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What causes ovarian cysts?
--ETIO: hormone imbalance, ov CA, mets, smoking, low BMI, early menarche, infert (4x), hypothyroid, neonatal cysts (common in babies of moms w/ DM, toxemia and Rh immunization)
--RISK factors: tamoxifen tx (10% incr risk), smoking (0-2x incr in incidence), hx of cysts

What are the possible sequelae of ovarian cysts?
--assoc w/ infertility and irregular menstrual bleeding
--hemorrhage, peritonitis, dysmenorrhea, dyspareunia, necrosis, sepsis, death
--may coexist with ectopic preg
--could cause adnexal torsion, more on R side (L cushioned by rectosigmoid), more when big

What is the pathophysiology ovarian cysts?
--disordered folliculogenesis: unruptured graafian follicle or ruptured one that sealed
--w/ hypothalamus-pitutiary dysfunction or dt anatomical defect
--follicular cysts are in first 2 wks of cycle, may secrete estrogen causing menses 2b irreg
--corpus luteal cysts form when corpus luteum doesn't degenerate in last 2 weeks of cycle, may secrete progesterone, may become inflamed or spontaneously hemorrhage

What is the pathophysiology of PCOS?
--enzyme (aromatase) malfx-->androgen biosynthesis is poorly regulated-->excessive androgen from theca-lutein cells of follicles in ovaries. Androstenedione-->estrone (E1) & testost

What is the morphology of PCOS?
--ovaries 2x the normal size, firm, gray white with smooth outer cortex, subcortical cysts .5-1.5 cm diameter filled w/ clear fluid, thickened superficial cortex and hyperplasia of theca interna (follicular hyperthecosis), corpora lutea frequently absent

What is the incidence of ovarian cancer?
--6% of all CA in women in US (excluding skin CA), ranking after cervical and endometrial CA
--numerous tumors of ovaries: 80% are benign and occur in women 20-45 years of age
--malignant more common in women 40-65

What is the mortality rate from ovarian cancer and why?
--Accounts for 1/2 of deaths from CA of the female reproductive tract, because there are few signs of an early ovarian cancer, they are rarely detected early. Many have spread before detection, seeding into the peritoneum or spreading by mets to all the usual places. Because early detection is rare and ovarian cancers "seed", the death rate if rather high.

What's the pathogenesis of ovarian cancer?
?? the usual?
--RISK factors: (not as clear as for other genital cancers): nulliparity, low parity, FHx, gonadal dysgenesis, genetics
--BRCA 1 & 2 incr likelihood 20-60% by age 70-->mostly cystadenocarcinoma
--PROTECTIVE factors: OCP's and tubal ligation decr incidence in women 40-59
--GENETICS: 30% of Ov adenocarcinomas express high levels of Her2/neu oncogene
--Her2/neu correlates with poor prognosis
--p53 mutations found in 50% of ov CA

What's the overall frequency of the various types by cell of origin?
1) surface epithelium-stromal tumors: 65-70% of all tumors, 90% of malig, over age 20
2) germ cell tumors: 15-20% of all, 3-5% of malig, 0-25 years
3) sex-cord stromal tumors: 5-10% of all, 2-3% of malig
4) mets: 5% of all, 5% of malig, any age
5) malignant, defies classification

What are the categories of Mullerian types of ovarian cancer?
serous
endometroid
mucinous

What are psammoma bodies and where are they found?
concentric, laminar, circular, acellular, eosinophilic calficications
seen under a microscope
found in papillary carcinomas of the:
ovary, prostate, kidney, thyroid, endometrium, mesothelioma, meningioma
from Greek word psammos meaning "sand"
assoc with papillary histomorphology
thought to arise from infarction/calcification of papillae tips
OR from calcification intralymphatic tumor thrombi

What is pseudomyxoma peritonei?
ov tumor with extensive mucinous ascites, cystic epithelial implants on peritoneum, and adhesions, may result in intestinal obstruction and death

What is a Brenner tumor?
uncommon adeonfibroma in which epithelial component is nests of transitional cells
like bladder lining, sometimes cysts contain microcysts or gladular spaces lined by columnar, mucin-secreting cells, sometimes found in mucinous cystadenomas
MORPH: mb solid or cystic, usu unilateral, vary from small to massive
fibrous stroma looks normal, nests with mucinous glands in center
sometimes stroma has plump fibroblasts like thecal cells, may have hormonal activity

What is the clinical picture/course for Mullerian tumors?
most Brenner tumors are benign but some are borderline or malig
most often found incidentally, usu no problem

What are CA 125 and osteopontin and what do they tell you?
--CA-125 (high-MW glycoprotein) present in >80% of serous, endometrioid carcinomas.
--Newer marker – Osteopontin was only faintly mentioned in SSL's notes as a way to monitor the course of ovarian cancer. OSTEOPONTIN is a glycoprotein that was originally discovered in bone, linking osteoclasts to the mineral components, but has since been found to be involved in immune regulation (chemotaxis, apoptosis blocker), scar formation, tumors, and lots more. Works as anti-apoptotic factor sometimes. Provokes release of IL-17. Has lots of other names but OPN is most common. Involved in alcoholic liver disease, rhemuatoid arthritis, glomerulonephritis and tubulointerstitial nephritis, and is found found in atheromatous plaques within arteries. It is expressed in macrophages, neutrophils, dendritic cells, and T and B cells. Osteopontin is overexpressed in a variety of cancers: lung, breast, CRC, stomach, ov, melanoma, mesothelioma.

Which ovarian tumor may produce 5-hydroxytryptamine and a carcinoid syndrome?
a monodermal or specialized teratoma
(of the germ cell tumors, only mature teratoma and dysgerminoma will be on the final)

What is 5-hydroxytryptamine?
serotonin

What kind of ovarian tumor is most likely to be bilateral?
serous, in general
cystadenocarcinomas specifically (66%)

What are Schiller-Duval bodies?
glomerulus-like structure composed of a central BV in germ cell lined space

What kind of ovarian cancer has Schiller-Duval bodies under the microscope?
endodermal sinus or yolk sac tumor
2nd mc germ cell malignancy

Who gets yolk sac tumors?
children or young women who present with abdominal pain and rapidly growing mass

What fetal marker may be produced by yolk sac tumors?
α-fetoprotein

Which ovarian tumor is the counterpart of the seminoma in the testes?
dysgerminoma

What kind of ovarian tumor is most likely to be bilateral?
endothelial

Which kind of ovarian tumor is most likely to secrete hormones?
sex-cord stromal tumors
tumors secrete hormones assoc with the cell type, estrogens (theca), androgens (Leydig)

Why is endometrial carcinoma diagnosed earlier in the US than ovarian cancers?
because it causes DUB

Why is cervical cancer diagnosed earlier in the US than ovarian cancers?
because we get PAP smears

What hormone might be produced by a dysgerminoma?
chorionic gonadotropin

What's the overall survival rate for dysgerminoma?
over 80%

What is the most common ovarian malignancy?
serous cystaenocarcinomas 40% of all OvCa, occur age 40-60

What ovarian cancer has the worst prognosis of all?
not sure of exact answer, what do you say?
notes:
90% of malignant ovarian CA comes from surface epithelium-stromal tumors
(from coelomic or ectopic endometrial epithel)
Her2/neu gene correlates with poor prognosis
PSEUDOMYXOMA PERITONEI is pretty bad, means seeding into peritoneum
clear cell adenoma pts rarely survive to 5 years if CA has spread past ovary
**choriocarcinoma usu unresponsive to chemotherapy and are often fatal (this may be the one)
rapid proliferation of trophoblastic cells (chemo very effective)

What kind of epithelium precedes mullerian?
coelomic
(coelomic epithelium-->mullerian epithel-->fallopian tubes, endometrium, endocervical glands)

What percentage of women with irregular periods have ovarian cysts?
50%

What sex cord tumor may produce large amounts of estrogen in a postmenopausal woman?
Granulosa-Theca Cell Tumor
5% of all ov CA
2/3 in postmenopausal women

What other hormones may be produced by granulosa-theca cell tumors?
androgens, or inhibin

What color are the areas of hormonal functionality in a G-T tumor?
bright yellow

What hormone is elevated in the serum of women carrying Down's syndrome fetuses?
(2nd trimester)
inhibin from thecal cells
also produced by sertoli cells in male

What ovarian cancer sends mets to lung, bone, vagina, brain, liver and kidney?
choriocarcinoma


PARATUBAL CYSTS
--mc lesion of fallopian tubes (not counting endometriosis)
--.1-.2 cm cysts w/ serous fluid inside
--larger near fimbiated end or in broad lig where they are called "hydatids of Morgagni"
--arise from remnants of the mullerian duct
--benign

OVARIAN CYSTS
--follicular and luteal
--cystic follicle = way common, unruptured graafian follicle or ruptured one that sealed, disordered folliculogenesis
--mc during childbearing yrs
--in 30% of wmn w/ regular menses, 50% of wmn w/ irreg menses, and 6% of postmenopausal wmn
--25% of all menstruating women have "mittelschmerz" which mb rupturing cysts
--follicular dysgenesis occurs w/ hypothalamus-pitutiary dysfunction or dt anatomical defect
--follicular cysts are in first 2 wks of cycle, may secrete estrogen causing menses 2b irreg
--corpus luteal cysts form when corpus luteum doesn't degenerate in last 2 weeks of cycle, may secrete progesterone, may become inflamed or spontaneously hemorrhage
--rupture of cyst may present w/ unilateral, sharp, severe pain (mittelschmerz)
--carcinomatous processes of the ovary are oft complicated by cystic degeneration
--cysts may cause adnexal torsion, more on R side (since L is cushioned by rectosigmoid), more when cysts are >4cm or when there's a tumor too, b9 dermoid cysts mc, danger: necrosis, inflam, infx, sepsis, death
--cysts may cause hemorrhage, peritonitis, dysmenorrhea, dyspareunia
--cysts may coexist with ectopic preg
--cysts may be assoc w/ infertility and irregular menstrual bleeding
--ETIO: hormone imbalance, ov CA, mets, smoking, low BMI, early menarche, infert (4x), hypothyroid, neonatal cysts (common in babies of moms w/ DM, toxemia and Rh immunization)
--RISK factors: tamoxifen tx (10% incr risk), smoking (0-2x incr in incidence), hx of cysts
--PROTECTIVE factors: H of OCP usage, late menarche
--MORPH: cystic follicles are up to 2cm, lined w/ gray, glistening membrane
--MORPH: follicular cysts are over 2cm, mb x w/ US or bimanual exam, cause pelvic pain, outer theca cells mb conspicuous with incr cytoplasm and palle appearance called hyperthecsis, may have increased estrogen production and endometrial abnormalities
--MORPH: granulosa luteal cysts are normally present in ovary, lined by rim of brightr yellow luteal tissue containing utenizing granulosa cells, may rupture causing peritoneal rxn, may look like endometriomas when combined with old hemorrhage and fibrosis

PCOS = POLYCYSTIC OVARIAN DZ
--you don't have to have cysts to have this diagnosis
--affects 3-6% of reproductive age women
--Sx: acne, numerous cystic follicles or follicular cysts, oligomenorrhea, persistent anovulation, obesity (40%), hirsuitism (50%), incr T-->hyperinsulinemia-->insulin resistant, sometimes virilism
--old name: Stein-Leventhal syndrome
--MORPH: ovaries 2x the normal size, firm, gray white with smooth outer cortex, subcortical cysts .5-1.5 cm diameter filled w/ clear fluid, thickened superficial cortex and hyperplasia of theca interna (follicular hyperthecosis), corpora lutea frequently absent
--Pathogenesis: thought to be dt enzyme (aromatase) malfx in which androgen biosynthesis is poorly regulated. Excessive androgen prodution from ovaries, from theca-lutein cells of follicles. Androstenedione then converted to estrone (E1) and testosterone.
--Tx: when insulin sensitivity is restored (metformin)-->ovulation resumes
--Tx: Turska formula--cysts gone in 4-6 weeks--1 oz bottle tincture made of 4.5 drams phytolacca, 1.5 drams gelsinium (yellow jasmine), .5 drams each aconite and bryonia. All four of these herbs are toxic so dosage is important and bottle should be well labelled and secured from children. CI: preg. Dosage is 5 drops in 1/2 glass water 2x/day. Also recommended: silica homeopathic in 1M, 1x/mo.
--stromal hyperthecosis mb seen at perimenopause or in younger women with PCOS, enlarged ovaries up to 7cm, microscope reveals hypercellular strome w/ luteinization of stromal cells, seen as discrete nests with vacuolated cytoplasm

OVARIAN TUMORS
--common neoplasia in women
--6% of all CA in women in US (excluding skin CA), ranking after cervical and endometrial CA
--usu not detected early so often fatal: accounts for 1/2 of deaths from CA of female tract
--numerous tumors of ovaries: 80% are benign and occur in women 20-45 years of age
--malignant more common in women 40-65
--RISK factors: (not as clear as for other genital cancers): nulliparity, low parity, FHx, gonadal dysgenesis, genetics
--BRCA 1 & 2 incr likelihood 20-60% by age 70-->mostly cystadenocarcinoma
--PROTECTIVE factors: OCP's and tubal ligation decr incidence in women 40-59
--GENETICS: 30% of Ov adenocarcinomas express high levels of Her2/neu oncogene
--Her2/neu correlates with poor prognosis
--p53 mutations found in 50% of ov CA
--tumors from four sources:
1) surface epithelium--mullerian epithelium (90% of malig),
2) germ cell tumors (from yolk sac, totipotential)
3) sex-cord stromal tumors
4) mets
--type 1) from mullerian epithelium which is incorporated into the ovarian cortex to form mesothelial inclusion cysts, origin of mucinous tumors is unclear, mb assoc w/ teratomas too
--most are nonfunctional and produce mild sx until they are HUGE
--epithelial tumors tend to be bilateral

OVARIAN CANCER ORIGINS (from text page 1093)

1) surface epithelium-stromal tumors (from coelomic or ectopic endometrial epithel)
(coelomic epithelium-->mullerian epithel-->fallopian tubes, endometrium, endocervical glands)
most primary cancers of ov are this type
(90% of malig)
three major groups: serous (tubal), mucinous (cervix), endometrioid (endometrial)
incr risk of malig w/ more discernible solid epithelial growth
MORPH: papilli, thickened tumor lining cyst spaces, or solid necrotic friable tissue
65-70% of all tumors, over age 20
these tumors occur predominantly in ovaries b/c this epithelium is incorporated into the ovarian cortex to form mesothelial inclusion cysts
in the endometroid category: clear cell, brenner tumor
cystadenofibroma = b9 (most endometrioid tumors are carcinomas)
epithelial tumors tend to be bilateral
Sx: abd pain, distention, urinary & GI sx dt compression or invasion, abd or vaginal bleeding
may be small or large

2) germ cell tumors
(germ cells migrate from yolk sac to ovary and are totipotential)
15-20% of all, 3-5% of malig
0-25 years
most are benign teratomas, the rest are found in kids/youth and are more malig
types: teratoma, dysgerminoma, endodermal sinus tumor, yolk sac tumor, mixed germ cell tumor,
choriocarcinoma
teratomas: mature are benign, immature are malig, monodermal are specialized and benign

3) sex-cord stromal tumors
tumor derived from ovarian stroma
(stroma of ovary contains sex cords of embryonic gonad, forerunners of endocrine apparatus)
5-10% of all, 2-3% of malig
all ages
types: granulosa-stromal cell tumors, fibroma, granulosa-theca cell tumor,
sertoli-leydig cell tumor
tumors secrete hormones assoc with the cell type, estrogens (theca), androgens (Leydig)
tumors mb feminizing (granulosa-theca cell tumors) or masculinizing (Leydig cell tumors)

4) mets
5% of all, 5% malig, any age

5) malignant, can't tell cell of origin
(defies classification)

SEROUS TUMORS
common cystic neoplasms
MORPH:
lined by tall, columnar ciliated epithelial cells
filled with clear serous fluid
accounts for about 30% of all ov tumors
75% of benign or borderline (age 20-50)
25% malig
serous cystaenocarcinomas 40% of all OvCa, are MOST COMMON MALIG, occur age 40-60
benign & borderline malignant occur most often in women 20-50 yo.
MORPH: 2 main types:
1) cystic lesion w/ intracystic papillary epithelium in fibrous walled cyst or
2)projecting from ov wall
bilaterality is common: 20% of b9 cystadenomas, 30% of borderline, 66% of cystadenocarcinomas
lining columnar epithelium with abundant cilia in b9!! microscopic papillae mb found
cystadenoma: solid tumor, complex growth, atypical, psammoma bodies
PSAMMOMMA BODIES = concentric calcium concretions in SEROUS tumors, also in prostate
Borderline tumors may arise from or extend to peritoneal sfcs as noninvasive implants
5 year survival for borderline and malig tumors confined within ov is 100% and 70% respectively
5 year survival if peritoneium is involved is 90% and 25% respectively
after 5 years many borderline tumors recur

MUCINOUS TUMORS
resemble serous
less common
25% of all ov neoplasms
usu in midlife, rare before puberty or after menopause
80% are B9 or borderline, approx 15% are malig
mucinous cystadenomcarcinoams are uncommon, only 10% of ovCa
MORPH: more cysts of variable size and rare sfc involvement
less bilateral (only 5%)
make larger cystic masses, weights can surpass 25kg
gross: multiloculated tumors filled with gelatinous fluid
HISTOL: tall columnar epithelial cells with apical mucin and no cilia
akin to B9 cervical or intestinal epithelia
endometriosis type: "mullerian mucinous" cystadenoma, uncommonly malig
more common: abundant gland-like or papillary growth with nuclear atypia and stratification
sim to tubular or villous adenomas of intestine,
mb precursor of cystadenocarcinoma
PSEUDOMYXOMA PERITONEI is ov tumor with extensive mucinous ascites, cystic epithelial implants on peritoneum, and adhesions, may result in intestinal obstruction and death

ENDOMETRIOID TUMORS
20% of all ov CA excluding endometriosis which is considered non-neoplastic
most are carcinoams
less common benign forms are cystadenofibromas
both: can tell from mucinous by the tubular glands, have solid and cystic areas
15% coexist with endometriosis

CLEAR CELL ADENOMA
uncommon pattern of sfc epithelial tumor of ov
characterized by large epithel cells with abundant clear cytoplasm
sometimes in assoc with endometriosis or endometrioid carcinoma of the ov
now thought to be of mullerian duct origin and variants of endometrioid adenocarcinoma
can be predominantly solid or cystic
if solid, arranted in sheets or tubules
if cystic, neoplastic cells line the spaces
5 year survival is 65% when confined to ovaries
with spread beyond ovary rare to live 5 years

CYSTADENOFIBROMA
variant with more pronounced prolif of fibrous stroma under columnar epithelium
benign
usu small and multilocular
small papillary processes that don't get as complicated and branching as ordinary cystadenoma
mb composed of mucinous, serous, endometrioid or transitional (Brenner) epithelium
mets are rare

BRENNER TUMOR
uncommon adeonfibromas in which epithelial component is nests of transitional cells
like bladder lining
sometimes cysts contain microcysts or gladular spaces lined by columnar, mucin-secreting cells
Brenner tumors sometimes found in mucinous cystadenomas
MORPH: mb solid or cystic, usu unilateral, vary from small to massive
fibrous stroma looks normal, nests with mucinous glands in center
sometimes stroma has plump fibroblasts like thecal cells, may have hormonal activity
most brenner tumors are benign but some are borderline or malig

OVARIAN CARCINOMA COURSE, DETECTION AND PREVENTION
--CA-125 (high-MW glycoprotein) present in >80% of serous, endometrioid carcinomas.
--Newer marker – osteopontin
--Tubal ligation & OC’s – assoc with sig. ↓ in risk
--Long term OC use for women with a FHX of OvCa confers 50% ↓ risk
--Tubal ligation confers >50% ↓ risk & mb effective in women with BRCA & FHX
--prophylactic oophorectomy in BRCA + women is standard allopathic care

TERATOMAS
Mature (Benign) mostly cystic, "dermoid cysts"
derived from the ectodermal differentiation of totipotential cells
usu in young women during reproductive yrs.
karyotype of all benign teratomas is 46,XX.
tumors probably arise from an ovum after the first meiotic division
MORPH: bilateral 10%-15% of cases
unilocular cyst containing hair & cheesy sebaceous material
may find teeth and other areas of calcification
HISTOL: cyst wall is stratified squamous epithelium with underlying sebaceous glands,
hair shafts, & other skin adnexal structures
other germ layers also present: cartilage, bone, thyroid tissue
~1% of dermoids-->malig-->thyroid carcinoma, melanoma, squamous cell carcinoma (most common)

Immature Malignant Teratomas
rare
component tissue resembles fetus or embryo rather than adult
usu in prepubertal adolescents & young women – mean age is 18 yo
grow rapidly & freq penetrate the capsule with local spread or mets
PROG: excellent at stage I
higher grade tumors confined to ovary txd with prophylactic chemo
most recurrences within 2 yrs, absence of dz beyond this time confers excellent prognosis
MORPH: bulky tumor with smooth external surface, solid structure,
areas of necrosis & hemorrhage present
hair, grumous material, cartilage, bone, & calcification mb present
primitive neuroepithelium
risk of spread outside ov incr in higher grades

What is grumous material?
coagulated blood

Monodermal or Specialized Teratomas
rare, most common being struma ovarii & carcinoid
unilateral
Struma ovarii is composed of entirely mature thyroid tissue may-->hyperthyroidism
Ovarian carcinoid arises from intestinal epithelium in a teratoma
mb fxning esp in lg tumors (>7 cm) producing 5-hydroxytryptamine & the carcinoid syndrome Primary carcinoids are malignant <2%

What is 5-hydroxytryptamine?
5-HTP = serotonin
a monoamine neurotransmitter
found extensively in the GI tract of animals
80-90% of human serotonin is found in the enterochromaffin cells in the gut
used to regulate intestinal movements
the rest is synthesized in serotonergic neurons in the central nervous system (CNS)
controls appetite, mood and anger
also found in many mushrooms and plants, including fruits and vegetables

CARCINOID SYNDROME
Cutaneous flushing and cyanosis
Diarrhea, cramping, nausea and vomiting
Cough, wheezing, dyspnea (1/3 of cases)
Hepatomegaly
Systemic fibrosis (cardiac valves, aorta, endocardium, retroperitoneal, pelvic, or pleural)

DYSGERMINOMA
ovarian counterpart of seminoma of the testes
uncommon: 2% of all OvCa
may occur in childhood, but 75% occur in 2nd & 3rd decades.
most have no endocrine fxn, a few produce ↑ levels of chorionic gonadotropin
all are malignant, but vary in histological atypia
only about 1/3 are aggressive
a unilateral tumor that hasn’t broken thru the capsule & not spread-->
has an excellent prognosis (96% cure rate) with simple salpingo-oopherectomy
also very radiosensitive
overall survival exceeds 80%
MORPH: unilateral – 80%-90%, soft and fleshy
solid tumors ranging from very small to masses that virtually fill the abdomen
gross exam reveals yellow-white to gray-pink appearance

ENDODERMAL SINUS (YOLK SAC) TUMOR
rare tumor
2nd most common malignant tumor of germ cell origin
derived from differentiation of malignant germ cells toward extraembryonic yolk sac structure rich in α1-antitrypsin.
HISTOL: glomerulus-like structure composed of a central BV surrounded by germ cells
w/I a space lined by germ cells (Schiller-Duval body)
hyaline droplets are present in all tumors
some can be stained for α-fetoprotein
most pts are young children or young women presenting with
abdominal pain & rapidly developing pelvic mass

CHORIOCARCINOMA
usu of placental origin, similar to the endodermal sinus tumor
most exist with other germ cell tumors
HISTOL: identical with placental lesions
ovarian primaries are aggressive tumors
usu mets to lungs, liver, bone & other viscera at the time of dx
↑ levels of chorionic gonadotropins
usu unresponsive to chemotherapy and are often fatal

SEX CORD THECAL TUMORS

GRANULOSA-THECA CELL TUMOR
composed of varying amounts of granulosa & theca cell differentiation
almost entirely composed of granulosa cells or a mixture of both
approx 5% of all ovarian tumors
2/3 occur in postmenopausal women
clinically important for 2 reasons:
(1) potential elaboration of lg amts of estrogen
(2) small hazard of malignancy in the granulosa cell forms
functional tumors in young girls may-->precocious puberty
in adult women-->endometrial hyperplasia, cystic breast dz, & endometrial Ca (10%-15%)
occasionally produce androgens
difficult to determine the biological behavior from the histology
malignant tumors usu have indolent course
recurrences may appear 10-20 yr after removal of original tumor
mostly of theca cells: rarely malignant
recently ↑ inhibin has been seen with granulosa cell tumors
strong immunohistochemical positivity with an antibody to inhibin characterizes these tumors
MORPH: usu unilateral, vary from microscopic foci--controls gametogenesis, embryonic, fetal development
inhibin-A elevated in serum of women carrying fetuses with Down syndrome
included in screening tests for Down syndrome in the second trimester of pregnancy

FIBROMA THECOMA
arise in the stroma of the ovary
composed of either fibroblasts (fibromas) or
plump spindle cells with lipid droplets (thecomas)
4% of all ovarian tumors
pure thecomas are rare, but are hormonally active
most are composed mostly of fibroblasts and are hormonally INactive.
unilateral in 90% of cases, usu solid, spherical or slightly lobulated,
encapsulated, hard, gray-white masses covered by intact ovarian serosa

Fibroma – Thecomas
Clinically – pain, pelvic mass, ascites (40% when tumors are > 6 cm), hydrothorax (usu only on 1 side).
These findings are designated Meigs syndrome.
Basal cell nevus syndrome is another unusual assoc.
When they pursue a malignant course they are termed fibrosarcomas.

Thecoma-fibroma composed of plump, differentiated stromal cells with thecal appearance. B, Large bisected fibroma of the ovary apparent as a white, firm mass (right). The fallopian tube is attached.

SERTOLI-LEYDIG CELL TUMORS
Sertoli – Leydig Cell Tumors (Androblastomas)
They are similar to the cells in the testes at various stages of dev.
Prod masculinization or at least defeminization.
Peak incidence is 2nd & 3rd decades.
Unilateral & are similar to granulosa-theca cell neoplasms.
Recurrence or mets is < 5%.
May block normal female sexual dev in children, in adults may see atrophy of the breasts, amenorrhea, sterility, & hair loss.
Syndrome may progress to striking virilization – hirsutism, male distribution of hair, hypertrophy of clitoris & voice changes.

Sertoli – Leydig Cell Tumors – Morphology

Histologically – well-differentiated tumors show tubules composed of Sertoli or Leydig cells interspersed with stroma.

Poorly differentiated tumors have sarcomatous pattern with disorderly disposition of epithelial cell cords. Heterologous elements such as mucinous glands, bone, cartilage, mb present.

Sertoli cell tumor. A, Gross photograph illustrating characteristic golden yellow appearance of the tumor

Photomicrograph showing well-differentiated Sertoli cell tubules.

METS

Overview
Most common are derived from mullerian origin: the uterus, fallopian tube, contralateral ovary, or pelvic peritoneum.
Most common extramullerian tumors are the breast & GI tract – colon, stomach, biliary tract & pancreas.

ECTOPIC PREG

Most common site is tubal (90%)
Occur in 1/150 pregnancies
Risk factors:
PID, chronic salpingitis
Peritubal adhesions secondary to appendicitis/endometriosis
IUDs

Severe abdominal pain 6 weeks after a normal menstrual flow
Pain is due to pelvic hemorrhage
Rapidly progressing shocklike state and acute abdomen.
Medical emergency
Treatment –methotrexate injection or surgery

METHOTREXATE

In determining whether a patient is a candidate for medical therapy, a number of factors must be considered. She must be:
hemodynamically stable with no signs or symptoms of active bleeding or hemoperitoneum
reliable, compliant, and able to return for follow-up
Another factor is size of the gestation, which should not exceed 3.5 cm at its greatest dimension on US measurement.

HYDATIDIFORM MOLE

Cystic swelling of the chorionic villi with trophoblastic proliferation.
Occurs in 1:1000 pregnancies
Patients present in the 4-5 month of pregnancy with vaginal bleeding and a uterus usually larger than expected for dates.
HCG levels tend to be very high

molar pregnancy illus

Complete hydatidiform mole suspended in saline showing numerous swollen (hydropic) villi.
(orange with blue bubbles)

A, Invasive mole presenting as a hemorrhagic mass adherent to the uterine wall.

CHORIOCARCINOMA
Neoplasm of trophoblastic cells
Rapidly invasive, widely metastasizing
1:20,000-30,000 pregnancies in the US
50% from hydatidiform moles (1 in 40)
25% from previous abortions
22% in normal pregnancies

Choriocarcinoma presenting as a bulky hemorrhagic mass invading the uterine wall.

Irregular spotting of bloody, brown sometimes foul smelling fluid
Can occur during pregnancy or after miscarriage (mb months later)
HCG levels are often very high
Mets to lung and bone are often present (also vagina, brain, liver and kidney)
Chemotherapy is spectacularly effective

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