Pineal Tumors

2023-03-02 Scott Ryall, PhD Affiliation

1.Brigham and Women's Hospital, Harvard Medical School, Boston , MA (USA)

Classification

Definition

The pineal gland is a pinecone-shaped structure located in the epithalamus comprised of two cell populations: pinealocytes and neuroglial support cells. The main function of the pineal gland is rhythm regulation, primarily through the production and release of melatonin. ¹

Tumors of the pineal region are a heterogenous group of rare neoplasms that more commonly arise in children than adults. Pineal parenchymal tumors are neuroepithelial neoplasms that arise from pineocytes and include pineocytoma (WHO grade 1), pineal parenchymal tumor of intermediate differentiation (PPTID; WHO grade 2–3), pineoblastoma (WHO grade 4), papillary tumor of the pineal region (PTPR; WHO grade 2-3), and desmoplastic myxoid tumor, SMARCB1-mutant (DMT, SMARCB1-mutant; WHO grade not yet assigned). These are rare tumors accounting for approximately 1% of primitive CNS tumors and 15-30% of pineal gland tumors. ¹ Unique histologic features, molecular events, and levels of aggressiveness manifest as distinct categories of pineal parenchymal tumors recognized by the WHO 2022 Central Nervous System Tumours to aid in diagnostics, prognostication, and therapeutic decision-making.

Pineal tumors	Genetic Event(s)
Pineocytoma	No recurrent genetic alterations, including chromosomal gains or losses, are present in pineocytoma. ² DNA methylation reveals a distinct pineocytoma profile which clusters as its own distinct subgroup from other pineal neoplasms. ³
Pineal parenchymal tumour of intermediate differentiation (PPTID)	Small recurrent in-frame insertions of KBTBD4 are characteristic and diagnostically desirable for PPTID. ⁴ Copy-number profiles are typically flat, with some cases showing broad gains (including 1q and 8q) or losses (including 10q and 16). ^2,3 DNA methylation analysis shows PPTID as a distinct molecular class that can be further separated into two subgroups with, as of yet, unknown prognostic significance. ³
Pineoblastoma	DICER1, DROSHA, or DGCR8 mutations or copy number alterations have been described in pineoblastoma. ^3,5-8 Additional copy number events include structural alterations of chromosome 1 and losses involving chromosomes 9, 13, and 16. ^2,9-11 DNA methylation analysis segregates pineoblastoma into four subtypes with distinct genetic and clinical features: Pineoblastoma, miRNA processing-altered_1 and 2 characterized by copy-number alterations and/or mutually exclusive mutations targeting DICER1, DROSHA, or DGCR8, ^3,7,8, Pineoblastoma, RB1-altered, ^3,8 and Pineoblastoma, MYC/FOXR2-activated. ^3,8
Papillary tumour of the pineal region (PTPR)	Recurrent chromosomal imbalances include chromosome 10 loss and gains of chromosomes 4 and 9. ^12-14 Genetic alterations of PTEN have also been reported. ¹⁵ DNA methylation analysis shows PTPR as a distinct molecular subgroup that can be further separated into two subtypes with, as of yet, unknown prognostic significance. ^3,14
Desmoplastic myxoid tumour (DMT) of the pineal region, SMARCB1-mutant	Alterations affecting the SMARCB1 region on chromosome 22q11 are considered a diagnostic requirement. Other chromosomal alterations are rare and non-recurrent. ¹⁶ DNA methylation profiling reveals DMT, SMARCB1-mutant as a single distinct molecular group. ¹⁷

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	33801639	2021	Pineal Gland Tumors: A Review.	Favero G et al
2	11107183	2001	Comparative genomic hybridization in pineal parenchymal tumors.	Rickert CH et al
3	31768671	2020	Molecular subgrouping of primary pineal parenchymal tumors reveals distinct subtypes correlated with clinical parameters and genetic alterations.	Pfaff E et al
4	30877433	2019	Recurrent KBTBD4 small in-frame insertions and absence of DROSHA deletion or DICER1 mutation differentiate pineal parenchymal tumor of intermediate differentiation (PPTID) from pineoblastoma.	Lee JC et al
5	25022261	2014	Germ-line and somatic DICER1 mutations in pineoblastoma.	de Kock L et al
6	30030436	2018	Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma.	Snuderl M et al
7	31802236	2020	Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials.	Liu APY et al
8	31820118	2020	Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.	Li BK et al
9	10421270	1999	Comparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors.	Russo C et al
10	17011992	2006	Cytogenetics of pineoblastoma: four new cases and a literature review.	Brown AE et al
11	21798848	2011	Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma.	Miller S et al
12	16640646	2006	Immunohistochemical profile and chromosomal imbalances in papillary tumours of the pineal region.	Hasselblatt M et al
13	21470326	2011	Common molecular cytogenetic pathway in papillary tumors of the pineal region (PTPR).	Gutenberg A et al
14	26113311	2016	Papillary Tumor of the Pineal Region: A Distinct Molecular Entity.	Heim S et al
15	25003235	2014	PTEN mutations and activation of the PI3K/Akt/mTOR signaling pathway in papillary tumors of the pineal region.	Goschzik T et al
16	3173280	1988	[Postoperative complications of adenotonsillectomy].	Tarantino V et al
17	31732806	2020	Desmoplastic myxoid tumor, SMARCB1-mutant: clinical, histopathological and molecular characterization of a pineal region tumor encountered in adolescents and adults.	Thomas C et al

External Links

Citation

Scott Ryall, PhD

Pineal Tumors

Atlas Genet Cytogenet Oncol Haematol. 2023-03-02