Choriocarcinoma Component Research Articles

Abstract 1088: Efficient detection of germ cell cancer related miRNAs in serum using the TaqMan miRNA ABC purification bead kit in combination with the Taqman advanced miRNA assays

Abstract Malignant germ cell tumors, also known as germ cell cancers (GCC), are the most frequent cancer in young Caucasian males, with an increasing incidence during the last decades. They are clinically and histologically subdivided into seminomas and nonseminomas. The last can be composed of different elements, including embryonal carcinoma (the stem cell component), teratoma (TE) (somatic lineage) as well as yolk sac tumor (YST) and choriocarcinoma (CHC) (extra-embryonic lineages). The currently used serum markers, informative for both diagnosis as well as follow-up are AFP and hCG, predominantly indicative for the presence of the YST and CHC components. Recently, we reported that a selected set of miRNAs are highly expressed in all histological elements of GCC, with the exception of TE, including the miR 371-3 cluster. In addition to the presence in the primary cancers, they can also be identified in the serum of patients with such a malignancy, outperforming the classical markers AFP and hCG (Gillis and Rijlaarsdam et al. Molec. Oncol. 2013; Rijlaarsdam et al. Andrology, 2015). Here we demonstrate the power of the TaqMan Advanced miRNA Assays (PN 478007, Applied Biosystems) in combination with the use of the TaqMan miRNA ABC Purification Kit (PN 4473087, Applied Biosystems), starting with 50 μL human serum. The protocol includes polyadenylation of the miRNA targets at the 3’ end, followed by an adapter ligation at the 5’ end. Universal forward and reverse primers are used for amplification, followed by detection using the Applied Biosystems 7500 RealTime PCR System. Quality controls were added using dilution experiments of the cell lines, also included as inter-plate control, as well as for cDNA synthesis and RT-PCR efficiency. The non-human spike-ins ath-miR159a and cel-miR-39-3p were added as exogenous controls, while hsa-miR-30b-5p was used as endogenous control for normalization (reference). In total 30 GCC-related sera as well as 10 normal controls proved the informativity as well as efficiency of the developed pipeline in a standardized laboratory setting. Citation Format: Leendert HJ Looijenga, Ton Van Agthoven, Ad Gillis. Efficient detection of germ cell cancer related miRNAs in serum using the TaqMan miRNA ABC purification bead kit in combination with the Taqman advanced miRNA assays. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1088.

Histological features of tumor-bearing tissues formed by human fibroblasts after reprograming by Piwil2

To observe the histological features of tumor-bearing tissues formed by human fibroblasts after reprograming by spermatogonial stem cell self-renewal key regulating gene Piwil2 (Piwil2-iCSC). Piwil2-iCSC tumor spheroids-like colonies were selected for tumor formation assay in four nude mice. Pathological features of Piwil2-iCSC tumors were observed by histology. Stem cell markers and common triploblastic markers were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) assay and immunohistochemistry. Germ cell tumor markers were detected by immunohistochemical examination. Two weeks after inoculation, subcutaneous tumors were formed in all the four nude mice with a tumor formation rate of 100%. In the Piwil2-iCSC tumor tissues, Piwil2-GFP(+) cells showed high-density nuclear expression and were widely observed in DAPI-stained sections. Numerous mitotic figure of the neoplastic cells were seen (>10 cells/field of vision under high magnification) in HE-stained sections. Enlarged abnormal cell nuclei were observed. RT-PCR assay showed that Piwil2-iCSC tumors still expressed Piwil2 and some self-renewal and pluripotent markers of stem cells and some markers of triploblastic differentiation. Immunohistochemical staining showed that the tumors expressed stem cell markers, triploblastic markers and germ cell tumor markers AFP and HCG. Piwil2-iCSC tumors are probably undifferentiated embryonic small cell carcinoma, most likely to be immature teratoma, mixed with yolk sac tumor and choriocarcinoma components. It can be used as a useful model for the research of origin or genesis mechanism of cancer stem cells and the treatment of relevant tumors.

Double Pathology: Malignant Epithelial Ovarian Tumor and Germ Cell Tumor (Choriocarcinoma), a Rare Coexistence

Surface epithelial stromal tumors account for approximately 60% of all ovarian tumors and approximately 90% of all ovarian malignancies. Sex cord stromal tumors account for 7% of all malignant ovarian tumors. Germ cell tumors make up only 3-7% of malignant ovarian tumors. A combination of serous carcinoma of the ovary and choriocarcinoma is rare. Until today such combination has been documented only in six cases in the English literature. Here, we describe a case of ovarian serous carcinoma, where histopathology revealed a combination of serous carcinoma with adjacent choriocarcinoma component in the extraovarian peritoneal deposits. A 64-year-old post-menopausal female was diagnosed to have stage IV ovarian cancer. She received six cycles chemotherapy. Subsequently she underwent optimal cytoreductive surgery. Microscopically, monomorphic histology (serous carcinoma) was noted in both the ovaries and dimorphic histologies (serous carcinoma and choriocarcinoma) in the sigmoid mesocolon nodule, omentum and left subdiaphragmatic nodules. Metronomic chemotherapy continued and patient is on regular follow-up for the past 1 year with stable disease. Recognition of choriocarcinomatous components in ovarian carcinomas is important because of its association with aggressive behavior. In spite of the aggressive histology, the patient is surviving for the past 1 year. Different chemotherapeutic regimens have been used in cases of mixed choriocarcinoma and carcinoma, but established chemotherapeutic regimens have not been described. Chemotherapeutic regimens that target both components have been advocated and used. The absence of choriocarcinoma in ovarian primary and its presence in the extraovarian peritoneal deposits have not been described in the English literature so far. This case is being presented for its rarity.

Immunohistochemical expression of SFRP1 and SFRP3 proteins in normal and malignant reproductive tissues of rats and humans.

Secreted frizzled-related proteins 1 and 3 (SFRP1 and SFRP3) act as Wnt signaling pathway antagonists and play an important role in embryonic development and carcinogenesis. The aim of the present study was to analyze immunohistochemically the distribution of 2 SFRP family proteins, SFRP1 and SFRP3, in an experimental rat model, in normal and intrauterine growth-restricted (IUGR) human placentas, and in a subset of the corresponding human trophoblastic tumors (pure choriocarcinomas and mixed germ cell tumors with choriocarcinoma component). In rats, expression of both SFRP1 and SFRP3 was pronounced in the perimetrium and myometrium, whereas decidual cells showed only occasional positive cytoplasmic staining. The most prominent expression of both proteins was found in blood vessel endothelial cells. Stereological variable of volume density (Vv, mm) showed statistically higher expression of SFRP1 and SFRP3 in human IUGR placentas than in normal pregnancy placentas (P<0.0001). Compared with adjacent normal/benign tissues, reduced expression of SFRP1 and SFRP3 was observed in human trophoblastic tumors (58.5% and 31.25%, respectively), although none of the examined tumors exhibited complete loss of either protein. Our study indicates that increased expression of both SFRP1 and SFRP3 may contribute to the pathogenesis of IUGR placental dysfunction, whereas the loss of these proteins may be involved in the development of human trophoblastic tumors.

Pubertad precoz y tumoración torácica: presentación de un caso

A case is reported of a 7 year old patient with progressive dyspnea and genital development according to Marshall and Tanner criteria at the G2 VP3 stage. A mass of regular and well-defined borders was found in the chest, with calcifications and cystic areas of heterogeneous content. Basal measurements of FSH, LH and testosterone were <10 mIU/mL, 12.2 mIU/mL and 724 ng/dL, respectively. α-fetoprotein was 145.1 ng/mL. Excising the tumor improved respiratory symptoms, diminished hormone levels and stopped the process of precocious puberty. Pathology of the mediastinal tumor corresponded to a germ cell tumor with a predominant component of mature teratoma and choriocarcinoma. Neoplastic causes of precocious puberty are uncommon; its diagnosis is essential in order to provide timely treatment.

HLA-G in Testicular Germ Cell Tumors

Background: HLA-G is a non-classical major histocompatibility complex class I molecule. HLA-G expression has been found in various types of solid and hematological malignancies. It is also expressed in normal testicular and epididymal tissue. However, expression of HLA-G in testicular germ cell tumors has not been extensively studied. The aim of this study was to investigate whether HLA-G protein is present in different components of testicular germ cell tumors. Patients and Methods: 34 testicular cancer patients, for whom tumor tissue was available, were included in the study. Immunohistochemical staining was performed on tissue sections from formalin-fixed, paraffin-embedded tissue samples. Results: 7 (20.6%) patients had positive HLA-G staining in at least 1 component of the tumor sample. In 3 of 7 patients with intratubular germ cell neoplasia, staining with HLA-G was seen in this component. All of the choriocarcinoma components were strongly positive, and about 40% of teratoma components had immunopositivity. The components of seminoma and embryonal carcinoma, and most yolk sac tumors were negative. HLA-G immuno-positivity was not associated with tumor size, retroperitoneal lymph node involvement, distant metastasis, or relapse/refractory status. Conclusion: This study demonstrated that testicular choriocarcinoma and some teratomas express HLA-G, but not seminoma, embryonal carcinoma, and yolk sac tumors.

Clinicopathologic Analysis of Choriocarcinoma as a Pure or Predominant Component of Germ Cell Tumor of the Testis

Although well recognized in the literature, the contemporary clinicopathologic data regarding choriocarcinoma (CC) as a pure or the predominant component of a testicular germ cell tumor (GCT) are limited. Herein, we present a series of pure CC and predominant CC in mixed GCT of the testis obtained from a single oncology institution. A comprehensive histologic review of 1010 orchiectomies from 1999 to 2011 yielded 6 (0.6%) pure CC and 9 (0.9%) mixed GCT cases with a predominant CC component. Patients' ages ranged from 20 to 39 years (median 29 y). All patients had markedly elevated serum β-hCG levels (median 199,000 IU/mL) at presentation. All tumors were unilateral and involved the right (9/15) and left (6/15) testis. The mean tumor size was 6.5 cm (range, 1.5 to 8 cm). Histology was similar for pure CCs and the CC component of mixed GCTs. CC commonly showed expansile hemorrhagic nodular cysts surrounded by variable layers of neoplastic trophoblastic cells (mononucleated trophoblasts and syncytiotrophoblasts). The syncytiotrophoblasts usually covered columns of mononucleated trophoblasts and occasionally formed plexiform aggregates and pseudovillous protrusions. Immunohistochemical stains suggested a mixture of cytotrophoblasts (p63+, HPL_) and intermediate trophoblasts (p63-, HPL weak +/-) in the columns of mononucleated cells. In the 9 mixed GCTs, CC comprised 50% to 95% (7/9 were ≥80% CC) of the tumor; 7 were combined with 1, and 2 were combined with 2 other GCT components. The non-CC components included teratoma (5/9), seminoma (2/9), yolk sac tumor (2/9), and embryonal carcinoma (2/9). Lymphovascular invasion, spermatic cord invasion, and tunica vaginalis invasion were present in 15/15, 5/15, and 1/12 cases, respectively. In mixed GCTs, these locally aggressive features were attributed to the CC component, except in 1 tumor in which it was also exhibited by the embryonal carcinoma component. Lymphovascular invasion was multifocal to widespread in 73% of tumors. The stages of the 15 tumors were: pT2 (10), pT3 (5); NX (1), N1 (4), N2 (5), N3 (5); and M1a (2) and M1b (13). Distant organ metastasis mostly involved the lungs (11) and liver (10). Follow-up information was available in 14 patients, all of whom received cisplatin-based chemotherapy. All 6 pure CC patients were dead of disease (range, 6 to 14 mo, median 9.5 mo). Follow-up of 8 patients with predominant CC (range, 10 to 72 mo, median 27 mo) showed that 5 died of the disease, and 1 was alive with disease and 2 were alive with no evidence of disease at 60 and 72 months of follow-up, respectively; these latter 2 patients were the only ones with M1a disease on presentation. This series confirms the proclivity for high-stage presentation including presence of distant metastasis, hematogenous spread, and poor outcome of testicular CC. Mixed GCT with a predominant CC component has similar tendency for high-stage presentation, marked elevation of serum β-hCG levels, and aggressive behavior compared with pure CC. This study also showed that distant metastasis by CC when only involving the lungs (M1a) may not be uniformly fatal with chemotherapy. The mononucleated trophoblastic columns in testicular CC appear to be a mixture of cytotrophoblasts and intermediate trophoblasts, similar to that described in gestational CC.

Endometrioid adenocarcinoma with choriocarcinomatous differentiation: A case report and review of the literature

A choriocarcinomatous component is rarely present in carcinomas of certain sites and few cases of choriocarcinomatous differentiation in endometrioid adenocarcinoma have been reported. The present study reports a case of endometrioid adenocarcinoma of the uterine corpus with choriocarcinomatous differentiation, and discusses the clinicopathological features of this rare tumor. A 59-year-old post-menopausal female presented with abnormal vaginal bleeding. Magnetic resonance imaging demonstrated a relatively well-circumscribed tumor in the uterine corpus and a total cystectomy was subsequently performed. A histopathological examination revealed two distinct components in the uterine corpus tumor. The first component comprised ~80% of the tumor and was composed of poorly-differentiated endometrioid adenocarcinoma. The remaining component consisted of mononucleated and syncytial giant cells containing rich eosinophilic cytoplasm and large pleomorphic nuclei with coarse chromatin. An immunohistochemical analysis revealed that these syncytial giant cells were positive for β-human chorionic gonadotropin (hCG). Therefore, a diagnosis of endometrioid adenocarcinoma with choriocarcinomatous differentiation was confirmed. The clinicopathological features of nine previously reported cases of this tumor were analyzed in addition to the present case. The majority of the patients were post-menopausal. Endometrial choriocarcinoma may be considered to have a highly aggressive clinical course, since nine of the 10 cases displayed metastases and four patients succumbed to the disease. The pathogenesis of the choriocarcinomatous component is not well understood. However, genetic studies have demonstrated that conventional carcinoma and choriocarcinomatous components share common genetic alterations. The choriocarcinomatous component represents aberrant differentiation of the conventional carcinoma, however, genetic analyses of endometrioid adenocarcinoma with choriocarcinomatous differentiation have not been performed.

Epithelioid trophoblastic tumor: clinicopathologic and immunohistochemical analysis of three cases.

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.

EPCAM–A novel molecular target for the treatment of pediatric and adult germ cell tumors

Germ cell tumors (GCTs) are thought to develop from totipotent primordial germ cells. Although the epithelial cell adhesion molecule (EPCAM) is expressed on embryonic stem cells as well as different tumor cells, it has not yet been extensively studied in GCTs. We analyzed EPCAM expression by quantitative RT-PCR in 48 fresh-frozen GCT specimens of different histology (10 mature teratoma, MT; 6 immature teratoma, IT; 7 dysgerminoma; 6 mixed malignant GCTs; 19 yolk sac tumor, YST) and in the GCT cell lines NCCIT, TE76.T, JAR and 2102Ep, and correlated its expression with AFP and hCG protein levels, histologic differentiation, and clinical follow-up data. EPCAM protein was visualized by immunohistochemistry of selected corresponding paraffin embedded tumor tissues. EPCAM was expressed in malignant but not in benign GCTs irrespective of age, sex, site and clinical stage of tumor (P = 0.001). In primary teratomas, EPCAM expression increased with their grade of immaturity (mean 2(-ΔCt) values: MT 0.23, IT 1.61, P = 0.007) and significantly correlated with serum AFP (P = 0.03) and hCG (P = 0.03) levels in malignant GCTs. Particularly high EPCAM levels were found in nonseminomatous GCTs such as YSTs (8.49) and choriocarcinoma (13.54). Immunohistochemical analysis verified gene expression data showing a distinct EPCAM staining in YST. Similarly in vitro, highest EPCAM expression was measured in GCT cell lines comprising yolk sac (2102Ep: 5.59) or choriocarcinoma (JAR: 10.65) components. This first comprehensive analysis of EPCAM in GCTs revealed high EPCAM expression in YSTs and choriocarcinomas. Thus, these nonseminomatous GCTs may be interesting targets for EPCAM immunotherapy, which has to be evaluated in further studies.

Clinical analysis of 15 cases of malignant ovarian germ cell tumors with lung metastasis

To investigate the clinical characteristics, diagnosis, treatment and prognosis of malignant ovarian germ cell tumors (MOGCT) with lung metastasis. Fifteen patients of MOGCT with lung metastasis treated in Peking Union Medical College Hospital from Jan. 1982 to Dec. 2010 was retrospectively analyzed. (1) Clinical characteristics: the average onset age of these 15 patients is (23 ± 11) years old (6 - 48 years). The majority of these patients presented with abdominal pain (8/15) or irregular vaginal bleeding (4/15) as their initial symptoms. The primary tumor located in the left ovary in 8 cases, right ovary in 6 cases, and both sides in only 1 case. Metastatic lesions were confined to the lung in 12 patients, while the other 3 patients were found to have multi-site distant metastasis. (2) DIAGNOSIS:all 15 cases included 9 pure non-gestational ovarian choriocarcinoma (NGOC), 3 MOGCT containing choriocarcinoma component (one mature teratoma with choriocarcinoma component, one endodermal sinus tumor with embryonal carcinoma and choriocarcinoma components, one choriocarcinoma with dysgerminoma component), 2 embryonal carcinoma, one immature teratoma. Only one patient in these 15 cases was correctly diagnosed before surgery. (3) Time of lung metastasis:of 12 MOGCT with choriocarcinoma component, 11 patients were found to have lung metastasis in the course of their primary treatment, only 1 had lung metastasis 2 months after the synthetic treatment finished. Three MOGCT patients without choriocarcinoma component were all found to have lung metastasis when tumor relapsed in the advanced stages of the disease. (4) TREATMENT:all 15 patients received multi-agent chemotherapy combined with surgery. The mean courses of chemotherapy for these patients were 16 courses (5 - 43 courses). (5) PROGNOSIS: of these 15 cases, complete remission was obtained in 10 patients of NGOC or mixed ovarian germ cell tumors with choriocarcinoma component, 3 patients (one NGOC, one endodermal carcinoma and one immature teratoma, respectively) died in the course of treatment as result of tumor progression, 2 progressed cases (one NGOC and one endodermal carcinoma respectively) abandoning therapy were lost to follow up. MOGCT with lung metastasis are more often to found in NGOC patients. These patients could obtain high complete remission rate after standard multi-agent chemotherapy combined with surgery. The prognosis of MOGCT with lung metastasis containing choriocarcinoma component are better than that of those without containing choriocarcinoma component.

Gastric adenocarcinoma with choriocarcinomatous and hepatoid differentiation

ABSTRACTWe report a patient with gastric adenocarcinoma with choriocarcinomatous and hepatoid differentiation. A 67‐year‐old man visited our hospital for further evaluations due to gastric adenocarcinoma. The gastric cancer was located in the prepyloric area and appeared to be a protruding mass with an infiltrative growth pattern. Initial pancreatic and postoperative hepatic and pulmonary metastases were detected radiologically. Microscopically, choriocarcinomatous and hepatoid differentiation was observed with a moderately differentiated adenocarcinoma. The choriocarcinomatous components were positive for β‐hCG and the hepatoid components were positive for α‐fetoprotein (AFP). These uncommon pathological patterns are supposed to arise from the retrodifferentiation pathway of primary gastric adenocarcinoma. The preoperative laboratory data revealed elevated serum AFP (773.4 ng/mL) and carcinoembryonic antigen (62.2 ng/mL), whereas other tests were unremarkable. The prognosis of gastric adenocarcinoma with choriocarcinomatous and hepatoid differentiation is very poor; our patient died 4 months after the operation.

Endometrioid Adenocarcinoma with High-Grade Transformation with Serous and Choriocarcinomatous Differentiation - A Case Report

A choriocarcinoma component with a malignant tumor is relatively rare. We present a case of an 85-year-old woman with mixed carcinoma, which was endometrioid adenocarcinoma with squamous differentiation, choriocarcinoma and a disseminated peritoneal nodule, which was papillary serous adenocarcinoma. The patient received surgery and conservative treatment. Twenty weeks after surgery, a recurring tumor appeared at the Douglas pouch. Histology showed that the recurring tumor was poorly differentiated carcinoma that was very different from the primary tumor. This case represents an unusual uterine corpus cancer with high-grade transformation with serous and choriocarcinomatous differentiation. This case also demonstrates the capacity of tumor cells to differentiate into divergent elements.

Mixed germ cell tumor and hemangioblastoma in the cerebellum: report of a rare coexistence

We report a case of a cerebellar tumor consisting of a mixed germ cell tumor (GCT) and a hemangioblastoma. A 22-year-old man presented with myoclonus and cerebellar ataxia. Magnetic resonance imaging showed a tumor mass in the left cerebellar hemisphere. The tumor was totally removed, and the histological diagnosis was an undetermined neoplasm. Ten months later, the patient returned with cerebellar hemorrhage at the site of the previous tumor. An emergency craniotomy was performed, and a tumor mass adjacent to the hematoma was resected. Microscopic examination revealed a mixed GCT consisting of a germinoma, choriocarcinoma, and mature teratomatous component. An area of hemangioblastoma was also found in the same tumor mass. A retrospective examination of the histological sample from the first operation indicated a germinoma. A primary GCT of the posterior fossa is very rare, and there are no other reports of the coexistence of a GCT and a hemangioblastoma. A metastatic GCT lesion of extracranial origin should be considered when the intracranial GCT is non-germinomatous and arises in an unusual site. The most probable hypothesis for the histogenesis of this case was a hemangioblastoma complicated by a "tumor-to-tumor" metastatic lesion of testicular GCT with "burnout" of the primary site.

Ovarian Clear Cell Carcinoma With Choriocarcinomatous Differentiation

Ovarian epithelial tumors of nongerm cell origin with true choriocarcinomatous differentiation are rare. To date, there are only 5 documented cases in the literature. In the reported cases, the epithelial component was of mixed cell types or of mucinous differentiation. To the best of our knowledge, an ovarian carcinoma exclusively of clear cell differentiation coexisting with a pure choriocarcinoma has not been reported earlier. A 48-year-old postmenopausal woman was found to have a large pelvic mass with lung and liver metastases. Trucut biopsy of the mass showed a poorly differentiated carcinoma that was immunoreactive for CK7 and hCG. She received 6 cycles of neoadjuvant chemotherapy that included 3 cycles of etoposide/cisplatin and 3 cycles of paclitaxel/etoposide-paclitaxel/carboplatin (TE/TP) with partial response. Debulking surgery was carried out subsequently. Pathologic examination showed an ovarian clear cell carcinoma with a second component of choriocarcinoma in which the bilaminar growth pattern of cytotrophoblast and syncytiotrophoblasts was striking. Despite additional therapy, which included 2 cycles of TE/TP and 2 cycles of gemcitabine/taxotere, the disease progressed and the patient died 11 months postoperatively. This report showed that ovarian clear cell carcinoma with choriocarcinomatous differentiation is a highly aggressive tumor and has a very poor prognosis. Nonetheless, there may be a role for neoadjuvant chemotherapy that targets both the clear cell and the choriocarcinoma components to reduce the volume of the disease before debulking surgery.

Salvage chemotherapy with methotrexate, etoposide and actinomycin D in men with metastatic nonseminomatous germ cell tumors with a choriocarcinoma component: A preliminary report

The objective of the present study was to assess the use of salvage chemotherapy using methotrexate, etoposide and actinomycin D (MEA) in men with nonseminomatous germ cell tumor (NSGCT) with a choriocarcinoma component. Nine patients were included. They had initially received bleomycin, etoposide and cisplatin, and high-dose ifosfamide, carboplatin and etoposide as induction chemotherapies. However, they failed to achieve the normalization of ß-human chorionic gonadotropin (ß-HCG). Therefore, MEA therapy (methotrexate: 450 mg/body on day 1, actinomycin D: 0.5 mg/body on days 1–5, etoposide: 100 mg/body on days 1–5) was subsequently administered. After MEA therapy (median: 3 cycles), serum ß-HCG was normalized in five of the nine patients. Of these five, three achieved long-term disease-free survival and one died of disease unrelated to NSGCT, whereas the remaining patient developed disease recurrence and died of disease progression. All four patients who failed to achieve the normalization of ß-HCG died of disease progression. Although several severe toxicities greater than grade 3, which were mainly associated with bone marrow suppression, occurred in all patients, there was no treatment-related death. Considering the current outcomes, MEA regimen could be an attractive option as a salvage chemotherapy for metastatic NSGCT patients with a choriocarcinoma component showing resistance to intensive conventional chemotherapies.

Undifferentiated carcinoma of the liver with extensive choriocarcinoma component

Undifferentiated carcinoma of the liver is very rare. Undifferentiated carcinomas with osteoclast-like giant cells or neuroendocrine features have been reported. As far as we know, undifferentiated carcinoma of the liver with extensive choriocarcinoma component has not been reported. Here we present a case report of undifferentiated carcinoma of the liver with extensive choriocarcinoma component in an old man. US and multiphasic contrast-enhanced CT showed a heterogenous hypovascular mass in spite of the extensive choriocarcinoma component, probably due to necrosis and poorly differentiated portion of the tumor.

Coexistent gastric primary choriocarcinoma and adenocarcinoma

Choriocarcinomas are commonly gestational and intrauterine or gonadal in origin. Nongestational and extragonadal disease, especially in the stomach is extremely rare with a poorer prognosis and early metastasis. We herein describe a case of primary gastric choriocarcinoma with liver metastasis in a 69-year-old male. The patient presented with abdominal pain and irregular bowel habits of one month duration. Both endoscopic and radiographic imaging revealed an ulcerated and necrotic circumferential tumor in the pyloric antrum of the stomach. The histopathologic findings of the resected tumor were that of an extensively necrotic and hemorrhagic neoplasm with combined choriocarcinomatous and adenocarcinomatous element. A strongly positive immunohistochemical staining for beta- subunit of human chorionic gonadotropin (beta-HCG) in the choriocarcinomatous component and a proper correlation with elevated serum beta-HCG levels confirmed the diagnosis.

Primary Gastric Choriocarcinoma: Two Case Reports and Review of the Literatures

Primary gastric choriocarcinoma (PGC) is a rare tumor, and its pathogenesis is still uncertain. Most PGCs have been reported to possess an adenocarcinoma component of variable extent, and pure PGC is especially rare. The diagnosis of PGC is confirmed by exhibition of choriocarcinomatous components on biopsy and exhibition of beta-hCG positive cell on immunohistochemical stain and elevation of the serum beta-hCG. Moreover it must be confirmed that no other site including gonads displays any tumor masses. The PGC tends to be more invasive and to have early metastasis. The median survival is known to be less than several months. We report two cases. The first case was a 62 year-old man who was diagnosed as advanced gastric cancer (AGC) by endoscopic biopsy with hepatic metastasis and received palliative chemotherapy with modified FOLFOX regimen and Genexol plus cisplatin regimen. He underwent subtotal gastrectomy due to perforation of the stomach during chemotherapy. On post-operative biopsy, He was re-diagnosed as PGC and received another palliative chemotherapy modified FOLFIRI, BEP, EMACO, VIP. However, multiple liver metastases were aggravated, and also serum AFP level increased. Ultimately, the patient died 10 months after initial diagnosis. Another case was a 45 year-old man. On endoscopic biopsy, he was diagnosed as AGC of adenocarcinoma. On Chest and Abdomen CT, multiple pulmonary and hepatic metastasis were also confirmed. On liver biopsy, He was diagnosed as PGC. The immunohistochemical stains were performed and the results were cytokeratin positive, EMA negative and beta-hCG weak positive. The serum beta-hCG level was highly elevated. BEP, VIP and EMA/CO combination therapy were administered, but he died at 12th months after the initial diagnosis.

Mixed serous carcinoma of the endometrium with trophoblastic differentiation: analysis of the p53 tumor suppressor gene suggests stem cell origin

The pathogenesis of mixed endometrial adenocarcinoma with trophoblastic differentiation is quite unclear at times. The present study examines a serous carcinoma with choriocarcinomatous differentiation. p53 staining was seen in the serous component and the cytotrophoblastic cells of the choriocarcinomatous component, but not in the syncytiotrophoblastic cells. p53 mutational analysis showed a heterozygotic mutation at exon 8 for the choriocarcinomatous component and a homozygote deletion at exon 7 for the serous component. These alterations suggest that the multidirectional tumor differentiation might occur from a common stem cell in these malignancies.