Chemotherapy combined with tislelizumab for a male patient with primary pulmonary choriocarcinoma: a case report and literature review

Abstract

Primary pulmonary choriocarcinoma (PPC) in males is an extremely rare extragonadal malignant trophoblastic tumor with an unclear pathogenesis. Its clinical manifestations are heterogeneous and often mimic more common conditions, leading to frequent misdiagnosis. Moreover, PPC is characterized by early metastatic potential, and currently, no standardized treatment guidelines exist. Here, we report the case of a male patient with PPC who was treated with a combination of chemotherapy and immunotherapy. We also provide a comprehensive review of the literature to enhance understanding of this rare entity, improve early diagnostic accuracy, and explore potential therapeutic strategies.

Introduction

Choriocarcinoma is a highly malignant tumor originating from trophoblastic cells and characterized by the secretion of human chorionic gonadotropin. It typically occurs secondary to normal or abnormal gestation and is most commonly seen in women of reproductive age. Nongestational extragonadal choriocarcinoma is rare and usually arises in midline structures such as the retroperitoneum and mediastinum, with the testis being the most frequent site in males. Primary pulmonary choriocarcinoma (PPC) is extremely rare, exhibits poor responsiveness to treatment, and is associated with a shortened survival time. In this report, we describe a case of PPC in a male patient. The diagnosis was established based on morphological features, serum β-HCG levels, and immunohistochemical findings. The patient responded well to a modified therapeutic regimen and remains in good clinical condition. In addition, we provide a brief literature review to enhance understanding of this rare disease, improve early diagnostic accuracy, and offer insights into potential treatment strategies.

Case presentation

The patient was a 60-year-old retired male worker who was admitted to our hospital on January 20, 2025, due to a one-month history of cough with sputum production and chest/back pain, as well as exertional chest tightness for one week. One month prior to admission, he developed intermittent coughing with frothy sputum, accompanied by dorsal pain. One week before admission, he began experiencing chest tightness and shortness of breath after exertion, which improved with rest. He subsequently presented to our hospital for evaluation. Chest computed tomography (CT) revealed a space-occupying lesion in the right upper lobe of the lung accompanied by multiple solid nodules within the lung parenchyma, suggestive of primary lung cancer with multiple intrapulmonary metastases. Additionally, multiple enlarged lymph nodes were observed in the right hilar and mediastinal regions, and a mass lesion was noted in the left adrenal gland, all of which were considered likely metastatic.

Upon admission, the patient underwent a series of examinations. Tumor marker evaluation showed CEA at 1.75 ng/mL (reference range: 0-5ng/mL), CYFRA21-1 at 31.6ng/mL (0-3.3 ng/mL), NSE at 12.5ng/mL(0-17ng/mL), and CA125 at 21.8U/mL (0-35U/mL). However, inflammatory markers were elevated, with C-reactive protein reaching 53.5 mg/L (0–10 mg/L) and D-dimer at 2.4 µg/mL (0–0.5 µg/mL). Additionally, serum sodium was decreased to 131.5mmol/L (137-145mmol/L).Contrast-enhanced chest CT revealed a large space-occupying lesion in the right upper lobe, with a maximum cross-sectional area measuring approximately 100 mm × 80 mm × 81 mm. The lesion was suspected to be malignant and was found to invade the adjacent pulmonary artery, right subclavian artery, superior vena cava, and pleura. Multiple metastatic lesions were also observed in both lungs and the left adrenal gland, along with lymph node metastases in the right supraclavicular region, right hilar area, and mediastinum (Fig. 1). To further confirm the diagnosis, the patient underwent endobronchial ultrasound and two CT-guided percutaneous lung biopsies. Histopathological analysis of the lung tissue revealed nests of atypical proliferating cells within extensive areas of necrosis. Combined with immunohistochemistry and laboratory findings, the features were consistent with choriocarcinoma. Immunohistochemical staining results were as follows: CK7 (+), TTF1(-),NapsinA(-),CK5/6(-),P40(-),Syn(-),SMARCA4(-),INI1(+),Ki-67(+ 90%),AE1/AE3(+),HCG(+),INSM1(-)(Fig. 2). Next-generation sequencing identified a TP53 missense mutation (specific mutation: 24.7%), a tumor mutational burden of 22.06muts/Mb, and PD-L1 assessed using the CST E1L3N antibody showed a TPS of 50% and CPS of 55. On January 27, 2025, serum β-HCG was measured and found to be 19857.5mIU/ml(normal < 5mIU/mL). Whole-body bone scintigraphy conducted on January 22, 2025, showed no significant abnormalities. Cranial MRI performed on January 24, 2025, revealed no clear intracranial lesions, but mild white matter hyperintensities (Fazekas grade 1) were noted, suggestive of ischemic changes. Bilateral breast ultrasonography (January 28, 2025) revealed no abnormalities beneath the areolae on either side, and no significantly enlarged lymph nodes were observed in either axilla. Abdominal and pelvic CT scan (performed on January 31, 2025) showed the following: A space-occupying lesion in the left adrenal gland and a nodule in the lower lobe of the left lung, suggestive of metastasis; multiple tiny pulmonary nodules were also seen, and follow-up is recommended with correlation to clinical findings and chest CT. Scrotal MRI with and without contrast (February 13, 2025) showed the following: (1) A small cyst in the right epididymis. (2) Minimal hydrocele within the tunica vaginalis on both sides. (3) A small lesion with abnormal signal in the right femoral neck, likely benign. (4) A subcutaneous calcified lesion in the left inguinal region. Based on a comprehensive multimodal evaluation—including cross-sectional imaging of the abdomen, pelvis, and scrotum; targeted breast imaging; confirmatory lung biopsy with supporting immunohistochemistry; and correlative serum β-HCG dynamics—we systematically ruled out other primary sites and firmly established the diagnosis of primary pulmonary choriocarcinoma.

Fig. 1.

Radiological findings. A, B, C Contrast-enhanced chest CT showing a mass in the right upper lung lobe with multiple solid pulmonary nodules

Fig. 2.

Histological findings. A, B Primary lesion from CT-guided percutaneous transthoracic lung biopsy demonstrating a malignant tumor composed of large cells with enlarged hyperchromatic nuclei (hematoxylin and eosin staining; ×200, ×400). C PD-L1 immunohistochemical staining showing 50% positivity. D AE1/AE3 immunohistochemical staining with strong positivity. E CK-7 immunohistochemical staining exhibiting strong positivity. F HCG immunohistochemical staining of the primary lesion revealing strong positivity. G Ki-67 immunohistochemical staining displaying strong positivity

On February 13, 2025, the patient began the first cycle of BEP combined with anti-PD-1 antibody therapy, consisting of: bleomycin 30 mg on days 1, 8, and 15; etoposide 150 mg on days 1 to 5; cisplatin 30 mg on days 1 to 5; and tislelizumab 200 mg on day 1. On February 24, 2025, routine blood tests showed: white blood cell count 1.2 × 10⁹/L, red blood cell count 3.09 × 10¹²/L, hemoglobin 84 g/L, absolute neutrophil count 0.3 × 10⁹/L, and high-sensitivity C-reactive protein 83.0 mg/L. Grade IV myelosuppression was considered; therefore, the bleomycin scheduled for day 15 was withheld. Tumor response was assessed through a multimodal framework, including radiological evaluation with serial chest CT scans interpreted using RECIST 1.1 criteria, serial monitoring of serum biomarker trends (β-HCG and CYFRA 21-1), and regular clinical evaluation of symptoms, physical signs, and performance status. On March 8, 2025, the patient was re-admitted. Follow-up blood β-HCG had decreased to 114.38 IU/L. Tumor marker re-evaluation showed a marked decrease in CYFRA21-1 to 5.62ng/mL. Chest CT revealed that, compared with the scan on January 21, 2025, the primary pulmonary lesion had significantly enlarged (maximum cross-sectional dimensions approximately 102 mm × 76 mm × 97 mm), with a notable increase in both the number and size of pulmonary nodules. According to RECIST 1.1 criteria, the increase in the longest diameter of the primary lesion did not meet the threshold for progressive disease (≥ 20% increase). Given the concurrent dramatic decline in serum tumor markers and the patient’s stable clinical condition, these imaging changes were considered suspicious for pseudoprogression related to immunotherapy. On March 10, the second cycle of BEP combined with anti-PD-1 antibody therapy was administered: bleomycin 30 mg on days 1 and 8; etoposide 100 mg on days 1 to 5; cisplatin 30 mg on days 1 to 5; and tislelizumab 200 mg on day 1.

On March 31, 2025, the patient was hospitalized again for evaluation and treatment. Chest CT revealed no significant changes in the pulmonary lesions compared with the scan from March 8, 2025. Tumor marker assessment showed that both serum CYFRA21-1 and β-HCG had returned to normal ranges. On April 2, the third cycle of BEP combined with anti-PD-1 antibody therapy was administered, consisting of: bleomycin 30 mg on days 1 and 8; etoposide 100 mg on days 1 to 5; cisplatin 30 mg on days 1 to 4; and tislelizumab 200 mg on day 1. On April 26, the fourth cycle of treatment was given, including: etoposide 100 mg on days 1 to 5; cisplatin 30 mg on days 1 to 4; and tislelizumab 200 mg on day 1.

On May 15, 2025, the patient was readmitted for evaluation and treatment. Chest CT showed that the pulmonary lesions, with a maximum cross-sectional area of approximately 82 mm × 64 mm × 80 mm, had decreased in size compared with the scan on March 8, 2025, including both the primary lesion and pulmonary nodules. Tumor markers revealed that serum CYFRA21-1 and β-HCG had returned to normal levels. The fifth and sixth cycles of antitumor therapy were administered on May 17 and June 9, respectively, consisting of etoposide 100 mg on days 1 to 5, cisplatin 30 mg on days 1 to 4, and tislelizumab 200 mg on day 1.

On July 1, 2025, the patient was again hospitalized. Chest CT demonstrated that the primary lesion and pulmonary nodules remained stable compared with the scan on May 15, 2025. Tumor marker tests again showed that serum CYFRA21-1 and β-HCG levels were within normal range. The seventh and eighth cycles of antitumor therapy were given on July 2 and July 23, respectively, consisting of etoposide 100 mg on days 1 to 5 and tislelizumab 200 mg on day 1. The patient returned for a follow-up visit on August 8th. A repeat chest CT scan showed continued reduction in lesions (including some pulmonary nodules) compared to the July 1st scan. Serum tumor markers CYFRA21-1 and β-HCG levels remained within normal limits.The overall treatment process and changes in chest CT imaging and serum markers CYFRA21-1 and β-HCG levels are shown in Fig. 3.

Fig. 3.

Serial chest CT findings and serum CYFRA 21-1 and β-HCG levels. A Longitudinal changes in the lung mass and nodules from February 13, 2025 (initiation of therapy). B, C Longitudinal changes in serum CYFRA 21-1 and β-HCG levels from February 13, 2025 (initiation of therapy)

The patient’s general condition is currently good. He has no fever, mild cough and sputum production, no chest tightness or shortness of breath, no hemoptysis, and no chest or back pain. His PS score is 1. He is currently undergoing regular systemic antitumor therapy as planned.

Methods

We conducted a systematic search of the PubMed database using the keywords “primary pulmonary choriocarcinoma” and “male” to identify all reported and pathologically confirmed cases of primary pulmonary choriocarcinoma (PPC) in male patients up to July 17, 2025. The earliest reported case can be traced back to 1953 [1], and the most recent publication was in 2025 [2]. Inclusion Criteria: All case reports or series in PubMed database describing pathologically confirmed primary pulmonary choriocarcinoma in male patients were screened. Exclusion Criteria: Articles were excluded if the tumor was confirmed to be metastatic from an extrapulmonary primary site (e.g., testicular) or if essential clinical data (age, diagnostic method, treatment, or survival outcome) were not reported.

The initial search yielded 25 articles. After applying the exclusion criteria (6 cases were excluded due to insufficient data), 19 cases were included in the final qualitative synthesis.

Data extracted included: age, underlying comorbidities, initial symptoms, smoking history, tumor location, maximum tumor diameter, metastatic status, PD-L1 expression, serum β-HCG level, serum CYFRA21-1 level, diagnostic method, treatment regimen, and overall survival. Overall survival (OS) was defined as the time from diagnosis to death from any cause or last follow-up and was considered the primary outcome measure. Statistical analysis was performed using GraphPad Prism version 9.0. A two-sided P value of ≤ 0.05 was considered statistically significant.

Literature review and discussion

Choriocarcinoma is a highly vascularized and aggressive malignant tumor that typically originates in the gonads, including the ovaries and testes [3]. Its pathological hallmark is biphasic proliferation of cytotrophoblasts and syncytiotrophoblasts, along with secretion of β-HCG. While pulmonary metastasis of choriocarcinoma is common, PPC is extremely rare, and no standardized clinical treatment guidelines are currently available.

In this study, a total of 19 male cases were included in the final analysis, with detailed clinical characteristics summarized in Table 1. The youngest patient was 4 months old [4], and the oldest was 72 years old [5], with a median age of 65 years. Underlying comorbidities were reported in 7 patients, including pulmonary tuberculosis [6], gastric ulcer [6], diabetes mellitus [7], bronchial asthma [8], bronchiectasis [9], hypertension [9], hyperlipidemia [9], and history of coronary artery bypass grafting [10]. The most commonly reported symptoms included hemoptysis, cough, dyspnea, breast swelling, and chest pain. 5 patients were asymptomatic at presentation. A history of long-term smoking was noted in 11 cases. The tumor was located in the left lung in 10 cases, in the right lung in 7 cases, and involved both lungs in 2 cases. Tumor maximum diameter was explicitly described in 16 cases, with a median size of 60 mm. Lymph node metastases were confirmed in 5 patients, and distant metastases were reported in 9 patients. PD-L1 testing of tumor tissue was performed in 3 cases. Serum β-HCG levels were assessed in 15 patients. Serum CYFRA21-1 levels were measured in 5 patients, with significant elevation observed in 3 of them. Surgical treatment was performed in 12 patients, chemotherapy in 11 patients, radiotherapy in 3 patients, and immunotherapy in 2 patients. The shortest reported OS was 8 days [11], and the longest exceeded 3 years [12]. Liang X et al. [2] reported a case of a 67-year-old male with PPC who presented with significantly elevated serum HCG levels and positive PD-L1 expression in tumor tissue (70%, 22C3 antibody). He received a combination treatment regimen consisting of cisplatin, etoposide, paclitaxel, and sintilimab. Four months after initiating treatment, chest CT revealed marked tumor shrinkage. This study suggested that immune checkpoint inhibitors (ICIs) combined with chemotherapy may prolong OS in patients with PPC and that ICIs could be a promising therapeutic option for such patients. Iso H et al. [5] reported a case of a 72-year-old male with recurrent PPC after surgery, presenting with multiple pulmonary nodules and an intracardiac mass. PD-L1 expression in tumor tissue was negative. The patient was treated with a combination of carboplatin, paclitaxel, nivolumab, and ipilimumab. Two months after treatment, chest CT showed a reduction in the size of pulmonary nodules and the intracardiac mass. Zhang X et al. [13] described a 65-year-old male patient who underwent preoperative PET/CT evaluation, which revealed no obvious metastasis, followed by surgical resection. The study emphasized that patients who received active treatment had longer survival times than those who did not, and that patients who underwent surgery had better survival outcomes compared to those who did not. The authors concluded that a comprehensive treatment approach involving surgical resection, chemotherapy, and radiotherapy plays an important role in improving patient prognosis.

Table 1.

Clinical characteristics of 19 male cases

The clinical characteristics of PPC are highly variable. Patients commonly present with symptoms such as dyspnea, cough, chest pain, and hemoptysis, and some may develop pleural effusion. In male patients, signs of feminization, such as gynecomastia, loss of libido, and testicular atrophy, can be observed, which are associated with elevated levels of β-HCG. However, in the present case and those reviewed, no signs of feminization were noted, as confirmed by breast ultrasonography and testicular MRI. Although progressively rising β-HCG levels are generally useful for detecting choriocarcinomatous lesions, this biomarker is often overlooked in clinical practice, particularly in male patients. As a result, ectopic or primary choriocarcinomas are frequently misdiagnosed or missed altogether, making early diagnosis of PPC challenging. It is also noteworthy that elevated β-HCG levels may occur in other malignancies, such as lung cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and cholangiocarcinoma [14, 15], thus requiring histopathological confirmation to achieve a definitive diagnosis. Yamamoto S et al. [16] reported an extremely rare autopsy case of PPC with coexisting adenocarcinoma components. Autopsy findings revealed extensive necrosis and hemorrhage within the primary pulmonary lesion, displaying the characteristic biphasic structure of choriocarcinoma. Morphological analysis showed that moderately to poorly differentiated adenocarcinoma tissue partially surrounded the choriocarcinoma component. This suggests that the development of PPC may be closely associated with conventional pulmonary adenocarcinoma, a hypothesis that warrants further investigation. Similarly, Chen F et al. [17] reported a case of a 61-year-old male diagnosed with pulmonary adenocarcinoma coexisting with focal areas of choriocarcinoma, initially presenting with hemoptysis. Although the exact pathogenesis of the two coexisting carcinoma types remains unclear, the clinical course of the disease could still be followed and pathologically confirmed in this case.

The decision to employ a combination of BEP chemotherapy and the anti-PD-1 agent tislelizumab as first-line treatment was based on both the patient’s specific tumor biology and emerging evidence from the literature. In our case, the tumor exhibited a high PD-L1 expression (TPS 50%), an elevated tumor mutational burden (22.06 muts/Mb), and a TP53 mutation, collectively suggesting potential susceptibility to immune checkpoint inhibition. This rationale is supported by the 19 male PPC cases, where patients with similar biomarker profiles (e.g., high PD-L1) demonstrated promising responses to PD-1/PD-L1 inhibitors combined with chemotherapy.

The assessment of treatment response in patients receiving immunotherapy can be complicated by atypical patterns such as pseudoprogression. In the present case, the first follow-up CT scan showed an increase in the size of the primary pulmonary lesion and in the number of intrapulmonary nodules, which initially raised concern for radiographic progression. However, this was accompanied by a dramatic concurrent decline in serum β-HCG and CYFRA21-1 levels and a stable clinical status. Although the increase in the longest diameter of the primary lesion did not meet the conventional RECIST 1.1 threshold for progression (≥ 20%), the overall imaging changes warranted caution. Guided by the iRECIST principle of “unconfirmed progression,” which emphasizes continued clinical and radiologic evaluation in the setting of discordant biomarker and symptomatic findings, the original chemoimmunotherapy regimen was maintained. Subsequent imaging confirmed a reduction in tumor burden, validating the initial suspicion of pseudoprogression. This experience underscores the importance of integrating serum biomarkers, clinical evaluation, and immune-specific response criteria (iRECIST) when interpreting early imaging changes during immunotherapy for rare tumors like PPC, in order to avoid premature discontinuation of potentially effective treatment.

Limitations of this single-case report include the inability to definitively attribute the clinical response specifically to chemotherapy, immunotherapy or their synergy. Given the extreme rarity of PPC, these findings cannot be generalized and require validation in future multicenter studies or disease registries.

Conclusion

Our literature review indicates that PPC in males is extremely rare and generally associated with a poor prognosis. Chest CT findings may present as either nodular or mass-like lesions. There are currently no standardized treatment guidelines, and therapeutic approaches have primarily included surgery, chemotherapy, radiotherapy, and immunotherapy. This was the first reported case in which BEP chemotherapy combined with an ICI was administered to a male patient with primary pulmonary choriocarcinoma. Based on the observed therapeutic efficacy, we adopted the same BEP plus ICI regimen for our patient. The use of combined chemotherapy and immunotherapy may offer a potential survival benefit for male patients with primary pulmonary choriocarcinoma.

Author contributions

Xue Pan and Yongjian Pei are the co-first authors, and Yuehua Xu and Minhua Shi are the co-corresponding authors. Xue Pan and Yongjian Pei drafted the main text of the manuscript, Xue Pan and Ting Chen prepared Figs. 1, 2 and 3; Table 1.

Funding

This work was supported by the Suzhou Science and Technology Innovation Project for Applied Basic Research (grant no. SYWD2024113) and the Suzhou Science and Education Strengthening HealthProject (grant no. QNXM2024019).

Data availability

All data generated or analyzed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

The studies involving humans were approved by Clinical Research Ethics Committee of Second Affiliated Hospital of Soochow University (approval no.JD-LK2024035-IRO1; Suzhou, China).The studies were conducted in accordance with the local legislation and institutional requirements. For this case report, written informed consent for participation in the study and for the publication of any potentially identifiable images or data included in this article was obtained from the patient’s family members. Written informed consent for participation in the study was obtained from family members of the patient.

Consent for publication

Written informed consent was obtained from family members of the patient for the publication of this case report.

Competing interests

The authors declare no competing interests.