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CASE REPORT Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 2  |  Page : 242-244
Epithelioid trophoblastic tumor of uterus presenting as an ovarian mass: A diagnostic and therapeutic dilemma


1 Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, India
2 Department of Gynecology, Oncology, Tata Memorial Hospital, Parel, Mumbai, India
3 Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, India

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   Abstract 

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor and often poses a diagnostic and therapeutic challenge to the involved clinicians. We report a case of epithelioid trophoblastic tumor in a young woman which involved the uterus, parametrium and the right ovary. Misdiagnosis as a choriocarcinoma led to improper treatment and progressive disease. Microscopically it revealed a relatively monotonous population of epithelioid cells arranged in nests with hyaline-like matrix surrounding the tumor cells. Differential diagnosis between placental site trophoblastic tumor and carcinoma was ruled out based on histology and immunohistochemistry. The patient developed lung and brain metastasis after 10 months and is alive with disease 1˝ years thereafter and is taking palliative chemotherapy. The patient had
β-HCG level of 85.1 mIU/mL at the time of diagnosis; but just before metastasis, the levels rose. Awareness of the histological features of ETT is essential to avoid misdiagnosis, as it represents a tumor which is primarily treated by surgery rather than with chemotherapy.

Keywords: Epithelioid trophoblastic, intermediate trophoblast

How to cite this article:
Shet T, Parage M, Maheshwari A, Nair R, Gupta S, Tongaonkar H, Chinoy R. Epithelioid trophoblastic tumor of uterus presenting as an ovarian mass: A diagnostic and therapeutic dilemma. Indian J Pathol Microbiol 2008;51:242-4

How to cite this URL:
Shet T, Parage M, Maheshwari A, Nair R, Gupta S, Tongaonkar H, Chinoy R. Epithelioid trophoblastic tumor of uterus presenting as an ovarian mass: A diagnostic and therapeutic dilemma. Indian J Pathol Microbiol [serial online] 2008 [cited 2014 Oct 22];51:242-4. Available from: http://www.ijpmonline.org/text.asp?2008/51/2/242/41669



   Introduction Top


Mazur et al. described an unusual metastatic lung trophoblastic tumor in autopsy material from patients who had died after intensive chemotherapy for a gestational choriocarcinoma. [1] Similar tumors were subsequently described in patients with molar gestations in the uterus. [2] The term "epithelioid trophoblastic tumor" (ETT) was coined for these lesions by Mazur and Kurman in 1994. [3] This tumor presents a diagnostic challenge to an unaware pathologist as it has a wide range of differential diagnoses and because of its rarity. Likewise, clinicians treating these patients often face problems in treating this tumor.

We describe a case of ETT of the uterus involving the ovaries occurring in a young married woman treated with Wertheim's hysterectomy and choriocarcinoma chemotherapy but who developed lung and brain metastasis subsequently.


   Case History Top


Clinical history

A 30-year-old married woman presented with complaints of bleeding per vaginum. The patient was also being investigated for primary infertility and gave a history of missed abortion 6 years back. A USG abdomen showed a 6 × 4 × 2-cm leiomyoma in the fundus of the uterus. A myomectomy was done. On histology, this was labeled as a choriocarcinoma by the local pathologist. At this time, the serum β-HCG was 85.1 mIU/mL. The patient was given 5 cycles of EMACO [etoposide (100 mg/m 2 ), methotrexate (100 mg/m 2 ), D-actinomycin (0.5 mg/m 2 ), cyclophosphamide (600 mg/m 2 ) and vincristine (1 mg/m 2 )] chemotherapy. In view of disease progression, within 10 months the patient was then referred to our hospital for further treatment.

At our institute, on review this tumor was labeled as a tumor of the intermediate trophoblast and a possibility of placental site trophoblastic tumor was suggested. A USG abdomen revealed a residual lesion in the posterior myometrium and a right-side adnexal mass measuring 7 × 5 × 3 cm. The β-HCG level was 169.6 mIU/mL. A total abdominal hysterectomy with right salphingo-oophorectomy was done. Post surgery, the β-HCG level was 134.7 mIU/mL. Following the diagnosis of ETT and high-stage disease, the patient was given 3 cycles of BEP (bleomycin, etoposide, and prednisolone). Seven months later, she complained of vomiting, headache and low-grade fever; and a CT scan of brain showed two metastatic lesions in the right cerebral hemisphere in the frontal and parieto-occipital regions. She was given whole-brain radiotherapy and prednisolone for the same. Her β-HCG level decreased to 29.93 mIU/mL. The patient was given 3 additional cycles of holoxan and carboplatin. One year later (overall follow-up, 3 years), she stopped further chemotherapy and opted for supportive care only. Eight months since, she has developed progressive local disease and neck nodal metastasis, for which she is taking palliative chemotherapy, as of February 2006.

Pathological findings

On gross examination, a firm necrotic tumor measuring 4 × 2.5 × 2 cm was seen in the uterine wall, involving the isthmus. Microscopically, the tumor was fairly circumscribed, with a sharp tumor and uterine muscle junction [Figure 1]. The tumor was composed of cells arranged in nests and trabeculae which were intimately surrounded by an eosinophilic, fibrillary, hyaline-like material; and necrotic debris [Figure 2]. Predominant cells were large and polygonal, with distinct cell borders, clear/eosinophilic cytoplasm and single large nucleus. Nuclei of the cells were convoluted and showed occasional nucleoli. Occasional large synctitial cells with multiple nuclei were also seen. Tumor showed brisk mitotic activity of 8-10/10 hpf. The tumor infiltrated three fourths of the uterine wall. The right parametrium, ovary and peritoneum showed metastatic deposits.


   Discussion Top


Epithelioid trophoblastic tumor (ETT) is a distinct but rare gestational trophoblastic tumor occurring in women in the reproductive age group. [1-5] In view of the history of prior molar pregnancies, in most patients ETTs are most often confused with choriocarcinoma. However, most of the patients have low serum β-HCG levels at the time of diagnosis, [5] as in our case. A high level of serum β-HCG in ETT is reported to be associated with a large tumor mass and unusually high mitotic activity. [6] Rising levels of β-HCG after therapy may be an indication of failure of treatment, as seen in our case.

Till today, 90 cases have been reported, [7] mostly as case reports; and the only series is by Shih and Kurman, who described the clinicopathological and immunohistochemical features of 14 cases. [5] Besides occurring in the uterus [5],[8] and cervix, [7],[8] it has been reported in the broad ligament, [6] vaginal deposits,  Fallopian tube More Details and lungs. [1],[9] The involvement of the latter is usually metastatic, [9] and most patients give history of antecedent molar pregnancies. Even when they develop without history of abnormal pregnancy, they are regarded as heterotrophic gestational choriocarcinoma derived from antecedent term pregnancies or unnoticed miscarriages. [9] ETT is also recorded in postmenopausal women and may occur as late as 17 years after molar pregnancy. [10] For diagnosis of ETT in uterus and at odd sites, a high index of suspicion and awareness is necessary as it may simulate an invasive squamous carcinoma, specially so in the cervix. [7],[8],[10] However, awareness of the histology of ETT; absence of clear-cut keratinization; and expression of β-HCG, at least focally on immunohistochemistry, help in the diagnosis. In our case, the serious differential diagnoses were tumors arising from intermediate trophoblast, mainly placental site trophoblastic tumor (PSTT). But in contrast to PSTT, ETT grows in an expansile fashion and the tumor stroma junction is sharp. Tumor cells in ETT grow in nests and cords, a pattern not observed in PSTT. [5] The hyaline matrix in ETT is also diagnostic. [10] Blood vessels in ETTs are often surrounded by tumor cells, but vascular permeation is not a striking feature as opposed to PSTT. [5],[9] Recent observations have suggested that a positive immunostaining of p63 protein is highly specific to epithelioid trophoblastic tumor, in contrast to an absence of the staining in placental site trophoblastic tumor cells. [7] A diagnosis of choriocarcinoma was unlikely in view of the persistent low level of β-HCG and lack of the biphasic nature of the tumor cells on histology in our case. However, cases of ETTs coexisting with choriocarcinoma in the lung and post-term choriocarcinoma in uterus and with a PSTT in the uterus are described. [11] Epithelioid smooth-muscle tumors usually display areas of typical smooth-muscle cells in addition to epithelioid areas and immunohistochemical muscle markers are strongly positive. [5],[6]

On immunohistochemistry, ETTs express epithelial antigens, E-cadherin, epidermal growth factor receptor and α inhibin. [5] Some ETTs also express hPL, hCG, PLAP and Mel-CAM (melanoma adhesion molecule expressed by intermediate trophoblast). [5] Though this immunohistochemistry may not help differentiation from a PSTT, it helps rule out other differentials, especially carcinomas.

The behavior of ETT is linked to that of PSTT, whereby both tend to behave in a benign fashion; but metastasis and death occur in 10% of the patients. [10] While the primary treatment for choriocarcinoma is chemotherapy, PSTT tends to be chemoresistant and the recommended primary treatment is surgical intervention. [10] Given the similarities in behavior between PSTT and ETT, it is reasonable to treat ETT like PSTT, by surgery, rather than like choriocarcinoma, as done in the treatment of other types of gestational trophoblastic disease. [5]

We believe that high-stage and high-grade ETT is a more aggressive disease than PSTT and should be treated prospectively with prompt surgery. In our case, the overall disease progression could have been controlled by early surgery. Chemotherapy should be considered in ETT if surgical therapy fails. [10] Though it is difficult to predict which tumors will behave worse, tumors with high mitoses are usually seen to behave aggressively, [5] just as in our case.

Although the pathogenesis is largely unknown, trophoblastic origin of epithelioid trophoblastic tumor is confirmed and ETT shows immunophenotypic similarity to the putative "chorionic-type" intermediate trophoblasts. [11] Additional evidence for etiopathogenesis of ETT is still emerging. ETT is thought to be closely related to the placental site nodule as there are tumors with both these lesions and ETT is probably the neoplastic counterpart of that lesion. [5] The other school of thought believes that chemo-resistant antecedent choriocarcinoma or hydatidiform mole may develop phenotypic alterations and can produce ETT. [12]

Thus to summarize, ETT represents a potentially aggressive form of gestational trophoblastic tumor which may kill if not promptly treated by surgical intervention.

 
   References Top

1.Mazur MT, Lurain JR, Brewer JI. Fatal gestational choriocarcinoma: Clinicopathological study of patients treated at a trophoblastic disease center. Cancer 1982;50:1833-46.  Back to cited text no. 1  [PUBMED]  
2.Mazur MT. Metastatic gestational choriocarcinoma: Unusual pathologic variant following therapy. Cancer 1989;63:1370-7.  Back to cited text no. 2  [PUBMED]  
3.Twiggs LB, Hartenbach E, Saltzman AK, King LA. Metastatic placental site trophoblastic tumor. Int J Gynaecol Obstet 1998;60:S51-5.  Back to cited text no. 3  [PUBMED]  
4.Mazur MT, Kurman RJ. Gestational trophoblastic disease. In : Kurman RJ, editor. Blaustein's pathology of the female genital tract. New York: Springer-Verlag; 1994. p. 1049-96.  Back to cited text no. 4    
5.Shih IM, Kurman RJ. Epithelioid trophoblastic tumor: A neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol 1998;22:1393-403.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Kuo KT, Chen MJ, Lin MC. Epithelioid trophoblastic tumor of the broad ligament: A case report and review of the literature. Am J Surg Pathol 2004;28:405-9.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Fadare O, Parkash V, Carcangiu ML, Hui P. Epithelioid trophoblastic tumor: Clinicopathological features with an emphasis on uterine cervical involvement. Mod Pathol 2006;19:75-82.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Meydanli MM, Kucukali T, Usubutun A, Ataoglu O, Kafkasli A. Epithelioid Trophoblastic tumor of the endocervix: A case report. Gynecol Oncol 2002;87:219-24.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Hamazaki S, Nakamato S, Okino T, Tsukayama C, Mori M, Taguchi K, et al . Epithelioid trophoblastic tumor: Morphological and immunohistochemical study of three lung lesions. Hum Pathol 1999;30:1321-7.  Back to cited text no. 9    
10.Coulson LE, Kong CS, Zaloudek C. Epithelioid trophoblastic tumor of the uterus in a postmenopausal woman: A case report and review of the literature. Am J Surg Pathol 2000;24:1558-62.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Shen DH, Khoo US, Ngan HY, Ng TY, Chau MT, Xue WC, et al. Coexisting epithelioid trophoblastic tumor and choriocarcinoma of the uterus following a chemoresistant hydatidiform mole. Arch Pathol Lab Med 2003;127:e291-3.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Shih IM, Kurman RJ. The pathology of intermediate trophoblastic tumors and tumor-like lesions. Int J Gynecol Pathol 2001;20:31-47.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Tanuja Shet
309/31, Prabhudarshan, S.S. Nagar, Amboli, Andheri (W), Mumbai - 400 058, Maharashtra
India
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DOI: 10.4103/0377-4929.41669

PMID: 18603694

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    Figures

  [Figure 1], [Figure 2]

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