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Table of Contents    
Year : 2019  |  Volume : 67  |  Issue : 2  |  Page : 503-504

Pineal tumors: Rare but challenging entity

1 Department of Pathology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication13-May-2019

Correspondence Address:
Dr. Sujata Chaturvedi
Department of Pathology, Institute of Human Behaviour and Allied Sciences, New Delhi - 110 095
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.258023

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How to cite this article:
Chaturvedi S, Suri V. Pineal tumors: Rare but challenging entity. Neurol India 2019;67:503-4

How to cite this URL:
Chaturvedi S, Suri V. Pineal tumors: Rare but challenging entity. Neurol India [serial online] 2019 [cited 2021 Jan 27];67:503-4. Available from:

One of the last brain parts to be discovered, the pineal gland or the “third eye” got its name from its pine cone shape. Located in the deep center of the brain within a complex epithalamic anatomical compartment, the pineal gland secretes melatonin and is responsible for maintaining body's circadian rhythms. Pineal region tumors (PRTs) are rare, accounting for <1% of all intracranial neoplasms. However, the spectrum is wide with the region being involved by benign cysts, arteriovenous malformations, gliomas including tectal plate gliomas, tentorial meningiomas, choroid plexus meningiomas, germ cell tumors, papillary tumors of the pineal region (PTPRs) and even, metastases.[1] Primary neuronal tumors arising intrinsically within the pineal gland are referred to as pineal parenchymal tumors (PPTs) and constitute approximately 27% of pineal region tumors and 0.3% of all central nervous system tumors. The recent World Health Organization (WHO) classification of tumors of the central nervous system categorizes PPTs as pineocytomas (PC) grade I, pineal parenchymal tumors of intermediate differentiation (PPTID) [which can be of grade II or III] and pineoblastomas (PB) [of grade IV].[2] Though having a common origin, PPTs differ in their epidemiology and outcome. PBs arise in the pediatric population and have a high rate of recurrence and propensity for neuraxial spread. PCs and PPTIDs usually occur later in life. PCs have a favorable prognosis, and PPTIDs, as the name suggests, are an intermediate entity. PTPRs are rare neuroepithelial tumors of the pineal region, originating from the ependymal cells of subcommisural origin. They were first described in 2003, and are distinct from PPTs. PTPRs affect both children and adults, but mostly young adults in the third decade. The biologic behavior of PPTRs may correspond to grade II or III.[3] Pineal anlage tumors (PATs) are extremely rare tumors, considered as a subtype of PB and not a separate entity. PAT has been defined as a primary pineal tumor with both neuroepithelial and ectomesenchymal differentiation but without endodermal differentiation.[4]

The clinical symptoms of PPTs are the same as for other PRTs. Obstruction of the cerebral aqueduct leads to obstructive hydrocephalus manifesting as headaches, nausea, vomiting, impaired vision, oculomotor dysfunction and even loss of consciousness. Hypothalamic compression can lead to diabetes insipidus, and cerebellar encroachment to gait abnormalities. High-grade PPTs disseminate through the cerebrospinal fluid (CSF). The complex symptomatology and anatomic location warrant a multidisciplinary approach. Though certain characteristics have been defined on imaging, they are not very accurate and tissue diagnosis becomes mandatory. PCs appear rounded, well-demarcated with pushing rather than infiltrative borders, while PBs exhibit a more infiltrative appearance. Neuroimaging features of PPTID have not been clearly established. They may present as bulky masses with local invasion and may show peripheral exploded calcification. PTPRs appear as well-circumscribed, heterogeneous, solid-cystic masses. On histopathology, PCs are moderately cellular, well-differentiated with prominent pineocytic rosettes. PBs are highly cellular, have a patternless architecture, and resemble small, blue round cell tumors; PPTIDs have an intermediate appearance and exhibit two types of patterns: (i) diffuse, neurocytoma or oligodendroglioma like; and/or (ii) lobulated with vessels delineating vague lobules. Some authors have defined small and large cell subtypes of PPTIDs.[5] PTPRs are epithelial resembling tumors with papillary formations.

Given the relative rarity of PPTs in general, and PPTIDs in particular, the outcome data are largely limited to retrospective case series. Verma A et al., in their article “Primary pineal tumors – Unravelling histological challenges and certain clinical myths” published in this issue present one of the largest single-institutional studies, especially from our subcontinent. The histomorphological spectrum (including proliferation indices) of PPTs (PC, PPTIDs, and PB) and PTPRs have been meticulously described. Significant epidemiologic variations from previously published data are present in this study reported by Verma et al.,[6] in terms of the incidence of various categories of PPTs, but the authors justifiably explain it by the fact that their institute is a tertiary care referral centre. The challenging aspect of grading PPTIDs and PTPRs has been practically dealt with by Verma et al.,[6] using easily available tools. PPTID is a potentially aggressive neoplasm but definite histological criteria for grading it into II or III remain to be defined.[2] A wide range of mitotic counts have been reported. The authors, Verma et al., rightly point out that several factors related to fixation and processing affect the mitotic counts and, therefore, they have relied more on the MIB labelling index (LI).[6] Fevre-Montagne M et al., had reported a mean MIB LI of 5.2 ± 0.4 in grade II and 11.2 ± 2.0 in grade III PPTIDs.[3] Verma et al., have taken a cut off MIB LI of 10%, with grade II PPTIDs having a MIB LI 3-10% and grade III having a MIB LI ranging from 11-20%.[6] The biologic behavior of PTPRs is variable and may correspond to grade II or III but for it too, the grading criteria is yet to be established. The authors have classified the tumors with a mitotic count >5/10 high power fields (hpf) and/or MIB LI >10% as grade III. Attempt has also been made to assess the utility of immunohistochemical markers in prognosticating PPTs. Arivazhagan et al., reviewed the histological and immunohistochemical features of 33 PPTS. All PCs stained positive for neurofilament protein (NFP) while most PBs failed to show immunoreactivity with NFP. Higher chances of disease free state, irrespective of the histological subgroup, were seen in NFP positive tumors. No significant role of synaptophysin was elicited.[7] Verma et al., have reported focal NFP positivity in two cases of PB, thereby cautioning the readers about the reliability of NFP immunohistochemistry in grading PPTs. PTPRs are known to be immunoreactive for pancytokeratins (panCK) like AE1/AE3 and particularly CK18. According to Verma et al., the most important feature of PTPRs is the histological lack of fibrillary matrix with conspicuous immunonegativity for glial fibrillary acidic protein (GFAP), coupled with immunopositivity for at least one epithelial marker (CK or epithelial membrane antigen [EMA]) but without the perinuclear dot like positivity pattern.

Efforts are being made to identify prognostic factors, clinical and/or histomorphological, which determine outcome. Raleigh et al., suggested that tumor histology, including the PPTID subtype (small cell vs large cell), the extent of resection, and the neuraxial spread at diagnosis are the most important factors determining outcome.[5] In their series, Verma et al., have reported that the tumors with cytoplasmic vacuolation and prominent melanin pigmentation had an aggressive biologic behavior.[6] To identify the biologic outcome of such histology, more such documentations would be required. Similarly, the criteria of reporting according to the predominant morphology needs to be looked into. Robust outcome analyses are needed to analyze whether the biologic behavior is determined by the predominant morphology or the highest grade morphology seen. Many such areas of ambiguities exist and, maybe, high-resolution genomic analyses will be able to identify molecular markers which are able to guide therapeutic decisions. Double stranded ribose nucleic acid (RNA) specific endoribonuclease (DICER1) inactivation, microRNA deregulation, mutations in chromatin remodelling gene ARID1A and histone demethlylase gene KDM5C have been considered important in the pathogenesis of sporadic pineoblastomas but need further validation. Such markers can hold the key for differentiating various types of PPTs and also other look-alikes.

Equally complex are the treatment options with microsurgery as the standard modality but stereotactic radiosurgery, as an alternative and adjuvantive treatment to surgery for selected cases, also holds promise. Patients with malignant and/or residual grade II or grade III PPT after surgery are seen to benefit from adjuvant therapy. Intensive multimodal adjuvant therapy is recommended for patients with evidence of neuraxial dissemination, and prophylactic multimodal adjuvant therapy is recommended for all patients with PB and PPTIDs with adverse features such as subtotal resection and large cell morphology.[5] Databases such as “Surveillance, Epidemiology and End Results (SEER)” are emerging and providing inputs regarding the patient demographics, primary tumor site, tumor histology type and grade, stage at diagnosis, first course of treatment, and follow-up for determining the vital status and patient survival data regarding pineal gland tumors. In that regard, studies such as that by Verma et al., published in this journal are important not only for generating data from our region but for also highlighting the histomorphologic nuances, diagnostic approaches and challenges, which are likely to have therapeutic implications.

  References Top

Westpahl M, Emami P. Pineal lesions: A multidisciplinary challenge. Adv Tech Stand Neurosurg 2015;42:79-102.  Back to cited text no. 1
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO classification of tumours of the central nervous system. Revised 4th ed. International Agency for Research on Cancer. Lyon: World Health Organisation. Acta Neuropathol 2016;131:803-20.  Back to cited text no. 2
Fèvre Montange M, Vasiljevic A, Champier J, Jouvet A. Papillary tumor of the pineal region: Histopathological characterization and review of the literature. Neurochirurgie 2015;61:138-42.  Back to cited text no. 3
Ahuja A, Sharma MC, Suri V, Sarkar C, Sharma BS, Garg A. Pineal anlage tumour-a rare entity with divergent histology. J Clin Neurosci 2011;18:811-3.  Back to cited text no. 4
Raleigh DR, Solomon DA, Llyod SA, Lazar A, Garcia MA, Sneed PK, et al. Histopathology review of pineal parenchymal tumours identifies novel morphologic subtypes and prognostic factors for outcomes. Neuro Oncol 2017;19:78-88.  Back to cited text no. 5
Verma A, Epari S, Bakiratharajan D, Chinnaswamy G, Sahay A, Goel N, et al. Primary pineal tumours – Unravelling histological challenges and certain clinical myths. Neurol India 2019;67:491-503.  Back to cited text no. 6
  [Full text]  
Arivazhagan A, Anandh B, Santosh V, Chandramouli BA. Pineal parenchymal tumours-utility of immunohistochemical markers in prognostication. Clin Neuropathol 2008;27;325-33.  Back to cited text no. 7


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