Gestational Trophoblastic Disease (GTD) - Past Lecture Notes (OB)

**OUTLINE** I. **Gestational Trophoblastic Tumors (GTT)** II. **Benign Gestational Trophoblastic Tumors** III. **Malignant Gestational Trophoblastic Tumors** IV. **Summary** V. **Reference** VI. **Appendix** +-----------------------+-----------------------+-----------------------+ | **LEGEN...

**OUTLINE** I. **Gestational Trophoblastic Tumors (GTT)** II. **Benign Gestational Trophoblastic Tumors** III. **Malignant Gestational Trophoblastic Tumors** IV. **Summary** V. **Reference** VI. **Appendix** +-----------------------+-----------------------+-----------------------+ | **LEGEND** | | | +=======================+=======================+=======================+ | ⭐ | 🖊️ | 📖 | | | | | | Must | Lecture | Book | | | | | | Know | *\[lec\]* | *\[bk\]* | +-----------------------+-----------------------+-----------------------+ GESTATIONAL TROPHOBLASTIC TUMORS (GTT) {#gestational-trophoblastic-tumors-gtt.TransOutline} ====================================== - ⭐General term for proliferative abnormalities for the trophoblast - What is the serum marker for pregnancy? - Beta-hCG - analogous to the alpha subunit of hCG - similar to the other hormones which are LH, FSH, and TSH - explains some of the effects of GTN and molar pregnancies including the theca lutein cysts from thyroid storm - Things that are important for us to know regarding GTN and molar pregnancy: mnemonic: "RCS" - **R**ECOGNIZE disease - Effective **C**HEMO - **S**TATUS surveillance with Beta-hCG - Gestational trophoblastic disease (GTD) - a heterogenous spectrum of disease of abnormal trophoblastic proliferation ranging from benign to malignant, with varying predilections toward local invasion to distant metastasis - most curable of all gynecologic malignancies - GTN is diagnosed based on clinical, laboratory, and histologic criteria; and those tumors have a tendency to invade and metastasize. TYPES OF GTT {#types-of-gtt.TransSubtopic1} ------------ - **BENIGN** - hydatidiform mole/molar pregnancy (complete or incomplete) - complete mole - no embryo - incomplete - with embryo and with the dilated trophoblasts - **MALIGNANT** - invasive mole - Choriocarcinoma (chorioepithelioma) - Placental site trophoblastic tumor - Least common and more dangerous BENIGN GTT {#benign-gtt.TransOutline} ========== HYDATIDIFORM MOLES {#hydatidiform-moles.TransSubtopic1} ------------------ - characterized by the presence of **avascular cystic villi** - 89.6% of all trophoblastic disease; the majority of trophoblastic diseases - abnormal pregnancies characterized histologically by: - trophoblastic proliferation (both syncytiotrophoblast & cytotrophoblast) - edema of the villous stroma (hydropic) - based on the degree and extent of these tissue changes, they are characterized as either: - **Complete** -- complete absence of normal villi - **Partial** -- presence of some normal villi with anucleated RBCs EPIDEMIOLOGY AND ETIOLOGY {#epidemiology-and-etiology.TransSub-subtopic2} ------------------------- - European incidence - 1/2500 pregnancies - Asia: 1/250, more common - Philippines: 1/14 pregnancies accdg to POGS - Risk factors: - ⭐ Multiparity - ⭐Previous molar pregnancy (\>10-40 times) - Maternal age \45 y/o - N \< B race (50%) - Advanced paternal age - ⭐Smoking, oral contraceptives - Maternal blood group A - Malnutrition and vitamin deficiency *-- in 3^rd^ world countries* PATHOGENESIS {#pathogenesis.TransSub-subtopic2} ------------ - Abnormal growth of the zygote under paternal nucleus (spermatozoan), while maternal nucleus (oocyte) is absent or inactivated. - This leads to an anomalous growth of trophoblast that maintains the ability to infiltrate the decidua and the endocrine properties (B-hCG) - *Tumataas pathologically yung B-hCG* - *spermatozoa play an important role* DIFFERENTIAL DIAGNOSIS {#differential-diagnosis.TransSub-subtopic2} ---------------------- - Abortion - Multiple pregnancy - *because usually yung GTD, the uterus is greater than what is expected in normal pregnancy.* - Polyhydramnios - Fibroid of ovarian tumor with pregnancy - The reason being, this pertains to the type of mole with complete mole. The uterus is a bit larger compared to the AOG (multiple pregnancies, polyhydramnios, fibroid) COMPLICATIONS {#complications.TransSub-subtopic2} ------------- - **[IMMEDIATE]** - hemorrhage and shock - bleeding is common - sepsis - perforation of uterus - pre-eclampsia - *d/t high b-hCG levels* - acute pulmonary insufficiency - for those with lung metastasis - coagulation failure - **[LATE]** - Choriocarcinoma -- following H mole ranges between 2-10% GENETICS {#genetics.TransSub-subtopic2} -------- #### COMPLETE MOLE {#complete-mole.TransSub-subtopic3} - ⭐Paternal component only - Silent oocyte - fertilization of "empty egg" by single sperm (23X) duplicated to diploid (46XX) - *instances where yung pregnancy, the oocyte is fertilized by 2 spermatozoa so 46 XX pa siya* - Usually diploid (85% of cases) - Risk of malignancy is high (15-25%) ***Figure 1**. Schematic diagram of a complete and partial mole (A -- complete mole; B -- partial mole)* #### PARTIAL MOLE {#partial-mole.TransSub-subtopic3} - ⭐Paternal and maternal components kasi may embryo ka nga - 2 haploid sperm fertilizes haploid egg - Karyotype: 69XXX or 69XXY usually triploid (85% of cases) - Risk of malignancy is low (5-15%), but the incidence is lower - Rare cases: (+) non-viable fetus with multiple congenital defects PATHOLOGY {#pathology.TransSub-subtopic2} --------- #### COMPLETE MOLE {#complete-mole-1.TransSub-subtopic3} - ⭐ Gross cysts **"bunch of grapes"** appearance ***Figure 2.** Gross picture of a complete mole ("bunch of grapes")* #### PARTIAL MOLE {#partial-mole-1.TransSub-subtopic3} - Ultrasound - One way of diagnosis of partial and complete mole ***Figure 3.** UTZ "white spots" represents crushed parts of the embryo* - Gross: fetal parts present ***Figure 4.** Gross picture of a partial mole with a placenta and fetus* HISTOLOGY {#histology.TransSub-subtopic2} --------- - Normal pregnancy *ng trophoblasts* ***Figure 5.** Histology of a normal pregnancy* #### COMPLETE MOLE {#complete-mole-2.TransSub-subtopic3} - (-) fetus or villi present - (-) blood vessels in villi - Trophoblastic proliferation - Marked villous hydrops A purple and white cell Description automatically generated with medium confidence ***Figure 6.** Histology of a complete mole* #### PARTIAL MOLE {#partial-mole-2.TransSub-subtopic3} - (+) fetus and some normal villia - (+) blood vessels and RBCs - Focal villous hydrops - *Hindi siya masyadong hydrophic* ***Figure 7.** Histology of a partial mole* {#section.TransSub-subtopic2} ⭐THECA LUTEIN CYSTS {#theca-lutein-cysts.TransSub-subtopic2} ------------------- - presence is established by palpation and often confirmed by ultrasound - The condition of ovarian enlargement secondary to the development of multiple luteinized follicular cysts is termed ***hyperreaction luteinalis*** - Cause: **overstimulation of theca cells by high B-hCG levels** - vary in size - from being a few centimeters to as big as 20-30 cm and it can be bilateral - almost always bilateral and produce moderate to massive enlargement of the ovaries - more common in complete moles - may manifest as adnexal masses - **Gross:** External lining is smooth, glistening and yellowish in color - usually regress after treatment - No active management unless complications occur (torsion, infection, or hemorrhage) - ⭐progresses usually after treatment and there is no active treatment unless there are complications - cysts are also discovered in the latter months of pregnancies, often with conditions that produce a large placenta, such as twins, diabetes, and Rh sensitizations ***Figure 8.** UTZ of theca lutein cyst. If you notice the gradation on the lef, 1 solid bar is 1 cm. Mga 6 cm ang size.* ***Figure 9**. Gross picture of theca lutein cyst.* *It's even bigger than the uterus and it can be bilateral. Makikita mo na malalaking left and right structures lateral to your uterus will be your ovaries and corpus luteum cyst. We are assuming that when we cut this, we will see multiple grape-like vesicles and on the bilateral adnexa we see theca lutein cysts.* CLINICAL CHARACTERISTICS {#clinical-characteristics.TransSub-subtopic2} ------------------------ #### COMPLETE MOLE {#complete-mole-3.TransSub-subtopic3} - Clinical presentation - **1^st^ or 2^nd^ trimester** - ☤ Usually we detect it earlier because the patient bleeds earlier - Large for date uterus (50% of cases) - Contents expelled earlier (10-16 weeks) - ☤ Minsan nag papass out ng sago like material yung patient. - Early onset of Pre-eclampsia - ☤ So if pre-eclampsia occurs before 20 weeks, we think of H. mole - B-HCG is higher than partial mole - UTZ: No fetal parts - Increased risk of Choriocarcinoma #### PARTIAL MOLE {#partial-mole-3.TransSub-subtopic3} - Clinical presentation: **2^nd^ Trimester** - Normal or small for date uterus - Contents are expelled later (10-26 weeks) - Normal sxs for pregnancy - B-HcG titer is lower than complete mole - UTZ: (+) fetal components - Lower risk of Choriocarcinoma {#section-1.TransSub-subtopic2} METASTASIS {#metastasis.TransSub-subtopic2} ---------- - Common sites for the malignant variant - **Lungs** - **Liver** - **Brain** - ☤ These are very highly vascular tissues. as with other malignancies ito rin naman yung more common sites of metastasis  Figure 10. Gross picture of liver metastasis. Figure 11. Gross picture of brain metastasis. COMMON COMPLAINTS {#common-complaints.TransSub-subtopic2} ----------------- - **★ Vaginal bleeding - 86%** - Hypogastric pain - 14.2% - ✐ Most likely due to the contraction of the uterus because the uterus is trying to expel the products of conception. - Amenorrhea - 8.5% - ✐ A complaint or concern because when you get pregnant you experience amenorrhea. - Enlargement of abdomen - 3.9% - ✐ Common especially for those who are not aware that they are pregnant. - Others: - No FHT by Doppler after 12 weeks - ✐ Then after 12 weeks we check for viability of pregnancy and rule out H. mole - Hyperemesis gravidarum - Sxs of pre-eclampsia - ✐ Below 20 weeks - Sxs of hyperthyroidism - Lung, Liver, Brain involvement ☤ For malignant lesions - ✐ For stage 3 and 4 disease DIAGNOSIS {#diagnosis.TransSub-subtopic2} --------- - ★ Clinical symptoms - 🕮 When uterine enlargement is more than 14 to 16 weeks, 25% of patients will have medical complications related to the high levels of β-hCG commonly seen in CHM and proportional to the volume of trophoblastic hyperplasia. - ★ UTZ: "Snowstorm appearance" - ✐ There is a snow-storm appearance for our complete mole. And for our incomplete mole, aside from the snow-storm appearance of the placenta, you have your embryo or fetus. - ✐ A transvaginal US may show the interface between molar tissue, endometrium, and dilated vesicles in the first trimester better, but it can worsen vaginal bleeding in the setting of metastatic disease to the vagina. +-----------------------------------+-----------------------------------+ | **Table 1. Features suggestive of | | | CHM and PHM on UTZ** | | +===================================+===================================+ | **Complete H. mole** | **Partial H. mole** | +-----------------------------------+-----------------------------------+ | Absence of fetal or | Presence of fetal or | | | | | embryonic tissue | embryonic tissue | | | | | Absence of amniotic Fluid | Presence of amniotic fluid | | | | | Enlarged placenta with | Abnormal placenta with | | | | | multiple cysts | multiple cysts or increased | | | | | Ovarian theca lutein cysts | echogenicity of chorionic villi | | | | | | Increased transverse | | | | | | diameter of gestational sac | | | | | | Absence of theca lutein cysts | +-----------------------------------+-----------------------------------+  Figure 12. UTZ snowstorm or honeycomb pattern of H. mole ✐ So, this is an ultrasound picture of a uterus and within the uterus are multiple vesicles. That is the snowstorm or honeycomb appearance of the uterine contents which is pathognomonic of complete H. mole. - ★ B-HCG Titers: \>100,000 IU/I on 100th day from LMP - \*Normal pregnancy -\> HCG goes down on the 60^th^ -70^th^ day from LMP - ✐ An unexpectedly elevated β-hCG level during pregnancy may suggest the diagnosis of CHM. - 🕮 β-hCG typically plateaus in pregnancy at approximately 10 weeks' gestation, with levels peaking at 100,000 IU/L and then falling thereafter - 🕮 Outside of pregnancy, B-HCG signifies the following: - GTN, - Non-gestational tumors secreting hCG - False positives - Menopause (secondary to LH elevation and cross reactivity of assays). - ✐ We put everything together from history, physical exam and diagnostic modalities to come up with a diagnosis of H. mole Figure 13. Chart of B-HCG levels - ☤ As you can see pag molar pregnancy it's way higher than the normal range - ✐ Basically, eto lang yung representation nung levels ng β-hCG ng normal preggy at ng may trophoblastic disease. Mag peak ang β-hCG at \>100,000 daw at 100th day (\~3months) pag meron ka nung disease. Not sure sa values but definitely lower sa trophoblastic disease at 10weeks (\~2months) yung peak ng normal preggy then magdecline na yung levels at the 60th-70th day (\~2months) \*\*Note lang na yung nasa figure is at thousands of IU/L kaya you might think na mababa yung values sa picture OTHER TESTS {#other-tests.TransSub-subtopic2} ----------- - ☤ For patients with partial mole na we are entertaining metastasis - CXR - R/O Lung metastasis - ★ "Cannon-ball" exudates  Figure 14. CXR with "cannonball" exudates. - SGPT/SGOT - R/O liver metastasis - Baseline liver function prior to chemotherapy - BUN/ Creatinine - Baseline kidney function prior to chemotherapy - CBC with platelet count - ✐ We check the hemoglobin and hematocrit because of the bleeding - ✐ Pregnancy Test - May result to false negative with higher levels of B-hCG due to prozone or hook effect - Prozone/hook effect -- zone of relatively high antibody concentration within which no reaction occurs - Sa sobrang taas ng B-hCG levels, na-reach na niya yung upper limit ng mga pregnancy tests kaya nag false negative na siya. - What do you need to do? Dilute the urine wit saline solution and after that kung magpositive na siya, ibig sabihin it's super high. - Minimum level of hCG detected in pregnancy test = 25 mIU/mL - ✐ Blood typing with Rh factor - RhD is expressed on trophoblasts - Patients who are Rh- with and Rh+ or Rh unknown partner should be treated with Rho(D) immune globulin post evacuation - ✐ Thyroid function tests - ✐ Urinalysis - ✐ Histopathology - Gold standard - Immunostaining -- p57kip2 (a paternally imprinted, maternally expressed gene) - Negative: CHM - Positive: PHM - Sa immunostaining, yung maternal gene yung nadedetect kaya nagpopositive for partial H. mole - ✐ Cytogenetic and molecular biologic examinations - When the diagnosis is in doubt DIFFERENTIAL DIAGNOSES {#differential-diagnoses.TransSub-subtopic2} ---------------------- - Mutliple pregnancy - Polyhydramnios - ✐ Large for gestational age - ✐ Normal AFI= 5-24 cm - ✐ For differential diagnosis, as we said earlier because the uterus is larger than age of gestation, multiple gestation is a consideration as well as polyhydramnios since polyhydramnios may cause enlargement of the uterus way larger than the age of gestation - Placenta previa - ✐ For bleeding and pain - ☤ For bleeding - Abruptio Placenta - ✐ For bleeding and pain - Threatened abortion - ✐ For bleeding and pain - ✐ Of course, since she is pregnant, especially for the compete mole which bleeds earlier as opposed to the incomplete/partial mole, threatened abortion is always a differential diagnosis TREATMENT {#treatment.TransSub-subtopic2} --------- - Termination of molar pregnancy - ✐ The cervix is serially dilated and then a large suction curette is advanced just past the endocervix into the endometrial canal. - ✐ For complete mole wala sya embryo so there are no ethical issues. But for incomplete/partial mole there is an embryo or fetus so there is an ethical issue - ★ Evacuation by suction curettage - IV oxytocin given - ☤ To make the uterus contract, to help expel the H. mole as well as make the uterus contract to avoid perforation - Low incidence of uterine perforation and embolization - ✐ One of the complications is uterine perforation and the reason is iatrogenic. Because the uterus is soft and if we do suction curettage - Fertility is preserved. - ✐ Advantage of suction curettage. If the patient is still highly desire of pregnancy, then this is the option. - ★ Hysterectomy with mole in situ - Preferred for pxs with completed family size or those \>40 years old due to increased incidence of Choriocarcinoma after molar pregnancy. - ✐ We have to advice the patient properly and counsel them well. There are a lot of complication when there is advancing maternal age. When we talk about H. mole there is an increasing incidence of molar pregnancy, to take away that risk we offer the patient hysterectomy. - Replacement of blood loss. ☤ Since the patient may bleed profusely, we replace the blood loss. - Treatment of infection if present. ☤ As you know blood is a good medium for infection so the risk for it is high for patients with H. Mole. - Prophylactic chemotherapy - Can be given before or after evacuation or hysterectomy. - Methotrexate - Actinomycin #### METHOTREXATE TREATMENT {#methotrexate-treatment.TransSub-subtopic3} - 5 Day MTX protocol - 0.4mg/kg IV or IM daily x 5 days - CBC, platelet count daily - (+) response: retreat at the same dose - (-) response: increase dose to 0.6mg/kg - OR switch to Actinomycin D - Pulse MTX: 40 mg/m2 IM weekly - MTX with folinic Acid Rescue - Day 1, 3, 5, 7: MTX 1.0 mg/kg/day IM or IV - Day 2, 4, 6, 8: Folinic 0.1 mg/kg/day #### ACTINOMYCIN D {#actinomycin-d.TransSub-subtopic3} - 5 Day Actinomycin D: - 12ug/kg IV daily x 5 days - CBC, platelet count, SGOT daily - (+) response: retreat at the same dose - (-) response: add 2 ug/kg to the initial dose or switch to MTX - Pulse Actinomycin D: 1.25 mg/m2 q 2 weeks FOLLOW-UP {#follow-up.TransSub-subtopic2} --------- - ★ Beta-HCG titers q weekly until negative (less than 5 mIu/ml) ☤ Pre-pregnancy state for 3 consecutive determinations then q 1-3 months until 1 year - CXR q 3 months for 1 year - For early detection of lung metastasis. - Prevent pregnancy for 1 year. ☤ The patient should avoid - Combination OCPs - Monitoring of B-HCG titers - B-HCG should decline steadily to undetectable levels within 12-16 weeks. - Normal value = \< 5mIu/ml - ★ If BHCG levels plateau or rises at any time\...start chemotherapy Figure 16. Normal Regression Curve of B-HCG after Molar Evacuation PROGNOSIS {#prognosis.TransSub-subtopic2} --------- - Good Prognosis - Duration \< 4 months - Pre-evacuation B-hCG \< 1000,000 IU/L - B-HCG undetectable in 4 weeks - Histologic type: Partial mole is better than Complete mole. - Risk of developing a 2nd molar pregnancy is 1-3% MALIGNANT GTT {#malignant-gtt.TransOutline} ============= - INVASIVE MOLE - CHORIOCARCINOMA - PLACENTAL SITE TROPHOBLASTC TUMOR (PSTT) - PERSISTENT GTT  **Figure 17.** FIGO Staging for GTTs - Stage II: Vagina, pelvis or both - Stage III: Pulmonary metastases - Stage IV: Involves all other metastatic sites INVASIVE MOLE {#invasive-mole.TransSubtopic1} ------------- - H. mole that has **invaded deeply into the myometrium** or has produced metastases or both. - Synonyms:  - Chorioadenoma destruens or Malignant mole HISTOLOGY {#histology-1.TransSub-subtopic2} --------- - Trophoblastic proliferation + deep penetration into myometrium and/or adjacent structures - Hemorrhage can occur **Figure 18.** Myometrium invaded by the dilated chorionic villi CLINICAL COURSE {#clinical-course.TransSub-subtopic2} --------------- - Persistent bleeding after evacuation of H. mole - Failure of Uterine involution - Plateauing or Increasing B-hCG titers DIAGNOSIS {#diagnosis-1.TransSub-subtopic2} --------- - ★ **Definitive Dx** - **Histopathologic or post-hysterectomy**  - Curettage - Ultrasound - Focal area of altered echogenicity within uterus - Doppler Scanning - Focal area of increased blood flow  **Figure 19.** Focal area of increased blood flow seen in **doppler color flow**. TREATMENT {#treatment-1.TransSub-subtopic2} --------- - Single agent Chemotherapy: ☤ fortunately responsive - ★ **MTX or Actinomycin D** - 2 additional clean-up courses - With or without hysterectomy  - ☤ As we said earlier, we are trying to preserve fertility with a risk of developing malignancy later down the line. PROGNOSIS {#prognosis-1.TransSub-subtopic2} --------- - Generally self-limiting - 80 -- 100% survival rate CHORIOCARCINOMA {#choriocarcinoma.TransSubtopic1} --------------- - Epithelial tumor composed of syncytiotrophoblast and cytotrophoblast - Antecedent pregnancy: - H. mole 50% - Normal pregnancy 25% - Abortion/Ectopic 25% PATHOLOGY {#pathology-1.TransSub-subtopic2} --------- - Gross: Necrotic or Hemorrhagic masses or nodules in the uterus **Figure 20.** Gross appearance #### TUMOR SPREAD AND STAGING {#tumor-spread-and-staging.TransSub-subtopic3} - Choriocarcinoma spreads hematogenously and may involve: - Lungs 57-80% - Vagina 30% - Pelvis 20% - Brain 17% - Liver 10% - Since B-hCG titers accurately reflect he clinical disease, histological verification is not required for diagnosis. - Staging should be based on history, clinical examination and appropriate laboratory and radiological studies. - ☤ It's the same as FIGO earlier. HISTOLOGY {#histology-2.TransSub-subtopic2} --------- - Histopathology: - Trophoblastic overgrowth - Lack of villous architecture - Necrosis of blood vessels  **Figure 21.** Choriocarcinoma TREATMENT {#treatment-2.TransSub-subtopic2} --------- - Chemotherapy: Principal mode - Single agent or combination Tx depending on risk assessment. - Surgery: Controversial - May decrease number of chemotherapies needed. - Indicated in removal of primary lesions, tumor, perforation, uncontrolled bleeding, or drug resistance. - Lobectomy for pulmonary lesions - Brain lesions -- removed only to relieve intracranial pressure. - Vaginal lesions -- not excised or biopsied due to vascularity. A blue screen with white text Description automatically generated **Figure 22.** WHO Prognostic Scoring System - Low Risk: 1-6 (Good Prognosis) - Single agent treatment - IM Methotrexate alternating with folinic acid for 1 week - Monitor hCG - High Risk: 7 or more (Poor Prognosis) - Combination Tx - EMA-CO Regimen - EMA-CE Regimen - After normal hCG, continue for 6 weeks (RCOG 2010)  **Figure 22.** Schematic diagram for Gestational Trophoblastic Neoplasia depending on the risk factors. #### BASELINE LABS PRIOR TO CHEMOTHERAPY {#baseline-labs-prior-to-chemotherapy.TransSub-subtopic3} - B-hCG titers - CBC with platelet count - Liver profile (SGPT/SGOT) - Renal profile (BUN/Crea) - Chest x-ray #### CONTRAINDICATION TO CHEMOTHERAPY {#contraindication-to-chemotherapy.TransSub-subtopic3} - Hgb \ - Hgb, WBC, or platelets decrease to critical levels - Liver function test increases to 5x the normal - Shift to other drug if hCG levels rise or plateau for 3 consecutive determinations #### COMBINATION CHEMOTHERAPY {#combination-chemotherapy.TransSub-subtopic3} - MAC Drug Combination - Methotrexate (MTX) 0.3 -- 0.4 mg/kgBW/day IM on days 1-5 - Actinomycin D 10-12 ug/kgBW/day on days 1-5 - Cyclophosphamide 3 mg/kgBW PO on days 1-5 - Chlorambucil 0.2 mg/kgBW PO on days 1-5 - EMA-CO (Course 1) - Day 1 - Etoposide 100 mg/m^2^ IV in 200 mL saline - Dactinomycin 0.5 mg IV stat - MTX 100 mg/m^2^ IV initially then 200 mg/m^2^ IV infusion over 12 hours - Day 2 - Etoposide 100 mg/m^2^ IV in 200 mL saline over 30 minutes - Dactinomycin 0.5 mg IV stat - Folinic Acid 15 mg IM or PO q 12 to begin 24 hours after giving MTX - EMA-CO (Course 2) - Day 8: Vincristine 1 mg/m^2^ IV - Cyclophosphamide 600 mg/m^2^ IV over 30 minutes FOLLOW-UP {#follow-up-1.TransSub-subtopic2} --------- - ★ **Serum B-hCG monitoring** - Q 2 weeks until 3 consecutive (-) titers - Then, monthly up to 2 years - Then, every 3 months up to 4 years - Then, every 6 months - Pelvic exam every follow-up - Chest x-ray q 6 months - ★ **Pregnancy avoided for 1-2 years.** - Prescribe combination OCPs REMISSION RATES {#remission-rates.TransSub-subtopic2} --------------- - Low risk GTT: 100% - High risk GTT: 60-80% PLACENTAL SITE TROPHOBLASTIC TUMOR (PSTT) {#placental-site-trophoblastic-tumor-pstt.TransSubtopic1} ----------------------------------------- - Very rare form of GTT - Consists predominantly of intermediate trophoblasts and few syncytial elements. - High potential for metastases and death - Produce small amounts of B-hCG and hPL - ★**Relatively insensitive to Chemotherapy** - ★**Surgical resection of the diseases is mainstay of treatment.** HISTOLOGY {#histology-3.TransSub-subtopic2} --------- A close-up of a microscope Description automatically generated **Figure 23.** PSTT PERSISTENT GESTATIONAL TROPHOBLASTIC TUMORS {#persistent-gestational-trophoblastic-tumors.TransSubtopic1} ------------------------------------------- - Rare - Occurs after trophoblast removal / Salpingectomy. - Identified by stable or rising B-hCG levels. - Additional surgical or medical therapy is necessary. TREATMENT {#treatment-3.TransSub-subtopic2} --------- - Single-dose MTX 50 mg/m^2^ x BSA - With evidence of tubal rupture and bleeding - Surgery SUMMARY POINTS {#summary-points.TransOutline} ============== - GTN represents a spectrum of human tumors - H. mole: Ddx for first-trimester vaginal bleeding - Frequent findings - Discordant uterine size - Ovarian cystic enlargement - Hyperemesis - Hyperthyroidism - Pre-eclampsia - Evacuation of H. mole: - Suction curettage if fertility needs to be preserved - Hysterectomy with mole in situ if fertility is not desired - Caution: Trophoblastic spread and pulmonary embolization - Individualization of therapy is critical for successful treatments of patients with GTN - Chemotherapy is the primary modality for therapy - Surgery and radiotherapy may also have a role - B-hCG - Sensitive and reliable marker - Used in diagnosis, monitoring, and maintain follow-up evaluation REFERENCES {#references.TransOutline} ========== - Cunningham, F. G. (2022). Williams Obstetrics (26th ed.).McGraw-Hill Companies - 2025COM-Transcription APPENDIX ======== +-----------------------+-----------------------+-----------------------+ | | **Complete H. mole | **Partial H. mole | | | (diandric, | (diandric, | | | diploidy)** | triploidy)** | +=======================+=======================+=======================+ | **Pathogenesis** | - Paternal | - 1 maternal (23X) | | | chromosome only | and 2 paternal | | | plus empty ovum | chromosomes (23X, | | | | 23Y) | | | - Gives rise to | | | | generalized | - Maternal | | | swelling of | chromosome gives | | | placental villi | rise to fetal | | | with marked | component | | | trophoblastic | | | | proliferation and | - Paternal | | | absent fetal | chromosome causes | | | component | focal swelling of | | | | placental villi | | | | and milder form | | | | of trophoblastic | | | | invasion | +-----------------------+-----------------------+-----------------------+ | **Genetics** |  | from | | | | fertilization of | | | - 80% are | a normal ovum by | | | homozygous 46XX | two sperm | | | resulting from | | | | duplication of | | | | the haploid | | | | genome of a | | | | single sperm | | | | following | | | | fertilization of | | | | an ovum | | | | | | | | - The remaining | | | | arise by | | | | dispermic | | | | fertilization of | | | | an ovum | | +-----------------------+-----------------------+-----------------------+ | **Karyotype** | - Diploid | - Triploid | | | | | | | - 46XX | - 69XXX or 69XXy | +-----------------------+-----------------------+-----------------------+ | **Preliminary | - Molar gestation | - Missed abortion | | diagnosis** | | | +-----------------------+-----------------------+-----------------------+ | ***Gross | - "bunch of grapes" | - Fetal parts | | morphology*** | | present | | | - Absent | | | | embryo-fetus | - May detect FHT | | | | depending on AOG | | | - No FHT | | | | | - Presence of | | | - Large vesicles | placenta-like | | | | tissues with | | |  | | +-----------------------+-----------------------+-----------------------+ | ***Histologic |  | | +-----------------------+-----------------------+-----------------------+ | **Villi** | - Edematous | - Presence of large | | | | and | | | | regularly-sized | | | | villi | +-----------------------+-----------------------+-----------------------+ | **Trophoblastic | - Moderate to | - Focal, slight to | | proliferation** | severe | moderate | | | | | | | - Marked | - Mild | | | trophoblastic | trophoblastic | | | atypia | atypia | +-----------------------+-----------------------+-----------------------+ | **Blood vessels** | - present | - absent | +-----------------------+-----------------------+-----------------------+ | **Fetal Components** | - absent | - present | +-----------------------+-----------------------+-----------------------+ | **Immunostaining** | - negative | - positive | +-----------------------+-----------------------+-----------------------+ | **Manifestations** | | | +-----------------------+-----------------------+-----------------------+ | **Common | - vaginal bleeding | | | presentation** | (most common) or | | | | amenorrhea | | | | | | | | - positive | | | | pregnancy test | | +-----------------------+-----------------------+-----------------------+ | **Uterine size** | - larger than AOG | - same size or | | | | smaller than AOG | +-----------------------+-----------------------+-----------------------+ | **Beta HCG level** | - \100,000 mIU/mL | - \45 years old increases risk | | | for complete but not partial | | | mole | +-----------------------------------+-----------------------------------+ | **OB history** | - Previous molar pregnancy | +-----------------------------------+-----------------------------------+ | **Racial Factors** | - Asians, Hispanic, | | | American-Indian | +-----------------------------------+-----------------------------------+ | **Diet and nutrition** | - Decreased dietary carotene & | | | animal fat | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **Management** | | +===================================+===================================+ | **Intervention** | **Remarks** | +-----------------------------------+-----------------------------------+ | **Suction curettage** | - Preferred treatment, | | | regardless of uterine size | | | | | | - Cervix dilated to allow | | | insertion of a suction | | | curette | +-----------------------------------+-----------------------------------+ | **TAHBS +/- BO with mole | - For those with completed | | in-situ** | family size | | | | | | - Decreases risk for local | | | invasion | +-----------------------------------+-----------------------------------+ | **Chemoprophylaxis** | - First line: methotrexate | | | | | | - Second line: actinomycin D | +-----------------------------------+-----------------------------------+ | **Follow-up** | | +-----------------------------------+-----------------------------------+ | **Post-evacuation bHCG | - 1 week after surgical | | monitoring** | evacuation | | | | | | - Every 2 weeks until bHCG | | | becomes normal for 2 | | | consecutive tests | | | | | | - Every 1 month for first 6 | | | months | +-----------------------------------+-----------------------------------+ | **Follow-up advice** | - **Avoid pregnancy during | | | monitoring period** | | | | | | - Use low-dose OCP for | | | contraception | +-----------------------------------+-----------------------------------+ | **For succeeding pregnancies** | - Do early ultrasound to r/o | | | molar pregnancy | | | | | | - Perform quantitative serum | | | bHCG 6 weeks postpartum | | | | | | - Placenta submitted for | | | histopathologic exam | +-----------------------------------+-----------------------------------+