Non-small-cell lung cancer, histologically classified into adenocarcinoma (AD) and squamous cell carcinoma, is one of the most deadly malignancies worldwide. Lung AD (LUAD) could benefit of a plethora of target therapies and, in the last few years, also of immunotherapies. Here we focused on a real-life cohort of LUAD and The Cancer Genome Atlas (TCGA)-LUAD dataset aiming to gain insights into the immune contexture of such a malignancy. We explored the mutational status of 41 genes and the expression of 94 genes, related to immune-checkpoint, inflammation, and stromal microenvironment. Surprisingly, we found that our cohort has a very low mutational burden if we consider our panel as its surrogate. Regarding gene expression data, we identified 31 genes significantly deregulated in tumor tissues compared with a pool of normal samples. Unsupervised hierarchical clustering of the deregulated genes is able to identify two clusters of tumor samples, differently enriched in alterations in actionable genes. In particular, we identified a cluster enriched in patients carrying KRAS alterations. In silico deconvolution, that is the inferring of tumor microenvironment composition by gene expression data, through TIMER algorithm has been performed to explore immune microenvironment. Estimation performed on our gene expression matrix showed that B cell infiltration is lower in the KRAS-mutated enriched cluster, as in the TCGA-LUAD dataset. Such a finding has been validated in situ through immunohistochemistry in an independent cohort. Moreover, cases in LUAD-TCGA with low B cell infiltration have a significantly worse overall survival than those with higher levels. In the real-life cohort we observed that cases belonging to cluster enriched in KRAS-mutated patients have a poor outcome. LUAD driven by KRAS mutation represents an unmet clinical need, being refractory to pharmacological inhibition. Our results link KRAS mutations to B cell infiltration. Thus, the present findings could be helpful in a better definition of immunotherapeutic approaches for KRAS mutated patients.
A few cases of malignant fibrous histiocytoma (MFH) of the larynx have been reported to date. All ages may be affected, but the tumor is more prevalent in the sixth and seventh decade of life. We describe a case of MFH in a 71-year-old Italian man who 8 years before underwent a right cordectomy and radiotherapy for squamous cell carcinoma. Recurrent tumor was found to be MFH. The clinico-pathological features of this tumor are presented and the possible relationship between radiotherapy and MFH discussed. The neoplasm was characterized by spindle-shaped atypical cells arranged in a diffuse storiform pattern. Mitoses were prominent, numerous, and often atypical. Immunohistochemically, neoplastic cells were strongly positive for vimentin and alpha1-antichymotrypsin but were negative for cytokeratins and S-100 protein. These findings confirmed the diagnosis and excluded possible sarcomatoid carcinoma, inflammatory pseudotumor, and a new carcinosarcoma. The risk of sarcoma after radiotherapy for squamous cell carcinoma in the larynx is very low when considering the frequent use of radiotherapy, but long follow-ups are required.
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