PMC10095823_01
Summary of radiology, pathology, and next-generation sequencing (NGS) results (A-C). (A) Radiological evaluation of the patient before and after neoadjuvant crizotinib for 1 and 5 months. PL, primary lung cancer; LN, lymph nodes. (B) H&E and IHC staining. The result demonstrated at the time of diagnosis of NSCLC (scale bar, 100 mum). (C) H&E staining post-operation. The result showed no residual viable cancer cells after adjuvant crizotinib treatment (scale bar, 100 mum). H&E, hematoxylin and eosin; IHC, immunohistochemistry.
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Figure 1A ). Further, a biopsy of the right supraclavicular lymph node was performed and showed poorly differentiated metastatic lung adenocarcinoma ( Figure 1B ). Five months later, a re-examination using chest CT detected that the size of a nodule in the right lung had clearly decreased, with dimensions of approximately 8 mm * 5 mm ( Figure 1A ). There were no definite tumor residues in the primary lesion and lymph nodes (ypT0 ypN0) ( Figure 1C ).
ALK fusions detected by the targeted NGS assay and FFPE FISH. (A) Sequencing reads of INTS10-ALK fusion and EML4-ALK fusion rearrangements at the time of diagnosis. Taking the INTS10-ALK fusion as an example, the top part of the picture describes the position of the gene on the chromosome. INTS10 on chromosome 8 (8 exons) fused with ALK on chromosome 2 (20 exons). In the bottom part, each row represents a read. Furthermore, for each row, the normal bases of each gene in each row are in gray, and the colored bases belong to another gene. For example, the gray bases in INS-10 are normal bases, and the colored mutilation bases in INST-10 belong to ALK. Similarly, the gray bases in ALK are normal bases, and the colored mutation bases in ALK are part of INST-10 bases. The same principle can annotate the sequencing results of EML4-ALK. (B) FISH result. Using ALK break-apart probe shows ALK rearrangements. Green signals represent the 5'-ALK gene, red signals represent 3'-ALK, and yellow signals represent intact ALK gene. Therefore, arrows point to ALK rearrangements because of the separation of red and green signals. FISH, fluorescence in situ hybridization; NGS, next-generation sequencing; FFPE, formalin-fixed paraffin-embedded.
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As a result, an unreported dual ALK arrangement:INTS10-ALK fusion (I18: A20, 25.85%) and EML4-ALK fusion (E6: A20, 12.64%):was detected ( Figure 2A ). ALK was conducted and confirmed ALK rearrangement ( Figure 2B ). As such, the patient was diagnosed with right lung adenocarcinoma with mediastinal and right supraclavicular lymph node metastasis (stage IIIB, cT1cN3M0).