Characteristics of glioblastomas and immune microenvironment in a Chinese family with Lynch syndrome and concurrent porokeratosis.

Background: Lynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we analyzed the clinicopathological and genetic characteristics of LS-associated GBMs and concurrent porokeratosis, as well as evaluated the tumor immune microenvironment (TIME) of LS-associated GBMs. Methods: Immunohistochemical staining was used to confirm the histopathological diagnosis, assess MMR and PD-1/PD-L1 status, and identify immune cell subsets. FISH was used to detect amplification of EGFR and PDGFRA, and deletion of 1p/19q and CDKN2A. Targeted NGS assay analyzed somatic variants, MSI, and TMB status, while whole-exome sequencing and Sanger sequencing were carried out to analyze the germline mutations. Results: In the LS family, three members (I:1, II:1 and II:4) were affected by GBM. GBMs with loss of MSH2 and MSH6 expression displayed giant and multinucleated bizarre cells, along with mutations in ARID1A, TP53, ATM, and NF1 genes. All GBMs had TMB-H but not MSI-H. CD8+ T cells and CD163+ macrophages were abundant in each GBM tissue. The primary and recurrent GBMs of II:1 showed mesenchymal characteristics with high PD-L1 expression. The family members harbored a novel heterozygous germline mutation in MSH2 and FDPS genes, confirming the diagnosis of LS and disseminated superficial actinic porokeratosis. Conclusion: LS-associated GBM exhibits heterogeneity in clinicopathologic and molecular genetic features, as well as a suppressive TIME. The presence of MMR deficiency and TMB-H may serve as predictive factors for the response to immune checkpoint inhibitor therapy in GBMs. The identification of LS-associated GBM can provide significant benefits to both patients and their family members, including accurate diagnosis, genetic counseling, and appropriate screening or surveillance protocols. Our study serves as a reminder to clinicians and pathologists to consider the possibility of concurrent genetic syndromes in individuals or families.

A Rare Case of Craniocervical Penetrating Injury by a Steel Bar.

RATIONALE: Non-missile penetrating injuries caused by foreign bodies, such as knives or sharp wood, are infrequent. We report a 49-year-old male suffering from severe craniocervical penetrating injury by a steel bar was successfully treated by surgery. CHIEF COMPLAINT: The male patient was a 49-year-old builder. Although working on the construction site, an approximately 60 cm steel bar penetrated the patient's brain vertically through the left top of the head presenting with unconsciousness and intermittent irritability. DIAGNOSIS: Computed tomography of the head showed the entrance and exit of the skull damaged by the steel bar. Three-dimensional reconstruction showed that the steel bar entered the skull from the posterior left coronal suture and penetrated the ipsilateral occipital bone, about 5 cm into the neck soft tissue. INTERVENTION: We successfully performed the operation and removed the steel bar. OUTCOMES: The patient was followed up for 5 years; muscle strength returned to normal. LESSONS: Penetrating injuries caused by steel bars are rare, which always cause severe intracranial injury combined with peripheral tissue injury, by sharing our experience in the treatment of this rare case, we hope to provide a reference for similar injuries in the future.