CNS & pituitary tumors
Pineal tumors
Pineocytoma
Author: Eman Abdelzaher, M.D., Ph.D.
Editorial Board Member: P.J. Cimino, M.D., Ph.D.
Last staff update: 20 December 2024 (update in progress)
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: Pineocytoma
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Abdelzaher E. Pineocytoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorpineocytoma.html. Accessed December 21st, 2024.
Definition / general
- Well differentiated pineal parenchymal neoplasm composed of isomorphic cells typically forming large pineocytomatous rosettes
- Pleomorphic pattern shows pleomorphic cells with gangliocytic differentiation
- CNS WHO grade 1
Essential features
- Rare, well differentiated pineal parenchymal neoplasm
- Corresponds to WHO grade 1
- Mainly affects adults
- Histologically characterized by uniform cells forming large pineocytomatous rosettes
- Excellent prognosis
ICD coding
- ICD-O: 9361/1 - pineocytoma
- ICD-11: 2A00.20 & XH1K94 - tumors of the pineal gland or pineal region & pineocytoma
Epidemiology
- Rare (Surg Neurol 2003;59:250, Neuro Oncol 1999;1:14, Clin Neuropathol 2008;27:325, Brain Pathol 2000;10:49, Cancer 1993;72:870, Neuropathology 2002;22:66)
- Pineal region tumors account for < 1% of all intracranial neoplasms
- Pineal parenchymal tumors constitute ~27% of pineal region tumors
- Pineocytomas constitute ~25% of pineal parenchymal tumors
- Age: most frequently affects adults (range: 1.1 - 85 years, with a median of 44 years) (Clin Neuropathol 2008;27:325, Brain Pathol 2000;10:49, Cancer 1993;72:870, Neuropathology 2002;22:66, Ultrastruct Pathol 1994;18:69)
- Female predominance (M:F = 0.6:1)
Sites
- Pineal region
- Typically remains localized, with common compression of adjacent structures and protrusion into the posterior third ventricle
Pathophysiology
- Pinealocyte, a cell with photosensory and neuroendocrine functions, is the proposed cell of origin
- Evidence that pineocytomas are biologically linked to pinealocytes stems from the numerous ultrastructural features shared between pineocytoma cells and normal mammalian pinealocytes; in addition, pineocytomas immunohistochemically express CRX, a transcription factor involved in the development and differentiation of pineal cell lineage (PLoS One 2009;4:e7932, Am J Surg Pathol 2017;41:1410)
Etiology
- No syndromic associations or genetic susceptibilities
- Familial pineocytoma is rarely reported (Acta Neurochir (Wien) 2012;154:1413)
Clinical features
- Clinical picture is indistinguishable from other pineal region masses (Cancer 1980;45:1408, Childs Nerv Syst 1998;14:53, J Neurooncol 2010;100:255, Coll Antropol 2013;37:35, Cancer 1993;72:870)
- Signs and symptoms related to increased intracranial pressure due to aqueductal obstruction
- Neuroophthalmological dysfunction due to compression of the tectal plate (e.g., impairment of upward gaze [Parinaud syndrome])
- Brainstem or cerebellar dysfunction
- Long interval between onset of symptoms and surgery (Cancer 1980;45:1408)
Diagnosis
- Neuroimaging (Neuroradiology 2000;42:509)
- Biopsy
- WHO essential diagnostic criteria
- Demonstration of pineal parenchymal differentiation by histopathological and immunophenotypic features (e.g., positivity for synaptophysin)
- Absence of criteria qualifying for the diagnosis of pineal parenchymal tumor of intermediate differentiation or pineoblastoma
- Low proliferative / mitotic activity
- Pineal region location
Radiology description
- Computed tomography (CT)
- Hypodense, globular, well delineated masses (J Comput Assist Tomogr 1995;19:509)
- May show calcification
- Magnetic resonance imaging (MRI)
- Well circumscribed mass
- Tumor size: usually < 3 cm (Cancers (Basel) 2022;14:3646)
- T1 weighted: hypointense or isointense
- T2 weighted: hyperintense
- Strong homogeneous contrast enhancement (Neuroradiology 2000;42:509)
Radiology images
Images hosted on other servers:
Hydrocephalus
Brain CT
Prognostic factors
- Excellent prognosis (5 year survival rate ranges from 86% to 91%) (Int J Radiat Oncol Biol Phys 2000;46:959, Cancer 1996;78:2564)
- Extent of surgical resection is the major prognostic factor (J Neurooncol 2010;100:255)
- Not associated with cerebrospinal fluid seeding (Int J Radiat Oncol Biol Phys 2000;46:959)
- Pleomorphism in pleomorphic pineocytoma is prognostically insignificant
Case reports
- Young girl with coincident pineocytoma and probable brainstem glioma (BMJ Case Rep 2022;15:e249232)
- 51 year old woman with pineocytoma associated with hemorrhage (Int Med Case Rep J 2022;15:307)
- 58 year old man with malignant transformation of pineocytoma and leptomeningeal metastasis (Indian J Pathol Microbiol 2023;66:141)
- 72 year old man with mixed pineocytoma / pineoblastoma (Acta Neurochir (Wien) 2002;144:389)
Treatment
- Surgical resection
Gross description
- Well circumscribed
- Cut surface: grayish tan, homogeneous or granular (Cancer 1980;45:1408, Brain 1979;102:289, Brain Tumor Pathol 1999;16:1)
- Degenerative changes may occur (e.g., cystic change and hemorrhage) (Hum Pathol 1995;26:20)
Gross images
Images hosted on other servers:
In toto removal
Distorted rostral brain stem
Microscopic (histologic) description
- Well differentiated and moderately cellular
- Growth pattern
- Arranged primarily in sheets with a stromal delicate network of vascular channels supported by scant reticulin fibers
- Typical: large, irregular, pineocytomatous rosettes formed of peripheral nonregimented tumor cells surrounding anucleate centers composed of delicate, enmeshed tumor cell cytoplasmic processes resembling neuropil (Cancer 1980;45:1408, Brain Pathol 2000;10:49, J Cancer Res Clin Oncol 1994;120:683, Cancer 1993;72:870)
- Poorly defined lobules may be seen
- Tumor cells
- Uniform and relatively small (resembling pinealocytes)
- Nuclei are round to oval, with inconspicuous nucleoli and stippled chromatin
- Cytoplasm is scant to moderate and homogeneously eosinophilic
- Processes are conspicuous and end in club shaped expansions (demonstrated by neurofilament immunostaining or silver impregnation)
- Some cases show a pleomorphic cytological pattern (pleomorphic pineocytoma) characterized by large ganglion cells or multinucleated pleomorphic giant cells (Brain Pathol 2008;18:354, Acta Neuropathol 1994;88:448, Hum Pathol 1995;26:20, Cancer 1993;72:870)
- Occasional: microcalcifications (usually corresponds to calcifications of the residual pineal gland)
- Mitotic figures are rare or absent, including pleomorphic cases (Brain Pathol 2000;10:49, Neuropathology 2012;32:647, Brain Pathol 2008;18:354)
Microscopic (histologic) images
Contributed by P.J. Cimino, M.D., Ph.D. and Eman Abdelzaher, M.D., Ph.D.
Rosettes
Pleomorphic cells
Synaptophysin
GFAP
Olig2
Ki67
Virtual slides
Images hosted on other servers:
Pineocytoma in a 32 year old man
Cytology description
- Smear preparation
- Numerous single cells and small tissue fragments
- Uniform cells with isomorphic round nuclei and delicate cytoplasmic processes (Cancer 2005;105:80, Neupsy Key: Neoplasms of the Pineal Gland [Accessed 8 October 2024])
- Perivascular arrangement of tumor cells with formation of tight, branching papillary-like structures (Cancer 2005;105:80)
- Well formed rosettes (Cancer 2005;105:80)
- Background shows numerous naked tumor cell nuclei resembling lymphocytes
- No mitotic figures, no tumor necrosis (Cancer 2005;105:80)
Cytology images
Images hosted on other servers:
Smear preparation
Monomorphic round nuclei
Well formed rosette
Positive stains
- Synaptophysin: strong and diffuse, especially in the pineocytomatous rosettes (Clin Neuropathol 1992;11:298, Brain Pathol 2008;18:354)
- NSE: strong (Clin Neuropathol 1992;11:298, Brain Pathol 2008;18:354)
- NFP: strong, especially in the pineocytomatous rosettes; highlights ganglionic differentiation in pleomorphic pineocytoma (Brain Pathol 2008;18:354)
- Other neuronal markers (e.g., class III β tubulin, the microtubule associated protein tau, chromogranin A and the neurotransmitter serotonin [5-HT]): variable staining (Clin Neuropathol 1992;11:298, Acta Neuropathol 1994;88:334, Brain Pathol 2000;10:49, Acta Neuropathol 1994;88:448, J Cancer Res Clin Oncol 1994;120:683, Neuropathology 2002;22:66)
- CRX (100%) (PLoS One 2009;4:e7932, Am J Surg Pathol 2017;41:1410)
- Mean Ki67 proliferation index is < 1% (Neuropathol Appl Neurobiol 2012;38:87, Neuropathology 2012;32:647, Cancers (Basel) 2022;14:3646)
Negative stains
- GFAP: positive in reactive astrocytes (Brain Pathol 2008;18:354, Neuropathology 2002;22:66, Acta Neuropathol 1998;95:532, Pathol Res Pract 2006;202:85)
- S100 (Acta Neuropathol 1998;95:532)
- CD34 (Brain Pathol 2008;18:354)
- FOXJ1 (Am J Surg Pathol 2017;41:1410)
Electron microscopy description
- Pineocytoma cells share numerous ultrastructural features with normal mammalian pinealocytes with evidence of neurosensory differentiation (e.g., the presence of vesicle crowned rodlets, cilia [9+0] and fibrous filaments) (Acta Neuropathol 1998;95:532)
- Pineocytoma is composed of clear cells and various numbers of dark cells joined with zonulae adherens (Acta Neuropathol 1983;62:31, Brain 1979;102:289, Acta Neuropathol 1994;88:334, Ultrastruct Pathol 1994;18:69)
- Relatively abundant cytoplasm with well developed organelles
- Tapering cytoplasmic processes terminating in bulbous ends with occasional synapse-like junctions
- Membrane bound, dense core granules and clear vesicles are present in the cytoplasm and cellular processes
Electron microscopy images
Images hosted on other servers:
Premature synapse-like structure
Molecular / cytogenetics description
- No recurrent genetic alterations (Genes Chromosomes Cancer 2001;30:99)
- Has distinct DNA methylation profile, grouped within a distinct subgroup in close proximity to normal pineal gland tissue (Acta Neuropathol 2020;139:243)
- Has high expression of genes coding for enzymes related to melatonin synthesis and genes related to phototransduction in the retina (OPN4, RGS16 and CRB3) (J Neuropathol Exp Neurol 2006;65:675)
- No KBTBD4 alterations (Acta Neuropathol 2020;139:243, Acta Neuropathol 2019;137:851)
Videos
Pineocytoma with ganglion cell differentiation
Sample pathology report
- Pineal region mass lesion, gross total resection:
- Pineocytoma
- CNS WHO grade 1
Differential diagnosis
- Normal pineal gland:
- Conspicuous lobular architecture
- No pineocytomatous rosettes
- Pineal cyst:
- Typical layered architecture of pineal cyst wall composed of
- Inner GFAP positive piloid gliotic layer without ependymal or epithelial lining, often with Rosenthal fibers
- Outer synaptophysin / NFP positive pineal parenchymal layer with lobular architecture and no pineocytomatous rosettes
- Distinction may be difficult in small specimens, especially when the pineal parenchyma is distorted and has lost its normal lobular architecture
- Typical layered architecture of pineal cyst wall composed of
- Pineal parenchymal tumor of intermediate differentiation:
- Increased proliferative / mitotic activity
- KBTBD4 alterations (Acta Neuropathol 2020;139:243, Acta Neuropathol 2019;137:851)
- Pineoblastoma:
- Mostly occurs in children
- Highly cellular
- No pineocytomatous rosettes
- Mitoses, necrosis
- Staining for NFP is less frequent than in pineocytomas (Acta Neurochir (Wien) 2002;144:389)
- High Ki67 index
- Ganglioglioma:
- Neoplastic glial component
- Tumoral CD34 expression
- BRAF p.V600E mutation
- Papillary tumor of pineal region:
- Vague epithelial features
- Cytokeratins positive, especially CK18 (Neuropathol Appl Neurobiol 2006;32:278, J Neuropathol Exp Neurol 2006;65:1004, Ann Clin Lab Sci 2011;41:174, J Clin Neurosci 2011;18:1007)
- Synaptophysin: negative or focal and weak (J Clin Neurosci 2011;18:1007, J Neuropathol Exp Neurol 2006;65:1004, Neuropathol Appl Neurobiol 2006;32:278)
- FOXJ1 positive (Am J Surg Pathol 2017;41:1410)
- Germ cell tumors:
- Distinctive morphology of different subtypes
- Immunoreactivity for germ cell markers (e.g., SALL4) (J Clin Neurosci 2011;18:1007)
- Metastatic carcinoma:
- Epithelial features
- Positive for cytokeratin and epithelial membrane antigen
- Mitoses, necrosis
- Neurocytoma:
- Nearly identical histologically
- Differentiated by location
Additional references
Board review style question #1
A 44 year old woman presented with a headache and impairment of upward gaze. MRI showed a well circumscribed enhancing pineal region mass lesion. Gross total resection of the mass was done and the histopathological features of the lesion are shown in the figure above. Immunohistochemistry showed diffuse strong positive reaction for synaptophysin and a low proliferative index by Ki67 (1%). Which of the following is the most likely diagnosis?
- Papillary tumor of the pineal region
- Pineal parenchymal tumor of intermediate differentiation
- Pineoblastoma
- Pineocytoma
Board review style answer #1
D. Pineocytoma. Pineocytoma is histologically characterized by the formation of large pineocytomatous rosettes and is diffusely and strongly positive for synaptophysin. Proliferative activity is low. Answer A is incorrect because papillary tumor of the pineal region is characterized by a papillary growth pattern with epithelial-like cells and is negative or only focally and weakly positive for synaptophysin. Answer B is incorrect because pineal parenchymal tumors of intermediate differentiation feature increased proliferative activity. Answer C is incorrect because pineoblastoma predominately affects children. Histologically, it is a highly cellular tumor resembling embryonal tumors with a high proliferative activity.
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Reference: Pineocytoma
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Board review style question #2
Which of the following is typical of pineocytomas?
- Frequent leptomeningeal dissemination
- Immunonegative for synaptophysin
- Pineal region location
- Predominates in children
Board review style answer #2
C. Pineal region location. Pineocytomas are located in the pineal region. Answer A is incorrect because pineocytomas do not cause leptomeningeal dissemination. Answer B is incorrect because pineocytomas are typically immunoreactive for synaptophysin. Answer D is incorrect because pineocytomas mainly affect adults.
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Reference: Pineocytoma
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Reference: Pineocytoma
