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Department of Pathology
Gadjah Mada University School of Medicine
Jogjakarta, I N D O N E S I A
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Female Genital Tract
Department of Pathology
Gadjah Mada University School of Medicine
Jogjakarta, I N D O N E S I A
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Developmental Disorders
Mullerian Duct Anomalies
• Embryologic fusion anomalies organ agenesis,
abnormal septation, organ duplication, etc.
Gardner’ Duct Cyst
• Arise in women from remnants of the degenerated
mesonephric/wolffian duct
• Submucosa of anterolateral vaginal wall, 1-2 cm in size
Imperforate Hymen
• May not be recognized until puberty complain of
failure to menstruate retain blood: hematocolpos,
hematometria, hematosalpinx
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Sexually Transmitted -
Infectious Diseases
A. VIRAL
B. BACTERIAL
C. CHLAMYDIA
D. SYPHILIS
E. CANDIDA
F. TRICHOMONAS
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Sexually Transmitted Infectious Diseases
A. VIRAL
HERPES (Herpes simplex II virus)
• Painful red papules group of vesicles ulcerate
• Intraepidermal vesicles formed by acantholysis due
to baloon degeneration of infected epidermal cells
CONDYLOMA ACCUMINATA (HPV)
• Veneral warts flat or verrucous alteration of
squamous epithelia
• Affects: skin of perianal/perineal; mucosa of vagina,
cervix, others
• Verrucous condyloma with hyperkeratosis,
parakeratosis, acanthosis, koilocytosis
AIDS
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Condyloma accuminatum (VIN)
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Sexually Transmitted Infectious Diseases
B. BACTERIAL
1. GONORRHEA
• Initial site: Bartholin’gland, Skene’s glands, endocervix
• Acute inflammation of Bartholin’s gland occlusion
abscess resolution Bartholin’s cyst
• Cervical infection endometrium purulent salpingitis
pyosalpinx reabsorbed hydrosalpinx
• Consequences: secondary infertility
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Sexually Transmitted Infectious Diseases
B. BACTERIAL
2. BACTERIAL VAGINOSIS
• Etiology: gardnerella vaginalis (hemophilus gardnerella)
• Non-specific vaginitis produces a thin, scaty, malodorous
discharge
• The organism does not penetrate mucosa, and does not
incite much inflammatory response
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Sexually Transmitted Infectious Diseases
B. BACTERIAL
3.CHANCROID
• Etiology: H. ducreyi genital chancre (“soft chancre”)
and regional lymphadenitis inguinal abscess (bubo)
• Mic: luminal occlusion and thrombosis of blood vessel
beneath the ulcer
• The organism is a gram-negative rod
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Sexually Transmitted Infectious Diseases
B. BACTERIAL
4. GRANULOMA INGUINALE
• Etiology: Calymmatobacterium granulomatis
• Location: perianal or genital, as a solitary lesion or small
group of ulcers filled with granulation tissue peripheral
extension, with dense infiltrates of lymphocytes and
macrophages, occasional microabscess
• Intracytoplasmic inclusion bodies within macrophage
Donovan bodies
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Sexually Transmitted Infectious Diseases
C. CHLAMYDIA
(C.trachomatis)
A.Non-specific Uretritis, Cervicitis, Salpingitis
• Chlamydia is probably responsible for a majority of the
cases of salpingitis resulting in infertility
B. Lymphogranuloma Venereum
• Different serotype of C.trachomatis ulcerative and
papular skin lesion
• Lymphatic involvement fibrosis, scaring, and strictures
of anus and rectum
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Sexually Transmitted/Infectious Diseases
D. SYPHILIS
• T. pallidum
E. CANDIDA
• C. albicans
F. TRICHOMONAS
• T. vaginalis
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VULVA/VAGINA
A. INFLAMMATORY DISEASE
B. VULVAR DYSTROPHY
C. VULVAR NEOPLASIA
D. VAGINAL NEOPLASIA
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A. INFLAMMATORY DISEASE
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B. VULVAR DYSTROPHY
• Atrophic dystrophy
• Hypertrophic dystrophy
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Atrophic Dystrophy: Lichen Sclerosus
(Chronic Atrophic Vulvitis)
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Atrophic Dystrophy: Lichen Sclerosus
(Chronic Atrophic Vulvitis)
-Epithelial atrophy
-Dense band of hyalin collagen
beneath the epithelium
-A band like lymphocytic
infiltration
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Hypertrophic Dystrophy: Squamous
Hyperplasia
-Hyperkeratosis, acanthosis
with or without atypia
-Clinically resembles atrophic
dystrophy
-10% potential to cancer
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Schematic composition
of atrophic and
hypertrophic dystrophy
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C. VULVAR NEOPLASIA
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EXTRAMAMMARY PAGET’S DISEASE
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D. VAGINAL NEOPLASIA
• SCC
- mostly in fornix posterior, with vaginal discharge
- prognosis: 5-year survival rate : 20-90%
• Adenocarsinoma
- Arising is the anterior wall of vagina
- clear cell carcinoma DES and in young (15 – 27 yo)
• Sarcoma botryoides
- rhabdomiosarcoma, polypoid grape-like appearance
- In general the prognosis is poor
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SARCOMA BOTRYIOIDES
(embryonal rhabdomyosarcoma)
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CERVIX
A. INFLAMMATORY DISEASE
B. POLYPS
C. CARCINOMA
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The Development
of uterine cervix
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CERVIX
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A. INFLAMMATORY DISEASE
Acute
• Neisseria gonorrhoica: the most common
etiologic agent
• Chlamydia: more common but less symptomatic
more difficult to diagnose
• post-abortion, post-partum, post-traumatic
Chronic
• Follicular cervicitis
• Nabothian cyst
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FOLLICULAR CERVICITIS
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Cerviciis - metaplasia
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SQUAMOUS METAPLASIA
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B. POLYPS
Inflammatory
• 5% of women
• From endocervical canal – sessile or pedunculated,
fibromyxoid
Hyperplastic
• Microglandular hyperplasia consists of tightly pack
hypaerplastic endocervical glands
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POLYPS
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C. CARCINOMA
Etiology
The bottom line risk factor:
• Early onset of sexual activity
• Increasing numbers of sexual partners
• The promiscuity of those sexual partners
Etiologic factor:
• HPV: strain 16, 18, and 31 (high risk)
• HSV II: antibodies to HSV II antigen is higher
in women with dysplasia or neoplasia
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Condyloma
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C. CARCINOMA
Pathogenesis
• Location: squamo-collumnar junction
• Dysplasia (CIN) neoplasia
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Spectrum of CIN
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Cytology: normal CIN III
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CIN III with micro-invasion
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C. CARCINOMA
Diagnosis (evaluation)
1. PAP Smears
- 95% reliable (5% false negative)
2. Schiller Test
- staining of the cervix with iodine and potassium iodide
normal-brown (glycogen content) biopsy
3. Colposcopy
- magnification: 20X biopsy
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C. CARCINOMA
Morphology
• Grossly: infiltrative, ulcerative, exophytic
• Mic: SCC keratinizing, non-keratinizing
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CIN III
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SCC, keratinized
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C. CARCINOMA
Behavior
• Depends on the spreading: bladder, ureter, rectum,
vagina
• Lymphatic: paracervical, hypogastric, external iliac
• Blood: unusual
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C. CARCINOMA
Prognosis
- Related to grade and stage of
tumors
- Overall FYSR: 60%
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Staging
• Stage 0 Carcinoma in situ
• Stage Ia Microinvasive and confined to cervix
• Stage Ib Invasive and confined to cervix
• Stage IIa Extends to upper vagina but not to para-
metrium
• Stage IIb Involve parametrium
• Stage III Extension to pelvis sidewall or lower vagina
• Stage IV Beyond the pelvis or involvement of rectal or
bladder mucosa
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U T E R U S
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DYSFUNCTIONAL UTERINE BLEEDING 1
Abnomal uterine bleeding in the absence of organic lesion of endometrium
1. ANOVULATORY CYCLE
• Failure of ovultion results in prolonged estrgenic
stimulation without progesteron-induced secretory
changes hyperplasia that occur generally just afer
menarche and before menopause
• Etiology unknown:
- endocrine dysfunction: thyroid, adrenal, pituitary
- ovarian abnormalities: polycystic ovary, functional
neoplasm
- metabolic abnormalities: obesity, malnutrition, chroni
disease
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DYSFUNCTIONAL UTERINE BLEEDING 1
Abnomal uterine bleeding in the absence of organic lesion of endometrium
2. OVULATORY CYCLE
• INADEQUATE LUTEAL PHASE
- results from low progesterone output by corpus
luteum infertility, amenorrhea, increased bleeding
• IRREGULAR SHEDDING
- delayed involution of corpus luteum prolonged
rogesterone stimulation secretory endometrium
maybe admixed with proliverative endometrium ->
profuse, regular menstrual bleeding lasting 1-2 weeks
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INFLAMMATORY DISEASE
A. Acute endometritis
• Post-abortion, post-partum states with retaind placental
parts
• Suppurative inflammation + microabscess pyometra
obstruction of endocervical canal
B. Chronic endometritis
• Contination of acute endometritis, could be associated
with IUD, 15% with unknown etiology
• Pelvic pain, abnormal bleeding, infertility
• Characteristic: infiltration by plasma cells
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ENDOMETRIOSIS 1
INTERNAL ENDOMETRIOSIS
(ADENOMYOSIS)
• The presence of endometrial tissue (gland
and stroma) buried within the myometrium
myometrial hypertrophy
• Thought to arise from abnormal downgrowth
of basal endometrium
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ADENOMIOSIS
(Endometriosis interna)
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ENDOMETRIOSIS 1
EXTERNAL ENDOMETRIOSIS
• 20% of adult female (3rd to 4th decade)
• The presence of benign, potentially functional endometrial
tissue outside of the uterus significant cause of
infertility
• Pathogenesis: focal differentiation of the coelomic
epithelium into endometrial tissue, regurgitation of
endometrial tissue outside of the uterus during menses,
lymphatic and hematogenous dissemination
• Clinical: depends on location, generally dysmenorrhea
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“CHOCOLATE” CYST
(external endometriosis of the ovary)
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ENDOMETRIAL POLYPS
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ENDOMETRIAL HYPERPLASIA
• Mostly occur in post-menarchal or peri-menopausal
associated to prolonged or excessive estrogen stimulation
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ENDOMETRIAL HYPERPLASIA
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ENDOMETRIAL GLANDULAR TUMORS
• 60% - 75% : G1 – G3
• 20% - 30% : with squamous differentiation
adenoacanthoma & adenosquamous carcinoma
• Prognosis is better predicted by the grade of
glandular component
• Spreading: myometrium adjacent tissue
• Lymphatic regional and periaortic lymphnode
• Hematogenous lung, liver, bone, etc.
• In older women tend to be less-differentiated
and more invasive then younger women
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ENDOMETRIAL GLANDULAR TUMORS
STAGING 5 yr survival
• Confined to corpus (80%) 95%
• Involves corpus and cervix 30-50%
• Outside uterus but within pelvis <20%
• Bladder or rectal mucosal
involvement or outside pelvis 15%
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ENDOMETRIAL GLANDULAR TUMORS
GRADING
• G1. Well differentiated adenocarcinoma
• G2. Differentiated adenocarcinoma with partly
solid areas
• G3. Predominantly solid or entirely undifferen-
tiated carcinoma
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ENDOMETRIAL GLANDULAR TUMORS
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ENDOMETRIAL STROMAL TUMORS
• BENIGN STROMAL NODULES, appear as expanding
nodules of endometrial stroma burried within the
endometrium
• ENDOLYMPHATIC STROMAL MYOSIS, this represents
a low-grade sarcoma invade the myometrium tend to
invade lymphatics and blood vessels
• ENDOMETRIAL STROMAL SARCOMA, this usually
arises high in the fundus fills the endometrial cavity
grows into myometrium extensive vascular invasion
• 5yr survival : 25%
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MALIGNANT MIXED MULLERIAN TUMORS
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MYOMETRIAL TUMORS
LEIOMYOMA
• Most common neoplasm in women during reproductive life (25%), 3rd
to 4th decade, tending to decrease in size in menopause
• Malignancy is extremely unusual (<0.1%)
• Symptom: pain of degeneration, bleeding, symptom related to size
pressure on rectum and bladder, sensation of heaviness
LEIOMYOSARCOMA
• Uncommon, as fleshy mass invading into uterine wall, or polypoid
• Arising de novo rather than from a pre-existing leiomyoma
• 5 yr survival is 40 – 50 %
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MYOMETRIAL TUMORS
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LEIOMYOMA
A. Well demarcated white appearance mass bulging into the uterine cavity
B. Well differentiated spindle shaped cells in interlacing bundles
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LEIOMYOSARCOMA
A. Large hemorrhagic tumor mass distends to the lower corpus and flanked
by two leiomyomas
B. The tumor cells are irregular in size & shape, with hyperchromatic nuclei
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FALLOPIAN TUBES
Inflammatory disease
• Specific: Tbc infertility
• Non-specific suppurative salpingitis pyosalpinx
hydrosalpinx infertility
Salpingitis isthmica nodosa
• The process and morphology similar to adenomyosis
Cyst
• Embryologic remnants of the muellerian and wolffian
Ectopic pregnancy
Tumors
• Very rare, mostly secondary
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ECTOPIC PREGNANCY
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OVARY
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NON-NEOPLASTIC
OVARIAN ENLARGMENT
A. “Germinal” Inclusion Cyst
- common cyst in pre-menopausal period, result of down growth
and entrapment of the surface epithelium into the ovarian cortex
B. Physiologic or Functional Cyst
- follicle cyst
- corpus luteum cyst
- theca lutein cyst
C. Polycystic ovaries
D. Stromal Hyperplasia
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POLYCYSTIC OVARIES
-Bilateral and multiple cyst, as one of the more common cause of infertility
-Lined by granulosa-theca cells (may be luteinized & androgen secreting)
-Symptom: varies from hyperestrinism (abnormal bleeding) to virilization
(amenorrhea, hirsutism)
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NEOPLASTIC (80% are benign)
OVARIAN ENLARGEMENT (1)
A. TUMORS DERIVED FROM SURFACE (GERMINAL) EPITHELIUM
1. Serous Tumors
a. Serous cystadenoma
b. Serous cystadenocarcinoma
c. Serous borderline tumor
2. Mucinous Tumors
a. Mucinous cystadenoma
b. Mucinous cystadenocarcinoma
c. Mucinous borderline tumor
3. Endometrioid Tumors
4. Brenner Tumors
5. Serous surface papilloma, cystadenofibroma, etc.
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Serous Tumor
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Mucinous Cystadenoma
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Borderline Serous Cystadenoma & Cystadenocarcinoma
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Borderline Serous Cystadenoma
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Brenner Tumor
Brenner tumor
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NEOPLASTIC
OVARIAN ENLARGEMENT (2)
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NEOPLASTIC
OVARIAN ENLARGEMENT (3)
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Histogenesis and inter-relationship of
tumors of germ cell origin
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Mature Cystic Teratoma (dermoid cyst)
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Immature Teratoma
Primitive
neuroepithelium
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Seminoma Testis
Tumor cells
Lymphocytic infiltration
In stroma
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Yolk-sac Carcinoma
Schiller-Duval bodies
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Granulosa Cell Tumor
-Most (90%) are unilateral, solid, round, firm, white masses 5-10 cm in size
-Some time a thecal componant may be present fibrothecoma
-When the size >6cm 40% patients will develop ascites and right-sided
pleural effusion (Meig’s syndrome)
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Sertoli Cell Tumor
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Pseudomyxoma Peritonei from appendix
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PLACENTA
Pars fetalis
(fetal surface)
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PLACENTAL DISORDERS
DISORDERS OF EARLY PREGNANCY
• Spontaneous abortion
• Ectopic pregnancy
DISORDERS OF LATE PREGNANCY
• Placental abnormalities & twin placentas
• Placental inflammations & infections
• Toxamia of pregnancy (eclampsia & pre-eclampsia)
GESTATIOINAL TROPHOBLASTIC DISEASE
• Hydatidiform mole (complete & partial)
• Invasive mole
• Choriocarcinoma
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Twin Placenta
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Acute Chorioamnionitis
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GESTATIONAL TROPHOBLASTIC DISEASE
A. Complete Hydatidiform Mole
- content all of hydropic villi
- etiology: lost or inactivation of maternal chromosome in the fertilized egg
- bleeding and high hCG level in the urine
B. Incomplete (Partial) Mole
- admixture of normal and hydropic villi
C. Invasive Mole (chorioadenoma destruen)
- invasion of molar villi & trophobastic tissue into / through myometrium
D. Choriocarcinoma
- arise from normal pregnancy (20%) and abnormal pregnancy (50%
hydatidiform mole)
-very high level of urine hCG
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Fertilization pattern of compete & partial mole
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HYDATIDIFORM MOLE
Normal-looking villi
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INVASIVE MOLE
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CHORIOCARCINOMA
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