Non-gestational Choriocarcinomas Research Articles

Imaging in gynecological disease (22): clinical and ultrasound characteristics of ovarian embryonal carcinomas, non-gestational choriocarcinomas and malignant mixed germ cell tumors.

To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor. This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non-gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition. One patient with embryonal carcinoma, five patients with non-gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14-77) years. Beta-human chorionic gonadotropin levels were highest in non-gestational choriocarcinomas and alpha-fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38-216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular-solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours. A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Primary Pure Non-Gestational Ovarian Choriocarcinoma: A Case Report

Introduction: Pure non-gestational ovarian choriocarcinoma is a rare malignant condition with aggressive behavior. The tumor arises from germ cells of ovarian. Few cases have been reported in the literature. We present a case of pure ovarian choriocarcinoma with disseminated tumor in pelvic. Case Presentation: A 16-year-old girl was referred to Ghaem hospital, Mashhad University of Medical Sciences, Mashhad, Iran in April 2016 with acute abdominal pain, abdomino pelvic mass and vaginal bleeding. In addition, an extremely high level of sub unit of human chorionic gonadotropin β-hCG was detected. Based on the emergency condition, she underwent laparotomy and left salpingo-oophorectomy with suboptimal resection of the tumor. Histopathology revealed a tumor compatible with pure non-gestational ovarian choriocarcinoma. Adjuvant chemotherapy was performed based on 4 courses of bleomycin-etoposide-cisplatin (BEP) regimen. She is now under chemotherapy. Conclusions: We recommend the use of minimally invasive, fertility-preserving surgeries in patients with non-gestational ovarian choriocarcinomas.

Genomic profile in gestational and non-gestational choriocarcinomas

IntroductionGestational (GC) (derived from the placenta) and non-gestational (NGC) choriocarcinomas are trophoblastic diseases originated from abnormal proliferation of trophoblastic cells. These rare tumors share similar morphology and pathological features and differ on chemotherapy response, genetic origin and prognosis. In this study, the genomic profile of choriocarcinomas was performed according to their origin (GC or NGC) aiming to better understand these poorly characterized diseases. MethodsThirteen patients were included in this study; 10 presented previous history of hydatidiform mole and six developed metastasis. Twelve polymorphic microsatellite markers (D15S659, APOC2, D5S816, BAT25, D3S1614, D3S1311, D1S1656, APC-D5S346, D3S1601, D18S70, D8S1110 and D11S1999) were investigated to distinguish GC from NGC. All choriocarcinomas were evaluated by copy number alterations using array CGH. ResultsEight cases were classified as GC and five as NGC. Although potentially polymorphic, NGC exhibited significant gain of 21p11. Rare copy number alterations (CNA) were detected as a frequent event in GC including gains of 1p36.33-p36.32 (3 cases), 17q25.3 (4 cases), and losses of 9q33.1 (5 cases), 17q21.3 (3 cases) and 18q22.1 (4 cases) (varying from 724 to 3,053 Kb). DiscussionTwo tumor suppressor genes are candidates to be involved in GC: TRIM32 (9q33.1) and CDH19 (18q22.1). Gains of CBX2, CBX4 and CBX8 were frequently found in high risk prognostic score in GC. The in silico functional interaction analysis revealed the involvement of PTEN and PI3K-Akt signaling pathways. These data pointed out significant genomic alterations in GC, opening new avenues to better characterize the pathobiology of this disease.

Choriocarcinome gingivo-mandibulaire primitif

Primary non-gestational extragonadal choriocarcinomas are uncommon and their head and neck localization more exceptional. We report on a primary choriocarcinoma case of the mandibular gingivae in a 26-year-old woman who presented with pulmonary and renal metastasis. Complete response (clinical, biological and radiological) was achieved with combined chemotherapy according to APE regimen associating actinomycin, cisplatin and etoposid. The patient was free of disease 4 years after therapy completion. Primary gingival mandibular choriocarcinoma is very rare. Clinical presentation is atypical; diagnosis is based on histopathological examination and positivity for HCG. Our case report showed high chemo-sensitivity and comparable outcome to the other localizations.

Seröses Endometriumkarzinom mit choriokarzinomatöser Komponente

Non-gestational extragonadal choriocarcinomas are extremely rare. A 61-year-old G3 and P3 underwent hysterectomy and bilateral salpingo-oophorectomy and pelvic lymph node sampling for endometrial carcinoma. Histologic examination revealed a serous carcinoma with a choriocarcinomatous component. Postoperatively serum HCG was 225000IU/l. Because of diffuse pulmonary metastatic disease with respiratory problems the patient was initially treated with methotrexate and folinic acid rescue. After three cycles chemotherapy was switched to the EMA-Co scheme because of rising HCG levels. After five cycles of EMA-Co HCG values declined and partial resolution of pulmonary metastatic disease was seen. Because of the metastatic disease and most likely due to the chemotherapeutically induced immunodeficiency, the patient died from pneumonia two months after the initial diagnosis. Endometrial adenocarcinoma with a choriocarcinomatous component is an aggressive neoplasm and should be treated as gestational choriocarcinoma.

Serous Carcinoma of the Endometrium with Choriocarcinomatous Differentiation

Nongestational choriocarcinomas rarely occur outside the gonads or teratomas. We report a serous carcinoma of the endometrium with a choriocarcinomatous component and review of the literature. A 61-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy for a serous carcinoma with choriocarcinomatous component. Immunohistochemistry showed a strong p53 staining of the serous component and the cytotrophoblastic cells of the choriocarcinomatous component; the syncytiotrophoblast was negative. The initial serum human chorionic gonadotropin (hCG) was 225,000 IU/L. Postoperatively, the patient developed diffuse pulmonary metastatic disease. Despite chemotherapy, the patient died 2 months after initial diagnosis. Abstracting the data from the reported cases and from the literature, it can be assumed that 2 different tumor types exist. The first one is morphologically and clinically more related to the gestational choriocarcinoma with strongly elevated serum hCG levels, early onset of (distant) metastatic disease, and consecutively rapid and often fatal clinical course. The second type presents as an endometrial carcinoma with single syncytiotrophoblast-like cells, associated with low serum hCG, no distant metastatic disease, and, consequently, a better prognosis. The prognostically relevant component for long-time survival in the latter variant is the nontrophoblastic component.

Detection of non-maternal components of gestational choriocarcinoma by PCR-based microsatellite DNA assay

Objective. Gestational and non-gestational choriocarcinomas have distinctly different tissues of origin, parental genotypes, natural histories, and responses to therapy. Our objective was to develop a convenient, fast, and reliable assay that would, using only patient tissue, allow separation of gestational from non-gestational choriocarcinomas. Method. Benign and malignant tissues, preserved in paraffin blocks and separated by microdissection, were examined using a commercial PCR-based tissue identity assay (ABI AmpFlSTR Profiler Plus Kit and ABI 377 DNA sequencer) to detect genetic profiles of 9 microsatellite markers, along with X and Y chromosome markers. Cases included 6 choriocarcinomas. Controls included eight non-germ cell reproductive tract tumors and two hydatidiform moles. Results. The microsatellite markers identified the five choriocarcinomas diagnosed on clinical and histological grounds as gestational, to be of genetically non-maternal (androgenic) origin. The neoplasm previously classified as a non-gestational choriocarcinoma was demonstrated to be of maternal origin, as were the non-germ cell reproductive tract tumors. Samples from hydatidiform moles contained either androgenic markers only or a mix of maternal and androgenic markers, as previously seen in complete and partial moles, respectively. Conclusion. A commercially available microsatellite DNA diagnostic assay is a quick and convenient way to discriminate between gestational and non-gestational choriocarcinoma.

Rectal adenocarcinoma with choriocarcinomatous differentiation: Clinical and genetic aspects

Nongestational choriocarcinomas are rare tumors. In the gastrointestinal tract, they are characterized by a biphasic tumor growth with separated areas of adenocarcinomatous and choriocarcinomatous differentiation. We here report a case of a combined adenocarcinoma-choriocarcinoma of the rectum. The tumor showed an aggressive clinical behavior with metastasis to the liver and lungs. A transient partial remission was achieved after 4 cycles of cisplatinum, etoposide, and ifosfamide chemotherapy, with normalization of serum β-human chorionic gonadotropin levels. At this time, viable residual choriocarcinoma cells were found in surgically resected lung metastasis. The patient succumbed 8 months after initial diagnosis to a rapid abdominal relapse. We used comparative genomic hybridization (CGH) and fluorescence in situ hybridization to elucidate the genetic relationship of adenocarcinoma and choriocarcinoma in this neoplasm. We found genetic changes characteristic for colorectal adenocarcinomas, a loss of chromosomal regions 8p21-pter as well as 18q21-pter, and a gain of 5p and 20q, in both tumor parts. This provides evidence for the common origin of both components. A differential pattern of additional genetic changes suggests a clonal evolution from a common ancestor cell. In contrast to findings from a comparative study on a choriocarcinoma of the renal pelvis, we did not find an amplification of the germ cell cancer-associated chromosomal region 12p11.2-p12.1 in the areas of choriocarcinoma but found instead a loss of Xp11.3-pter. To our knowledge, this is the first report of a CGH comparision of the adenocarcinomatous and choriocarcinomatous tumor parts in a nongestational choriocarcinoma of the gastrointestinal tract.

Concurrent ovarian-type primary peritoneal adenocarcinoma and peritoneal choriocarcinoma. A case report and review of the literature

Background. Nongestational choriocarcinomas are aggressive tumours occurring either as a global event or as a focal change in solid tumours. The latter is responsible for coexistence of trophoblastic histology with other malignancies. Case. A 65-year old female with stage IV primary peritoneal carcinoma, ovarian type, underwent surgical cytoreduction followed by two courses of paclitaxel/carboplatin chemotherapy. A choriocarcinomatous component was later identified in the resection specimens, as chemotherapy resulted in a differential response of the two malignant variants. Commencement of EMA/CO chemotherapy (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) resulted in symptom palliation and tumour regression, further consolidated with platinum-based EP/EMA (etoposide, cisplatin, methotrexate, actinomycin D). Two months later, relentless choriocarcinomatous disease progression followed, leading to the patient's death while the peritoneal adenocarcinomatous variant remained biochemically quiescent. Conclusion. Choriocarcinomas may coexist with typical ovarian-type peritoneal cancer, creating diagnostic and therapeutic dilemmas. Aggressive weekly chorio-type chemotherapy appears to be warranted despite the low likelihood of cure, as it provides significant symptom palliation.

Malignant trophoblastic neoplasms with different modes of origin

The genetic origin of 24 trophoblastic neoplasms was determined using PCR polymorphisms. Based on pregnancy history, these tumors included nine postmolar trophoblastic tumors, 12 tumors preceded by live birth or abortion, and three nongestational tumors. Androgenetic origin was defined in eight post-molar trophoblastic tumors, and the remaining one might have arisen from a normal fertilization. Six tumors retained genetic features carried by the homozygous complete mole. Two tumors showed PCR polymorphism compatible with that of the heterozygous complete mole. All 12 tumors in the second class had alleles of both paternal and maternal contribution. However, discordance of sex between the antecedent pregnancy product and the tumor was recognized in three choriocarcinomas. The absence of paternal contribution suggested a parthenogenetic origin of three nongestational choriocarcinomas. The findings that PCR polymorphisms were either homozygous in certain loci or heterozygous in others may mean that the tumor was derived from a germ cell after meiosis I. As a result, at least three subtypes with different modes of origin were demonstrated in the 24 trophoblastic tumors. These findings underscore the importance of precise genetic marker analyses in a large series to clearly identify clinical and biologic characteristics of each subset of tumors.

Immunohistochemistry of germ cell and trophoblastic neoplasms

The immunoprofiles of 121 germ cell and trophoblastic neoplasms were defined, using a battery of antibodies against cytokeratin (CK), vimentin (VIM), epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), S-100 protein, leukocyte common antigen (LCA), UCHL-1, LN-2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), chromogranin A, Leu-7, alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), and the beta subunit of human chorionic gonadotropin (BHCG). In addition to 85 neoplasms of testicular origin, the cases included eight ovarian germ cell tumors and 28 extragonadal neoplasms. All tissues had been subjected to formalin fixation and paraffin embedding. Similar immunoreactivity patterns were seen in gonadal and extragonadal neoplasms, gestational and nongestational choriocarcinomas, components of mixed germ cell tumors and their pure counterparts, and metastatic and primary lesions. Placental alkaline phosphatase was a sensitive marker of germ cell differentiation, and expression of this marker in the absence of EMA appeared to be a staining pattern unique to germ cell tumors. Both LCA and S100 were absent in neoplastic germ cells, and thus were useful in differentiating these tumors from malignant lymphoma and malignant melanoma, respectively. Cytokeratin was helpful in distinguishing seminomas/dysgerminomas from nonseminomatous germ cell tumors, although 10% of seminomas showed focal or diffuse cytokeratin reactivity. Finally, 75% of all germ cell neoplasms displayed NSE, calling the specificity of this determinant into question.

Cornual choriocarcinoma presenting as an ectopic pregnancy

Ectopic pregnancy is a common event—less so, however, in the cornu of the uterus than elsewhere in the fallopian tube. Gestational choriocarcinoma is an infrequent event in the Western Hemisphere, and origin at an ectopic site is extremely uncommon. A 35-yr-old Central-American patient came to surgery after having had the usual evaluation for a common disorder. That the actual findings were those of an uncommon disease was a surprise. Physical examination, laboratory and radiographic results, and even the appearance of the lesion at the time of surgery were not inconsistent with a cornual pregnancy. Unfortunately histopathologic examination revealed a much more significant lesion, which proved rapidly fatal. Prior to surgery the patient had had no menstrual periods for 3 mth: A 2-min pregnancy test was positive, and a D&C was performed, which yielded only decidua. When an adnexal mass was palpated 3 wk later, an office pregnancy test was still positive, and the patient was readied for surgery. A preoperative pelvic ultrasound examination demonstrated a mass in the left adnexa with a normal sized uterus. At surgery a haemorrhagic mass in the left uterine cornu necessitated a hysterectomy. Both ovaries were inspected visually by the gynaecologic surgeon, considered normal, and not removed. Pathological evaluation revealed an infiltrative lesion which was characteristic of choriocarcinoma microscopically. Although an associated ectopic pregnancy was not demonstrated, the lesion was presumed to be gestational rather than a metastasis from a germ cell tumour of ovary because the patient was of reproductive age. exhibited the signs and symptoms of pregnancy, and had ovaries grossly normal at the time of surgery, an important feature since non-gestational ovarian choriocarcinomas are usually associated with other germ cell-derived tumour elements, and small scars or ‘tombstones’ are not recognized as tumour precursors in the ovary, unlike in the testis. Despite methotrexate therapy the patient expired in 4 mth.

Chemotherapeutic and immunological aspects of choriocarcinoma.

There are two types of choriocarcinoma, namely that originating from the placenta, the result of union of two genetically different germ-cells, and that from the primordial cells in gonads of both sexes, or, very uncommonly, in various extragonadal sites consisting of the host's genetic element. Both gestational and nongestational choriocarcinomas are characterized by rapid cellular proliferation and dissemination, causing a mortality rate of over 90% in untreated patients. Multiple hormonal production, particularly chorionic gonadotropin is a unique feature. In 1956 Li, Hertz, and Spencer documented the extreme sensitivity of gestational choriocarcinoma to a folic acid antagonist, methotrexate, as evidenced by complete tumor resolution, and that the urinary chorionic gonadotropin titre was a very sensitive and reliable index of tumor response. 1 Subsequent national and international studies reported a five- to ten-year cure rate in about 50% of the patients so treated. 2 In 1961 Li further found dactinomycin effective against