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.