A 69-year-old non-smoker man was admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China) on 11 April 2022 and complained of cough and expectoration with bloody sputum for 2 weeks. In March 2022, he visited a local hospital due to cough and expectoration with bloody sputum, but there were no chills, fever, fatigue, or gastrointestinal complaints. A chest computed tomography (CT) scan in the local hospital on 1 April showed a patchy shadow in the right lower lobe. Physicians at the local hospital recommended that the patient should be transferred to the higher-level hospital for further diagnosis and treatment. The patient had a history of kidney calculi disease and denied the history of malignant tumor, other diseases, and surgery. Physical examination at admission showed no obvious positive signs. On 13 April, the lung-enhanced CT scan in Tongji Hospital showed a massive soft tissue shadow, about 46 x 35 mm in the lower lobe of the right lung ( Figure 1A ). To further confirm the diagnosis, the neoplasm samples in the lower lobe of the right lung were obtained using CT-guided fine-needle aspiration (FNA).
Immunohistochemical assays showed that the tumor was positive for CK7, CDX-2, C-MET, and villin; focally positive for P40, CD10, MUC6, ROS1, and mesothelin; and negative for thyroid transcription factor-1 (TTF-1), ALK, SATB2(-), MUC2(-), MUC5AC(-), PAX8(-), GATA3(-), PSA(-), NKX3.1(-), napsin A, and CK20 ( Figure 2 ). Further pathological examination resulted in a diagnosis of intestinal-type adenocarcinoma of the right lung.
The laboratory data showed that cytokeratin-19 fragment antigen21-1 (CYFRA21-1, 9.57 mug/L) and carbohydrate antigen 19-9 (CA19-9, 106.60 U/ml) levels were increased compared with normal levels. To exclude a diagnosis of colorectal adenocarcinoma, gastroscopy and rectal colonoscopy had been performed respectively. Gastroscopy showed chronic hemorrhagic gastritis and gastric body polyp. Histological examination of the gastric body polyp showed gastric fundus gland polyp. Rectal colonoscopy showed multiple polyps of the sigmoid colon, which was determined as tubular adenoma by histological examination. These pathological and immunohistochemical findings excluded lung metastases of intestinal adenocarcinoma, and the patient was finally diagnosed with pulmonary intestinal adenocarcinoma.
In order to investigate the mutation profile of the neoplasm samples, we obtained the permission of patients to use NGS for gene analysis, which is designed to identify somatic variations of 32 cancer-related genes, including EGFR, KRAS, NRAS, BRAF, RET, PIK3CA, and TP53. Gene analysis of the neoplasm samples was undertaken by GREENIKON Medical Laboratory Co., Ltd (Shanghai, China) using Illumina NovaSeq 6000 platform (Illumina, San Diego, CA). Among the 32 genes examined by this assay, only the EGFR, KRAS, and TP53 genes were mutated. EGFR showed a missense mutation (c.2257C>T, p.P753S) of exon 19. KRAS showed a missense mutation (c.35G>T, p.G12V) of exon 2. TP53 showed a missense mutation (c.401T>C, p.F134S) of exon 5 ( Table 1 ). In addition, the expression level of PD-L1 in tumor tissues of patients was detected, and IHC staining results of tissue sections showed that the tumor proportion score (TPS) of PD-L1 was 0%, indicating negative expression. From 30 April, the patient received four cycles of chemotherapy (pemetrexed + cisplatin) combined with immunotherapy (penpulimab). On 4 July, the lung-enhanced CT scan showed that the tumor was smaller than that on 13 April ( Figure 1 ).