GTD Case Study
GTD Case Study
GTD Case Study
http://www.ayubmed.edu.pk/JAMC/PAST/21-94 1/Khairunnisa.pdf
GESTATIONAL TROPHOBLASTIC DISEASE: EXPERIENCE AT
NAWABSHAH HOSPITAL
Khairunnisa Nizam, Gulfareen Haider*, Nizamuddin Memon**, Ambreen Haider†
Department of Obstetrics and Gynaecology, Nawabshah Medical College Hospital, Nawabshah, *Department
of Obstetrics and
Gynaecology, Isra University Hospital, **Department of Radiology, †Department of Cardiology, Liaquat
University of Medical Health
Sciences Hospital, Hyderabad, Pakistan
Background: Gestational Trophoblastic Disease (GTD) is a heterogeneous group of diseases that
includes partial and complete hydatidiform mole, invasive mole, choriocarcinoma and placental site
trophoblastic tumour. The incidence of GTD varies in different parts of the world. The malignant
potential of this disease is higher in South East Asia in comparison to western countries. Objectives of
study were to determine the frequency, clinical presentation and management outcomes of GTD. This
retrospective, descriptive case series was conducted in the Department of Obstetric and Gynaecology
Nawabshah Medical College Hospital, from 1st Jan 2007 to 30th Dec 2007.
Methods: The case records
of all the gestational trophoblastic cases during study period were analysed regarding their history,
clinical examination, investigations, treatment and follow-up. The main outcomes were measured in
terms of duration, antecedent pregnancy, investigations, treatment and the follow-up.
Results: There
were a total of 1056 Obstetric admissions during the study period, which included 30 cases of
trophoblastic disease with a frequency of GTD was 28 per 1000 live births. Of these 30 cases, 21 (70%)
patients had hydatidiform mole, 7 (23.3%) patients had invasive disease and 2 (6.6%) patients had
choriocarcinoma. Twenty three patients (76.6%) received chemotherapy while 25 (83.3%) patients had
suction evacuation and 4 (13.3%) patients underwent hysterectomy. Among all patients, 29(96.7%)
fully recovered and 1 (3.3%) died because of extensive disease; metastasis extending up to brain.
Conclusion: Frequency of GTD was higher compared to national and international studies. The disease
was common in extremes of ages, low para and grand multiparous women. Hydatidiform mole was the
commonest type of trophoblastic disease in these patients. Most common presenting complaint was
bleeding per vagina followed by pain in lower abdomen.
Keywords: Gestational trophoblastic disease, Hydatidiform mole, Management
Developmental anomaly of the placenta that converts the chorionic villi into a mass of clear fluid-filled
vesicles.
Two types of moles:
Pathophysiology
Trophoblastic villi cells located in the outer ring of the blastocyst (the structure that develops via cell division
around 3 to 4 days after fertilization) rapidly increase in size, begin to deteriorate, and fill with fluid.
The cells become edematous, appearing a grapelike clusters of vesicles.
As a result, the embryo falls to develop past the early stages.
Causes
Assessment findings
Disproportionate enlargement of the uterus; possible grapelike clusters noted in the vagina on pelvic
examination.
Excessive nausea and vomiting, abdominal cramping.
Intermittent or continuous bright red or brownish vaginal bleeding
Passage of tissue resembling grapelike clusters.
Symptoms of gestational hypertension before 20 weeks’ gestation.
Absence of fetal heart tones.
Test Results:
Radioimmunoassay of human chorionic gonadotropin (hCG) levels reveals extremely elevated levels of
early pregnancy.
Histologic examination may reveal the presence of vesicles.
Ultrasonography performed after 3 months’ gestation reveals grapelike clusters rather than a fetus, an
absence of fetal skeleton, and evidence of a snowstorm-like pattern.
Hemoglobin level, hematocrit, red blood cells (RBC) count, prothrombin time, partial thromboplastin time,
fibrinogen levels, and hepatic and renal function findings are all abnormal.
White blood cells count and erythrocyte sedimentation rate are increased.
Treatment:
Nursing Interventions:
Introduction
Background
Gestational trophoblastic disease (GTD) can be benign or malignant. Histologically, it is classified into hydatidiform
mole, invasive mole (chorioadenoma destruens), choriocarcinoma, and placental site trophoblastic tumor (PSTT).
Those that invade locally or metastasize are collectively known as gestational trophoblastic neoplasia (GTN).
Hydatidiform mole is the most common form of GTN. While invasive mole and choriocarcinoma are malignant, a
hydatidiform mole can behave in a malignant or benign fashion.
Histologic section of a complete hydatidiform mole stained with hematoxylin and eosin. Villi of different sizes
are present. The large villous in the center exhibits marked edema with a fluid-filled central cavity known as
cisterna. Marked proliferation of the trophoblasts is observed. The syncytiotrophoblasts stain purple, while
the cytotrophoblasts have a clear cytoplasm and bizarre nuclei. No fetal blood vessels are in the
mesenchyme of the villi.
[ CLOSE WINDOW ]
Histologic section of a complete hydatidiform mole stained with hematoxylin and eosin. Villi of different sizes
are present. The large villous in the center exhibits marked edema with a fluid-filled central cavity known as
cisterna. Marked proliferation of the trophoblasts is observed. The syncytiotrophoblasts stain purple, while
the cytotrophoblasts have a clear cytoplasm and bizarre nuclei. No fetal blood vessels are in the
mesenchyme of the villi.
No methods exist to accurately predict the clinical behavior of a hydatidiform mole by histopathology. The clinical
course is defined by the patient's serum human chorionic gonadotropin (hCG) curve after evacuation of the mole. In
80% of patients with a benign hydatidiform mole, serum hCG levels steadily drop to normal within 8-12 weeks after
evacuation of the molar pregnancy. In the other 20% of patients with a malignant hydatidiform mole, serum hCG
levels either rise or plateau.1,2
Pathophysiology
A hydatidiform mole is considered malignant when the serum hCG levels plateau or rise during the follow-up period
and an intervening pregnancy is excluded. This occurs in 15-20% of hydatidiform moles.1,2,3
A hydatidiform mole with a fetus or fetal tissue and a triploid karyotype is known as a partial or incomplete mole.
Partial moles also have malignant potential, but only 2-3% become malignant.4,5,6 Cases of partial hydatidiform moles
with lung metastasis have been reported and at least one case of choriocarcinoma on a biopsy from a vaginal
metastasis has been reported in a patient being observed for a partial hydatidiform mole.7,8
An invasive mole has the same histopathologic characteristics of a hydatidiform mole, but invasion of the
myometrium with necrosis and hemorrhage occurs or pulmonary metastases are present.
Histologically, choriocarcinomas have no villi, but they have sheets of trophoblasts and hemorrhage.
Choriocarcinomas are aneuploid and can be heterozygous depending on the type of pregnancy from which the
choriocarcinoma arose. If a hydatidiform mole preceded the choriocarcinoma, the chromosomes are of paternal
origin. Maternal and paternal chromosomes are present if a term pregnancy precedes the choriocarcinoma. Of
choriocarcinomas, 50% are preceded by a hydatidiform mole, 25% by an abortion, 3% by ectopic pregnancy, and the
other 22% by a full-term pregnancy.1 Choriocarcinoma has also been associated with ectopic pregnancy with a
theoretic incidence of 1 in 5333 ectopic pregnancies.9
Placental site trophoblastic tumor is a rare form of gestational trophoblastic neoplasia, with slightly more than 200
cases reported in the literature.10,11 In patients with PSTT, intermediate trophoblasts are found infiltrating the
myometrium without causing tissue destruction. The intermediate trophoblasts contain human placental lactogen
(hPL).12 These patients have persistent low levels of serum hCG (100-1000 mIU/mL). However, serum hCG levels as
high as 108,000 mIU/mL have been reported in patients with PSTT.13 The treatment of PSTT is hysterectomy with
ovarian conservation.14 If the tumor recurs or metastases are present at initial diagnosis, chemotherapy is
administered with variable results.15,16 Radiation therapy may provide local control.
The most frequent sites of metastases of malignant gestational trophoblastic neoplasia are the lungs, lower genital
tract, brain, liver, kidney, and gastrointestinal tract.
In this microphotograph of a choriocarcinoma metastatic to the brain, the neuropil is seen on the right and
the biphasic (2 cell populations) choriocarcinoma is seen to the left with hemorrhage at the left border of the
photograph (H&E stain).
Frequency
United States
Gestational trophoblastic neoplasia is diagnosed in 15-20% of patients with a complete hydatidiform mole and 2% of
partial hydatidiform moles. Lung metastases are found in 4-5% of patients with complete hydatidiform moles and
rarely in cases of partial hydatidiform moles.
International
The international rate of choriocarcinoma has been reported to be as high as 1 in 500-600 pregnancies in India to 1
in 50,000 pregnancies in Mexico, Paraguay, and Sweden.17,19,20 These differences are probably due to differences in
methodology (eg, identification of cases, accuracy of denominator).17,19
Mortality/Morbidity
Patients who have a malignant hydatidiform mole, an invasive mole, or a choriocarcinoma should undergo a
systematic search for metastases. Patients who have metastases are classified as high-risk or low-risk according to
the National Institutes of Health classification.2 The criteria for high-risk metastatic gestational trophoblastic neoplasia
include hepatic or brain metastasis, serum hCG levels greater than 40,000 mIU/mL prior to the initiation of
chemotherapy, duration of disease longer than 4 months, prior unsuccessful chemotherapy, and malignant
gestational trophoblastic neoplasia following a term pregnancy.
Patients with malignant nonmetastatic or metastatic low-risk gestational trophoblastic neoplasia have an
almost 100% probability of cure with chemotherapy. The probability of cure after chemotherapy for patients
with metastatic high-risk gestational trophoblastic neoplasia is approximately 75%.21
The probability of a late recurrence after the patient has been in remission (normal serum beta-hCG titers)
for 1 year is less than 1%.2,22
Race
Little information is available on international ethnic or racial differences of the incidence of choriocarcinoma.
In the United States, African Americans have the highest incidence of choriocarcinoma and the lowest
survival rates.23
Sex
Gestational trophoblastic neoplasia affects women during their reproductive years. However, placental site
trophoblastic tumors have been diagnosed when patients were postmenopausal.
Age
The incidence of choriocarcinoma increases with age and is 5-15 times higher in women 40 years and older than in
younger women.19
Clinical
History
Most cases of gestational trophoblastic neoplasia are diagnosed when the serum hCG levels plateau or rise in
patients being observed after the diagnosis of hydatidiform mole. If metastases are present, signs and symptoms
associated with the metastatic disease, such as hemoptysis, abdominal pain, hematuria, and neurologic symptoms,
may be present.
Physical
Metastasis to the lower genital tract present as purple to blue-black papules or nodules. These are
extremely vascular and might bleed profusely if biopsied.24
Abdominal tenderness may be present if liver or gastrointestinal metastases have occurred.
Abdominal guarding and rebound tenderness may be present if a hemoperitoneum has occurred due to
bleeding from an abdominal metastasis. Bleeding from a metastasis could also result in signs and symptoms
of hemorrhagic shock.25,26
Neurologic deficits, from lethargy to coma, can be encountered if brain metastasis has occurred.
Jaundice may be present if liver metastasis causes biliary obstruction.
Causes
Why some hydatidiform moles become malignant and others do not is unknown. However, mounting evidence shows
different molecular profiles between nonmalignant and malignant gestational trophoblastic disease
Treatment
Medical Care
Patients with gestational trophoblastic disease (GTD) do not require medical therapy. Because 20% of patients with
hydatidiform mole develop malignant disease, such as persistent hydatidiform mole with or without metastasis, some
have suggested the use of a prophylactic dose of methotrexate in noncompliant patients.39,40 However, observing
patients with weekly serum hCG levels is preferable, and only patients with rising or plateauing titers, as occurs in
patients with gestational trophoblastic neoplasia (GTN), should be treated with chemotherapy.1
Patients with nonmetastatic GTN or metastatic low-risk GTN are treated with single-agent chemotherapy.41,42,43,44,45,46
Many in the United States prefer methotrexate. However, actinomycin D can be used in patients with poor liver
function. During treatment, the serum hCG levels are monitored every week. One additional course of chemotherapy
is administered after a normal serum hCG level. After 3-4 normal serum hCG levels, the levels are observed once per
month for 1 year. A switch from methotrexate to actinomycin D is made if the patient receiving methotrexate for
nonmetastatic or metastatic low-risk GTN develops rising or plateauing serum hCG levels.
A randomized clinical trial comparing 30 mg/m2 methotrexate given weekly to patients with low-risk GTN versus 1.25
mg/m2 of actinomycin D given every other week showed a higher complete response rate with actinomycin D.47
Patients with high-risk metastatic GTN are subdivided into 2 groups: those with a WHO score of less than 7 and
those with a score of 7 or higher and who are at high risk of therapy failure.
Patients with a WHO score of less than 7 can be treated with single-agent chemotherapy (methotrexate or
actinomycin) because their chances of achieving a cure are high.48 AT least 1 additional course of
chemotherapy is administered after a normal serum hCG level is achieved.
Patients with WHO scores of 7 or higher
o These patients are treated with a combination of etoposide, methotrexate, and actinomycin D
administered in the first week of a 2-week cycle and cyclophosphamide and vincristine (Oncovin)
administered in the second week.49,50,51,52 This is known as the EMA-CO regimen.
o Some substitute cisplatin and etoposide for cyclophosphamide and vincristine during the second
week. This is known as the EMA-CE regimen.53 Some reserve the EMA-CE regimen for patients in
whom EMA-CO fails.
o At least 2 additional courses of EMA-CO or EMA-CE are administered after a normal serum hCG
level.
o Patients with metastasis to the brain receive whole brain irradiation (3000 cGy) in combination with
chemotherapy.54,55,56 Corticosteroids (dexamethasone) with systemic effect are administered to
reduce brain edema. This is the most common approach in the United States.
o Early neurosurgical intervention for solitary lesions or stereotactic radiotherapy for multiple lesions
or solitary lesions in locations at high risk for surgical morbidity is used at the Charing Cross
Hospital in the United Kingdom and has been reported by physicians from Duke University in North
Carolina.57 At Charing Cross, neurosurgery is followed by moderate- and high-dose intravenous
methotrexate and intrathecal methotrexate. However, intrathecal methotrexate is not routinely used
by others. A therapeutic level of methotrexate is achieved in the cerebrospinal fluid at doses of
methotrexate >600 mg/m2 given intravenously to patients with brain metastases.57
o In patients not receiving whole brain irradiation, the dose of methotrexate on day 1 of the EMA-CO
or EMA-CE regimen is increased to 1000 mg/m2. Instead of 4 doses of folinic acid, 8 doses are
given starting 24 hours after the methotrexate infusion. Patients with liver metastasis are
considered for liver irradiation (2000 cGy).58
Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO
score is less than 7, which is uncommon.
After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed
with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is
evaluated for possible intervening pregnancy, or persistent or recurrent disease.
Surgical Care
A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Hysterectomy may reduce the
total number of chemotherapy cycles needed to achieve remission.36,37
Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control
hemorrhage. Hepatic artery embolization has been used successfully to control hemorrhage from hepatic
metastases.25
A repeat D&C in the presence of persistent tissue on pelvic ultrasonography may reduce the number of
chemotherapy cycles needed to achieve remission.59
Craniotomy may be needed to control bleeding and provide decompression.57,51
Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a
remission.60,61,62
Consultations
Diet
No restrictions
Activity
No restrictions
Medication
The goals of pharmacotherapy are to reduce morbidity and to eradicate the neoplasm.
Antineoplastics
Gestational trophoblastic tumors are sensitive to many antineoplastic agents, especially those that act in the S phase
or the M phase of the cell cycle.