Diseases of Ovary II

..today• Germ cell tumor• Teratoma• Dysgerminoma• Yolk sac tumor• Embryonal carcinoma• Choriocarcinoma

• Sex cord stromal tumor• Granulosa theca cell tumor• Fibroma, thecoma• Sertoli-Leydig cell tumor

• Metastatic tumor

Germ cell tumor Germ cell tumors arise from primordial germ cells of

the ovary . Of these ovarian lesions, 97% are benign

proliferations (ie, mature teratomas); the remaining 3% are malignant.

In the first two decades of life, almost 75% of ovarian tumor are germ cell origin

Clinical Features Symptoms and signs – Grow rapidly (except for

benign cystic teratoma)

Pelvic pain related to capsular distension, hemorrhage or necrosis, torsion and rupture

Pelvic mass and pressure symptoms

Ascites in advanced cases.

– Menstrual irregularities in menarcheal patients.

– Precaucious puberty in patient whose tumor produce hCG.

–

Germ cell tumor and their marker substances

NEOPLASM AFP hCG DYSGERMINOMA _ +/_ ENDODERMAL SINUS (Y S)TUMOR + _ IMMATURE TERATOMA _ _ MIXED GERM CELL TUMOR +/_ +/_ CHORIOCARCINOMA _ + EMBRYONAL CARCINOMA + + NOTE: PLAP and LDH are produce in 95% of

Dysgerminoma

TeratomaTYPES-• Mature• Immature• Monodermal

Mature (benign) Teratomas • Also known as Dermoid cyst• Women during

reproductive age group• Excellent prognosis, even

if peritoneal implants are present

C/F • Abdominal mass, pain, • Acute abdomen• May rupture into peritoneal

cavity - simulates metastatic carcinoma or miliary tuberculosis• May present with paraneoplastic

syndrome- inflammatory limbic encephalitis• Or with hemolytic anemia/

virilization

terms..a/w..teratoma• Dermoid cyst: usually

means teratoma resembles skin

• Gliomatosis peritonei: peritoneal implants exclusively composed of mature glial tissue and other teratomatous elements are absent

Gross features• cystic or solid• cystic content -greasy material

composed of sebaceous material • keratin, hair, calcification,

teeth, or contains partial mandible• rarely is “fetiform” (partial

human body-like structure) • Rokitansky’s protuberance-a

well defined nipple-like structure covered with hair

Microscopical features..all three germ• ectodermal structures in 100%, • mesodermal in 93%, endodermal in

71%; • Cyst wall lined by skin (with sweat

sebaceous glands, hair shaft) or other type epithelium

• Other tissues e.g. mature cartilage, mature bone or thyroid tissue

• Presence of glial tissue common; • prostate tissue in 10%; • still considered mature if

microscopic foci of immature tissue

• This teratoma has cartilage, adipose tissue, and

• intestinal glands at the right,

• thyroid tissue at the left.

May be seen in associated with• Mucinous cystadenoma• Dysgerminoma

Malignant change in cystic teratoma

• Squamous cell carcinoma• most common

• Adenocarcinoma • Thyroid carcinoma• Malignant melanoma

• Teratoma with squamous cell carcinoma show flakes of keratin, cellular tissue fragments • Inset: atypical

cells with individual cell keratinization

Immature (malignant) teratoma• Mixture of adult & embryonal/ fetal tissue, mainly

immature neuroepithelial component.• Usually prepubertal or young women (mean 18 years)

Gross

• Bulky • Smooth external surface• Solid or predominantly

solid or cystic with areas of necrosis, hemorrhage• Hair, sebaceous material,

cartilage, bone or calcification +/-

Micro:• Premature

neurogenic elements (GFAP+);

• mesodermal elements common;

• some tumors derived primarily of esophageal, liver and intestinal structures (endodermal)

Grading: histologic grade is based on proportion of tissue containing immature neuroepithelium• Norris grading system (correlates best with extraovarian

spread, survival)• 1 - rare foci neuroepithelium occuping <1 low power

fields in any one slide, abundant mature tissue, loose mesenchymal tissue with occasional mitoses, immature cartilage, tooth anlage• 2 - less mature tissue than grade 1, foci of

neuroepithelium with mitoses, < 4 low power fields in any one slide• 3 - little/no mature tissue; numerous neuroepithelial

elements merging with cellular stroma occupying 4+ low power fields

Monodermal teratomas• Strauma ovarii• Carcinoids• Ependymomas

Struma ovarii • Rare monodermal teratoma composed predominantly of mature

thyroid tissue

• May show pathologic changes of thyroid gland including hyperfunctioning; malignancies are usually papillary thyroid carcinoma

• Associated with • mucinous cystadenoma, • Brenner tumor, • carcinoid tumor

Strauma ovariiGross:

• resembles red-brown thyroid tissue

• unilateral

• usually multilocular cystic

• Micro: • thyroid follicles

with colloid• other

teratomatous elements may be present

Carcinoid tumors

• 15% have cystic teratoma or mucinous neoplasm in contralateral ovary• 1/3 are associated with

carcinoid syndrome• Low malignant potential-

5%

Dysgerminoma• Most common malignant germ cell tumor (30-40%)• Analogous to Seminoma of male testis.• 10-15% are bilateral• May arise in gonadal or • Extragonadal sites,

midline structure from pineal gland, mediastinum and the retroperitoneum.

• 5% : before the age of 10 years, 75% : between the ages of 10 and 30 years rarely occur after 50 years of age.

Dysgerminoma 5% are discovered in abnormal gonads – Associated with pure gonadal dysgenesis (46,XY) , -- mixed gonadal dysgenesis(45,X/46,XY) -- and androgen insensitivity syndrome(46,XY)

– Therefore should be determined karyotype in premenarcheal patients

Dysgerminoma a/w …• May coexist with • Immature teratoma,• Choriocarcinoma, • Endodermal sinus tumor

•

• 20-30% of ovarian malignancies associated with pregnancy are Dysgerminoma.

Gross appearance• Size varies widely,

usually Φ 5-15 cm.• Capsule is slightly

bosselated • Cut surface is soft and

fleshy, pale pink or yellow-white in colors .

Histological characteristicsLarge, round, ovoid or

polygonal cells.Clear, very pale staining

cytoplasm, centrally placed regular nuclei and prominent nucleoli,

Fibrous septa with lymphocytes

Mitotic figures are usually numerous.

Syncitiotrophoblastic cells +/-

Immunohistochemistry Prognosis

• Oct 3• Oct 4• Nanog• c-KIT• PLAP

• Responds well to chemotherapy• Overall survival >80%

Endodermal sinus tumor• Derive from primitive

yolk sac.(yolk sac tumor)• The second most

frequent malignant germ cell tomors.

• Median age 16-18 years.• Abdominal pain, 75%• Secrete AFP

Endodermal sinus tumor• Soft grayish brown • 10-30cm, • capsule is intact• Cut surface gray yellow

with solid- cystic, hemorrhagic and necrotic change.• Unilateral 100%• biopsy of opposite ovary

is contraindicated

Endodermal sinus tumor• Scattered tubules lined by single

layers of flattened cuboidal cells.

• Loose reticular stroma

• Papillary structure with a central blood vessel (Schiller Duval body)

• Polyvesicular vitelline, hepatoid, glandular

Endodermal sinus tumor….hyaline globule• Eosinophilic intracellular

or extracellular • PAS +• Diastase-resistant • Most often found in the

reticular and endodermal sinus patterns.• Immunohistochemical

staining positive for AFP, alfa1-AT

Embryonal carcinoma• Rare• Median age 15 yrs, aggressive

• More than 50% cases present with isosexual pseudoprecosity, painful abdominal mass, abnormal uterine bleeding, amenorrhea

• Increased serum hCG and AFP levels

• Extraovarian spread in 40% cases

• Median diameter 17cm• External

surface: • smooth and

glistening

• Cut surface: predominantly solid and variegated

Extensive areas of necrosis and hemorrhage

•Solid sheets and nests •Large anaplastic cells: pale vacuolated cytoplasm; large pleomorphic nuclei; prominent nucleoli.

•Occasionally forming papillae and abortive glandular structures

•Frequently syncytiotrophoblast-like tumor cells scattered

Polyembryoma• consists of small embryoid bodies having a central

‘germ disc’ composed of embryonal carcinoma like epithelium and two cavities

• Tumor marker: Increased hCG, AFP

Embryoidbody having a

core of embryonal carcinoma like cell, a

dorsal amniotic

cavity, and a ventral

component of yolk sac

tumor

Choriocarcinoma• Rare• Below age 20 yrs• Clinical Features: abdominal mass, pain isosexual

pseudoprecosity, menstural irregularities.• Component of mixed germ cell tumor• Very high hCG

Gross • Soft• Hemorrhagic• Necrotic• pink tan in color

Histopathology• Clusters of cytotrophoblast

separated by streaming masses of syncytiotrophoblast:

• Cytotrophoblast: centrally placed hyperchromatic nuclei, prominent nucleoli, clear cytoplasm, well defined cell border

• Syncytiotrophoblast: multinucleated

• characteristic dimorphic plexiform pattern 15%

• hemorrhage

• necrosis

• Villi characteristically absent

Metastases IHCLungbrainliverkidneybowel

Choriocarcinoma cells: positive for: • hCG• keratin

Granulosa theca cell tumor• varying proportions of granulosa and theca cell

differentiation• postmenopausal women

• elaborate large amounts of estrogen • distinct hazard of malignancy

Gross • usually unilateral • vary in size• solid, and cystic encapsulated masses• Tumors that are hormonally active have a yellow coloration to their cut surfaces, due to intracellular lipids• The pure thecomas are solid, firm tumors

Microscopy • The small, cuboidal to

polygonal cells • Cells have scant cytoplasm

and grooved nucleus(coffee bean)• may grow in anastomosing

cords, sheets, or strands• Small, distinctive, gland-like

structures filled with an acidophilic material similar to immature follicles (Call-Exner bodies)

Immunohistohemistry • Inhibin

Fibromas, Thecomas, Fibrothecomas• Tumors arising in the ovarian stroma - fibroblasts

(fibromas) or• Plump spindle cells with lipid droplets (thecomas) • Many tumors contain a mixture of these cells and are

termed fibromathecomas

• Meigs syndrome• Fibroma ovary• Hydrothorax• Ascitis

Sartoli leydig cell tumorAlso known as Androblstoma

Second and third decade

Virilisation

Tubules composed of Sertoli cells or Leydig cells

interspersed with stroma

Other sex cord stromal tumor• Hilus cell tumor-• Reinke crystal• Virilizing tumor

• Gonadoblastoma• Both germ cell and sex cord stromal derivatives• Coexsisting Dysgerminoma in 50% cases

• Pregnancy leuteoma

Metastatic tumor• Uterus• Fallopian tubes• c/l ovary• Pelvic peritoneum

• Ca breast• GIT• Krukenberg tumor

Krukenberg tumor…

Thank

you