Epithelioid trophoblastic tumour, ETT

Definition

A rare post-gestational trophoblastic tumour composed of epithelioid cells.

Epidemiology

This tumour occurs in women of reproductive age some years after a gestation, which may be a term delivery, spontaneous abortion or molar gestation.

Clinical features

Presentation is usually with bleeding per vaginam, sometimes with amennorhea. Serum human chorionic gonadotrophin is usually mildly raised (<2500 mIU/ml).

Macroscopic appearances

The tumour commonly occupies the uterine cervix or lower segment.

Histopathology

The tumour forms nodules which are usually well demarcated but may show focal infiltration. They are composed of nests or sheets of mononuclear epithelioid cells. The abundant cytoplasm is eosinophilic or clear. The centre of tumour nodules often show hyalinisation or eosinophilic material resembling keratin. The margins of the nodules infiltrate the surrounding tissues. Within the endocervix, there may be replacement of the endocervical epithelium, mimicking intraepithelial neoplasia. Mitoses are present in variable numbers. There may be geographical necrosis. The adjacent stroma may be decidualised.

Immunohistochemistry

	bHCG	5/51
	hPL	5/5(usually staining of individual cells)1
	AE1/AE3	positive1
	p63	positive1
	CK18	positive1
	HLA-G	positive1
	Inhibin	positive1
	Ki-67	10% to 86% of cells1

Ultrastructure

Differential diagnosis

Other trophoblastic lesions:

Benign placental site nodule. The lesion may present years after a pregnancy but is small (<1 cm). Cellularity is lower and geographic necrosis is lacking. Distinction may be difficult in curettings. Less than 10% of nuclei are positive for Ki-67. There is much less expression of cyclin E than is seen in epithelioid trophoblastic tumour2. Atypical placental site nodules may be positive for cyclin E and may represent an intermediate lesion between placental site tumour and epithelioid trophoblastic tumour2.
Placental site trophoblastic tumour occurs in younger women. There is diffuse permeation of the myometrium. hPL is diffusely positive but p63 is negative.

Morphologically, epithelioid trophoblastic tumour resembles a carcinoma:

Cervical squamous cell carcinoma: the eosinophilic material seen in epithelioid trophoblastic tumour may mimic the keratin of squamous cell carcinoma. Most cases of cervical carcinoma are positive for p16, in contrast to the consistent negativity in epithelioid trophoblastic tumour and all other trophoblastic lesions2. Epithelioid trophoblastic tumour is positive for CK18 and HLA-G, whereas most cervical squamous carcinomas are negative2.
Poorly differentiated endometrioid carcinoma, which may show focal syncytiotrophoblastic differentiation.
Outside the uterus: epithelioid mesothelioma.

Management

Epithelioid trophoblastic tumour may not be as responsive to chemotherapy as are other types of gestational trophoblastic disease. Surgical excision or hysterectomy has therefore been recommended2.

Prognosis

In most cases, the behaviour is benign. Metastases occur in about 25% of cases and about 10% of cases prove fatal. A high mitotic index may be associated with malignant behaviour.

References

1 Fadare O, Parkash V, Carcangiu ML, et al. Epithelioid trophoblastic tumor: clinicopathological features with an emphasis on uterine cervical involvement. Mod Pathol 2006; 19:75-82

2 Mao TL, Seidman JD, Kurman RJ, et al. Cyclin E and p16 Immunoreactivity in Epithelioid Trophoblastic Tumor-An Aid in Differential Diagnosis. Am J Surg Pathol 2006; 30:1105-1110

This page last revised 23.9.2006.