Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Gupta P, Mehta V. Epithelioid trophoblastic tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testisepithelioidtrophoblastictumor.html. Accessed December 4th, 2024.
Definition / general
- Testicular trophoblastic tumors show a morphologic spectrum analogous to the trophoblastic tumors of the female genital tract including choriocarcinoma, epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT)
- Other than choriocarcinoma, these other trophoblastic tumors are very rare in the testis but have been reported on occasion in association with a history of other germ cell tumor types
Essential features
- Epithelioid trophoblastic tumor (ETT) is an unusual trophoblastic tumor, distinct from choriocarcinoma and placental site trophoblastic tumor (PSTT) with morphologic features similar to a carcinoma
- ETT has a squamoid appearance, with mostly mononucleated trophoblastic cells and a variable amount of fibrinoid material surrounding the tumor clusters and vessels
- Both morphologic and immunohistochemical studies show that ETT is mainly composed of chorionic type intermediate trophoblastic cells
Terminology
- Atypical choriocarcinoma
ICD coding
- ICD-O: 9105/3 - trophoblastic tumor, epithelioid
- ICD-11: 2C80.Y & XH8FW3 - other specified malignant neoplasms of testis & trophoblastic tumor, epithelioid
Epidemiology
- Rare gestational trophoblastic neoplasm with only 6 ETTs described in men (Am J Surg Pathol 2009;33:1902, Am J Surg Pathol 2015;39:1468, Indian J Urol 2022;38:230)
- Typically occurs in young men between 19 and 43 years
- Mean age: 44 (range: 20 - 68 years) (Hum Pathol 2024;153:105673)
Sites
- Usually at metastatic sites (lymph nodes, lung) (Hum Pathol 2024;153:105673)
- Rarely testis (Hum Pathol 2024;153:105673)
Pathophysiology
- Pathogenesis is not clear but it has been suggested that the tumor arises within a mixed germ cell tumor after reprogramming in the differentiation of the neoplastic cytotrophoblasts to produce ETT (Lancet Oncol 2007;8:642)
- Chemotherapy may contribute to the differentiation of choriocarcinoma into ETT, which is more refractory to chemotherapy owing to its low proliferation activity; consequently, the ETT cells survive after the destruction of choriocarcinoma (Lancet Oncol 2007;8:642, Pathology 2018;50:88)
Etiology
- Seems to develop from the neoplastic transformation of cytotrophoblastic cells that assume a differentiation toward the chorionic type intermediate trophoblastic cells that are normally found in chorion laeve (fetal membrane)
Clinical features
- Usually found in metastases (Am J Surg Pathol 2015;39:1468, Indian J Urol 2022;38:230, Am J Surg Pathol 2009;33:1902, Hum Pathol 2024;153:105673)
- Metastases and recurrence can occur years after orchiectomy despite chemotherapy (mean: 11 years) (Am J Surg Pathol 2015;39:1468, Indian J Urol 2022;38:230, Am J Surg Pathol 2009;33:1902, Hum Pathol 2024;153:105673)
Diagnosis
- Based on characteristic morphology and immunoprofile
Laboratory
- May be associated with mild elevation of beta human chorionic gonadotrophin (βhCG)
Radiology description
- No characteristic features
Prognostic factors
- A subset of cases have an aggressive course (Hum Pathol 2024;153:105673)
Case reports
- 31 year old man with metastatic epithelioid trophoblastic tumor in retroperitoneal nodes (Indian J Urol 2022;38:230)
- 39 year old man with metastatic epithelioid trophoblastic tumor (Am J Surg Pathol 2009;33:1902)
Microscopic (histologic) description
- Several growth patterns may be present including cohesive nests of squamoid cells with abundant pink cytoplasm and lacking associated hemorrhage
- Tumor cells have single pleomorphic and hyperchromatic nuclei with prominent nucleoli and occasional multinucleation along with well defined cytoplasmic membranes without discernible intercellular bridges
- Intracytoplasmic vacuoles containing fibrinoid cellular debris, sometimes with pyknotic nuclear fragments can be identified
- Extracellular hyaline material and lymphocytes at the periphery with Infiltrating tumor nests and single squamoid cells can also be recognized
- Mitotic count ranges from few to several in different fields
- Occasional central cystic degeneration containing fibrinoid material is noted
- Most striking histologic feature is an absent biphasic pattern of cytotrophoblasts and syncytiotrophoblasts
Microscopic (histologic) images
Positive stains
Negative stains
- GPC3, OCT4, CD117, CD30, AFP
- TTF1, CDX2, CK5/6, MelCAM (CD146)
- Reference: Hum Pathol 2024;153:105673
Sample pathology report
- Retroperitoneal lymph node, lymph node dissection:
- Metastatic testicular germ cell tumor, teratoma (60%) and epithelioid trophoblastic tumor (40%) (see comment)
- Comment: The epithelioid trophoblastic tumor expresses AE1 / AE3, inhibin, p63 and GATA3.
Differential diagnosis
- Choriocarcinoma:
- Regressing choriocarcinoma:
- Large mononucleated trophoblast cells with pale to eosinophilic cytoplasm
- Absent biphasic pattern of cytotrophoblasts and syncytiotrophoblasts with necrosis and fresh hemorrhage along with hyalinized fibrous background and numerous hemosiderin laden macrophages
- Few mitotic figures
- Prominent Leydig cell hyperplasia in the surrounding testis
- Placental site trophoblastic tumor:
- Sheets of discohesive cells with focal hemorrhage
- More infiltrative growth instead of nodules and nests
- Larger cells with more pleomorphic nuclei
- p63 negative
- Squamous cell carcinoma, as a component of teratoma with somatic malignancy:
- Squamous cell carcinoma, nontesticular in origin:
Additional references
Board review style question #1
A patient with a history of testicular germ cell tumor treated with chemotherapy now has an enlarged cervical lymph node that is diffusely involved by the tumor (shown above). There is only a minor elevation of serum βhCG. The tumor is formed by large, solid nodules of cells with a squamoid appearance. 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. What is the best diagnosis?
- Choriocarcinoma
- Cystic trophoblastic tumor
- Epithelioid trophoblastic tumor
- Myoid gonadal trophoblastic tumor
Board review style answer #1
C. Epithelioid trophoblastic tumor (ETT). Essential diagnostic criteria of ETT (WHO 5th edition) include squamoid appearing, mostly mononucleated trophoblastic cells with a variable amount of fibrinoid material surrounding the tumor clusters and vessels. Desirable diagnostic criteria of ETT (WHO 5th edition) include positive staining for p63 and Ki67 index > 10%.
Answer A is incorrect because choriocarcinoma has a biphasic pattern of syncytiotrophoblastic and mononucleated trophoblast cells and patients with a substantial burden of choriocarcinoma have high serum βhCG. Answer B is incorrect because cystic trophoblastic tumors have a degenerative appearance with cysts lined by squamoid appearing cells with smudged, irregular nuclei, abundant eosinophilic cytoplasm with intracytoplasmic lacunae and associated fibrinoid material. Answer D is incorrect because myoid gonadal trophoblastic tumor is a pure spindle cell tumor lacking sex cord differentiation and is positive for both actin and S100.
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Reference: Epithelioid trophoblastic tumor
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Reference: Epithelioid trophoblastic tumor