DOI: https://doi.org/10.21203/rs.3.rs-231642/v4
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: A rapid and correct diagnosis of PPC is necessary. When the patient has massive haemoptysis, we should 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.
Choriocarcinoma is a highly malignant tumour that originates from anaplastic trophoblastic tissue. Choriocarcinomas occur in the female reproductive tract after a gestational event[1]. Extragonadal choriocarcinoma, which accounts for only 2–5% of all germ cell tumours[2], generally occurs in the midline of the body, including the retroperitoneum, mediastinum, and pineal gland as well as intracranially. Primary pulmonary choriocarcinoma (PPC) in males is easily misdiagnosed or can have a delayed diagnosis; therefore, potentially curative chemotherapy or surgery may also be delayed[3]. Furthermore, choriocarcinoma syndrome (CS) is a lethal haemorrhagic complication characterized by high-volume choriocarcinomatous elements and markedly elevated β-HCG[1, 4]. Herein, we report a case of a 59-year-old PPC patient and describe the clinicopathological features, treatment, and prognosis of PPC and CS with a short review of the literature.
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. Chest X-ray was significant for bilateral pulmonary nodules. Doppler ultrasound of the testes and mammography of breasts were negative for malignancy. To determine whether the tumour occurred primarily within the lung, systemic screening was performed by positron emission tomography-computed tomography (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). 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 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. 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. 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. The pathological and hormone level evidence met the diagnostic criteria for PPC.
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. The chest radiograph showed multiple clusters and nodular shadows scattered in both lungs. 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.
As PPC is a rare disease, diagnosis before surgery is difficult[5]. In our case, 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. Therefore, a rapid and correct diagnosis of choriocarcinoma is necessary. 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. Nevertheless, PET-CT showed multiple bilateral pulmonary nodules and multiple metastases throughout the body, so the primary tumour was not definitively in the lungs, and the possibility of metastasis from occult lesions in other locations could not be entirely ruled out.
Choriocarcinoma syndrome (CS) is a rare and serious complication of choriocarcinoma tumours. CS occurs shortly after the administration of chemotherapy, is connected with a high risk of fatal bleeding from metastatic lesions, and is frequently accompanied by acute respiratory failure with a high mortality rate at an early phase of treatment induction[7]. Usually, haemorrhage appears shortly after the introduction of chemotherapy, but there are also cases with pre-treatment onset reported in the literature[8]. The basic mechanism of choriocarcinoma syndrome is probably massive lung metastases, massive intra-alveolar tumour lysis, early necrosis of tumour cells, and consecutive superinfection, which can lead to acute respiratory failure (ARDS)[9]. The release of cytokines is probably due to the systemic inflammatory response to multiorgan failure[10]. However, this patient's CS likely resulted from the surgical procedure. There has also been a report of CS after surgery, but CS in that case occurred one and a half months after surgery[1], while CS in our case developed only three days after surgery. This prompts us to find that for such advanced cases, minimally invasive or even non-invasive procedures, such as aspiration biopsy, are more suitable to avoid inducing CS. Furthermore, we should be alert to the occurrence of CS, especially when we found that the patient had massive haemoptysis. The outcome of choriocarcinoma tumours relies on early recognition and chemotherapy. Chemotherapy should be started as soon as the results of the pathological evaluation and biological markers are known. Chemotherapy, including bleomycin, etoposide, and cisplatin; surgery; and postoperative radiotherapy are all acceptable treatments that will improve the prognosis[11].
In conclusion, PCC is highly malignant, progresses rapidly, often exhibits blood metastases at the time of diagnosis, and has a poor prognosis. A 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.
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, Pei Zhao
Project Administration: Zhenjun Liu, Song Lu
Resources: Juan Ji, Xiuli Li
Supervision: Qian Zhao
Acknowledgements
My sincere appreciation goes to the participants from West China Hospital of Sichuan University, who participated this study with great cooperation.