Choriocarcinoma Syndrome of Primary Pulmonary Choriocarcinoma after Lung Lobe Resection: A Case Report and Review of the Literature

Introduction: Primary pulmonary choriocarcinoma (PPC) is extremely rare, especially in males. It is characterized by a poor response to therapy and shortened survival times. Here, we report a PPC case which was complicated by choriocarcinoma syndrome (CS) and a review of the literature. Case presentation: A 59-year-old man with 30-pack-year smoking history was referred to our hospital because of hemoptysis and chest pain. Positron emission tomography-computed tomography (PET-CT) showed multiple bilateral pulmonary nodules and multiple metastases throughout the body. The patient underwent single-port thoracoscopic wedge resection of the right lung upper lobe. Histological examinations veried the diagnosis of choriocarcinoma. Three days after the operation, the patient developed massive hemoptysis. A bronchoscopic examination showed bleeding from the bilateral main bronchus. Despite management in the intensive care unit (ICU), the patient died two weeks after surgery. Conclusions: A rapid and correct diagnosis of PPC is necessary. When the patient has massive hemoptysis, we should be alert to the occurrence of CS. Surgery and modied chemotherapy, based on the physical condition of the patient, may currently be the best therapy for PPC.


Introduction
Choriocarcinoma is a highly malignant tumor which originates from anaplastic tropho-blastic tissue.
Most of the choriocarcinoma usually occur in the female reproductive tract after a gestational event [1] .
Extragonadal choriocarcinoma, which accounts for only 2-5% of all germ cell tumors [2] , generally occurs in the midline of the body, such as the retroperitoneum, mediastinum, pineal gland, and intracranially.
Primary pulmonary choriocarcinoma (PPC) in males is easy to misdiagnose or delay the diagnosis; therefore, a potentially curative chemotherapy or surgery may also be delayed [3] . Furthermore, choriocarcinoma syndrome (CS) is a lethal hemorrhagic comolication, containing high-volume choriocarcinomatous elements and markedly elevated β-HCG [1,4] . Herein, we reported a 59-year-old PPC case and described the clinicopathological features, treatment, and prognosis of PPC and CS with a short review of the literature.

Case Presentation
A 59 years old man complaining of hemoptysis and chest pain presented to our hospital. Four months prior to admission, Chest computed tomography (CT) revealed a 43×26 mm parenchymal nodule in the posterior right upper lung lobe accompanied by emphysema, while no treatment was performed. The patient had hemoptysis without obvious inducement, accompanied by progressive shortness of breath, chest pain, intermittent fever, drenching night sweats, diminished appetite and a 5-kg weight loss over 3 months. The patient a smoking history for 30 years with one pack per day and a drinking history for 40 years with 200g per day.
There were no abnormalities on physical examination, including genital examination. Chest x-ray was signi cant for bilateral pulmonary nodules. Doppler ultrasound of the testes and mammography of breasts were negative for malignancy. To determine whether the tumor occurred primarily within the lung systemic screenings were performed by positron emission tomography-computed tomography (PET-CT).
The results showed that multiple high metabolic nodules throughout the body (Fig. 1), multiple bilateral pulmonary nodules (Fig. 2), especially large mass in the upper lobe of the right lung (Fig. 3), a 22 mm metastatic lesion in the pancreas (Fig. 4), and multiple bone metastases (Fig. 5). The patient underwent single-port thoracoscopic wedge resection of the right lung upper lobe. Extensive metastases in the right lung were observed during the operation, with tumor diameters ranging from 2-6 cm. Histopathologic workup of excised tumor showed poorly differentiated carcinoma and hemorrhage, with the few viable islands demonstrating syncytiotrophoblastic and cytotrophoblastic like cells (Fig. 6).
Immunohistochemical phenotype of pathological sections was that CK7(+), TTF-1 ( Three days after the operation, the patient suddenly appeared consciousness disorder, sweating profusely and pinpoint pupils. Subsequently, hemodynamic instability and acute respiratory failure appeared. The patient was admitted to the ICU with tracheal intubation for respiratory support. A large amount of bloody uid was sucked out of the bilateral main bronchus using bronchoscopy. The chest radiograph showed that multiple cluster and nodular shadows scattered in both lungs. Laboratory data was signi cant for white blood cell 13.85 900/mm which prompt the pneumonia. Subsequently, the patient developed cardiac dysfunction, manifested by increased myocardial markers. Cardiac color doppler ultrasound revealed that ventricular wall motion is not coordinated; left ventricular diastolic function decreased; ejection fraction was 60%. Therefore, the patient was treated with anti-infection and myocardial nutrition. Simultaneously, the patient suffered acute renal failure, the endogenous creatinine clearance rate continued to decrease, to a minimum of 10.01 (ml/min/1.73m 2 ), and urea and creatinine continued to rise. Despite renal supportive treatment, the patient's condition continued to deteriorate. Due to multiple organ failure, the patient has no indications for chemotherapy and eventually died. Diagnosis of death: 1. Pulmonary choriocarcinoma with metastasis to the lung, brain, bone, pancreas, and lymph nodes 2.

Discussion
Due to infrequency of PPC, diagnosis before surgery is di cult [5] . In our case, the patient's single parenchymal nodule rapidly progresses to multiple bilateral pulmonary nodules combined with multiple metastases throughout the body during three months. It was not until postoperative pathology and β-HCG examination that we nally established the diagnosis of PPC. Therefore, a rapid and correct diagnosis of choriocarcinoma is necessary. The diagnostic criteria for PPC includes the lack of a previous urological malignancy, solitary or predominant lung lesion without a primary gonadal site, elevated serum β-HCG levels that normalize following surgery or chemotherapy, and pathologic con rmation of the disease [6] . In our case, genital exam and doppler ultrasound failed to nd the lesions of the reproductive system. Nevertheless, PET-CT showed multiple bilateral pulmonary nodules and multiple metastases throughout the body, so the primary tumor is not de nitely at lungs, the possibility of a metastasis from occult lesions in other locations could not be ruled out entirely.
The choriocarcinoma syndrome (CS) is a rare and serious complication of the choriocarcinoma tumor. CS occurs shortly after the administration of chemotherapy and is connected with a high risk of fatal bleeding from metastatic lesions and frequently with acute respiratory failure with a high mortality rate at an early phase of the treatment induction [7] . Mostly, the hemorrhage appears shortly after the introduction of the chemotherapy, but there are also cases with pretreatment onsets reported in literature [8] . The basic mechanism of choriocarcinoma syndrome is probably massive lung metastases, massive intra-alveolar tumor-lysis, early necrosis of tumor cells, and consecutive superinfection, which can lead to acute respiratory failure (ARDS) [9] . Releasing of the cytokines is probably raising to systemic in ammatory response directing to multiorgan failure [10] . However, the patient's CS was likely resulted by the surgical procedure. There also have been report of CS after surgery, but the CS in that case occurred one and a half months after surgery [1] , while the CS in our case developed only three days after surgery. This prompts us, for such advanced case, minimally invasive or even non-invasive procedure such as aspiration biopsy is more suitable to avoid inducing CS. Especially when we found that the patient has massive hemoptysis, we should be alert to the occurrence of CS. The outcome of choriocarcinoma tumor relies on its early recognition and chemotherapy. Chemotherapy should be started as soon as the results of the pathological evaluation and biological markers were known. We can use chemotherapy including bleomycin, etoposide, cisplatin, surgery and postoperative radiotherapy, and the prognosis will be improved [11] .

Conclusion
In conclusion, PCC is highly malignant, progresses rapidly, and often has blood metastases at the time of diagnosis, and the prognosis is poor. The comprehensive treatment method of surgery combined with chemotherapy is advocated, but the effect is not satisfactory. Through clinical combined imaging and pathological examination, early detection, early diagnosis and early treatment are the keys to improving the prognosis of this disease.

Declarations
Ethics approval and consent to participate PET-CT revealed that multiple high metabolic nodules throughout the body. PET-CT revealed that multiple bilateral pulmonary nodules.    Histologic ndings showing that the tumor was consisted of the poorly diffenrentiated adenocarcinoma, hemorrhage and islands demonstrating syncytiotrophoblastic and cytotrophoblastic like cells (hematoxylin and eosin stain; original magni cation, ×200 and ×400).

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download.