Patologi

Tr Genitalia
Wanita
Rizki Hanriko
Bagian Anatomi, Patologi Anatomi & Histologi
FK UNILA
2017
 VULVA
Cysts and abscesses of Bartholin glands
• chronic bacterial inflammation, especially from
gonorrhea
• The lining of the cyst, which is usually of transitional
or squamous type, can be destroyed partially or totally
by the inflammatory infiltrate.
• The nature of the cyst can be established by the
presence of residual mucinous glands in the fibrotic
and inflamed connective tissue that forms the cyst
wall.
• The secretion product is a nonsulfated sialomucin
 Condyloma Acuminatum
• Venereal disease caused by HPV, usually type 6.
• Grossly by one or several soft elevated masses.
• Microscopically: a complicated papillary
arrangement of well-differentiated undulating
squamous epithelium supported by delicate, well-
vascularized connective tissue stalks containing
mononuclear inflammatory cells (mainly CD4+
and CD8+ cells).
• Koilocytosis  perinuclear cytoplasmic clearing
and wrinkling of the nuclear membrane (nuclear
‘raisins’).
VAGINA
• Squamous cell carcinoma: Associated with
HPV (see CIN).
• Clear cell adenocarcinoma: Occurs in young
females whose mothers received
diethylstilbestrol (DES) during pregnancy;
vaginal adenosis is the precursor lesion.
 CERVICAL INTRAEPITHELIAL
NEOPLASIA

• Infection with HPV.

• Early age at first intercourse, multiple sexual partners,
male partner with multiple sexual partners,multiparity,
and smoking.As with most cancers, the risk of
cervical cancer increases with increasing age.
• Low-grade SIL and CIN I lesions are caused by HPV
types 6, 11, 42, and 44, and have a low risk for
progression to squamous cell carcinoma.
• High-grade SIL and CIN II–III lesions are caused by
HPV types 16, 18, 31, 33, 35, 39, 45, and 52, and
have a high risk for progression.
Significance of CIN and SIL:
• Low-grade SIL and CIN I lesions are likely to
regress;
• high-grade SIL and CIN II–III lesions are more
likely to progress to an invasive squamous cell
carcinoma.

Pathogenesis of CIN and SIL

• Protein E6, produced by HPV, binds to and induces
degradation of p53.
• Protein E7, produced by HPV, binds to and inhibits
RB.
 NON-NEOPLASTIC DISEASES OF
THE UTERUS

• Six of the more common and clinically important

conditions are acute endometritis, chronic
endometritis, adenomyosis, endometriosis, abnormal
uterine bleeding, and endometrial hyperplasia
• Endometrial hyperplasia is a precursor for
endometrial adenocarcinoma
ACUTE ENDOMETRITIS
• Acute infection of the endometrium caused by
polymicrobial infection with vaginal flora.
• Symptoms: Postpartum fever, foul-smelling vaginal
discharge, uterine tenderness.
• Risk factors: Cesarean delivery, retained products of
conception, and PID (in the nonobstetric population).

CHRONIC ENDOMETRITIS
• Causes: PID, tuberculosis, retained placental tissue,
intrauterine (contraceptive) devices.
• Microscopic : Plasma cells in endometrium.
 ENDOMETRIOSIS

• Endometriosis interna = adenomyosis

• Endometriosis eksterna
 ADENOMYOSIS
• Presence of normal endometrial tissue within
the myometrium of the uterus; it may represent
downgrowth of endometrium into the
myometrium.
• Symptoms: Many cases are asymptomatic, but
patients may have pelvic pain, dyspareunia,
abnormal bleeding, and infertility.
• Signs: Enlarged uterus.
 ENDOMETRIOSIS

• Endometrial tissue in an abnormal location outside of

the uterus: Ovaries, pouch of Douglas, uterine
ligaments, fallopian tubes; rarely intestine or lungs.
• Theories of the mechanism for endometriosis
■ Regurgitation of endometrial tissue into the
peritoneum from the uterine cavity.
■ Metaplastic differentiation of coelomic epithelium.
■ Vascular or lymphatic dissemination.
• Complications : Infertility, dysmenorrhea, pelvic
pain.
• Gross: Cyst filled with thick, brown-red fluid
(chocolate cyst).
• Micros: endometrial glands & stroma, or
hemosiderin.
• Symptoms: Pelvic and abdominal pain,
dyspareunia, and infertility.
• Signs: enlarged, tender retroflexed uterus,
nodularity of the cul-de-sac, and adnexal masses.
• Visualization of “chocolate cysts” on laparoscopy
is diagnostic.
 ABNORMAL UTERINE BLEEDING
• Profuse or prolonged bleeding during
menstruation (menorrhagia) or
• bleeding between menstrual cycles
(metrorrhagia).
• The most common cause is anovulation.
• Abnormal uterine bleeding as a result of
anovulation is referred to as dysfunctional uterine
bleeding (DUB).
• Mechanisms of abnormal uterine bleeding
■ Inadequate luteal phase.
■ Contraceptive-induced bleeding.
■ Failure of ovulation (result of excess estrogen
relative to progesterone).
• Causes
~ Beginning or ending of reproductive life.
~ Dysfunction of hypothalamic-pituitary axis.
~ Excess estrogen as a result of adrenal disease,
pituitary tumors, granulosa cell tumor, PCOD,
obesity, or malnutrition
 ENDOMETRIAL HYPERPLASIA

• results from increased estrogen levels from

failure of ovulation,
• exogenous estrogen, or
• estrogen-secreting conditions such as
polycystic ovaries or granulosa cell tumor.
Risk factors:
• Any condition that increases lifetime estrogen
exposure
• Hyperplasia leads to dysplasia, which leads to
carcinoma.
Mutation:
• Inactivation of PTEN (phosphatase and tensin
homologue).Without PTEN, endometrial cells
are more sensitive to estrogen stimulation.
• Gross : Thickening of the endometrium.

Microscopic :
• Simple hyperplasia: Cystic hyperplasia; very
uncommonly progresses to carcinoma.
• Complex hyperplasia: Crowded, back-to-back
glands (50% of tissue is glands).
• Complex hyperplasia with atypia: Crowded
back-to-back glands with nuclear pleomorphism
and mitotic figures. It can be difficult to separate
complex hyperplasia with atypia from invasive
carcinoma.
Clinical presentation of endometrial hyperplasia
• Vaginal bleeding, especially in a postmenopausal
woman.
• Widened endometrial stripe on transvaginal
ultrasound and
• Endometrial or atypical glandular cells on PAP
smear.
• Endometrial biopsy is diagnostic.
 Endometrial Polyps
• >>> not true neoplasms but probably represent
circumscribed foci of hyperplasia,
• possibly due to a decreased expression of hormone
receptors in the stromal component.
• Grossly, they protrude into the endometrial cavity and
often exhibit secondary changes.
• The glands usually show some degree of cystic
change. They may be lined by an active
pseudostratified epithelium containing mitotic figures
or, in the postmenopausal patient, by a flat, inactive
epithelium
 TUMORS OF THE UTERUS
• The most common endometrial carcinoma is
endometrial adenocarcinoma.
• Leiomyomas are the most common tumor
overall of the uterus.
• Leiomyosarcoma, is not common.
ENDOMETRIAL ADENOCARCINOMA
• Many occur about age 55 years or older.
Risk factors:
• increased estrogen levels, by early menarche & late
menopause, nulliparity, and PCOD;
• exogenous estrogen via estrogen-only contraception
and hormone replacement therapy (HRT);
• Obesity causes increased estrogen levels through
peripheral conversion of androstenedione to estrone
via aromatase in adipose tissue.
• Diabetes mellitus and hypertension.
• Precursor lesion: Endometrial hyperplasia.

Mutations:
• ± 35% mutation of PTEN (10q23) : tumor
suppressor gene arrest of the cell cycle at G1
apoptosis.
• mutation of β-catenin.

• Symptoms: Vaginal bleeding.

Endometrial
Adenocarcinoma
Grade 1, 2 & 3
 LEIOMYOMA
• Benign, Reproductive years.
• Subserosal, intramural, or subendometrial
locations, usually multiple in number.
• Mutations: t(12;14) and del 7.
• Leiomyomas are estrogen sensitive and
increase in size with pregnancy and decrease in
size with menopause.
Complications:
• Menorrhagia with severe anemia.
• Infertility, abortion, and premature labor.
• Compression of the bladder or ureter, causing
hydroureter or hydronephrosis.
•  Leiomyosarcoma extremely rare
• The most important risk factor for malignant
degeneration to leiomyosarcoma is prior pelvic
irradiation.
 LEIOMYOSARCOMA
• Malignant tumor of smooth muscle.
• Females between ages 40 and 60 years.
• Clinical presentation:
• Rapidly enlarging pelvic mass.May present in
a woman with a history of leiomyomas.
• Metastases to lungs, bone, and brain.
 Polycystic ovarian disease (PCOD)
• Result in excessive production of estrogen and
androgens, which are converted to estrone. Estrone
then inhibits FSH.
• Increased risk for endometrial hyperplasia and cancer,
diabetes mellitus, and metabolic syndrome.
• Obesity, hirsutism and acne, and infertility.
• Multiple follicular cysts or cystic follicles with
varying degrees of luteinization of the theca interna,
covered by a dense fibrous capsule.
OVARIAN TUMORS
 SURFACE EPITHELIAL TUMORS
• Approximately 80% are benign.
• Borderline (i.e., low malignant potential) tumors
exhibit features of anaplasia with no or little invasion
of stroma. In many cases, peritoneal “metastases” do
not invade.
• Benign: between the ages of 20 and 45 years.
• Malignant: between the ages of 40 and 65 years.
• CA-125 is elevated in patients with ovarian epithelial
tumors.
• About 90% of ovarian cancers are derived from surface
epithelium,
 Serous Tumors
• Most common ovarian malignancy (40% ).
• 30% of all ovarian tumors; 70% are benign or
borderline.
• Prognosis is linked to stage and tumor grade; even
with extensive extra-ovarian spread, lowgrade tumors
can progress relatively slowly.
• 5YSR for borderline and malignant tumors confined
to the ovary are 100% and 70%, respectively; 5YSR
for similar tumors involving the peritoneum is 90%
for borderline tumors and 25% for malignant tumors.
• Nulliparity, gonadal dysgenesis, family history, and
hereditable mutations are important risk factors.
• BRCA1 and -2 mutations incur a risk of ovarian
cancer developing by age 70 years in 20% to 60% of
patients; most are high-grade.
• Low-grade tumors tend to arise in serous borderline
tumors and have KRAS and BRAF mutations;
• High-grade tumors have a high frequency of p53
mutations.
• Many of these tumors appear to arise from the
fimbriated end of the fallopian tube.
 Mucinous Tumors
• Roughly 30% of all ovarian neoplasms; Primary <5%
of all ovarian malignancies.
• 80% are benign or borderline.
• Smoking is a risk factor, and KRAS mutations are a
common feature.
• These tumors can seed the peritoneum with numerous
implants that produce extensive mucinous ascites,
called pseudomyxoma peritonei
• Five-year survival rates for stage I disease are more
than 90%.
 Endometrioid Tumors
• 20% of all ovarian cancers;
• About 15% to 20% of cases occur in the setting of
concurrent endometriosis, although direct origin from
the ovarian surface is also possible.
• In 15% to 30% of cases, independent endometrial
carcinomas also occur.
• PTEN, KRAS, and b-catenin mutations occur
frequently, as well as microsatellite instability; p53
mutations are common in poorly differentiated
tumors.
• 5YSR for stage I disease is 75%.
 Clear Cell Adenocarcinoma
• Uncommon; it is considered a variant of
endometrioid adenocarcinoma.
• Tumors can be cystic or solid;
• the large epithelial cells contain abundant clear
cytoplasm.
• Patients with cancer confined to the ovary have 5-
year survivals of 65%;
• with extra-ovarian spread, 5-year survival is
unusual.
 Brenner Tumor
• Brenner tumor is a variably sized (1 to 30 cm),
solid tumor (adenofibroma)
• Characterized by dense fibrous stroma and
nestsof epithelium resembling urinary
transitional or rarely columnar epithelium.
• They are usually unilateral; the vast majority of
these tumors are benign.
 Germ Cell Tumors
• Germ cell tumors represent 15% to 20% of all
ovarian tumors;
• most are benign cystic teratomas.
• They are similar to male germ cell tumors
• and arise from neoplastic transformation of
totipotential germ cells capable of
differentiating into the three germ cell layers.
 Teratomas
• Typically arise in young women.
• The karyotype of virtually all benign teratomas is
46XX, and they likely arise from an ovum after the
first meiotic division.
• Mature teratomas are characteristically cystic masses
lined by squamous epithelium with adnexal structures
including hair shafts and sebaceous glands; tooth
structures and tissues from other germ cell layers can
often also be identified (e.g., cartilage, bone, thyroid,
and neural tissues).
• Tumors are bilateral in 10% to 15% of cases. The vast
majority of such tumors are cured by excision; 1%
undergo malignant transformation, most commonly as
squamous cell carcinoma.
• Monodermal Teratoma  The most common is
struma ovarii, composed entirely of mature thyroid
tissue; ovarian carcinoid is another variant.
• Although they grow rapidly and frequently penetrate
the capsule, low-grade tumors have an excellent
prognosis, and even high-grade malignancies can
respond well to chemotherapy.
Benign
Teratoma
Immature (Malignant) Teratoma
• Grade I : Abundance of mature tissues, intermixed
with loose mesenchymal tissue with occasional
mitoses; immature cartilage; tooth anlage
• Grade II : Fewer mature tissues; rare foci of
neuroepithelium with common mitoses, not
exceeding three low-magnification (×40) fields in
any one slide
• Grade III : Few or no mature tissues; numerous
neuroepithelial elements, merging with a cellular
stroma occupying four or more low-magnification
fields.
Immature
teratoma
Struma
Ovarii
 Dysgerminoma
• Ovarian counterpart of testicular seminoma.
• 2% of all ovarian cancers but about half of the
malignant germ cell tumors.
• Most occur between ages 20 and40 years, and most
have no endocrine function.
• Oct3, Oct4, and Nanog transcription factor expression
by dygerminomas maintain pluripotency; the tumors
also express the c-KIT receptor tyrosine kinase.
• All dysgerminomas are malignant, but only about one
third are highly aggressive; because they are
chemosensitive, overall survival exceeds 80%.
 Endodermal Sinus (Yolk Sac) Tumor
• Rare malignancy resulting from differentiation of
germ cells toward yolk sac structures.
• Histologically, there are glomerulus-like structures
with a central vessel enveloped by germ cells within a
cystic space lined by additional germ cells (Schiller-
Duvall body).
• Intracellular and extracellular hyaline droplets are
conspicuous and can contain a-fetoprotein (AFP).
• The tumors occur in children and young women and
grow aggressively, although they are
chemoresponsive.
 Choriocarcinoma
• Extra-embryonic differentiation of malignant
germ cells; most such tumors exist in
combination with other germ cell tumors.
• Histologically, they are identical to placental
malignancies and elaborate chorionic
gonadotropins.
• Ovarian choriocarcinomas are highly
malignant, metastasize widely,
• Much more resistant to chemotherapy than
their placental counterparts.
 Sex Cord–Stromal Tumors
• These tumors originate from ovarian stroma,
• Derives from the sex cords of the embryonic
gonad.
• The tumors frequently produce estrogens or
androgens.
 Granulosa–Theca Cell Tumors
• 5% of all ovarian tumors;
• Two thirds occur in postmenopausal women.
• Inhibin produced by granulosa cells can be a useful
biomarker to diagnose and monitor tumors.
• These tumors can elaborate large amounts of estrogen and
thus produce precocious sexual development and
endometrial hyperplasia; they predispose to endometrial
carcinoma.
• Occasionally, granulosa cell tumors produce masculinizing
androgens.
• While 5% to 25% of granulosa cell tumors are malignant,
most have an indolent course, with 10YSR of 85%.
• Purenthecomas are virtually always benign
Call exner bodies
& Coffe bean
nuclei
 Fibromas, Thecomas, & Fibrothecomas
• 4% of all ovarian neoplasms; >>> benign.
• Usually unilateral, solid, hard, gray-white masses.
• The fibroma component is composed of well-
differentiated fibroblasts and scant collagenous
connective tissue;
• the thecoma portion contains plump spindle cells with
lipid droplets.
• 40% of tumors are associated with ascites and
occasionally right-sided hydrothorax (Meigs
syndrome).
• They can also be associated with BCNS
 Sertoli–Leydig Cell Tumors
(Androblastomas)

• Sertoli–Leydig cell tumors (androblastomas)

recapitulate the cells of the testes
• Commonly produce masculinization or
defeminization.
• They are usually unilateral
• Consist of tubules composed of Sertoli cells
and/or Leydig cells interspersed with stroma.
• Well-differentiated (Meyer type I) (11%). Composed
of tubules lined by Sertoli-like cells separated by
variable numbers of Leydig-like cells. Sometimes
those tubules have a hollow ‘pseudoendometrioid’
appearance, the tumor thus simulating a borderline or
malignant endometrioid neoplasm.
• Intermediate (Meyer type II) (54%). Characterized by
the formation of cords, sheets, and aggregates of
Sertoli-like cells, separated by spindle stromal cells
and recognizable Leydig cells (Fig. 19.324).
• Poorly differentiated (sarcomatoid; undifferentiated;
Meyer type III). Composed of masses of spindle-
shaped cells arranged in a ‘sarcomatoid’ pattern .
 Metastatic Tumors
• Metastatic tumors of the ovary most commonly
derive from tumors of müllerian origin (e.g.,
uterus, fallopian tube, contralateral ovary, or
pelvic peritoneum);
• the sources of the most common extra- müllerian
metastases are carcinomas of the breast and
gastrointestinal tract.
• Krukenberg tumors are ovarian cancers (often
bilateral) caused by metastatic mucin-producing
signet cells, usually originating from the stomach.
Terima Kasih