CT and biomarkers support small cell lung cancer diagnosis in unbiopsied patient

In a two-patient case report, researchers described how characteristic computed tomography findings, a markedly elevated tumor marker and clinical symptoms supported a clinical diagnosis of small cell lung cancer in a 67-year-old man whose recent coronary stents and antiplatelet therapy made biopsy medically hazardous. The patient declined every invasive sampling procedure after his cardiologist assessed the risk of in-stent thrombosis during a clopidogrel washout as high. He received etoposide and carboplatin followed by radiotherapy; follow-up imaging showed marked tumor shrinkage, and he remained without detected recurrence for approximately 27 months. The report does not establish CT or biomarker testing as a replacement for pathology. Instead, it presents a multidisciplinary, image-led approach for the difficult clinical situation in which tissue cannot safely be obtained.

The other patient in the report was a 56-year-old man whose small cell lung cancer had already been confirmed by bronchoscopic biopsy before admission to Guang’anmen Hospital in Beijing. He had experienced two months of facial and head swelling and cough with blood-tinged sputum. On examination, dilated superficial veins on his chest wall and pitting edema of his face and upper limbs were consistent with superior vena cava syndrome. Chest CT and PET-CT showed right-sided lung cancer, extensive nodal disease and vascular involvement, leading to a diagnosis of extensive-stage small cell lung cancer. His case served as the pathologically confirmed comparison for the 67-year-old man whose biopsy was declined.

Two radiologists independently reviewed the 56-year-old patient’s CT images. The scan showed an obstructive lesion in the right upper lung, fused hilar and mediastinal nodal masses, invasion of the superior vena cava and possible involvement of the brachiocephalic and right pulmonary veins. Filling defects in the left subclavian and common carotid veins were considered possible tumor thrombi. Small pleural and pericardial effusions were also present. The combination of coalescent lymph-node masses around the hilum and mediastinum and compression of adjacent major vessels explained the patient’s visible symptoms and reinforced the suspicion of small cell lung cancer. This pattern was described as characteristic of the disease, but not unique to it.

The 56-year-old patient began etoposide plus carboplatin three days after admission, receiving etoposide on days one through five of each cycle and carboplatin on day one. The carboplatin dose was increased from 400 mg in the first cycle to 450 mg in the second because his estimated glomerular filtration rate had improved without severe hematological toxicity; the adjustment was calculated with the Calvert formula. He then received proton radiotherapy at another hospital. His edema and vascular dilation improved, and a CT scan six weeks after the second chemotherapy cycle showed substantial regression of the primary tumor, nodal metastases, venous invasion, tumor thrombi and effusions. The treatment response was classified as partial because residual disease remained. He declined prophylactic cranial irradiation and chose brain MRI surveillance. About eight months after initial treatment, MRI detected an occipital metastasis that received cranial radiotherapy. He later restarted chemotherapy with immunotherapy and remained alive under continuous treatment as of July 2025, although the intracranial metastasis was stable and no new systemic lesions were reported.

The unbiopsied patient had different clinical circumstances. He was 67 years old and had chest tightness and hemoptysis for two months. His medical history included hypertension, coronary heart disease and an old inferior myocardial infarction. He had undergone coronary stent implantation twice, with two stents at each procedure, most recently in 2017, and was taking clopidogrel and aspirin to prevent thrombosis within the stents. At another hospital, chest radiography had shown an irregular mass-like opacity in the left upper lobe, while neuron-specific enolase, or NSE, measured 71 ng/mL against a reference range of 1–16.2 ng/mL. A repeat test one week later produced a markedly higher result of 221 ng/mL.

After the available diagnostic options and their risks were explained, the patient and his family declined fine-needle aspiration and other invasive biopsies. His cardiologist considered the danger of in-stent thrombosis during a clopidogrel washout period to be high. A multidisciplinary team reviewed the CT findings, NSE measurements, symptoms and available staging examinations. These included whole-body bone imaging and head CT, neither of which detected distant metastases. The team made a clinical diagnosis of limited-stage small cell lung cancer, classified as cT3N2M0, or stage IIIB under the AJCC TNM system. Importantly, the disease category was a tentative clinical determination rather than a pathological diagnosis. The report notes that this approach was intended for circumstances in which reasonable attempts at tissue sampling had not been feasible, not as a general substitute for pathology.

Treatment began six days after admission with the same etoposide and carboplatin combination used in the 56-year-old patient. His chest tightness and hemoptysis improved after one cycle. The hospital’s CT showed several soft-tissue masses around the left upper-lobe hilum that were partly fused, with the largest measuring approximately 66 by 68 mm, along with enlarged hilar and mediastinal nodes. Another mass beneath the left apical pleura measured approximately 31 by 64 mm, and small pleural nodules and a 3.5-mm ground-glass nodule were also visible. After three cycles, follow-up contrast-enhanced CT showed that most of the hilar masses had disappeared, the apical pleural mass was largely no longer visible and the involved nodes had diminished. The largest remaining aortic-window node measured about 1.2 cm in short diameter. The response was assessed as partial, and the patient subsequently received a fourth chemotherapy cycle and radiotherapy at another hospital.

Later imaging documented a clinical complete response, with tumor disappearance and no detected recurrence during approximately 27 months of follow-up. He was then lost to contact in January 2020, so the duration and durability of that outcome remain uncertain. Because the diagnosis was not histologically confirmed, the multidisciplinary team did not recommend prophylactic cranial irradiation. The striking response was clinically encouraging, but the authors cautioned that a complete response in this individual case cannot be assumed to represent the typical outcome for small cell lung cancer. The report also does not compare the clinical diagnostic strategy with a control group, calculate its diagnostic accuracy or establish whether similar patients generally fare better with an imaging-based approach than with delayed or omitted treatment.

Both cases exhibited the same central imaging pattern: bulky, coalescent hilar and mediastinal lymph nodes surrounding a central lung lesion. The authors linked this morphology to small cell lung cancer’s tendency to arise near bronchi, grow invasively and involve regional nodes early. They contrasted it with the more scattered nodal enlargement often seen in non-small cell lung cancer, although they emphasized that the pattern is not unique. Lymphoma, sarcoidosis, tuberculosis, metastatic small-round-cell tumors and other neuroendocrine tumors can produce overlapping findings. Likewise, NSE is not specific to small cell lung cancer: it may rise in other neuroendocrine tumors and even in nonmalignant conditions such as brain injury or inflammatory disease. The imaging and biomarker findings therefore had to be interpreted with symptoms, the medical history, alternative diagnoses and multidisciplinary review rather than treated as definitive proof.

Several limitations constrain the report’s conclusions and its relevance to current practice. The 67-year-old patient’s brain evaluation used head CT rather than MRI, the more sensitive standard for detecting small brain metastases, potentially resulting in understaging. The case occurred in 2017, before circulating tumor DNA testing was widely available; the authors note that such molecular testing could now provide additional specificity when tissue is unobtainable. ProGRP, described in the report as a marker with better diagnostic performance than NSE, was also unavailable at the hospital laboratory at the time. The risk-benefit assessment for treating without pathology was documented qualitatively rather than through a formal quantitative analysis, no ethics committee consultation was sought, and the 67-year-old patient’s unusually favorable outcome may not be reproducible. For patients whose biopsies can be performed safely, pathological confirmation remains the diagnostic gold standard. These cases instead show how imaging, biomarkers, symptoms and specialist judgment can support an urgent treatment decision when pathology is genuinely inaccessible.

Subject of Research: CT and biomarker assessment of small cell lung cancer when pathological sampling is not feasible

Article Title: Two case reports of small cell lung cancer: typical CT manifestations, with one case illustrating adjunctive CT-based diagnosis without pathological confirmation

Article References: Zhu, Y., Wang, Q., Yu, M., Qin, Y., Sun, L., Ye, M., Li, J., & Huang, H. (2026). Two case reports of small cell lung cancer: typical CT manifestations, with one case illustrating adjunctive CT-based diagnosis without pathological confirmation. Frontiers in Oncology, 16, Article 1865534. https://doi.org/10.3389/fonc.2026.1865534

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1865534

Keywords: small cell lung cancer, computed tomography, clinical diagnosis, neuron-specific enolase, tumor markers, biopsy risk, coronary stents, chemoradiotherapy, multidisciplinary care, case report, case, reports