Placenta
Gestational trophoblastic disease
Epithelioid trophoblastic tumor

Author: Sonali Lanjewar, M.D., MBBS (see Authors page)
Editor: Raavi Gupta, M.D.
Editoral Board Member Review: Carlos Parra-Herran, M.D.

Revised: 20 October 2017, last major update May 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Placenta epithelioid trophoblastic tumor

Cite this page: Lanjewar, S. Epithelioid trophoblastic tumor. PathologyOutlines.com website. http://pathologyoutlines.com/topic/placentaETT.html. Accessed November 22nd, 2017.
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
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

Images hosted on other servers:

Trophoblastic cells in nests and sheets

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 question #1
All of the following are features of epithelioid trophoblastic tumor except:

  1. Calcification
  2. Diffusely positive for hPL
  3. Presence of geographic necrosis
  4. Tumor is well circumscribed and grows in nests, cords or solid masses
Board review answer #1
B. Diffusely positive for hPL