Placenta
Gestational trophoblastic disease
Neoplasms
Epithelioid trophoblastic tumor
Editorial Board Member: Carlos Parra-Herran, M.D.
Topic Completed: 1 May 2017
Minor changes: 11 October 2021
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PubMed Search: Placenta epithelioid trophoblastic tumor
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 October 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
Contributed by Sonali Lanjewar, M.D., M.B.B.S.
Mononucleate intermediate trophoblasts
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
