Solitary fibrous tumor in the pineal region: A series of 5 cases and literature review

Abstract

INTRODUCTION

Solitary fibrous tumors (SFTs) are rare fibroblastic neoplasms that arise in multiple regions of the body and have the potential for malignant behavior and high rates of recurrence.^1,2 Although central nervous system (CNS) SFTs were once considered histologically distinct from hemangiopericytomas (HPCs), the identification of the NAB2::STAT6 gene fusion due to a shared inversion at chromosome 12q13 present in both SFTs and HPCs has resulted in the re-classification of these 2 tumor entities into a single term of SFT with the 2021 WHO classification system of CNS tumors.^3–5 The histologic features of SFTs are heterogeneous, ranging from hypocellular variants to hypercellular presentations showing “patternless patterns” of alternating cellularity with collagenous stroma and thin-walled, staghorn-shaped blood vessels.^3,6 With this wide range of morphology comes a somewhat unpredictable behavior, although stratification criteria based on mitotic activity and degree of necrosis, along with clinical factors such as tumor size and patient’s age, continue to evolve in their ability to predict prognosis.^7–9

SFTs most frequently occur within the pleura, soft tissue, muscle and cranium.¹ SFTs constitute <1% of all CNS tumors but have been reported widely along the neuraxis, with most tending to be dural-based and occurring within the cranium (80%) or spine (20%).^10–12 They demonstrate a slight predilection for supratentorial over infratentorial locations. Non-dural based locations include the skull base, sellar region, and pineal region. Although pineal SFTs have been described in the literature since Olson and Abell (1969), the rarity of this tumor occurring in the pineal region makes predicting behaviors and directing treatment difficult.¹³ We aim to summarize the diverse clinical and histopathological findings of pineal SFTs reported thus far in the literature and present 5 new cases of pineal SFTs from our institutions to further elucidate the clinical presentation, histologic features, treatment modality and outcomes. In particular, we highlight the first case of a pineal region SFT with extracranial metastasis.

METHODS

We retrospectively reviewed medical charts and electronic medical records within the neuropathology and neurosurgery divisions at Dartmouth-Hitchcock Medical Center (1994-2024) and Columbia University Irving Medical Center (1969-2019). From these records, we reviewed clinical notes, operative reports, imaging, and pathology reports for each identified case. The following data were collected for each case: (1) demographics, (2) clinical presentation, (3) imaging, (4) treatment and outcomes. Slides and tissue blocks from 3 cases (including the index case from Dartmouth-Hitchcock Medical Center) were available for review. For these 3 cases, a whole exome-based sequencing assay was performed.¹⁴ The Foundation One CDx (Cambridge, MA) assay was also performed on one of the intracranial metastases resected from the index case.

In addition, we performed a review of the literature according to Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines to identify reported cases of SFT/HPC arising in the pineal gland. We searched PubMed for publications describing pineal SFT and/or HPC tumors given the relatively recent reclassification of these previous distinct diagnoses into 1 entity. Of the results, 22 articles were deemed relevant to this study. Two publications from these search results were excluded as the full texts were unable to be accessed in the English language. One additional published abstract was excluded as it did not contain sufficient detail describing the tumor presentation, histology or outcome. The following data were collected, when available, from each of the remaining 19 articles, each presenting a single case of pineal SFT/HPC: (1) patient demographics, (2) clinical presentation, (3) imaging findings, (4) histology findings, (5) treatment and longitudinal outcomes.

RESULTS

We retrospectively reviewed all pineal region lesions resected at Dartmouth-Hitchcock Medical Center over a 30-year period between 1994 and 2024. A total of 34 lesions were identified. These included 16 pineal parenchymal tumors (47.1%), 6 germ cell tumors (17.6%), 5 cysts (14.7%), 3 glial neoplasms (8.8%), 3 meningiomas (8.8%), 1 metastasis (2.9%), and 1 SFT (2.9%). Since no additional SFTs were identified, we then examined the large cohort of patients surgically treated for pineal region lesions at Columbia University Irving Medical Center over a 50-year period between 1969 and 2019.^15,16 Four additional patients with SFT in the pineal region were found (Table 1). The mean age at initial surgical diagnosis of a pineal region SFT for the 5 patients was 40.6 years (range 26-53 years), with a 2:3 male-to-female ratio. MRI showed large contrast enhancing masses in the pineal region, averaging 4.65 cm in greatest diameter. Gross total resection (GTR) was performed in 4 patients. Microscopic examination of the tumors revealed densely cellular tumors with variable amounts of branching, thin-walled blood vessels and fibrous tissue. Given the varied clinical courses and extensive follow-up for these 5 patients, we describe each patient in detail below.

Case 1

The patient was a 48-year-old woman who presented with dizziness, nausea, ataxic gait, and imbalance. MRI showed a 2.2 × 4.4 × 3.3 cm mass in the pineal region with mass effect on the cerebellum and hydrocephalus (Figure 1B and C). She underwent a GTR, followed by radiation to a total of 63 Gy. The tumor cells appeared jumbled in dense sheets, with irregularly round and hyperchromatic nuclei. Neoplastic cells were separated by numerous small, thin-walled blood vessels. Seven mitotic figures per 10 high-powered fields (HPF) were observed in the most worrisome fragments without any observable areas of necrosis (Figure 1A). CD34 was variable, with some regions showing dense positivity. Epithelial membrane antigen (EMA) was negative in tumor cells (not shown). Whole exome sequencing (DH-CancerSeq assay) did not reveal any pathogenic alterations (not shown).

Figure 1.

Index case of patient with pineal region solitary fibrous tumor (SFT) that metastasized intracranially and to lung. (A) H&E-stained section of a pineal region SFT shows a densely cellular neoplasm with relatively little fibrous tissue. (B, C) Pre-operative MRI showing a mass in the pineal region measuring 2.2 × 4.4 × 3.3 cm. (D) H&E-stained section of recurrent SFT shows highly cellular tumor with morphology similar to original tumor. (E, F) MRI showing a 0.8 × 0.9 × 1.3 cm enhancing lesion along the left paramedian falx, presenting 6 years from original tumor resection. (G) H&E-stained section of highly cellular tumor. (H) Strong and diffuse nuclear STAT6 immunostaining. (I) MRI showing a 1.5 cm recurrent lesion along the posterior falx, presenting 11 years from original tumor resection. (J) H&E-stained section of metastatic SFT [T] adjacent to normal [N] lung parenchyma. (K) Diffusely positive STAT6 staining in tumor [T] tissue, with scant STAT6 positive cells infiltrating normal [N] parenchyma. (L) CT scan shows 0.7 cm right upper lobe lung nodule, 12 years from original diagnosis.

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Seven years later, asymptomatic surveillance MRI showed a new 8 × 9 × 13 mm enhancing lesion along the left paramedian falx (Figure 1E and F). Given concern for intracranial metastasis, the patient underwent a second GTR followed by 54 Gy radiation. The resected specimen consisted of densely packed, small, polygonal tumor cells that resembled the pineal region tumor. There was a brisk mitotic rate (up to 4 mitotic figures per 10 HPF) without necrosis. Numerous small diameter blood vessels were scattered through the tumor (Figure 1D), and CD34 staining was positive in blood vessels and tumor cells (not shown). Four years after that, asymptomatic surveillance MRI showed a new 1.5 cm enhancing mass along the left posterior falx (Figure 1I). She underwent a GTR and subsequent fractionated radiosurgery to a total of 27 Gy to the surgical bed. Hematoxylin and eosin (H&E)-staining of this resection specimen resembled the 2 prior tumors. 13 mitoses in 10 HPF were observed without necrosis (Figure 1G). Strongly positive STAT6 in tumor cells (Figure 1H) confirmed the diagnosis of SFT. Interestingly, a NAB2::STAT6 fusion was not identified with the FoundationOne CDx sequencing assay (not shown).

The following year, the patient underwent a wedge resection of a 7 mm nodule in the right lung apex that was seen on staging PET-CT (Figure 1L). The tumor was similar morphologically (Figure 1J) and immunophenotypically to the intracranial lesions. The tumor was positive for STAT6, confirming the diagnosis of extracranial metastatic SFT (Figure 1K). A further spine MRI showed metastatic nodules on the spinal cord at C7-T1 without evidence of leptomeningeal disease and negative CSF. The nodules were treated with radiation to 30 Gy. The patient remains well without further recurrence at the time of this report.

Case 2

The patient was a 53-year-old man who presented with complaints of difficulty writing, vision changes and balance issues for the prior 7 months. An MRI performed at an outside hospital showed a heterogeneously enhancing, solid and cystic, pineal region mass measuring 5.6 × 5.2 × 3.7 cm (not shown). He underwent a stereotactic guided right parietal craniotomy with inter-hemispheric approach for a radical subtotal tumor resection with external ventricular drain placement. The tumor grossly appeared quite vascular, with firm areas adherent to the tentorium and soft areas at the dorsal surface of the tumor. Microscopic examination showed a neoplasm comprised of densely packed spindle cells with intervening staghorn and ectatic blood vessels and fibrous bands (not shown). Necrosis was absent, and mitotic figures were rare (less than 1 per 10 HPF). The tumor cells were positive for CD34, BCL-2, and STAT6 (not shown). The Ki67 proliferation index was low, with ∼3%-5% of all cells staining positive (not shown). Sequencing of this tumor revealed a NAB2 exon 4::STAT6 exon 2 fusion that correlates with classic SFT morphology.¹⁷ Five months after the tumor resection, a small enhancing nodule was seen at the falcotentorial junction on surveillance imaging (not shown), consistent with residual tumor. Gamma knife radiosurgery, with administration of 16 Gy, was performed. The patient is alive 12 years after initial presentation.

Case 3

The patient was a 51-year-old woman who had a nondiagnostic biopsy of a periventricular mass at age 46. Three years later, an MRI showed a large multicystic and enhancing lesion centered in the atrium of the right lateral ventricle with extension into the right parietal lobe. This enhancing mass extended into the posterior aspect of the third ventricle and enveloped the pineal gland. The inferior extent of this lesion was at the level of the sylvian aqueduct within the midbrain, where there was a solid 2.0 cm nodule on the right paramedian side (not shown). Only the mass from the trigone occipital horn was removed and eventually diagnosed as a SFT (not shown). She was treated with adjuvant chemotherapy (cisplatin and another agent for 3 cycles), followed by VP shunt placement for hydrocephalus at an outside hospital. She developed leg weakness, diplopia, and confusion.

MRI revealed an enlarging heterogeneous cystic mass in the pineal region that was then partially removed via a suboccipital craniotomy with a supracerebellar infratentorial approach. Microscopic examination showed alternating highly cellular areas and loose areas, resembling the portion of tumor resected from the trigone occipital horn. Two mitoses in 10 HPF were identified, and there was no necrosis.

Three months after this resection, she presented with progressive gait ataxia, headache, and cognitive difficulty. Upon physical examination, she exhibited signs of Parinaud syndrome; her gait was somewhat wide-based and she had difficulty with tandem walking. MRI showed an increase in size of the pineal region mass (not shown). She underwent placement of a right VP shunt. She reportedly received fractionated radiation therapy at an outside hospital (5760 cGy). Five years later, she underwent gamma knife stereotactic radiosurgery surgery (20 Gy) to a left ventricular horn lesion. One month later, MRI showed an 8 mm round, enhancing lesion at the frontal horn of the left lateral ventricle. Additionally, there was abnormal enhancement along the right parietal resection cavity, extending into the right lateral ventricle and the pineal region. A stereotactic guided right parietal craniotomy with GTR of the recurrent tumor was performed. Microscopic examination revealed a highly cellular neoplasm interrupted by variably ectatic, thin-walled branching blood vessels and areas of fibrosis (Figure 2A). In some areas, the tumor cells were spindle-shaped (Figure 2B) and in other areas, they were ovoid (Figure 2C). Mitotic activity was elevated, with up to 8 mitoses in 10 HPF, and necrosis was present. The Ki67 proliferation index was elevated to 30% (Figure 2D). Sequencing of this tumor revealed a NAB2 exon 6::STAT6 exon 16 fusion that correlates with poor outcomes.¹⁷

Figure 2.

Histologic characteristics of a solitary fibrous tumor that spread to the pineal region. (A) Low-magnification H&E-stained section showing a highly cellular neoplasm interrupted by variably ectatic, thin-walled blood vessels and areas of fibrosis. (B) In some foci, the neoplastic cells are spindle-shaped with ill-defined borders. A mitotic figure is present in the center of the micrograph. (C) In other areas, the neoplastic cells are closely packed, oval-shaped and contain relatively little cytoplasm. A mitotic figure is present in the center of the micrograph. (D) The Ki67 proliferation index is ∼30%.

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Two years later, she had 2 lesions in the third ventricle, 1 posteriorly and 1 more anteriorly that had progressed from previous scans (not shown). She was administered 20 Gy of radiation for both lesions. Fifteen months later, she had an additional lesion in the tentorium and one in the left ventricle. She underwent gamma knife radiosurgery (16 Gy for both lesions). Over the next 2 years, she had significant regrowth along the right brainstem margin. On her imaging, the lesion measured 3.4 cm in diameter at the level of the tentorial incisura (not shown). She underwent gamma knife radiosurgery-13 Gy for the right temporal lesion, 12 Gy for the right ponto-medullary lesion, and 10 Gy for a chiasm lesion. Despite these treatments, she passed away 6 months later at the age of 63.

Case 4

The patient was a 44-year-old man with history of resection of a pineal neoplasm at an outside hospital (diagnosed as angioblastic meningioma vs HPC) at the age of 28.¹⁸ He had 5 years of annual imaging scans that did not reveal any tumor. Eleven years after the termination of surveillance scans, he had mild mental confusion with short-term memory loss, and mild difficulty with incoordination. A CT scan showed hydrocephalus (not shown), and a VP shunt was placed. He underwent a GTR of the recurrent pineal region mass. Microscopic examination reportedly revealed a highly cellular spindle cell neoplasm vascularized by a rich network of capillaries. The nuclei of the neoplastic cells contain coarsely clumped chromatin and occasional inconspicuous nucleoli. There were rare mitotic figures, and no areas of necrosis were identified (not shown). Three years later, a follow-up MRI showed a 1 × 1 cm nodular, enhancing mass lateral to the intraoperative area (not shown), and he was treated with gamma knife radiosurgery. He passed away 19 years later, at the age of 66.

Case 5

This 26-year-old woman presented with progressively worsening headache and neck pain that began 5 months earlier. She had bouts of nausea and vomiting 2 months before hospital admission. An MRI showed a pineal region mass 5 cm in greatest dimension with hydrocephalus (not shown). On examination, there was some mild papilledema with intact extraocular movements and mild light near dissociation. A VP shunt was placed. Six days later, she underwent a right parietal craniotomy with an inter-hemispheric approach to the tumor. The mass seemed to originate just below the straight sinus and attached to both sides of the tentorium. It compressed the cerebellum, quadrigeminal plate, and pushed the corpus callosum forward and superiorly. The mass was somewhat reddish in color and there were parts that were fibrous and others that were somewhat soft (not shown). A GTR was performed. Microscopic examination reportedly revealed a moderately cellular, highly vascular neoplasm containing a proliferation of small capillaries to larger, ectatic vessels, many of which had a staghorn appearance. The neoplastic cells had ovoid to spindle-shaped nuclei and eosinophilic cytoplasm with poorly defined borders. Up to 8 mitotic figures in 10 HPF were identified. There was no tumor necrosis. While vimentin was expressed diffusely in the tumor cells, cytokeratin and EMA were focally expressed (not shown). Postoperatively, her only deficit was gait ataxia that improved considerably by the time of her discharge.

A follow-up scan 15 months later showed a recurrence along the vein of Galen, to the right of the pineal gland, at the medial aspect of the tentorium, measuring under 2 cm in size. She underwent radiosurgery, with a total of 2000 cGy to the 80% isodose line delivered in 5 arcs. Three years later, a routine follow-up MRI showed new recurrence outside of the stereotactic field. She was treated with external beam radiation therapy to a total dose of 5400 cGy. Over the next 2 years, she had right-sided trigeminal neuralgia which eventually led to a diagnosis of multiple sclerosis. Thirteen years after her initial presentation, she was found unresponsive. CT revealed hemorrhage in the quadrigeminal plate, involving the rest of midbrain, upper pons and ventricular system. She remained in a vegetative state and passed away 1 year later.

DISCUSSION

SFTs are uncommon intracranial neoplasms based primarily in supratentorial dura that have a propensity for recurrence and metastasis. Due to the rarity of pineal region SFTs, the epidemiology, pathology, treatment, and outcome for these patients are poorly understood. We report the clinical course of a 48-year-old woman with a pineal region SFT who subsequently developed metastatic left para-falcine parieto-occipital and right lung upper lobe SFTs over the next 12 years. Examination of the Dartmouth-Hithcock cohort of 33 additional pineal region lesions did not reveal additional SFTs. Therefore, we reviewed the larger Columbia University Irving Medical Center cohort of pineal region lesions and found 4 additional SFT cases (Table 1). All patients underwent surgical resection of their primary tumors, with 4 cases achieving GTR and 1 with subtotal resection (STR) of tumor. The patient with residual tumor was treated with gamma-knife radiosurgery and no known recurrence at the time of this publication. The remaining 4 cases, however, had recurrences. Three patients are deceased, with overall survival of 14, 14.5, and 22 years after initial resections of their pineal region masses at CUIMC.

Our literature search identified 19 previously reported patents with SFTs involving the pineal region (Table 2).^13,19–36 This cohort included 9 male patients and 10 female patients, with age ranging from 24 to 80 years at initial presentation with a mean age of 43.6 years. Eighteen of these cases have clinical, imaging, treatment and/or outcome data available. The most common presenting symptom was headache, present in all patients. Second most common was nausea/vomiting (8/18 cases), followed by vision changes (6/18 cases). Resection was performed as the initial treatment in 17/18 cases, with 9 cases being reported as GTR and 8 STR cases. 4 GTR patients and 4 STR patients also received adjuvant radiation therapy. Tumor recurrence occurred in 7 cases, although this number may be an underestimation as follow-up data was not available for 3 cases. In addition, for several published cases, follow-up time was limited.

As a whole, intracranial SFTs have an age-adjusted incidence rate of 3.77 per 10 000 000 people.³⁷ Typical presenting symptoms of intracranial SFTs, such as papilledema, headaches, hemiparesis, gait disturbance and ataxia, are largely due to mass effects and increases in intracranial pressure.³⁸ There are no radiologic findings specific to intracranial SFTs, posing a challenge in differentiating them from other dural-based lesions such as meningiomas. Like meningiomas, SFTs may have thickened dural “tails” and bony erosion on imaging; however, they typically do not have intratumor calcification or adjacent skull hyperostosis as compared to meningiomas.³⁹ Furthermore, a meta-analysis completed by El-Abtah et al. (2023) reported that features of SFTs on preoperative MRIs including a higher apparent diffusion coefficient, lack of dural tail, presence of narrow-based dural attachments, less peritumoral edema, and serpentine flow voids can be used to differentiate them from meningiomas.⁴⁰ Generally, the most prominent imaging feature of SFTs is their intense contrast enhancement on both CT and MRI, largely due to their increased vascularity.^41,42 On pre-contrast CT, tumors often appear as sharply demarcated, heterogeneous iso-attenuating masses. Appearance on MRI is variable, although SFTs often appear isointense to slightly hyperintense on T1 weighted images, and hyperintense or mixed intensity on T2 weighted images.¹² This variability is attributable to the heterogeneity of the tumors themselves, with low-grade tumors having higher amounts of collagenous stroma and high-grade tumors displaying hypercellularity and hypervascularity.⁴²

Solitary fibrous tumors display a spectrum of histology, ranging from a hypocellular phenotype with abundant stromal collagen to a hypercellular phenotype with little to no stroma and possible focal areas of necrosis. Compared to meningiomas, SFTs lack psammoma bodies, calcifications and nuclear pseudoinclusions.⁴³ Per 2021 WHO CNS classification, CNS WHO grade 1 tumors have a mitotic count <5 per 10 HPF, CNS WHO grade 2 tumors ≥5 mitoses per 10 HPF without necrosis and CNS WHO grade 3 tumors ≥5 mitoses per 10 HPF with necrosis. Furthermore, CNS WHO grade 1 tumors typically are highly collagenous with low cellularity, with increasing cellularity, less fibrosis and associated “staghorn” vasculature being seen in higher grade tumors.⁴⁴ SFTs have the potential for a phenomenon known as sequential deterioration; that being recurrent or metastatic lesions demonstrating an ability for de-differentiation and progression in malignancy with more proliferative and higher grade features as compared with their primary tumors.³²

Immunohistochemistry is crucial in distinguishing SFTs from other intracranial tumors such as meningiomas. SFTs show strong immunoreactivity for CD34, CD99, BCL-2, and vimentin; however, these markers are less specific and sensitive to SFTs than STAT6.^45,46 SFTs typically are EMA-, S-100-, cytokeratin-, and desmin-negative.^12,43 In the pineal region, pineal parenchymal tumors can be distinguished from SFTs by the presence of neuroendocrine differentiation in the former.⁴⁷ The presence of the NAB2::STAT6 gene fusion, which can be assessed by detection of nuclear immunoreactivity for STAT6, is highly specific and sensitive for SFT.^5,48

Many different breakpoints in NAB2 and in STAT6 have been identified in SFTs, leading to different fusion transcripts. One family of fusion transcripts involves NAB2 exon 5, 6, or 7 fused to STAT6 exon 16 or 17 (the STAT6 transactivation domain). Another family involves NAB2 exon 4 fused to STAT6 exon 2 or exon 3.¹⁷ In extracranial SFTs, there are associations between fusion type and SFT clinicopathologic features (reviewed in Ren et al.⁴⁹), In a recently published multi-institutional cohort of patients with meningeal SFT, tumors with the NAB2 exon 4::STAT6 exon 2-3 fusions exhibited a hypocellular fibrous phenotype while tumors with patients with NAB2 exon 5-7::STAT6 exon 16-17 fusions had shorter metastasis-free survival.¹⁷ In potential support, our patient with predominantly fibrous morphology and no recurrence had a NAB2 exon 4::STAT6 exon 2 fusion (patient #2, Table 1). One of our patients with multiple recurrences had a NAB2 exon 6::STAT6 exon16 fusion (patient #3, Table 1). Interestingly, 12% of tumors in the multi-institutional cohort did not have a NAB2::STAT6 fusion.¹⁷ In our cohort, the patient with metastasis to the lung, a NAB2::STAT6 fusion was not identified in either the original pineal tumor or the second recurrence despite high STAT6 expression (patient #1, Table 1 and Figure 1).

Prior studies have demonstrated variable overall survival (OS) data for intracranial SFTs.³⁷ Shin et al. (2021) reported a significantly longer OS in low-grade tumors as compared to high-grade tumors, with median OS of 218 months for CNS WHO grade 1 tumors compared to 105 months for CNS WHO grade 3 tumors.⁴⁴ Similarly, Kim et al. (2018) reported patients with lower-grade tumors (CNS WHO grades 1 and 2) had an OS of 220.8 months, and patients with grade 3 tumors had an OS of 194.8 months.⁵⁰ Surgery is the mainstay of SFT treatment, specifically GTR when possible, given the improved survival as compared to STR or stereotactic surgery.^2,11,37 The role of adjuvant radiotherapy is less definitive, although generally utilized especially in cases of STR or for high-grade tumors. A meta-analysis by Rutkowski et al. (2010) reported that the use of post-operative radiotherapy following GTR had no survival advantage compared to GTR alone.⁵¹ Conversely, several more recent studies, including a 2017 meta-analysis by Ghose et al. and a 2023 meta-analysis by Kwon et al. have demonstrated improved survival with use of adjuvant radiation.^52,53

Intracranial SFTs have been characterized by their high rates of recurrence, seen in up to 40% of cases, and potential for extraneural metastasis.^2,54,55 Our case of extracranial metastasis to lung of a pineal region SFT is the first reported case originating from the pineal region. Given the potential for extracranial metastasis, common sites of metastasis such as lung, abdomen and bone should periodically be imaged. At this time, there are no clear guidelines for surveillance, with follow-up imaging protocols being largely institution specific.

In summary, we present a comprehensive literature review of 19 previously reported cases of SFTs in the pineal region, with an additional presentation of 5 new cases from our own institutions, including the first known case with extracranial metastasis. The standard of care treatment option for these tumors is gross total surgical resection when possible, supplemented by adjuvant radiation therapy for high-grade tumors and gamma knife radiosurgery. Histologic features of increased mitotic activity and presence of necrosis correlate with aggressive tumor behavior and worse prognosis. Although rare, SFTs should be considered in the differential diagnosis of pineal region tumors.

FUNDING

The authors acknowledge the support of the Clinical Genomics and Advanced Technology Section in the Department of Pathology and Laboratory Medicine of the Dartmouth Hitchcock Health System and the Pathology Shared Resource (RRID: SCR_023479) at the Dartmouth Cancer Center with NCI Cancer Center Support Grant 5P30 CA023108-37.

CONFLICTS OF INTEREST

The authors declare they have no conflicts of interest.

REFERENCES