Gestational Trophoblastic Disease by MWEBAZA VICTOR .pptx

gestational trophoblastic disease slides

1. M W E B A Z A VICTOR. J MBchB 5 TH YEAR(OBGYN) Ugandan [email protected] Kampala international university western campus Jinja site light under the care of Jinja Regional Referral Hospital OBGYN dept GESTATIONAL TROPHOBLASTIC DISEASES Presentation TWO 1 st /AUG/2022 @ 8:00AM Modulated and Mentored by Doctor petrus ( gynaecology and obstetrics CONSULTANT) @ KIUWC

2. Topic : Gestational trophoblastic disease (GTD) Gestational trophoblastic disease (GTD) is a heterogeneous spectrum of diseases with abnormal trophoblastic proliferation ranging from benign to malignant state. It has varying degree of spread from local invasion to distant metastasis. Simple recap on embryogenesis for5to10minutesusing langhman embryology textbook 8 th edition 9/1/2022 MWEBAZA VICTOR GTD presentation

3. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to form the placenta during pregnancy . There are several different types of GTD. Hydatidiform moles are benign in most cases, but sometimes may develop into invasive moles , or, in rare cases, into choriocarcinoma , which is likely to spread quickly, but which is very sensitive to chemotherapy , and has a very good prognosis. 9/1/2022 MWEBAZA VICTOR GTD presentation

4. Types of G.T.D one benign tumour , and four malignant tumours The benign tumour Hydatidiform mole The four malignant tumours Invasive mole Choriocarcinoma Placental site trophoblastic tumour Epithelioid trophoblastic tumour 9/1/2022 MWEBAZA VICTOR GTD presentation

5. Risk factors for Development of GTN Advanced maternal age (>40 years) b-hCG >100,000 IU/L Increased uterine size Bilateral ovarian enlargement (>8 cm) USG—uterine invasion Increased uterine vascularity (USG Doppler) 9/1/2022 MWEBAZA VICTOR GTD presentation

6. Classification of GTD (WHO). A. Benign trophoblastic lesions Placental site nodule Exaggerated placental reaction B. H ydatidiform moles (HM) Complete hydatidiform mole „Partial hydatidiform moles C. Gestational trophoblastic neoplasia „Invasive mole Choriocarcinoma „Placental site trophoblastic tumor „Epithelioid trophoblastic tumors 9/1/2022 MWEBAZA VICTOR GTD presentation

7. Risk factors of GTD. Race: Asians compared to North Americans or Europeans Age: Extremes of age (<16 and >45) Parity: Increasing parity Diet: Risks of CHM is increased when dietary intake of animal fat, beta-carotene or vitamin A is less Genetics: Autosomal recessive disorder (familial recurrent HM) chromosome 19q Risk of recurrence is increased up to 25% when there is previous 2 or more molar pregnancy (CHM: complete hydatidiform mole) 9/1/2022 MWEBAZA VICTOR GTD presentation

8. Incidence of GTD The incidence of GTN is about 1 in 5,000 pregnancies in oriental countries and 1 in 50,000 in Europe and North America . More than 50% occur after molar pregnancy, about 25% after abortion and/or ectopic pregnancy and a few after normal pregnancy. Non metastatic ( locally invasive ) lesions develop in 15% and metastatic lesions develop in about 4% of patients after molar evacuation . While GTD overwhelmingly affects women of child-bearing age, it may rarely occur in postmenopausal women. 9/1/2022 MWEBAZA VICTOR GTD presentation

9. 1. HYDATIDIFORM MOLE—MOLAR PREGNANCIA Molar pregnancy is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and will fail to come to term. A molar pregnancy is a gestational trophoblastic disease which grows into a mass in the uterus that has swollen chorionic villi . These villi grow in clusters that resemble grapes . 9/1/2022 MWEBAZA VICTOR GTD presentation

10. An hydatidiform mole is a pregnancy or conception in which the placenta contains grape like vesicles (small sac) that are usually visible with the naked eyes These vesicles are due to distention of the chorionic villi by fluids On microscopy there is hypertrophy of the trophoblastic cells NOTICE Hydatidiform mole will almost always end as a spontaneous abortion 9/1/2022 MWEBAZA VICTOR GTD presentation

11. Molar pregnancies are categorized as partial moles or complete moles, with the word mole being used to denote simply a clump of growing tissue, or a growth. 9/1/2022 MWEBAZA VICTOR GTD presentation

12. 1.1. Complete mole An "empty" ovum (i.e. absent or inactivated maternal chromosome) is fertilized by either a haploid sperm that then duplicates or two separate spermatozoa. Have a 46XX / 46YY karyotype 4 and 8% have 46,xy karyotype. These arise from dispermy i.e. fertilization of the ‘empty’ ovum by two separate haploid sperms There is absence of embryonic material Its diffuse in nature, Hyperplasia usually present to variable degrees Uterine size large for dates 9/1/2022 MWEBAZA VICTOR GTD presentation

13. Complete hydatidiform moles have a 2–4% risk of developing into choriocarcinoma in Western countries and 10–15% in Eastern countries and a 15% risk of becoming an invasive mole . About the theca lutein cysts, >25% develop depending on the diagnostic modality About immuno staining its negative for P57 No fetal parts Increased or elevated hCG All villi hydropin with no normal adjacent villi Risk of choriocarcinoma is 15% Post molar invasion and malignancy is 15% and 4% respectively 9/1/2022 MWEBAZA VICTOR GTD presentation

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15. Classic signs and symptoms a complete mole. Vaginal bleeding Hyperemesis ( severe vomit) Size inconsistent with gestational age( with no fetal heart beating and fetal movement) Preeclampsia Theca lutein ovarian cysts Hyperthyroidism signs and symptoms Sometimes symptoms of hyperthyroidism are seen, due to the extremely high levels of hCG, which can mimic the effects of thyroid-stimulating hormone . 9/1/2022 MWEBAZA VICTOR GTD presentation

16. Differentials of complete molar Hyperemesis gravidarum Hypertension in pregnancy Hyperthyroidism Abortion Multiple pregnancy Polyhydramnios 9/1/2022 MWEBAZA VICTOR GTD presentation

17. 1.2. Partial mole 90% of the time, they exhibit triploidy. The additional haploid component is paternal (diandry). An oocyte retains its female nucleus but is fertilized by two haploid sperms  69 XXX, 69 XXY, rarely 69 XYY 9/1/2022 MWEBAZA VICTOR GTD presentation

18. Embryonic material present Focal in nature, Hyperplasia mild and focal Small for the dates or norm About immuno staining there is a positive P57 Development of theca lutein cysts is rare Post molar invasion and malignancy is <5% Mild to norm increase in hCG Fetal parts present Risk of choriocarcinoma 0.5% Normal adjacent villi may be present 9/1/2022 MWEBAZA VICTOR GTD presentation

19. Signs and Symptoms of Partial Mole Vaginal bleeding Absence of fetal heart tones Uterine enlargement and preeclampsia is reported in only 3% of patients. Theca lutein cysts rare. Hyperemesis is rare. 9/1/2022 MWEBAZA VICTOR GTD presentation

20. Diagnosis of hydatidiform mole Quantitative beta-HCG; Serum beta-hCG (raised more than 100,000 i.u. per ml ) CBC CXRAY Ultrasound is the criterion standard for identifying both complete and partial molar pregnancies. The classic image On ultrasound, the mole resembles a bunch of grapes ("cluster of grapes" or "honeycombed uterus" or "snow-storm ") definitive diagnosis requires histopathological examination . 9/1/2022 MWEBAZA VICTOR GTD presentation

21. The most common symptom of a mole is vaginal bleeding during the first trimester however very often no signs of a problem appear and the mole can only be diagnosed by use of ultrasound scanning. (routine check) Occasionally, a uterus that is too large for the stage of the pregnancy can be an indication. NOTE : Vaginal bleeding does not always indicate a problem! 9/1/2022 MWEBAZA VICTOR GTD presentation

22. Management of a complete mole Suction dilation and curettage : To remove benign hydatidiform moles When the diagnosis of hydatidiform mole is established, the molar pregnancy should be evacuated. An oxytocic agent should be infused intravenously after the start of evacuation and when moderate amount of trophoblastic tissue has been removed to avoid risk of dissemination of trophoblastic tissue into circulation and continued for several hours to enhance uterine contractility 9/1/2022 MWEBAZA VICTOR GTD presentation

23. Suction curettage should be followed by gentle sharp curettage to obtain tissue for histology The procedure should be done in operation theatre under GA or SA with blood available, If the uterus is larger than 14 weeks one hand should be placed on top of the fundus, uterus should be massaged to stimulate uterine contraction and reduce the risk perforation. 9/1/2022 MWEBAZA VICTOR GTD presentation

24. Removal of the uterus (hysterectomy) : used rarely to treat hydatidiform moles if future pregnancy is no longer desired. If the patient desires surgical sterilization, hysterectomy may be performed with the mole in situ. Ovaries may be preserved at the time of surgery, even though prominent theca lutein cysts are present. Large ovarian cysts may be decompressed by aspiration. Hysterectomy does not prevent metastasis , therefore patient will still require follow-up with assessment of hCG levels. 9/1/2022 MWEBAZA VICTOR GTD presentation

25. Chemotherapy with a single-agent drug Prophylactic (for prevention) chemotherapy at the time of or immediately following molar evacuation may be considered for the high-risk patients( to prevent spread of disease ) 9/1/2022 MWEBAZA VICTOR GTD presentation

26. High-risk postmolar trophoblastic tumor Pre-evacuation uterine size larger than expected for gestational duration Bilateral ovarian enlargement (> 9 cm theca lutein cysts) Age greater than 40 years Very high hCG levels (>100,000 m IU/ml) Medical complications of molar pregnancy such as toxemia, hyperthyrodism and trophoblastic embolization (villi come out of placenta ) repeat hydatidiform mole 9/1/2022 MWEBAZA VICTOR GTD presentation

27. Follow-up Patients with molar pregnancy are curative over 80% by treatment of evacuation. The follow-up after evacuation is key necessary uterine involution, Regression cystic ovarian enlargement (theca lutein cysts) cessation of bleeding Quantitative serum hCG levels should be obtained every 1-2 weeks until negative for three consecutive determinations, Then monthly for 6 months, Followed by every 3 months for 1 years. @Weekly to non-detectable levels (i.e. <5MIu/ml) on 3 m .Then monthly for 6 months. Then bimonthly for 6 months 9/1/2022 MWEBAZA VICTOR GTD presentation

28. Follow-up Physical examination to r/o metastatic disease is equally important. Ask for headache, visual disturbance, cough, difficult in breathing, involution of the uterus Investigations; FBC, base line chest X-ray and abdominal and pelvic US scan Contraception should be practiced during this follow-up period for atleast 1 yr. 9/1/2022 MWEBAZA VICTOR GTD presentation

29. NOTE : Avoid IUCD --- Risk of perforation Avoid Depo---Irregular bleeding At completion of follow-up pregnancy may be undertaken 9/1/2022 MWEBAZA VICTOR GTD presentation

30. Hemorrhage Sepsis Perforation during Evacuation Thyroid storm Persistent GTD Complications of molar pregnancy 9/1/2022 MWEBAZA VICTOR GTD presentation

31. Persistent gestational trophoblastic neoplasia (GTN) Persistent GTN is evidenced by persistence of trophoblastic activity following evacuation of molar pregnancy . This is clinically diagnosed when the patient presents with Irregular vaginal bleeding; Subinvolution of the uterus; Persistence of theca lutein cysts ; Level of hCG either plateaus or re-elevates after an initial fall. 9/1/2022 MWEBAZA VICTOR GTD presentation

32. After molar evacuation serum β-hCG becomes normal in about 7–9 weeks. Post molar GTN of serious nature may be either invasive mole or choriocarcinoma but GTN after nonmolar pregnancy is always a choriocarcinoma. 9/1/2022 MWEBAZA VICTOR GTD presentation

33. All patients with persistent GTT should undergo a careful pre-treatment evaluation, include:- Complete history and physical exam. Serum h CG level. LFT, RFT, Thyroid fn test. Peripheral WBC & platelet counts. Metastatic work –up should include CXR, CT-Scan USS or CT-Scan of abdomen and pelvis CT or MRS Scan of the head. 9/1/2022 MWEBAZA VICTOR GTD presentation

34. HINT ON Theca lutein cyst Theca lutein cyst is a type of bilateral functional ovarian cyst filled with clear, straw-coloured fluid . To be classified a functional cyst, the mass must reach a diameter of at least three centimetres. These cysts result from exaggerated physiological stimulation (hyperreactio luteinalis) and are usually associated with markedly elevated levels of beta- human chorionic gonadotropin (beta-hCG). They are thus associated with gestational trophoblastic disease ( molar pregnancy ), diabetes mellitus , alloimmunisation to Rh-D, and multiple gestations. 9/1/2022 MWEBAZA VICTOR GTD presentation

35. Women who smoke have a twofold increase for functional cysts. 9/1/2022 MWEBAZA VICTOR GTD presentation

36. 2. PLACENTAL SITE TROPHOBLASTIC TUMOR PSTT tumour arises from the trophoblasts of the placental bed . Incidence is less than 1% of all patients with GTN. 40–50% of these patients develop metastases. Tumor cells infiltrate the myometrium and grow between smooth-muscle cells Syncytiotrophoblast cells are generally absent, instead intermediate trophoblast cells are predominant . β-hCG secretion is low but human placental lactogen (hPL) is secreted and this is monitored during the follow up. 9/1/2022 MWEBAZA VICTOR GTD presentation

37. The entity is not responsive to chemotherapy. Hysterectomy is the preferred treatment. Serial serum hPL may be a reliable marker and hPL is useful for immunohistochemical staining to confirm the diagnosis. Tend to remain confined to the uterus, metastasizing late in their course. In contrast to other trophoblastic tumors, placental site tumors are relatively INSENSITIVE to chemotherapy. 9/1/2022 MWEBAZA VICTOR GTD presentation

38. Management of Non-metastatic PGTD Single agent is used. Methotrexate or Actinomycin D. For those beyond 40 yrs and /or have completed their families or have more than 4 children chemotherapy followed by surgery on the 3 rd day is recommended. 9/1/2022 MWEBAZA VICTOR GTD presentation

39. 3. EPITHELIOID TROPHOBLASTIC TUMOR (ETT): It is a variant of PSTT (WHO, 2003). Both are relatively chemoresistant and recurrence rate for the both are high (20–30%) despite surgery or chemotherapy. 9/1/2022 MWEBAZA VICTOR GTD presentation

40. 4. INVASIVE GTN (Chorioadenoma destruens) Invasive mole comprises about 15% of all GTN. The prominent features of this type of mole are invasive and destructive potentialities . Invasive mole shows abnormal penetration through the muscle layers of the uterus. The uterine wall may be perforated at multiple areas showing purple, fungating growth with massive intraperitoneal hemorrhage . The neoplasm may invade the pelvic blood vessels and metastasizes to vagina or distant sites as like those in choriocarcinoma. 9/1/2022 MWEBAZA VICTOR GTD presentation

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42. Diagnosis of invasive mole On laparotomy: Perforation of the uterus through which purple fungating growth is visible Hemoperitoneum. Histology: There is penetration of the uterine wall by the hyperplasic trophoblastic cells which still retain villus structures . There is no evidence of muscle necrosis . The materials for uterine curettage are often deceptive as the lesion may be deep inside the myometrium. Persistent high level of urinary or serum hCG 9/1/2022 MWEBAZA VICTOR GTD presentation

43. 5. CHORIOCARCINOMA A malignant form of GTD which can develop from a hydatidiform mole or from placental trophoblast cells associated with a healthy fetus ,an abortion or an ectopic pregnancy. Characterized by abnormal trophoblastic hyperplasia and anaplasia , absence of chorionic villi 9/1/2022 MWEBAZA VICTOR GTD presentation

44. Choriocarcinoma is a highly malignant tumor arising from the chorionic epithelium Is purely an epithelial tumor composed of anaplastic syncytiotrophoblastic and cytotrophoblastic cells Histologically – No villi. Sheets of anaplastic trophoblastic cells on a background of Hemorrhage and necrosis. Occurs in about 5% of patients after molar pregnancy evacuation 9/1/2022 MWEBAZA VICTOR GTD presentation

45. About 3–5% of all patients with molar pregnancies develop choriocarcinoma. Amongst all patients with choriocarcinoma, around 50% develop following a hydatidiform mole Trophoblastic disease following a normal pregnancy is either choriocarcinoma or PSTT and not a benign or invasive mole. 9/1/2022 MWEBAZA VICTOR GTD presentation

46. Pathology The primary site is usually anywhere in the uterus. Rarely, it starts in the tube or ovary. Ovarian choriocarcinoma (nongestational) may also be associated with malignant teratoma or dysgerminoma. The lesion is usually localized nodular type . It looks red, hemorrhagic, and necrotic. At times, the lesion is diffuse involving the entire endometrium. 9/1/2022 MWEBAZA VICTOR GTD presentation

47. Ovarian Enlargement due to’ Bilateral lutein cysts are present in about 30%. These are due to excessive production of chorionic gonadotropin. 9/1/2022 MWEBAZA VICTOR GTD presentation

48. Cause of choriocarcinoma Choriocarcinoma of the placenta during pregnancy is preceded by: hydatidiform mole (50% of cases) spontaneous abortion (20% of cases) ectopic pregnancy (2% of cases) normal term pregnancy (20–30% of cases) hyperemesis gravidarum 9/1/2022 MWEBAZA VICTOR GTD presentation

49. Signs and symptoms increased quantitative chorionic gonadotropin (the "pregnancy hormone") levels vaginal bleeding shortness of breath haemoptysis (coughing up blood) chest pain chest X-ray shows multiple infiltrates of various shapes in both lungs can present with decreased thyroid-stimulating hormone (TSH) due to hyperthyroidism. 9/1/2022 MWEBAZA VICTOR GTD presentation

50. Treatment of gestational choriocarcinoma Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy . The cure rates, even for metastatic gestational choriocarcinoma, more than 90% when using chemotherapy for invasive mole and choriocarcinoma. 9/1/2022 MWEBAZA VICTOR GTD presentation

51. Medical management. As of 2019, treatment with either single-agent Methotrexate or Actinomycin-D is recommended for low-risk disease, while intense combination regimens including EMACO ( etoposide , Methotrexate , Actinomycin D , cyclophosphamide and vincristine ( Oncovin ) are recommended for intermediate or high-risk disease 9/1/2022 MWEBAZA VICTOR GTD presentation

52. EMA-CO Chemotherapy for poor Prognostic Disease Etoposide(VP-16) 100mg/M 2 IV daily×2 days (over 30-45 minutes) Methotrexate 100mg/M 2 IV losding dose, then 200mg/M2 over 12 hours day 1 Actinomycin D 0.5mg IV daily×2 days Folinic acid 15mg IM or p.o. q 12 hours×4 starting 24 hours after starting methotrexate Cyclophosphamide 600mg/M 2 IV on day8 Oncovin (vincristine) 1mg/M 2 IV on day8 (Repeat every 15 days as toxicity permits) 9/1/2022 MWEBAZA VICTOR GTD presentation

53. Surgical management Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding. 9/1/2022 MWEBAZA VICTOR GTD presentation

54. ANATOMICAL STAGING OF GTT (FIGO) Stage I . [confirmed to uterus] Stage II [extends outside uterus but limited to the pelvic structures (adnexae, vagina, broad ligaments)] Stage III [Extend to the lung with/without genital tract involvement.] Stage IV [Metastasis to the liver, Brain, Kidney, GIT etc] 9/1/2022 MWEBAZA VICTOR GTD presentation

55. WHO Prognostic Scoring System Score Prognostic factor 1 2 4 Age(years) ≤40 >/=40 — — Pregnancy history Hydatidiform mole Abortion, ectopic Term pregnancy — Interval (months) of treatment <4 4-6 7-12 >12 Initial hCG(mIU/ml) <10 3 10 3 -10 4 10 4 -10 5 >10 5 Largest tumor(cm) <3 3-5 >5 — Sites of metastasis Lung Spleen, kidney GI tract Liver, Brain No. of metastasis — 1-4 4-8 >8 Previous failed chemotherapy (treatment) — — Single drug 2 or more drugs MWEBAZA VICTOR GTD presentation

56. In this scoring system, women with a score of 7 or greater are considered at high risk. 9/1/2022 MWEBAZA VICTOR GTD presentation

57. FIGO Staging System for Gestational Trophoblastic Tumors Substages assigned for each stage as follows: A: No risk factors present B: One risk factor C: Both risk factors Risk factors used to assign substages: 1. Pretherapy serum hCG > 100,000 mlU/ml 2. Duration of disease >6 months 9/1/2022 MWEBAZA VICTOR GTD presentation

58. Becoming pregnant again after GTD Most women with GTD can become pregnant again and can have children again. In the past, it was seen as important not to get pregnant straight away after a GTD . Specialists recommended a waiting period of 6 months after the hCG levels become normal. Recently, this standpoint has been questioned. New medical data suggest that a significantly shorter waiting period after the hCG levels become normal is reasonable for approximately 97% of the patients with hydatidiform mole. 9/1/2022 MWEBAZA VICTOR GTD presentation

59. GTD coexisting with a normal fetus, also called "twin pregnancy" In some very rare cases, a GTD can coexist with a normal fetus. This is called a " twin pregnancy ". These cases should be managed only by experienced clinics, after extensive consultation with the patient. Because successful term if the mother wishes, following appropriate counselling. The probability of achieving a healthy baby is approximately 40%, but there is a risk of complications, e.g. pulmonary embolism and preeclampsia 9/1/2022 MWEBAZA VICTOR GTD presentation

60. Treatment summary on GTD Nonmetastatic GTD Low-Risk Metastatic GTD High-Risk Metastatic GTD 9/1/2022 MWEBAZA VICTOR GTD presentation

61. Treatment of Nonmetastatic GTD Hysterectomy is advisable as initial treatment in patients with Nonmetastatic GTD who no longer wish to preserve fertility This choice can reduce the number of course and shorter duration of chemotherapy. Adjusted single-agent chemotherapy at the time of operation is indicated to eradicate any occult metastases and reduce tumor dissemination. 9/1/2022 MWEBAZA VICTOR GTD presentation

62. Single-agent chemotherapy is the treatment of choice for patients wishing to preserve their fertility. Methotrexate(MTX ) and Actinomycin-D are generally chemotherapy agents Treatment is continued until three consecutive normal hCG levels have been obtained and two courses have been given after the first normal hCG level. 9/1/2022 MWEBAZA VICTOR GTD presentation

63. Treatment of Low-Risk Metastatic GTD Single-agent chemotherapy with MTX or Actinomycin-D is the treatment for patients in this category If resistance to sequential single-agent chemotherapy develops, combination chemotherapy would be taken Approximately 10-15% of patients treated with single-agent chemotherapy will require combination chemotherapy with or without surgery to achieve remission 9/1/2022 MWEBAZA VICTOR GTD presentation

64. Treatment of High-Risk Metastatic GTD Multiagent chemotherapy with or without adjuvant radiotherapy or surgery should be the initial treatment for patients with high-risk metastatic GTD EMA-CO regimen formula is good choice for high-risk metastatic GTD Adjusted surgeries such as removing foci of chemotherapy-resistant disease, controlling hemorrhage may be the one of treatment regimen 9/1/2022 MWEBAZA VICTOR GTD presentation

65. Follow-up After Successful Treatment Quantitative serum hCG levels should be obtained monthly for 6 months, every two months for remainder of the first year, every 3 months during the second year Contraception should be maintained for at least 1 year after the completion of chemotherapy. Condom is the choice. 9/1/2022 MWEBAZA VICTOR GTD presentation

66. Final Prognosis Cure rates should approach 100% in nonmetastatic and low-risk metastatic GTD Intensive multimodality therapy has resulted in cure rates of 80-90% in patients with high-risk metastatic GTD 9/1/2022 MWEBAZA VICTOR GTD presentation

67. A GIRL CHILD NEED TO BE LOVED AND CARED FOR. FEMALE LIVES MATTER – MWEBAZA VICTOR

68. References of Mwebaza victor’s work DC Dutta’s Textbook of Gynecology ^  " choriocarcinoma " at Dorland's Medical Dictionary ^  Rosenberg S, DePinho RA, Weinberg RE, DeVita VT, Lawrence TS (2008). DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology . Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-7207-5. OCLC  192027662 . ^  Kufe D (2000). Benedict RC, Holland JF (eds.). Cancer medicine (5th ed.). Hamilton, Ont: B.C. Decker. ISBN 1-55009-113-1. OCLC  156944448 . ^  Gerson RF, Lee EY, Gorman E (November 2007). "Primary extrauterine ovarian choriocarcinoma mistaken for ectopic pregnancy: sonographic imaging findings". AJR. American Journal of Roentgenology . 189 (5): W280–W283. doi: 10.2214/AJR.05.0814 . PMID  17954626 . 9/1/2022 MWEBAZA VICTOR GTD presentation

69. Gestational trophoblastic disease: Epidemiology, clinical manifestations and diagnosis. Chiang JW, Berek JS. In: UpToDate [Textbook of Medicine]. Basow, DS (Ed). Massachusetts Medical Society, Waltham, Massachusetts, USA, and Wolters Kluwer Publishers, Amsterdam, The Netherlands. 2010. ^  Chittenden B, Ahamed E, Maheshwari A (August 2009). "Choriocarcinoma in a postmenopausal woman". Obstetrics and Gynecology . 114 (2 Pt 2): 462–5. doi: 10.1097/AOG.0b013e3181aa97e7 . PMID  19622962 . S2CID  35996436 . ^  Gestational trophoblastic disease: Pathology. Kindelberger DW, Baergen RN. In: UpToDate [Textbook of Medicine]. Basow, DS (Ed). Massachusetts Medical Society, Waltham, Massachusetts, USA, and Wolters Kluwer Publishers, Amsterdam, The Netherlands. 2010 ^  "Gestational Trophoblastic Disease Treatment (PDQ®)–Patient Version - National Cancer Institute" . www.cancer.gov . 2020-05-11. Retrieved 2021-02-16. 9/1/2022 MWEBAZA VICTOR GTD presentation