Molar pregnancy Flashcards
General findings
NB La mola causa/predispone PREECLAMPSIA
Complete mole is the result of paternal disomy!
Partial mole is the result of triploidy!
Gestational trophoblastic diseases (GTD) include hydatidiform moles (both complete and partial), invasive moles, and choriocarcinoma. They typically arise from the abnormal fertilization of the ovum. Hydatidiform moles are benign, whereas invasive moles and choriocarcinoma are malignant lesions with a tendency to metastasize to other organs, especially the lungs. Patients with GTD frequently present with vaginal bleeding and pelvic tenderness. Complete hydatidiform moles are associated with several additional clinical features (e.g., enlarged uterus, hyperemesis gravidarum, preeclampsia). Diagnosis is established based on a significantly elevated serum β-HCG and ultrasound findings (e.g., a mass that resembles a bunch of grapes in complete hydatidiform moles). If malignancy is suspected, workup must include an x-ray of the chest to screen for lung metastases. Hydatidiform moles are normally treated via dilation and curettage, whereas choriocarcinoma typically requires chemotherapy.
Definizione
NB Pur se considerata maligna, la mola invasiva a livello istologico non dimostra atipie tipiche di malignità.
Classified as complete or partial moles (see “Etiology” below)
!Benign trophoblastic disease
Proliferates within the uterus without myometrial infiltration or hematogenic dissemination
May develop malignant traits and become an invasive mole
No histologic signs of malignancy in the primary tumor
Trophoblasts infiltrate the myometrium and gain access to the vascular system.
Hematogenic dissemination leads to metastatic growth in different organs (brain, lungs, liver).
Risk factors
- Prior molar pregnancy
- History of miscarriage🧨
- Patients ≤ 15 and ≥ 35 years
Complete mole
46 XX
Does not contain any fetal or embryonic parts💥
Caused by fertilization of an empty egg that does not carry any chromosomes → The (physiological) haploid chromosome set contributed by the sperm is subsequently duplicated.
!In rare cases, the formation of a complete mole may also result from simultaneous fertilization of an empty egg by two sperms.
Fetal karyotypes
-46XX: more common (∼ 90% of cases)👓
-46XY: less common (∼ 10% of cases)
Partial mole
Contains fetal or embryonic parts in addition to trophoblastic tissue!
Caused by fertilization of an egg containing a haploid set of chromosomes with two sperms (each of them containing a haploid set of chromosomes as well)
Fetal karyotypes: 69XXX, 69XXY, 69XYY
Pathophysiology
Hydropic degeneration of chorionic villi with concomitant proliferation of cytotrophoblasts and syncytiotrophoblasts → death of the embryo
Invasive mole: trophoblasts invade the myometrium → increased risk of bleeding and hematogenous spread (Metastases without histological signs of malignancy.)
Clinical features
PREECLAMPSIA prima della 20th settimana!💥
I livelli di β-HCG sono maggiori nella mola completa
✔Complete mole
-Vaginal bleeding during the first trimester
-Uterus size greater than normal for gestational age
-Passage of vesicles that may resemble a bunch of grapes through the vagina
-Endocrine symptoms
1.Preeclampsia (before the 20th week of gestation)
2.Hyperemesis gravidarum
3.Ovarian theca lutein cysts: bilateral, large, cystic,
adnexal masses that are tender to the touch
-Hyperthyroidism
✔Partial mole
- Less severe symptoms due to β-HCG levels that are lower than in complete moles
- Vaginal bleeding
- Pelvic tenderness
Diagnostics
NB La mola idatiforme completa ha totale assenza di tessuto embrionale, di conseguenza non c’è liquido amniotico, tantomeno battito cardiaco!
Invece nella mola parziale è possibile visualizzare strutture fetali cosi come il liquido amniotico e la presenza di battito cardiaco. 👓
La diagnosi definitiva è ISTOPATOLOGICA🧨
Some moles may not produce HCG at all!
The diagnosis of a molar pregnancy might be suspected based on a number of clinical features: abnormal vaginal bleeding in early pregnancy is the most common presentation👓; uterus large for dates (25%); pain from large benign theca-lutein cysts (20%); vaginal passage of grape-like vescicles (10%); exaggerated pregnancy symptoms including hyperemesis (10%), hyperthyroidism (5%), early preeclampsia (5%).
Nowadays ultrasound scan often permits to diagnose molar pregnancy before 12 weeks, showing a fine vascular or honeycomb appearance. Later a complete mole is characteristically described as snowstorm appearance of mixed echogenicity, representing hydropic villi and intrauterine hemorrhage. The ovaries often contain multiple large theca-lutein cysts as a result of increased ovarian stimulation by excessive beta-hCG
In women with a complete mole, the quantitative serum beta-hCG level is higher than expected, often exceeding 100,000 IU/L. In case of a partial mole, the level of beta-hCG is often within the wide range associated with normal pregnancy and the symptoms are usually less pronounced. For these reasons the diagnosis of a partial mole is often missed clinically and made from subsequent histologic assessment of the abortive material 🧨
- Laboratory tests: β-HCG level measurement (initial test of choice), which should reveal β-HCG that is markedly elevated (higher than expected for the gestational age) (B-hcg raddoppia circa ogni 48 ore)
- Transvaginal ultrasound
✔Complete hydatidiform mole
- Theca lutein cysts
- Echogenic mass interspersed with many hypoechogenic cystic spaces that represent hydropic villi (referred to as “swiss cheese,” “bunch of grapes,” or “snowstorm”)
- No amniotic fluid
- Lack of fetal heart tones
✔Partial mole
- Fetal parts may be visualized.
- Fetal heart tones may be detectable.
- Amniotic fluid is present.
- Increased placental thickness
- Uterine evacuation (for definite diagnosis and treatment): histopathological examination of evacuated uterine specimen
- Chest x-ray: in case of dyspnea or chest pain
Treatment
1.Uterine evacuation by dilation and suction curettage: Complete moles have a 20% risk of becoming invasive and a 2% risk of developing into choriocarcinoma. Therefore, complete evacuation of the uterine cavity is the mainstay of treatment.👓
Monitor β-HCG levels until in reference range (usually 8–12 weeks)
In case of a suspected mole, further investigations include a complete blood count, measurement of creatinine and electrolytes, liver - kidney - thyroid function tests, and a baseline quantitative beta-hCG measurement. A careful pelvic and abdominal ultrasound scan should be done to look for evidence of an invasive mole, exclude a coexisting pregnancy, and look for possible metastatic disease. Computed tomography or magnetic resonance imaging may provide further information. Chest radiography or computed tomography should be considered if there are symptoms that suggest pulmonary metastases.
Suction curettage is the preferred method of evacuation regardless of uterine size in patients who desire to preserve fertility. It is best to avoid prior cervical preparation, oxytocic drugs and sharp curettage or medical evacuation, to minimize the risk of dissemination of tissue leading to metastatic diseaseh. Oxytocic agents and prostaglandin analogues are best used only after uterine evacuations when there is significant hemorrhage.
Total abdominal hysterectomy is a reasonable option for patients who do not wish to preserve their fertility. Hysterectomy is particularly advisable for patients >40 years whose risk of developing GTD is significantly increased. Though hysterectomy eliminates the risk of locally invasive disease, it does not prevent metastases and reduces the subsequent risk of persistent trophoblastic disease by up to 50%
- Chemotherapy (usually methotrexate) if unresolved, as indicated by any of the following: (mola invasiva)
- β-HCG values do not decrease.
- Histological features of malignant GTD are present.
- If metastases are present on chest x-ray.
Prognosis
Most patients achieve normal reproductive function after recovery!
NB associare terapia estroprogestinica per tutta la durata del trattamento con metotrexate!🧨
Follow-up
The aims of follow-up are to confirm successful treatment and to identify women with persistent or malignant GTD who may require adjuvant chemotherapy or surgery at an early stage. Persistent vaginal bleeding and above all elevation of serum beta-hCG levels are the main indicators of residual disease.
The outcome of a partial hydatidiform mole after uterine evacuation is almost always benign. Persistent disease occurs in 1.2% to 4% of cases; metastasis occurs only in 0.1% of cases (10). In complete moles, these risks are approximately 5 times greater after treatment with uterine evacuation and 2-3 times greater after hysterectomy
Persistence of detectable hCG for more than 6 months after molar evacuation: diagnosis of postmolar gestational trophoblastic disease
Use of reliable hormonal contraception is recommended while hCG values are being monitored. Oral contraceptives do not increase the incidence of postmolar gestational trophoblastic disease or alter the pattern of regression of hCG values . Frequent pelvic examinations are performed while hCG values are elevated to monitor the involution of pelvic structures and to aid in the early identification of vaginal metastases. Although pregnancies after molar evacuation usually are normal gestations, pregnancy obscures the value of monitoring hCG levels during this interval and may result in a delayed diagnosis of postmolar malignant gestational trophoblastic disease. A new intrauterine pregnancy should be ruled out on the basis of hCG levels and ultrasonography, especially when there has been a long delay in follow-up of serial hCG levels and noncompliance with contraception. After completion of documented remission for 6-12 months, women who desire pregnancy may discontinue contraception, and hCG monitoring may be discontinued. 👓Patients with prior partial or complete moles have a 10-fold increased risk (1-2% incidence) of a second hydatidiform mole in a subsequent pregnancy . Therefore, all future pregnancies should be evaluated by early obstetric ultrasonography.
Complete molar pregnancy is well recognized to have the potential for local invasion and distant spread. After evacuation, local uterine invasion occurs in about 15% and metastases in 4%. Complete molar pregnancy is usually divided into low and high risk for persistence based on signs and symptoms of marked trophoblastic proliferation at the time of evacuation, i.e.: hCG >100,000 mIU/Ml; excessive uterine enlargement; theca-lutein ovarian cyst >6 cm in diameter; older maternal age; a previous molar pregnancy. The risk of postmolar GTD is significant less with partial molar pregnancy and is seen in approximately 1-6% (15). Unfortunately there are no distinguishing clinical or pathologic features for predicting persistence after complete molar pregnancy.
Although controversial, the use of chemoprophylaxis at the time of evacuation of high-risk complete molar pregnancy has been shown to significantly decrease the development of GTD from approximately 50% to 10-15%
