PMC9178119_01
Treatment history and clinical information of the presented case. (A-I) PET/CT images of primary and metastatic lesions were found at different time points as shown by the time scale. (J) Multiple serum tests of SCC antigen, CYFRA21-1, and CEA were performed. (K, L, N, O) Pathological examination of primary and metastatic lesion biopsy. The magnificence of the H&E staining images was 100x. (M, P) The IHC examination of PD-L1 expression. The tumor proportion score of the metastatic SCC lesion and the chest wall lesion were > 50% and < 1%, respectively. RTx, radiotherapy; *, during the first month of afatinib treatment, anlotinib was co-administrated, which was discontinued due to side effects.
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Positron emission tomography (PET) and computed tomography (CT) examinations revealed the presence of a lesion in the right upper lobe ( Figure 1A ) and multiple lymph nodes metastases at the right hilum of the lung, right mediastinum, the right-side clavicle, and pleural effusion in the right side. The percutaneous biopsy and immunohistochemistry (IHC) analysis revealed a poorly differentiated adenocarcinoma (ADC,  Figure 1K ) with positive expression of Napsin A, thyroid transcription factor-1 (TTF-1), and negative CK5/6. Partial response (PR) was achieved after one month ( Figure 1B ) and progression-free survival (PFS) was 27 months for the first-line gefitinib treatment. As shown in  Figures 1C, D , the two CT images taken with an interval of 19 days (2019.12.06 and 2019.12.25) showed over two times size increase on multiple metastatic sites. TTF-1. The SCC antigen and CYFRA21-1 levels in serum were significantly increased compared to the baseline tests ( Figure 1J ). Then, the IHC test showed a positive PD-L1 expression with a tumor proportion score (TPS) of over 50% ( Figure 1M ). The follow-up examination after one cycle of combined treatment showed that the rapidly progressed metastatic lesions had been under control ( Figure 1E ). CYFRA21-1 in serum ( Figure 1J ). Compared to the mutational profile of the metastatic SCC lesion, the progressed ADC maintained the oncogenic EGFR (L858R) mutation. Multiple metastatic sites were found by repeat PET-CT including kidney, liver, and chest wall ( Figure 1G ) with a dramatic increase in carcinoembryonic antigen (CEA) level ( Figure 1J ). The metastatic chest wall lesion was pathologically identified as ADC ( Figure 1O ) with the same genetic alterations as the progressed ADC ( Table 1 ). Due to the clearance of the gene amplification of CD274 and PDCD1LG2, the IHC test of PD-L1 was negative for the chest wall lesion ( Figure 1P ). With the progression on the metastatic chest wall lesion ( Figure 1H ), afatinib (40 mg/d) and anlotinib (10 mg/d) were administrated to the patient, but anolotinib was discontinued after one month because of severe side effects, including hemoptysis and tooth loss. Afatinib monotherapy relieved chest pain and led to a PR of the metastatic chest wall lesion as shown by the CT scan in December 2021 ( Figure 1I ).