Gestational trophoblastic tumor

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    • Gestational trophoblastic neoplasms
      • include
        • hydatidiform mole (complete and partial)
        • invasive mole (chorioadenoma destruens)
        • choriocarcinoma,
        • placental-site trophoblastic tumor (PSTT).
      • they develop from an aberrant fertilization event and hence arise from fetal tissue within the maternal host.
      • They are composed of both syncytiotrophoblastic and cytotrophoblastic cells, with the exception of PSTT, which is derived from intermediate trophoblastic cells (MCQ)
      • Hydatidiform mole
        • most common form of gestational trophoblastic disease
        • benign in nature.
        • incidence is higher in (MCQ)
          • women younger than 20
          • women older than 40 years of age
          • in nulliparous women,
          • in patients of low economic status
          • in women whose diets are deficient in protein, folic acid, and carotene.
        • Blood Group association
          • blood group A women impregnated by group O men have an almost 10-fold greater risk of developing choriocarcinoma than group A women impregnated by group A partners(MCQ)
          • women with blood group AB tend to have a relatively worse prognosis. (MCQ)
        • Hydatidiform mole should be suspected in any woman with (MCQ)
          • bleeding in the first half of pregnancy
          • passage of vesicles
          • hyperemesis gravidarum
          • onset of preeclampsia prior to 24 weeks.
        • physical examination findings that further support the diagnosis (MCQ)
          • Absent fetal heart tones
          • a uterus too large for the estimated gestational age
      • Invasive mole
        • reported in 10–15% of patients who have had primary molar pregnancy.
        • considered a benign neoplasm
        • invasive mole is locally invasive and may produce distant metastases.
      • Choriocarcinoma
        • incidence is higher in Asia(MCQ)
        • antecedent gestational event of choriocarcinoma(MCQ)
          • In about half of all cases of –  hydatidiform mole
          • One-fourth of cases follow a term pregnancy
          • remaining one-fourth follow an abortion.
      • PSTT
        • may arise either from a (MCQ)
          • hydatidiform mole
          • less commonly, from a normal-term pregnancy.
        • The tumor is generally confined to the uterus
        • metastasizes late in its course.
        • Syncytiotrophoblastic cells are generally absent from this tumor(MCQ)
          • minimal secretion of Beta -hCG in relation to tumor burden
        • human placental lactogen (hPL) is secreted and its levels can be monitored to follow response. (MCQ)
      • Clinical dictum
        • Any woman with a recent history of molar pregnancy, abortion, or normal pregnancy who presents with vaginal bleeding or a tumor in any organ should have at least one Beta -hCG assay to ensure that metastatic gestational trophoblastic neoplasia is not the cause. (MCQ)
        • This is important given that the cure rate of properly treated metastatic gestational trophoblastic neoplasia approaches 90%.(MCQ)
    • Etiology & Pathogenesis
      • Gestational trophoblastic tumors arise in fetal rather than maternal tissue.
      • Cytogenetic studies
        • Complete moles (MCQ)
          • usually (perhaps always) euploid
          • paternal in origin(MCQ)
          • sex chromatin-positive—46 XX or 46 XY. (MCQ)
          • A complete mole arises when an empty ovum (with an absent or inactivated nucleus) is fertilized by (MCQ)
            • one haploid sperm that duplicates its chromosomes
            • two haploid sperms
        • partial mole(MCQ)
          • triploid
            • 69 XXY (70%),
            • 69 XXX (27%),
            • 69 XYY (3%).
          • It arises when an ovum with an active nucleus is fertilized by a (MCQ)
            • one haploid sperm that duplicates its chromosomes
            • two haploid sperms
    • Pathology
      • Hydatidiform mole
        • an abnormal pregnancy characterized grossly by
        • multiple grapelike vesicles filling and distending the uterus
        • usually it occurs in the absence of an intact fetus
      • Microscopically, moles may be identified by three classic findings(MCQ)
        • edema of the villous stroma
        • avascular villi
        • nests of proliferating syncytiotrophoblastic or cytotrophoblastic elements surrounding villi

    6

    • Invasive mole (chorioadenoma destruens)
      • occurs in 20% of patients who have undergone evacuation of a molar pregnancy.
      • It is essentially a hydatidiform mole that invades the myometrium or adjacent structures
      • It has the potential to completely penetrate the myometrium and cause subsequent uterine rupture and hemoperitoneum
      • it also has the ability to spontaneously regress
    • Choriocarcinoma (MCQ)
      • a pure epithelial tumor
      • composed of syncytiotrophoblastic and cytotrophoblastic cells
      • may accompany or follow any type of pregnancy
      • It usually presents as late vaginal bleeding in the postpartum period
      • physical exam findings(MCQ)
        • An enlarged uterus
        • enlarged ovaries
        • vaginal lesions
      • Histologic examination of the tumor
        • sheets or foci of trophoblasts on a background of hemorrhage and necrosis but no villi.
    • Placental-site trophoblastic tumor
      • derived from the intermediate trophoblasts of the placental bed, with minimal or absent syncytiotrophoblastic tissue(MCQ)

    Clinical Findings

      • Abnormal uterine bleeding, usually during the first trimester, is the most common presenting symptom (MCQ)
        • Three-fourths of these patients present prior to the end of the first trimester.
      • Nausea and vomiting (MCQ)
        • About half of patients will have a uterine size that is greater than that appropriate for their gestational age.
      • Multiple theca lutein cysts (MCQ)
        • cause enlargement of one or both ovaries
        • enlarged ovaries may be a source of pain.
        • Involution of the cysts
        • proceeds over several weeks
        • usually parallels the decline of Beta hCG values.
        • Surgical treatment of these cysts is indicated only if
          • rupture, torsion, or hemorrhage occur,
          • enlarged ovaries become infected.
      • Preeclampsia in the first trimester or early second trimester—an unusual finding in normal pregnancy—has been said to be pathognomonic for a hydatidiform mole(MCQ)
      • Hyperthyroidism
        • Occur from stimulation of thyrotropin receptors by hCG
        • usually subclinical and most patients remain asymptomatic.
    • Laboratory findings
      • Beta -hCG.
        • used for diagnosis, treatment, and follow-up of the disease process.
        • its levels correlate closely with the number of viable tumor cells present
        • In most instances, the Beta -hCG values exhibit a progressive decline to nondetectable levels within 14 weeks following evacuation of a molar pregnancy. (MCQ)
    • Ultrasonograph findings
      • diagnostic method of choice for patients with suspected molar pregnancy(MCQ)
      • complete molar pregnancy
        • characteristic multiple hypoechoic areas corresponding to hydropic villi
        • described as a "snowstorm" pattern. (MCQ)
        • A normal gestational sac or fetus is not present
        • Theca lutein cysts may also be seen.
      • Partial mole
        • focal areas of trophoblastic changes
        •  fetal tissue may be noted
      • An ultrasonograph should be obtained in any patient who presents with bleeding in the first half of pregnancy and has a uterus greater than 12 weeks gestational size. (MCQ)
      • Even when the uterus is appropriate for gestational age, ultrasonography can be key in differentiating between a normal pregnancy and a hydatidiform mole.
    • Treatment of Hydatidiform mole
      • Evacuation
        • Suction curettage is the method of choice(MCQ)
          • It is safe, rapid, and effective in nearly all cases.
        • Intravenous oxytocin (MCQ)
          • should be started after a moderate amount of tissue has been removed
          • may be continued for 24 hours postevacuation if necessary.
          • can be safely accomplished even when the uterus is the size of a 28- week gestation.. (MCQ)
        • When a large hydatidiform mole (> 12 weeks in size) is evacuated by suction curettage, a laparotomy setup should be readily available, as hysterotomy, hysterectomy, or bilateral hypogastric artery ligation may be necessary if perforation or hemorrhage occurs. (MCQ)
      • Hysterectomy
        • remains an option for
          • good surgical candidates not desirous of future pregnancy
          • older women (who are more likely to develop malignant sequelae).
        • If theca lutein cysts are encountered at hysterectomy, the ovaries should remain intact, because regression to normal size will occur as the hCG titer diminishes.
        • Hysterectomy does not eliminate the need for careful followup with Beta -hCG testing,
        • the likelihood of metastatic disease following hysterectomy for gestational trophoblastic disease decreases from 20% to 3.5%.(MCQ)
        • Current recommendations restrict hysterotomy to cases complicated by hemorrhage. (MCQ)
      • After the completion of the evacuation, all Rh-negative patients should receive Anti-D immune globulin. (MCQ)
    • Complications
      • Acute pulmonary insufficiency(MCQ)
        • The maternal–fetal barrier contains leaks large enough to permit passage of cellular and tissue elements
        • As a result, deportations of trophoblastic tissue to the lungs are frequent.
        • A patient can present with dyspnea and cyanosis within 4–6 hours after evacuation of the molar pregnancy
      • Pulmonary edema leading to high-output congestive heart failure can also result from
        • excessive fluid administration
        • preeclampsia
        • anemia
        • hyperthyroidism.
    • Surveillance Following Molar Pregnancy
      • Following evacuation of a hydatidiform mole, the patient should have serial Beta -hCG determinations
        • begin within 48 hours after evacuation
        • then at weekly intervals until serum Beta -hCG declines to nondetectable levels on three successive assays.
      • If titer remission occurs spontaneously within 14 weeks and without a titer plateau, the Beta -hCG titer should then be repeated monthly for at least 1 year before the patient is released from close medical supervision
      • in cases of partial moles, Beta -hCG may be followed for 6–12 months(MCQ)
      • Factors that predict increase in the risk of persistent disease. (MCQ)
        • In general, at diagnosis, the larger the uterus and the higher the Beta-hCG titer, the greater the risk for malignant gestational trophoblastic disease.
        • The combination of theca lutein cysts and uterine size excessive for gestational age is associated with an extremely high risk (57%) of malignant sequelae
        • Pathologic specimens with marked nuclear atypia, presence of necrosis or hemorrhage, and trophoblastic proliferation may also
      • Effective contraceptive measures should be implemented
        • Oral contraceptives are the most widely used method. (MCQ)
      • If preevacuation chest radiography reveals pulmonary metastases
      • chest radiographs
        • should be repeated at 4-week intervals until spontaneous remission is confirmed
        • then at 3-month intervals during the remainder of the surveillance period.
      • Can the patient can become pregnant later
        • A patient who has entered into spontaneous remission with negative titers, examinations, and chest radiographs for 1 year and who is desirous of becoming pregnant may terminate contraceptive practices.
        • Successful pregnancy is usual, and complications are similar to those of the general population.
    • Abnormal Beta-hCG regression curve that mandates treatment during follow up
      • The most critical period of observation is the first 4–6 weeks postevacuation. (MCQ)
      • Beta-hCG should normalize by the 8th week
    • Indications for initiating chemotherapy during the postmolar surveillance period(MCQ)
      • Beta -hCG levels rising for 2 successive weeks or constant for 3 successive weeks
      • Beta -hCG levels elevated at 15 weeks postevacuation
      • rising Beta-hCG titer after reaching normal levels
      • postevacuation hemorrhage.
      • Treatment should also be instituted whenever there is a tissue diagnosis of choriocarcinoma.
    • Malignant Gestational Trophoblastic neoplasia
      • Malignant gestational trophoblastic neoplasia may be diagnosed in the setting of invasive mole, choriocarcinomas, placental-site trophoblastic tumors, and plateauing or rising postmolar Beta -hCG values
        • a plateau of 4 values ± 10% over a period of 3 weeks
        • a rise in Beta -hCG of > 10% of 3 values over a period of 2 weeks
        • persistence of detectable Beta -hCG > 6 months after evacuation
      • The most common site of metastases is the lung
    • Nonmetastatic Gestational Trophoblastic Disease
      • Therapy includes
      • single-agent chemotherapy
      • combined chemotherapy and hysterectomy (MCQ)
        • surgery done on the third day of drug therapy – Prerequisites
          • the patient does not wish to preserve reproductive function
          • her disease is known to be confined to the uterus.
      • Single-agent chemotherapy using methotrexate or dactinomycin
      • Methotrexate is contraindicated (MCQ)
        • in the presence of hepatocellular disease
        • when renal function is impaired
    • Categorization of Gestational Trophoblastic Neoplasia.
      • Good-prognosis metastatic disease—(MCQ)
        • Short duration (< 4 months).
        • Serum Beta-hCG < 40,000 mlU/mL.
        • No metastasis to brain or liver.
        • No significant prior chemotherapy.
      • Poor-prognosis metastatic disease(MCQ)
        • Long duration (> 4 months).
        • Serum Beta -hCG > 40,000 mlU/mL.
        • Metastasis to brain or liver.
        • Unsuccessful prior chemotherapy.
        • Gestational trophoblastic neoplasia following term pregnancy.

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      • Good-prognosis patient
        • Single-agent chemotherapy is generally successful.
        • Methotrexate is considered the drug of choice(MCQ)
        • Dactinomycin or patients who experience severe side effects with methotrexate.
      • Poor-prognosis patients
        • EMACO Regime provides the best response rate (MCQ)
          • etoposide, methotrexate
          • actinomycin D, cyclophosphamide
          • vincristine
          • chemotherapy
        • EP-EMA Regime(MCQ)
          • Salvage therapy for disease not responsive to EMACO
          • substitutes cisplatin and etoposide (EP-EMA) for cyclophosphamide and vincristine (CO)
        • Close monitoring of renal function is required
          • Nephrotoxicity can occur  secondary to cisplatin
          • methotrexate is renally excreted.
      • Placental-Site Trophoblastic Tumor
        • PSTT is generally is resistant to chemotherapy
        • hysterectomy is the recommended route of treatment. (MCQ)


      Gestational trophoblastic disease
      gestational trophoblastic disease
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      Gyn ch 06 01 fix Gestational Trophoblastic Neoplasia
      fix Gestational Trophoblastic Neoplasia
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