Primary non-gestational mediastinal choriocarcinoma metastatic to the brainstem.

Choriocarcinoma is a highly malignant tumour emerging from the syncytiotrophoblast divided into gestational and non-gestational presentations. Primary choriocarcinoma of the mediastinum is rare. Metastases to the brain often occur; however, brainstem involvement has not been reported for non-gestational choriocarcinoma. We described a middle-aged man who developed a complete left oculomotor nerve paralysis secondary to a brainstem tumour at the midbrain. The workup for the primary source of the brainstem tumour included a chest CT scan, which revealed a mediastinal mass. A mediastinal mass needle biopsy confirmed the diagnosis of primary mediastinal choriocarcinoma. Despite aggressive chemotherapy, the patient died 6 months after the initial presentation from neurological complications and multiorgan failure.

Primary mediastinal choriocarcinoma presenting as cutaneous metastasis with resistance to chemotherapy: case report and literature review.

Cutaneous metastases of choriocarcinoma are rare. They may indicate poor prognosis and resistance to chemotherapy. In this report, we present a case of a 25-year-old man who presented with central pleuritic chest pain and right upper arm mass for about a week. The patient also had significant weight loss during the last 5 months along with an episode of generalized seizure. Chest computed tomography scan revealed an 8 cm anterior mediastinal mass. A skin punch biopsy from the right upper arm mass revealed a malignant neoplasm with morphology consistent with metastatic choriocarcinoma. Further work-up revealed multiple lung and brain lesions. Ultrasound of the testes revealed no abnormalities. Several chemotherapy regimens were tried; however, there was no response and the disease showed progression. The patient died 6 months after initial presentation.

Clinical Experience of Male Primary Choriocarcinoma at the Samsung Medical Center.

PURPOSE: The objective of this study was to describe and analyze the clinicopathological features of primary choriocarcinoma (PCC) observed in male patients treated at the Samsung Medical Center between 1996 and 2020. MATERIALS AND METHODS: We reviewed the clinical records of 14 male patients with PCC retrospectively to assess their demographic, histological, and clinical characteristics at the time of diagnosis as well as identify the treatment outcomes. RESULTS: The median age of the patients was 33 years. The primary tumor site was the testicles in seven cases (50%), the mediastinum in six cases (43%), and the brain in one case (7%). The most common metastatic site was the lungs (79%), followed by the brain (43%). All patients with PCC received cytotoxic chemotherapy. Twelve patients had records of their response to cytotoxic chemotherapy; of these 12 patients, eight (8/12, 67%) achieved an objective response, and four (4/12, 33%) achieved stable disease response as the best response during chemotherapy. CONCLUSION: It is known that most male PCC patients eventually develop resistance to cytotoxic chemotherapy and die. Factors such as poor response to chemotherapy, high disease burden, brain metastasis, and hemoptysis at the time of diagnosis are associated with shorter survival time in male PCC patients. Programmed death-1/programmed death-ligand 1 blockade therapy can be a salvage treatment for chemotherapy-resistant male PCC patients.

Cutaneous Metastasis of Choriocarcinoma in 2 Male Patients: A Rare Presentation of an Aggressive Malignancy That Dermatopathologists Must Recognize.

Testicular choriocarcinoma needs to be considered in the differential diagnosis of cutaneous metastases in young adult men because of its propensity for early hematogenous dissemination. Furthermore, the diagnosis may not be suspected in many cases in which there is clinically no testicular enlargement. This highly aggressive germ cell tumor typically metastasizes to the liver, lungs, and brain. Skin metastasis is exceedingly rare with only 22 cases previously reported in the world literature. We herein report 2 additional cases: a 25-year-old man and a 32-year-old man, both of whom were treated for mixed germ cell tumors and developed multiple cutaneous metastases to the head.

Spontaneous renal hemorrhage secondary to choriocarcinoma in a man with congenital hypospadias and cryptorchidism: a case report and literature review.

BACKGROUND: Choriocarcinoma is a rare malignant germ-cell tumour, most commonly found in adult women. It infrequently presents as spontaneous renal haemorrhage (SRH). Genital malformation and SRH secondary to choriocarcinoma has previously been only reported in females. We present what we believe to be the first case of a male patient with genital malformation (hypospadias and cryptorchidism) and SRH at presentation of choriocarcinoma. CASE PRESENTATION: A 25-year-old man presented to the department with intense pain in the right flank region and lower back. Initial investigations showed spontaneous renal haemorrhage, for which an emergency partial nephrectomy was performed. Clinical, radiological, and pathological investigations suggested a diagnosis of testicular choriocarcinoma with metastases to the right kidney, both lungs, and brain. Initial treatment was with a chemotherapy regimen of cisplatin, etoposide and bleomycin and whole brain radiotherapy; however, 6 months after diagnosis the patient developed liver metastasis, after which time the BEP protocol was switched to ITP with oral apatinib. Despite best efforts, the liver and lung metastasis continued to grow and a decision was made to discontinue active treatment and provide only palliative care until the patient passed away. CONCLUSION: Choriocarcinoma is a difficult cancer to diagnose pre-operatively. In male patients with early metastasis, prognosis may be much poorer than in the commoner gestational choriocarcinoma. A multidisciplinary with comprehensive post-surgical intervention is of great importance in the treatment of these patients.

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.

Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.

INTRODUCTION: Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. PATIENTS AND METHODS: We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. RESULTS: Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. INTERPRETATION: We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted.

Primary mediastinal choriocarcinoma with brain metastasis in a female patient.

Nongestational choriocarcinoma is very rare and carries a poor prognosis in female patients. In this report, the authors present a case of nongestational choriocarcinoma with brain metastasis in a female. A 58-year-old female with intermittent back pain was referred to a private hospital. On examination, a mediastinal tumor and a pancreatic tumor were detected. Endoscopic ultrasound-guided fine needle aspiration biopsy of the tumor was performed for histological evaluation. Pathological diagnosis was difficult because only a small amount of tissue was collected. Head MRI showed multiple metastatic tumors in the brain. The patient was diagnosed with primary mediastinal choriocarcinoma with brain metastasis. She was treated with one course of an etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine regimen, but her general condition gradually deteriorated, and she died on day 41. Nongestational choriocarcinoma is drug resistant, whereas gestational choriocarcinoma has better chemotherapeutic sensitivity.

Urgent embolization of hemorrhagic choriocarcinoma liver metastases--case report and review of the literature.

We present a rare case of 23-year-old patient with metastatic choriocarcinoma that presented life threatening abdominal bleeding from liver metastases shortly after initiation of treatment with chemotherapy and was treated by emergency embolization of the hepatic vessels. Although the bleeding was controlled, the patient succumbed to the disease on the 15th day after admission. Conclusions: Incontrollable hemorrhagic complications are the most common cause of death in choriocarcinoma metastatic patients. Angioembolization is an effective way of ceasing the bleeding and a potentially life saving measure.

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 ß-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 ß-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.

A rare case of primary choriocarcinoma in the sigmoid colon.

Primary colorectal choriocarcinoma is an extremely rare neoplasm and is usually associated with a poor prognosis. Only 13 cases of colorectal choriocarcinoma have previously been reported. There is no standard chemotherapeutic regimen for this tumor type. A 68-year-old man presented with melena and was diagnosed with sigmoid colonic adenocarcinoma with multiple liver metastases. He underwent a laparoscopic sigmoidectomy. Pathology revealed choriocarcinoma with a focal component of moderately differentiated adenocarcinoma of colon origin. Based on the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) results, mFOLFOX6 and bevacizumab were administered, which suppressed aggressive tumor growth for 4 mo. The patient died 9 mo after the initial diagnosis. Our study results suggest that the standard chemotherapy regimen for colorectal cancer might have suppressive effects against primary colorectal choriocarcinoma. Moreover, CD-DST may provide, at least in part, therapeutic insight for the selection of appropriate antitumor agents for such patients.

Complete response to multidisciplinary therapy in a patient with primary gastric choriocarcinoma.

Primary gastric choriocarcinoma is a rapidly growing neoplasm with an average survival of several months in untreated patients. Gastrectomy with lymph node dissection followed by chemotherapy is the treatment of choice. Regimens used for gastric adenocarcinoma are usually selected. However, median survival remains less than six months. In this case report, we describe a case of primary gastric choriocarcinoma with a clinical complete response to multidisciplinary treatment including surgery, chemotherapy, and radiofrequency ablation (RFA). The patient was originally referred for general malaise. Esophagogastroduodenoscopy demonstrated a large tumor occupying the fornix, and total gastrectomy with lymph node dissection was performed. Seven days later, multiple liver metastatic recurrences with high serum levels of beta-human chorionic gonadotropin (ß-hCG) were recognized. Chemotherapy with a gonadal choriocarcinoma regimen consisting of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO), was initiated. After three cycles, serum ß-hCG decreased markedly and the tumors disappeared. Six months later, multiple lung metastatic recurrences were found. After one cycle of EMA/CO, only one nodule remained. Computed tomography-guided RFA was performed for this oligometastatic tumor. The patient has been alive with no evidence of disease for 10 years after the initial diagnosis. To the best of our knowledge, this patient with recurrent primary gastric choriocarcinoma has achieved the longest survival. The present case is the first report of choriocarcinoma metastatic to the lung successfully treated with RFA. From our retrospective analysis of recurrent or unresectable primary gastric choriocarcinoma, we propose that gonadal choriocarcinoma regimens can be considered as first-line for primary gastric choriocarcinoma.

Primary hepatic choriocarcinoma in a 49-year-old man: report of a case.

We report a case of hepatic choriocarcinoma in a man diagnosed at autopsy after a rapid downhill clinical course. The patient was a 49-year-old man who presented with acute right-sided abdominal pain. There were no masses palpable on physical examination. Radiographic findings showed large multi-nodular tumors mainly in the right lobe of the liver. Fludeoxyglucose-positron emission tomography scan showed uptake only in the liver, and no uptake in the testes. We initially planned to perform a liver resection for the presumed diagnosis of intra-hepatic cholangiocarcinoma. However, the tumors grew rapidly and ruptured. Multiple lung metastases rapidly developed resulting in respiratory failure, preventing liver resection or even biopsy. He died 60 d after initial presentation with no pathological diagnosis. Postmortem studies included histopathological and immunohistological examinations which diagnosed a primary choriocarcinoma of the liver. Primary hepatic choriocarcinoma is very rare but should be considered in the differential diagnosis of a liver tumor in a middle aged man. Establishing this diagnosis may enable treatment of the choriocarcinoma. Liver biopsy and evaluation of serum human chorionic gonadotropin are recommended in these patients.

Pathological complete response and two-year disease-free survival in a primary gastric choriocarcinoma patient with advanced liver metastases treated with germ cell tumor-based chemotherapy: a case report.

Choriocarcinoma is an early metastasizing and highly invasive tumor and characterized as a high-level human chorionic gonadotropin-secreting tumor. It normally arises in the gestational trophoblast, gonads and much less frequently in the stomach. Primary gastric choriocarcinoma appears to have a poor prognosis; especially with liver metastasis, the survival period is expected to be <1 month. This unfavorable clinical outcome is partly due to the lack of defined chemotherapy against primary gastric choriocarcinoma. We herein report a case of a 68-year-old male primary gastric choriocarcinoma patient with advanced liver metastases in which germ cell tumor-based chemotherapy achieved a pathological complete response and 2-year disease-free survival.

A rare case of bilateral massive hemothorax from spontaneous rupture of a primary mediastinal mixed germ cell tumor.

Spontaneous rupture of a mediastinal germ cell tumor, while rare, is always accompanied by bleeding. In this report, we describe a case of a primary mediastinal mixed germ cell tumor that presented with bilateral massive hemothorax and hemorrhagic shock. An urgent thoracotomy, which was performed to control bleeding, confirmed bilateral hemothorax secondary to a ruptured mediastinal tumor. Pathologic diagnosis revealed the mediastinal tumor to be mixed choriocarcinoma and immature teratoma, with lung metastatic choriocarcinoma. The patient recovered well from the operation and received salvage chemotherapy. Two years after diagnosis, the patient remains in remission with no evidence of disease.

Developing retroperitoneal anaplastic carcinoma with choriocarcinoma focus after ovarian non-gestastional choriocarcinoma: a case report.

INTRODUCTION: Choriocarcinoma is a malignant form of gestational trophoblastic neoplasm (GTN). It is a rare event but also a curable malignancy. In the majority of instancies it developes after any gestational event. In some cases it developes as non-gestational extrauterine malignancy. Prognosis of choriocarcinoma is poor when invasion and metastases appear early and spread fast. This form of choriocarcinoma can lead to incurable and letal outcome. CASE REPORT: We presented a 20-year-old patient with abdominal and retroperitoneal malignancy--anaplastic carcinoma combined with choriocarcinoma metastases in. Tumor developed three months after left adnexectomy which had been done because of adnexal tumor. Choriocarcinoma was immunohistochemicaly confirmed in adnexal masses. Two courses of chemotherapy, metotrexate + folic acid (MTX+FA) regimen, were administrated. The initial serum beta human chorionic gonadotropin level stayed unknown as well as the last one after the treatment. The patient came from the other country and was hospitalized because of pelvic and abdominal pain and palpable abdominal masses in hypogastrium with progressive anemia. The human chorionic gonadotropin level was 38 mIU/L. Tumor biopsy was done and choriocarcinoma metastases were immunohistochemicaly confirmed with predominant anaplastic carcinoma. Five day course of MTX + cyclophosphamide regimen was administrated and the patient was prepared for operative treatment. Relaparotomy was perforemed and tumor completely exceeded. Tumor mass mostly developed retroperitonely and partialy in abdominal cavity infiltrating intestinal wall with rupture of sigmoid colon. Anaplastic carcinoma, with large fields of necrosis and bleeding, was confirmed after histological examination. Immunohistochemical examination excluded choriocarcinoma in tumor mass. After 20 blood units transfusion, one course of chemotherapy and tumor excision, the patient left hospital on the 9th postoperative day. The patient rejected chemotherapy which was recommended according to the protocol and died one month after the operation. CONCLUSION: Non-gestational metastatic choriocarcinoma complicated with another type of malignancy with early spread of the disease and low responsiriness to chemotherapy has poor prognosis and leads to lethal outcome.

Unusual presentation of primary gastric choriocarcinoma in a 24-year-old female patient.

We report a case of a young female patient presenting with a high serum beta-HCG levels, amenorrhea, nausea and anemia which mimicked pregnancy followed by upper gastrointestinal bleeding. A gastric tumor was shown on endoscopy. Histopathologic evaluation revealed Primary Gastric Choriocarcinoma (PGC). The patient was treated with three cycles of standard nongestational choriocarcinoma chemotherapy. Tumor persistence was evidenced by CT Scans and high serum beta-HCG levels. The patient died approximately six months after diagnosis. Our case report suggest that PGC is a highly aggressive tumor that is often associated with liver and lungs metastasis without evidence of pelvic organ abnormality and is associated with some hormonal effects, such as amenorrhea, anemia, nausea and vomiting mimicking pregnancy in young adult female