Module 3: Ovaries: Germ Cell Tumors & Sex Cord

Question 1

Next primary ovarian tumor class are the germ cell tumors which make up about 15-20% of ovarian tumors. First is the mature cystic teratoma/Dermoid cyst. What are the symptoms and what is the gross/histology seen on 6a/6b.

Answer 1

Women of reproductive age
Loves the right ovary
–asymptomatic (incidental finding of calcified tooth on xray or ultrasound)
Histology 6b: 2 layers
**Top layer: Keratinized epidermis made of ectoderm with teeth and hair (Hair follicle seen in image)
**Lower Layer: sebaceous glands and sweat glands made from mesoderm

Question 2

What are the complications seen with mature cystic teratoma?

Answer 2

Rupture
Torsion
Infertility (unknown reasons)
1% of ectoderm can become invasive squamous cell carcinoma

Question 3

Immature teratomas are the next type of teratomas, what age of patients are these seen in and what is the histological appearance?

Answer 3

Solid Malignant — cant see hair or teeth
Prepubertal/teenage girls
Histology: presence of neruoepithelium = really aggressive
remember its solid so it can undergo torsion

Question 4

Now moving on to the specialized teratoma (monodermal teratomas). There are two types, first type is Struma Ovarii. What are the symptoms ?

Answer 4

Women of reproductive age

• -non functional and asymptomatic
• -however can in rare cases make thyroid hormones (T3,4) and patients become hyperthyroid (weight loss, fine tremor, palpitations, sweating, and heat intolerance)
• -if this goes on for long periods the thyroid becomes atrophied due to low TSH
• -if you do a radioactive iodine uptake on these patients you will see the uptake in the ovary not the thyroid because its atrophied

Question 5

What is the histological 6c image of struma ovarii?

Answer 5

Histology: well differentiated thyroid follicles lined by simple cuboidal epithelium with a colloid in the lumen of the follicle

Question 6

The second specialized teratoma (monodermal teratoma) is Carcinoid timor. What are the symptoms?

Answer 6

Asymptomatic: rarely functional
IF functional: Elevated serotonin
—carcinoid syndrome: flushing, wheezing and diarrhea
–5-HIAA in the urine

Question 7

If carcinoid syndrome results from a carcinoid tumor of the ovary what are the findings?

Answer 7

Chromogranin and synaptofysin in the blood
Neuroendocrine (Kolchisky) cells of origin
–salt and pepper chromatin
Histology: nests of well differentiated neuroendocrine cells (salt and pepper cells)

Question 8

The next germ cell tumor to be discussed is a dysgerminoma. What is seen on gross and histology for this? Slide 7

Answer 8

Gross: Solid Soft Flesh Primary Ovarian Tumor
Histology: Fried egg appearance: nests/sheets of monomorphic cells with prominent nucleus and nucleolus with pale cytoplasm that contains glycogen (pale b/c H and E not PAS)
–scanty fibrostroma: containing non-neoplastic reactive lymphocytes

Question 9

Dysgerminoma is asymptomatic and generally seen in what kind of patients?

Answer 9

Gonadal Dysgenesis

–Turners Syndrome

Question 10

What are the tumor markers for Dysgerminoma?

Answer 10

LDH main tumor marker

–beta hCg if fried eggs make syncytiotrophobalsts

Question 11

Dysgerminoma tumor is malignant ,what is the spread and prognosis?

Answer 11

Spread (same as all other malignant primary ovarian tumors): lymph nodes – iliac and para-aortic
Radio and Chemo sensitive so good prognosis

Question 12

Fried egg appearance seen on histology is similar in appearance to what other tumors?

Answer 12

Medullary carcinoma

Seminoma Testis

Question 13

The third germ cell tumor is Ovarian Choriocarcinoma (non-gestational). What do you see on histology for this tumor? Slide 8

Answer 13

Malignant Cytotrophoblasts
--single nucleus (mono-nucleated) 
---pale (toward left)
Synctiotrophoblasts (toward right)
--multi nucleated 
--basophilic

Question 14

What is the tumor marker for Choriocarcinoma?

Answer 14

BetaHCG

Question 15

What is the presentation for a choriocarcinoma?

Answer 15

Worst prognosis of ovarian cancers
–unilateral and solid (highly aggressive)
Young/teenage girls
–hyperemesis in the morning due to elevated betaHCG
–disruption of normal menstruation
–positive pregnancy in urine and blood

Question 16

What is seen on ultrasound for a patient with a choriocarcinoma?

Answer 16

Nothing in uterus or fallopian tubes

–see a solid, unilateral and malignant mass on ovary

Question 17

What are the complications seen in a patient with choriocarcinoma?

Answer 17

Luteal cysts in the opposite ovary (due to elevated betaHCG)
Hematogneous spread
Cough and Hemoptysis
Hematuria
Lots of blood wherever it goes (due to invasion by the trophoblasts and breaking blood vessels)
syncytiotrophoblasts no cell membrane (so thats why it can invade the blood quick)

Question 18

What is the prognosis for a patient with choriocarcinoma?

Answer 18

Not chemosensitive because it lacks paternal antigens
(however gestational choriocarcinomas are chemosensitive)
Patients usually die
Spreads via blood not lymph!!

Question 19

A 13 y.o girl with menorrhea at age 11 comes into your office stating for the past 3 months she has been experiencing secondary amenorrhea. patient started complaining of morning sickness. patient denies sexual activity. patients pregnancy test came back positive. Patients ovaries and fallopian tubes showed no evidence of a baby, what a single solid ovarian tumor found. What is the tumor?

Answer 19

Ovarian Choriocarcinoma

Question 20

Finally the last germ cell tumor to be discussed will be Endodermal Sinus Tumor (aka yolk sac tumor). What patients present with these tumors?

Answer 20

Children and Young Women

–most common primary ovarian tumor in kids

Question 21

What are the tumor markers for yolk sac tumors?

Answer 21

AFP and alpha 1 antitrypsin

Question 22

What is seen on histology and gross in patients with a yolk sac tumor?

Answer 22

Gross: Solid (malignant)
Histology: Schiller-Duval Bodies: resemble primitive glomeruli
–cytoplasm pink inclusion: alpha fetoprotein

Question 23

Now moving onto Sex-Cord Stromal Tumors they are more predominant in post-menopausal women. The first one to discuss is Granulosa Theca Cell Tumor. What are some general features?

Answer 23

Peri/Post-Menopausal Women
Solid — malignant
Unilateral
Produces Estrogen (Excess estrogen)— endometrial hyperplasia — vaginal bleeding

Question 24

What affect do Granulosa Theca Cell tumors have on young girls?

Answer 24

Precocious Puberty (Early onset) if it occurs in young girl 
--due to excess estrogen!!!!

Question 25

Biopsy is the best investigation for women with Granulosa Theca Cell. What is seen on histology? slide 9

Answer 25

Slide 9:
Call-Exner Bodies: Cuboidal Granulosa Cells with hyperchromatic (Coffee-bean) nucleus arranged around a central lumen
–looks like a rosette
Large polygonal cells and spindle cells forming gland like structures around an acidophilic core recapitulating immature follicles
Theca: Lipid laden cells

Question 26

What are complications of Granulosa Theca Cell?

Answer 26

Torsion (Solid)
Metastasis (usual)
FCC/Breast Cancer
Endometrial hyperplasia that can progress into carcinoma

Question 27

Due to the increased estrogen in granulosa theca cell tumors, what do women and young girls get?

Answer 27

Women: tumor in ovary + endometrial thickening

Young Girls: 10 yr old with early onset menarchy, heavy periods and precocious puberty

Question 28

What are the tumor makers for Granulosa Theca Cell Tumors?

Answer 28

Inhibin or Estrogen

Question 29

The next sex-cord stromal tumor is Sertoli-Leydig Cell Tumor (aka androblastoma). What is the tumor marker?

Answer 29

Sertoli: Inhibin
Leydig: Testosterone
Ovary: both do testosterone

Question 30

What are general features of sertoli-leydig cell tumor?

Answer 30

Solid: malignant

Unilateral

Question 31

What do you see on histology for sertoli-leydig cell tumor?

Answer 31

Reinke Crystals

–sheets of large cells with round central nucleus

Question 32

What is the presentation of a patient with a sertoli-leydig cell tumor?

Answer 32

Defeminization: atrophy of breasts, amenorrhea, sterility, loss of hair
Masculinization (increased androgens): hirsutism, male distribution of hair, hypertrophy of clitoris, voice changes, and virilization

Question 33

The third and last sex cord tumor is a fibrothecoma. What are some general features?

Answer 33

Pure fibroma
Pure Thecoma
–both are possible
Solid but BENIGN

Question 34

Describe slide 10, gross and microscopy images, of the fibrothecoma

Answer 34

Gross:
White: Fibroma
Yellow: thecoma
Histology:
Thecoma is lipid laden so its clear on H and E
Fibroma: is well differentiated fibroblasts laying down collagen so darker part on histology.

Question 35

What are the complications of a fibrothecoma?

Answer 35

Torsion: because its solid

Question 36

What is Meig’s Snydrome?

Answer 36

Pure Fibroma + right sided pleural effusion + ascites

–histology: well differentiated fibroblasts because just fibroma not thecoma

Question 37

What is Ghorlin (basal cell nevus) syndrome?

Answer 37

Ovarian Fibroma 
Multiple benign nevi (moles) on the skin (disfiguring) (basal cell carcinoma) 
Medullo Blastoma (tumor in the brain of the cerebellar vermis)

Question 38

What is the tumor marker for Fibrothecoma?

Answer 38

none :)

Question 39

Finally to touch on Krukenberg Tumor again. What are features?

Answer 39

Bilateral
Secondary ovarian tumor due to metastasis to both ovaries
E-cadherin mutation
CEA = tumor maker

Question 40

What three sites do Krukenberg tumors come from?

Answer 40

2. Colon cancer
3. Diffuse intestinal gastric carcinoma
4. Invasive lobular carcinoma of the breast

Question 41

What does histology look like for Krukenberg tumors?

Answer 41

Signet ring cells with eccentric nuclei and mucin in the cytoplasm.

Question 42

Review: what tumors are all PAS positive?

Answer 42

Krukenberg
Dysgerminoma
Mucinous