Gynecological oncology Flashcards
What is the histology of partial mole vs complete mole?
Partial mole
* Presence of fetal tissue (gestational sac/fetal parts)
* Trophoblastic proliferation
* Focal vesicular swelling of placental villi
Complete mole
* Absence of fetal tissue
* Excess trophoblsatic proliferation
* Extensive vesicular swelling of placental villi
- Ploidy status
- IHC staining for p57
What is the follow up for GTD after surgical evacuation?
Weekly BhCG until normalized than monthly
Partial mole: single additional confirmatory normal BhCG measurement 1 month after 1st hCG normalization is recommended.
Complete mole: monthly hCG measureemnts should be obtained for only 6 months after hCG normalization
Advise not to concieve until completion of follow up.
What is the classification of endometrial hyperplasia?
Hyperplasia with atypica (non neoplastic)
Atypical hyperplasia (endometrial intraepithelial neoplasm)
Define endometrial hyperplasia
Proliferaetion of endometrial glands or irregular size and shape with an increase in endometrial gland: stroma ratio >50% compared with normal proliferative enometrium
Frequently results from chronic unopposed estrogen stimulation without the counterbalancing effects of progesterone
What are the RF for endometrial hyperplasia?
What are the Ix done for endometrial hyperplasia?
What is the treatment of endometrial hyperplasia without atypia vs endometrial hyperplasia with atypia?
What is the FU for patients with endometrial hyperplasia?
What is the medical treatment for endometrial hyperplasia?
Only for endometrial hyperplasia without atypia
What is surgical treatment for endometrial hyperplasia and who is indicated?
What is the management algorithm for endometrial hyperplasiia?
What is the type and grading of endometrial cancer?
What is mode of spread?
What are protective factors for endometrial cancer?
- Pregnancy
- Oral contraceptives: progestin component of oral contraceptives suppress endometrial proliferation. Progestin only contraceptives is used for treatment of endometrial hyperplasia. Endometrium does not proliferate uncontrollably due to regular menstrual cycles and less chance of metaplasia and hyperplasia
- Physical activity: decrease obesity and central adiposity
What SS and PE for endometrial cancer?
What basic Ix and procedural Ix done for endometrial cancer?
What imaging Ix done for endometrial cancer?
What is FIGO staging of carcinoma of corpus?
What is post treatment FU for CA endometrium?
What is surgical treatment for endometrial carcinoma?
What is management algorithm for patients with endometrial carcinoma at different stages?
What are the different types of ovarian epithelial malignancy?
What are non epithelial ovarian malignancy?
What is the source of metastasis for ovarian cancer?
What are the types of ovarian sex cord stromal tumors (1% of ovarian cancer)?
What are the types of ovarian germ cell tumors?
What is the most common ovarian germ cel tumor?
What is it composed of?
Teratoma: develops from totipotent germ cells (primary oocyte) of ovary and therefore can give rise to all kinds of cells and tissues
Ectoderm = skin/sebaceous gland/hair follicles
Mesoderm = muscle/urinary
Endoderm = lung/ GI
What is mature teratoma and its complications?
What is USG appearance?
Majority of teratoma are cystic and composed of mature well differentiated elements which are better known as dermoid cysts
Complications
* Torsion of the dermoid cyst
* Rupture of the dermoid cyst
* Malignant transformation into SCC
USG appearance: heterogenous echogenic. Presence of hyperechoic nodule within the mass with distal acoustic shadowing: strong indicator of teratoma, signifies the presence of bone or tooth
What is mx of mature teratoma?
Cystectomy is preferred via laparoscopy or laparotomy: make a definitive dx, preserve ovarian tissues. Avoid complications such as torsion, rupture and malignant transformation
What is the grading of immature teratoma?
What is Mx?
Immature teratoma are solid and composed of immature undifferentiated elements
Histologically graded from grade 1 (well differentiated) to grade 3 (poorly differentiated) based upon proportion of tissue containing immature neural elements.
Mx
* Usually surgery followed by chemo
* Unilaterael oophorectomy is adequate provided the other ovary is not affected
* TAHBSO is suggested if patient has completed family
What is dysgerminoma?
Clinical manifestation?
Dx?
Mx?
Female version of male seminoma –> comprised of immature germ cells.
Most common malignant germ cell tumor of the ovary.
Clinical manifestation: torsion due to presence of a long ovarian pedicle. Rupture with haemoperitoneum
Dx: contains syncytiotrophoblastic giant cells that produce placental ALP and LDH
Mx: surgery followed by chemo
Unilateral salpoingooophorectomy (USO) is usually curative an the contralateral ovary and uterus can be preserved for fertiity.
What are the biochemical tests done for ovarian tumor?
What is the radiological ix done for ovarian tumor?
What is FIGO staging for carcinoma of ovary?
What is the post treatment FU for CA ovary?
What is medical treatment for CA ovary?
What is surgical treatment for ovarian tumor?
What is Mx of early stage CA ovary?
What is management of advanced stage CA ovary?
What is Mx of recurrent CA ovary?
What is Mx of germ cell tumor?
What is Mx of sex cord tumor?
What is the prognostic factor for ovarian cancer?
What are the complications of ovarian cancer?
What are the 2 main types of cervical cancer?
What are the routes of metastasis?
What are the high and low risk HPV genotypes?
High risk HPV: 16, 18
Low risk HPV (non oncogenic –> LSIL/anogenital warts): 6, 11
What is the junction and zone at t the cervix?
Squamocolumnar junction (SCJ): ectocervix is the surface of the cervix that protrudes into the vagina and is covered with stratified squamous epithelium. Endocervix is the cervical canal which is lined with columnar epithelium.
Transformation zone: during reproductive age the cervix is under the influence of estrogen, it tends to evert leading to exposure of columnar epithelium on ectocervix.
* After exposure to estrogen, the glycogen from exfoliated vaginal cells is converted into lactic acid
* Acidity stimulates the columnar epithelium to be replaced by squamous epithelium (metaplasia)
Transformation zone contains embyronic cells that may be especially vulnerable to infection with HPV and to oncogenic transformation
What are the 4 steps in cervical cancer development?
Expression of HPV oncogene E6 and E7 are commonly detected in cervical cancer
What is the histological grading of cervical cancer?
What is SS of cervical cancer?
Presentation of advanced disease
What is the decision flowchart for cervical screening?
Who is not recommeded cervical screening?
- Women who never had sex before
- Hysterectomy with removal of cervix
- Pregnancy to avoid inducing bleeding and anxiety
When is 1st pap smear done?
- 1st pap smear screening starting at age 25 (1,1,3 yearly cycle).
- 2nd pap smear 12 months later if result is normal
- Repeat smear at least every 3 years if result is normal
Rationale behind 1,1,3 yearly cycle: abnormal cervical cells usually take around 5-10 years to develop into cancer. Screening at 3 year interval is frequent enough to pick up changes
What are the different types of pap smear?
What are contraindications of pap smear?
- Cervix cannot be seen
- Blood in vagina or cervix during menstruation
- Obvious or gross growth on cervix
What is a unsatisfactory pap smear?
- Scanty cells
- Marked inflammation (increased PMNs)
- Heavily blood stained (increased clotted blood)
- Artefacts (air dried or too thick)
How to interpret the results of pap smear?
What is FU for pap smear biopsy confirmed normal?
o Repeat smear every 6 months
o Return to normal screening if normal x2
o Refer colposcopy again if ASCUS/ LSIL x2 or more severe abnormalities
What is FU for pap smear biopsy confirmed CIN1/HPV?
o Repeat smear every 6 months
o Return to normal screening if normal x3
o Continue screening for at least 3 times even if women reaches age of 65
o Refer colposcopy again at 24 months if ASCUS/ LSIL persists
o Alternatively: FU at 12 months with smear and HPV testing: If both negative, then repeat at 24 months before return to routine screening; If either one positive during the 24-month period, refer to colposcopy
What is FU for pap smear biopsy CIN2 and CIN3?
o Repeat smear x3 every 6 months, then
o Repeat smear every 1 year for 10 years, then
o Return to normal 3-yearly screening
o If ASCUS/ LSIL within 12 months, then follow up with smear o If low-grade smear persists > 1 year then refer colposcopy
What is FU for pap smear biopsy post hysterectomy for CIN with clear margin?
o Repeat vaginal cytology at 6 and 18 months
o If both normal, no further cytology needed
What is FU for pap smear biopsy post hysterectomy for CIN with incomplete clearance or uncertain margin?
o Repeat vaginal cytology at 6 and 12 months, then
o Repeat vaginal cytology every 1 year for 10 years, then
o Life-long vaginal cytology every 3 years
What is the triage for atypical squamous cells of undeteremind sequence (ASC-US) on pap smear?
What is the PE for cervical cancer?
What are the indications for colposcopy in suspected cervical cancer?
How is colposcopy done and cervical biopsy achieved?
What treatments are available for precancerous cervical lesions?
Indications for large loop excision of transformation zone (LLETZ)?
Complications?
Staging for cervical cancer?
Treatment for CA cervix according to staging
What is post treatment FU for CA cervix?
What is medical treatment for CA cervix>
What is surgical treatment for CA cervix?
What HPV vaccination available
What histology of vaginal cancer?
Is primary vaginal cancer common?
Majority is SCC. Less is adenocarcinoma, sarcoma, primary malignant melanoma
Primary vaginal cancer is rare whereas metastastic disease to vagina or local extension from adjacent gynecological structures are more common
What is the site of distribution of vaginal cancer?
Posterior wall of the upper 1/3 of vagina is the most common site of primary CA
Distribution of primary cancer: upper 1/3 =50%, middle 1/3 =20%, lower 1/3 =30% which has a much poorer prognosis partly because lymphatic spread to inguinal LNs is quicker and chance of bladder involvement
What is the mode of spread of vaginal cancer?
- Direct extension to pelvic soft tissue structure: parametrium, bladder, urethra, rectum, bony pelvis
- Lymphatic spread: upper 2/3 drains into pelvic LNs and into paraaortic LNs. Lower 1/3 = drains into inguinal and femoral LNs and into pelvic LNs
- Haematogenous spread: lungs, liver, bone
What are the SS of vaginal cancer?
What are the SS of local extension?
What is the PE, Ix and imaging done for suspected vaginal cancer?
What is the staging for vaginal cancer?
What is the Mx algorithm of vaginal cancer?
What are the types of vulval cancer?
What is the site of distribution?
What is the mode of spread?
What are the RF for vulval cancer?
What are the SS of vulval cancer?
What are symptoms of local extension?
What to observe for in PE of suspected vulval cancer?
What Ix and imaging done?
What is the staging of vulval cancer?
What is the Mx of stage 1/2 CA vulva?
What is the Mx of stage 3/4 CA vulva?
What is hydatidiform mole?
Is there malignant potential?
Mole/molar pregnancy (growth of growing tissues)
Originates in the placenta and has the potential to locally invade uterus and metastasize. Considered benign but premalignant since it can develop into gestational trophoblastic neoplasia
Define gestational trophoblastic disease
Lesions characterized by abnormal proliferation of trophoblast of the placenta
Comprises of benign non neoplastic lesions including hydatidiform mole, placental site nodule or exaggerated placental site
Define gestational trophoblastic neoplasia
- Group of malignant neoplasms that consist of abnormal proliferation of trophoblastic tissues which arises from molar pregnancy (hydatidiform mole) or a non molar pregnancy
- Molar pregnancy =50%: GTN that develops from molar pregnancy is usually invasive mole or choriocarcinoma, or rarely PSTT or ETT
- Non molar pregnancy: miscarriage/tubal pregnancy = 25%, term or preterm pregnancy =25%.
In the absence of tissue for definitive histopathologic dx, disease is diagnosed as a result of persistent elevation of hCG after evacuation of a molar pregnancy
* Invasive mole
* Choriocaricnoma
* Placental site trophoblastic tumor (PSTT)
* Epitheloid trophoblastic tumor (ETT)
What is the pathogenesis of mole (GTD)?
Hydatidiform mole occurs after aberrant fertilization but not after non molar pregnancy: non molar pregnancy includes preterm or term delivery, spontaneous or induced abortion and ectopic pregnancy.
Originates in villous trophoblast and characterized by abnormal chorionic villi with trophoblast hyperplasia as a consequence of overexpression of paternal genes.
What is a complete mole vs partial?
Karyotype
Fetal/embyronic tissues
hCG level
IHC
How do patients with hydatidiform mole normally present?
- Typically presents to clinics with missed menstrual periods, positive pregnancy test and signs and symptoms consistent with early pregnancy complications
- Usually presents between 8-24 weeks of gestation with peak at 14 weeks
What are common and early SS of hydatidiform mole?
What are less common and late SS of hydatidiform mole?
How is the dx of a hydatidiform mole done?
- Molar pregnancy is suspected based upon unusualy high hCG levels or only after pathology evaluation of a failed pregnancy
- Clinical presentation in early stages are early pregnancy complications and therefore clinicians will suspect more common pregnancy complications or an abnormal non molar pregnancy rather than molar pregnancy
- Partial mole is often misdiagnosed as incomplete or silent miscarriage and correct dx is made only after pathology review
What is history taking and PE done for molar pregnancy?
What are the biochemical tests done for molar pregnancy and why?
What is the main imaging done for suspected molar pregnancy?
- Transvaginal USG pelvis
- If the initial hCG level is high <100,000 mIU/mL, transvaginal ultrasound should be done
- If USG shows normal singleton gestation, hCG and USG should be repeated in 1 week to exclude possibility of twin conception with normal fetus and co-existent molar pregnancy
What are transvaginal USG features of complete mole?
What are transvaginal USG features of partial mole?
What medical treatment is contraindicated in molar pregnancy?
Use of uterotonics (misoprostol, mifepristone, oxytocin) to induce uterine contractions is contraindicated since it will increase the risk of trophoblastic embolization to the lungs
Obtaining a complete specimen for histological dx of hydatidiform mole is also more difficult with medication only evacuation
What must you counsel the patient on during molar pregnancy?
Must be advise to use reliable contraception during the entire interval of hCG monitoring
New pregnancy during this period will make it difficult or impossible to interpret hCG results and would complicate management
Contraception should be practised for at least 1 year after hCG has returned to normal before trying to get pregnancy again.
Patients usually enjoy normal reproductive function after treatment
What is the follow up for molar pregnancy?
- Serial monitoring of serum B-hCG until undetectable level is reaeched and is maintained for several months
- Regular monitoring to detect relapse which usually occurs within the 1st 12 months
Surveillance protocol
* Every month until non detectable for 3 weeks, then
* Every month for 6 months for partial mole
* Every month for 12 months for complete mole
Is medical treatment 1st line for molar pregnancy?
WHat are the indications for medical treatment?
No, surgery is 1st line
Prophylactic chemotherapy indicated in high risk patients after suction evacuation to decrease the risk of subsequent progression and risk of GTN
High risk features include
* Pre evacuation uterine size larger than dates
* hCG levels >100,000mIU/mL
* Bilateral ovarian enlargement due to theca lutein cysts
What is the surgical treatment for molar pregnancy?
What are the indications?
What is invasive mole derived from?
Is it common to metastasize?
How is it mx?
Presence of edematous chorionic villi with trphoblastic proliferation invading the myometrium. Always preceded by hydatidiform mole (molar pregnancy)
15% remains localized to uterus, and 5% are metastasis (metastasis to lung and vagina common, but liver and CNS system can also happen)
* Deep myometrial invasion can occur (less readily removed by suction evacuation).
* Uncontrolled intraperitoneal hemorrhage and utereine perforation (rupture) can occur if deep myometrial invasion is left untreated
Dx confirmed by histological exam of uterus after hysterectomy which is rarely performed unless there is uncontrolled bleeding or perforation
Usually managed as residual trophoblastic disease with chemotherapy
What is choriocarcinoma derived from?
Is it aggressive? Where will metastasis be?
Invasive, highly vascular and anaplastic trophoblastic tissue made up of cytotrophoblasts and syncytiotrophoblasts without villi
Arises from products of gestation or ovaries (germ cell tumor)
* Molar pregnancy: choriocarcinoma is more common after a complete mole rather than a partial mole
* Non molar pregnancy: chorciocaricnoma is the most common type of GTN following non molar pregnancy
* PSTT (placental site trophoblastic tumor) or epitheloid trophoblastic tumor (ETT) only makes up only 1-2% of GTN
Most aggresssive histologic type of GTN and is highly malignant and characterized by vascular invasion and widespread metastasis.
* Dx is often delayed following a non molar pregnancy and thus metastases are more common than after a molar pregnancy.
* Highly malignant with invasion and necrosis of uterine wall
* Most common sites of metastasis is lung
What is placental site trophoblastic tumor (PSTT) derived from?
Is it aggressive?
- Develop from extravillous, intermediate trophoblast
- Arises most commonly after non molar pregnancy or miscarriage although it can also occur after a molear pregnancy
- Secretes low levels of hCG (in comparison to invasive mole and choriocarcinoma)
- Associated with less vascular invasion, necrosis and hemorrhage than choriocarcinoma
- Tends to remain localized in uterus for long periods before metastasizing to regional LNs and other metastastic sites
What is placental site trophoblastic tumor (PSTT) derived from?
Is it aggressive?
- Develops from neoplastic transformation of chorionic type extravillous trophoblast
- Dx is typically late due to slow growth, paucity of symptoms and low/absent hCG production
- 50% patients present with metastatic disease
What are the SS of gestational trophoblastic neoplasia?
When to suspect GTN from molar pregnancy?
- Serial measurement of hCG is part of the post-treatment surveillance
o Elevation, plateau or persistence (remains elevated) of hCG level that does not return to undetectable level suggests development of GTN
When to suspect GTN from non-molar pregnancy?
What are the biochemical tests for gestational trophoblastic neoplasia (GTN) and why are they done?
When should serum quantitative hCG should be drawn in patients with suspected GTN?
o Previous molar pregnancy
o Previous non-molar pregnancy
o Any women of reproductive age with metastatic symptoms without an obvious primary site of malignancy
How may serum hCG levels vary across histological types of GTN?
o High levels = Invasive mole and choriocarcinoma
o Low levels = PSTT and ETT
What is the diagnostic criteria for GTN by FIGO?
If there is persistent low hCG following molar evacuation (quiescent GTN) what does this mean and what should you suspect?
What are the imaging done for GTN?
What is the FIGO staging for GTN?
- Stage I = Disease confined to the uterus
- Stage II = GTN extends outside of uterus to the adnexa or to the vagina but is limited to genital structures
- Stage III = GTN extend to the lungs, with or without uterine, pelvic or vaginal involvement
- Stage IV = Metastatic disease outside of the lungs, pelvis and vagina
What is the modified WHO prognostic scoring system for gestational trophoblastic neoplasm?
What is treatment for gestational trophoblastic neoplasia acoring to stage and risk category?
What is the maximum number of LEEPs that can be done for HSIL?
3 LEEPs is max for HSIL (preferred over ablative therapy (as no histology obtained): includes electrocoagulative diathery, laser vaporization, cryosurgery (cold probe to freeze away abnormal cells)
Any more than 3 –> suspect its carcinoma and opt for hysterectomy
If cervical cancer is seen with naked eye, what stage is it at least?
At least 1b
If CIN3 found in cervical smear, how to decide during colposcopy whether to do LEEP or cold knife colonization (CKC)?
- LEEP associated with lower incidence of cervical incontinence. An obstretics complication causing preterm, hence if there is fertility desire may do LEEP instead of CKC.
- LEEP is also an office procedure (look and deal with) in comparison to CKC which requires RA/GA
What are the indications of colposcopy?
- ASCUS x2
- ASCUS with high risk HPV
- LSIL or above
- AGC-NOS or above