PMC9493008_01
A series of CT findings during the clinical course. On admission, a primary lesion (A) in the right upper lobe of the lung and multiple metastases (B) in the left lower lobe of the lung were identified. Treatment with icotinib was performed, and after three months, partial remission was found (right, C; left, D). Treatment with icotinib was performed, and after six months, progressive disease was found (right, E; left, F; brain MRI, G). Treatment with osimertinib was performed, and after one month, partial remission was found (right, H; left, I). Treatment with osimertinib was performed, and after three months, progressive disease was found (right, J).
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The contrast-enhanced thoracic computed tomography (CT) revealed a primary lesion (lesion 1, 92x58 mm) in the right upper lobe of the lung and multiple metastases with a maximum size of 37x24 mm (lesion 2) in the left lower lobe of the lung, and distant spread to mediastinal lymph nodes was suspected ( Figures 1A, B ). In March 2020, the thoracic CT revealed that the primary tumor and metastases decreased in size ( Figures 1C, D ): lesion 1 (42x39 mm) and lesion 2 (20x15 mm). Figures 1E, F ). Furthermore, multiple metastases were found in the left cerebellum and right frontal lobe by brain magnetic resonance imaging (MRI,  Figure 1G ). Figures 1H, I ), lesion 2 (30x18 mm), and lesion 3 (10x6 mm) all decreased in size. Furthermore, an improvement was revealed by the brain MRI. However, in August 2020, lesion 3 increased in size (25x14 mm,  Figure 1J ), and the pathological evidence of lung biopsies obtained by CT-guided procedures confirmed the squamous cell carcinoma ( Figure 2E ) with P40(+) ( Figure 2F ), CK5/6(+) ( Figure 2G ), CK7(-), NapsinA(-), TTF-1(-), CgA(-), CD56(-), Syn(-), Ki67(30% +), EGFR exon19 deletion, T790M mutant, MET amplification (high-throughput sequencing), and PD-L1 TPS 20%.
Histologic transformation from adenocarcinoma to squamous cell carcinoma: (A) lymph node specimens (EBUS-TBNA), adenocarcinoma (H&E, x200); (B) adenocarcinoma CK7 (+); (C) adenocarcinoma TTF; (+) (D) adenocarcinoma NapsinA (+); (E) lung biopsies (CT-guided sampling), squamous cell carcinoma (H&E, x400); (F) squamous cell carcinoma P40 (+); (G) squamous cell carcinoma CK5/6 (+).
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TTF-1(+) ( Figure 2B ), NapsinA(+) ( Figure 2C ), CK7(+) ( Figure 2D ), D2-40(-), CD56(-), Wilms tumor(-), Caplonin(-), CDX-2(-), SATB2(-), Ki67(60% +), EGFR exon19 deletion and PD-L1 TPS 15%. Finally, the diagnosis of lung adenocarcinoma (T4N3M1a, stage IVA) with an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 1 was made based on the clinical findings. Then, 125 mg of icotinib was orally administered, three times daily. However, in August 2020, lesion 3 increased in size (25x14 mm,  Figure 1J ), and the pathological evidence of lung biopsies obtained by CT-guided procedures confirmed the squamous cell carcinoma ( Figure 2E ) with P40(+) ( Figure 2F ), CK5/6(+) ( Figure 2G ), CK7(-), NapsinA(-), TTF-1(-), CgA(-), CD56(-), Syn(-), Ki67(30% +), EGFR exon19 deletion, T790M mutant, MET amplification (high-throughput sequencing), and PD-L1 TPS 20%.