Female GU

Question 1

Ovarian tumours:

Answer 1

Question 2

Types of Ovarian Cancer

Answer 2

Question 3

Types of Ovarian Cancer

Answer 3

Question 4

Frequency of Major Ovarian Tumours

Answer 4

Question 5

Epithelial tumours: arise from surface epithelial cells

Answer 5

• Cystadenoma/cystadenocarcinoma Serous cystadenoma
• Ovarian serous cystadenocarcinoma
• Borderline serous cystadenoma
• Ovarian mucinous cystadenoma
• Ovarian mucinous cystadenocarcinoma
• Primary peritoneal serous carcinoma associated with BRCA1

Question 6

Ovarian cystadenom

Answer 6

Ovarian cystadenoma is a broad term given to a certain types of ovarian epithelial tumours. This can include

• ovarian serous cystadenoma
• ovarian borderline serous cystadenoma
• ovarian mucinous cystadenoma
• ovarian borderline mucinous cystadenoma
• ovarian cystadenofibroma

Question 7

Serous cystadenoma

Answer 7

• Most common tumour of the ovary
• Benign
• Commonly bilateral (15%)
• Present as large cystic lesions, usually unilocular, the lining of the cyst is flat or may contain small papillary projections.
• Pancreatic serous cystadenomas also contain stroma similar to ovarian stroma

Question 8

Ovarian serous cystadenocarcinoma

Answer 8

malignant form of ovarian serous tumour

• It is the most common type of ovarian malignancy (50-80% of all malignant epithelial ovarian tumours)
• Usually high grade (80%), p53 positive
• high grade nuclear features (e.g. nuclear pleomorphism, abnormal mitotic figures)
• characterised by intratumoural heterogeneity
• nearly ubiquitous p53 positivity
• low grade (5%)
• Though to represent malignant degeneration of serous cystadenoma
• Incidence peaks in 60-70s

**Risk factors: **
oestrogen exposure (nulliparity, early menarche, late menopause)

**Markers: **
elevated CA-125 (>90% of cases)

Imaging features:
* Cystic mass with substantial solid component
* Calcification uncommon but may be seen (12%)
* Frequently BILATERAL (65%)
* Ascites and peritoneal nodularity → metastatic disease

**MRI: **
cystic portions are T1 dark unless there has been intralesional haemorrhage (keep in mind mucinous tumours also have a brighter T1 appearance in the cystic component), solid components restrict and enhance

Theorised that serous carcinomas may arise from fallopian tube or ovary → therefore patients who are high risk (BRCA) have salpingo-oopherectomy rather than simple oopherectomy
Almost all ovarian carcinomas arising in women with BRCA1 or BRCA2 mutations are high-grade serous carcinomas with TP53 mutations.

Question 9

Borderline serous cystadenoma

Answer 9

• lie in the intermediate range in the spectrum of ovarian serous tumours and represent approximately 15% of all serous tumours
• Present at younger age than cystadenocarcinoma
• Cystic lesions with profuse papillary projections - middle of the road between cystadenoma and cystadenocarcinoma
• Prognosis better than for cystadenocarcinoma, even in presence of transovarian spread
• CA-125 typically mildly elevated

Question 10

Ovarian mucinous cystadenoma

Answer 10

• Benign
• Less common than serous
• Comprise of 80% of mucinous ovarian tumours, and 25% of all benign ovarian tumours
• tumours are lined by columnar epithelium, typically similar to endocervical epithelium. These cells secrete thick, gelatinous mucin which fills the locules

Imaging features:
* Larger than serous at presentation, unilateral, multilocular
* Bilateral 5%
* MRI multiple locules with fluid of various viscosity → “stained glass” appearance on T1 and T2

• Mutation of KRAS proto-oncogene
• Associated with psuedomyxoma peritonei, marked by extensive mucinous ascites, cystic epithelial implants on the peritoneal surfaces, adhesions, and frequent involvement of the ovaries
• Most common cause of pseudomyxoma is actually appendiceal in origin
• Causes death by SBO
• Because the majority of primary mucinous ovarian tumors are unilateral, bilateral presentation of mucinous tumors always requires exclusion of a non-ovarian origin.
• Primary peritoneal serous carcinoma associated with BRCA1
• The nodular pattern of disease and presence of disease in the gastrohepatic ligament are associated with significantly higher odds of BRCA1 mutant disease.

Question 11

Ovarian mucinous cystadenocarcinoma

Answer 11

• Rare 5-10% of all ovarian mucinous tumours, malignant
• development of mucinous cystadenocarcinoma has been very rarely associated with malignant transformation of a mature cystic teratoma

Imaging features:
* Multilocular, stained glass, unilateral, similar to mucinous cystadenoma
* Greater solid. Nodular tissue suggestive of malignancy

• Tx: tumour debulking, neoadjuvant chemo pre/post op
• estimated median survival when presenting at an advanced stage is significantly shorter (14 months) compared to ovarian serous cystadenocarcinoma (42 months)

Question 12

Primary peritoneal serous carcinoma associated with BRCA1

Answer 12

The nodular pattern of disease and presence of disease in the gastrohepatic ligament are associated with significantly higher odds of BRCA1 mutant disease.

Question 13

Endometrioid

Answer 13

Definition:
Malignant epithelial neoplasm of the ovary. Commonly associated with endometrial carcinoma.
Both endometrioid and clear cell carcinomas are frequently associated with endometriosis

Epidemiology and Associations:
* 2nd most common ovarian ca, 10-15% of all ovarian cancers. Epithelium resembles benign or malignant endometrium.
* 15-20% of cases occur in the setting of concurrent endometriosis although direct origin from ovarian surface is possible.
* In 15-30% of cases an independent endometrial carcinoma is seen.
* synchronous endometrial carcinoma or endometrial hyperplasia may be present in up to a third of cases
* the endometrial abnormality is thought to represent an independent, primary lesion rather than metastatic disease
* endometrioid carcinoma is the most common malignant neoplasm arising within an endometrioma, although overall this is an uncommon occurrence

Pathogenesis/Organisms:
* PTEN, KRAS and catenin mutations frequently occur.
* TP53 mutations are common for poorly differentiated tumours.
* 5 yr survival for stage 1 disease is 75%.

Morphology:
* Distinguished from serous or mucinous cancers by the presence of tubular glands resembling benign or malignant endometrium.
* Endometrial carcinomas present with solid and cystic areas of growth.
* 40% involve both ovaries and such bilaterality usually implies extension of the neoplasm beyond the genital tract.
* Low grade tumours with glandular pattern.

Complications:
* Metastasis
* Recurrence

Clinical Presentation:
* Abdominal fullness
* pain
* incidental.
* PV bleeding.

Question 14

Brenner tumour

Answer 14

• Uncommon surface epithelial tumour of the ovary - 3% of ovarian epithelial neoplasms
• also known as transitional cell tumours if malignant (made up of >50% malignant cells)
• Most are benign, borderline malignant types are rare, if made up of more than 50% malignant cells they are known as TCC of the ovary
• Originally known as a transitional cell tumour due to histological similarity to urothelium (bladder) (histo: transitional cells covered by fibrous stroma, similar to neoplasms of the urothelium)
• Can rarely occur in other locations, including the testis
• Most commonly incidental findings at laparoscopy
• Brenner tumours are associated with another epithelial ovarian neoplasm of either the ipsilateral or contralateral ovary in ~30% of cases

Imaging features:
* small (usually <2cm) multilocular cystic mass with solid component, or mostly solid mass, calcifications ~85%
* Even with large tumour >10cm, there is often lack of local invasion, differentiating from other malignant ovarian neoplasms

Question 15

Germ cell tumours: arise from oocytes

Answer 15

• Ovarian teratoma
  Can contain bone, epithelium, muscle, fat, nerve, skin replete with hair, sebaceous glands, and tooth structures
• Yolk sac tumor
• Dysgerminoma
• Ovarian choriocarcinoma (ie non-gestational choriocarcinoma)

Question 16

Ovrian Teratoma

Answer 16

Subtypes
* Mature teratoma
* Immature teratoma
* Monodermal/Highly Specialised:

Question 17

Mature teratoma

Answer 17

Definition:
Germ cell tumour of the ovary seen in young women in reproductive years.

Epidemiology and Associations:
* Karyotype is usually 46,XX
* Likely arising from ovum after first meiotic division.
* Characteristically cystic masses lined by squamous epithelium with adnexal structures
* Associated with paraneoplastic syndromes such as limbic encephalitis which can remit following tumour removal.

Morphology:
* Bilateral 10-15% of the time.
* Unilocular cyst containing hair and sebaceous material
* May find teeth and other calcified structures internally.
* Sometimes incorporated into the wall of a mucinous cystic neoplasm.
* 1% undergo malignant transformation, usually to SCC.
* Rarely there is no cystic component

Complications:
* Malignant degeneration most commonly to SCC
* Rupture
* Torsion

Question 18

Immature teratoma

Answer 18

• Rare. Tissues resemble embryonal immature fetal tissue.
• Seen in prepubertal adolescents and young women. Mean age of 18 yrs.
• Bulky lesions with smooth external surface.
• Hair, sebaceous material, cartilage, bone and calcs may be present along with necrosis and haemorrhage.
• Immature neuroepithelium, cartilage, bone, muscle, other elements present
• Histological grade 1-3 based on proportion of tumour containing immature neuroepithelium.
• Grow rapidly, frequently penetrate the capsule and spread either locally or distant.
• Higher grade tumour confined to ovary treated with adjuvant chemo. Most recur within 2 yrs, and absence of disease beyond this point has excellent prognosis.

Question 19

Monodermal/Highly Specialised:

Answer 19

Rare. Includes struma ovarii and carcinoid
ALWAYS unilateral

Struma Ovarii
* Falls under the umbrella of monodermal or highly specialised tumours.
* Thyroid tissue is the dominant or sole component
* Associated with thyroglobulin - can be a cause of hyperthyroidism
* Colloid components of Struma ovarii will likely be T2 dark. Signal dropout associated with fat within the lesion.

Carcinoid
* can produce sufficient 5-hydroxytryptamine to cause the carcinoid syndrome even in the absence of hepatic metastases, since ovarian veins are directly connected to systemic circulation.
* Primary ovarian carcinoid (always unilateral) must be distinguished from metastatic intestinal carcinoid, which is virtually always bilateral.

Struma carcinoid
* well differentiated neuroendocrine tumor admixed / juxtaposed with thyroid tissue
* Presumably arises from intestinal tissue found in teratomas

**Neuroectodermal cyst **
* lined by ependymal cells

Epidermoid cyst
* lined by squamous epithelium (no sebaceous glands present)

Question 20

Dysgerminoma

Answer 20

• Dysgerminoma is the ovarian counterpart of testicular seminoma
• Some occur in patients with gonadal dysgenesis, including pseudohermaphroditism
• Seminoma of the ovary.
• Tend to occur in young adult females and adolescents.
• All are malignant but varying degrees of atypia. approximately ⅓ are aggressive
• If confined to ovary there is a 96% cure rate.
• responsive to chemotherapy, and even those that have extended beyond the ovary can often be cured. Overall survival exceeds 80%
• Unilateral in 80-90%
• Range in size from tiny to filling the pelvis.
• Grey-white. Soft and fleshy. Grow in sheets and cords.

Imaging features
* More aggressive lesion which will demonstrate restricted diffusion.
* T1 dark. T2 iso to dark
* Homogeneous enhancement pattern

Question 21

Ovarian choriocarcinoma (ie non-gestational choriocarcinoma)

Answer 21

• Similar to testicular. Similar morphology to choriocarcinoma of placental origin.
• Extraembryonic origin, like yolk sac tumour.
• Histologically identical to more common placental lesions
• It is generally held that a germ cell origin can be confirmed only in prepubertal females, because after this age an origin from an ovarian ectopic pregnancy cannot be excluded
• Commonly exists in combination with other ovarian germ cell tumours, rarely seen as a pure choriocarcinoma.
• Ovarian choriocarcinoma is aggressive and have usually metastasised heamatogenously to the lungs, liver, bone and other sites at the time of diagnosis.
• Elevated hCG which helps with detecting recurrences.
• In contrast to choriocarcinomas arising in placental tissue, those arising in the ovary are generally unresponsive to chemotherapy and are often fatal.

Question 22

Sex-cord stromal tumours:

Answer 22

• These ovarian neoplasms are derived from the ovarian stroma, which in turn is derived from the sex cords of the embryonic gonad.
• The undifferentiated gonadal mesenchyme eventually produces specific types of cells in both male (Sertoli and Leydig) and female (granulosa and theca) gonads, and tumors resembling all of these cell types can be identified in the ovary.
• Moreover, because some of these cells normally secrete estrogens (granulosa and theca cells) or androgens (Leydig cells), their corresponding tumors may be either feminizing (granulosa/theca cell tumors) or masculinizing (Leydig cell tumors).

arising from stroma of ovarian cells, can secrete hormones
* Granulosa cell tumour
* Sertoli-Leydig cell tumour
* Fibroma
* thecoma
* Meig’s Syndrome

Question 23

Granulosa cell tumour

Answer 23

• Resemble granulosa cells of developing follicle.
• broadly divided into adult and juvenile granulosa cell tumors largely based on the age of the patient, but also on morphologic findings.
• ⅔ occur in post menopausal women
• 5% of all ovarian tumours. 95% are adult type.
• Granulosa cell tumors are of clinical importance for two reasons:
• (1) they may elaborate large amounts of estrogen, and
• (2) they may behave like low-grade malignancies
• Functionally active in prepubertal (juvenile type) → precocious puberty
• Functionally active in post menopausal/adult → endometrial hyperplastia, post menopausal bleeding, endometrial carcinoma, proliferative breast disease
• Occasionally produce androgens, masculinising patient
• Elevated tissue and serum levels of inhibin, a product of granulosa cells, are associated with granulosa cell tumors.
• Usually unilateral. Can be microscopic to huge.
• Call-Exner bodies may be present
• All granulosa cell tumours are potentially malignant, but difficult to tell malignant potential on histology
• Thecoma components may be present, and if thecoma cells are predominant, then almost never malignant
• Sometimes secrete large amounts of oestrogen:
• Proliferative breast disease
• Endometrial hyperplasia and carcinoma → PV bleeding
• (granulosa is your drag queen name → oestrogen secreting)
  *

Question 24

Sertoli-Leydig cell tumour

Answer 24

• Can be functional causing masculinisation and defeminisation (opposite of granulosa cell) (Yes, SIRtoli → masculinisation)
• Occur in women of all ages with peak in 2nd and 3rd decades.
• May block normal sexual development in children.
• Hilus cell tumors - (pure Leydig cell tumors), produce predominantly testosterone

Question 25

Fibroma, thecoma and fibrothecomas

Answer 25

• Tumors arising in the ovarian stroma that are composed of either fibroblasts (fibromas) or plump spindle cells with lipid droplets (thecomas), or a mixture of both (fibrothecomas)
• Pure thecomas are rare but tumours in which these cells are predominant may be hormonally active
• Usually only occur in post menopausal women
• In contrast, fibromas as a rule are hormonally inactive
• Most common in middle aged women.
• T1 and T2 dark lesions without restriction (high ADC)
• Varying degrees of enhancement, usually delayed.
• Association with Meigs syndrome (Meg needs Fibre) (ascites and unilateral pleural effusion)
• Also associated with basal cell nevus syndrome

Fibroma
* Most common in middle aged women.
* T1 and T2 dark lesions without restriction (high ADC)
* Varying degrees of enhancement, usually delayed.
* Association with Meigs syndrome (Meg needs Fibre)

Question 26

thecoma

Answer 26

Generally only occur in postmenopausal women.

Question 27

Meig’s Syndrome

Answer 27

defined as the presence of ascites and pleural effusion in association with a benign, usually solid ovarian tumour, most commonly an ovarian fibroma (80-90%), but can be with others
Pleural effusion tends to be right sided (70% of cases)

Benign effusions, which resolve after resection of the primary pelvic tumour

**Ddx: **
* malignant ascites and pleural effusion in the presence of an aggressive ovarian tumour
* pseudo-Meigs syndrome: benign reversible pleural effusion in the presence of a primary tumour other than solid ovarian tumours, e.g. broad ligament leiomyoma

Question 28

Ovarian cancer staging: FIGO:

Answer 28

Stage 1
Confined to ovary (one or both)/fallopian tubes

Stage 2
pelvic/peritoneal extension within the pelvis

Stage 3
Extrapelvic peritoneal mets, retroperitoneal LN

Stage 4
Distant mets, malignant effusion

Question 29

Paraovarian cystadenoma

Answer 29

• usually benign adnexal tumour that does not arise from the ovary.
• Association with von Hippel Lindau syndrome
• Typically unilateral cystic adenexal lesion, majority have thick septations/irregular wall (compared with paraovarian cyst)
• Similar to paraovarain cysts, can cause torsion, or rupture
• No beaking with the ovary → not ovarian in origin

Question 30

Gestational trophoblastic disease

Answer 30

Placental Site Trophoblastic Disease:
* Comprises of 2% of gestational trophoblastic neoplasms.
* Neoplastic proliferations o fextravillous trophoblasts, intermediate trophoblasts.
* In normal pregnancy extravillous trophoblasts are found in implantation site, as clusters of cells within the placental parenchyma and in the placental membranes.
* Presents as a uterine mass accompanied by either PV bleeding, amenorrhoea, moderately elevated hCG.
* Malignant trophoblastic cells typically diffusely infiltrate the endo and myometrium.
* May follow a normal pregnancy (50%), spontaneous abortion, hydatiform mole.
* Patients with localised disease have an excellent prognosis but 10-15% mortality with metastatic disease

Question 31

Clear cell carcinoma

Answer 31

• Large epithelial cells with abundant clear cytoplasm. An appearance that resembles hypersecreational gestational endometrium
• May occur in association with endometriosis or endometriod carcinoma of the ovary, and resemble clear cell carcinoma of the endometrium
• Clear cell carcinoma now thought of to be variants of endometroid carcinoma
• Can be predominantly solid or cystic
• Good prognosis if stage 1 (90% 5 year survival), but confers a poorer prognosis in advanced stage
  *

Question 32

Yolk sac tumour

Answer 32

• thought that to be derived from malignant germ cells that are differentiating along the extraembryonic yolk sac lineage
• Similar to the normal yolk sac, the tumor cells elaborate α-fetoprotein
• Most patients are children or young women presenting with abdominal pain and a rapidly growing pelvic mass that usually appears to involve a single ovary.
• With combination chemotherapy, there is greater than 80% survival independent of disease stage.
  *

Question 33

Other Germ Cell Tumors

Answer 33

These include
1. embryonal carcinoma, a highly malignant tumor of primitive embryonal elements that is histologically similar to embryonal carcinoma arising in the testes
2. polyembryoma, a malignant tumor containing so-called embryoid bodies; and
3. mixed germ cell tumors containing various combinations of dysgerminoma, teratoma, yolk sac tumor, and choriocarcinoma.

Question 34

Metastatic ovarian tumours:

Answer 34

• The most common metastatic tumors of the ovary are derived from tumors of müllerian origin: the uterus, fallopian tube, contralateral ovary, or pelvic peritoneum.
• The most common extra-müllerian tumors metastatic to the ovary are carcinomas of the breast and gastrointestinal tract, including colon, stomach, biliary tract, and pancreas.
• Krukenberg tumor, characterized by bilateral metastases composed of mucin-producing, signet-ring cancer cells, most often of gastrointestinal origin
  *

Question 35

Meig’s Syndrome

Answer 35

• defined as the presence of ascites and pleural effusion in association with a benign, usually solid ovarian tumour, most commonly an ovarian fibroma (80-90%), but can be with others
• Pleural effusion tends to be right sided (70% of cases)
• Benign effusions, which resolve after resection of the primary pelvic tumour

**Ddx: **
* malignant ascites and pleural effusion in the presence of an aggressive ovarian tumour
* pseudo-Meigs syndrome: benign reversible pleural effusion in the presence of a primary tumour other than solid ovarian tumours, e.g. broad ligament leiomyoma
*

Question 36

Ectopic pregnancy

Answer 36

• most common location fallopian tube 90%
• Other sites include the ovary, the abdominal cavity, and the intrauterine portion of the fallopian tube (cornual pregnancy)
• Most important predisposing condition is PID (seen in up to 50% of ectopics)
• Peritubal scarring from appendicitis, endometriosis, previous surgery also risk factors
• IUD 2x risk fo ectopic
• Ectopic is the most common cause of hematoma salpinx, and if seen should have high suspicious
• Typically presents 6-8 weeks post LMP
  *

Question 37

Placental anatomy:

Answer 37

• The placenta is composed of chrionic villi that aprout from the chorion to provide contact area between the foetal and maternal circulations a the intervillous space
• In a mature placenta the bloo enters the intervillous space via endometrial spiral arteries and circulates around the villi to allow gas and nutrient exchange, and the flows back to the decidua and enters the endometrial veins
• Deoxygenated foetal blood enters placenta through 2 umbilical arteries ahat then branch radially to form the chorionic arteries in the villi, where it forms an extensive capillary system in the intervillous space.
• Gas and nutrient exchange occurs and then oxygenated blood returns to the foetus via single umbilical vein
  *

Question 38

Twin placentas:

Answer 38

• Twin pregnancies arise from fertilization of two ova (dizygotic) or from division of one fertilized ovum (monozygotic). There are three basic types of twin placentas
• Diamniotic dichorionic
• Diamniotic monochorionic
• Monoamnionic monochorionic
• Monochorionic placentas imply monozygotic (identical) twins
• One complication of monochorionic twin pregnancy is twin-twin transfusion syndrome.
• Monochorionic twin placentas have vascular anastomoses that connect the circulation of the twins and may enclave AV shunts, which preferentially increase blood flow to one twin causing fluid overload and under perfuse the other
  *

Question 39

Abnormalities of placental implantation:

Answer 39

• Placenta previa is a condition in which the placenta implants in the lower uterine segment or cervix, often leading to serious third-trimester bleeding. A complete placenta previa covers the internal cervical os and thus requires delivery via cesarean

Praevia is divided into four grades depending on the relationship and distance to the internal cervical os:
* grade I: low-lying placenta: placenta lies in the lower uterine segment, lower edge 0.5-2.0 cm from internal os).
* grade II: marginal praevia: placental tissue reaches the margin of the internal cervical os, but does not cover it
* grade III: partial praevia: placenta partially covers the internal cervical os
* grade IV: complete praevia: placenta completely covers the internal cervical os
* Sometimes grades I and II are termed a “minor” or “partial” placenta praevia, and grades III and IV are termed a “major” placenta praevia

Placenta accreta is caused by partial or complete absence of the decidua, such that the placental villous tissue adheres directly to the myometrium, which leads to a failure of placental separation at birth.
It is an important cause of severe, potentially life-threatening postpartum bleeding. Common predisposing factors are placenta previa (in up to 60% of cases) and history of previous cesarean section.

Question 40

Placental infections:

Answer 40

2 pathways:
* Ascending infection through birth canal
* Haematogenous (transplacental) infection

• Ascending most common and almost always bacterial → premature rupture of membranes and preterm delivery
• The infection often elicits a vasculitis response from the umbilical cord
• Several hematogenous infections, classically components of the TORCH group (toxoplasmosis and others [syphilis, tuberculosis, listeriosis], rubella, cytomegalovi rus, herpes simplex), can affect the placenta

Question 41

Preeclampsia and eclampsia:

Answer 41

• Preeclampsia is a systemic syndrome characterized by widespread maternal endothelial dysfunction that presents during pregnancy with hypertension, edema, and proteinuria
• Occurs in 3-5% of pregnant women, usually in last trimester and more commonly in primiparas
• If convulsions → eclampsia
• Approximately 10% of women with severe preeclampsia develop microangiopathic hemolytic anemia, elevated liver enzymes, and low platelets, referred to as the HELLP syndrome
• Also associated with hypercoaguable states that may lead to small thrombi in capillaries throughout body, particularly the liver, kidneys, brain and pituitary → small infarcts/haemorrhages may be seen
• Pathogenesis: likely inadequate perfusion of placenta leading to release of placenta-derived factor(s) released into the maternal circulation that cause an imbalance in circulating angiogenic and anti-angiogenic factors; this in turn leads to systemic maternal endothelial dysfunction and the clinical symptoms of the disease
• most commonly starts after 34 weeks of gestation but begins earlier in women with hydatidiform mole or preexisting kidney disease, hypertension, or coagulopathies.
• Presents with HTN and oedema, with proteinuria developing in next few days. Headaches and visual disturbances indicative of severe syndrome
  *

Question 42

Gestational trophoblastic disease

Answer 42

• Gestational trophoblastic disease encompasses a spectrum of tumors and tumor-like conditions characterized by proliferation of placental tissue, either villous or trophoblastic.
• The major disorders of this type are hydatidiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor (PSTT)

Question 43

Hydatidiform mole:

Answer 43

• Characterised by cystic swelling of the chorionic villi with variable trophoblastic proliferation
• associated with an increased risk of persistent trophoblastic disease (invasive mole) or choriocarcinoma
• More common at the 2 ends of reproductive life - late teens and 40-50s
• Associated with high bHCG for stage in pregnancy

2 types of benign non-invasive moles:
Complete mole
* results from fertilization of an egg that has lost its female chromosomes, generic material completely paternal
* 90% 46,XX karotype stemming from duplication of genetic material of a sperm
* 10% fertilisation of empty egg by 2 sperm which may have 46,XX or 46,XY karotype
* Patients have 2.5% risk of subsequent choriocarcinoma and 15% risk of persistent or invasive mole.

Partial mole
* Partial moles result from fertilization of an egg with two sperm. In these moles the karyotype is triploid (e.g., 69,XXY) or occasionally tetraploid (92,XXXY).
* Fetal tissues are typically present.
* Partial moles have an increased risk of persistent molar disease, but are not associated with choriocarcinoma.

Invasive moles
* Invasion of the myometrium by hydropic chorionic villi, penetrates or perforates the uterine wall
* The tumor is locally destructive and may invade parametrial tissue and blood vessels. Hydropic villi may embolize to distant sites, such as lungs and brain, but do not grow in these organs as true metastases
* Event without chemotherapy they eventually regress.
* The tumor is manifested clinically by vaginal bleeding and irregular uterine enlargement. It is always associated with a persistently elevated serum HCG. The tumor responds well to chemotherapy but may result in uterine rupture and necessitate hysterectomy.

Question 44

Choriocarcinoma

Answer 44

• Gestational choriocarcinoma is a malignant neoplasm of trophoblastic cells derived from a previously normal or abnormal pregnancy, such as an extrauterine ectopic pregnancy.
• Choriocarcinoma is rapidly invasive and metastasizes widely, but once identified responds well to chemotherapy.
• Invades underlying myometrium, penetrating blood vessels and may extent to the uterine serosa and into adjacent structures
• High propensity for haematogenous spread
• most common sites are the lungs (50%) and vagina (30% to 40%), followed by, in descending order of frequency, the brain, liver, bone and kidney
• Histologically, it does not produce chorionic villi and consists entirely of proliferating syncytiotrophoblasts and cytotrophoblasts
• 50% arise in COMPLETE hydatiform moles, 25% in previous abortions and 20% from normal pregnancies
• rarely, a nongestational choriocarcinoma may develop from germ cells in the ovaries or the mediastinum.
• Usually has areas of necrosis and haemorrhage
• bHCG usually even higher than that seen in hydatidiform moles, unless the tumour is so necrotic that the bHCG is low
• Chemotherapy results in nearly 100% remission and a high rate of cures.
• Many of the cured patients have had normal subsequent pregnancies and deliveries.
• By contrast, nongestational choriocarcinomas that arise outside of the uterus are much more resistant to therapy.
  *

Question 45

Placental Site Trophoblastic Tumour:

Answer 45

• Comprises of 2% of gestational trophoblastic neoplasms.
• • Neoplastic proliferations of extravillous trophoblasts, aka intermediate trophoblasts.
• • In normal pregnancy extravillous trophoblasts are found in implantation site, as clusters of cells within the placental parenchyma and in the placental membranes.
• • Presents as a uterine mass accompanied by either PV bleeding, amenorrhoea, moderately elevated hCG.
• • Malignant trophoblastic cells typically diffusely infiltrate the endo and myometrium.
• • May follow a normal pregnancy (50%), spontaneous abortion, hydatiform mole.
• • Patients with localised disease have an excellent prognosis but 10-15% mortality with metastatic disease.

Question 46

Condyloma

Answer 46

• Condylomata acuminata are benign genital warts caused by low oncogenic risk HPVs, mainly types 6 and 11.
• may be solitary, but are more frequently multifocal, and may involve vulvar, perineal, and perianal regions as well as the vagina and, less commonly, the cervix.
• The lesions are identical to those found on the penis and around the anus in males
• Condylomata acuminata are not precancerous lesions.
  *

Question 47

Bartholin gland abscess

Answer 47

Typically e coli or staph aureus

Question 48

Vulvar carcinoma

Answer 48

• Squamous cell carcinoma is the most common histologic type of vulvar cancer
• vulvar squamous cell carcinomas are divided into two groups:
• Basaloid and warty carcinomas related to infection with high risk HPVs (30% of cases), most commonly HPV-16. These are less common and occur at younger ages.
• develop from an in situ precursor lesion called classic vulvar intraepithelial neoplasia (VIN), risk factors for VIN are same as HPV
• Keratinizing squamous cell carcinomas unrelated to HPV infection (70% of cases). These are more common and occur in older women.
• occurs most often in individuals with long-standing lichen sclerosus or squamous cell hyperplasia and is not related to HPV.
  *

Question 49

Vaginal tumours:

Answer 49

**SCCs: **
* Virtually all primary carcinomas of the vagina are squamous cell carcinomas associated with high risk HPVs
* Most often the invasive tumor affects the upper vagina, particularly the posterior wall at the junction with the ectocervix.
* The lesions in the lower two thirds of the vagina metastasize to the inguinal nodes, whereas lesions in the upper vagina tend to spread to regional iliac nodes.

Embryonal Rhabdomyosarcoma, Also called sarcoma botryoides
* malignant embryonal rhabdomyoblasts is most frequently found in infants and in children younger than 5 years of age.
* These tumors tend to grow as polypoid, rounded, bulky masses that have the appearance and consistency of grapelike clusters (hence the designation botryoides, or grapelike)
* The tumors tend to invade locally and cause death by penetration into the peritoneal cavity or by obstruction of the urinary tract
*

Question 50

PID

Answer 50

• Pelvic inflammatory disease (PID) is an infection that begins in the vulva or vagina and spreads upward to involve most of the structures in the female genital system
• acute complications of PID include peritonitis and bacteremia, which in turn may result in endocarditis,meningitis, and suppurative arthritis.
• The chronic sequelae of PID include infertility and tubal obstruction, ectopic pregnancy, pelvic pain, and intestinal obstruction due to adhesions between the bowel and pelvic organs.

Gonococcus
* Gonococcal infection is characterized by marked acute inflammation of involved mucosal surfaces
* If infection spreads, the endometrium is usually spared (for unclear reasons), but within the fallopian tubes, an acute suppurative salpingitis ensues
* exudate then leaks out of the fimbriated end, infections spread to the ovary to create a salpingo-oophoritis → tubo-ovarian abscess/pyosalpinx
* With time the infecting organisms may disappear, but the tubal plicae, denuded of epithelium, adhere to one another and slowly fuse in a reparative, scarring process that forms glandlike spaces and blind pouches, referred to as chronic salpingitis → prevent passage of oocytes → infertility/ectopic pregnancy

Puerperal
* Infections after spontaneous or induced abortions and normal or abnormal deliveries
* Typically polymicrobial and may be caused by staphylococci, streptococci, coliforms, and Clostridium perfringens
* thought to spread upwards from the uterus through the lymphatics or venous channels rather than on the mucosal surfaces. Therefore, these infections tend to produce more inflammation within the deeper layers of the organs than gonococcal infections.
* compared to gonococcal infections, puerperal non-gonoccal PID show less involvement of the mucosa and the tube lumen, and more inflammation within the deeper tissue layers.
* These infections often spread throughout the wall to involve the serosa and the broad ligaments, pelvic structures, and peritoneum.
* Bacteremia is a more frequent complication of streptococcal or staphylococcal PID than of gonococcal infections.

Question 51

HSV 1 and 2

Answer 51

• Genital ulceration + vesicles
• Fever, malaise, tender inguinal LN
• during the acute infection the virus
• migrates to the regional lumbosacral nerve ganglia and establishes a latent infection. Because of viral latency, HSV infections persist indefinitely and any decrease in immune function, as well as stress, trauma, ultraviolet radiation, and hormonal changes, can trigger reactivation of the virus and recurrence of the skin and mucosal lesions
• The gravest consequence of HSV infection is transmission to the neonate during birth.
• This risk is highest if the infection is active during delivery and particularly if it is a primary (initial) infection
  *

Question 52

Molluscum contagiosum

Answer 52

• is a skin or mucosal lesion caused by poxvirus - any area of skin
• The infections are common in children between 2 and 12 years, and transmitted through direct contact or shared articles (e.g., towels).
• In adults, molluscum infections are typically sexually transmitted and affect the genitals, lower abdomen, buttocks, and inner thighs.
• Diagnosis is based on the characteristic clinical appearance of pearly, dome-shaped papules
  *

Question 53

Cervical cancer

Answer 53

• The area of the cervix where the columnar epithelium abuts the squamous epithelium is termed the “transformation zone.” The unique epithelial environment of the cervix renders it highly susceptible to infections with HPV, the main cause of cervical cancer. Immature squamous metaplastic epithelial cells in the transformation zone are most susceptible to HPV infection, and as a result this is where cervical precursor lesions and cancers develop.
• HPVs infect immature basal cells of the squamous epithelium in areas of epithelial breaks, or immature metaplastic squamous cells present at the squamocolumnar junction. HPVs cannot infect the mature superficial squamous cells that cover the ectocervix, vagina, or vulva (which require epithelial breaks to infect)
• This difference in epithelial susceptibility to HPV infection explains the high frequency of cervical cancer in women and anal cancer in homosexual men and a relatively low frequency of vulvar and penile cancer.

High-risk HPVs are by far the most important factor in the development of cervical cancer.
* HPV-16 alone accounts for almost 60% of cervical cancer cases, and HPV-18
* High risk HPVs are also implicated in squamous cell carcinomas arising at many other sites, including the vagina, vulva, penis, anus, tonsil, and other oropharyngeal locations
* NB: low oncogenic risk HPVs are the cause of the sexually transmitted vulvar, perineal, and perianal warts (condyloma acuminatum)

LSIL and HSIL (replacing old CIN classifiction)
* LSIL(Low grade squamous intraepithelial lesion) does not progress directly to invasive carcinoma and in fact most cases regress spontaneously; only a small percentage progress to HSIL. For these reasons, LSIL is not treated like a premalignant lesion.
* In HSIL, there is a progressive deregulation of the cell cycle by HPV, which results in increased cellular proliferation, all HSILS are considered to be at high risk for progression to carcinoma.
* More than 80% of LSILs and 100% of HSILs are associated with high-risk HPVs, with HPV-16 being the most common HPV type in both categories of lesions.
* Although the majority of HSILs develop from LSILs, approximately 20% of cases of HSIL develop denovo, independent of any preexisting LSIL

• Squamous cell carcinoma is the most common histologic subtype, accounting for approximately80% of cases.
• The second most common tumor type is adenocarcinoma, which constitutes about 15% of cervical cancer cases and develops from a precursor lesion called adenocarcinoma in situ.
• Adenosquamous and neuroendocrine carcinomas are rare cervical tumors that account for the remaining 5% of cases.
  — More aggressive, less time needed to progress from in situ to invasive, later stage at presentation and worse prognosis
• All of the aforementioned tumor types are caused by high-risk HPVs
• Most patients with advanced cervical cancer die of the consequences of local tumor invasion (e.g., ureteral obstruction, pyelonephritis, and uremia) rather than distant metastases

Question 54

Cervical cancer staging: FIGO

Answer 54

Question 55

Cervical Cancer MRI

Answer 55

• Best sequence for parametrial invasion
• The parametrium is the anatomical space lateral to the cervix.
• MRI has a high negative predictive value in excluding parametrial invasion. If the T2 hypointense cervical ring is intact, then parametrial invasion is unlikely.
• DWI used an an adjunct in assessing this
  *

Question 56

Endocervical polyps

Answer 56

• Endocervical polyps are common benign exophytic growths that arise within the endocervical canal
• Their main significance is that they may be the source of irregular vaginal “spotting” or bleeding that arouses suspicion of some more ominous lesion.
• Simple curettage or surgical excision is curative.
  *

Question 57

Endometritis and retained products of conception (RPOC)

Answer 57

• endometrium and myometrium are relatively resistant to infections, primarily because the endocervix forms a barrier to ascending infection.
• Acute endometritis is limited to bacterial infections that arise after delivery or miscarriage, usually secondary to retained products of conception
• the causative agents include group A hemolytic streptococci, staphylococci, and other bacteria
• Removal of the retained gestational fragments by curettage, accompanied by antibiotic therapy, promptly clears the infection
• Chronic endometritis occurs in association with the following disorders:
• Chronic pelvic inflammatory disease (PID)
• Retained gestational tissue, postpartum or postabortion
• Intrauterine contraceptive devices
• Tuberculosis, either from miliary spread or, more often, from drainage of tuberculous salpingitis. Both are rare in Western countries

Question 58

Dysfunctional PV bleeding

Answer 58

• Most frequent cause of dysfunction bleeding is anovulation, most common at menarche and perimonpausal period
• failure of ovulation results in excessive endometrial stimulation by estrogens that is unopposed by progesterone
• Inadequate luteal phase also leads to dysfunctional bleeding
• refers to a condition that manifests clinically as infertility associated with either increased bleeding or amenorrhea.
• The cause is believed to be inadequate progesterone production during the post-ovulatory period.

Question 59

Endometriosis and Adenomyosis

Answer 59

• Endometriosis = ectopic endometrial tissue at a site outside of the uterus. Pelvic pain, dysmenorrhoea, interfility
• The abnormal tissue usually contains both endometrial glands and stroma, but may contain just stroma in some cases
• Occurs at following sites in order of frequency:
  1. ovaries
  2. uterine ligaments
  3. rectovaginal septum
  4. cul de sac
  5. pelvic peritoneum,
  6. large and small bowel and appendix
  7. mucosa of the cervix, vagina, and fallopian tubes
  8. laparotomy scars.
• Basically from the ovary, spreading outwards
• Uncommonly may “invade”/”spread” e/g. To brain, lung, bone

Pathogenesis: proposed 2 main categories
1. those that propose an origin from the uterine endometrium (retrograde menstruation and benign metastasis)
However retrograde menstruation is common, even in women without endometriosis and does not explain distant sites of disease like brain and lung, and endometriosis in men treated with high dose oestrogen with steroids
2. those that propose an origin from cells outside the uterus that have the capacity to give rise to endometrial tissue.
This may explain above outliers

• The endometrial deposits in endometriosis differ to endometria of women without endometriosis
• There is increased oestrogen production by endometrial stromal cells
• Release of proinflammatory factors such a prostaglandin and interlukin, VEGF
• In patients with endometriosis, these changes are present in both the endometrial deposits and in the uterine endometrium
• Association between endometriosis and both endometrioid and clear cell types of ovarian cancer
• Endometiotic lesions bleed in response to both extrinsic cyclic (ovarian) and interinstic hormonal stimulation. When lesions are extensive, causes organising haemorrhage which causes extensive fibrous adhesions
• Ovaries can become markedly distorted by large cystic masses filled with fluid from previous haemorrhage → endomteriomas aka “chocolate cysts”
• Atypical endometriosis on histology is likely precursor to endometriosis related ovarian cancer

Question 60

Adenomyosis

Answer 60

• Related to endometriosis, it is the present of endometrial tissue within the uterine wall/myometrium. Adenomyosis remains in continuity with the endometrium, presumably signifying downgrowth of endometrial tissue into and between the smooth muscle of the myometrium
• Common, 20% of pts

Question 61

Endometrial polyps:

Answer 61

• Exophytic masses projecting into the endometrial cavity
• Can be single or multiple, usually sessile, measuring up to 3cm
• May be asymptomatic or cause abnormal bleeding (intermenstrual, menometorrhaegia, postmenopausal bleeding) if they ulcerate or necrose
• The glands in polyps may be hyperplastic or atrophic, and may occasionally demonstrate secretory changes (functional polyps)
• Polyps may by become hyperplastic in association with generalized endometrial hyperplasia and are responsive to estrogen but show little or no response to progesterone
• Seen in association with tamoxifen as although tamoxifen
• Rarely adenocarcinoma may arise within endometrial polyps

Question 62

Endometrial hyperplasia

Answer 62

• Increased proliferation of endometrial glands relative to the stroma
• Presents as abnormal bleeding,
• Associated with prolonged oestrogen stimulation of the endometrium, which may be secondary to many things
• Anovulation, increase endogenous oestrogen production, exogenous oestrogen
• Obesity, menopause, PCOS functioning granulosa cell tumoru of the ovary
• frequent precursor to the most common type of endometrial carcinoma
  » Inactivation of the PTEN tumor suppressor gene is a common (20%) genetic alteration in both endometrial hyperplasias and endometrial carcinomas
  »patients with Cowden syndrome, which is caused by germline mutations in PTEN, have a high incidence of endometrial carcinoma and certain other tumors, particular breast cancer

**two major categories: **
* Non-atypical hyperplasia - rarely progress to adenocarcinoma (approx 1-3%)
* Atypical hyperplasia (endometrial intraepithelias neoplasia)
»Has cellular atypia, Has features which overlap with well differentiated endometrioid adenocarcinoma, and may be difficult to distinguish without hysterectomy
»25-50% found to have carcinoma when hysterectomy is performed
* atypical hyperplasia is managed by hysterectomy or, in young women who desire fertility, a trial of progestin therapy and close follow-up. Most often, hopefully after a successful pregnancy, lack of regression prompts removal of the uterus.

Question 63

Endometrial carcinoma

Answer 63

• Most common invasive carcinoma of the female genital tract (due to reduction in cervical cancer rates), peak incidence is in postmenopausal women 55 to 65 years
• Typically presents with postmenopausal bleeding
• Can be seen as a localised polypoid tumour, or as diffusely infiltrating tumour
• Direct spread of disease into adjacent structures (invasion to broad ligament may present as a palpable mass), then dissemination to regional lymph nodes, and in late stages distal mets elsewhere

2 broad categories: type 1 and type 2
* Type 1 - “endometroid carcinoma” most common, 80% of cases
*&raquo_space;>Well differentiated and mimic proliferative endometrial glands, therefore endometrioid carcinoma
*&raquo_space;>Usually arise in setting of endometrial hyperplasia
*&raquo_space;>Associated with: obesity, diabetes, HTN, infertility, unopposed oestrogen stimulation
*&raquo_space;>PTEN mutations, similar to endometrial hyperplasia
*&raquo_space;>increase signaling through the PI3K/AKT pathway, which is a hallmark of this particular tumor type.
*&raquo_space;>This is the type seen in HNPCC aka Lynch syndrome
*&raquo_space;>Loss of function mutation in TP53 seen in 50% of poorly differentiated carcinomas
Type 2 - “(Serous) carcinoma”
*&raquo_space;>Tend to occur in women approx 10 years older than type 1
*&raquo_space;>In contrast to type 1, usually arise in the setting or endometrial atrophy
*&raquo_space;>ARE BY DEFINITION POORLY DIFFERENTIATED (GRADE 3) TUMOURS, AND ARE APPROX 15% OF ENDOMETRIAL CARCINOMA
*&raquo_space;>Most common subtype is called serous carcinoma, as it has morphologic and biological overlap with ovarian serous carcinoma
*&raquo_space;>Other less common subtypes include clear cell, and malignant mixed mullarian tumour
*&raquo_space;>Mutations in TP53 are present in 90%, and these mutations are though to occur early in the evolution to carcinoma (as opposed to type 1 where it is thought to be a late occurrence
*&raquo_space;>The precursor lesion, serous endometrial intraepithelial carcinoma, consists of malignant cells identical to those of serous carcinoma that are confined to the epithelial surfaces
*&raquo_space;>Often large bulky tumours or deeply invasive into the myometrium
*&raquo_space;>Serous carcinoma, despite relatively superficial endometrial involvement, may be associated with extensive peritoneal disease, suggesting spread by routes (i.e., tubal or lymphatic transmission) other than direct tinvasion
*&raquo_space;>generally poorer prognosis is thought to be a consequence of a propensity to exfoliate, travel through the fallopian tubes, and implant on peritoneal surfaces like their ovarian counterparts
*&raquo_space;>Have generally spread outside of the uterus at time of diagnosis

Pathologic staging of both type I and II endometrial adenocarcinoma and malignant mixed müllerian tumors:
* Stage I—Carcinoma is confined to the corpus uteri itself.
* Stage II—Carcinoma involves the corpus and the cervix.
* Stage III—Carcinoma extends outside the uterus but not outside the true pelvis.
* Stage IV—Carcinoma extends outside the true pelvis or involves the mucosa of the bladder or the rectum.

Question 64

Malignant Mixed Mullerian Tumours (MMMTs)

Answer 64

• Also referred to as carcinosarcomas, are endometrial adenocarcinomas with a malignant mesenchymal component.
• carcinomas with sarcomatous differentiation - On histology, the tumors usually consist of adenocarcinoma (endometrioid, serous, or clear cell) mixed with the malignant mesenchymal (sarcomatous) elements
• Mutations found in MMMTs tend to involve the same genes that are mutated in endometrial carcinoma, such as PTEN, TP53, and PIK3CA, while alterations typical of those found in sarcomas are absent.
• MMMTs are often bulky and polypoid, and may protrude through the cervical os
• The only other known prognostic factor is the differentiation of the mesenchymal component - patients with tumors that have heterologous mesenchymal components do worse than those whose tumors do not
• Generally poor outcomes

Question 65

Tumours of endometrial stroma

Answer 65

• Adenosarcomas: present as large growths that protrude through the cervical os
• Generally low grade, but recurrences seen in 25%
• Can be hard to differentiate clinically from large endometrial polyp
• The distinction is important as adenosarcoma is oestrogen sensitive and responds to oopherectomy
• Stromal tumours
• Benign stromal nodules
• Endometrial stromal sarcomas
  High relapse rates, 5 year survival <50%

Question 66

Leiomyomas

Answer 66

• Aka fibroids - consist of smooth muscle similar to surrounding myometrium
• signs and symptoms include abnormal bleeding, urinary frequency due to compression of the bladder, sudden pain from infarction of a large or pedunculated tumor, and impaired fertility
• Myomas in pregnant women increase the frequency of spontaneous abortion, fetal malpresentation, uterine inertia (failure to contract with sufficient force), and post- partum hemorrhage.
• Malignant transformation to leiomyosarcoma, if it occurs at all, is extremely rare.
• Sharply circumscribed, discrete, round, firm tumors varying in size from small to massive tumors that fill the pelvis
• a subset contains MED12 mutations
• Found within the myometrium of the corpus. Only infrequently do they involve the uterine ligaments, lower uterine segment, or cervix
• Can occur within the myometrium (intramural), just beneath the endometrium (submucosal) or beneath the serosa (subserosal)
• Benign variants of leiomyoma include atypical or bizarre (symplastic) tumors with nuclear atypia and giant cells, and cellular leiomyomas. Both have a low mitotic index, helping to distinguish these benign tumors from leiomyosarcomas
• Extremely rare variant, benign metastasizing leiomyoma, is a uterine leiomyoma that extends into vessels and spreads hematogenously to other sites, most commonly the lung.
• Another variant, disseminated peritoneal leiomyomatosis, presents as multiple small peritoneal nodules.
• Both are considered benign despite their unusual behavior.
  *

Question 67

Leiomyosarcoma

Answer 67

• thought to arise from the myometrium or endometrial stromal precursor cells, rather than leiomyomas
• Like leiomyomas, a subset contains MED12 mutations, a genetic aberration that appears to be virtually unique to uterine smooth muscle tumors
• Leiomyosarcomas grow within the uterus in two somewhat distinctive patterns:
  1. bulky, fleshy masses that invade the uterine wall or
  2. polypoid masses that project into the uterine lumen
• Tumorus often recur post surgery, 50% eventually metastasize haematogenously and throughout the abdominal cavity
  *

Question 68

Polycystic ovarian syndrome (PCOS)

Answer 68

Rotterdam criteria (2003)
2 out of 3 of the following are required to make the diagnosis:
* Oligo- and/or anovulation (↑ LH:FSH ratio > 2)
* Clinical and/or biochemical signs of hyperandrogenism
* Polycystic ovaries (by ultrasound)
* Other aetiologies (congenital adrenal hyperplasias, androgen-secreting tumors, Cushing’s syndrome) must be excluded.

Ultrasound criteria: by TV US
* ≥ 12 follicles in each ovary measuring 2-9 mm in diameter, &/or
* Ovarian volume >10 mL
* One ovary fitting this definition is sufficient to define PCOS
* [Follicle distribution & ↑ stromal echogenicity and volume eliminated]

Endometrial thickening due to prolonged proliferative phase or hyperplasia → increased free oestrogen levels, increased risk of endometrial cancer
* Stromal hyperthecosis, also called cortical stromal hyperplasia, is a disorder of ovarian stroma most often seen in postmenopausal women, but it may overlap with PCOS in younger women.
* The disorder is characterized by uniform enlargement of the ovary (up to 7 cm)