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BENIGN CYSTS
Follicular cysts
2.5 to 10 cm (< 2.5 cm = cystic follicle).
unilateral with a thin, smooth lining
inner layer of granulosa cells
outer layer of theca cells
Corpus luteum cysts
>3 cm in diameter
filled hemorrhagic fluid with yellow lining
undulating wall of luteinized granulosa cells
intervening theca cells
Surface epithelial inclusion cysts
< 1 cm in diameter
single layer of bland flat, cuboidal, or ciliated
columnar cell
Psammoma bodies may be seen
Serous epithelial neoplasms arise from
these inclusions.
Endometriosis
endometrial epithelium or glands
and stroma with associated hemosiderin-laden
macrophages and fibrosis are diagnostic
SURFACE EPITHELIAL TUMORS (SET)
Serous cystadenoma
MC SET
reproductive-aged women
unilocular; smooth-walled cysts
single layer of columnar and usually ciliated
epithelium (resemblance to fallopian tube).
cystadenofibromas = cysts surrounded by a
variable amount of fibrotic tissue
adenofibromas = lesions without a cystic
component
surface papillomas = small papillary growths
with bland, serous-type epithelium
CK7, EMA, and WT1 positive
CK20 negative
Thecomas
postmenopausal
lobulated, yellow-tan cut surface
round to oval, lipid-laden theca cells in a
fibromatous stroma with little atypia or mitotic
activity
oil red o positive in RFS
inhibin positive
Sertoli-Leydig cell tumors (SLCT)
yellow-orange to red-brown, and frequently have
a nodular appearance with a central scar
Leydig cells often show lipidization
with foamy rather than eosinophilic cytoplasm
Leydig cell tumors
benign steroid cell neoplasms
arise within the ovarian hilus
cut surface is yellow-brown with areas of
hemorrhage
large polygonal cells with foamy or granular
eosinophilic cytoplasm and round nuclei
grow in cellular clusters separated by pink
acellular areas
Reinke's crystals (intracytoplasmic eosinophilic
rod-like structures) must
be identified.
Sertoli cell tumors
low-grade, nonfunctioning tumors
yellow-tan, solid, lobulated tumors
closely packed tubules separated by fibrous
stroma
tubules are lined by cuboidal to columnar cells
with abundant pale eosinophilic cytoplasm with
little atypia or
mitotic activity
Sex cord tumour with annular tubules (SCAT)
a component of Peutz-Jeghers syndrome
well-circumscribed, ring-shaped tubules that
contain central hyalinized material
tubules are lined by cells with pale cytoplasm
oriented toward the center of the
tubule (antipodal), with peripheral elongated
nuclei
GERM CELL TUMOR (GCT)
Mature teratomas
MC ovarian GCT
usually cystic (mature cystic), less commonly
solid (mature solid) with a single solid nodule
(Rokitansky protuberance)
may contain fat, teeth, bone, and many other
tissue types
dermoid cyst is commonly used to when lined by
squamous epithelium with appendages
can have malignant component (malignant
teratoma) – i.e SCCa, AdenoCa, carcinoid,
sebaceous Ca
Immature teratomas
unilateral and typically have solid and cystic
components
they contain immature or primitive tissue (derived
from any or all three germ cell layers)
MC immature element is neuroectodermal and
consists of rosettes, masses, or tubules of
primitive neural cells
graded based on the relative amount of immature
tissue (neuroectoderm) present
Grade 1 = immature neuroectoderm occupies
< 1 LPF
Grade 2 = immature neuroectoderm occupies
1-3 LPF
Grade 3 = immature neuroectoderm occupies
≥ 4 LPF
“Grade 0” = mature peritoneal implants
(so-called peritoneal gliomatosis)
Struma Ovarii
MC monodermal teratoma
mature teratoma composed either exclusively or
predominantly (>90 %) of thyroid tissue.
secondary changes such as hyperplasia, adenoma,
and even carcinoma may be seen
Other Monodermal Teratomas
Carcinoid – 2nd MC
Neuroectodermal-type
Prolactinoma
Corticotroph cell adenoma
Dysgerminoma
MC malignant GCT
pure dysgerminoma or mixed GCT
large and solid with a smooth external surface and
a lobulated gray-tan cut surface.
nests and sheets of uniform large polygonal cells
with abundant granular eosinophilic or clear
cytoplasm, large nuclei, and
prominent nucleoli.
the nuclear membrane is characteristically
angulated (“squared off”)
Tumor cells are separated by a lymphocyte-rich
fibrous stroma
PLAP, CD117 (c-KIT), SALL4, OCT-4 positive
NORMAL ENDOMETRIUM
Menstrual phase endometrium
characterized by glandular and stromal
breakdown
Proliferative phase endometrium
glands are simple tubular structures with
pseudostratified ciliated epithelium with loose
stroma
mitosis can be seen
gland-to-stroma ratio of about 1:1
Ovulation as occurs on day 14 of the cycle.
Early secretory phase endometrium
DAYS 16-18; 2nd–4th POD
The initial morphological feature of ovulation are
the subnuclear vacuoles (DAY 16)
Maximal between DAY 17-18 of the cycle (3rd
and 4th POD)
It is assumed that ovulation has occurred when
there are subnuclear vacuoles in at least 50% of
the cells in at least 50% of the glands
Mid secretory phase endometrium
DAYS 19-23; 5th-9th POD
Cytoplasmic vacuoles become supranuclear
Luminal secretions
INITIAL - DAY 19
MAXIMAL - DAY 21-22
Glands are usually angular in shape
Stromal edema maximal at DAY 22 - best time
for implantation ("day 22, I'm ready for you")
DAY 23: prominent spiral arterioles (thickened
walls, coiling and endothelial proliferation)
Late secretory phase endometrium
DAYS 24-28; 10th -14th POD
Day 24: perivascular predecidualization (stromal
cell hypertrophy with accumulation of
cytoplasmic eosinophilia); serrated / tortuous
glands
Day 26: confluence of predecidual tissue; stromal
granulocytes (probably lymphocytes) appear
Day 28: shedding, also called glandular and
stromal breakdown; prominent necrosis and
hemorrhage; predecidual stroma and glandular
exhaustion; nuclear dust at base of glandular
epithelium; condensed stroma with overlying
papillary-syncytial change; intravascular fibrin
thrombi; stromal granulocytes
Atrophy
CHANGES IN PREGNANCY & HORMONE THERAPY
BENIGN DISEASES
Acute endometritis
dense neutrophilic infiltration of the stroma
forming microabscesses, and in severe cases, up
to the epithelium of non-menstruating
endometrium
uncommon and is usually seen only
in postpartum or postabortive endometrium
Chronic endometritis
presence of plasma cells in the endometrial stroma
Chlamydia trachomatis, Ureaplasma urealyticum,
CMV, and HSV.
Actinomyces israelii or Neisseria gonorrheae
(mixed acute and chronic)
Mycobacterium tuberculosis, fungal, sarcoidosis,
and ablation therapy (granulomatous)
Tubal (ciliated cell) metaplasia
MC metaplasia
foci of normal tubal epithelium within the
endometrial glands
Squamous metaplasia
caused by chronic irritation and
often takes the form of squamous morules
Eosinophilic metaplasia
glandular epithelium with abundant eosinophilic
cytoplasm and a central round to oval nucleus
often associated with a neutrophilic infiltrate,
the formation of small epithelial papilla, and mild
nuclear atypia
Mucinous metaplasia
consists of columnar epithelium with basally
located oval nuclei and abundant apical mucin
Osseous metaplasia
Osseous tissue in the endometrial stroma
associated with a previous
history of abortion or instrumentation
Endometrial polyps
3 “major” criteria
Varisized glands
Fibrotic stroma
Sclerosed or thick-walled vessels
Other criteria
Gross polypoid appearance
Epithelial lining on 3 sides
Adenomyomatous polyps
polyps with stromal smooth muscle often near
blood vessels
Atypical polypoid adenomyoma
most commonly
located in the lower uterine segment
crowded irregular endometrial glands with a
complex architecture and mild to moderate
cytologic atypia in stroma that is predominantly
composed of smooth muscle
A characteristic histological feature that is present
in most, but not all, cases is abundant squamous
morule
formation
Disordered proliferative endometrium
mixture of cystically dilated, budding, and tubular
glands in a proliferative setting, with
only focal glandular crowding. It occurs during
anovulatory cycles.
Endometrial stromal breakdown
troma takes on a blurry blue look as it condenses
into
small dense aggregates (“blue balls”)
associated surface epithelium shows eosinophilic
metaplasia, becoming almost oncocytic in
appearance
EPITHELIAL TUMORS (BENIGN)
Endometrial hyperplasia without atypia
Benign endometrial hyperplasia
Simple and complex hyperplasia without atypia
≥ 5 mm thick
Glands
vary in size and shape and may be separated by
varying amounts of stroma including back-to-back
crowding
The epithelium is
of stratified columnar type, with frequent
mitotic figures.
EPITHELIAL TUMORS (PRECURSOR)
Atypical hyperplasia /
Endometrioid intraepithelial
neoplasia
Simple and complex hyperplasia with atypia
crowded aggregates of cytologically altered
tubular or
branching glands
distinction between endometrial
hyperplasia without atypia and AH/ EIN
is based on nuclear atypia which may
include enlargement, pleomorphism,
rounding, loss of polarity and nucleoli
EPITHELIAL TUMORS (MALIGNANT)
Endometrioid carcinoma (Type I)
raised to exophytic, pink tan, hemorrhagic mass
irregular, confluent, complex glandular or
villoglandular structures lined by pleomorphic
stratified columnar cells with pleomorphic nuclei
invasion is recognized by the presence of an
irregular endometrial-myometrial border or by an
associated desmoplastic and inflammatory stromal
response
Endometrioid carcinoma with squamous
differentiation defined as the
presence of sheets of squamous cells usually non
keratinizing
Endometrioid carcinoma with secretory
differentiation glands composed of cells with
supra or subnuclear
vacuoles resembling secretory endometrium
Grade 1 = 5% or less of solid growth
Grade 2 = 6 and 50% solid growth
Grade 3 = ≥ 50 % solid growth
Mucinous carcinoma (Type I)
> 50% of the neoplasm is composed of
mucinous cells
similar to mucinous carcinoma of the
endocervix
The panel of estrogen receptor (ER), vimentin,
CEA, and
p16 can usually reliably distinguish between
primary endometrial and
endocervical adenocarcinoma, since ER and
vimentin will be positive in
endometrial and negative in endocervical
adenocarcinoma, while CEA
will only be positive in endocervical
adenocarcinomas. Endocervical carcinomas are
typically diffusely positive for p16 whereas
endometrial carcinomas show only patchy
positivity.
Serous carcinoma (Type II)
complex papillary architecture
papilla is lined by
epithelial cells with large atypical nuclei,
prominent nucleoli, and brisk mitotic activity
Deep myometrial
and lymphovascular invasion are often present
p16 and PTEN stains are sensitive and specific
for high-grade serous adenocarcinoma
Clear cell adenocarcinoma (Type II)
papillary, solid,
and tubular structures, often admixed
characteristic feature is the presence of hyalinized
stromal cores
pleomorphic cells with hobnail nuclei (nuclei that
jut into the gland lumen), abundant clear or
eosinophilic cytoplasm, and distinct cell borders
Carcinosarcoma (malignant mixed mullerian tumor or
MMMT)
presence of both malignant epithelial and
mesenchymal (sarcomatous)
elements.
MYOMETRIUM
MESENCHYMAL TUMORS
Leiomyoma
white-tan cut surface and are sharply demarcated
(pseudo-encapsulated) from the adjacent
myometrium
interlacing fascicles of closely packed cells with
uniform elongated nuclei and eosinophilic
cytoplasm
Cellular leiomyomas
increased cellularity with sheets of
spindle cells
no pleomorphism,
increased mitotic activity, and necrosis
Epithelioid leiomyomas
predominantly epithelioid cells with
eosinophilic to clear cytoplasm
no pleomorphism,
increased mitotic activity, and necrosis
Symplastic (atypical / bizarre) leiomyoma
scattered enlarged, markedly atypical cells,
often with multiple nuclei
mitotic count is still < 10 / 10 HPF
Mitotically active leiomyoma
> 10 / 10 HPF
lacks cytological atypia and tumor cell necrosis
Lipoleiomyoma (lipomatous variant)
classic leiomyoma which contains islands of
mature adipocytes
other heterologous elements may also be seen
Myxoid leiomyoma
hypocellular with cells widely separated
by myxoid acid-mucin stroma
Benign metastasizing leiomyoma
classic leiomyoma but
it is found in the lungs of women with a
history of typical uterine leiomyomas
Intravascular leiomyomatosis
classic leiomyomas that grow into the lumen of
the uterine or pelvic veins.
free floating within the lumen or adherent to the
vessel wall.
diagnosis of IVL is reserved for cases where
worm-like growths of smooth muscle are
observed, grossly.
Diffuse leiomyomatosis
Innumerable hypercellular tumour nodules that
merge
Metastasizing leiomyoma
typical leiomyoma but
it is found in the lungs of women
prior history of hysteroscopy with dilatation and
curettage,
or other procedures such as myomectomy or
hysterectomy.
Smooth muscle tumour of
uncertain malignant potential (STUMP)
neoplasm that fall between leiomyoma and
leiomyosarcoma
banal leiomyoma with tumor cell necrosis; (2)
necrosis of uncertain type with ≥10 mitoses/
10 HPFs; (3) marked diffuse atypia and borderline
mitotic counts; (4) tumors with cytologic atypia
where it is difficult to be sure about mitotic
counts; and (5) tumors with early necrosis that is
difficult to classify
Leiomyosarcoma
cut surface is typically
soft, bulging, fleshy, necrotic and haemorrhagic
with irregular margins
Spindle cell leiomyosarcomas
Cells with eosinophilic fibrillary cytoplasm and
elongated blunt-ended nuclei
Diffuse moderate to severe cytologic atypia
≥ 10 mitoses/10 HPFs
CTCN – coagulative tumor cellular necrosis
defined as abrupt transition form viable cells
without a transition zone of hyalinization or
granulation
Epithelioid leiomyosarcomas
≥ 50% of the cells with an “epithelial-like”
appearance
Cells with eosinophilic granular or clear
cytoplasm and round or angular nucleus
≥ 5 mitoses/10 HPFs, diffuse moderate to severe
cytologic atypia, or tumor cell necrosis
Myxoid leiomyosarcomas
Typically hypocellular with abundant
extracellular myxoid matrix
Cells with stellate, spindle, or abundant cytoplasm
with marked degree of cytologic atypia
Diagnosis based on finding moderate to severe
cytologic atypia or tumor cell necrosis, and in
their absence finding ≥ 2 mitoses / 10 HPFs
Endometrial stromal nodule
grossly tan to yellow, well-circumscribed lesions
with a smooth border
composed of cells that resemble proliferative-
phase endometrial stroma
uniform small cells with scant cytoplasm, round
to oval nuclei and inconspicuous nucleoli and
minimal mitosis
stain strongly and are diffusely positive with
CD10
Endometrial stromal sarcomas
tan to yellow cut surface
with an infiltrative border into the surrounding
myometrium, often with foci
of hemorrhage and necrosis
cells same morphology with ESN but with higher
rate of mitosis, greater
nuclear pleomorphism, prominent stromal
vascularity, and areas of collagenized stroma
Extensive lymphatic invasion is the hallmark of
the tumor
Mixed epithelial and mesenchymal tumours
Adenomyoma
A benign tumour composed of a variable number
of endometrial glands and
endometrial-type stroma surrounded by
smooth muscle
Atypical polypoid adenomyoma
polypoid lesion composed of glands
showing cytologic atypia and usually architectural
complexity set in a fibromuscular stroma
often centered in the lower uterine segment
There is often prominent squamous metaplasia
(morules)
Adenofibroma
postmenopausal
layer of epithelium with bland nuclear cytology
that overlies a cellular fibrous
stroma composed of fibroblasts and endometrial
stromal cells
Adenosarcoma
postmenopausal
arises most commonly from the endometrium
benign or atypical glandular elements in a
malignant stroma that shows increased cellularity,
pleomorphism, and a mitotic rate of >2 mitotic
figures per 10 HPF
It may show heterologous elements
the stromal component is low-grade malignant.
When ≥ 25% of the tumour contains a high-grade
sarcomatous component it is classified as an
“adenosarcoma with sarcomatous overgrowth.”
Carcinosarcoma
biphasic tumour composed of highgrade
carcinomatous and sarcomatous elements
The epithelium is most often of
endometrioid or serous and the mesenchyme is a
high-grade, non-specific
sarcoma
GESTATIONAL TROPHOBLASTIC DISEAESE