Comparative analysis of clinical features, methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas: results from a multicenter study

Abstract Papillary craniopharyngioma (PCP) was previously believed to occur only in adults. Sporadic pediatric PCP (PPCP), confirmed by detection of the BRAF V600E mutation, has been reported since 2018. The differences between PPCP and adult PCP (APCP) remain unclear. This comprehensive study aimed...

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Main Authors: Ning Luo, Yi Lin, Jing Feng, Linbo Cai, Yongli Zhang, Xingfu Wang, Wenzhong Mei, Hao Li, Bei Liu, Xueling Qi, Zhixiong Lin
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-12662-8
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author Ning Luo
Yi Lin
Jing Feng
Linbo Cai
Yongli Zhang
Xingfu Wang
Wenzhong Mei
Hao Li
Bei Liu
Xueling Qi
Zhixiong Lin
author_facet Ning Luo
Yi Lin
Jing Feng
Linbo Cai
Yongli Zhang
Xingfu Wang
Wenzhong Mei
Hao Li
Bei Liu
Xueling Qi
Zhixiong Lin
author_sort Ning Luo
collection DOAJ
description Abstract Papillary craniopharyngioma (PCP) was previously believed to occur only in adults. Sporadic pediatric PCP (PPCP), confirmed by detection of the BRAF V600E mutation, has been reported since 2018. The differences between PPCP and adult PCP (APCP) remain unclear. This comprehensive study aimed to enhance understanding of PPCP and elucidate the distinctions between PPCP and APCP. We conducted a systematic analysis of cases of PPCP and APCP, focusing on BRAF V600E mutation, methylation profiles, histology, cell proliferation, imaging features, immune microenvironment, and prognosis. This study compiled 17 cases of PPCP from 6 medical centers, constituting 3.11% of the total 546 PCP cases. Both PPCP and APCP cases exhibited the BRAF V600E mutation with no differences in methylation patterns. However, imaging showed PPCP was predominantly cystic and located beneath the diaphragma sellae with some progression to the sella. APCP typically manifested as solid lesions, primarily located in the suprasellar region, inferior to the third ventricle. PPCP histologically displayed extensive inflammatory cellular infiltration, suppurative change, and occasional small granular calcifications, whereas APCP was largely devoid of calcifications. Compared to APCP, PPCP exhibited significantly lower PD-L1 (an immune checkpoint protein expressed on tumor cells) expression and higher expression levels of CD38 (an immunosuppressive marker), S100A8/A9 (a neutrophil marker), and MPO (myeloperoxidase, a neutrophil marker). Additionally, stromal expression of CD163 (an M2 macrophage marker) was lower in PPCP compared to APCP, while CD68 (an M1 macrophage marker), CD3 (T cell marker), and CD20 (B cell marker) expression showed no significant difference. Ki-67 expression exhibited a banded pattern on PPCP epithelium, contrasting with a punctate pattern in APCP, with significantly higher levels observed in PPCP. Postoperative prognosis did not differ between PPCP and APCP. While driver genes and methylation profiles may not differentiate PPCP from APCP, substantial discrepancies exist in tumor location, histology, imaging features, cell proliferation, and immune microenvironment.
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spelling doaj-art-721c41bfd2af4e9ca5747cee7e2cebe32025-08-20T03:04:33ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-12662-8Comparative analysis of clinical features, methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas: results from a multicenter studyNing Luo0Yi Lin1Jing Feng2Linbo Cai3Yongli Zhang4Xingfu Wang5Wenzhong Mei6Hao Li7Bei Liu8Xueling Qi9Zhixiong Lin10Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical UniversityDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical UniversityDepartment of Pathology, Sanbo Brain Hospital, Capital Medical UniversityDepartment of Oncology, Guangdong Sanjiu Brain HospitalDepartment of Neurosurgery, Kunming Sanbo Brain HospitalDepartment of Pathology, The First Affiliated Hospital of Fujian Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Fujian Medical UniversityDepartment of Neurosurgery, Children’s Hospital of Fudan UniversityDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical UniversityDepartment of Pathology, Sanbo Brain Hospital, Capital Medical UniversityDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical UniversityAbstract Papillary craniopharyngioma (PCP) was previously believed to occur only in adults. Sporadic pediatric PCP (PPCP), confirmed by detection of the BRAF V600E mutation, has been reported since 2018. The differences between PPCP and adult PCP (APCP) remain unclear. This comprehensive study aimed to enhance understanding of PPCP and elucidate the distinctions between PPCP and APCP. We conducted a systematic analysis of cases of PPCP and APCP, focusing on BRAF V600E mutation, methylation profiles, histology, cell proliferation, imaging features, immune microenvironment, and prognosis. This study compiled 17 cases of PPCP from 6 medical centers, constituting 3.11% of the total 546 PCP cases. Both PPCP and APCP cases exhibited the BRAF V600E mutation with no differences in methylation patterns. However, imaging showed PPCP was predominantly cystic and located beneath the diaphragma sellae with some progression to the sella. APCP typically manifested as solid lesions, primarily located in the suprasellar region, inferior to the third ventricle. PPCP histologically displayed extensive inflammatory cellular infiltration, suppurative change, and occasional small granular calcifications, whereas APCP was largely devoid of calcifications. Compared to APCP, PPCP exhibited significantly lower PD-L1 (an immune checkpoint protein expressed on tumor cells) expression and higher expression levels of CD38 (an immunosuppressive marker), S100A8/A9 (a neutrophil marker), and MPO (myeloperoxidase, a neutrophil marker). Additionally, stromal expression of CD163 (an M2 macrophage marker) was lower in PPCP compared to APCP, while CD68 (an M1 macrophage marker), CD3 (T cell marker), and CD20 (B cell marker) expression showed no significant difference. Ki-67 expression exhibited a banded pattern on PPCP epithelium, contrasting with a punctate pattern in APCP, with significantly higher levels observed in PPCP. Postoperative prognosis did not differ between PPCP and APCP. While driver genes and methylation profiles may not differentiate PPCP from APCP, substantial discrepancies exist in tumor location, histology, imaging features, cell proliferation, and immune microenvironment.https://doi.org/10.1038/s41598-025-12662-8Papillary craniopharyngiomaPediatricAdultDiagnosisPathophysiology
spellingShingle Ning Luo
Yi Lin
Jing Feng
Linbo Cai
Yongli Zhang
Xingfu Wang
Wenzhong Mei
Hao Li
Bei Liu
Xueling Qi
Zhixiong Lin
Comparative analysis of clinical features, methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas: results from a multicenter study
Scientific Reports
Papillary craniopharyngioma
Pediatric
Adult
Diagnosis
Pathophysiology
title Comparative analysis of clinical features, methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas: results from a multicenter study
title_full Comparative analysis of clinical features, methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas: results from a multicenter study
title_fullStr Comparative analysis of clinical features, methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas: results from a multicenter study
title_full_unstemmed Comparative analysis of clinical features, methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas: results from a multicenter study
title_short Comparative analysis of clinical features, methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas: results from a multicenter study
title_sort comparative analysis of clinical features methylation and immune microenvironment in pediatric and adult papillary craniopharyngiomas results from a multicenter study
topic Papillary craniopharyngioma
Pediatric
Adult
Diagnosis
Pathophysiology
url https://doi.org/10.1038/s41598-025-12662-8
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