2. Objectives
Introduction of FGT
Clinical manifestations of FGT pathology
Pathology of Valva
Pathology of Vagina
Pathology of Cervix
Pathology of Myometrium
Pathology of Endometrium
Pathology of Fallopian tube
Pathology of Ovary
Pathology Gestational and placental disorders
3. Female Reproductive System
-The female reproductive system consists of
-The ovaries
-Secondary sex organs - which are involved in coitus,
fertilization & development, birth & nursing of the
baby.
-
4.
5. Major Organs of FGT
Vulva
Vagina
Cervix
Uterus
Uterine tubes [ fallopian tubes]
Ovaries ( The gonads )
6.
7. DISEASES OF F.G.T. INCLUDE:
-Diseases of the vulva
-Diseases of the vagina
-Diseases of the cervix
-Diseases of the Body of Uterus And Endometrium
-Diseases of the Fallopian tubes
-Diseases of the Ovaries
-Gestational and Placental disorders
8. Pathological basis of signs & symptoms in the FGT
Sign or symptom Pathological basis
-Vaginal discharge Inflammation
-Vaginal bleeding
In pregnancy Hemorrhage from placenta
(placenta
(praevia), placental bed
(miscarriage) or decidua
(ectopic pregnancy)
Post-coital Hemorrhage from cervical
lesion (carcinoma, erosion)
Post-menopausal Hemorrhage from uterine
9. -Abnormal menstruation Psychological disturbance
(timing or volume of loss) Hormonal dysfunction
Defect in local haemostasis
Uterine lesions (Fibroid,polyp, IUD)
-Pain Pathologic distension/rupture
(tubal ectopic pregnancy),Muscular
spasm (uterine),Ischemia or
infarction (ovarian torsion),
menstrual pain due to
adenomyosis, functional etc
-Abdominal distension Ascites (Ovarian tumors involving
peritoneum), uterine enlargement
(pregnancy), ovarian cyst.
10. ABNORMAL UTERINE BLEEDING:
The most common gynecologic problem in women during active
reproductive life
- Polymenorrhea: cycles shorter than 3 weeks
- Oligomenorrhea: cycles longer than 6-7 weeks
- Metrorrhagia: intermenstrual bleeding (MC organic )
- Hypermenorrhea: excessive flow (MC organic )
- Menorrhea: prolonged duration of flow
- Menorrhagia: increase amount & duration of flow
- Menometrorrhagia: prolonged flow with irregular
intermittent spotting ( organic)
11. Causes of abnormal uterine bleeding according to age group
Age group Causes
Pre-puberty Precocious puberty ( hypothalamic, pituitary, or ovarian origin)
Adolescence Anovulatory cycles , coagulation disorders
Reproductive age - Complications of pregnancy ( abortion, ectopic pregnancy,
trophoblastic diseases)
- Organic lesions ( leiomyomas, adenomyosis, polyps,
endometrial hyperplasia , carcinomas)
- Anovulatory cycles
-Ovarian dysfunctional bleeding (i.e. inadequate luteal phase)
Perimenopausal -Anovulatory cycles
- Irregular shedding
Postmenopausal -Organiclesions ( carcinoma, hyperplasia, polyps)
- Endometrial atrophy
12. DYSFUNCTIONAL UTERINE BLEEDING (FUNCTIONAL
ENDOMETRIAL DISORDERS):
Definition: It is abnormal bleeding in absence of organic uterine lesions.
MCC is anovulatory cycles (hyperestrogenic states). It is due to:
- Endocrine disorders - : pituitary, adrenal, and thyroid diseases.
- Ovarian disorders - : polycystic ovaries, hormone secreting tumors.
- Metabolic causes - : obesity, malnutrition,..
- Unexplained causes - : (?? Cryptogenic).
Morphology:
- Premenstrual endometrial biopsy shows a persistent proliferation
pattern with variable degree of hyperplasia, cystic glandular change -
Sporadic endometrial breakdown & bleeding ( estrogen effect unopposed
by progesterone).
14. Inflammatory lesion of Valva
Non neoplastic disorders
Tumours of Valva
15. Inflammatory lesions of the Vulva:
All skin disorders can be seen
Herpes virus infection:
STD, HSV type 2,
Painful ulceration in the skin. Intraepithelial
blisters & viral inclusion & eosinophilic swelling
of epithelial cells
Syphilis:
Primary syphilis - : Chancer - indurated lesion with
central ulceration & LN – heals even without Tt.
Secondary syphilis: Condyloma latum (inflammed
hyperplasia of epithelium with underlying chronic
inflammation rich in plasma cells & end arteritis
obliterans), Silver stain demonstrates the
spirochetes.
18. Granuloma inguinale (Donovanosis):
STD affecting the genitalia, inguinal & perianal region ,
gram negative bacilli (Calymmatobacterium donovani) -
Chronic valvular papule/nodule/ ulceration, tropical areas,
can spread to other parts of FGT, ulcer margins show
epithelial hyperplasia & Ulcer bed filled with neutrophil
abscesses. Sliver stain demonstrates bacilli within
macrophages (Donovan bodies)
19. Lymphgranuloma venereum:
STD, Chlamydia trachomatis, tropical areas, vesicles that
rupture and form punched out painless ulcer, secondary
infection, abundant granulation tissue, fibrosis, fistula,
lymphatic obstruction (chronic form of the disease),
necrotizing granuloma may occur
20. Candidiasis :
Chronic irritation & inflammation, white thick
discharge, DM, may be associated with vaginitis
Diagnosis: ME of skin scrapping or culture,
nonspecific histological picture, fungi can be
demonstrated within the keratin layer or
superficial epithelium by sliver stain
Bartholin’sAbscessCyst:
inflammatory occlusion of the main duct of Bartholin’s
vulvo-vaginal gland, most common cause is gonorrhea
Vulvodynia (vestibular adenitis) : inflammation of the
minor vestibular glands (unkown cause) causing very
painful ulceration. Treatment is often surgical.
21. Infection involving the lower and the
upper genital tract
(Pelvic inflammatory disease =PID)
Definition: an ascending infection that
begins in he vulva & spreads upward to
involve the entire genital tract.
22. Causes:
1- Sexually transmitted disease (STD):
gonococcal (MC) or chlamydial infection:
acute suppurative inflammation confined
to mucosa and submucosa (spread via
mucosa).
2- Postabortal or postpartal; caused by
staphylococci, streptococci, E. coli &
clostridium perfringens. Spread is through
uterine wall leading to affection of serosa
and peritoneum.
23. Morphology: acute suppurative inflammation
of the Bartholin’s glands, periuretheral glands,
endocervical glands & fallopian tubes.
Pathological lesions & complications: Acute
salpingitis, salpingo-oophoritis, tubo-ovarian
abscess, pyosalpinyx (distention of the
fallopian tube with pus). It may cause
peritonitis, septicemia, fibrous adhesion
(intestinal obstruction), tubal occlusion &
infertility or ectopic pregnancy.
24. *Non-neoplastic epithelial disorders
(Vulvar Dystrophy- old name):
Benign (non-dysplastic) mucosal alterations of the vulva; of
unknown etiology predominantly in peri & postmenopausal
periods
Types: Two types that may coexist:
G)Lichen Sclerosus et Atrophicus
H)Lichen Simplex Chronicus
25. • Lichen Sclerosus et Atrophicus: gray, parchment-like areas, of
thin atrophic epithelium + sube-pithelial fibrosis+ mononuclear
peri-vascular reaction & occasionally marked hyperkeratosis.
B) Lichen Simplex Chronicus (Squamous Hyperplasia =
Hyperplastic Dystrophy):
- It is the physiologic outcome to rubbing the vulva mucosa in
response to pruritis .
- PP causes: irritant exposure, dermatitis, pre-invasive or invasive
neoplasm (biopsy is indicated)
- Morphology: white plaques (leukoplakia) of thick hyperplastic
& hyperkeratotic epithelium (without dysplasia) and
leukocytic dermal inflammation.
.
26. N.B.: Neither
lichen sclerosus
nor simplex
chronicus is
classified as
premalignant per
se, but
cytogenetic
abnormalities,
including P53
mutations, may
precede the onset
of atypia in these
lesions. Thus,
they are
considered “ Risk
Factors” for
vulvar neoplasia
28. Condyloma Accuminatum: multiple, benign, wart-like verrucous
STD, caused by HPV types 6&11. (vulva, perineum, vagina, rarely
cervix). It is squamous cell papilloma with marked
acanthosis,hyperkeratosis & parakeratosis, some showing cells with
cytoplasmic clearing and nuclear atypia (i.e. koilocytic atypia =
koilocytosis indicating viral infection).
29.
30. Papillary Hidradenoma: benign, well
circumscribed nodule of modified apocrine
sweat gland. It is composed of tubular
structures lined by both epithelial(columner) &
myoepithelial cells.
31. Vulvar Intraepithelial Neoplasia (VIN=
Vulvar Dysplasia):
- A premalignant intramucosal squamous neoplasm
that frequently precedes invasive carcinoma occurs 4th
– 5th decades.
- Mucosal lesions with cellular anaplasia and marked
nuclear atypia, caused by HPV type 16. Synonyms:
VIN III= carcinoma in situ (CIS)= Bowen’s disease.
Tends to progress to invasive carcinoma ( in old &
immunosuppressed patients).
-
32.
33. Differentiate (simplex) VINs are usually
HPV-negative, associated with Lichen
sclerosus or Lichen simplex chronicus. These
precancers usually arise after menopause and
leading to well differentiated keratinized
squamous cell carcinoma in the 6th – 8th
decade.
34. N.B.
HPV
- E6 protein of HPV type 16 & 18 can bind to P53 gene
leading to P53 inactivation
- E7 protein of HPV 16 & 18 binds to Rb gene products
Leading to promotion of neoplastic growth through:
1- deregulation of cell cycle
2- Production of genomic instability
3- Increase telomerase expression
-Types 6 & 11 of HPV with no or low risk of malignancy
do not form a complex with P53 & typically give rise to
benign condylomas
35. Invasive vulvar Squamous cell carcinoma: may
arise de novo or on top of VIN. Spreads to inguinal LNs & is
of poor prognosis. The prognosis depends on size, depth of
invasion, and lymph nodes status
Verrucous Carcinoma: A rare locally aggressive neoplasm.
Usually does not metastasize.
,
36. Extramammary Paget’s Disease:
- An eczyma-like, red crusted sharply demarcated map-like
areas ( on labia majora), characterized by large anaplastic
tumor cells, lying singly or in small groups within the
epidermis. The cytoplasm of the tumor cells is clear, and
mucin positive.
- Unlike Paget’s disease of the breast, the presence of
underlying adenocarcinoma of the vulva is uncommon.
Other rare tumors: Basal cell carcinoma, Malignant
melanoma
39. 1-Vaginitis & vulvovaginitis
Since both vulva and vagina are anatomically close to each
other, often inflammation of one affects the other.
Common infections –
Bacterial - streptococci,staphalococci, E.coli,
H. vaginalis
Protozoal - Trichomonas vaginalis
Viral - Herpes simplex
Fungal – Candida albicans
The most common causes of vaginitis are Candida
albicans ( monaliasis) and Trichomonas
( Trichomonaliasis )
41. Carcinoma: primary carcinoma of the vagina is rare, but 1-2%
women with cervical squamous cell carcinoma develop a
concomitant squamous cell carcinoma in the vagina. Age: 60-70
yrs. Morphology; plaque-like, fungating /ulcerative lesion that
infiltrates cervix, urethera, bladder or rectum.
Clear cell adenocarcinoma: is rare (MC in young women, whose
mothers had received Diethylstilbestrol (DES) during pregnacy for treatment of
threatened abortion). The tumor cells are vacuolated and contained glycogen.
42. Embryonal
rhabdomyosarcoma:
uncommon, a highly
malignant tumor of
infants and children;
polypoid bulky mass
(Botryoid= grape-like)
protruding from vagina.
That is why also known
as Sarcoma Botroides
43. Histopathology
It is composed of rounded malignant (embryonal)
rhabdomyoblasts, some tumor cells have a “tennis-
racket” shape with striated cytoplastmic extension.
Tumor cells are +ve for desmin & myosin
immunostain. These cells are characterstically lying
underneath the vaginal epithelium, called CAMBIUM
LAYER
The central core of polypoid masses composed of
loose and myxoid stroma with many inflammatory
cella
46. DISEASES OF THE CERVIX
Inflammation of Cervix: Cervicitis
Cervical Tumors
47. Inflammation of Cervix: Cervicitis
- May be acute or chronic; specific or non-specific
- Non-specific: Strept., Staph., enterococci, E. coli
- Specific (STD): gonococci, Chlamydia, Mycoplasma,
Trichomonas, Candida….
- Acute cervicitis: - rare (postpartal and nonspecific)
- Neutrophilic infiltration beneath the lining mucosa
48. Chronic cervicitis:
- More common Bacterial growth & alteration in
pH - May be specific, non-specific or of unknown cause
-- ----- - Common cause of leukorrhoea
Predisposing factors – sexual intercourse, trauma of child
birth, instrumentation and excess or deficiency of
estrogen.
49. Morphology:
Gross- eversion of ectocervix with hyperemea, edema and
granular surface.Nabothian(retention cysts) may be
grossly visible as pearly grey vesicles.
Histopathology - squamous metaplasia, chronic
inflammatory cells, columnar cell proliferation (micro-
glandular change), reactive epithelial atypia (mistaken for
CIN), and Nabothian cysts (due to occlusion of cervical
gland ducts ) & squamous metaplasia
54. Cervical Tumors
•Endocervical polyp: benign tumors composed of C.T. stroma
showing dilated endocervical glands and lined by endocervical
epithelium
•Squamous intraepithelial lesions (SIL)
CERVICAL INTRAEPITHELIAL NEOPLASIA(CIN)
-It is caused by a sexually transmitted disease; 2nd – 3rd decades ,
caused by cancer-related (high risk) HPV type
16,18,31,33,35,39,51,52,53,56,58,59.
- It usually precedes invasive squamous cell carcinoma (4th – 5th decades)
55. - Risk factors: early age of first intercourse,
multiple sex partners & high-risk male sex
partners; that suggests a sexually
transmitted oncogenic agent from male to
female at an early age. HPV acts as a
promotor, and herpes virus type II ,
tobacco, constitution , environment &
others may be cofactors.
56. Morpholgy:
CIN I = dysplasia in the deeper 1/3rd of the
epithelium & preserved maturation in the
upper 2/3rd.
CIN II = dysplasia in the deeper 2/3rd &
less maturation.
CIN III = dysplasia in all layers & no
maturation i.e carcinoma in situ (CIS)
58. Bethesda system : a new classification for CIN (National Cancer
Institute) for reporting cervical & vaginal cytology.
Besthesda HPV Morphology CIN Dysplasia
system type
-Low grade SIL 6,11 Koilocytic atypia, flat CIN I Mild
(L-SIL) – condyloma
-High grade SIL Progressive cellular
16,18 CIN II Moderate,
(H-SIL) atypia , loss of & CIN severe,
maturation III carcinoma in
situ
N.B.:
The oncoproteins (E6 &E7) of high-risk HPVs deregulate the cell cycle, produce
genomic instability, and increase telomerase expression. All these molecular events
promote neoplastic cell growth.
The low risk HPVs (HPV 6,11) do not possess these properties and typically give rise to
benign condyloma.
L-SIL –Low grade – Sq. Intraepithelial Lesion
59.
60. INVASIVE CERVICAL CARCINOMA:
-Up to 70% of CIN III (CIS) progress to invasive carcinoma.
-Gross: fungating, ulcerative or infiltrative lesions
-Histology: most cases are squamous cell carcinoma of varying degree
of differentiation (65% = large cell non-keratinizing, 25% large cell
keratinizing, 10% small cell poorly differentiated sq.c.c.)
-Other non-squamous carcinomas (adenocarcinoma, adenosquamous,
neuroendocrine=small cell undifferentiated) are less common and
strongly associated with HPV type 18.
64. Clinical staging:
- Stage 0: CIS Stage I: confined to the cervix
- Stage II: extending beyond the cervix but not into
- the pelvic wall; into vagina but not to
- lower 1/3 of vagina
- Stage III: reaching the pelvic wall or lower 1/3 of
- vagina
- Stage IV: spreading out side the pelvis
Prognosis: depends on stage ( 100% cure for stage 0 &
10% of stage IV).
65.
66.
67. DISEASES OF THE ENDOMETRIUM
ENDOMETRITIS:
ADENOMYOSIS & ENDOMETRIOSIS:
ENDOMETRIAL HYPERPLASIA
TUMORS OF THE ENDOMETRIUM
68. ENDOMETRITIS:
Acute endometritis:
Histological : Neutrophilic infiltration of the endometrium,
caused by Staph., Strept., …; following abortion, delivery or
instrumentation.
Chronic endometritis:
Clinically : Abnormal endometrial bleeding
Histological : Mononuclear (plasma cell & macrophages
infiltration of the endometrium.
Etiology : in chronic PID, tuberculous, in user of IUDs,
actinomycosis and due to retained gestational tissue.
69. ADENOMYOSIS & ENDOMETRIOSIS:
Adenomyosis : Defined as presence of nests of benign
endometrial glands & stroma within the myometrium, deep in the
wall of the uterus. It leads to uterine enlargement & irregular
thickening of the uterine wall.
-Possible cause – metaplasia or oestrogenic stimulation due to
endocrine dysfunction of ovary
-Clinically- menorrhagia, colicky dismenorrheoa and menstrual
pain in the sacral or sacrococcycygeal regions.
- Critaria for diagnosis – The minimum distance between the
endometrial islands within the myometrium and the basal
endometrium should be one low power microscopic field (2-3
mm ).
75. Endometriosis:
- Presence of nests of endometrial glands & or stroma
outside the uterus in ovaries, fallopian tubes, pelvic
peritoneum, uterine ligaments, and rarely in vulva,
vagina, laparotomy scar, umbilicus, and appendix.
- Ectopic endometrium may undergo cyclic menstrual
changes and periodic bleeding.
- Clinically: dysmenorrhea, dyspareunia , pelvic pain &
infertility.
- Diagnosis depends on the presence of 2 out of 3
following features :
1- Endometrial glands ,
2-Stroma, and
3- RBCs or hemosiderin pigment.
81. ENDOMETRIAL INTRAEPITHELIAL NEOPLASIA = EIN
( ENDOMETRIAL HYPERPLASIA )
Definition: It is abnormal proliferation of endometrial
glands.
The most common cause of dysfunctional uterine
bleeding (DUB) & is associated with
hyperestrogenemia.
82. Types:
1- Simple hyperplasia= cystic hyperplasia, mild hyperplasia:
Cystic dilated glands, non-neoplastic, due to
anovulatory cycles.
2- Complex hyperplasia= adenomatous hyperplasia:
Overcrowded, closely opposed glands. Some of these are
neoplastic (contain PTEN (Phosphatase and tensin
homolog ) mutations & considered as EIN). PTEN- tumor
suppressor gene
3-Atypical hyperplasia = complex / adenomatous hyperplasia
with atypia:
Overcrowded glands with cytological atypia. Most cases of
this category are neoplastic (EIN) and many contain
PTEN mutations
83. N.B.: Endometrial hyperplasia:
- It is an important cause of
abnormal uterine bleeding.
- A subset (EIN) is considered a
risk factor for endometrial
carcinoma.
-The risk of carcinoma increases
as function of the degree of
atypia.
- Both endometrial hyperplasia
and adenocarcinoma are
associated with
hyperestrogenism, microsatellite
instability, and mutation of PTEN
gene.
86. TUMORS OF THE ENDOMETRIUM
Endometrial polyp:
- Sessile tumors composed of endometrial glands and stroma.
- May be associated with hyperestrogenism or Tamoxifen therapy.
- Usually benign, but may show foci of hyperplasia or cancer.
87. Endometrial carcinoma:
- 7% of all invasive carcinomas in women
- Most common invasive cancer of the female genital
tract.
Epidemiologic & pathophysiologic types:
1- Endometrial adenocarcinoma: Common,55-65 yrs.
Old.
- Risk factors: Obesity, nulliparity, early menarche & late
menopause, granulosa cell tumor of the ovary, breast
cancer, diabetes, hypertension,infertility&unopposed
estrogen..
-
88. Gross: Fungating polypoid or infiltrating mass
(diffuse involving the entire endometrial surface).
- Histopathology: Adenocarcinoma usually well
differentiated with often associated with metaplastic
changes ( squamous, secretory or mucinous
differentiation). Other histological forms:
adenosquamous or clear cell adenocarcinoma.
- Containing mutations in PTEN gene, microsatellite
instability, often pre-exciting EIN.
89. 2) Papillary serous adenocarcinoma: -
Associated with older age , - Often arising in endometrial
polyps or endometrial surface epithelium, and - Associated
with multiple P53 mutations.
-Spread: invades the myometrium, and spread by
lymphatics & blood (MC to the lung). Serous tumors can
spread quickly, even when non-invasive
90. - Prognosis: depends on extend of spread (stage).
Excellent prognosis when the carcinoma is confined
to corpus uteri itself. However papillary serous tumor
spreads quickly even when non-invasive.
Biologically: more aggressive neoplasms are poorly
differentiated carcinomas including clear cell &
papillary serous carcinoma.
Clinically Abnormal uterine bleeding
91.
92.
93.
94.
95. ENDOMETRIAL STROMAL SRCOMA ( MALIGNANT MIXED
MESODERMAL = MULLERIAN TUMOR ): TUMORS WITH
STROMAL DIFFERENTIATION
-Rare tumors. Highly malignant. Derived from primitive stromal cells
(mullerian mesoderm origin). Consists of glandular (carcinomatous) &
stromal (sarcomatous) elements. The stromal elements may show
muscle, cartilage or osteoid differentiation.
--Gross: bulky polypoid tumor protruding into endometrial cavity and
vagina.
96. - Other variants of endometrial stromal
tumors:
1)Benign stromal nodules: discrete nodules of
stromal neoplasm within the myometrium.
2)Endometrial stromal sarcoma (Endolymphatic
stromal myosis): well & poorly differentiated
stromal neoplasm, may penetrate into lymphatic
channels.
3)High-grade sarcoma not otherwise specified:
high grade unclassified tumor capable of
widespread metastases. Occurs in postmenopausal
females; presents with uterine bleeding. Overall 5-
years survival is 25%.
97. TUMORS OF THE MYOMETRIUM
Benign tumors
♦ Leiomyoma
Malignant tumors
♦ Leiomyosarcoma
98. Leiomyoma:
-Benign smooth muscle tumor, MC overall tumor of females in
the active reproductive age, related to increased estrogen
stimulation, and associated with a number of specific cytogenetic
abnormalities.
- Sharply circumscribed, round
gray-white firm nodules, located -
1-within the myometrium (intramural),
2-beneath the serosa (subserous)
3-beneath the endometrium (submucous).
99. It may undergo cystic degeneration and
calcification.
- May be asymptomatic or associated with
abnormal uterine bleeding, pain, urinary
disorders.
- Malignant transformation is exceptionally rare (?
almost none).
100.
101.
102. LEIOMYOSARCOMA -:
- Uncommon, most arise de novo and not from leiomyomas.
- Bulky, fleshy, infiltrative mass in the uterine wall
-Disseminate in the peritoneal cavity & widely by blood stream.
- Overall 5-years survival is 40%
103. Histologically distinguished
from leiomyomas by:
1- More than 10 mitotic
figures/ 10 H.P.F. ( with or
without cellular atypia), or
2- Between 5-10 mitotic
figures with cellular atypia.
N.B.: Smooth muscle tumor of
uncertain malignant
potential: A subset of
smooth muscle tumors
displays some but not all of
the features of malignancy
104.
105.
106.
107.
108. DISEASES OF THE FALLOPIAN TUBES
1-INFLAMMATORY - SALPINGITIS:
2- TUMORS OF FALLOPIAN TUBE-
109. 1-INFLAMMATORY - SALPINGITIS:
Suppurative salpingitis:
-Infection by pyogenic organisms: streptococci, staphylococci,
& gonococci (PID)
-May cause tubo-ovarian abscesses, pyosalpinx, peritonitis &
“violin string” adhesion that may cause intestinal obstruction.
Tuberculous salpingitis:
-Hematogenous dissimination from other foci . May be
associated with T.B. of endometrium & peritoneum.
Histologically: caseating granulomas with giant cells.
-May cause infertility, or ectopic pregnancy
113. 2- TUMORS OF FALLOPIAN TUBE-
- Rare. Most common is adenocarcinoma (like
serous adenocarcinoma of the ovary).
- Recently, adenocarcinoma of the fallopian tubes
has been associated with BRCAI & BRCA 2
mutations?.
- Many arise in the fimbriated portion of the
tube.
117. Embryological development
Precursor Ovarian component Other female genital tract
structures
1.Coelomic epithelium Surface epithelium 1.Fallopian tubes( ciliated
2. Ectopic endometrial columnar serous cells)
epithelium—Mullerian 2.Endometrial lining(non
Epithelium ciliated columnar cells)
3. Endocervical glands
(mucinous non ciliated)
1.Yolk Sac Germ cells(toti potent)
1. Sex cords Stroma of the ovary Endocrine apparatus of post
natal ovary.
118. Importance of embryological
development
1.Primary Ovarian tumours are classified on the
basis of their site of origin.
2.Still some tumours do not fall in any of the
categories and are put into Malignant (Not
Otherwise Specified)
3.A third category of neoplasms of the ovary are
Metastatic tumours from non ovarian primaries.
119. OVARIAN DISEASES
Manifestations of ovarian diseases:
- Pelvic pain
- Menstrual irregularities ( abnormal pattern of ovarian
hormone secretion).
- Infertility; failure of ovulation (Stein-Leventhal).
- Ovarian mass : either non-neoplastic (cysts) or neoplastic
(cystic or solid).
120. INFLAMMATORY - OOPHORITIS:
- Inflammation of the ovaries is always secondary to
salpingitis or peritonitis.
- If chronic & bilateral leading to extensive fibrosis &
infertility.
121. NON-NEOPLASTIC OVARIAN CYSTS
1- Follicular and Luteal cysts: Common, 1-8
cm in diameter. They are lined by follicular
(granulosa) cells or luteinized cells.
Asymptomatic, but may rupture, causing
peritoneal reaction & pain.
2 - Chocolate cysts: Blood-filled cysts, due
to endometriosis of the ovaries.
122. 3 – Polycystic ovarian ( Stein - Leventhal
syndrome (PCOD) -:
It is important cause of infertility. There is excessive production
of androgens, increase conversion of androgens to estrogen,
insulin resistance, and inappropriate gonadotrophin production by
the pituitary.
Morphology: Ovaries are large, white, many subcortical follicular
cysts(0.5-1 cm.) in diameter, and covered by thickened fibrosed
outer tunica. No corpora lutea (= no ovulation).
Manifestations: Young females with Oligomenorrhea, infertility,
obesity & hirsuitism.
130. OVARIAN TUMORS
- Common forms of neoplasia in women.
- 80-90% of ovarian tumors are benign.
- Most ovarian tumors occur between 20-45 years.
- Ovarian cancer is second MC malignancy of the female genital tract
(after endometrial cancer).
- Most ovarian tumors are derived from surface epithelium, and
“CA-125” is the tumor marker for surface epithelial tumors of the
ovary.
- Malignant ovarian tumors present at a late stage, thus are associated
with high mortality rate.
- Known risk factors are nulliparity, family history, and specific
inherited mutations (BRCAI & BRCAII) genes.
131. Tumour types-- a basic classification
Site of origin Types Frequency Age group
Surface epithelial 1.Serous 60%-70% 20 years and greater
tumours 2.Mucinous
3.Endometroid
4.Clear cell
5.Brenner
Germ cell 1.Teratoma 15%-20% 0 to 25 years and
2.Dysgerminoma greater
3.Endodermal Sinus(Yolk Sac
Tumour)
4.Choriocarcinoma
Sex cord stromal 1.Granulosa Theca cell tumours 5%-10% All ages
tumours 2.Sertoli-Leydig cell tumours
3.Gynandroblastoma
Miscellaneous 1.Lipid cell tumour Variable variable
2.Gonadoblastoma
Metastasis Krukenberg tumours 5% variable
132. CLASSIFICATION OF OVARIAN TUMORS
(A) PRIMARY OVARIAN TUMORS:
(B) METASTATIC NON-OVARIAN CANCER (Krukenberg’s tumor)
A: PRIMARY OVARIAN TUMORS:
I. Surface mullerian epithelial tumors: (Benign, Borderline, and
Malignant)
II. GERM CELL TUMORS:
III. SEX CORD-STROMAL TUMORS:
133. I. Surface mullerian epithelial tumors: (Benign,
Borderline, and Malignant)
1-Serous tumors: composed of ciliated columnar
(tubal type) epithelium
2- Mucinous tumors: composed of mucus-secreting
(cervical canal type) epithelium
3- Endometrioid tumors: composed of glandular
(endometrium-like) epithelium.
4- Brenner’s tumors: composed of transitional
(urothelium-like) epithelium
5- Clear cell tumors.
134. II. GERM CELL TUMORS:
1- Teratoma
2- Dysgerminoma (seminoma ovarii)
3- Yolk sac tumor= Endodermal sinus tumor
4- Embryonal carcinoma (MC mixed with other
types)
5- Choriocarcinoma (MC mixed with other types)
135. III. SEX CORD-STROMAL TUMORS:
1- Granulosa-Theca cell tumor: secrete
estrogen
2- Sertoli-Leydig cell tumor: secrete androgens
3- Fibroma: associated with Meig’s syndrome
4- Sex cord stromal tumor with annual tubules
5- Gynandroblastoma
6- Steroid (Lipid)cell tumors
136.
137. SEROUS TUMORS
-The MC cystic neoplasms of the ovary.
- Cysts are lined by tall columnar, ciliated epithelial cells (fallopian tube
type) & filled with serous fluid. Types:
1-Benign Serous Tumors (Cystadenomas):
(60%), smooth lining & no papillary or solid areas. 20% are bilateral.
2- Borderline Serous Tumors (low malignant potential):
(15%), epithelial atypia, solid areas, but no stromal invasion. 30% are
bilateral.
3- Malignant Serous Tumors (Cystadenocarcinomas):
(25%); multilayered epithelium, solid areas & papillary structures
invasing the stroma. 65% are bilateral. The prognosis depends on stage, and
the presence of peritoneal implants means poor prognosis.
149. MUCINOUS TUMORS
Large cystic masses, huge size, and multiloculated. Cysts filled with sticky
gelatinous fluid. They either lined by tall columnar mucus-secreting epithelium
(intestinal-type mucinous cystomas) or show papillary architectures and focal
cilia (mullerian mucinous tumors), which may be associated with endometriosis.
Types:
1- Benign Mucinous Tumors (cystadenomas):
80%; large cysts with smooth lining & no atypia. 5% are bilateral.
2- Borderline Mucinous Tumors (of low malignant potential):
10-15%; cellular atypia, but no stromal invasion.
3- Malignant Mucinous Tumors (Cystadenocarcinomas):
5-10%; atypia, solid sheets & stromal invasion.
20% bilateral.
Seeding in the peritoneum with malignant deposits causes
pseudomyxoma peritonei.
Usually mucinous cystadenocarcinomas are of intestinal type.
153. SEROUS TUMOUR MUCINOUS TUMOUR
Serous papillary cystic tumor Mucinous cystic tumor of
of borderline malignancy. borderline malignancy,
There is extensive, orderly endocervical type. Many cells
invagination of the neoplastic have abundant eosinophilic
glands, most with intraluminal cytoplasm.
papillae, into the stromal
component of the neoplasm.
The stroma is unaltered in
appearance.
154. SEROUS MUCINOUS
TUMOURS TUMOURS
Cystadenocarcinomas– Cystadenocarcinomas– more
complex growth pattern, frank complex and solid growth
effacement of stroma, usual pattern with atypia and
features of malignancy and stratification, loss of glandular
extremes of atypia. Concentric architecture and necrosis.
calcifications (Psammoma
Bodies) may be seen.
155. ENDOMETROID TUMOURS
• 20% of all ovarian tumours.
• Majority are carcinomas, if benign forms are
present they are cyst adenofibromas.
• Distinguished from serous and mucinous
tumours by presence of tubular glands bearing
close resemblance to benign or malignant
endometrial glands.
• 30% associated with carcinoma endometrium
and 15% with endometriosis whereas 40%
involve both ovaries.
156. ENDOMETRIOD CARCINOMA
Gross: presence of both solid Microscopic: Tubular
and cystic areas glands resemble those of
typical endometrial
adenocarcinoma.
157. CLEAR CELL TUMOUR
These are uncommon and aggressive tumours.
Grossly can present in solid and or cystic pattern (figure
solid tumour with cysts and necrosis)
Microscopically: large epithelial cells with abundant clear
cytoplasm.
158. BRENNER TUMOUR
Uncommon adenofibromas
Epithelial components– nests of transitional cells
resembling urinary bladder.
Most are benign,variable size(1cm to 30 cm).
Gross—solid or cystic
Microscopic – fibrous stroma resembling normal
ovarian stroma seperated by sharply demarcated
nests of urinary tract, with mucinous glands.
159. BRENNER TUMOUR
Gross:A sharply Microscopically:Nests of
demarcated, yellow-white transitional cells, some
fibromatous tumor occupies containing cysts, lie in a
a portion of the sectioned fibromatous stroma.
surface of the ovary.
160. GERM CELL TUMORS
- 15-20% of all ovarian tumors. It arises from
totipotent germ cells capable of
differentiation into the three germ layers.
- Mostly benign cystic teratomas while Other
tumours are found principally in children
and young adults.
- Homologous to germ cell tumours in male testis.
161. II. GERM CELL TUMORS:
1- Teratoma
2- Dysgerminoma (seminoma ovarii)
3- Yolk sac tumor= Endodermal sinus tumor
4- Embryonal carcinoma (MC mixed with other
types)
5- Choriocarcinoma (MC mixed with other types)
163. 1-TERATOMAS
1-Mature (Benign) Teratoma: MC germ cell tumors of the ovary, cystic
(dermoid cysts), lined by skin & hairs, and filled with sebaceous secretion.
There may be mature cartilage, bone (teeth) & other structures. 10-15% are
bilateral. < 1% undergo malignant transformation (MC sq.c.c.).
2-Immature (Malignant) Teratoma: Rare , solid, bulky, with areas of hemorrhage
and necrosis. It contains embryonic elements of he three germ layers. Age:
adolescent & young women. Grading is based on the amount of immature
neuroepithelium. It causes wide spread extraovarian metatases depending on
the degree of the immaturity of the including tissues.
3- Monodermal (Specialized )Teratomas: differentiate along the line of single
tissue. Examples:- Strauma ovarii is MC (mature thyroid tissue) – Carcinoid
tumor.
164. MATURE CYSTIC TERATOMA
GROSS: unilocular cysts with hair MICROSCOPIC: cyst wall stratified
and cheesy material. Thin walled squamous epithelium and underlying
gray white wrinkled epidermis.hair, sebaceous,sweat glands and other
tooth and calcification are found adnexa.other structures like thyroid
within walls. tissue,cartilage bone may be seen.
171. 2- Dysgerminoma
The ovarian counterpart of testicular seminoma.
GROSS- Yellowish white to gray pink solid, fleshy
tumors, of children & young adults
-10% are bilateral.
Microscopic picture: sheets of large cells
separated by fibrous stroma infiltrated by small
lymphocytes
- Non-functional, but may be mixed with other
germ cell elements that produce hCG
- Malignant, but radiosensitive & chemosensitive, with
relative good prognosis if treated early.
172. DYSGERMINOMA
GROSS: Small nodules to Microscopic:large vesicular
very large size.Cut surface: cells, clear cytoplasm and well
yellow white to gray pink defined boundaries and
appearance and are soft centrally placed regular
and fleshy. nuclei.cells in sheets or cords
seperated by scant fibrous
stroma, which has mature
lymphocytes.
175. 3- Endodermal Sinus Tumor ( Yolk Sac Tumor =
Infantile embryonal carcinoma)
-It arises from mutlipotent embryonal carcinoma cells differentiating
towards yolk sac structures.
- Affects children & adolescents; grows rapidly & spreads widely, but
is radio- & chemosensitive.
- Histologically: it shows cystic spaces into which papillary structures
with central blood vessels , the cyst spaces and papillary
structures are lined by immature epithelium giving glomeruloid
or “Schiller-Duval” bodies; There are intracellular and
extracellular hyaline droplet (characteristic feature). Tumor
cells are positive for Alpha-fetoprotein (tumor marker).
177. 4- Choriocarcinoma
- It is due to teratogenous development of germ cells.
- Most cases exist in combination with other germ cell
tumors.
- Resembles gestational choriocarcinoma, highly
malignant, spreads widely & elaborates hCG (tumor
marker).
- Microscopic picture: malignat syncitiotrophoblasts
& cytotrophoblasts in a hemorrhagic stroma.
N.B. Gonadal choriocarcinomas are more resistant to
chemotherapy than Gestational choriocarcinomas.
178. III. SEX CORD-STROMAL TUMORS:
1- Granulosa-Theca cell tumor: secrete
estrogen
2- Sertoli-Leydig cell tumor: secrete androgens
3- Fibroma: associated with Meig’s syndrome
4- Sex cord stromal tumor with annual tubules
5- Gynandroblastoma
6- Steroid (Lipid)cell tumors
179. 1- GRANULOSA - THECA CELL TUMOR
- 5% of all ovarian tumors, of peri & post-menopausal
women.
- Usually unilateral, solid white yellow, consisting of theca
cells & granulosa cells, arranged in “Call-Exner” rosettes.
- Elaborated large amount of estrogen & may cause
precocious sexual development in children, endometrial
hyperplasia, cystic changes of the breast or endometrial
carcinoma (estrogen effects).
- Pure granulosa cell tumors are potentially malignant, clinical
malignancy occurs in 5-25% of cases, but they are slowly growing &
10-years survival is above 85%.
- Pure Theca cell Tumors - THECOMA
180. GRANULOSA CELL TUMOUR
Gross: small partly solid,
partly cystic and mostly
unilateral.The neoplasm
composed of yellow-
white tissue with
hemorrhage, some of
which is intracystic
181. Microscopically:
granulosa cell arranged in
various patterns like
micro,macro follicular,
trabecular,bands and
sheets.CALL-EXNER
BODIES characterstic
rosette like structures
having central rounded
pink mass surrounded by
granulosa
182.
183.
184.
185. THECOMA
Pure thecoma are almost always benign.
Occur in post menopausal women.
Oestrogen dominant tumours– endometrial
disorders , carcinoma and cystic disease of
breast.
If androgen secreting – virilizing effects.
186. THECOMA
Gross: a solid firm mass Microscopically : spindle
upto 10 cm in shaped theca cells along
diameter.Section shows. with variable amount of
solid, lobulated, yellow hyalinized collagen,
tissue. cytoplasm of these cells is
vacuolated and lipid laden.
187. 2- SERTLOI-LEYDIG CELL TUMORS ( Androblastoma=
Arrhenoblastoma= Hilus Cell Tumors = Gonadoblastomas)
.Androgen producing neoplasm (rarely produce estrogen)
-Recapitulate the testicular counterpart & produce
masculinization or defemenization (Androgen)
effeect.
-Usually unilateral & benign.
-Gross: cut surface is solid and colour gray to golden
brown.
-Microscopic picture: Tubules lined with Sertoli cells
and Leydig cells interspersed in the stroma.
3- GYNANDROBLASTOMA: Extremely rare
- It consists of a mixture of granulosa/theca & sertoli/
leydig cells.
189. 4) FIBROMA
Common ovarian tumours. Usually bilateral
Harmonally inactive
Meig’s syndrome: fibroma with pleural
effusion and benign ascites.
Gross large firm fibrous usually bi-lateral mass.
Microscopic composed of spindle shaped well
differentiated fibroblasts and collagen.
Fibrothecoma: combination of fibroma and
thecoma.
190.
191.
192. METASTATIC TUMOR
- Very common,
- The primary tumors is from abdominal and breast
tumors.
Krukenberg tumor
A bilateral metastatic ovarian carcinoma, composed of
mucin-producing signet ring cells, metastasizing from
GIT, mostly from the stomach, it may produce
pseudomyxoma peritonei like well differentiated
appendicial tumors.
197. ECTOPIC PREGNANCY : Disorders of early
pregnancy
Definition: implantation of the embryo in any site
other than uterus; Most common- the fallopian
tube (> 90%), rarely in ovary or abdominal
cavity.
Associated with PID & endometriosis; but 50%
occur with no known cause.
198. May end in:
1- Spontaneous regression with resorption of the products
of conception
2- Intratubal hemorhage (hematosalpinx)
3- Tubal abortion or rupture & extrusion into abdominal
cavity →
intraperitoneal hemorrhage and shock i.e. acute
abdomen
(medical emergency).
- Diagnosis:
High hCG, sonography & endometrial biopsy showing
decidual reaction but no chorionic villi.
199.
200.
201.
202.
203.
204. Disorders of late pregnancy
1- Placental inflammation or infection:
A) Disorder of ascending infection
(Chorioamnionitis):
- infection of the fetal membrane
- Usually ascending from the vagina, in case of
premature rupture of the membranes.
- Most common cause is group B streptococci.
- Acute suppurative inflammation of the chorion &
amnion, and acute vasculitis of the umbilical
cord (funisitis).
B) Hematogenous (transplacental ) infection:
- It is derived from maternal septicemia (Listeria,
streptococcus & TORCH = Toxoplasma, Rubella,
Syphilis, Cytomegalovirus, Herpes) → villous
inflammation (villitis) and acute intervillositis.
205. 2- Toxemia of pregnancy:
-Occurs in 6% of pregnancies, in the last trimester & most common in
primiparas.
1- Pre-eclaspia = hypertension , proteinuria & edema, headache & visual
disturbances
2- Eclampsia = severe pre-eclapsia + convulsions & coma.
Associated with widespread endothelial injury & DIC (Desseminated
Intravascular Coagulation) affecting kidneys, liver, brain & other
organs.
- Resembles GVH( Graft Versus Host Reaction , but etiopathogenesis is poorly
understood.
- Delivery is the only definitive treatment for pre-eclampsia and eclampsia.
Pathogenesis of Toxemia of pregnancy: Unclear;
- The primary cause may be immune or genetic factors → mechanical or functional
obstruction of the uterine spiral arterioles → placental ischemia → endothelial injury &
activation of disseminated intravascular coagulation, leading to decrease in glomerular
filtrate, CNS disturbances, abnormal liver functions, and fibrin thrombi and ischemia
in most organs.
206. THEORIES OT TOXEMIA OF PREGNANCY:
1- Inadequate placental implantation → decrease in
uteroplacental perfusion and placental ischemia → increase
production of vasoconstrictors (e.g. thromboxane ,
angiotensin) & decrease of vadodilators(e.g. prostaglandin
I2, prostaglandin E2)
→ arteriolar vasocontriction & hypertension.
2- Recently ; Factors imbalance → premature
termination of placental vascular growth. There is
abnormal increase in an anti-angiogenic factor (sflt-1)
and reduction in pro-angiogenic factors (Vascular
endothelial-derived growth factor= VEGF & placental
growth factor =PLGF ).
207. GESTATIONAL TROPHOBLASTIC DISEASES
1- HYADATIDIFORM (VESICULAR) MOLE: defined by-
1- Enlarged edematous and hydropic change of chorionic villi
which become vesicular(Cystic swelling). Gross -Grape like
2-Variable trophoblastic proliferation.
Two types:
- Complete (diploid) &
- Partial/Incomplete (triploid).
- 10% develop into invasive mole, and 2.5% develop into
choriocarcinoma.
2- INVASIVE MOLE:
- Penetrates the uterine wall, produce hemorrhage but does not
metastasize. - Responds well to chemotherapy.
208. Feature Complete mole Partial mole
-Karyotype -Diploid (46 xxor 46xy), two sperms -Triploid(69 ). Two sperms fertilize an egg
fertilize an empty egg. All genetic with normal chromosomes
material is paternal
-Rarely seen or absent
- Fetal parts - Usually present with abnormalities
- All villi - Some villi
- Villous edema
- Diffuse & circumferential - Focal and slight
- Trophoblastic
proliferation
- Atypia -Often present -Abscent
-Serum hCG - Elevated - less elevated
-hCG in tissue - ++++ - +
- Behavior - 2% choriocarcinoma - Rare choriocarcinoma
209.
210.
211.
212.
213.
214.
215.
216. 3- Choriocarcinoma:
- 50% follow hydatidiform mole & 25% follow normal
pregnancy, 20% follow abortion & 5% follow
ectopic pregnancy.
- Highly malignant & metastasize widely.
-Gross: Large, soft, yellowish white & fleshy with areas of
hemorrhage and necrosis.
-Histology: Abnormal proliferation of both cytotrophoblasts
& cyncytiotrophoblasts invading the endometrium, blood
vessels, lymphatics, no chorionc villi are seen.
- Spread:
To lung, bone marrow, liver & other organs.
217. Clinical features:
Vaginal bleeding & discharge in the course of
apparently normal prgnancy, after miscarriage, or high
hCG titers.
N.B.: All gestational trophoblastic
disorders are associated with high level of
hCG (tumor marker).
218.
219.
220.
221.
222. 4- Placental site trophoblastic Tumor:
- A rare tumor composed of proliferating
intermediate trophoblasts (larger than cytotrophoblasts
but mononuclear than cyncytial).
- D.D. from choriocarcinoma by the absence of
cytotrophoblastic elements and low level of hCG
production.
- Mostly are locally invasive only, but malignant
variants are distinguished by:
- A high mitotic index,
- Extensive necrosis, and
- local spread.
- About 10% result in metastases and death.
Each month the uterus goes through a cyclical change, first building up its endometrium or inner lining to receive a fertilized egg, then, if conception does not occur, shedding the unused tissue through the vagina in the monthly process called menstruation