Female Genital Tract

Department of Pathology

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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 acuminatum (VIN)

Numerous condylomas encircling Acantosis, hyperkeratosis, and

the introitus cytoplasmic vacuolization (koilocytosis)

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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: lumenal 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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 Chlamydia

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 Sexually Transmitted/Infectious Diseases

D. SYPHILIS
• T. pallidum
E. CANDIDA
• C. albicans
F. TRICHOMONAS
• T. vaginalis

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 TRICHOMONAS

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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

• Prone to infection: pre-pubertal period and post-

menopausal due to:
- the environment is warm and humid
- hypo-estrinism  decrease skin vascularization 
atrophy &
decreased cornification  sensitive to infection 
atrophic
vulvitis / vaginitis
• Infection: viral or bacterial
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 B. VULVAR DYSTROPHY

• Atrophic dystrophy
• Hypertrophic dystrophy

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 Atrophic Dystrophy: Lichen Sclerosus
(Chronic Atrophic Vulvitis)

The skin becomes pale gray and parchment-like  susceptible to infection

Atrophic labia and the introitus is narrowed

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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

A. Granular cell tumor

B. Hydradenoma papilliferum
C. Bowen’s disease
- often in labia, sometime perianal and
periclitoral
- histologically as a condilomatous lesion
- 80% HPV positive, 50% HSV positive
- pre-cancer lesion
D. Squamous cell carcinoma (SCC)
E. Extramammary Paget’s Disease

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 VIN

•Diffuse cellular atypia

•Nuclear crowding
•Pathologic mitosis

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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

Colposcopy: dotted line is Post-menopausal cervix

transformation zone

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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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 Cervicitis - 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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 Condloma

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 C. CARCINOMA

Pathogenesis
• Location: squamo-collumnar junction
• Dysplasia (CIN)  neoplasia

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 Spectrum of CIN

Cervical Intraepithelial Neoplasia (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 2
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 mya be
admixerd 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

-Often pedunculated, may be solitary

or multiple

-Commonly composed of hyperplastic

endometrium with cystically dilated
glands, cellular stroma, and thick
walled vessels

-May cause intermittent bleeding, 3%

harbor adenocarcinoma

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 ENDOMETRIAL HYPERPLASIA
• Mostly occur in post-menarchal or peri-menopausal 
associated to prolonged or excessive estrogen stimulation

LOW GRADE HYPERPLASIA

• Simple low grade hyperplasia  Swiss cheese
• Complex low grade hyperplasia
• Low to moderate risk of developing carinoma
HIGH GRADE (ATYPICAL) HYPERPLASIA
• High risk to develop carcinoma

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 ENDOMETRIAL HYPERPLASIA

Simple/Swiss cheese Complex hyperplasia

Atypical hyperplasia Squamous metaplasia

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 ENDOMETRIAL GLANDULAR TUMORS
(endometrioid carcinoma)
• The second most common genital malignancies in
Indonesia, and 90% occuring after menopause
• Principally the development of adenocarcinoma is related
to prolonged or excessive estrogen stimulation
• Risk factors: obesity, diabetes, hypertension, infertility
• May be associated with functional ovarian tumors, pre-
existing hyperplasia, and history of breast cancer
• Symptoms: irregular vaginal bleeding, leukorrhea

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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
• Elderly postmenopausal patients and present with bleeding
• Derived from muellerian mesoderm, consists of malignant
stromal and glandular component
• The stromal component may be homologous (stromal
sarcoma, leiomyosarcoma) or heterologous
(chondrosarcoma, rhabdomyosarcoma, etc.)
• 5 yr survival : 25%
• Other name: Carcinosarcoma

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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

- Most ectopic pregnancies involve the fallopian tube (90%)

- Predisposing factors include that inhibit tubal transport: chronic salpingitis,
peritubal adhesion, large cyst, tumors, etc.
- After 2-6 weeks growing  rupture  hematosalpinx (in tube), 12 weeks in
isthmus

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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

Serous epithelial tumor growth from the surface of the ovary

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 Mucinous Cystadenoma

Mucinous cystadenoma with multicystic Columnar cell lining

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Borderline Serous Cystadenoma & Cystadenocarcinoma

Delicate papillary tumor growth Large, bulky tumor mass

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 Borderline Serous Cystadenoma

Increased architectural complexity and epithelial cell stratification

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 Brenner Tumor

Brenner tumor

Benign cystic teratoma Characteristic epithelial nest within ovarial stroma

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 NEOPLASTIC
OVARIAN ENLARGEMENT (2)

B. TUMORS DERIVED FROM SEX CORD/STROMA

1. Granulosa-Theca Cell Tumors
2. Fibroma
3. Sertoli-Leydig Cell Tumor
4. Hilus (hilar) Cell Tumor
5. Sertoli Cell Tumors

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 NEOPLASTIC
OVARIAN ENLARGEMENT (3)
C. TUMORS DERIVED FROM GERM CELLS
1. Teratoma
- Mature Cystic Teratoma
- Immature (Malignant) Teratoma
2. Dysgerminoma
3. Endodermal Sinus (Yolk sac) Tumors
4. Embryonal Carcinoma
5. Choriocarcinoma
D. METASTATIC TUMORS

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 Histogenesis and inter-relationship of
tumors of germ cell origin

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 Mature Cystic Teratoma (dermoid cyst)

A mixture of tissues
Hair intermingled with
butter-like substance

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 Benign Cystic Teratoma

Brain tissue is layered by

skin tissue

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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

The tumor cells are arranged in sheets punctuated by small follicle-like structures
(Call-Exner bodies)

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 Fibroma -- fibrothecoma

-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

Well differentiated Sertoli cell tubules

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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

Greenish opaque membrane Band-like infalmmatory exudate

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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

Numerous swollen villi (hydropic degeneration)

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 HYDATIDIFORM MOLE
Normal-looking
villi

Partial mole Complete mole

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 INVASIVE MOLE

The mole invade into myometrium

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 CHORIOCARCINOMA

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