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case_images: Imaging evaluation and detection of serum tumor biomarkers during treatment. (a-g) Sequence of anticancer treatments and the corresponding imaging evaluations. Red arrows indicate the primary tumor, while red asterisks indicate newly developed intrapulmonary metastatic lesions. A remarkable shrinkage of the primary tumor and intrapulmonary metastases was observed after 5 and 14 months of treatment with selpercatinib. (h) Serum CEA and NSE were detected to monitor clinical response during the treatment.
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case_images: Computed tomography (CT) revealed a mass in her left upper lung (primary lesion, 4.1 cm) with obvious bilateral intrapulmonary and mediastinal lymph node metastases (Figure 1a), without bone, liver, kidney, and brain metastases. The patient showed progressive disease (PD) after 3 cycles of first-line chemotherapy (cisplatin, etoposide) combined with immunotherapy (atezolizumab), manifested as enlargement of the primary lesion (5.0 cm, Figure 1b). Fortunately, the patient achieved a partial response (PR) after four cycles (primary lesion, 2.6 cm; Figure 1c) and received prophylactic cranial irradiation (PCI) subsequently. Then, the patient developed PD during regular follow-up with new intrapulmonary metastases (Figure 1d). However, the lesions grew rapidly and additional metastases occurred (Figure 1e). Soon afterwards, the patient was administered 160 mg selpercatinib twice daily and achieved a PR in almost all lesions, including the primary tumor (3.1 cm) and metastatic lesions (Figure 1f). At the time of manuscript preparation, the patient was still taking selpercatinib with a progression-free survival (PFS) surpassing 14 months and ongoing response (primary lesion, 2.8 cm; Figure 1g). Meanwhile, the monitoring of serum carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) during the treatment course revealed these biomarkers may be related to therapeutic effects (Figure 1h).
case_images: Histological analysis of the transbronchial lung biopsy revealed two different tumor components. (a) Hematoxylin and eosin (H&E) staining showing C-SCLC (combined SCLC and LCNEC, 100x). (b) SCLC is characterized by the presence of diffuse sheets of small round-to-fusiform cells, with scant cytoplasm, and inconspicuous or no nucleoli with finely granular nuclear chromatin. Meanwhile, nuclear chromatin smearing, also termed crushed artifact, is common in SCLC (400x). (c) LCNEC is characterized by large cells, frequent presence of nucleoli and abundant cytoplasm (400x). (d-f) Both the SCLC and LCNEC components were positive for synaptophysin (Syn, 100x, 400x). (g) Different modes of PCK expression in C-SCLC (100x). (h) The so-called dot-like staining pattern of PCK in SCLC (400x). (i) The LCNEC component was diffusely positive for PCK in the cytoplasm (400x). (j-l) Different Ki67 levels were found in both tumor components (100x, 400x).
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case_images: Subsequently, a transbronchial biopsy of the tumor mass in the left upper lobe was carried out, and histological analysis revealed C-SCLC (Figure 2a) comprising SCLC (Figure 2b) and LCNEC (Figure 2c), without gland formation or keratinization. Immunohistochemistry (IHC) showed positive signals for synaptophysin (Syn, Figure 2d-f), pan-cytokeratin (PCK, Figure 2g-i), and Ki67 (MIB-1, Figure 2j-l), with a high proliferative index of 50% (average for SCLC and LCNEC).