Case report tracks aggressive pulmonary choriocarcinoma with brain metastases

A 41-year-old man with primary pulmonary choriocarcinoma and multiple brain metastases experienced rapid progression despite an intensive sequence of chemotherapy, radiotherapy, anti-angiogenic treatment and two immune checkpoint inhibitors. The case report also found that serial blood measurements of β-human chorionic gonadotropin closely tracked his tumor burden, while an exploratory review of previously published cases suggested an association between immune checkpoint inhibitor treatment and longer overall survival. Because the evidence consisted of one patient and a small, heterogeneous collection of case reports, the results remain hypothesis-generating rather than evidence of a proven treatment benefit.

Primary pulmonary choriocarcinoma is an exceptionally rare, non-gestational trophoblastic malignancy that occurs predominantly in the lung and is especially uncommon in men. The tumor is characterized by rapid growth, extensive hemorrhage and necrosis, early hematogenous spread and frequently poor response to chemotherapy. Its symptoms are nonspecific, commonly including cough, hemoptysis, chest pain and breathlessness, which can lead to an initial diagnosis of conventional lung cancer. There is currently no established standard treatment, and the optimal management and prognostic factors for the disease remain poorly characterized.

The patient in the case report had experienced intermittent cough for six months when he presented to Linyi Central Hospital in Shandong, China. Chest computed tomography showed a heterogeneous right upper-lobe mass measuring approximately 10.2 by 8.6 centimeters, together with multiple nodules in the opposite lung that were interpreted as intrapulmonary metastases. Brain magnetic resonance imaging demonstrated multiple lesions with surrounding edema, including a 3.6 by 3.3-centimeter mass in the right cerebellar hemisphere. Routine blood tests were otherwise largely unremarkable, but his serum β-HCG concentration exceeded 10,000 mIU/mL.

A CT-guided biopsy of the lung mass showed extensive hemorrhage and necrosis with a biphasic population of malignant cells: mononuclear cytotrophoblasts mixed with multinucleated syncytiotrophoblasts. The cells stained diffusely for β-HCG, cytokeratin 7, GATA3 and SALL4, while TTF-1, Napsin A, CK5/6 and Glypican-3 were negative. The Ki-67 labeling index was approximately 70%. Focal p40 positivity created a potential diagnostic trap because it could support a diagnosis of poorly differentiated squamous-cell carcinoma, but the combined morphology, immunophenotype and serum β-HCG findings favored pulmonary choriocarcinoma.

The investigators acknowledged an important limitation in establishing the tumor’s primary site. The large lung mass and absence of a palpable testicular abnormality supported a diagnosis of primary pulmonary choriocarcinoma, but scrotal ultrasonography and postmortem examination were not performed. An occult or regressed testicular primary therefore could not be completely excluded. Genomic profiling and testing for PD-L1 expression, tumor mutational burden and microsatellite instability were also unavailable because of financial constraints, leaving potential predictors of immune-checkpoint response unassessed. The investigators therefore described the diagnosis as the one most consistent with the available clinical and pathological evidence.

Treatment began with radiotherapy to the brain metastases on June 16, 2025, but it was stopped because of poor tolerance. The patient then received three cycles of EMA/CO chemotherapy. β-HCG initially declined but subsequently rose again, and imaging showed new metastases in the left cerebellar hemisphere, right frontal lobe and left thalamus. On August 31, the regimen was changed to EMA/EP, with the PD-1 inhibitor sintilimab administered during the first cycle and subsequent cycles continuing without it. The biomarker fell temporarily, but persistent pulmonary lesions and progressive intracranial disease showed that the response was not sustained. Further brain radiotherapy and later thoracic radiotherapy likewise failed to arrest progression.

A third-line combination of nab-paclitaxel, bevacizumab and the PD-1 inhibitor penpulimab was started on January 9, 2026, with additional cycles on January 31 and February 25. β-HCG again decreased temporarily, but the patient ultimately developed rapid pulmonary and intracranial progression. After discussion with his family, active anticancer treatment was stopped and best supportive and palliative care was provided. He was discharged on March 4, 2026, about 8.6 months after pathological diagnosis, still alive but in poor condition because of persistent intracranial and systemic disease. No objective laboratory or imaging follow-up was available after discharge.

One of the report’s most notable observations was the close relationship between serial β-HCG measurements and radiological changes. Temporary reductions in β-HCG accompanied periods of apparent treatment response, while renewed increases corresponded with disease progression. The authors report that changes in the marker sometimes preceded or occurred alongside changes visible on imaging, allowing clinicians to recognize resistance earlier. This case does not establish that β-HCG can replace imaging, but it shows how a relatively simple blood test tracked the course of a tumor that produced exceptionally high hormone concentrations in this patient.

The investigators searched PubMed for eligible English-language reports of confirmed male primary pulmonary choriocarcinoma, extracting clinical presentation, metastatic sites, pretreatment β-HCG, treatment and survival data. Their analyses included 33 metastatic cases with available survival information and a separate set of 18 cases with pretreatment β-HCG values suitable for prognostic analysis. In exploratory Kaplan–Meier analyses, patients receiving immune checkpoint inhibitor-based therapy had significantly longer overall survival than those treated without immunotherapy, and patients with lower pretreatment β-HCG also had longer survival than those with markedly elevated concentrations. These were associations in small, heterogeneous, published case cohorts, not randomized comparisons; differences in disease severity, treatment selection, follow-up and publication bias could influence the results.

Taken together, the case illustrates the diagnostic and therapeutic difficulty of male primary pulmonary choriocarcinoma while providing preliminary support for two areas of further study. Pathology must integrate morphology and multiple immunohistochemical markers with serum β-HCG rather than depend on any single stain, and treatment decisions in advanced disease remain unsupported by standardized guidelines or prospective trials. Dynamic β-HCG measurement may be useful for monitoring tumor burden in individual patients, while the pooled survival signal warrants investigation of checkpoint blockade in larger, multicenter cohorts. The authors emphasized that prospective studies incorporating genomic and immune biomarkers are needed to determine whether immunotherapy improves outcomes in this exceptionally rare and aggressive cancer.

Subject of Research: Clinical features, monitoring and treatment of male primary pulmonary choriocarcinoma with brain metastases

Article Title: Primary pulmonary choriocarcinoma with brain metastases in a male: a case report and literature review

Article References: Yin, Z., Xiao, Y., Zhang, D., Liu, B., & Liu, S. (2026). Primary pulmonary choriocarcinoma with brain metastases in a male: a case report and literature review. Frontiers in Oncology, 16, Article 1945521. https://doi.org/10.3389/fonc.2026.1945521

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1945521

Keywords: primary pulmonary choriocarcinoma, brain metastases, β-human chorionic gonadotropin, immune checkpoint inhibitors, trophoblastic malignancy, case report, survival analysis, tumor monitoring, immunohistochemistry, Primary, pulmonary, choriocarcinoma