Epithelioid Trophoblastic Tumor Presenting as an Adnexal Mass: Report of a Diagnostically Challenging Case

Abstract

Epithelioid trophoblastic tumor (ETT) is a rare neoplasm derived from chorionic intermediate trophoblast cells, representing less than 2% of all gestational trophoblastic neoplasms. Classically, ETT presents as a uterine mass in women of reproductive age following a term pregnancy. The time from pregnancy to tumor development varies from months to several years. ETT most often arises in the endometrium, followed by the cervix. Extrauterine ETT are extremely infrequent, with few cases reported in the literature. We report a case of a 41-year-old woman, with history of three term pregnancies who presented with abdominal pain and elevated beta human chorionic gonadotropin (β-hCG) level, ten years after her last pregnancy. Imaging reported a 3.5 cm adnexal mass, suspicious for ectopic pregnancy. Hysterectomy and mass resection revealed a 4.7 cm, tan-yellow, necrotic mass adjacent to the broad ligament. Histologic evaluation in conjunction with immunohistochemical stains revealed a tumor consistent with ETT. No connection to the endometrium was found grossly or microscopically. DNA fingerprinting analysis revealed the tumor to have two copies of paternal alleles, as seen in molar gestations. One of the primary differential diagnoses for ETT is squamous cell carcinoma due to similar morphologic features. In challenging cases, genetic analysis demonstrating paternally derived genes can establish the diagnosis. In this report, we discuss the challenges in the diagnosis of extrauterine ETT, due to its rarity and highly variable presentation, given that appropriate diagnosis is critical for correct patient management.

Extrauterine epithelioid trophoblastic tumour and its somatic carcinoma mimics: short tandem repeat genotyping meets the diagnostic challenges

“…Metastatic disease may develop in 15–25% of the cases. In recent years, extrauterine ETT without a documented cervical or uterine primary tumour has been reported in various organs, including the lung, vagina, ovary, fallopian tube and peritoneum 1,6,7,20,32 . As illustrated in the current series, three of the four tumours presented at extrauterine sites (two cases in the lung and one in the liver), with ETT as the major differential diagnosis (Table 1).…”

“…In recent years, extrauterine ETT without a documented cervical or uterine primary tumour has been reported in various organs, including the lung, vagina, ovary, fallopian tube and peritoneum. 1,6,7,20,32 As illustrated in the current series, three of the four tumours presented at extrauterine sites (two cases in the lung and one in the liver), with ETT as the major differential diagnosis (Table 1). The fourth patient presented with uterine lesion and extensive peritoneal involvement resulting in a 'frozen pelvis' and omental 'cake'.…”

“…In recent decades, ETT has been increasingly reported to present at extrauterine sites associated with ectopic pregnancy, including the fallopian tube, ovary and broad ligament 1,6–13 . In addition, metastases of ETT may also occur as an initial tumour presentation, 14,15 with reported metastatic sites including the lung, liver, gallbladder, kidney, pancreas, spine, vagina, bladder and ureter 11,16–20 …”

“…1,[6][7][8][9][10][11][12][13] In addition, metastases of ETT may also occur as an initial tumour presentation, 14,15 with reported metastatic sites including the lung, liver, gallbladder, kidney, pancreas, spine, vagina, bladder and ureter. 11,[16][17][18][19][20] ETT closely resembles squamous cell carcinoma at the histological and immunohistochemical levels, potentially leading to misdiagnosis and inappropriate management of patients. 7,21,22 To further complicate the matter, rare somatic carcinomas may present with trophoblastic differentiation that may simulate ETT histologically and immunohistochemically.…”

Epithelioid trophoblastic tumor with lung metastasis: A case report and literature review

“…ETT may be confused with squamous cell carcinoma (SCC) because of its frequent involvement of the lower uterine segment, the appearance of epithelioid histologic morphology, positivity for p63 and keratins, and its eosinophilic hyaline material similar to keratin. [31] The expression of P16 is helpful to differentiate ETT and SCC, as the latter is positive whereas ETT is negative. [32] Furthermore, Ki-67 proliferative index is always high (>50%) in SCC which is usually >10% in ETT.…”