Placenta

Gestational trophoblastic disease

Neoplasms

Epithelioid trophoblastic tumor



Last author update: 22 September 2022
Last staff update: 22 September 2022

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PubMed Search: Epithelioid trophoblastic tumor

Rachelle Mendoza, M.D.
Raavi Gupta, M.D.
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Cite this page: Mendoza R, Lanjewar S, Gupta R. Epithelioid trophoblastic tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/placentaETT.html. Accessed December 3rd, 2022.
Definition / general
  • Epithelioid trophoblastic tumor (ETT) is a very rare gestational trophoblastic tumor derived from neoplastic chorionic type intermediate trophoblasts
Essential features
  • Histologic features include nodular and expansile growth pattern of nests and cords of relatively uniform tumor cells with distinct cell borders, moderate eosinophilic to clear cytoplasm and associated extracellular eosinophilic, hyaline-like material
  • Presence of decidualized stromal cells in the periphery is a useful diagnostic clue
  • Diffuse immunohistochemical expression of p63 with essentially negative human placental lactogen (HPL) can help differentiate from placental site trophoblastic tumor
ICD coding
  • ICD-10:
    • C58 - malignant neoplasm of placenta
    • D39.2 - neoplasm of uncertain behavior of placenta
Epidemiology
Sites
Etiology
Clinical features
Diagnosis
  • Imaging
  • Clinical laboratory
  • Histopathologic diagnosis on biopsy or resection specimen
Laboratory
Radiology description
  • On ultrasound, it may appear as lobulated, echolucent or echogenic mass with intratumoral, scattered, branching vascularity and turbulent blood flow on color flow Doppler (Ultrasound Obstet Gynecol 2010;36:249)
  • Metastatic lesions may appear as mildly enhancing nodules on CT scan with clear boundaries and less uniform echoes (J Med Case Rep 2020;14:178)
  • MRI shows heterogeneously enhancing tumor with moderate hypointense signal on T1
Radiology images

Images hosted on other servers:

Ultrasound with Doppler

Abdominal wall mass CT

MRI of uterine masses

Prognostic factors
Case reports
Treatment
  • Surgical resection is the definitive treatment
  • Multi agent chemotherapy after surgery in metastatic disease (J Cancer 2019;10:11):
    • FAEV (5-fluorouracil, actinomycin-D, etoposide and vincristine)
    • EMA / CO (etoposide, methotrexate, actinomycin-D / cyclophosphamide and vincristine)
    • EMA / EP (etoposide, methotrexate, actinomycin-D / etoposide and cisplatin)
  • Recent benefit seen with administration of PD-1 / PDL1 immune checkpoint inhibitors (i.e., pembrolizumab) (Gynecol Oncol Rep 2021;37:100819)
Clinical images

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Hysteroscopy

Hysteroscopy

Laparoscopic surgery

Laparoscopic surgery

Gross description
  • Tumor presents as an expansile mass with white yellowish fleshy, solid appearance on cut surface and invades the underlying stroma
  • Necrosis and hemorrhage may also be present
  • Ulceration and fistula formation is common
Gross images

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Expansile mass with fleshy, solid appearance

Expansile mass with fleshy, solid appearance

ETT involving uterine fundus

ETT involving uterine fundus

Necrotic and hemorrhagic mass

Frozen section description
  • Nests and cords of epithelioid cells with eosinophilic to clear cytoplasm, distinct cell borders, moderate cytologic atypia and frequent mitosis; set in a hyaline matrix
  • Associated with geographic necrosis, apoptotic cells, focal calcifications and scattered decidualized stromal cells in the periphery
  • May be mistaken for squamous cell carcinoma
Frozen section images

Contributed by Rachelle Mendoza, M.D.
Nests and cords of epithelioid cells

Nests and cords of epithelioid cells

Large areas of necrosis

Large areas of necrosis

Microscopic (histologic) description
  • Tumor shows nodular, expansile growth of relatively uniform, medium sized tumor cells arranged in nests, cords or large sheets
  • Tumor cells have a moderate amount of finely granular, eosinophilic to clear cytoplasm with distinct cell membrane and round nuclei with small nucleoli
  • Moderate nuclear atypia is seen in most of the tumors
  • Well circumscribed tumor border is characteristic; however, focal infiltrative peripheral areas are not uncommon
  • Occasional syncytiotrophoblastic cells may be present; unless they represent a substantial population, they do not warrant a diagnosis of choriocarcinoma
  • Extensive or geographic necrosis is often present
  • Eosinophilic hyaline-like material is characteristically present in the center of some tumor nests, simulating keratin formation
  • The mitotic count ranges from 0 - 9 per 10 high power fields but as high as 48 per 10 high power fields has been observed
  • Focal areas of placental site nodule, placental site trophoblastic tumor and choriocarcinoma can rarely be identified within the tumor
  • Unique histologic features:
    • Scattered decidualized benign stromal cells may be present at the tumor periphery
    • Calcification is common
    • ETT tumor cells frequently colonize the mucosal surface or glandular epithelium of the cervix and endometrium and can simulate high grade squamous intraepithelial lesion or squamous epithelium
  • Reference: Am J Surg Pathol 1998;22:1393, Arch Pathol Lab Med 2019;143:65
Microscopic (histologic) images

Contributed by Rachelle Mendoza, M.D. and Sonali Lanjewar, M.D., M.B.B.S.
Nests

Nests

Epithelioid tumor cells Epithelioid tumor cells

Epithelioid tumor cells

Extensive necrosis

Extensive necrosis

Decidualized stroma in periphery

Decidualized stroma in periphery

ETT with chorionic-type intermediate trophoblasts

ETT with chorionic type intermediate trophoblasts


ETT with chorionic-type intermediate trophoblasts ETT with chorionic-type intermediate trophoblasts ETT with chorionic-type intermediate trophoblasts

ETT with chorionic type intermediate trophoblasts

p63

p63

CK5/6

CK5/6

Ki67

Ki67

Positive stains
Molecular / cytogenetics description
Molecular / cytogenetics images

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DNA genotyping analysis

Sample pathology report
  • Uterus and cervix; hysterectomy:
    • Epithelioid trophoblastic tumor (3.6 cm) involving the lower uterine segment and upper endocervix (see comment)
    • Comment: The partially necrotic tumor shows expansile growth of epithelioid tumor cells with eosinophilic to clear cytoplasm, distinct cell membranes and moderate nuclear atypia. Mitotic activity is moderately increased (up to 6 per 10 high power fields). Scattered decidualized stroma is present in the periphery. The tumor invades 1.2 cm into a 1.8 cm thick myometrium and extends 1.1 cm into a 2.3 cm thick cervix. Immunohistochemical stains show the tumor is positive for AE1 / AE3, p63, HLA-G, inhibin and cyclin E, with increased Ki67 proliferation index (20%) and negative for HPL, hCG, ER and PR. The overall findings support the above diagnosis.
Differential diagnosis
  • Cervical squamous cell carcinoma:
    • Definitive squamous intraepithelial lesion, true keratin formation, cell bridges, not associated with decidualized stromal cells at the periphery
    • hCG is not increased
    • Negative for trophoblastic differentiation markers
  • Endometrioid carcinoma:
    • Negative for trophoblastic differentiation markers, negative for p63
    • Associated with mismatch repair protein loss
    • ER and PR+
  • Placental site nodule (PSN):
    • Single to multiple, well circumscribed nodules usually < 5 mm in size
    • Mitotic activity is very low (Ki67 proliferation index < 8%)
  • Atypical placental site nodule:
    • Larger size of the nodule than PSN (> 5 to 10 mm), increased cellularity, marked nuclear atypia, moderately increased mitotic activity and Ki67 proliferation index between 8% and 10%
    • May have cyclin E expression
  • Placental site trophoblastic tumor:
    • Infiltrative pattern of growth
    • Negative for p63 with diffuse HPL expression
  • Choriocarcinoma:
    • Diffusely hemorrhagic, marked cytologic atypia, dimorphic trophoblastic population
    • Diffuse expression for hCG and very high Ki67 proliferation index (> 70%)
Board review style question #1
Epithelioid trophoblastic tumor Epithelioid trophoblastic tumor Epithelioid trophoblastic tumor


A 35 year old gravida 2 para 1 woman presents with vaginal bleeding. On ultrasound, a 2.5 cm fungating lower uterine mass / upper endocervical is identified. The findings from the biopsy specimen are shown in the images above. The immunohistochemical stains show positive expression for p63, HLA-G and inhibin and negative expression for HPL, PLAP, hCG and p16. What is the most likely diagnosis?

  1. Choriocarcinoma
  2. Epithelioid trophoblastic tumor
  3. Placental site trophoblastic tumor
  4. Squamous cell carcinoma of the cervix
Board review style answer #1
B. Epithelioid trophoblastic tumor

Comment Here

Reference: Epithelioid trophoblastic tumor
Board review style question #2
Which of the following immunohistochemical stains can help differentiate placental site trophoblastic tumor from epithelioid trophoblastic tumor?

  1. CD10
  2. hCG
  3. HSD3B1
  4. p63
Board review style answer #2
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