and decreased fertility. It is common in teenage girls or
young adults and can cause oligomenorrhea, hirsutism, infertility, and obesity. The ovary is gray
white, gray with a smooth outer cortex, and is characterized by subcortical cysts 0.5 to 1.5 cm
in diameter. Histologic examination shows a thickened capsule with cystic follicles lined by
granulosa cells and a hyperplastic luteinized theca interna.

Tumors of the ovary

In the United States, over 20,000 ovarian cancer cases are expected to be diagnosed in 2016,
leading to over 14,000 deaths. Tumors of the ovary are diverse, with neoplasms of epithelial
origin accounting for the majority of ovarian tumors and malignant forms accounting for almost
90% of ovarian cancers. Germ cell and sex cord-stromal cell tumors are less frequent,
accounting for 20% to 30% of ovarian tumors but collectively responsible for less than 10% of
malignant tumors. The majority of ovarian tumors arise from the fallopian tube or epithelial
cysts in the cortex of the ovary. Studies have shown that many of the tumors thought to arise
from the coelomic epithelium now appear to arise from the fimbriated end of the fallopian
tube. These epithelial tumors can become metaplastic or undergo neoplastic transformation,
leading to various types of tumors.
Some ovarian epithelial tumors fall into an intermediate category called borderline tumors,
which can recur and progress to carcinoma. Risk factors for ovarian cancer include nul liparity,
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. Prolonged
use of oral contraceptives reduces the risk. Around 5% to 10% of ovarian cancers are familial,
most of which are associated with mutations in the BRCA1 or BRCA2 tumor suppressor genes.
Mutations in BRCA1 and BRCA2 are also associated with hereditary breast cancer. The average
lifetime risk for ovarian cancer is approximately 30% in BRCA1 carriers, while the risk in BRCA2
carriers is somewhat lower. Serous tumors are the most common of the ovarian epithelial
tumors and make up the greatest fraction of malignant ovarian tumors. About 60% of benign
tumors are benign, 15% are borderline, and 25% are malignant. Benign lesions are typically
encountered in patients between 30 and 40 years of age, while malignant serous tumors are
more commonly seen between 45 and 65 years of age.
There are two types of serous carcinomas: low-grade and high-grade. Low-grade tumors arise
from benign or borderline lesions and progress slowly to become invasive carcinoma. High-
grade serous tumors develop rapidly, often arising in the fimbriated end of the fallopian tube
via serous tubal intraepithelial carcinoma.
High-grade serous carcinoma patients have poor prognosis, even after surgery and
chemotherapy, and depends on the disease stage. Women with carcinoma confined to one
ovary have a 5-year survival rate of about 90%, but higher stage tumors can lead to less than
40% survival. Borderline tumors have nearly 100% survival. Women with BRCA1/2 mutations
have better prognosis. Mucinous tumors are less likely to be malignant, with only 10%
malignant, 10% borderline, and 80% benign.
Mucinous cystadenocarcinoma has a better prognosis than its serous counterpart, but stage is
the major determinant. Mutations in KRAS are detected in about 50% of ovarian mucinous
carcinomas, but this doesn't differentiate them from metastatic GI tumors with high KRAS
mutation frequencies. Endometrioid tumors can be solid or cystic.

Endometrioid tumors
, sometimes associated with endometriosis, are malignant ovarian tumors with tubular glands
within cystic spaces. They are bilateral in 30% of cases and 15% to 30% of women with these
tumors have a concomitant endometrial carcinoma. These tumors often have mutations in the
PTEN tumor suppressor gene and other genes that upregulate PI3K-AKT signaling. The Brenner
tumor is an uncommon solid, usually unilatrular ovarian tumor with abundant stroma and
transitional-type epithelium nests. Brenner tumors are smooth, gray-white, and can arise from
surface epithelium or urogenital epithelium trapped within the germinal ridge. Although most
are benign, both malignant and borderline tumors have been described.
Teratomas, which are germ cell and sex cord stromal tumors, are the most common type of
ovarian tumors. Teratomas constitute 15% to 20% of ovarian tumors, with a higher likelihood of
malignancy in the first 2 decades of life. Over 90% of these germ cell neoplasms are benign
mature cystic teratomas, with the immature, malignant variant being rare. Benign (mature)
cystic teratomas are marked by the presence of mature tissues derived from all three germ cell
layers: ectoderm, endoderm, and mesoderm.
They are often found in young women as ovarian masses or found incidentally on abdominal
radiographs or scans. About 90% are unilateral, with the right side more commonly affected.
These cystic masses are often filled with sebaceous secretion and matted hair, sometimes with
a nodular projection. Malignant transformation, usually to squamous cell carcinoma, occurs in
about 1% of cases. Immature malignant teratomas are found early in life, with a mean age at
clinical detection of 18 years. They are bulky and appear solid on cut section, often containing
areas of necrosis. On microscopic examination, the distinguishing feature is the presence of
immature elements or minimally differentiated cartilage, bone, muscle, nerve, or other tissues.
Specialized teratomas are rare subtypes composed entirely of specialized tissue, such as struma
ovarii. These tumors are more common in young women and are more likely to produce
infertility and require surgical intervention.
Teratomas in ovary, primarily mature thyroid tissue, can cause hyperthyroidism and carcinoid
syndrome.

Clinical feature
Ovarian neoplasms are a challenging clinical challenge due to their advanced nature. Surface
epithelial tumors are usually asymptomatic until they cause local pressure symptoms. About
30% of ovarian neoplasms are discovered incidentally on routine gynecologic examinations.
Larger masses, particularly common epithelial tumors, may cause abdominal girth increase.
Smaller masses, like dermoid cysts, can cause severe abdominal pain. Metastatic seeding of
malignant serous tumors can cause ascites, while functioning tumors produce
endocrinopathies. Unfortunately, treatment for ovarian tumors remains unsatisfactory.
Since the mid-1970s, survival rates have increased, but screening methods for early tumor
detection are limited. CA-125, a protein elevated in 75% to 90% of women with epithelial
ovarian cancer, is undetectable in up to 50% of ovary-limited cancers and often elevated in
benign conditions and nonovarian cancers. Its usefulness as a screening test in asymptomatic
postmenopausal women is limited. CA-125 measurements are currently valuable for monitoring
therapy response.