RESEARCH BREAKTHROUGHS IN GESTATIONAL TROPHOBLASTIC DISEASES

Gestational trophoblastic diseases (GTD) are a group of rare tumors that develop from the cells that would normally form the placenta during pregnancy.

The main types of trophoblastic tumors

Trophoblastic tumors are a group of rare cancers that develop from cells in the placenta. These tumors can be classified into several types based on their characteristics and behavior. The main types of trophoblastic tumors include:

1. Hydatidiform Mole: Also known as a molar pregnancy, this type of trophoblastic tumor occurs when there is an abnormal fertilization of the egg, leading to the growth of abnormal tissue in the uterus. Hydatidiform moles can be complete or partial, with complete moles having no fetal tissue and partial moles containing some fetal tissue.
2. Invasive Moles: Invasive moles are a type of trophoblastic tumor that grows into the muscle layer of the uterus and can invade nearby tissues. These tumors are more aggressive than hydatidiform moles and may require more intensive treatment.
3. Choriocarcinoma: Choriocarcinoma is a highly malignant trophoblastic tumor that develops from placental cells. This type of tumor can spread rapidly to other parts of the body, such as the lungs, liver, or brain. Choriocarcinoma is considered one of the most aggressive forms of gestational trophoblastic disease.
4. Placental Site Trophoblastic Tumor (PSTT): PSTT is a rare type of trophoblastic tumor that arises from the placental implantation site after a normal pregnancy or molar pregnancy. This tumor is characterized by slow-growing masses in the uterus and has a lower risk of metastasis compared to choriocarcinoma.
5. Epithelioid Trophoblastic Tumor: Epithelioid trophoblastic tumors are extremely rare and arise from placental tissue. These tumors are characterized by epithelioid cells with clear cytoplasm and distinct cell borders. Epithelioid trophoblastic tumors have a low potential for metastasis but can be locally aggressive.

Overall, trophoblastic tumors are rare but can have significant implications for reproductive health and require specialized management by healthcare providers familiar with these conditions.

The pathology of trophoblastic tumors

Trophoblastic tumors, including placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT), are rare gestational trophoblastic diseases. PSTT is characterized by the proliferation of intermediate trophoblasts at the placental implantation site, while ETT is derived from neoplastic chorionic type intermediate trophoblasts.

Pathological Features of Placental Site Trophoblastic Tumor (PSTT):

• Consists of aggregates or sheets of large, predominantly mononucleated cells composed of implantation site intermediate trophoblastic cells.
• Characteristic vascular invasion often present, with tumor cells replacing myometrial vessel walls.
• Positive for markers like HPL, CD146, and HSD3B1, but only focally positive for hCG and negative for PLAP.
• Serum beta hCG levels are low (< 1,000 mIU/mL).
• Typically diagnosed through biopsy or hysterectomy specimens.

Pathological Features of Epithelioid Trophoblastic Tumor (ETT):

• Nodular and expansile growth pattern of nests and cords of uniform tumor cells with distinct cell borders.
• Moderate eosinophilic to clear cytoplasm with associated extracellular eosinophilic, hyaline-like material.
• Presence of decidualized stromal cells in the periphery can aid in diagnosis.
• Immunohistochemical markers like p63 can help differentiate ETT from PSTT.

Epidemiology:

• PSTT: Occurs in patients usually in the reproductive age group, following full-term pregnancies or hydatidiform moles. Recurrence rate is around 25 – 30%.
• ETT: Typically seen in women aged 15 – 48 years, with a small percentage arising in premenopausal and postmenopausal women.

In summary, trophoblastic tumors exhibit distinct pathological features based on their subtype (PSTT or ETT), with specific immunohistochemical markers aiding in accurate diagnosis.

Diagnosis of Trophoblastic Tumors:

The diagnosis of trophoblastic tumors, including hydatidiform moles and gestational trophoblastic neoplasia (GTN), typically involves a combination of clinical evaluation, imaging studies, and laboratory tests. The following steps are commonly taken in the diagnostic process:

1. Clinical Evaluation: Patients with trophoblastic tumors may present with symptoms such as abnormal vaginal bleeding, an enlarged uterus, pelvic pain, or other signs like anemia, hyperemesis gravidarum, hyperthyroidism, or preeclampsia. A thorough medical history and physical examination are essential in the initial assessment.
2. Human Chorionic Gonadotropin (hCG) Levels: Since most trophoblastic tumors are associated with elevated hCG levels, a blood test to measure hCG levels is crucial. Persistently high or rising hCG levels can raise suspicion for trophoblastic disease.
3. Imaging Studies: Pelvic ultrasound is often used to visualize the uterus and detect abnormalities such as molar tissue or tumors. Transvaginal ultrasound may provide more detailed images in some cases.
4. Histopathological Examination: Definitive diagnosis of trophoblastic tumors is usually confirmed through histopathological examination of tissue samples obtained via procedures like dilation and curettage (D&C) or biopsy. This examination helps differentiate between different types of GTD, including hydatidiform moles and GTN.

Management and Treatment of Trophoblastic Tumors:

The management and treatment of trophoblastic tumors depend on various factors such as the type and stage of the disease, patient’s age and desire for future fertility, as well as overall health status. The main approaches to managing trophoblastic tumors include:

1. Hydatidiform Moles (HM):
   • Complete HM: Treatment often involves suction evacuation (D&C) to remove molar tissue from the uterus.
   • Partial HM: Similar management as complete HM but may require closer monitoring due to a higher risk of persistent disease.
2. Gestational Trophoblastic Neoplasia (GTN):
   • Chemotherapy: GTN is typically treated with chemotherapy regimens based on the risk category determined by factors like stage, hCG levels, and extent of disease spread.
   • Surgery: In some cases, surgical interventions like hysterectomy may be considered for resistant or advanced GTN.
3. Follow-Up Care:
   • Regular monitoring of hCG levels post-treatment is essential to assess response to therapy and detect any recurrence.
   • Psychological support and counseling are important for patients dealing with the emotional impact of trophoblastic tumors.

Overall, a multidisciplinary approach involving gynecologic oncologists, pathologists, radiologists, and other specialists is crucial in providing comprehensive care for patients with trophoblastic tumors.