Pineoblastomas (PBs) represent the most aggressive of the pineal parenchymal tumors. Routine treatment consists of operative management of obstructive hydrocephalus and cerebrospinal fluid studies followed by maximal resection and adjuvant chemotherapy/radiotherapy, resulting in a median survival of 20 months. Important prognostic factors for survival of patients with PB include extent of resection, age at presentation, disseminated disease, and craniospinal radiotherapy. Novel strategies being evaluated for the treatment of PB include high-dose chemotherapy with autologous stem cell therapy, stereotactic radiosurgery, and histone deacetylase inhibitors.
Pineal tumors comprise 1% of all primary central nervous system (CNS) neoplasms. Germ cell tumors (GCTs) are the most common pineal tumors (35%), followed by pineal parenchymal tumors (PPTs, 30%). Other less common pineal region tumors include astrocytomas and ependymomas. A new class of tumors termed papillary pineal tumors was introduced by the World Health Organization (WHO) in 2007. Among the PPTs, there are 3 major subgroups: pineocytoma (WHO grade I), PPTs of intermediate differentiation (WHO grade II/III), and pineoblastoma (PB) (WHO grade IV).
PBs comprise 25% to 50% of PPTs and are most commonly seen in children and adolescents, with an average age at diagnosis of 13 years. These tumors are considered primary neuroectodermal tumors (PNETs) of the pineal region and exhibit aggressive clinical behavior with frequent metastases throughout the craniospinal axis. Histologic analysis of PBs reveals hypercellularity, high nuclear-to-cytoplasm ratio, and frequent mitoses (17%–40%). Homer-Wright or Flexner-Wintersteiner rosettes may also be present ( Fig. 1 ). Immunohistochemical markers characteristic of PB include synaptophysin and neuron-specific enolase, along with variable staining for glial fibrillary acidic protein, chromogranin A, and neurofilaments. Recent genetic analyses of PB demonstrate several upregulated genes (UBEC2, SOX4, TERT, TEP1, PRAME, CD24, POU4F2, HOXD13) and chromosomal abnormalities (1p rearrangement, 22q loss). Standard of care in the United States includes maximal surgical resection with adjuvant craniospinal irradiation and systemic chemotherapy, resulting in a median survival of 16 to 25 months and a 5-year survival rate of 10%. This review discusses the principles of contemporary management of PB.
Clinical presentation and initial management
Patients with PB most commonly present with findings of elevated intracranial pressure (ICP) (headache, nausea/vomiting, and decreased level of consciousness) as a result of obstructive hydrocephalus from compression of the cerebral aqueduct by the tumor mass. Patients may also exhibit Parinaud syndrome (upgaze paralysis, convergence nystagmus, and near-light dissociation) as a result of compression of the dorsal midbrain structures. Focal neurologic deficits are present in approximately 25% of patients and are found incidentally in 5%.
Initial workup includes a careful neurologic history and physical examination, including a fundoscopic examination. In particular, the presence or absence of focal neurologic deficits, altered level of consciousness, papilledema, and extraocular movement abnormalities are noted. If a significant level of suspicion is present, the next step is intracranial imaging, typically brain magnetic resonance imaging (MRI) with and without contrast. Key features are the characteristics of the pineal mass (size, enhancement pattern, and solid vs cystic) as well as the presence and degree of obstructive hydrocephalus ( Fig. 2 ). Patients with signs of elevated ICP (papilledema, decreased visual acuity) and obstructive hydrocephalus should be admitted for urgent cerebrospinal fluid (CSF) diversion (see the section on Hydrocephalus treatment and CSF sampling). An important distinction among pineal masses is that of a pineal cyst, which is a common benign lesion isointense to CSF. These lesions can be followed with serial MRI scans and in most cases do not require further intervention. Given the propensity of some pineal tumors to metastasize to the spinal column (PB, ependymoma, or germinoma), a baseline contrast-enhanced MRI of the entire spinal axis should be obtained. In addition to further imaging, the presence of a pineal tumor should also prompt sampling of GCT markers (β-human chorionic gonadotropin or α-fetoprotein) from serum and/or CSF. Most commonly, CSF is obtained during the initial CSF diversion procedure (see the section on Hydrocephalus treatment and CSF sampling) and sent for GCT markers and cytology.
Hydrocephalus treatment and CSF sampling
Given that most patients with pineal tumors present with symptoms related to hydrocephalus, a common first procedure is an endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunt. Either procedure allows for both CSF sampling (important for ruling out GCTs as discussed above) and alleviation of obstructive hydrocephalus, which is the most pressing concern during acute management of patients with PB. Patients with CSF positive for GCT markers should then receive adjuvant therapy without the need for further surgical intervention. Among the CSF diversion options, most neurosurgeons prefer ETV because it offers permanent relief of hydrocephalus without indwelling hardware and the possibility of an endoscopic biopsy during the same surgical procedure.
Related posts:
On the Surgery of the Seat of the Soul: The Pineal Gland and the History of Its Surgical Approaches
Preoperative Evaluation of Pineal Tumors
Stereotactic Biopsy Considerations for Pineal Tumors
Surgical Approaches to the Pineal Region
Minimally Invasive Approaches to the Pineal Region
Contemporary Management of Pineocytoma
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