Table of Contents
Definition / general | Sites | Etiology | Clinical features | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Lanjewar S, Gupta R. Epithelioid trophoblastic tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/placentaETT.html. Accessed January 25th, 2021.
Definition / general
- Trophoblastic tumor of neoplastic chorionic type intermediate trophoblast
- Rare type of gestational trophoblastic disease with only 110 case reports in the literature (Gynecol Oncol 2017;144:208)
Sites
- Common locations are:
- Uterus / lower uterine segment (40% of cases)
- Cervix (31% of cases) and lungs (19% of cases)
- Rarely it may arise in other locations:
- Vagina
- Broad ligament
- Fallopian tubes
- Other pelvic organs
Etiology
- ETT usually occurs in women of reproductive age (15 to 66 years); rarely, it can occur in postmenopausal women (Rom J Morphol Embryol 2016;57:1365, Gynecol Oncol 2002;87:219)
- Usually seen after normal term pregnancies but can occur after any pregnancy event including molar pregnancy
Clinical features
- ETTs exhibit slow growth and remain confined to the uterus for extended periods of time; as a result, patient commonly present with vaginal bleeding or amenorrhea
- Most common presenting symptom is vaginal bleeding, which is associated with mild elevation of serum β hCG (< 2,500 IU/l) (Gynecol Oncol 2002;87:219)
- Prior gestational trophoblastic tumor present in ~20% of cases, prior normal pregnancy in 63% of cases and prior spontaneous abortion in 17% of cases (Acta Cytol 2014;58:198)
- Average interval between the preceding gestation and the diagnosis of ETT is more than 6 years (range is 2 weeks to 30 years) (Acta Cytol 2014;58:198, Int J Gynecol Pathol 2001;20:31)
- Epithelioid trophoblastic tumors (ETTs) are resistant to chemotherapy
- Mitotic count of > 6/10 HPF is an unfavorable prognostic factor (Am J Obstet Gynecol. 2011;204:11, Kurman: WHO Classification of Tumours of Female Reproductive Organs, 4th Edition, 2014)
- Metastasis occur in 25% of cases and 10% die of the disease
- Survival is 100% when confined to the uterus but decreases to 50 - 60% in patients with metastasis
Treatment
- Stage I disease is treated with hysterectomy
- Metastatic disease is treated with surgery and chemotherapy
Gross description
- Discrete nodules or cystic hemorrhagic masses deeply infiltrate the surrounding structures
- Cut surface is white to tan brown with hemorrhage and necrosis
- Ulceration and fistula formation is common
Microscopic (histologic) description
- Nodular and well circumscribed, focally infiltrative at the periphery
- Tumor cells are relatively uniform, mononucleate arranged in nests and cords
- Tumor nests are intimately associated with an eosinophilic, fibrillar, hyaline-like material (composed of type IV collagen and fibronectin of oncofetal and adult types)
- Extensive geographic necrosis is present
- Calcification is common in epithelioid trophoblastic tumors, which is unique among all gestational trophoblastic diseases / GTDs; i.e. calcification is NOT present in placental site trophoblastic tumor / PSTT or choriocarcinoma
- Chorionic type intermediate trophoblast has moderate eosinophilic to clear (glycogen rich) cytoplasm with distinct cell membranes, round nuclei and distinct small nucleoli
- Decidualized stromal cells may be found at the periphery of the tumor (Mod Pathol 2006;19:75, Kurman: WHO Classification of Tumours of Female Reproductive Organs, 4th Edition, 2014)
- Focal areas of placental site nodule, PSTT and choriocarcinoma can rarely be identified within the tumor (Gynecol Oncol Rep 2015;14:31, Kurman: Blaustein's Pathology of the Female Genital Tract, 6th Edition, 2011)
- ETT can replace and reepithelialize endocervical or endometrial surface epithelium and can mimic squamous epithelium
Microscopic (histologic) images
Positive stains
Negative stains
Molecular / cytogenetics description
- Most tumors have no Y chromosome complement
Differential diagnosis
- Atypical placental site nodule: characterized by trophoblastic cytologic atypia (moderate or severe) and borderline proliferation index (Ki67 8 - 10%); usually incidental
- Keratinizing squamous cell carcinoma of the cervix: particularly challenging, immunoprofile of CK18- and CK5 / 6+, p16+ helps differentiate from ETT
- Placental site nodule: usually microscopic lesion discovered incidentally, less cellular, bland nuclear morphology, extensive hyalinization, no calcification, no necrosis, paucity of mitotic activity and low Ki67 index (less than 8%)
- Placental site trophoblastic tumor: infiltrative growth, no calcification, no necrosis; diffuse expression of Mel-CAM and hPL, Ki67 (10 - 30%)
Board review style question #1
All of the following are features of epithelioid trophoblastic tumor except:
- Calcification
- Diffusely positive for hPL
- Presence of geographic necrosis
- Tumor is well circumscribed and grows in nests, cords or solid masses
Board review style answer #1