PMC6549664_01
Imaging and histopathological characteristics of the patient before crizotinib treatment.. (A and B) PET/CT scans showed increased FDG uptake in multiple lymphatic metastases in the whole body and no FDG uptake in the small nodule located in the posterior segment of the right upper lung. (C) H&E staining confirmed the right neck lymph nodes as poorly differentiated metastatic carcinomas. (D and E) Immunohistochemical staining of the right neck lymph nodes showed positive staining of CK7 (2+) and negative staining of TTF-1 (x400).. Note: The red arrow in figure B indicates the small nodule located in the right upper lung.. Abbrevations: CK7, cytokeratin 7; FDG, fluorodeoxyglucose; H&E, hematoxylin & eosin; PET/CT, positron emission tomography/computed tomography; TTF-1, thyroid transcription factor-1.
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PET/CT showed 1) multiple nodular soft tissue density shadows in the right neck, right upper and lower clavicular regions, right axilla and mediastinum, besides increased fluorodeoxyglucose (FDG) metabolism (SUVmax =10.8), which was considered as metastatic lymph nodes (Figure 1A); 2) nodular shadows in the posterior segment of the right upper lung, with not-so-high FDG metabolism (Figure 1B); and 3) multiple cerebral infarctions, splenomegaly, and multiple cysts in the left kidney.
Molecular analysis of the patient before crizotinib treatment.. (A) NGS analysis based on tissue samples showed MET and CCND1 copy-number amplification. (B) NGS analysis based on plasma samples showed NTRK1c.339-2 A>C mutation. (C and D) IHC staining of tissue samples showed positive staining of MET protein (2 to 3+, x100, and 400, respectively) in metastatic lesions.. Abbrevations: CCND1, cyclin D1; GATA3, GATA binding protein 3; HIST2H3D, histone cluster 2 H3D; IHC, immunohistochemistry; MCL1, myeloid cell leukemia 1; MET, mesenchymal-epithelial transition factor; NGS, next-generation sequencing; N.S., no significance; NTRK1, neurotrophic tyrosine receptor kinase 1; PI3KCG, phosphatidylinositol 3-kinase catalytic subunit gamma.
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PET/CT showed 1) multiple nodular soft tissue density shadows in the right neck, right upper and lower clavicular regions, right axilla and mediastinum, besides increased fluorodeoxyglucose (FDG) metabolism (SUVmax =10.8), which was considered as metastatic lymph nodes (Figure 1A); 2) nodular shadows in the posterior segment of the right upper lung, with not-so-high FDG metabolism (Figure 1B); and 3) multiple cerebral infarctions, splenomegaly, and multiple cysts in the left kidney. The targeted NGS analysis of neck metastatic carcinoma revealed EGFR mutation (-), ALK fusion (-), ROS1 fusion (-), BRAF mutation (-), RAS mutation (-), MET gene amplification (9.12 times) (Figure 2A), NTRK1 gene c.339-2A > C mutation (+) [at a mutant allele frequency (MAF) of 16.17%] (Figure 2B), Cyclin D1 (CCND1) gene amplification (4.75 times) (Figure 2A), and However, targeted NGS of ctDNA only identified NTRK1 (at a MAF of 0.42%) (Figure 2B) and TP53 gene mutation (at a MAF of 0.39%). IHC was performed against MET to verify the findings of the gene test, and the results indicated that the protein staining was positive and the expression level was high (2+ to 3+) (Figure 2C,D).
Chest CT scans showing dynamic changes in metastatic right axillary lymph nodes (A) before, (B) 1 month after, (C) 4 months after, and (D) 8.5 months after crizotinib treatment.. Note: The red arrows in all figure parts indicate the metastatic lesions located in the right axillary fossa.. Abbrevation: CT, computed tomography.
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Scans demonstrated a complete response (CR) after 1 month of treatment (Figure 3), and the tumor markers returned to normal levels.
Abdominal CT scans showing dynamic changes in renal cysts (A) before, (B) 1 month after, and (C) 8.5 months after crizotinib treatment.. Note: The red arrows in all figure parts indicate the cysts located in both kidneys.. Abbrevation: CT, computed tomography.
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During the administration of crizotinib, the main AEs were grade II creatinine elevation, grade I localized edema, and a new cyst in the right kidney (Figure 4).