Module 3: Ovaries: Germ Cell Tumors & Sex Cord Flashcards
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.
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
What are the complications seen with mature cystic teratoma?
Rupture
Torsion
Infertility (unknown reasons)
1% of ectoderm can become invasive squamous cell carcinoma
Immature teratomas are the next type of teratomas, what age of patients are these seen in and what is the histological appearance?
Solid Malignant — cant see hair or teeth
Prepubertal/teenage girls
Histology: presence of neruoepithelium = really aggressive
remember its solid so it can undergo torsion
Now moving on to the specialized teratoma (monodermal teratomas). There are two types, first type is Struma Ovarii. What are the symptoms ?
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
What is the histological 6c image of struma ovarii?
Histology: well differentiated thyroid follicles lined by simple cuboidal epithelium with a colloid in the lumen of the follicle
The second specialized teratoma (monodermal teratoma) is Carcinoid timor. What are the symptoms?
Asymptomatic: rarely functional
IF functional: Elevated serotonin
—carcinoid syndrome: flushing, wheezing and diarrhea
–5-HIAA in the urine
If carcinoid syndrome results from a carcinoid tumor of the ovary what are the findings?
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)
The next germ cell tumor to be discussed is a dysgerminoma. What is seen on gross and histology for this? Slide 7
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
Dysgerminoma is asymptomatic and generally seen in what kind of patients?
Gonadal Dysgenesis
–Turners Syndrome
What are the tumor markers for Dysgerminoma?
LDH main tumor marker
–beta hCg if fried eggs make syncytiotrophobalsts
Dysgerminoma tumor is malignant ,what is the spread and prognosis?
Spread (same as all other malignant primary ovarian tumors): lymph nodes – iliac and para-aortic
Radio and Chemo sensitive so good prognosis
Fried egg appearance seen on histology is similar in appearance to what other tumors?
Medullary carcinoma
Seminoma Testis
The third germ cell tumor is Ovarian Choriocarcinoma (non-gestational). What do you see on histology for this tumor? Slide 8
Malignant Cytotrophoblasts --single nucleus (mono-nucleated) ---pale (toward left) Synctiotrophoblasts (toward right) --multi nucleated --basophilic
What is the tumor marker for Choriocarcinoma?
BetaHCG
What is the presentation for a choriocarcinoma?
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
What is seen on ultrasound for a patient with a choriocarcinoma?
Nothing in uterus or fallopian tubes
–see a solid, unilateral and malignant mass on ovary
What are the complications seen in a patient with choriocarcinoma?
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)
What is the prognosis for a patient with choriocarcinoma?
Not chemosensitive because it lacks paternal antigens
(however gestational choriocarcinomas are chemosensitive)
Patients usually die
Spreads via blood not lymph!!
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?
Ovarian Choriocarcinoma
Finally the last germ cell tumor to be discussed will be Endodermal Sinus Tumor (aka yolk sac tumor). What patients present with these tumors?
Children and Young Women
–most common primary ovarian tumor in kids
What are the tumor markers for yolk sac tumors?
AFP and alpha 1 antitrypsin
What is seen on histology and gross in patients with a yolk sac tumor?
Gross: Solid (malignant)
Histology: Schiller-Duval Bodies: resemble primitive glomeruli
–cytoplasm pink inclusion: alpha fetoprotein
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?
Peri/Post-Menopausal Women
Solid — malignant
Unilateral
Produces Estrogen (Excess estrogen)— endometrial hyperplasia — vaginal bleeding
What affect do Granulosa Theca Cell tumors have on young girls?
Precocious Puberty (Early onset) if it occurs in young girl --due to excess estrogen!!!!
Biopsy is the best investigation for women with Granulosa Theca Cell. What is seen on histology? slide 9
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
What are complications of Granulosa Theca Cell?
Torsion (Solid)
Metastasis (usual)
FCC/Breast Cancer
Endometrial hyperplasia that can progress into carcinoma
Due to the increased estrogen in granulosa theca cell tumors, what do women and young girls get?
Women: tumor in ovary + endometrial thickening
Young Girls: 10 yr old with early onset menarchy, heavy periods and precocious puberty
What are the tumor makers for Granulosa Theca Cell Tumors?
Inhibin or Estrogen
The next sex-cord stromal tumor is Sertoli-Leydig Cell Tumor (aka androblastoma). What is the tumor marker?
Sertoli: Inhibin
Leydig: Testosterone
Ovary: both do testosterone
What are general features of sertoli-leydig cell tumor?
Solid: malignant
Unilateral
What do you see on histology for sertoli-leydig cell tumor?
Reinke Crystals
–sheets of large cells with round central nucleus
What is the presentation of a patient with a sertoli-leydig cell tumor?
Defeminization: atrophy of breasts, amenorrhea, sterility, loss of hair
Masculinization (increased androgens): hirsutism, male distribution of hair, hypertrophy of clitoris, voice changes, and virilization
The third and last sex cord tumor is a fibrothecoma. What are some general features?
Pure fibroma
Pure Thecoma
–both are possible
Solid but BENIGN
Describe slide 10, gross and microscopy images, of the fibrothecoma
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.
What are the complications of a fibrothecoma?
Torsion: because its solid
What is Meig’s Snydrome?
Pure Fibroma + right sided pleural effusion + ascites
–histology: well differentiated fibroblasts because just fibroma not thecoma
What is Ghorlin (basal cell nevus) syndrome?
Ovarian Fibroma Multiple benign nevi (moles) on the skin (disfiguring) (basal cell carcinoma) Medullo Blastoma (tumor in the brain of the cerebellar vermis)
What is the tumor marker for Fibrothecoma?
none :)
Finally to touch on Krukenberg Tumor again. What are features?
Bilateral
Secondary ovarian tumor due to metastasis to both ovaries
E-cadherin mutation
CEA = tumor maker
What three sites do Krukenberg tumors come from?
- Colon cancer
- Diffuse intestinal gastric carcinoma
- Invasive lobular carcinoma of the breast
What does histology look like for Krukenberg tumors?
Signet ring cells with eccentric nuclei and mucin in the cytoplasm.
Review: what tumors are all PAS positive?
Krukenberg
Dysgerminoma
Mucinous
