Testis & paratestis

• 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

• Atypical choriocarcinoma

• 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)

• 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)

• May be associated with mild elevation of beta human chorionic gonadotrophin (βhCG)

• No characteristic features

Contributed by Debra L. Zynger, M.D.

• Choriocarcinoma:
  • Very high serum βhCG
  • Shows a biphasic pattern of syncytiotrophoblastic and mononucleated trophoblast cells and significant fresh hemorrhage, often with extensive necrosis
  • Higher mitotic activity
  • βhCG and HPL expression are diffuse rather than focal
• 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:
  • Also has concurrent testicular germ cell tumor with other components or a history of testicular germ cell tumor with subsequent metastasis
  • Keratin pearls or more overt, classic squamous appearance
  • Inhibin, βhCG, HPL negative
• Squamous cell carcinoma, nontesticular in origin:
  • Correlation with history of other malignancies and current imaging required
  • Keratin pearls or more overt, classic squamous appearance
  • Inhibin, βhCG, HPL negative

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?

1. Choriocarcinoma
2. Cystic trophoblastic tumor
3. Epithelioid trophoblastic tumor
4. Myoid gonadal trophoblastic tumor

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