Choriocarcinoma Component Research Articles

A decade in focus: mixed germ cell tumors with choriocarcinoma components

Introduction: This 10-year registry review aimed to investigate the clinical behaviour and outcomes of mixed germ cell tumours with choriocarcinoma components, a rare and aggressive subtype of testicular cancer, in Saudi Arabia. The study explores the demographic characteristics of affected patients, tumour profiles, and the mortality rate associated with this malignancy. Methods: Utilizing data from the Saudi Cancer Registry, the authors identified 33 cases of mixed germ cell tumours with choriocarcinoma components among 1001 testicular cancer cases recorded between 2008 and 2017. Demographic information, including age, marital status, region of residency, year of diagnosis, and 10-year survival status, were collected. Tumour factors, such as the basis of diagnosis, origin site, behaviour, grade, extension, and laterality, were also analyzed. Results: The majority of cases (78.8%) occurred in the young age group (18–45 years), and most tumours (97%) originated in normally descended testes. Grade IV (undifferentiated anaplastic) tumours and distant metastasis were present in 45.5% of patients. All cases exhibited malignant tumour behaviour. The overall mortality rate was 15%, with a mean time from diagnosis to death of 7.72 months (range: 0.5–21.5 months). Conclusion: Mixed germ cell tumours with choriocarcinoma components are rare and tend to affect younger populations. These tumours demonstrate aggressive clinical behaviour, with a significant proportion presenting with high-grade lesions and metastasis at diagnosis. The observed mortality rate underscores the poor prognosis associated with this malignancy. Our study provides essential insights into the clinical characteristics of this rare tumour subtype in the Saudi Arabian population, emphasizing the need for further research to identify prognostic factors and optimize management strategies for affected patients.

Impact of tumor markers on diagnosis, treatment and prognosis in CNS germ cell tumors: correlations with clinical practice and histopathology

Tumor markers in CNS germ cell tumors (GCTs) include human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP), which have significant diagnostic implications, as elevation of either one leads to clinical diagnosis of non-germinomatous GCTs without histopathological confirmation, justifying intensified chemotherapy and irradiation. The current study, based on an international cohort of histopathologically verified GCTs that underwent biopsy (n = 85) or resection (n = 76), sought to better define the clinical role and prognostic significance of tumor markers from serum and CSF in this challenging patient population. We found that HCG was elevated only in cases with a germinoma or choriocarcinoma component, and there existed a clear cut-off HCG value between the two. AFP was often elevated in GCTs without a yolk sac tumor component, especially immature teratoma. HCG was elevated only in CSF in 3-of-52 cases, and AFP was elevated only in serum in 7-of-49 cases, emphasizing the potential utilization of both serum and CSF studies. Immature teratoma demonstrated unfavorable prognosis independent of tumor marker status, with 56% 5-year overall survival; however, co-existent germinoma components indicated a more favorable prognosis. Taken together, the study findings emphasize the importance for routine assessment and guarded interpretation of tumor markers in CNS GCTs.

Successful surgical management of massive hemoretroperitoneum caused by spontaneous rupture of retroperitoneal lymph node metastases in a patient with advanced mixed germ cell tumor: a COVID-19 pandemic-related surgical challenge

BackgroundSpontaneous rapture of a germ cell tumor (GCT) metastases causing massive hemoretroperitoneum in a patient without choriocarcinoma component who has not received previous systemic chemotherapy is an exceedingly rare event. In such a devastating case scenario, a high index of clinical suspicion for early diagnosis and appropriate management is crucial.Case presentationWe report on a 25-year-old male patient with a 4-month history of orchiectomy for testicular GCT (tGCT), who presented in the emergency department with acute abdomen and hemodynamic instability. Urgent computed tomography scan depicted a retroperitoneal mass measuring approximately 13 × 11.4 × 15 cm and massive intraperitoneal hemorrhage. Hemoperitoneum caused by spontaneous rapture of the metastatic retroperitoneal mass was suspected. COVID-19 pandemic-related deviation from the oncologic surveillance standards combined with COVID-19-related patient’s emotional distress and self-neglect had led to loss of opportunity for appropriate adjuvant chemotherapy, obviously leading to the development of this devastating complication. An emergency, surgical exploration was decided. The bleeding mass was adequately exposed following a Cattell–Braasch maneuver and active bleeding was controlled by a challenging resection of approximately 80% of the lymph node mass volume. Pathological evaluation of the specimen revealed teratoma with low volume of yolk sac tumor component and extensive necrosis, findings compatible with the patient’s history. Postoperative recovery was uneventful, followed by early start of adjuvant chemotherapy. Two years after the operation the patient is doing well with no evidence of recurrent disease.ConclusionsMassive hemoperitoneum is a devastating event that exceedingly rarely can complicate the clinical course of patients with advanced tGCT. Emergency surgical intervention is usually necessary however, sound judgement and careful surgical techniques are required for a positive and uneventful outcome. During COVID-19 pandemic, first-line medical personnel push their limits further not only to ensure health care services standards but also, to manage unpredictable, life-threatening cancer-related complications, associated with COVID-19-related deviation from appropriate oncologic surveillance and care.

RADT-37. THE OUTCOMES OF INTRACRANIAL GERM CELL TUMOR PATIENTS WITH CHORIOCARCINOMA COMPONENT AND/OR Β-HCG HIGHER THAN 500IU/L UNDER RADIOTHERAPY-BASED TREATMENTS

Abstract BACKGROUND In the previous studies, intracranial germ cell tumor (iGCTs) patients with pure choriocarcinoma or mixed germ cell tumors containing choriocarcinoma components showed similar dismal prognoses with median overall survival of 22 months and a one-year survival rate around 60%. However, those conclusions need update since radiotherapy, a milestone for this disease, was not applied to many patients in the published reports. Patients and METHODS Clinical data of iGCTs patients with histologically confirmed choriocarcinoma component and/or β-HCG > 500IU/L were collected from the archive of our institute and studied retrospectively. RESULTS Totally, 76 patients were eligible for the study. 11 patients took surgery as initial treatment, followed by chemoradiotherapy in terms of treatments. Sixty-one patients initiated their treatments with chemotherapy. Among them, twelve patients received second-look surgery due to residue disease. Subsequently, all received radiotherapy except for two early deaths. Four patients received radiotherapy initially, followed by chemotherapy. The median follow-up time was 63 months. The 5-year EFS and OS were 81.5% and 84.1%, respectively. Among patients who did not suffer from early death or progressed disease after induction chemotherapy (n = 68), multivariate analysis found chemotherapy cycles ( > 4 vs ≤ 4) (Hazard ratio [HR] for EFS 0.156, p = 0.021; HR for OS 0.110, p = 0.032), β-HCG level ( > 3000IU/L vs ≤ 3000IU/L) (HR for EFS 4.512, p = 0.052; HR for OS 6.604, p=0.028), and intertumoral hemorrhage (Yes vs No) (HR for EFS 23.177, p = 0.006; HR for OS 12.173, p = 0.081) were independent factors for survival. While radiation field (CSI vs non-CSI) was not proved to be a prognostic factor, either for EFS or OS. CONCLUSIONS iGCTs patients with choriocarcinoma component or β-HCG > 500IU/L showed improved survival with radiotherapy-based treatments. Patients with higher β-HCG levels and hemorrhage had a poorer prognosis. More chemotherapy cycles could bring additional survival benefits.

Uterine choriocarcinoma arising from serous carcinoma in a postmenopausal woman: an analysis of next-generation sequencing and PD-L1 immunochemistry

BackgroundUterine somatic choriocarcinoma is a rare, clinically aggressive malignant tumor. They frequently concur with other cancer. However, the molecular pathogenesis between somatic choriocarcinoma and the concurrent carcinoma has rarely been addressed to date.Case presentationWe report a 68-years old Chinese woman with a uterine choriocarcinoma arising from serous carcinoma. The patient underwent radical surgery including total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy and pelvic lymph node resection. She received 10 courses of post-operative chemotherapy. She died of disease 13 months after her surgery. Microscopically, the tumor showed a biphasic pattern of choriocarcinoma and serous carcinoma. The choriocarcinomatous component showed a combination of cytotrophoblast, intermediate trophoblast and syncytiotrophoblast with hemorrhage and necrosis. The component of serous carcinoma was characterized by solid sheets of small cells with marked nuclear atypia and occasional glandular and papillary formation. PD-L1 was exclusively expressed in the choriocarcinomatous component. Next-generation sequencing revealed that the genetic abnormalities were overlapping between the two components.

Spindle cell thymoma (WHO type A) - Choriocarcinoma: An unusual association: A clinicopathological and immunohistochemical study of 3 cases.

Three cases of an unusual association between spindle cell thymoma (WHO type A) and choriocarcinoma are presented. The patients are three men between the ages of 58 and 68 years. Clinically, all the patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Clinical history and physical examination did not reveal the presence of any prior malignancy. Diagnostic imaging showed in the three patients the presence of a large anterior mediastinal mass. A core needle biopsy was obtained in the three patients. In two patients the biopsy showed the classic histology of a spindle cell thymoma while in one patient the biopsy showed the association of two tumors - spindle cell thymoma and choriocarcinoma. Surgical resection via thoracotomy was performed in the three patients. The mediastinal tumors measured between 9 and 17cm in greatest diameter and were described as solid and lobulated with areas of hemorrhage. Histologically, all the tumors showed similar histological features of spindle cell thymoma (WHO type A) associated with a high-grade neoplasm composed of round and multinucleated giant cells compatible with choriocarcinoma. Immunohistochemical stains showed positive staining for keratin 5/6, and p40 in the spindle cell component, while the choriocarcinomatous component showed positive staining for human chorionic gonadotropin and human placental lactogen. The cases herein presented highlight not only the unusual association of spindle cell thymoma and choriocarcinoma but also raises some issues regarding the histogenesis of germ cell tumors, in this case choriocarcinoma.

S2626 Metastatic Testicular Choriocarcinoma Causing Gastrointestinal Bleeding in a Young Adult Male

Introduction: Testicular germ cell tumors are rare and account for less than 1% of malignancies in males. Although there are multiple subtypes of germ cell tumors, choriocarcinoma is the most aggressive and least common subtype. Metastasis typically occurs via hematogenous spread, usually affecting the lungs, liver and brain. We present a case of a 34-year-old male with metastatic testicular choriocarcinoma presenting with melena due to metastatic foci of disease involving the stomach. Case Description/Methods: A 34-year-old male with recently diagnosed stage IIIC metastatic germ cell tumor with known metastasis to the brain, lung, and liver presented to the hospital for initiation of cisplatin-based chemotherapy. He reported a two-week history of melena for which gastroenterology was consulted. His abdomen was soft and non-tender. Digital rectal exam did not reveal any overt bleeding. Labs were notable for a hemoglobin of 6.8 g/dL and a hematocrit of 22.3%. Esophagogastroduodenoscopy was performed revealing numerous nodular islands of abnormal tissue in the gastric body. Biopsies of the tissue were obtained and sent to pathology. Biopsies of the mucosa were positive for cytokeratin7, human-chorionic-gonadotropin (HCG), and a minimal number of cells expressing CD30. The tumor cells were negative for cytokeratin 20, alpha-fetoprotein (AFP), and placental-alkaline-phosphatase (PLAP) on immunohistochemistry staining. These findings supported the diagnosis of metastatic germ cell tumor with predominant choriocarcinoma component. Following esophagogastroduodenoscopy, the patient was placed on acid suppression therapy and proceeded with chemotherapy. Discussion: Testicular choriocarcinoma is a rare subtype of germ cell tumor that affects young adult males. It is an aggressive tumor that metastasizes early via hematogenous spread. Patients can present with hemorrhage from metastatic lesions which can be spontaneous or in response to chemotherapy. Metastasis to the gastrointestinal tract is seen in less than 5% of cases involving primary testicular choriocarcinoma. In such cases, the stomach is the most common location of metastasis. This case highlights the importance of knowing that malignant germ cell tumors can present with gastrointestinal bleeding and should be placed in the differential when a young man presents with gastrointestinal bleeding.

The core four - A panel of immunohistochemistry markers to diagnose and subtype testicular germ cell tumors.

Context:Immunohistochemistry (IHC) to differentiate germ cell tumors.Aims:The aim of the study is to differentiate seminomatous and nonseminomatous germ cell tumors (GCTs) with morphological overlap using a minimal and affordable panel of IHC markers.Settings and Design:This is a retrospective observational study.Subjects and Methods:All testicular GCTs (TGCT) which were diagnosed on biopsies and/or resection specimens (prechemotherapy) between January 2014 and June 2019. The demographic, clinical, and imaging findings were noted from the medical records. Hematoxylin and eosin (H and E)-stained sections were reviewed for morphology. The IHC markers constituted Octamer-binding transcription factor (OCT) 3/4, glypican 3 (GPC3), CD117, CD30, placental-like alkaline phosphatase, Sal-like protein 4, and β-human chorionic gonadotropin (HCG). IHC markers were performed in various combinations depending on the morphology, and a panel constituting OCT 3/4, CD117, GPC3, and CD30 was performed on cases with diagnostic dilemma and morphological overlaps.Statistical Analysis Used:Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) were calculated for suggested panel of IHC OCT 3/4, CD117, GPC3, and CD30.Results:The study included 36 patients with TGCT with a mean age of 27 (15–58) years. Nonseminomatous tumors were the most common (86%). The concise panel was performed in 20/36 (56%) tumors to resolve the diagnosis. The sensitivity, specificity, PPV, and NPV for OCT3/4 were 80%, 55%, 31%, and 92% in seminomas and 65%, 100%, 100%, and 46% in embryonal carcinomas (EC), for CD117 was 89%, 82%, 73%, and 93% in seminomas and 60%, 77%, 60%, and 77% in yolk sac tumors (YST), for GPC3 was 95%, 90%, 95%, and 90% in YST, CD30 96%, 100%, 100%, and 91% in ECs, respectively.Conclusions:Designing a novel concise and affordable IHC panel constituting OCT 3/4, CD117, GPC3, and CD30 has good sensitivity and specificity in differentiating seminomas, YST, and EC, respectively. Additional markers, namely β-HCG, can be used in identifying the choriocarcinoma component.

Non-gestational choriocarcinoma of the ovary complicated by dysgerminoma: a case report

Background: Non-gestational ovarian choriocarcinoma (NGOC) is a highly malignant tumor derived from germ cells, accounting for <0.1% of ovarian germ cell tumors. Mixed germ cell tumor (MGCT) containing a choriocarcinoma component is extremely rare. Dysgerminoma is one of the most common malignant primordial germ cell tumors, accounting for 3–5% of all malignant tumors of the ovary. The coexistence of these two tumors is even rarer.

Malignant Mixed Germ Cell Tumors of the Ovary: An Analysis of 100 Cases Emphasizing the Frequency and Interrelationships of Their Tumor Types.

One hundred malignant mixed germ cell tumors of the ovary that occurred in patients 3 to 55 years (mean: 20 y) of age are described. The clinical presentation was usually that of any highly malignant tumor of the ovary (abdominal pain and distension), but rarely (3 cases) endocrine manifestations were present. The tumors were usually unilateral (96%), ranged from 4 to 38 cm (mean: 16 cm), and were uniformly solid or, more often, solid and cystic; occasionally the typical appearance of dysgerminoma could be appreciated. The most common tumor type was yolk sac tumor (91%), followed by dysgerminoma (61%), immature teratoma (58%), embryonal carcinoma (38%), and choriocarcinoma (11%). A variety of admixtures were encountered; dysgerminoma and yolk sac tumor was the most common combination (25% of the tumors) with the 2 components often being sharply demarcated. Immature teratoma and yolk sac tumor was the next most common pairing (20%) followed by yolk sac tumor and embryonal carcinoma, with or without immature teratoma (16%). Tumors with a choriocarcinoma component had the most varied combinations of tumor types. Embryoid bodies were seen in 21% of the tumors, most often as fragmented forms arranged in a nodular manner with yolk sac tumor and/or embryonal carcinoma; uncommonly they occurred singly or in clusters. Numerous confluent well-formed embryoid bodies (polyembryoma) were prominent in 2 tumors. Three tumors had a focal diffuse embryoma pattern. The specific tumor types showed the known diverse spectrum of microscopic appearances, but the frequent haphazard arrangement of 2 or more subtypes often resulted in complex morphology. Overgrowth of another neoplastic component, most often primitive neuroectodermal tumor, occurred in 10% of the tumors further complicating the histologic picture. This is the largest series of ovarian malignant mixed germ cell tumors reported and details their characteristics including associations of their subtypes and the frequent apparent role of embryoid bodies in giving rise to yolk sac tumor and embryonal carcinoma components.

S1398 Biliary Stricture in a Patient With Metastatic Mixed Germ Cell Tumor (MGCT) of the Testis: A Case Report

INTRODUCTION: Testicular cancer is the most common malignancy in American males between the ages of 15–35. Up to 95% of testicular cancers are GCTs and the most common site for metastatic spread is the retroperitoneal lymph nodes. However, the spread of the retroperitoneum rarely involves the biliary tree. We present an unusual case of MGCT of the testis with metastases to the retroperitoneal lymph nodes causing biliary stricture and common bile duct dilation. To the best of our knowledge, this is the first reported case of biliary stricture caused by metastatic testicular cancer. CASE DESCRIPTION/METHODS: An 18-year-old man with no significant past medical history presented to our emergency department with a two-week history of progressive abdominal pain and weight loss. A complete physical examination was normal except for a tender abdomen without rebound tenderness. Laboratory findings on admission revealed signs of obstructive jaundice with elevated transaminases and elevated total bilirubin. CT of the abdomen showed large retroperitoneal masses measuring 14.2 cm extending into porta hepatis region with dilatation of the biliary ducts. Further evaluation including testicular palpation and ultrasound revealed a small testicular nodule. There was an abnormal elevation of testicular markers (serum beta-human chorionic gonadotropin level was 77,193 IU/ml) which subsequently led to suspicion of testicular cancer. He underwent a biopsy of the retroperitoneal mass, which confirmed a metastatic MGCT with embryogenic and choriocarcinoma components originating from the testis. He underwent a cycle of chemotherapy with etoposide, ifosfamide, and cisplatin during his hospital stay. ERCP performed showed a severe irregular biliary stricture over the lower third of the main bile duct with malignant appearance, and the upper third of the main bile duct was severely dilated secondary to stricture. A biliary sphincterotomy was performed and biliary tree balloon sweep was conducted with no significant findings. A plastic stent was placed into the common bile duct to maintain patency and demonstrated good flow. Follow-up labs demonstrated improvement in LFTs and bilirubin levels. DISCUSSION: This is a rare case of obstructive jaundice and biliary stricture in a patient with a MGCT (non-seminomatous) of the testis that metastasized to the retroperitoneal space. After ERCP with endoscopic bile duct stenting, it was noted that the jaundice and bile duct dilation resolved and symptoms improved.Figure 1.: Coronal contrast – enhanced CT image of upper abdomen demonstrates intra- and extra hepatic biliary dilation with abrupt cut-off at the upper common bile duct (black arrow), caused by confluent retroperitoneal lymphadenopathy extending into the hepatic hilum (white arrow).

Frequent EGFR expression/EGFR amplification and lack of activating mutation in testicular choriocarcinoma

Choriocarcinoma (CC) is the rarest but most aggressive histological component of adult testicular germ cell tumor (TGCT). Although we previously reported a putative role of epidermal growth factor receptor (EGFR) alterations in the progression of CC, little is known about the kinase-activating mutation status of EGFR, which predicts the response to EGFR-tyrosine kinase inhibitors. In this study, we clinicopathologically reviewed a total of 12 cases of mixed TGCTs with CC components. Immunohistochemistry, fluorescence in situ hybridization, and direct sequencing was performed to investigate EGFR expression, EGFR copy number alterations, and functional mutation of EGFR in these CC components, respectively. Four (33%) of 12 cases exhibited predominant CC components (>50%), and all these patients died due to disease within 62 months. Overexpression of EGFR, higher copy number of EGFR, and amplification of EGFR was observed in 12 (100%), 10 (83%), and 9 (75%) of 12 CC components, respectively. None of the cases showed any mutational events in exons 18 to 24, which encode the tyrosine kinase domain of EGFR. These results confirm an important role of EGFR in the tumor aggressiveness of testicular CCs and may suggest its possible innate resistance against conventional anti-EGFR therapies.

Lineage-Specific Alterations in Gynecologic Neoplasms with Choriocarcinomatous Differentiation: Implications for Origin and Therapeutics.

Choriocarcinoma is most commonly gestational (androgenetic or biparental) but can be of germ cell origin or can develop as a component of a somatic neoplasm (genetically related to the patient). The latter type are aggressive neoplasms for which the underlying genetic alterations are not well characterized. To investigate the relationship between the different components of somatic neoplasms with choriocarcinomatous elements, the genetic differences between gestational and nongestational tumors, and identify potential targetable alterations, we analyzed 23 samples from 11 tumors, including five gynecologic-type somatic neoplasms with choriocarcinomatous differentiation (two to three different components each) and six pure choriocarcinomas, for somatic mutations, single-nucleotide polymorphisms, and PD-L1 expression. In mixed tumors, gynecologic-type carcinoma components demonstrated lineage-characteristic and lineage-specific alterations, with choriocarcinomatous components sharing some of these as well as demonstrating novel alterations, supporting a clonal relationship with divergent differentiation of the choriocarcinoma from the somatic carcinoma. TP53 mutation only occurred in nongestational tumors. Diffuse PD-L1 expression was characteristic of choriocarcinoma in both pure and mixed tumors but not seen in the gynecologic-type carcinoma components. Given that the somatic carcinomatous and choriocarcinomatous components of mixed tumors have distinct genetic alterations and biomarker expression, separate analysis of these components is required to guide targeted therapy. High PD-L1 expression suggests a role for checkpoint inhibitor-based immunotherapy in tumors with a choriocarcinoma component. The underlying mechanisms by which cancer stem cells reprogram and initiate trophoblastic retrodifferentiation in some somatic tumors warrant further investigation.

The Clinical Significance of a Small Component of Choriocarcinoma in Testicular Mixed Germ Cell Tumor (MGCT).

The clinical significance of limited choriocarcinoma in a malignant mixed germ cell tumor (MGCT) is unknown. Men with a MGCT with ≤5% choriocarcinoma at radical orchiectomy (RO) between 2000 and 2016 from our consult service were studied. Of 50 men in our cohort, we had clinical information for 30 men. Median follow-up was 41 months (1 to 168 mo). Median tumor size was 4.5 cm (1.1 to 8.0 cm). In total, 22/30 (73%) cases were pT1, 6/30(20%) cases were pT2, and 2/30 (7%) cases were pT3. In total, 4/30(13%) cases had lymph node metastases and 2/30 (7%) cases had distant metastases at the time of RO. In 30 cases with RO we had information on immediate postorchiectomy treatment: 14/30 (46.7%) active surveillance, 4/30 (13.3%) retroperitoneal lymph node dissection, 10/30 (33.3%) chemotherapy (chemotherapy), 1/30 (3.3%) retroperitoneal lymph node dissection followed by chemotherapy, and 1/30 (3.3%) resection of a distant metastasis. Preoperative serum human chorionic gonadotropin (hCG) levels ranged between 0.1 and 60,715 mIU/mL (mean, 4796; median, 485). One patient had an hCG level of 6367 mIU/mL and another 60,715 mIU/mL with the remaining cases <5000 mIU/mL. In total, 4/30 (13%) patients had elevated serum markers after surgery, 3 of them normalized following chemotherapy while the fourth one continued to have elevated serum alpha fetoprotein levels after chemotherapy. All patients were alive at last follow-up. In total, 7/30 (23.3%) patients subsequently developed metastatic disease to lymph nodes or distal organs, the histology of the metastasis consisted mainly of teratoma and yolk sac tumor. Embryonal carcinoma was present in 2 metastatic sites. One lung metastasis was suggestive for choriocarcinoma. Definitive choriocarcinoma was not present in any of the metastasis. A small component of choriocarcinoma in a MGCT is typically associated with relatively low-level elevations of serum hCG levels, and is not associated with aggressive disease. The presence of limited choriocarcinoma (≤5%) does not add to the prognostic information provided by standard TNM staging, which uses levels of serum markers (hCG, alpha fetoprotein, lactate dehydrogenase) as surrogates for extent of disease.

Chemotherapy for metastatic testicular cancer: The first nationwide multi-institutional study by the Cancer Registration Committee of the Japanese Urological Association.

To assess clinicopathological data and oncological outcomes focused on metastatic testicular cancer patients, who received chemotherapy as the initial treatment, in the nationwide multi-institutional study by the Cancer Registration Committee of the Japanese Urological Association. A testicular cancer survey was carried out by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. Among 1121 registered patients, 278 patients with metastases who received chemotherapy as the initial treatment and could be categorized by the Japanese Urological Association classification were eligible for the analysis. As first-line chemotherapy, bleomycin, etoposide and cisplatin, and etoposide and cisplatin therapies were chosen for 260 patients (93.5%). As second-line therapy, vinblastine, ifosfamide and cisplatin/etoposide, ifosfamide and cisplatin; and paclitaxel, ifosfamide and cisplatin/paclitaxel, ifosfamide and nedaplatin therapies were carried out in 23 out of 63 (36.5%) and 29 out of 63 (46.0%) patients, respectively. The response rate and serum tumor marker normalization rate were 93.4% and 81.3% at first line, 75.4% and 60.7% at second line, and 41.7% and 16.7% at third line, respectively. The Japanese Urological Association classification (≥IIIB2 vs ≤IIIB1) and choriocarcinoma component in primary histology were independent prognostic factors of overall survival before starting chemotherapy. Furthermore, in patients with non-seminomatous germ cell tumors, serum tumor marker normalization was an independent factor that was associated with better outcome of overall survival after completion of the initial series of chemotherapies. The initial accurate diagnosis and risk stratification is an important prognostic factor to achieve better oncological outcomes. In patients with non-seminomatous germ cell tumors, aiming for serum tumor marker normalization with continuous sequential chemotherapy could improve overall survival.

Endometrial Carcinoma With Trophoblastic Components: Clinicopathologic Analysis of a Rare Entity.

Somatic endometrial carcinomas with trophoblastic components have only rarely been described. To better characterize this distinctive combination of histotypes, we report herein 4 new cases, representing the largest cohort reported thus far, and review previously reported cases. The 4 new patients ranged in age from 61 to 77 yr (mean, 68 yr). The first patient had a grade 2 endometrioid carcinoma, surgical International Federation of Gynecology and Obstetrics stage IA, that recurred 5 months later at the vaginal apex with purely choriocarcinoma elements, suggestive of unsampled trophoblastic areas in the uterus. The 3 other patients were all International Federation of Gynecology and Obstetrics stage III, and included 2 cases of dedifferentiated endometrial carcinoma with 40% and 20% choriocarcinoma components, and 1 case of grade 1 endometrioid carcinoma with a 40% choriocarcinoma component. Postoperative serum β-human chorionic gonadotropin was elevated in all patients. All received adjuvant combination chemotherapy, but all were dead of disease with distant metastases at an average of 11.75 mo (range, 7-16 mo) after primary staging. Data from our cases were combined with those from 24 cases that had previously been reported in the literature between 1972 and 2016. Analysis of this combined data indicates that endometrial carcinoma with trophoblastic component is a rare neoplasm that occurs primarily in postmenopausal patients. The trophoblastic component is most commonly a choriocarcinoma and the somatic component is most commonly an endometrioid carcinoma or an adenocarcinoma/carcinoma reported without further specification; the somatic component may be a diverse array of histotypes or histotype admixtures. Serum and/or urine β-human chorionic gonadotropin is elevated in almost all patients, and fluctuations of β-human chorionic gonadotropin generally correlated with tumor relapses or recurrences. The stage distribution and patient outcomes in the current and previously reported patients suggests that trophoblastic differentiation usually, but not invariably denotes clinical aggressiveness.

Biphasic gastric adeno-choriocarcinoma in a patient with known lynch syndrome – A case report

Primary gastric choriocarcinoma is a rare aggressive tumour accounting for less than 0.1% of all cases of gastric cancer. The majority of reported cases possess an adenocarcinoma component. Here we report a 46-year-old woman with known Lynch syndrome with MLH1 germline mutation, and a history of descending colon mucinous adenocarcinoma at age 39 presenting with a gastric tumour with multiple liver metastases and a solitary lung metastasis. Serum beta-hCG and CEA were markedly elevated at 185,000 U/L and 101.7 μg/L, respectively. Biopsy of the tumour showed a poorly differentiated biphasic carcinoma comprising 50% adenocarcinoma and 50% choriocarcinoma components. Adenocarcinoma was positive for CK7, CDX2, and Villin, whereas choriocarcinoma was positive for CK7, hCG, and p40. Interestingly, whilst the choriocarcinoma component showed loss of MLH1 and PMS2, the adenocarcinoma component showed normal mismatch repair protein immunohistochemistry. The patient subsequently underwent palliative radiation therapy. To the best of our knowledge, this is the first case of Lynch syndrome associated gastric cancer with an unequivocal choriocarcinoma component. The differential pattern of mismatch repair protein expression suggests early clonal separation of cancer progenitor cells during tumorigenesis.

Clear Cell Carcinoma of the Cervix With Choriocarcinomatous Differentiation: Report of an Extremely Rare Phenomenon Associated With Mismatch Repair Protein Abnormality

The presence of trophoblastic differentiation or nongestational choriocarcinoma in a carcinoma is rare but has been described in various organs, including in the female genital tract. We report a cervical clear cell carcinoma admixed with a component of choriocarcinoma in a 52-year-old woman, only the second report of this combination in the literature. Immunohistochemically, the tumor exhibited isolated loss of staining with the mismatch repair protein MSH6. We review the literature on trophoblastic differentiation in cervical carcinoma.

Extragonadal choriocarcinoma of the colon - incidence, diagnosis, and treatment - a case report

Background Choriocarcinoma is a malignant trophoblastic cancer. It could be gestational and non-gestational. The primary extragonadal choriocarcinoma of the colon is an exceptionally rare tumor. There are only 12 cases of this tumor described in the literature. Only four of these 12 cases are pure primary choriocarcinomas of the colon. In the other eight cases, there is an adenocarcinoma with a choriocarcinoma component. In that reason, rare case like this is advisable to be reported. Case presentation The purpose of this report was to systematize the existing information about the frequency, diagnosis, and treatment of primary choriocarcinoma of the colon and to present our experience with diagnostic and therapeutic approaches to this exceptionally rare and not well-known tumor. Primary extragonadal choriocarcinoma is most frequently found in the retroperitoneal space, mediastinum, pituitary gland and, very rarely, in the gastrointestinal tract. The stomach is the most frequent localization in the gastrointestinal tract. In our case, an extended right hemicolectomy was performed according to the principles of oncologic resection. Chemotherapy for gonadal choriocarcinoma was started. At present - four months after the surgical intervention, the Bulgarian patient does not show progression of the disease and is in good general health. Conclusion There is still no algorithm for treatment of primary choriocarcinoma of the colon because this is an extremely rare tumor. The behavior in this type of tumors remains a challenge for clinicians.

Choriocarcinoma syndrome after resection of primary pulmonary choriocarcinoma: report of a case.

BackgroundChoriocarcinoma syndrome is known as a lethal complication from tumoral hemorrhage, which frequently occurs at the site of tumor metastasis.Case presentationA 59-year-old man with 60-pack-year smoking history was referred to our hospital because of hemoptysis. Chest computed tomography (CT) showed a 28 × 18 mm spiculated nodule with a cavity infiltrating the left upper lobe. A transbronchial lung biopsy was performed, and histopathological examinations revealed adenocarcinoma. No distant or regional metastasis was observed, and therefore, the patient underwent a left upper lobectomy with lymphadenectomy. Histological examinations showed that the tumor consisted of poorly differentiated adenocarcinoma cells and a choriocarcinomatous component; no multiple pulmonary metastases and mediastinal lymph node metastasis were observed. Immunohistochemical analysis showed a positive immunoreaction for human chorionic gonadotropin in the syncytiotrophoblastic cells of the choriocarcinoma. One month after the operation, the patient developed massive hemoptysis. CT showed diffuse alveolar infiltration in both the lungs. A bronchoscopic examination showed bleeding from the right upper bronchus. Aspiration cytology showed carcinoma. Despite blood transfusion and management in the intensive care unit, the patient died one and a half month after diagnosis.ConclusionsWe herein report a case of a man who developed choriocarcinoma syndrome 1 month after resection for combined choriocarcinoma and adenocarcinoma of the lung. Choriocarcinoma syndrome is a rare and life-threatening complication which may occur in patients with primary pulmonary choriocarcinoma. However, we need to consider the risk of this syndrome while dealing with patients who have massive hemoptysis.