Primary Anterior Medistinal Choriocarcinoma in Male with Lung Metastasis and Pituitary Microadenoma: A Case Report Open Access

Choriocarcinoma is an aggressive tumor, which is usually gestation-associated and occurs in female population, sometimes occurs in the testicles of males. Extragonadal choriocarcinoma in male is extremely rare and it is characterized by easily being misdiagnosed, early hematogenous spreading, poor response to therapy, and short survival time. The current study presents a case of primary choriocarcinoma of anterior mediastinum metastasis to bilateral lung accompanied with pituitary microadenoma in a 29-year-old male. The aim of this report was to explore the accurate diagnosis and optimal treatment of primary choriocarcinoma of anterior mediastinum.

A 29-year-old male with no significant past medical history presented gradually bilateral breast enlargement for last 2 months accompanied with pain exacerbated when touched, with no galactorrhea, redness, or swelling. He denied history of exposure to systemic or topical exogenous estrogenic compounds. His weight was 65 kg, height was 171 cm, and body mass index was 22 kg/m². On examination, patient had Tanner II breast development on both sides. Testicles were equal in size and pubic hair development was Tanner V and the penis was 8 cm when flaccid.

Patient was afebrile with a heart rate of 82 bpm (beats per minute), respiratory rate of 16/min, and blood pressure of 102/70 mm Hg. The cardiac and abdominal examinations were unremarkable. Pectoral auscultation and percussion were normal. Pathological reflex was negative. His medical and family history was not significant. The results of GnRH stimulation test were as follows: luteinizing hormone 0.15 - 0.15 - 0.22 - 0.26 - 0.25 - 0.57 mIU/mL, follicle-stimulating hormone <0.050<0.050<0.050<0.050–0.06 mIU/mL, testosterone 29.85-27.84-30.95-32.86-31.73-29.0 ng/mL, estradiol 2 (E2) 530-525-522-541-516-539 pg/mL. Serum β-human chorionic gonadotropin (HCG) was 14,306.60 mIU. Breast ultrasound showed hyper echo under mammilla, which was considered as breast development. The results of routine laboratory examinations were all normal. Positron emission tomography-computed tomography revealed solid-appearing mass on the right side of anterior superior mediastinum, extending to pleura and pericardium, whose metabolic activity was classified as malignant (Fig. 1). There were also extensive and multiple bilateral pulmonary nodules with metabolically active, which are deemed as lung metastases. Magnetic resonance imaging of pituitary gland demonstrated pituitary microadenoma. Patient underwent resection and biopsy of right middle lung nodules under thoracoscopy under general anesthesia. The microscopic pathological examination showed that the center of the neoplasm was composed of necrotic and hemorrhagic areas. Cells surrounded were arranged in nests flake, cellular atypia, abundant cytoplasm, nuclear vacuoles, visible nucleoli, and nuclear fission (Fig. 2). Immunohistochemical staining results were as follows: CK(+), PLAP(−), AFP(−), HCG(+), CD30(−), Oct3/4(−), CK7(+), TTF-1(−), CD117(−), Ki 67(80+), CK5/6(−), EMA(partial+), inhibin(partial+), indicating choriocarcinoma. Based on the above findings, a diagnosis of primary anterior mediastinal choriocarcinoma metastasis to bilateral lung accompanied with pituitary microadenoma was confirmed (Table 1).

The patient received four cycles of T-BEP [1, 2] scheme consisting of Taxol (300 mg/m², intravenous [IV] drip d1), cisplatin (30 mg/m², IV drip d1-5), etoposide (170 mg/m², IV drip d1-5), bleomycin (30 mg/m², IV drip d2, 8, 15). Patient developed a fever after using bleomycin and the patient’s temperature dropped to normal after symptomatic treatment. After the first course of chemotherapy, patient developed IV grade myelosuppression, so we injected recombinant human granulocyte colony-stimulating factor (G-CSF) and the suppression was alleviated. The patient also received three times of lumbar puncture and intrathecal methotrexate 12 mg. Since the second course of chemotherapy, we did prophylactic recombinant human G-CSF injection and patient had not had any fever or myelosuppression. After the patient finished four cycles of T-BEP scheme, radiology examination revealed that solid-appearing mass on the right side of anterior superior mediastinum became smaller and metabolic activity decreased (Fig. 3). Some of the metastatic bilateral pulmonary nodules began to shrink, while others became larger and there were also new nodules appeared. The metabolic activities were mild to moderate. Serum β-HCG was 10.27 mIU. Because there were still residual cancer focus, we changed chemotherapy scheme to classic EMA/CO scheme, consisted of etoposide (170 mg/m², IV drip d1-2), methotrexate (170 mg/m², IV drip), actinomycinD (0.5 mg/m², IV drip d1-2), cytotoxin (1,000 mg/m², IV drip d8), and vincristine (1.7 mg/m², IV drip d8). Patient was in good condition during this course but Serum β-HCG did not decrease. So, after one cycle treatment, we changed the scheme to GOP scheme consisted of gemcitabine (1.3 mg/m², IV drip d1), Taxol (120 mg/m², IV drip d1), and oxaliplatin (220 mg/m², IV drip d1). Since immunohistochemical staining results showed PD-L1 was 80–90% positive, we added immunotherapy and changed the scheme to classic EMA/CO scheme, including opdivo (180 mg/m², IV drip d0), etoposide (170 mg/m², IV drip d1-2), methotrexate (170 mg/m², IV drip), actinomycinD (0.5 mg/m², IV drip d1-2), cytotoxin (1,000 mg/m², IV drip d8), and vincristine (1.7 mg/m², IV drip d8). Chemotherapy combined with immunotherapy continued until the patient died of complications (Table 1). Secondary anemia accompanied by granulocyte maturation disorder in patients during chemotherapy, so hematopoietic stem cell transplantation was recommended. However, when all the prerequisites for cell transplantation are ready, the patient experienced a sudden death (Fig. 4).

Choriocarcinoma is generally gestational related, which often occurs with spontaneous abortion, hydatidiform moles, ectopic pregnancy, or normal delivery. Based on the data, it affects 1–9.2 in 40,000 pregnancies and 1 in 40 hydatidiform moles. Nongestational choriocarcinoma is rare, and the incidence ratio of gestational choriocarcinoma to nongestational choriocarcinoma was 79:1. Nongestational choriocarcinoma can occur in both male and female and a ratio of male-to-female is 13:33 among patients according to the statistics by Jiang et al. [3, 4] In males, choriocarcinoma is generally considered a nonseminomatous germ cell tumor, which represents less than 5% of all germ cell tumors in males [5]. The median age of nongestational choriocarcinoma in male is 30 years old and the most common primary tutor location is mediastinum, followed by the retroperitoneum and the brain [6]. In some researches, it is said that primary tumor location is associated with ages, to be more precise, primary mediastinum choriocarcinoma presents more commonly in young patients while choriocarcinoma of parenchymal organs tends to affect older patients. There is also an interesting finding that extragonadal germ cell tumors occur more frequently in the Korean population than in western countries, so that genetic and dietary factors may possibly be explanations for the difference [7]. An investigation based on 97 patients with male choriocarcinoma revealed that the median overall survival time was 7.7 months and the 6-month mortality rate was 45.4% [8]. Some case reports also indicate that biochemical remission may not be associated with clinical remission in male mediastinal choriocarcinoma [9].

In this case, the patient was 29, at an age which choriocarcinoma is highly developed, and presented gynecomastia so that it was easy to consider about some diseases associated with increased estrogen or decreased androgen, such as choriocarcinoma, hyperthyroidism, liver disease, adrenal neoplasms, and ectopic production of β-HCG by lung, kidney, and liver cancer. Exposure to some drugs such as estrogen and anabolic steroids can also contribute to gynecomastia. As a consequence, serum β-HCG was examined and found abnormal increasing which was considered a predominant diagnosis of choriocarcinoma and meanwhile, testicles were examined, nothing abnormal found. Pathological and immunostaining results confirmed the diagnoses.

However, majority of extragonadal choriocarcinoma patients present no symptoms of fatigue, weight loss, and so on, which are not characteristic and often fail to notice. In some cases, patients present cough, dyspnea, and chest pain, owing to the hematogenous dissemination to lung. These symptoms are usually not distinct and may lead to misdiagnosis of lung cancer or other diseases. That’s the reason why a majority of patients’ prognosis with extragonadal choriocarcinoma appears to be poor.

There is no standard treatment for primary choriocarcinoma of anterior mediastinum now, and surgery, chemotherapy, and radiotherapy are traditional treatments. Different tumor locations tend to have different treatments, brain tumor patients are more prone to receive beam radiation, and mediastinum tumor patients are less likely to receive surgery. However, some study surprisingly finds that beam radiation or surgery could not prolong survival time [4]. Surgery is usually not the first-line treatment for mediastinum choriocarcinoma due to distant metastasis and surgical difficulties. But it has to be performed under emergent circumstances such as superior vein cava syndrome, dysphagia, hemothorax, and so on [10]. Chemotherapy is generally considered as the primary initial treatment [11], though sometimes it may not work well and there are no standard protocols. Numerous studies had tried various chemotherapy regimens, such as methotrexate/actinomycin/chlorambucil and 5-fluorouracil/leucovorin/oxaliplatin, but these were shown to be unsuccessful in this disease [12, 13].

According to the cases reported early, nongestational choriocarcinoma was more insensitive to chemotherapy, so we decided to use the first-line treatment: BEP, and added Taxol to enhance the treatment effect. Because of the side effect of myelosuppression, we prophylactically injected recombinant human G-CSF and also informed the patient and family members of possibility of infertility. The patient and family members refused to do sperm cryopreservation. In this case, patient received four cycles of T-BEP scheme at first, we could find that the level of β-HCG decreased sharply at first two cycles, but since the third cycle, the level of β-HCG did not change and remained above the normal which indicated chemotherapy resistance. CT demonstrated there was still cancer residual, so the scheme changed to EMA/CO for one cycle and β-HCG didn’t drop, then the scheme was changed to GOP scheme for one cycle and then changed back to EMA/CO again. The β-HCG was still above the normal, which indicated insensitive to chemotherapy. The patient was tested PD-L1 80–90% positive so that in the circumstance, we tried immunotherapy and opdivo was used. The patient has been treated for 6 months, although there is still cancer residual, he is in fine condition: his liver function and renal function were generally good despite a low level of globulin and increase of uric acid sometimes and blood routine were tested after every cycle. Despite adding immunotherapy, the results of treatment were still not good.

This case inspire us to think of the possibility of choriocarcinoma when a man presents gynecomastia or lung metastatic symptoms and, the treatment outcomes for choriocarcinoma in men are usually poor, introducing Opdivo to the classic chemotherapy regimen for choriocarcinoma might not improve final treatment outcomes. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000533476).

We thank Yuxin Wang, Peigen Chen, and Chenhao Fan for the help of collecting clinical data and patient’s follow-up.

Ethical approval is not required for this study in accordance with local guidelines. Written informed consent was obtained from the patient’s mother for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

Funding was not required; hence, funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Dong Liu and Yuebo Yang were responsible for the design of the study and interpretation of the data. Qingjian Ye and Minjuan Ye were responsible for the data acquisition, selection and analysis, and clinical interpretation of the data. Dong Liu involved in the drafting of the report. Yuebo Yang and Dong Liu have read, revised, and approved the final manuscript. All authors read and approved the final version of the manuscript.

All data generated or analyzed are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.