case_images: PMC8804208_01
case_images: Computed tomography (CT) images of this patient. CT image was collected before (left) and after (right) surgery, and the tumor mass was labeled within the red box.
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case_images: PMC8804208_01_fonc-11-794744-g001.jpg
case_images: f1
case_images: A 59-year-old man was transferred to our hospital in May 2015, with a 4.8 x 3.5 cm nodule with clear boundaries in the right lower field revealed by the chest computed tomography ( Figure 1 ). To find out whether the cells were polyploid, HER2, CEP17, and TP53 were also tested, and three copies of HER2, CEP17, and TP53 ( Figure 3 ) were detected in the large-cell component, but less than three copies of HER2, CEP17, and TP53 were detected in the small-cell component ( Supplemental Figure S1 ). These results indicated that the large and small components of the tumor had different ploidy, which were also validated by the evaluation of the single nucleotide polymorphism (SNP) frequency generated by WES of the tumor and non-tumoral lymph node samples.
case_images: Immunohistochemistry staining of the SCLC and LCNEC regions. (A) H&E staining (400x); (B) immunohistochemistry staining of KI67, CK19, TFF1, CD56, and SYN (200x). The large-cell components were labeled within the red box.
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case_images: PMC8804208_01_fonc-11-794744-g002.jpg
case_images: f2
case_images: The pathological evaluation showed a 6.0 x 4.0 x 3.3 cm tumor mass, and by hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) staining, it was demonstrated that 30%-35% of the tumor cells were LCNEC, and the rest 65%-70% were SCLC ( Figure 2A ). The Ki67 staining was positive for both the small- and the large-cell components, with the small cells having a high percentage of positive cells (67.5% versus 47.5%,  Figure 2B ). Additional whole chromosome trisomy was found on Chr3, 21, and 22; regional trisomy was found on Chr5, 9, and 11, and loss of heterozygosity (LOH) was found on Chr11 and 13 ( Supplemental Figure S2 ).
case_images: Results of MET, HER2, and TP53 FISH in large- and small-cell components. (A) FISH images of MET, HER2, and TP53 FISH in LCNEC (left) and SCLC components (right). The magnification was 1,000x. (B) Quantification of MET, HER2, and TP53 copy number in FISH. LCNEC, large-cell neuroendocrine lung carcinoma; SCLC, small-cell lung cancer.
case_images: fonc-11-794744-g003.jpg
case_images: PMC8804208_01_fonc-11-794744-g003.jpg
case_images: f3
case_images: The MYH8 p.Q1814K and PTPN5 p.M40I had not been reported in the COSMIC database, indicating that they are likely to be novel mutations. Furthermore, fluorescence in situ hybridization test ( Figure 3 ) showed that MET was amplified in the large-cell components with an average copy number of 5.51, whereas for the small-cell component, the MET copy number was gained to 4.22 but did not reach the threshold of five copies per cell. To find out whether the cells were polyploid, HER2, CEP17, and TP53 were also tested, and three copies of HER2, CEP17, and TP53 ( Figure 3 ) were detected in the large-cell component, but less than three copies of HER2, CEP17, and TP53 were detected in the small-cell component ( Supplemental Figure S1 ). These results indicated that the large and small components of the tumor had different ploidy, which were also validated by the evaluation of the single nucleotide polymorphism (SNP) frequency generated by WES of the tumor and non-tumoral lymph node samples.