Background: In multiple primary lung adenocarcinomas (MPLAs), the relationship between imaging and gene mutations remains unclear. This retrospective study aimed to identify the correlation of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) status with CT characteristics in MPLA patients. Methods: Sixty-seven patients (135 lesions) with MPLAs confirmed by pathology were selected from our institution. All subjects were tested for EGFR mutations and ALK status and underwent chest CT prior to any treatment. The criteria for MPLA definitions closely adhered to the comprehensive histologic assessment (CHA). Results: Among MPLA patients, EGFR mutations were more common in females (p = 0.002), in those who had never smoked (p = 0.010), and in those with less lymph node metastasis (p < 0.001), and the tumours typically presented with ground-glass opacity (GGO) (p = 0.003), especially mixed GGO (p < 0.001), and with air bronchograms (p = 0.012). Logistics regression analysis showed that GGO (OR = 6.550, p = 0.010) was correlated with EGFR mutation, while air bronchograms were not correlated with EGFR mutation (OR = 3.527, p = 0.060). A receiver operating characteristic (ROC) curve yielded area under the curve (AUC) values of 0.647 and 0.712 for clinical-only or combined CT features, respectively, for prediction of EGFR mutations, and a significant difference was found between them (p = 0.0344). ALK-positive status was found most frequently in MPLA patients who were younger (p = 0.002) and had never smoked (p = 0.010). ALK positivity was associated with solid nodules or masses in MPLAs (p < 0.004) on CT scans. Logistics regression analysis showed that solid nodules (OR = 6.550, p = 0.010) were an independent factor predicting ALK positivity in MPLAs. For prediction of ALK positivity, the ROC curve yielded AUC values of 0.767 and 0.804 for clinical-only or combined CT features, respectively, but no significant difference was found between them (p = 0.2267). Conclusion: Among MPLA patients, nonsmoking women with less lymph node metastasis and patients with lesions presenting GGO or mixed GGO and air bronchograms on CT were more likely to exhibit EGFR mutations. In nonsmoking patients, young patients with solid lesions on CT are recommended to undergo an ALK status test.

Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) exhibit heterogeneous tumor characteristics, distinct responses to immunotherapy, and different survival outcomes. However, it is unclear whether gut microbiota is distinct between CRCs with different MMR status. In this study, we used immunohistochemistry for four major MMR proteins to determine the MMR status in 230 CRC patients. The gut microbiota was profiled in cancerous and adjacent normal tissues by using bacterial 16S rRNA sequencing. The differences in microbiota diversity, composition and related metabolic pathways between patients with dMMR and pMMR CRCs were explored. Linear discriminant analysis effect size (LEfSe) analysis was further applied to validate the significant taxonomic differences at the genus level. In our study cohort, dMMR status was identified in 29 of 230 (12.61%) tumors. The richness (alpha-diversity) of gut microbiome in dMMR tumor tissue was higher compared with pMMR tumor tissues. The microbial community composition (beta-diversity) between the two groups was significantly different. The dMMR group was enriched considerably for some microbiota, including Fusobacteria, Firmicutes, Verrucomicrobia, and Actinobacteria at the phylum level and Fusobacterium, Akkermansia, Bifidobacterium, Faecalibacterium, Streptococcus, and Prevotella bacteria at the genus level. However, the pMMR group was dominated by Proteobacteria at the phylum level and Serratia, Cupriavidus and Sphingobium at the genus level. Moreover, a wide variety of microbiota associated functional pathways were observed with different MMR status. KEGG pathway analysis indicated a higher abundance of the biosynthesis and metabolic pathways of glycan and nucleotide, cell growth and death pathways, genetic replication and repair pathways in dMMR samples compared with the pMMR group. These findings demonstrate that CRC patients with different MMR status have distinct gut bacterial community richness, compositions and related metabolic pathways, suggesting basis that may explain the effectiveness of immunotherapy in dMMR tumors.

Inflammatory myofibroblastic tumor (IMT) of the stomach is extremely rare in adults and exhibits a variable biological behavior that ranges from frequently benign lesions to more aggressive variants. Here we report a case of gastric IMT with lymph node metastasis in an adult who had undergone total colectomy for familial adenomatous polyposis (FAP). A 37-year-old man presented gradual-onset epigastric discomfort; he had undergone total colectomy for FAP 6 years before. The upper endoscopy revealed diffuse polyposis in the body of stomach and a submucosal protruding tumor of approximately 4.5 × 3.5 cm in the gastric angular incisure, appearing like gastrointestinal stromal tumor. Histology after surgery verified the diagnosis of fundic gland polyposis (FGPs) and gastric IMT with lymph node metastasis. Both the primary IMT tissue and its metastatic lesion but not the FGP or FAP tissue were positive for anaplastic lymphoma kinase (ALK) on immunohistochemical staining. Fluorescent in situ hybridization confirmed the existence of ALK rearrangement in IMT tissues. However, the patient exhibited no abnormalities in microsatellite instability or mismatch repair-system components, including MSH6, MSH2, MLH1 and PMS2, in IMT, FGP or FAP tissue. This case allowed for exploring the relationship among IMT, FGP and FAP and indicates that gastric IMT should be considered in the diagnosis of a gastric mass in patients with FAP. ALK may be a useful biomarker in the diagnosis of IMT and its metastatic lesions.

Background: To clarify the relationship between p53 immunohistochemistry (IHC) staining and TP53 alterations (including mutations and deletions) in large B-cell lymphomas (LBCLs) and to explore the possibility of p53 IHC expression patterns as surrogate markers for TP53 alterations. Methods: A total of 95 patients diagnosed with LBCLs were selected, and paraffin samples were taken for TP53 gene sequencing, fluorescence in situ hybridization and p53 IHC staining. The results were interpreted by experienced pathologists and molecular pathologists. Results: Forty-three nonsynonymous TP53 mutations and p53 deletions were detected in 40 cases, whereas the remaining 55 cases had wild-type TP53 genes. The majority of TP53 mutations (34/43, 79.1%) occurred in exons 4-8, and R248Q was the most common mutation codon (4/43, 9.3%). The highest frequency single nucleotide variant was C > T (43.6%). p53 expression was interpreted as follows: Pattern A: p53 staining was positive in 0%-3% of tumor cells, Pattern B: p53 staining was positive in 4-65% of tumor cells, Pattern C: more than 65% of tumor cells were stained positive for p53. The p53 IHC expression patterns were associated with TP53 alterations. Gain of function variants and wild-type TP53 tended to exhibit type C and B p53 expression patterns, but loss of function variants were exclusively seen in type A cases. Additionally, interpretation of the staining by various observers produced significant reproducibility. Conclusions: The p53 IHC expression patterns can be used to predict TP53 alterations and are reliable for diverse alteration types, making them possible surrogate biomarkers for TP53 alterations in LBCLs.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and unconventional non-small-cell lung cancer (NSCLC) that appears to be aggressive, with a poor prognosis and response to conventional treatment. Approximately 30% of PSCs have potentially targetable genomic alterations, but few studies have involved RET gene fusions, and corresponding targeted therapies are lacking. Case presentation: In this report, we describe a patient with PSC harboring a KIF5B-RET gene fusion who was initially diagnosed with stage IVb lung cancer. Due to the poor performance status, the patient was unable to tolerate any radiotherapy or chemotherapy. Based on the next-generation sequencing (NGS) result of RET gene fusion, the patient was treated with pralsetinib. Two months after the treatment, the patient achieved a partial response. Conclusions: Our case indicates that RET is one of the main driver oncogenes of PSC and provides useful information for precise RET inhibitor administration in the future. Thus, the use of comprehensive genomic profiling may provide important treatment options for PSC.