Choriocarcinoma syndrome of primary pulmonary choriocarcinoma after lung lobe resection: A case report and review of the literature

Abstract

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 that was complicated by choriocarcinoma syndrome (CS) and present a review of the literature.

Case presentation:

A 59-year-old man with a 30-pack-year smoking history was referred to our hospital because of haemoptysis 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 verified the diagnosis of choriocarcinoma. Three days after the operation, the patient developed massive haemoptysis. 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

For advanced choriocarcinoma cases, minimally invasive or even non-invasive procedures are more suitable to avoid inducing CS. When patients with a high tumour mass and elevated tumour markers, we need to be alert to the occurrence of CS. Surgery and modified chemotherapy, based on the physical condition of the patient, may currently be the best therapy for PPC.

Case Presentation

A 59-year-old man complaining of haemoptysis 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, although no treatment was performed. The patient had haemoptysis 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 had a smoking history for 30 years of one pack per day and a drinking history for 40 years of 200 g per day.

There were no abnormalities on physical examination, including genital examination. Tumour markers showing abnormal increases were ferritin > 320.00 µg/L, lung tumour antigen (LTA) 136.20 ng/L and tissue polypeptide specific antigen (TPS) > 4500.00 U/L. To determine whether the tumour occurred primarily within the lung, systemic screening was performed by PET-CT. The results showed multiple highly metabolic nodules throughout the body (Fig. 1); multiple bilateral pulmonary nodules (Fig. 2), especially a 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). In order to clarify the pathological diagnosis of the lung mass, we introduced multiple techniques to obtain tissue pathological diagnosis, including thoracoscopic surgical biopsy and ultrasound guided puncture. The patient chooses thoracoscopic surgical biopsy and underwent single-port thoracoscopic wedge resection of the right lung upper lobe. Extensive metastases in the right lung were observed during the operation, with tumour diameters ranging from 2–6 cm. A histopathologic workup of the excised tumour showed a poorly differentiated carcinoma and haemorrhage, with the few viable islands demonstrating syncytiotrophoblastic and cytotrophoblast-like cells (Fig. 6). The immunohistochemical phenotype of the pathological sections was CK7(+), TTF-1(-), CK(+), CD34(-), CD117(-), OCT3/4(-), SALL4(+), HCGα(+), Ki67(+ 90%), and vimentin(-). Thus, we measured serum β-HCG levels, and the result was > 10000.00 mlU/ml. The measured concentrations of the sex hormones were testosterone 0.83 ng/mL, oestradiol 716.10 pg/mL, and follicle-stimulating hormone (FSH) 0.26 mIU/mL. Doppler ultrasound of the testes and mammography of breasts were negative for malignancy. Combined with the patient's symptoms, imaging and pathological examinations, we finally determined the diagnosis of PPC in this patient.

Three days after the operation, the patient suddenly exhibited consciousness disorder, profuse sweating and pinpoint pupils. Subsequently, haemodynamic instability and acute respiratory failure manifested. The patient was admitted to the ICU with tracheal intubation for respiratory support. A large volume of bloody fluid was sucked out of the bilateral main bronchus using bronchoscopy. Laboratory data were significant for white blood cells 13.85 × 10⁹ cells/liter, which was prompted by the pneumonia. Subsequently, the patient developed cardiac dysfunction, manifested as increased myocardial markers. Cardiac colour Doppler ultrasound revealed that ventricular wall motion was not coordinated, left ventricular diastolic function decreased, and the ejection fraction was 60%. Simultaneously, the patient suffered acute renal failure, the endogenous creatinine clearance rate continued to decrease to a minimum of 10.01 (ml/min/1.73 m²), and serum urea and creatinine continued to rise. Despite supportive treatment, the patient’s condition continued to deteriorate. Due to multiple organ failure, the patient had no indications for chemotherapy and eventually died. Cause of death was diagnosed as 1. pulmonary choriocarcinoma with metastasis to the lung, brain, bone, pancreas, and lymph nodes, 2. severe pneumonia and respiratory failure, 3. acute renal failure and 4. acute coronary syndrome.

Discussion

As PPC is a rare disease, diagnosis before surgery is difficult [5]. The diagnostic criteria for PPC include a 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 pathological confirmation of the disease [6]. In our case, a genital exam and doppler ultrasound failed to find lesions in the reproductive system. The patient’s single parenchymal nodule rapidly progressed to multiple bilateral pulmonary nodules combined with multiple metastases throughout the body for three months. It was not until postoperative pathology and β-HCG examination that we finally established the diagnosis of PPC. Nevertheless, the primary tumour might also be in extrapulmonary organs, and the possibility of metastasis from occult lesions in other locations could not be entirely ruled out. The patient had a smoking history, which might be a risk factor for choriocarcinoma. It has been reported that formaldehyde and benzene, the main components of cigarette smoke, induce the growth and migration of human choriocarcinoma cells via regulation of the cell cycle and activation of oxidative stress[5]. However, research also showed that acrylonitrile, one of main components of cigarette smoke, has the potential to induce apoptosis of human choriocarcinoma cancer cells by activating ROS[6]. Due to the complex composition of cigarettes smoke, the effect of smoking on choriocarcinoma has not yet been determined. To our best knowledge, we could not find researches about the effect of alcoholism on choriocarcinoma.

CS is a rare and serious complication of advanced germ cell cancer, consists of hemorrhagic manifestations of metastases[7]. Our study includes a literature review of CS cases published from 2012 to 2021. These cases are included in Table 1[4, 7–26]. The patients with clinical data in the publications were aged from 8 to 64 years. The median age of patients was 29.5 years. The age of CS patients exhibited a high prevalence rate in the second and third decades of life. Diffuse alveolar hemorrhage is the most common manifestation as seen; however, literature describes bleeding at other metastatic sites including the liver, kidneys, bone, small intestines, and brain[4]. The symptom of CS in one patient was ARDS without obvious bleeding. The basic mechanism of CS is probably massive metastases, massive intra-alveolar tumour lysis, early necrosis of tumour cells, and consecutive superinfection, which can lead to acute respiratory failure (ARDS)[27]. The release of cytokines is probably due to the systemic inflammatory response to multiorgan failure[16]. Usually, metastasis haemorrhage appears within a few hours after the initiation of systemic chemotherapy [17, 28, 29], but there are also some cases that syndrome develops before treatment [25, 30]. In our case, the patient's CS developed only three days after surgery. There has also been a report of CS after surgery, but CS in that case occurred one and a half months after surgery[1]. According to national comprehensive cancer network (NCCN) non-small cell lung cancer clinical practice guidelines, for patients with suspected non-small cell lung cancer (NSCLC), routinely used diagnostic tools include: image-guided transthoracic core needle biopsy or video-assisted thoracoscopic surgery (VATS) and open surgical biopsy, et al. Since we did not confirm the diagnosis of choriocarcinoma preoperatively, performing thoracoscopic surgical biopsy was in line with the clinical practice guidelines. However, this case prompts us that when performing a surgical biopsy, the possibility of choriocarcinoma needs to be considered. For such advanced choriocarcinoma cases, minimally invasive or even non-invasive procedures are more suitable to avoid inducing CS. The symptoms of CS in this patient are characterized by bronchial aspirate as massive bloody fluid, but we did not perform a pathological examination of the bronchial aspirate due to the PPC diagnosis has been established. To the best of our knowledge, there is no report on the diagnosis of PPC or CS by bronchial aspirate. For patients with a high tumour mass, multiple metastases and elevated tumour markers, we need to be alert to the occurrence of CS and treat in a timely manner.

All cases show in table 1 have data about the treatment: 8 patients were treated with surgery and chemotherapy; 7 were treated with chemotherapy alone; 2 was treated with chemotherapy and radiotherapy; 1 were treated with chemotherapy and ECMO; and 3 patients did not receive treatment and died quickly. The longest follow-up period was 17 months. 52% (11/21) of patients survived treatment. Therefore, although CS is dangerous, it is not completely untreatable. The primary treatment of choice for advanced germ cell tumours consists of three or four cycles of bleomycin, etoposide, and cisplatin (BEP), depending on the risk classification[31]. While in patients with widespread lung metastases, high risk of development of haemorrhage, 2–3 days of full dose cisplatin and etoposide are suggested, with continuation of chemotherapy when the patient has recovered [32] Unfortunately, we did not recognize the risk of CS in this case early, and the patient did not receive corresponding chemotherapy in a timely manner. Moreover, because the patient's syndrome progressed rapidly, the opportunity for chemotherapy was completely lost. The outcome of choriocarcinoma tumours relies on early recognition and chemotherapy. Afterwards, more reports of CS cases are warranted to establish optimal management.

Declarations

Ethics approval and consent to participate

All the investigation got the approval by Medical Institutional Ethics Review Board of West China Hospital of Sichuan University.

Consent for publication

Written informed consent was obtained from the participant and his family members before the study began. All authors have approved the manuscript.

Availability of data and materials

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Competing interests

The authors in this article declare that they have no competing interests.

Funding

This work was supported by Dr. Qian Zhao and Song Lu, members of West China Hospital of Sichuan University, who provided funding to conduct the analysis and prepare the manuscript.

Author Contribution

Conceptualization: Chen Chen

Investigation: Chen Chen, Yi Li

Project Administration: Zhenjun Liu

Resources: Juan Ji

Supervision: Pei Zhao

Acknowledgements

My sincere appreciation goes to the participants from West China Hospital of Sichuan University, who participated this study with great cooperation.

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