Female

Vulva - Condyloma Accuminata

Gross: Verrucous lesion (papillary, wart-like), solitary or

multiple, white plaques

Histo: Koilocytosis, lg. hyperchromatic nuclei, halo/clearing

around nucleus, rasinoid nucleus (irregular outline, like a

raisin); see the same histology from the same virus (low

grade HPV) in different locations (vaginal intraepithelial

lesion 1 and cervical intraepithelial lesion 1)

Lecture: Caused by low risk HPV (6 & 11),

sexually transmitted, may disappear, persist or

recur.









Vagina – Clear Cell Carcinoma

Gross: On anterior wall of vagina

Histo: Abundant clear cytoplasm due

to increased glycogen; the spaces btw.

cells are dilated glands

Lecture: Adenocarcinoma in young

women whose mothers were **treated

with DES during pregnancy** Tx by

surgery or radiation. Clear cell

carcinoma may be seen in other parts

of the body, but those are not assoc.

w/ DES.



Vagina - Embryonal Rhabdomyosarcoma

Gross: grape-like

structures

Histo: Cambium layer w/

fibromyxomatous and

edematous stroma with

inflammatory cells.

Cambium layer = The

inner osteogenic layer of





1

the periosteum, a highly cellular zone immediately beneath the epithelium covering a

botryoid sarcoma.

Lecture: Uncommon; tx w/ surgery and chemo



Cervix

Histo: Normal Cervix – top 1/3 is superficial/mature layer;

non-keratizing, stratified squamous epithelium

Lecture: HPV!! Do Pap smear (screening, not diagnostic) at

squamous/columnar junction. Low risk HPV types 6 and 11

 condyloma, vaginal and cervical intraepithelial lesion 1.

High risk HPV types 16 and 18  CIN (cervical

intraepithelial neoplasia) II and III. If get an abnormal Pap,

need to do a biopsy to make the dx. Dx as low or high grade

CIN, not as LSIL or HSIL.









Cervix – Low grade squamous intraepithelial lesion (LSIL)

LSIL = CIN I (cerv intraepi neoplasia I) Normal squamous cell

Histo: Koilocytosis (cells have halo – sm., pyknotic nuclei,

nuclei). Cells affected in top 1/3 layer. abudent cytoplasm

Raisinoid nucleus.

Lecture: Caused by low risk HPV 6 & 11.

Tx – wait & watch, Raisinoid Nucleus

cryotherapy,

All found in

most will top 1/3 Halo

regress on

their own in 2-3 yrs.









2

Cervix – High grade squamous

intraepithelial lesion (HSIL)

HSIL = CIN II and III Normal squamous cell



Histo: Irregular, large, dark nuclei.

Mitotic figures in whole epithelium.

Lecture: From high risk HPV 16. CIN III

may progress to invasive carcinoma. Tx

w/ Leep or cold knife cone (after biopsy

and CIN III

dx).









In situ – hasn’t

broken thru BM









Squamous Cell Carcinoma

Microinvasive – early stromal invasion < 5mm

Gross: fungating (a CA growing under the skin

breaks through to create an open wound),

exophytic (tendency to grow outward),

ulcerating mass

Histo: In top slide, frank invasion –

nests of dysplastic/malignant cells

surrounded by stroma. In bottom slide,

nest of malignant cells inciting

lymphatic response.

Lecture: Direct spread to urinary

bladder, peritoneum, ureters, rectum

and vagina. From high risk HPV.

Degree of invasion (stage) important for

prognosis. Treatment for invasive is

radiation/chemotherapy, surgical.









3

Uterus – Endometrial Cycle

Proliferative Phase

Lecture: Estrogen at this phase!

Histo: Tubular glands – pseudostratified columnar epithelium. Lots of space between

the glands – not crowded. Lot of mitotic activity in

the glands and stroma. Mitotic figures not abnormal

b/c it’s proliferating.









Secretory Phase

Lecture: Progesterone at this phase! Early and late parts of this phase.

Histo: Secretory vacuoles and exhaustion. Prominent spiral arterioles. Serrated glands.

Secretion in gland lumens.



Clear space under nucleus is

a vacuole of secretion









Menstrual Phase

Lecture: Disintegration of

functionalis

Histo: Blood and inflammatory

cells in stroma









4

Abnormal Uterine Bleeding due to an Organic Lesion – Endometrial Polyp

Lecture: Benign,

assoc. w/ Posterior

Endometrium

administration of

Tamoxifen,

chromosome 6p21 Bisected

rearrangements endometrium

Gross: Single or

multiple

Polyp









Abnormal Uterine Bleeding due to an Organic Lesion – Leiomyoma (Fibroid)

Lecture: Benign, highly frequent. Pathogenesis: smooth muscle layer pushes against

endometrial layer  atrophies endometrial layer  bleeding



Endometrial layer



Also see in

myometrium

section









Abnormal Uterine Bleeding due to Infection – Chronic Endometritis

Chronic inflammation of the endometrium

Lecture: Commonly due to PID, TB, Chlamydia, or retained gestational tissue

following a birth or abortion.

Histo: Plasma cells in stroma (as

opposed to the microabscesses and

neutrophils w/in the glands of

acute endometritis). Plasma cells:

abundant cytoplasm, clearing

adjacent to nucleus, clockface

nuclei.









5

Abnormal Uterine Bleeding due to an Organic Lesion – Simple Endometrial

Hyperplasia (“cystic hyperplasia” or

“cystic atrophy”)

Lecture: prolonged estrogen stimulation

 anovulation or incr. production.

Assoc. w/ (etiologies?) menopause,

polycystic ovarian disease, granulosa cell

tumors of the ovary, estrogen tx. Due to

unopposed, increased estrogen, not

normal hormonal stimulation. Not a

precursor of carcinoma  treat

conservatively.

Histo: proliferative phase glands w/

cystic dilation (wouldn’t see in normal

proliferation); glands are more crowded but not bumping into e/o.



Abnormal Uterine Bleeding due to an Organic Lesion – Complex Endometrial

Hyperplasia

Histo: increased # and

size of glands; crowded

– not respecting e/o

space; cribiform

arrangement, weaving

in and out of e/o; lots

of branching









Abnormal Uterine Bleeding due to an Organic Lesion – Atypical Hyperplasia

Lecture: Atypical is associated with cancer. Could be simple hyperplasia with atypia

or complex hyperplasia with atypia.



Endometrial Intraepithelial Neoplasia (EIN)

Lecture: Incr. risk for CA. Always proliferative – increased sensitivity to estrogen.

Assoc. w/ PTEN tumor suppressor gene inactivation  glands more sensitive to

estrogen stimulation.









6

Histo: Glands always proliferative. Precancerous – crowded, hyperchromatic









Abnormal Uterine Bleeding due to an Organic Lesion – Endometrial

Adenocarcinoma (endometrioid type)

Lecture: Most common invasive CA of the female genital tract; 55-65 YO; Assoc. w/

obesity, DM, HTN, infertility. PTEN inactivation, estrogen, DES, p53 mutation.

Robbins: May be derived from transplanted endometriosis (located in another organ of

the female genital tract other than the endometrial lining); solid or cystic; CA-125 is the

marker in 80%









Cribiform, touching e/o, frank invasive adenocarcinoma

(beyond hyperplasia)









Lymphatic invasion









7

Papillary Serous Adenocarcinoma

Lecture: bad prognosis; p53 mutation

Histo: Can do a p53 stain;

On right: Papillary structure; cells look clear due

to increased glycogen

Below: hyperchromatic, irregular nuclei









Abnormal Uterine Bleeding due to an Organic Lesion – Clear Cell Adenocarcinoma

Lecture: high grade tumors, poor prognosis

Histo: Abundent clear cytoplasm









Uterus (Myometrium) – Leiomyoma (Fibroids)

Lecture: Most common tumor (75% of

women); subserosal, submucosal, or

intramural; 40% w/ chromosomal

abnormality

Gross: Well-circumscribed, firm, gray-

white tumors

Histo: Whorled pattern of smooth

muscle spindle cells





8

Uterus (Myometrium) – Leiomyosarcoma

Lecture: Uncommon malignant neoplasm, pre and

postmenopausal women, recur after removal and

distant metastasis

Gross: Bulky, fleshy mass that invades the wall or a

polypoid mass that projects into the lumen

Histo: Nuclear atypia, mitotic figures, tumor cell

necrosis









Malignant Features – blue  hyperchromatic,

lighter  necrosis

Cells – atypical features w/ abundant mitotic figures







Endometriosis

The presence of endometrial glands or stroma in an abnormal location outside the

uterus. Commonly in ovaries, uterine ligaments, rectovaginal septum, vulva,

peritoneum, umbilicus, vagina, appendix. ENDOMETRIOSIS IS NOT CANCER.

Lecture: Symptoms are bleeding, pelvic pain, dysmennorhea, infertility. There are 3

potential explainations regarding the origin, incl. lymphatic dissemination,

regurgitation through the fallopian tubes, and extrapelvic dissemination through the

pelvic veins.





9

Gross: Chocolate cyst (endomytrioma filled with blood; happens b/c outside the uterus

the cells will still cycle and bleed into itself)

Histo: lot of macrophages (to clean up bleeding); endometrial stroma and glands









Polycystic Ovary Disease (PCOD) (Stein-Leventhal Syndrome)

Lecture: 3-6% reproductive age women (single cyst are

frequent), usu. in cortex, oligomenorrhea, anovulation,

hirsutism, obesity

Gross: multiple cystic follicles, ovaries are twice normal

size

Histo: Stromal hyperthecosis (Diffuse hyperplasia of the

theca cells of the graafian follicles); cysts filled w/ clear,

pink fluid; hypercellular stroma









10

Ovarian Tumors









Lecture: classified as benign, LMP/borderline, or malignant. Assoc. w/ nullparity,

family hx, BRCA 1&2 mutations, tumor suppressor gene p53, Her2/neu oncogene



Serous Cystadenoma

Lecture: Most common; 40-50 YO; non-

specific symptoms (pelvic and back pain);

treatment is cystectomy or unilateral

salpingo-oophorectomy (removal of fallopian

tube and ovary)

Gross: Bilateral

Histo: Cysts lined by tall columnar ciliated

epithelium (normally the epi seen in the

fallopian tubes); no mitosis, no invasion, no

hyperplasia



Mucinous Cystadenoma

Lecture: a spongy cystic tumor; less

common, middle age, assoc. w/

pseudomyxoma peritonei (peritoneal

cavity filled with this fluid)

Gross: larger tumor than serous w/

diff size cysts, filled with thick,

viscous, gelatinous fluid; mucinous

epithelium





11

Brenner Tumor (urothelial)

Lecture: uncommon

adenofibromas, mostly benign,

unilateral

Gross: solid or cystic

Histo: nests of transitional

epithelium surrounded by more

cellular stroma









Brenner tumor (solid)



Benign Cystic Teratoma









Benign Cystic Teratoma (Dermatoid Cyst)

Lecture: benign, mature germ cell tumor;

bilateral in 10-15%; young women; 1% have

malignant change – SCC (squamous cell

carcinoma), thyroid carcinoma; to dx, see tissue

from 3 layers

Ectoderm – skin, appendages, teeth

Mesoderm – CT, smooth muscle, cartilage

Endoderm – Gut, respiratory

Neuro - glail

Gross: unilocular (single compartment) cyst w/

hair, teeth, and sebaceous material

Histo: Several types of mature adult-type epithelium (skin, hair, teeth, sebaceous

glands, brain/glial/neuro, cartilage, adipose, GI)









mature brain









12

Fibroma (Thecoma)

Lecture: Meigs Syndrome is the joint presentation of the ovarian

tumor with ascites and hydrothorax); also assoc. w/ basal cell nevus

syndrome

Gross: Unilateral, solid, white/gray, well-circumscribed (resembles a

fibroid)

Histo: Forms in ovarian stroma; usu. a combination of

fibroblasts (fibromas) and lipid droplets (thecomas)









Borderline (LMP – low malignant potential) Neoplasms

Three types: Transitional, Serous, and Mucinous (serous and mucinous between

cystadenoma and carcinoma)

Borderline Serous Tumor

Histo: proliferation of serous epi but no

invasion into stroma

Lecture: cystic, surface involvement,

intracystic proliferation (contained, not

invading), epithelial stratification

Gross: papillary projections into the lumen









Epithelial Malignant Neoplasm – Serous Adenocarcinoma

Lecture: most common ovarian CA; 45-65 YO; serum level of

CA-125 elevated; dissemination in pelvic and abdm cavities;

pain; ascites; Px - stage

Histo: Multilocular cystic, complex papillary

architecture with marked atypia, invasion

Gross: necrotic (yellow) and hemorrhagic 

Smooth cystic lining nearly

indicate invasion replaced by papillary architecture









13

Psammoma Body – concentric, laminated calcifications









Malignant Epithelial Neoplasia - Mucinous

Adenocarcinoma

Histo: Marked complex architecture, marked

atypia, invasion, not bland anymore,

hyperchromatic

Gross: Hemorrhagic









Malignant Germ Cell Tumor - Dysgerminoma

Lecture: Uncommon; young

women; ovarian counterpart of

seminoma in the testis;

radiosensitive  excellent

prognosis; unilateral

Histo: Big nucleoli, abundant

cytoplasm (clear due to dissolved

glycogen), heavy

lymphoplasmacytic infiltrate

surrounding nests of cells









14

Malignant Germ Cell Neoplasm – Yolk Sac Tumor

Lecture: Rare; in children and young

women; aggressive

Histo: Schiller-Duval Body (also

called a rose setting??) - a glomerulus-

like structure with central blood vessel

surrounded by embryonal cells lying

within a space also lined by

embryonal cells. Conspicuous intra

and extra cellular hyaline globules of

alpha-fetoprotein are seen. The AFP is

secreted and appears in the blood as a

biologic marker for the tumors used

both for diagnosis and monitoring

response to therapy.



Malignant Germ Cell Neoplasm – Choriocarcinoma

Lecture: Placental origin;

extraembryonic differentiation of

malignant germ cells (ctyotrophoblasts

surrounded by syncytiotrophoblasts

that produce/store hCG); in

combination w/ other germ cell

tumors; aggressive; 50% from pre-

existing complete mole, 25% after

abortion, 25% after normal pregnancy;

may present as a metastases to the

brain; responsive to chemotherapy

Gross: (showing a bisected uterus)

Highly invasive, hemorrhagic mass









15

Malignant Sex Cord Stromal Tumor - Granulosa Cell Tumor

Lecture: Postmenopausal women; precocious sexual development in young women

and endometrial hyperplasia or

endometrial carcinoma in

postmenopausal women

Gross: Unilateral, solid

Histo: Cal-Exner bodies (spaces lined by

the granulosa cells to give a follicle-like

appearance), nests of tumor cells,

“coffee beans”; rose setting (granulose

cells surrounding BV)







Treatment for Ovary Carcinoma

TAH-BSO, Omentectomy, LN dissection, adjuvant or neoadjuvent chemotherapy





Ectopic Pregnancy

Lecture: Most common location is

fallopian tubes

Gross: Embryo in fallopian tube

Histo: Immature chorionic villi

consistent w/

placenta









Pelvic Inflammatory Disease

Caused by gonococci, chlamydia, enteric bacteria

Assoc. w/ acute salpingitis, salpingo-oophoritis, tubo-ovarian abscess, pyosal pinx,

adhesions, hydrosalpinx

Complications incl. peritonitis, intestinal obstruction, bacteremia, infertility, sepsis,

ectopic pregnancy (healing and scarring  adhesions)

Treatment: i.v. antibiotics, surgical









16

Histo: Fallopian tube epi but dilated and filled w/ mixed inflamm infiltrate









Placenta – Acute Chorioamnionitis

Lecture: Ascending infection through the birth canal (bacterial most common) or

transplacental (hematogenous) infection (TORCH – toxoplasmosis, rubella, CMV,

herpes); premature rupture of membranes

Gross: (Looking at the fetal

side) Opaque, green tinge

(normally clear/pinkish)

Histo: Neutrophils  acute

chorioamnionitis









17

Molar Pregnancy/Hydatiform Mole

(http://pregnancy.about.com/cs/pregnancyloss/a/aa072599.htm - A molar pregnancy refers to a pregnancy that

is a type of gestational trophoblastic disease.)

Lecture: May precede choriocarcinoma; sx: vaginal bleeding; any age (teens, 40-50)

Histo: cystic swelling of chorionic villi and variable trophoblastic proliferation

Treatment: Evacuation, serial β-hCG evaluation









Bunch of fluid-filled grapes









Complete Mole: (This occurs when the Partial Mole: (This most frequently occurs

nucleus of an egg is either lost or inactivated. when two sperm fertilize the same egg. There

The sperm then duplicates itself b/c the egg was may be partial placentas, membranes or even a

lacking genetic information. Usually there is no fetus present in a partial mole. However, there

fetus, no placenta, no fluid and no amniotic are usually genetic problems with the baby.)

membranes.) Triploid karyotype (69XX or Y)

Diploid karyotype (46XX or Y) focal trophoblastic proliferation

circumfrential trophoblastic proliferation HALF villi edematous/hydropic

ALL villi edematous/hydropic serum β-hCG less elevated

serum β-hCG elevated choriocarcinoma rare

2% risk of choriocarcinoma fetal parts can be identified

no fetal parts





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