Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases

Zhichao Wu¹, Karen Dazelle¹, Zied Abdullaev¹, Hye-Jung Chung¹, Sonika Dahiya², Matthew Wood³, Han Lee⁴, Calixto-Hope G Lucas⁵, Qinwen Mao⁶, Lorraina Robinson⁶, Igor Fernandes⁷, Matthew McCord⁸, Peter Pytel⁹, Kyle S Conway¹⁰, Rebecca Yoda¹¹, Jennifer M Eschbacher¹², Ossama M Maher¹³, Martin Hasselblatt¹⁴, Bret C Mobley¹⁵, Jack M Raisanen¹⁶, Kimmo J Hatanpaa¹⁶, Joshua Byers¹⁷, Norman L Lehman¹⁸, Patrick J Cimino¹⁹, Drew Pratt¹, Martha Quezado¹, Kenneth Aldape²⁰

Affiliations

¹ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr., Room 2S235, Bethesda, MD, 20892, USA.
² Division of Neuropathology, Washington University, St. Louis, MO, USA.
³ Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, OR, USA.
⁴ Neuropathology Division, Department of Pathology, University of California Davis, Sacramento, CA, USA.
⁵ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Department of Pathology, Primary Children's Hospital, Salt Lake City, UT, USA.
⁷ Laboratorio Bacchi, São Paulo, Brazil.
⁸ Department of Pathology, Northwestern Memorial Hospital, Chicago, IL, USA.
⁹ Department of Pathology, University of Chicago, Chicago, IL, USA.
¹⁰ Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI, USA.
¹¹ Department of Pathology, University of Washington, Seattle, WA, USA.
¹² Department of Neuropathology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
¹³ Division of Pediatric Neuro -Oncology, Pediatric Hematology and Oncology, Kidz Medical Services, Nicklaus Children's Hospital, Miami, FL, USA.
¹⁴ Institute of Neuropathology, University Hospital Münster, Münster, Germany.
¹⁵ Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA.
¹⁶ Division of Neuropathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁷ Department of Laboratory Medicine, University of California-San Francisco, San Francisco, CA, USA.
¹⁸ Department of Pathology, Baylor College of Medicine, Baylor Scott & White Medical Center, Temple, TX, USA.
¹⁹ Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
²⁰ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr., Room 2S235, Bethesda, MD, 20892, USA. kenneth.aldape@nih.gov.

PMID: 39014393
PMCID: PMC11251120
DOI: 10.1186/s40478-024-01781-4

Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases

Zhichao Wu et al. Acta Neuropathol Commun. 2024.

. 2024 Jul 16;12(1):117.

doi: 10.1186/s40478-024-01781-4.

Authors

Affiliations

¹ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr., Room 2S235, Bethesda, MD, 20892, USA.
² Division of Neuropathology, Washington University, St. Louis, MO, USA.
³ Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, OR, USA.
⁴ Neuropathology Division, Department of Pathology, University of California Davis, Sacramento, CA, USA.
⁵ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Department of Pathology, Primary Children's Hospital, Salt Lake City, UT, USA.
⁷ Laboratorio Bacchi, São Paulo, Brazil.
⁸ Department of Pathology, Northwestern Memorial Hospital, Chicago, IL, USA.
⁹ Department of Pathology, University of Chicago, Chicago, IL, USA.
¹⁰ Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI, USA.
¹¹ Department of Pathology, University of Washington, Seattle, WA, USA.
¹² Department of Neuropathology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
¹³ Division of Pediatric Neuro -Oncology, Pediatric Hematology and Oncology, Kidz Medical Services, Nicklaus Children's Hospital, Miami, FL, USA.
¹⁴ Institute of Neuropathology, University Hospital Münster, Münster, Germany.
¹⁵ Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA.
¹⁶ Division of Neuropathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁷ Department of Laboratory Medicine, University of California-San Francisco, San Francisco, CA, USA.
¹⁸ Department of Pathology, Baylor College of Medicine, Baylor Scott & White Medical Center, Temple, TX, USA.
¹⁹ Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
²⁰ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr., Room 2S235, Bethesda, MD, 20892, USA. kenneth.aldape@nih.gov.

PMID: 39014393
PMCID: PMC11251120
DOI: 10.1186/s40478-024-01781-4

Abstract

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.

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Conflict of interest statement

Ethics approval was received in the form of IRB approval with a waiver of informed consent from the national Institutes of health. The authors declare that there are no conflicts of interest. The content of the manuscript has not been published or submitted for publication elsewhere.

All authors have no competing interests to declare.

Figures

**Fig. 1**
DNA methylation identified three distinct subtypes of PTPR tumors. a Unsupervised UMAP plot of collected PTPR tumors and in-house RELA fusion positive supratentorial ependymoma (EPN), and pineal parenchymal and retinal tumors (including PPTID-A/B, PB-GRP1A/GRP1B/GRP2, PIN-CYT). b–c UMAP plot (b) and cluster-heatmap (c) of PTPR tumors in this cohort. d boxplot of genomic mean methylation across the three PTPR tumor subtypes

**Fig. 2**
Histopathology of PTPR tumors. Representative histopathologic images of PTPR tumors show a variety of histologic patterns, including prominent papillary architecture (BA83, CF35, DB32) and/or solid morphology with occasional ependymoma-like (AB29, BX20, CB63, DU68, DP18) areas. One case (AO93) showed tumor in association with prominent sclerosis. Tumors were typically positive for cytokeratins, including CK 8/18 (DP 18). Vertical bar in lower left of images = 100 microns

**Fig. 3**
DNA copy number analysis and clinical outcome of PTPR tumors. a boxplot of CNV load across PTPR subtypes. b CNV heatmap of PTPR tumor samples. c progression-free survival of PTPR subtypes

See this image and copyright information in PMC

References

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Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases

Affiliations

Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Molecular Biology Databases

Research Materials