Female Genital Tract

Question 1

What are some ovarian tumors and how are they classified?

Answer 1

80% of ovarian tumors are benign and occur mostly in young women. Malignant tumors occur at a slightly older age.
The classification is based on the most probable tissue of origin. They can be surface epithelial tumors, germ cell tumors or sex cord stromal tumors.

Question 2

Which are the surface epithelial tumors?

Answer 2

Ovarian serous, ovarian mucinous, endometroid ovarian, clear cell and transitional.

Question 3

What are ovarian serous tumors?

Answer 3

Cystic neoplasms most common among ovarian cancers. Inheritable mutations like BRCA1 and BRCA2. Type I is a low grade serous carcinoma which is well differentiated and Type II is a high grade carcinoma which is poorly differentiated. High grade tumors also show deletions of TP53 and RB deletion.
Morphologically they are large, spherical to ovoid, cystic structure 30 to 40 cm in diameter. 25% of benign ones are bilateral. Histologically they contain a single layer of tall columnar epithelial cells that line the cysts. Psammoma bodies are common as well. Ovarian tumors can invade the peritoneum, LNs, liver, lungs and GI tract. They are also associated with ascites.

Question 4

What are ovarian mucinous tumors?

Answer 4

Account for 20-25% of all ovarian neoplasms. Commonly benign 80%. 10% of them are malignant carcinomas. The main genetic defect is KRAS. They tend to produce larger cystic masses.

Question 5

What are endometroid ovarian tumors?

Answer 5

Not frequent but tend to be malignant and bilateral although benign forms exist like endometroid adenofibroma. They are distinguished form serous or mucinous because they present tubular glands resembling endometrium. Endometriosis is associated to these carcinomas as in shared alteration in KRAS. Also associated to carcinoma of the endometrium.

Question 6

What are clear cell adenocarcinomas?

Answer 6

Very uncommon. Composed of large epithelial cells with abundant clear cytoplasm. Considered a variant of endometroid carcinomas since they share the same genetic abnormalities

Question 7

What are transitional cell tumors?

Answer 7

aka Brenner Tumors, contain neoplastic epithelial cells resembling urothelium in a fibroblastic stroma, are usually benign and unilateral. Borderline Brenners tumors have been reported.

Question 8

What are germ cell tumors and which are they?

Answer 8

Constitutes 15 to 20% of all ovarian tumors. Most are benign cystic teratomas. Teratomas, dysgerminomas, yolk sac tumor and choriocarcinoma.

Question 9

What are teratomas?

Answer 9

They contain embryonic structures and can be divided in three groups.
◦ Mature Benign Teratomas : Cystic, found in young women. Composed of mature tissues like skin, cartilage and bone.
◦ Immature Malignant Teratomas : Rare tumors that resemble embryonal and immature fetal tissue. Grow rapidly and can spread locally or distantly.
◦ Monodermal or Specialized Teratomas : Unilateral, rare group of tumors which are composed of mature thyroid tissue which may be functional and ovarian carcinoid.

Question 10

What are dysgerminomas?

Answer 10

50% of malignant ovarian GC tumors. Most common in young women. It is the ovarian counterpart of testicular seminoma. They produce chorionic gonadotropin which can be used as a bio marker. They express TFs like OCT3.4 and NANOG. They are all malignant but only one third are aggressive.

Question 11

What are yolk sac tumors?

Answer 11

It is an extra embryonic tumor. They produce alpha feto protein. It affect children or young women and shows a rapidly growing pelvic mass. Schiller Duvall Bodies are the histological feature special to them, they are glomerulus like structures made of a central blood vessel enveloped by tumor cells.

Question 12

What is a choriocarcinoma?

Answer 12

It is an extra embryonic tumor of placental origin. Similar morphologically to undifferentiated adenocarcinomas. Produce high levels of hCg and can metastasize hematogenously to the lungs, liver and bone.

Question 13

What are sex cord stromal tumors and which are they?

Answer 13

These arise from ovarian stroma which is derived by the sex cords of the embryonic gonad. They are granulosa cell tumor, sertoli leydig cell tumors and ovarian Fibromas and thecomas.

Question 14

What are granulosa cell tumors?

Answer 14

Composed of cells that resemble granulosa cells of a developing follicle. Two thirds of these tumors occur post menopausal. The granulosa cells are important as they elaborate large amounts of estrogen and may behave like low grade malignancies. In juveniles cases it may be associated with precocious sexual development and in adults associated with breast disease and endometrial hyperplasia. Histologically they present Call Exner Bodies which are gland like structures filled with acidophilus material.

Question 15

What are sertoli leydig cell tumors?

Answer 15

They arise from the stroma of the gonads. They are often functional and produce masculinization or defeminization. They occur in women of all ages but more frequently in the second or third decade of life.

Question 16

What are ovarian Fibromas and thecomas?

Answer 16

They are indolent and associated with ascites. Fibromas are made up of hormonally inactive fibroblasts while thecomas are made of plump spindle cells with lipid droplets and are hormonally active. Most of them are benign. There are two syndromes associated ;
◦ Meigs Syndrome which is a combination of ovarian tumor with ascites.
◦ Basal Cell Nevus Syndrome which has the propensity to develop nevi on skin.

Question 17

What are some infections in the female genital tract?

Answer 17

• HSV : aka as herpes simplex virus. Commonly infects cervix, vagina and vulva. Symptoms are systemic ones like fever and malaise. HSV infections can persist and decrease immune function.
• Molluscum Contagiosum : Skin or mucosal lesion caused by pox virus. Dome shaped papules with dimpled center.
• Candida : Yeast infection, it is part of normal microflora so it is typically a disturbance by diabetes, antibiotic and pregnancy.
• Pelvic Inflammatory Disease : PID, caused by Neisseria Gonorrhoeae and by staphylococci.
• HPV : High-risk HPV, such as HPV-16 and HPV-18, cause preneoplastic intraepithelial lesions in the lower genital tract, most often in the cervix and vagina.

Question 18

What is uterine cervical dysplasia and cancer?

Answer 18

Cervical carcinoma is the third most common cancer in women. Almost all cervical precursors and cervical carcinomas are caused by high risk HPV types. HPV16 alone accounts for also set 60% of cases and HPV18 for another 10%. HPVs infect the immature basal cells of squamous epithelium. Its role as a carcinogen depends on the viral proteins E6 and E7. The latter is involved in degradation of RB and E6 promotes p53 degradation.

Cervical precursors include Cervical Intraepithelial Neoplasia (CIN) : CIN I, CIN II and CIN III with severe dysplasia. CIN I is aka Low grade Squamous Intraepithelial Lesion, LSIL, and CIN III aka HSIL. LSILs don’t typically progress to carcinoma. But HSILS are at high risk of progression to carcinoma.

Question 19

What is endometrial hyperplasia and cancer?

Answer 19

It is an important cause of bleeding and frequent precursor to endometrial carcinoma. It is defined as increased proliferation of endometrial glands in respect to the stroma. It is associated with prolonged estrogenic stimulation, obesity, menopause etc. WHO divides endometrial hyperplasia into Non Atypical Hyperplasia and Atypical Hyperplasia.

Question 20

What are endometrial carcinomas?

Answer 20

Endometrial Carcinoma : Most common invasive cancer of the female genital tract. It is classified into Type I Endometrioid Carcinoma which is the most common 80%. Arises in a setting of endometrial hyperplasia so it is linked to obesity, diabetes and hypertension. Type II Serous Carcinoma generally occur in older women and it occurs in a setting of endometrial atrophy. The tumors are poorly differentiated. P53 mutation has big impact.

Question 21

What are endometrial stromal tumors?

Answer 21

Tumors of Endometrial Stroma : They are uncommon. Include Adenosarcomas and pure stromal neoplasms. The first presents polypoid growths with the presence of malignant appearing stroma, and are generally low grade. Stromal Tumors are divided into Benign Stromal Nodules and Endometrial Stromal Sarcomas.

Question 22

What are malignant mixed mullarian tumors of the uterus?

Answer 22

MMMTs are endometrial adenocarcinomas with a malignant mesenchymal component. The latter can take different forms such as stromal sarcoma or leiomyosarcoma. The epithelial and stromal components appear to arise form the same founding cell. It can be considered a collision tumor. They have poor prognosis, very much based on the mesenchymal component.

Question 23

DDX between carcinosarcoma and adenosarcoma?

Answer 23

Regarding the differences between carcinosarcoma and adenosarcoma, remember that in carcinosarcoma both elements of these neoplasms are malignant, whereas adenosarcoma are mixed epithelial and mesenchymal tumor in which the epithelial component is benign or atypical and the stromal component is low-grade malignant.

Carcinosarcoma is defined as a biphasic tumour composed of high-grade carcinomatous and sarcomatous components; while adenosarcoma is a biphasic neoplasm composed of a benign epithelial component and a malignant stromal component.