Journal of Pathology and Translational Medicine

Case Study

Epithelioid Trophoblastic Tumor: Clinicopathologic and Immunohistochemical Analysis of Three Cases: Woo Jung Sung, Hyeong Chan Shin, Min-Kyung Kim, Mi Jin Kim; Korean J Pathol. 2013;47(1):67-73. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.67

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Epithelioid trophoblastic tumor is an unusual type of trophoblastic tumor. Here we report on the clinicopathologic and immunohistochemical features of three cases of epithelioid trophoblastic tumor. All three patients were of reproductive age and presented with vaginal bleeding and mild elevation of human chorionic gonadotropin (hCG). All patients underwent a hysterectomy. The tumors consisted of epithelioid intermediate trophoblastic cells that were mononucleated and eosinophilic, or showed clear cytoplasm on microscopic examination. One case presented with a focal choriocarcinoma component. Immunohistochemically, the tumors displayed diffuse positivity for cytokeratin 18, E-cadherin, epidermal growth factor receptor, and p53 and focal positivity for p63 and hCG. However, expression of α-inhibin and placental alkaline phosphatase was almost negative. Tests for human placental lactogen and epithelial membrane antigen were also negative in all cases.

Citations

Citations to this article as recorded by

Epithelioid Trophoblastic Tumour: A Case with Genetic Linkage to a Child Born over Seventeen Years Prior, Successfully Treated with Surgery and Pembrolizumab
David Pisani, Jean Calleja-Agius, Riccardo Di Fiore, John J. O’Leary, James P. Beirne, Sharon A. O’Toole, Ana Felix, Ian Said-Huntingford
Current Oncology.2021; 28(6): 5346. CrossRef
Epithelioid Trophoblastic Tumor
Stephanie M. McGregor, Larissa V. Furtado, Anthony G. Montag, Rebecca Brooks, Ricardo R. Lastra
International Journal of Gynecological Pathology.2020; 39(1): 8. CrossRef
Epithelioid trophoblastic tumor in a postmenopausal woman: A case report and review of the literature in the postmenopausal group
Seyran Yigit, Eylul Gun, Bulent Yilmaz, Zafer Kolsuz
Indian Journal of Pathology and Microbiology.2020; 63(5): 98. CrossRef
Double trouble: Extrauterine epithelioid trophoblastic tumor with uterine choriocarcinoma - An autopsy report
Kusum Jashnani, Alshifa Yagana, Niraj Mahajan
Indian Journal of Cancer.2020;[Epub] CrossRef
Epithelioid trophoblastic tumor coexisting with choriocarcinoma around an abdominal wall cesarean scar: a case report and review of the literature
Chunfeng Yang, Jianqi Li, Yuanyuan Zhang, Hanzhen Xiong, Xiujie Sheng
Journal of Medical Case Reports.2020;[Epub] CrossRef
Placental site trophoblastic tumor and epithelioid trophoblastic tumor: Clinical and pathological features, prognostic variables and treatment strategy
Angiolo Gadducci, Silvestro Carinelli, Maria Elena Guerrieri, Giovanni Damiano Aletti
Gynecologic Oncology.2019; 153(3): 684. CrossRef
Diagnosis and Management of Mixed Gestational Trophoblastic Neoplasia: A Study of 16 Cases and a Review of the Literature
Yujia Kong, Guangshi Tao, Liju Zong, Junjun Yang, Xirun Wan, Wenze Wang, Yang Xiang
Frontiers in Oncology.2019;[Epub] CrossRef
A Case Series of Five Patients With Pure or Mixed Gestational Epithelioid Trophoblastic Tumors and a Literature Review on Mixed Tumors
Ka Yu Tse, Keith Wan Hang Chiu, Karen Kar Loen Chan, Mandy Man Yee Chu, Siew Fei Ngu, Annie Nga Yin Cheung, Hextan Yuen Sheung Ngan, Philip Pun Ching Ip
American Journal of Clinical Pathology.2018; 150(4): 318. CrossRef
MR Imaging of Uterine Epithelioid Trophoblastic Tumor: A Case Report
Sakiko KAGEYAMA, Masafumi KANOTO, Yukio SUGAI, Takeshi SUTO, Satoru NAGASE, Mitsumasa OSAKABE, Takaaki HOSOYA
Magnetic Resonance in Medical Sciences.2016; 15(4): 411. CrossRef
Pharmacotherapy of placental site and epithelioid trophoblastic tumours
Fiona Taylor, Barry W Hancock
Expert Opinion on Orphan Drugs.2015; 3(1): 75. CrossRef
A Well-Circumscribed Border with Peripheral Doppler Signal in Sonographic Image Distinguishes Epithelioid Trophoblastic Tumor from Other Gestational Trophoblastic Neoplasms
Jiale Qin, Weiwen Ying, Xiaodong Cheng, Xiaodong Wu, Bingjian Lu, Yun Liang, Xinyu Wang, Xiaoyun Wan, Xing Xie, Weiguo Lu, Hai-Yan Lin
PLoS ONE.2014; 9(11): e112618. CrossRef

Original Articles

Histological and Immunohistochemical Findings of the Intermediate Trophoblasts in Normal Full Term and Pre-eclamptic Placentas.: Sang Hak Han, Kyu Rae Kim, Yonghee Lee, Jae Y Ro; Korean J Pathol. 2010;44(1):63-69.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.63

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Abstract PDF: BACKGROUND
Recent studies have suggested that implantation site intermediate trophoblasts (ISITs) and chorionic type intermediate trophoblasts (CTITs) show different immunohistochemical findings, and that each type has specific location in placentas. However, we observed that both subtypes are intimately admixed in many areas of the placentas and both types are proliferated around the infarcts.
METHODS
In order to examine the site specificity in their distribution and the changes of intermediate trophoblasts (ITs), if any, in the pre-eclamptic placentas, quantitative analyses of ISITs and CTITs using p63, CD146, placental alkaline phosphatase, human placental lactogen, and alpha-inhibin were performed in normal and pre-eclamptic placentas containing infarcts.
RESULTS
In the fetal membranes of both normal and pre-eclamptic placentas, CTITs and ISITs were equally identified, forming distinct layers. ISITs were predominant in the intervillous septum and basal plate, while CTITs were predominant in the subchorionic area. At the margin of infarcts in pre-eclamptic placentas, both subtypes were increased in number, forming distinct layers.
CONCLUSIONS
The subtypes of ITs do not have site specificity in placentas. Increased number of ITs and zonal distribution around infarcts suggest that CTITs and ISITs have differentiation associated relationship, and the differentiation might be related to the microenvironment of placenta, such as intraplacental oxygen concentration.

Composite Adenocarcinoma and Choriocarcinoma of the Sigmoid Colon with Hepatic Metastasis of the Choriocarcinomatous Component.: Young Ha Oh, Won Mee Lee, Kyung Sook Kim, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1997;31(8):788-793.

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Abstract PDF: A rare case of hepatic metastasis with a choriocarcinomatous component from a composite adenocarcinoma and choriocarcinoma of the sigmoid colon in a 60-year-old man is reported. The hepatic metastasis displayed choriocarcinoma with extensive hemorrhagic necrosis. The tumor cells were poorly differentiated with scattered foci of bizzare syncytiotrophoblastic cells. Retrospective examination of the previous colonic carcinoma proved that the tumor was composed of two distinctive elements. One was a moderately well differentiated adenocarcinoma located in mucosa and submucosa. The other was a deep seated and undifferentiated carcinoma which was made up of hyperchromatic bizzare cells with syncytiotrophoblastic cells. There were transitional foci from adenocarcinoma to undifferentiated carcinoma with trophoblastic cells. Immunohistochemical staining showed beta-hCG expression in the undifferentiated cells of both the primary and the metastatic tumors. Implications for the possible origin and cause of tumor cell heterogeneity are briefly discussed.

Case Report

Choriocarcinoma of the Colon.: Youn Mee Kim, Mee Youn Cho, Soon Won Hong, Soon Hee Jung; Korean J Pathol. 1997;31(8):794-797.

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Abstract PDF: Choriocarcinoma of the gastrointestinal tract is rare. Among them, that of the stomach is the most common. Six cases of choriocarcinoma of the colon were found in the review of the literature. All of these previously reported cases had multiple metastatic foci in the liver, lung, lymph nodes and the prognosis seemed to be very poor. Therefore we think that choriocarcinoma of the colon should be distinguished from conventional adenocarcinoma. A 66-year old female patient, described in this case, was operated on under the impression she was suffering from acute appendicitis. The resected ascending colon revealed extensive hemorrhagic necrosis and perforation with fibrous adhesion in the cecum. On the cut section, the mural tumorous thickening was not definite. Histologically, the tumor showed a focus of typical adenocarcinoma arising from glandular epithelial cells, which were transformed into highly anaplastic tumor cells. There were frequent vascular invasions of tumor cells, similar to syncytiotrophoblasts. In the immunohistochemical stains, both glandular and highly anaplastic tumor cells reacted with cytokeratin. The glandular cells were also reactive for carcinoembryonic antigen (CEA) and anaplastic tumor cells for human chorionic gonadotrophin (hCG). This is the first report of choriocarcinoma of the colon in Korea. We describe this case with a review of the literature.

Original Articles

The Expression of G1-S Cell Cycle Inhibitors in Normal Placenta and Gestational Trophoblastic Diseases.: Yan Hua Xuan, Kyung Hee Kim, Yoon La Choi, Geung hwan Ahn, Seoung Wan Chae, Ho chang Lee, Ok Jun Lee, Seok Hyung Kim; Korean J Pathol. 2008;42(2):67-74.

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Abstract PDF: BACKGROUND
The objective of this study is to determine the expression pattern of G1-S inhibitor molecules in normal trophoblasts and gestational trophoblastic diseases, including hydatidiform moles and choriocarcinoma.
METHODS
A total of 157 cases comprising 47 normal placentas and 110 gestational trophoblastic diseases such as choriocarcinoma (19 cases) and hydatidiform moles (91 cases of which 58 were complete, 12 were partial and 21 were invasive mole) were immunohistochemically analyzed on paraffin blocks using anti-p21, antip27, anti-p16, anti-p53, anti-pRb antibodies.
RESULTS
The results revealed that in the normal placenta, all the G1-S cell cycle inhibitors were maximally expressed by the first-trimester trophoblasts and these levels decreased with gestational age. The expression of p21 and p53 was greatly enhanced in the gestational trophoblastic diseases, particularly in invasive mole and choriocarcinoma, whereas the p27 expression was significantly downregulated in choriocarcinoma. Especially, Rb expression was typically enhanced in the invasive mole, but not in choriocarcinoma. The expression level of p16 was low in all the cases, and particularly in choriocarcinoma.
CONCLUSIONS
In conclusion, we demonstrated that the expression of G1/S cell cycle inhibitors correlates well with normal trophoblast differentiation, and these expressions are considerably altered in the gestational trophoblastic diseases, including complete/partial/ invasive hydatidiform mole and choriocarcinoma.

Sequential Ultrastructural Change of Chorionic Villi in Human Placenta by Gestational Period.: Tae Dong Park, Tae Jung Kwon, Je G Chi; Korean J Pathol. 1993;27(5):468-484.

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Abstract PDF: A study was performed to observe the sequential morphological change of the human placental barrier by means of light microscopy, immunohistochemistry, scanning electron microscopy and transmission electron microscopy. The examined placentas ranged in age from 4 weeks gestation to the full-term(40 weeks). Sixty seven placental specimens were obtained immediately after delivery. With the progression of gestation, the microvilli on the surface of syncytinum tended to be fewer, shorter and blunter. The syncytiotrophoblasts were getting thinner with formation of vasculo-syncytial membrane. The cytotrophoblasts formed a continuous layer which progressively disappeared but still present in the mature villi. In view of presence of intermediate cells and remnant of desmosomes, the cytotrophoblasts appeared to form the syncytiotrophoblasts. In early pregnancy, capillary formation took place by the aggregation and differentiation of the proliferation and aggregation of endothelial cells and pericytes. Myofibroblasts in villous stroma were examined by desmin immunohistochemical staining, and detected from 19 weeks to the full-term. During last period of pregancy definitive smooth muscle cells could be demonstrated, suggesting that the presence of myofibroblasts or smooth muscle cells are closely related to the placental maturity. Scanning electron microscopy of the early placenta showed numerous syncytial sprouts representing stages in the formation of new villi, but in the late period of gestation syncytial sprouts were diminished. It is concluded that the syncytiotrophoblast is originated from the cytotrophoblast in early pregnancy as the placental barrier is formulated. Moreover, myofibroblasts and smooth muscle cells in villous stroma play important role in placental maturation.

Immunohistochemical Study of Cytokeratin in Human Trophoblastic Tissue.: Jeong Hee Kang, Kang Suek Suh; Korean J Pathol. 1992;26(5):459-465.

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Abstract PDF: The use of human chorionic gonadotropin(hCG), human placental lactogen(hPL) as markers for trophoblastic tissue has been well documented in the literature. However, it is not widely recognized that cytokeratin is a very sensitive and reliable marker for various types of trophoblastic tissue. The authors have studied 15 cases of human placental tissue ranging in age from first to third trimesters. Unlike hCG and hPL, which stain only the syncytiotrophoblast and intermediate trophoblast, cytokeratin(low molecular weight) stains all three types trophoblastic tissue. The staining of placental tissue for cytokeratin is marked and very consistent throughout pregnancy. Because of its high sensitivity and ability to stain cytotrophoblast, it is believed that it could be very useful in detecting trophoblasts of early pregnancy and in the study of the pathologic process of trophoblastic diseases.

Placental Site Nodules & Plaques: A clinicopathologic analysis of 14 cases.: Kyu Rae Kim, Sun Won Hong, Kyung Sub Cha, In Pyong Kwak, Tae Ki Yoon; Korean J Pathol. 1992;26(1):53-61.

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Abstract PDF: Placental site nodules and plaques have been recently described to designated single or multiple, well-circumscribed, rounded lesions at the placental site, composed of viable or degenerating intermediate trophoblastic cells and extensive hyalinization between the cells. We described clinicopathologic findings of 14 cases of placental site nodules and plaques. The age of 14 patients ranged from 25 to 39(average 33) years and all of them had been pregnant in the past. Ten of them presented with vaginal spotting, which was preceded by recent pregnancy in only 3 cases. Three patients presented with secondary infertility and one with secondary infertility and vaginal spotting. Urine pregnancy tests were negative in all 14 cases at the time of presentation. Ultrasonographic examination disclosed abnormalities in only 3 cases and the remaining cases were normal. Hysterosalpingography was performed in 3 patients who presented with 2 degrees infertility and revealed moderate to severe intrauterine adhesions. Microscopically, chronic endometritis of varying degrees evidenced by plasma cells and eosinophiles were present in all cases and these were more prominent in the vicinity of the lesions. It is presumed that the placental site nodules and plaques are not sloughed at the time of menstruation and it may cause chronic endometritis or intrauterine adhesions at any time after previous delivery.

Case Report

Placental Site Trophoblastic Tumor(PSTT) with Vaginal Metastasis: A case report.: Yee Jeong Kim, Kyu Rae Kim, Soon Hee Jeong, Ho Geun Kim, Jang Yeon Kwon; Korean J Pathol. 1991;25(6):570-575.

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Abstract PDF: PSTT has been established as a separate entity distinct from choriocarcinoma since 1983, because of its different morphological features, biologic behavior and response to chemotherapy. Most cases of PSTT have indolent clinical courses, but there have been several reports showing malignant behavior resulted in death of the patient. We report a case of PSTT showing vaginal metastatis. In biopsy specimen, it was difficult to make differential diagnosis from squamous cell carcinoma of uterine cervix due to uniform and mononuclear cytologic characteristics. Immunohistochemical stains for hPL and hCG were not typical for either PSTT or choriocarcinoma. We suggest that poorly differentiated PSTT may synthesize the lesser amount of hPL than typical PSTT and it may behave more aggressively.

Original Articles

Primary Undifferentiated Carcinoma of the Endometrium with Small Cell and Trophoblastic Differentiation.: Chul Hwan Kim, Seoung Hye Park, In Sun Kim, Seung Yong Paik; Korean J Pathol. 1990;24(1):58-64.

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Abstract PDF: This report describes a very rare case of primary undifferentiated carcinoma of the endometrium with small cell and trophoblastic differentiation. The patient was 54-year-old woman with complaints of vaginal bleeding and palpable lower abdominal mass. The light microscopic findings revealed predominantly small cells with round nuclei, spindle cells, and large cells with hyperchromatic bizarre nuclei. Foci of syncytiotrophoblastic giant cells are scattered, especially in the hemorrhagic areas. Immunohistochemical stainging for neuron specific enolase and beta-hCG showed positive reactions to small cells and syncytiotrophoblastic giant cells, respectively. Argentaffin and argyrophil stains, however, showed negative reactions to small cells. The histogenesis of small cell undifferentiated carcinoma of the endometrium remains unclear; however, it may arise from epithelial precursors instead of neuroendocrine cells, and syncytiotrophoblastic cells may be differentiated or dedifferentiated from the undifferentiated carcinoma cells.

Light and Electron Microscopical Studies on the Stroma of Hydatidiform Mole.: Jong Tae Park, Sang Woo Juhng, Kyu Hyuk Cho; Korean J Pathol. 1987;21(4):240-248.

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Abstract PDF: Many investigators were interested in the pathogenesis and the relationship between microscopical features and clinical behavior of hydatidiform mole. Trophoblastic cells in the trophoblastic disease were intensively examined histologically, ultrastructurally, immunohistochemically, and with hormone assay method, etc. But ultrastructural study on the stroma of hydatidiform mole was scarcely reported. In this paper, hydatidiform mole was examined at light and electron microscopic levels, with emphasis on the stroma. The results were as follows: 1) Hydropic degeneration of H-mole is more severe in the center of stroma and is not related with the degree of trophoblastic proliferation. Hofbauer cell and vascular structure are extremely rarely observed in the periphery of stroma which has relatively preserved cellular components. 2) Basement membrane is sometimes separated from trophoblastic layer. Degenerated cells in the stroma contain vacuoles, autophagosomes, and lipid droplets. Collagen is abundant in the loose interstitium. Hofbauer cells have no lysosome or phagosome. Vascular lumen is patient and endothelial cells are degenerated. From the above results, H-mole may be produced due to abnormal changes of trophoblasts and stromal changes may be a secondary process, so called autolysis. Hofbauer cells are not engaged in the stromal degeneration and may be different from usual tissue macrophages.

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