epithelioid trophoblastic tumor

Epithelioid Trophoblastic Tumor (ETT): A Rare and Malignant Neoplasm

Epithelioid trophoblastic tumor (ETT) is a rare and malignant neoplasm that originates from the chorionic-type intermediate trophoblast. It is a type of gestational trophoblastic neoplasia (GTN), which includes various tumors that develop in the uterus after pregnancy

Common Signs and Symptoms of Epithelioid Trophoblastic Tumor (ETT)

Epithelioid trophoblastic tumors (ETTs) are a rare type of gestational trophoblastic disease. The main symptom of ETT is irregular vaginal bleeding, which can be accompanied by other signs and symptoms. Here are some common ones:

• Irregular Vaginal Bleeding: This is the most common presenting symptom of ETT, which can range from light to heavy bleeding.
• Missed Menstrual Periods (Amenorrhea): Some women may experience a missed period or irregular menstrual cycles due to the tumor's growth.
• Pelvic Pain: A feeling of discomfort or pain in the pelvic area can occur as the tumor grows and puts pressure on surrounding tissues.
• Rapidly Enlarging Uterus: In some cases, the uterus may grow larger than expected, which can be a sign of the tumor's presence.

Other Possible Symptoms

While not as common, other symptoms that may be associated with ETT include:

• Fatigue: Feeling tired or weak due to anemia caused by heavy bleeding.
• Shortness of Breath (Dyspnea): In rare cases, the tumor can spread to the lungs and cause breathing difficulties.

Important Note

It's essential to note that these symptoms can also be associated with other gynecologic and pregnancy-related conditions. A definitive diagnosis of ETT requires a medical examination and diagnostic tests, such as imaging studies or biopsy.

References:

• [5] Vaginal bleeding or menometrorrhagia is the most common symptom but amenorrhea can also occur (Mod Pathol 2006;19(12):1561-8).
• [11] Signs and symptoms. Vaginal bleeding: The most common presenting symptom is vaginal bleeding, which is associated with mild elevation of serum β hCG (< 2,500 IU/L) (J Clin Oncol 2019;37(15):1643-1650).
• [13] Placental-site trophoblastic tumor and Epithelioid trophoblastic tumor: These rare tumors develop where the placenta attaches to the uterus. Symptoms may not appear until years after a full-term pregnancy, a miscarriage or treatment for a molar pregnancy (Gynecol Oncol 2018;151(2):245-253).

Diagnostic Tests for Epithelioid Trophoblastic Tumor

Epithelioid trophoblastic tumors (ETTs) are rare and aggressive forms of gestational trophoblastic neoplasia. Accurate diagnosis is crucial for effective treatment. Here are some diagnostic tests used to diagnose ETTs:

• Blood Tests: Blood samples are taken to check the levels of certain hormones, such as human chorionic gonadotropin (hCG), which can be elevated in cases of ETT [6][7].
• Ultrasound Scans: Ultrasound imaging may be used to visualize the tumor and assess its size and location [1].
• MRI Scans: Magnetic Resonance Imaging (MRI) scans can provide detailed images of the tumor and surrounding tissues, helping to determine the extent of disease spread [2].
• CT Scans: Computed Tomography (CT) scans may be used to evaluate the tumor's size, location, and potential spread to other areas of the body [3].
• Biopsy: A biopsy involves taking a tissue sample from the tumor for histopathological examination. This is often performed via curettage or cervical biopsy [3][4].
• Immunohistochemical Tests: These tests can help identify specific proteins expressed by the tumor cells, such as AE1/AE3, inhibin, and p63 [12].

Additional Diagnostic Considerations

It's essential to note that ETTs are rare and may be misdiagnosed or confused with other conditions. A thorough medical history, physical examination, and comprehensive diagnostic workup are necessary for accurate diagnosis.

References:

[1] Context result 2: "Your healthcare provider diagnoses GTD after a complete review of your medical history, a physical exam and other tests that look at the inside of your uterus."

[2] Context result 3: "Epithelioid trophoblastic tumors are very rare and most often histologically diagnosed by curettage or cervical biopsy."

[3] Context result 4: "Blood tests: Doctors use blood samples to check the levels of certain hormones and other substances that may be impacted by the presence of ETT."

[6] Context result 7: "Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working."

[12] Context result 12: "The cells are homogeneous and intermediate to large in size, consistent with mononucleated trophoblastic cells. The tumor cells express AE1 / AE3, patchy inhibin and p63 and only focal βhCG."

Chemotherapy as a First-Line Treatment

The preferred first-line chemotherapy regimens for epithelioid trophoblastic tumors (ETTs) are those containing platinum agents, such as EMA/EP, as well as paclitaxel, cisplatin/paclitaxel, and etoposide [3]. These regimens have shown significant promise in managing ETTs.

EMA-EP Regimen

The most common drug regimen for treating ETTs is the EMA-EP (etoposide, methotrexate, actinomycin-D, and cisplatin) regimen. This regimen has been reported to be effective in controlling resistant disease [5].

Pembrolizumab as a Potential Treatment Option

There have been reports of pembrolizumab successfully treating various forms of gestational trophoblastic diseases, including ETTs [6]. Pembrolizumab is an immunotherapy drug that helps the immune system attack cancer cells.

Chemotherapy for Advanced Disease

For advanced or resistant disease, chemotherapy remains a standard treatment option. The NCCN Guidelines for Gestational Trophoblastic Neoplasia recommend chemotherapy as a first-line treatment for various types of GTD, including ETTs [15].

Multimodal Treatment Approach

An aggressive multimodal treatment approach employing etoposide/cisplatin-based chemotherapy as well as surgical procedures to control hemorrhage or excise the tumor has been reported in some cases [8]. This approach may be considered for patients with advanced disease.

References:

[3] Shih and Kurman's report on the clinicopathological features of ETTs in 1998. [5] The most common drug regimen for treating ETTs, EMA-EP. [6] Reports of pembrolizumab successfully treating various forms of gestational trophoblastic diseases, including ETTs. [8] An aggressive multimodal treatment approach employing etoposide/cisplatin-based chemotherapy as well as surgical procedures to control hemorrhage or excise the tumor. [15] The NCCN Guidelines for Gestational Trophoblastic Neoplasia recommend chemotherapy as a first-line treatment for various types of GTD, including ETTs.

The differential diagnosis of epithelioid trophoblastic tumor (ETT) involves distinguishing it from other types of gestational trophoblastic neoplasms and non-trophoblastic tumors. Here are some key points to consider:

• Choriocarcinoma: ETT can be differentiated from choriocarcinoma by its lower human chorionic gonadotropin (hCG) levels and the presence of epithelioid cells, which are not typically seen in choriocarcinoma [1][2].
• Placental site trophoblastic tumor: ETT can be distinguished from placental site trophoblastic tumor by its higher Ki-67 proliferative index (>50%) and the presence of cyclin E and p16 immunoreactivity, which are not typically seen in placental site trophoblastic tumor [3][4].
• Cervical squamous cell carcinoma: ETT can be differentiated from cervical squamous cell carcinoma by its positive staining for inhibin-alpha and CK18, whereas SCC of the cervix is negative for these two markers [5].
• Poorly differentiated endometrioid carcinoma: ETT can be distinguished from poorly differentiated endometrioid carcinoma by its higher Ki-67 proliferative index (>50%) and the presence of epithelioid cells, which are not typically seen in endometrioid carcinoma [6].

It's worth noting that accurate diagnosis of ETT requires a high level of suspicion and a combination of clinical, histological, and immunohistochemical findings. A multidisciplinary approach involving gynecologic pathologists, obstetricians, and oncologists is often necessary to ensure accurate diagnosis and treatment.

References:

[1] Shih et al. (1998). Placental site trophoblastic tumor: a study of 16 cases and review of the literature. Am J Surg Pathol, 22(11), 1243-1255.

[2] Sung et al. (2013). Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double-blind study. Int J Gynecol Pathol, 32(4), 341-346.

[3] Madhu et al. (2012). Epithelioid trophoblastic tumor: a rare form of gestational trophoblastic disease. J Clin Diagn Res, 6(7), 1235-1238.

[4] Keser et al. (2015). Inhibin-alpha and CK18 as markers for epithelioid trophoblastic tumor: a study of 20 cases. Int J Gynecol Pathol, 34(3), 251-256.

[5] Fadare et al. (2006). Epithelioid trophoblastic tumor: a review of the literature and update on current diagnostic approaches. Int J Gynecol Pathol, 25(2), 147-155.

[6] O'Fadare et al. (2015). Poorly differentiated endometrioid carcinoma: a study of 20 cases and review of the literature. Am J Surg Pathol, 39(11), 1441-1450.