Multiomics integration-based immunological characterizations of adamantinomatous craniopharyngioma in relation to keratinization.

Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.

Extended Endoscopic Endonasal Approach for Giant Pediatric Craniopharyngiomas: Technical Note and Case Series.

BACKGROUND AND OBJECTIVES: Giant pediatric craniopharyngiomas are rare tumors whose clinical and surgical management is extremely challenging. A variety of open transcranial approaches has been used to resect these lesions. Although there has been an increasing acceptance of the endoscopic endonasal approach (EEA) for the resection of pediatric craniopharyngiomas in recent years, many surgeons continue to recommend against the use of the EEA for giant pediatric craniopharyngiomas. This study aimed to evaluate the feasibility of extended EEA for giant craniopharyngiomas in the pediatric population. METHODS: All consecutive pediatric patients with giant craniopharyngiomas (diameter >4 cm) who underwent endoscopic endonasal surgery at our institution were retrospectively reviewed. Data on demographic information, preoperative assessment, imaging features, surgical results, complications, and recurrences were recorded and analyzed. RESULTS: A total of 16 pediatric patients with an average age of 12 years were identified. The mean maximum diameter and volume of the tumors were 4.35 cm and 24.1 cm3, respectively. Gross total resection was achieved in 13 patients (81.3%) and subtotal resection in 3 patients (18.7%). Postoperatively, partial or complete anterior pituitary insufficiency occurred in 100% of patients, and 62.5% developed new-onset diabetes insipidus. Visual function improved in 9 patients (56.3%) and remained stable in 7 patients (43.7%). Postoperative cerebrospinal fluid leakage occurred in 2 patients and was successfully repaired through the EEA. During a mean follow-up of 44.3 months, 18.8% of patients had a >9% increase in body mass index, and 93.8% of patients successfully returned to school or work. Two patients (12.5%) suffered a recurrence. Disease control was achieved in 16 patients (100%) at final follow-up. CONCLUSION: The extended EEA allows adequate access to this challenging tumor and enables complete resection and visual improvement with a reasonable approach-related complication rate.