Pediatric primary spinal atypical teratoid rhabdoid tumor: a case series and review of the literature

Daphne Li Department of Neurological Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois;

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Daniel M. Heiferman Department of Neurological Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois;

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Hasan R. Syed Department of Neurological Surgery, Division of Pediatric Neurosurgery, University of Virginia Health System, Charlottesville, Virginia;

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João Gustavo Santos Department of Neurological Surgery, University of São Paulo School of Medicine, São Paulo, Brazil;

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Robin M. Bowman Department of Surgery, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children’s Hospital of Chicago; and
Departments of Neurological Surgery and

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Arthur J. DiPatri Jr. Department of Surgery, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children’s Hospital of Chicago; and
Departments of Neurological Surgery and

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Tadanori Tomita Department of Surgery, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children’s Hospital of Chicago; and
Departments of Neurological Surgery and

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Nitin R. Wadhwani Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois

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Tord D. Alden Department of Surgery, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children’s Hospital of Chicago; and
Departments of Neurological Surgery and

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Atypical teratoid rhabdoid tumors (ATRTs) are rare malignant central nervous system tumors, commonly occurring before 3 years of age. Median overall survival (OS) of patients with these tumors is about 1 year, despite aggressive multimodal therapy. Pediatric primary spinal ATRTs are even more rare, with fewer than 50 cases reported. The authors present a series of four patients who were treated at Ann and Robert H. Lurie Children’s Hospital of Chicago in the period from 1996 to 2017.

These patients, with ages 2–11 years, presented with pain and a decline in motor functions. They were found to have lesions in the lumbar, thoracic, and/or cervical spine. One patient’s tumor was intramedullary with exophytic components, while another patient’s tumor had both intra- and extradural components. All patients underwent resection followed by chemotherapy (systemic and intrathecal). Two patients had fractionated radiation therapy and one had an autologous stem cell transplant. Three patients are known to be deceased (OS 8.5–45 months). The fourth patient was in remission 19 years after her initial diagnosis. To the authors’ knowledge, this is the largest series of pediatric primary spinal ATRTs documented at a single institution. These cases illustrate a variety of presentations of spinal ATRT and add to the body of literature on this aggressive pathology.

A systematic MEDLINE search was also conducted using the keywords “atypical teratoid rhabdoid tumor,” “pediatric spinal rhabdoid tumor,” and “malignant rhabdoid tumor spine.” Reports were included for patients younger than 21 years, without evidence of intracranial or systemic disease at the time of diagnosis. Clinical characteristics and outcomes of the four institutional cases were compared to those in the literature. This review yielded an additional 48 cases of primary pediatric spinal ATRTs reported in the English-language literature. Patients (ages 2 months to 19 years) presented with symptoms of pain, regression of motor function, and spinal cord compression. The majority of tumors were intradural (14 extramedullary, 8 intramedullary, 1 both). Eleven cases in the literature described tumors limited to extradural structures, while 10 tumors involved the intra- and extradural spine. Four reports did not specify tumor location. Although rare, spinal ATRT should be considered in the differential diagnosis of pediatric patients presenting with a new spinal mass.

ABBREVIATIONS

ASCR = autologous stem cell rescue; ATRT = atypical teratoid rhabdoid tumor; CNS = central nervous system; DFCI = Dana-Farber Cancer Institute; EVD = external ventricular drain; GTR = gross-total resection; IDEM = intradural extramedullary; IDIM = intradural intramedullary; OS = overall survival; PFS = progression-free survival.

Atypical teratoid rhabdoid tumors (ATRTs) are rare malignant central nervous system tumors, commonly occurring before 3 years of age. Median overall survival (OS) of patients with these tumors is about 1 year, despite aggressive multimodal therapy. Pediatric primary spinal ATRTs are even more rare, with fewer than 50 cases reported. The authors present a series of four patients who were treated at Ann and Robert H. Lurie Children’s Hospital of Chicago in the period from 1996 to 2017.

These patients, with ages 2–11 years, presented with pain and a decline in motor functions. They were found to have lesions in the lumbar, thoracic, and/or cervical spine. One patient’s tumor was intramedullary with exophytic components, while another patient’s tumor had both intra- and extradural components. All patients underwent resection followed by chemotherapy (systemic and intrathecal). Two patients had fractionated radiation therapy and one had an autologous stem cell transplant. Three patients are known to be deceased (OS 8.5–45 months). The fourth patient was in remission 19 years after her initial diagnosis. To the authors’ knowledge, this is the largest series of pediatric primary spinal ATRTs documented at a single institution. These cases illustrate a variety of presentations of spinal ATRT and add to the body of literature on this aggressive pathology.

A systematic MEDLINE search was also conducted using the keywords “atypical teratoid rhabdoid tumor,” “pediatric spinal rhabdoid tumor,” and “malignant rhabdoid tumor spine.” Reports were included for patients younger than 21 years, without evidence of intracranial or systemic disease at the time of diagnosis. Clinical characteristics and outcomes of the four institutional cases were compared to those in the literature. This review yielded an additional 48 cases of primary pediatric spinal ATRTs reported in the English-language literature. Patients (ages 2 months to 19 years) presented with symptoms of pain, regression of motor function, and spinal cord compression. The majority of tumors were intradural (14 extramedullary, 8 intramedullary, 1 both). Eleven cases in the literature described tumors limited to extradural structures, while 10 tumors involved the intra- and extradural spine. Four reports did not specify tumor location. Although rare, spinal ATRT should be considered in the differential diagnosis of pediatric patients presenting with a new spinal mass.

In Brief

The authors report on the largest single-center series of pediatric primary spinal atypical teratoid rhabdoid tumor. The cases presented illustrate the diverse and rare presentations of this disease, as well as the longest documented progression-free survival. A comprehensive literature review and discussion of the diagnosis and subsequent multimodal management add to the body of literature and the medical community’s understanding of this aggressive and rare pathology.

Atypical teratoid rhabdoid tumor (ATRT) is a rare malignancy of childhood, comprising 1%–2% of pediatric brain tumors and most commonly occurring before 3 years of age.9,45,66 Prior to 3 years of age, ATRT has a slight male preponderence.9 According to the Central Brain Tumor Registry of the United States, ATRT accounts for 1.6% of all pediatric central nervous system (CNS) tumors and 4.4% of CNS tumors in the age group 0–5 years.43 Recently, it has been shown that ATRT is the most common CNS malignancy in children younger than 6 months of age.22 Historically, most patients have a median survival of about a year after diagnosis, with factors such as an age < 2 years, metastatic disease at diagnosis, and delayed initiation of radiation therapy portending a worse prognosis.20,64

Primary spinal ATRT is a rare subset of ATRT, with few cases documented in the English-language literature. Often presenting with symptoms of pain and myelopathy due to spinal cord compression, these highly malignant tumors must be promptly diagnosed and aggressively treated. The radiographic appearance of these rare tumors can be confused with more common tumors found in the spine, such as chordomas and even nerve sheath tumors.3,12,55 However, histological examination of the tissue and the use of immunohistochemical staining for BAF-47 and INI-1 have been well-established to reliably aid in diagnosis.9,12

We present four unique cases of pediatric primary spinal ATRT—varying in location and response to treatment—in an effort to add to the body of literature for this highly malignant disease. To our knowledge, this is the largest reported single-center case series of pediatric primary spinal ATRT. In addition, one of our cases has the longest documented progression-free survival (PFS) among pediatric primary spinal ATRT patients in the English-language literature, and another case is only the second reported instance of this pathology presenting as an intradural intramedullary (IDIM) lesion with exophytic extension.

Methods

Our systematic review was conducted according to PRISMA guidelines.40 We performed a systematic MEDLINE search of the English-language literature (Fig. 1) using the keywords “atypical teratoid rhabdoid tumor,” “pediatric spinal rhabdoid tumor,” and “malignant rhabdoid tumor spine.” The reference lists from these publications were also examined for relevant articles and historical reports. We only considered reports on patients 21 years of age or younger but excluded them from review if there was evidence of intracranial disease or it was unclear whether the patient’s spinal ATRT was a primary lesion.

FIG. 1.
FIG. 1.

PRISMA flowchart depicting citations identified and evaluated for the purposes of the literature review.

We also conducted a retrospective chart review of primary spinal ATRT cases cared for at Ann and Robert H. Lurie Children’s Hospital of Chicago in the period from 1996 to 2017. Clinical characteristics, management, and outcomes of these cases were compared to those in the literature. A clinical case review was deemed not to be human subjects research and thus was exempt from requiring consent or approval by our institutional review board.

Illustrative Cases

Case 1

This 2-year-old girl presented to our institution with increasing neck pain and progressive loss of function over the past month (Table 1). She had lost her ability to stand and had stopped using the left side of her body, using her right hand to bring her left hand to her mouth. MRI performed in the emergency room revealed a hemorrhagic IDIM mass spanning C2–6 (Fig. 2A–C) without evidence of intracranial or systemic disease. Differential diagnosis at the time included ependymoma or astrocytoma. The day after presentation, she was taken for a C3–6 laminoplasty for gross-total resection (GTR) of her intramedullary mass as well as an exophytic component that was noted intraoperatively at C4 (Fig. 2D–E and Video 1).

VIDEO 1. Case illustration and operative video for the patient in case 1. Copyright Ann and Robert H. Lurie Children’s Hospital of Chicago. Published with permission. Click here to view.

TABLE 1.

Summary of data for pediatric patients who presented with primary spinal ATRT in this institutional case series

Case No.Age at DxSexSymptoms at DxLocation of Primary TumorSurgeryChemoRTRecurrence/ MetastasesSubsequent InterventionsSubsequent Chemo/RTOther Subsequent ProceduresOutcome
12 yrs 4 mosFNeck painC2–6 IDIM, exophyticC3–6 laminoplasty for GTRDFCI ATRT (Ommaya for IT)NoneAt 8 mos: local & cauda equinaC7–T1 laminectomy for GTRNoneIVH & HCP s/p EVDDOD 8.5 mos after initial presentation
25 yrs 4 mosFLeg painT12–L1 IDEMT12–L1 laminectomy for GTR (OSH)DFCI ATRT (Ommaya for IT)T11–L3 proton beam at 3 mosAt 20 mos: IC, leptomeningeal, T5–7 IDEMT5–7 laminectomies for GTRNoneHCP due to IC tumor burden s/p VPSDOD 22 mos after initial Dx
311 yrs 3 mosMBack pain, lt > rt arm weakness, & lt foot dropC5–T1 IDEM & C7–T1 EDC4–T1 laminoplasty for GTR, lt neck & brachial plexus dissection for STR EDDFCI ATRT (IT via lumbar puncture)Neck at 4 mosAt 24 mos: L3 IDEML3 laminectomy for GTRPBTC 031 A phase 1 trial of p28DOD 45 mos after initial Dx
At 27 mos: S2 IDEMPED-MA-2010 (no IT) & focal spinal RT
At 35 mos: rt CPA, lt IACOral topotecan → palliative cranial RT w/ pst fossa boost
42 yrs 5 mosFLeg weaknessT3–5 IDEMT3–5 laminoplasties for STR followed by redo for GTR 3 days laterCyclophosphamide, doxorubicin, cisplatin, etoposide & IT MTX, cytarabine → carboplatin, thiotepa, etoposide, myeloablative chemo, & ASCRNoneNoneNANA10–14 yrs later: thoracic laminectomies ×2 for syrinx & cyst fenestration, syringopleural shunt placementLast seen at 19 yrs after Dx w/o recurrent diseasex
15 yrs later: thoracolumbar correction of postlaminectomy kyphosis

→ = transitioned; chemo = chemotherapy; CPA = cerebellopontine angle; DOD = died of disease; Dx = diagnosis; ED = extradural; HCP = hydrocephalus; IAC = internal auditory canal; IC = intracranial; IT = intrathecal; IVH = intraventricular hemorrhage; MTX = methotrexate; NA = not available; OSH = outside hospital; PBTC = Pediatric Brain Tumor Consortium; pst = posterior; RT = radiation therapy; s/p = status post; STR = subtotal resection; VPS = ventriculoperitoneal shunt.

FIG. 2.
FIG. 2.

Case 1. Preoperative sagittal T2-weighted (A), T1-weighted noncontrast FLAIR (B), and T1-weighted postcontrast (C) MRI demonstrated a heterogeneously enhancing IDIM expansile mass extending from C2 to C6 with surrounding cervical cord edema and intratumoral hemorrhage. Sagittal T2-weighted (D) and postcontrast T1-weighted FLAIR (E) imaging demonstrated postoperative changes without definite residual enhancing tumor. Interval imaging with evidence of a recurrent C6 enhancing lesion on sagittal T2-weighted (F) and sagittal and axial T1-weighted postcontrast (arrows, G and H) MRI, with restricted diffusion on a diffusion-weighted sequence (I). Interval postcontrast T1-weighted MRI (J) demonstrated new enhancement along the thoracic spinal cord, conus medullaris, and cauda equina. Interval postcontrast T1-weighted MRI (K) demonstrated a 4-mm enhancing nodule (arrow) along the right cauda equina nerve roots at approximately the L4 level. Histological examination of tumor tissue with the loss of normal nuclear INI-1 demonstrated on BAF-47 immunohistochemical staining (L) and eosinophilic cells with a rhabdoid appearance on routine H & E preparation (M). Original magnification ×40. Figure is available in color online only.

Histological examination of tissue and immunohistochemistry (Table 2 and Fig. 1L–M) were consistent with WHO grade IV ATRT.

TABLE 2.

Histopathological examination of surgical specimens in this institutional case series

ImmunohistochemistryMicroscopic Examination
Case No.Location of Resected TumorFrozen SectionPositiveNegativeNuclear BAF-47/INI-1Ki-67Tumor CellsMitosesApoptosis or NecrosisBackground
1C2–6 IDIMHigh-grade lesionNANANegativeNAOccasional rhabdoid cellsPresentPresentNA
C7 IDIMRecurrent ATRTNANANegativeNARecurrent ATRT
2T12–L1 IDEMCellular neoplasm, possible schwannomaEMA, vimentin, NF200, FLI1, beta-catenin, c-myc (70%)GFAP, S100, CD99, synaptophysin, CK8/18, Neu-NNegative50%Highly cellular sheets of spindled, round, & oval cells w/ prominent nucleoli & eosinophilic cytoplasm; evidence of mesenchymal, neural, & epithelial differentiationNumerousPresentCD45 lymphocytes
T5–7 IDEMRecurrent ATRTNANANegativeNARecurrent ATRT
3C5–T1 IDEMNAEMA, S100 (weak, focal), SMA (rare), GFAP (rare)DesminNegativeNAHypercellular in sheets & cords, infiltrative rhabdoid morphologyPresentPresentMyxoid
C7–T1 EDNANANANANACellular malignant neoplasm (ATRT) w/ areas of necrosis
L3 IDEMNASimilar to originalSimilar to originalNegativeNASimilar to prior specimen
4T3–5 IDEMNANANANANANA

EMA = epithelial membrane antigen; GFAP = glial fibrillary acidic protein; SMA = smooth muscle actin.

Three weeks later, the patient had an Ommaya reservoir placed for intrathecal chemotherapy per the Dana-Farber Cancer Institute (DFCI) ATRT protocol,17 with the decision to delay fractionated radiation therapy until after the completion of chemotherapy. Almost 8 months after her initial resection, follow-up MRI demonstrated recurrent tumor in the cervical spine (Fig. 2F–I). The plan, formed after discussion with the multidisciplinary team and the patient’s family, was to return to the operating room for resection of the recurrent tumor. Unfortunately, in the interim, she presented with acute hydrocephalus secondary to intraventricular hemorrhage of unclear etiology and without evident intracranial tumor spread. The patient was admitted and had her Ommaya reservoir removed and replaced with a new external ventricular drain (EVD), which allowed for stabilization of her clinical condition.

During this hospitalization, repeat MRI of the patient’s spine demonstrated new metastases to the cauda equina (Fig. 2J–K). After further discussion with the family, the decision was made to proceed with the planned resection of the recurrent cervical lesion. The patient underwent a C7 laminectomy and resection of a hemorrhagic tumor. Recurrent ATRT was confirmed on histological analysis (Table 2). Postoperatively, the patient’s course was complicated by seizures and continued bloody drainage from her EVD. For these reasons, and after extensive discussions between the family and the multidisciplinary team consisting of neurosurgery, palliative care, and hematology/oncology, the family decided to withdraw care. The patient died shortly thereafter, 8.5 months after initial presentation.

Case 2

A 5-year-old girl first presented to an outside institution with progressively worsening leg pain, worse upon waking (Table 1). She was diagnosed with an intradural extramedullary (IDEM) mass spanning the T12–L1 levels without evidence of other CNS or systemic disease (Fig. 3A–G). This presentation favored a differential diagnosis of myxopapillary ependymoma or schwannoma. A few days later, T12–L1 laminectomies were performed for resection of the mass (Fig. 3H–K). Tissue analysis (Table 2) was consistent with a diagnosis of ATRT, both on initial evaluation and on reanalysis at our institution. Shortly thereafter, the patient’s oncological care was transferred to our institution.

FIG. 3.
FIG. 3.

Case 2. Preoperative MRI of the entire spine was performed on initial presentation to an outside institution, demonstrating an IDEM lesion in the right lateral aspect of the spinal canal at the level of L1–2. The lesion demonstrated predominantly T2 hypointensity with small internal cystic areas on sagittal (A) and axial (F) T2-weighted MRI sequences. There was associated restricted diffusion on diffusion-weighted (D) and apparent diffusion coefficient (E) sequences. The lesion demonstrated mild heterogeneous contrast enhancement on sagittal precontrast T1-weighted (B) and sagittal (C) and axial (G) postcontrast T1-weighted FLAIR imaging. Axial T2-weighted (F) and T1-weighted postcontrast (G) MRI showed significant stenosis of the spinal canal at this level and displacement of the conus medullaris (arrows) to the left. Postoperative MRI of the lumbar spine demonstrated no definite residual enhancing lesion on sagittal (H) and axial (I) T2-weighted imaging and sagittal (J) and axial (K) T1-weighted postcontrast imaging. Sagittal postcontrast T1-weighted MRI of the entire spine was performed 20 months after her initial diagnosis, demonstrating several thoracic enhancing foci, with a dominant lesion along the left aspect of the spinal cord at the T6–7 level (arrow, L). A new nodularity and increased enhancement along the margins of the resection site, as well as diffusely throughout the cauda equina nerve roots, was also seen (M). Coronal (N), axial (O), and sagittal (P) postcontrast T1-weighted imaging of the brain was performed 35 months from initial diagnosis, demonstrating a prominent midline lesion likely arising from the parasagittal meninges along the cingulate gyrus distorting the corpus callosum (arrow, P). A dominant lesion involving the right cerebellopontine angle (arrow, N) is visible, as are several areas of additional leptomeningeal thickening consistent with metastatic disease (arrow, O). Figure is available in color online only.

One month later, she had an Ommaya reservoir placed for intrathecal chemotherapy per the DFCI ATRT protocol.17 Two and a half months after her initial resection, the patient received proton beam therapy to the T11–L3 region. She was doing well, with serial imaging demonstrating stable postoperative findings and no evidence of recurrent disease. However, on MRI performed 6 months after completion of therapy (20 months after her initial diagnosis), there was evidence of disseminated intracranial disease with leptomeningeal metastases and frontal ependymal lesions (Fig. 3N–O). She was also found to have numerous metastases throughout her spine and an associated syrinx (Fig. 3L–M).

The patient was taken for T5–7 laminectomies for GTR of the three largest IDEM lesions. Histopathological analysis confirmed recurrent ATRT (Table 2). The patient tolerated this procedure well but required placement of a ventriculoperitoneal shunt 1 month later for progressive hydrocephalus secondary to an enlarging intracranial lesion. She died just over 22 months after her initial diagnosis.

Case 3

An 11-year-old boy presented to our institution with back pain, progressively worsening weakness, and a new finding of dragging his left foot while walking, prompting medical evaluation (Table 1). On examination, he was myelopathic with weakness of both distal upper extremities (left worse than right), he had a left foot drop, and he had diffuse hyperreflexia with bilateral clonus. He was found to have an IDEM lesion extending from C5 to T1 and significant extradural extension at C7 and T1 with involvement of the left paraspinal muscles and brachial plexus (Fig. 4A–G). The patient had no evidence of disease elsewhere at this time. Differential diagnosis at the time included neurofibroma, schwannoma, or rhabdoid tumor.

FIG. 4.
FIG. 4.

Case 3. Preoperative MRI of the cervical spine with sagittal T2-weighted (A), precontrast T1-weighted (B), and postcontrast T1-weighted (C) sequences, as well as axial T2-weighted (D) and T1-weighted postcontrast (E) sequences and coronal postcontrast T1-weighted sequences through the intradural (F) and extradural (G) components. There was a heterogeneous and multilobulated mass with solid components of varying enhancement characteristics in both the spinal canal and the left paraspinal tissues, contiguous through an expanded left C7–T1 intervertebral foramen. The intraspinal component of the mass caused severe compression of the spinal cord at the cervicothoracic junction, and the extraspinal component caused mass effect upon many adjacent structures including the left vertebral artery origin, the esophagus, and the left lung apex. Two-year post-diagnosis MRI of the entire spine showed no evidence of local recurrence on sagittal T2-weighted (H) and T1-weighted postcontrast (I) sequences of the cervical spine but did show evidence of new cauda equina metastases, the largest at L3 (arrow) on sagittal (J) and axial (K) T1-weighted postcontrast sequences. Repeat MRI 2 months after GTR of the L3 lesion revealed postsurgical changes, no recurrent lesion, but a new S2 enhancing lesion (arrow) on sagittal T2-weighted (L), T1-weighted precontrast (M), and T1-weighted postcontrast (N) sequences. Brain MRI 6 months later with axial postcontrast T1-weighted sequences demonstrated a new right cerebellopontine angle mass (arrow, O) and new left internal auditory canal nodule (arrow, P). Repeat sagittal postcontrast T1-weighted MRI demonstrated a new T3 lesion (arrow, Q) and enlarging right cerebellopontine angle mass (arrow, R) despite radiation therapy. Figure is available in color online only.

A staged approach was planned for resection of this extensive tumor: 1) a posterior approach for decompression of the spinal cord and resection of the intradural tumor and 2) an anterior approach for extradural tumor resection, brachial plexus decompression, and neck dissection. The patient was taken for C4–T1 laminoplasty with GTR of the IDEM tumor and dissection of the involved nerve roots (C7–T1). Neuromonitoring with somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) ensured safe dissection and enabled resection of an abnormal C8 nerve root that did not respond to intraoperative stimulus. Given the extensive extradural component, we together with otolaryngology took the patient for a left neck and brachial plexus dissection 3 weeks later. The patient tolerated both of these procedures well with significant improvements in his motor exam and only residual weakness in his left hand, in the distribution innervated by the C7 and C8 nerve roots. Histopathological analysis (Table 2) from both specimens was similar, and immunohistochemical staining corroborated a diagnosis of ATRT. Molecular testing demonstrated homozygous deletion of the nine coding exons of SMARCB1/INI1 on 22q11.2.

The patient was initiated on the DFCI ATRT protocol 1 month after surgery, although intrathecal chemotherapy was withheld.17 He received radiotherapy to his neck 4 months after surgery and completed chemotherapy a year later. The patient did well and was followed with routine serial imaging. Two years after his initial diagnosis, he was found to have a metastasis at L3 and was taken shortly thereafter for an L3 laminectomy and GTR of his new IDEM lesion (Fig. 4H–K). Histopathological analysis at this time confirmed metastatic ATRT (Table 2).

The patient was then enrolled in Pediatric Brain Tumor Consortium (PBTC) 031 A phase 1 trial of p28 (a non–HDM2-mediated peptide inhibitor of p53 ubiquitination) starting 2 weeks after the second surgery.34 Three months after his second surgery, serial imaging demonstrated a new left-sided intradural mass at the second level of the sacrum (S2; Fig. 4L–N). The patient still did not have evidence of recurrent or intracranial disease at this time. Given some evidence of improved PFS, our patient was initiated on PED-MA-2010 therapy without intrathecal chemotherapy.44 Despite this, serial imaging 6 months after his second surgery showed progressive spinal disease. The patient underwent focal spinal radiation therapy for the next 2 months, but imaging 2 months after completing radiation therapy revealed a new 9-mm lesion at his right cerebellopontine angle, as well as a 5-mm nodule in his left internal auditory canal, suggestive of leptomeningeal metastases (Fig. 4O–P). The patient was started on oral topotecan 2 weeks later.

Re-imaging 3 months later continued to show progressive disease, and the patient underwent palliative cranial radiation therapy with a boost to the posterior fossa. Three months later, follow-up MRI showed improvement of his cranial lesions but a new enlarging thoracic mass (Fig. 4Q–R). After extensive discussions between his family and the multidisciplinary team of oncologists, radiation oncologists, and neurosurgeons, the decision was made to transition the patient to hospice, and he succumbed to his disease 45 months after his initial diagnosis.

Case 4

A 2-year-old girl presented to our institution with several days of leg weakness and was diagnosed with a T3–5 IDEM mass (Table 1). Shortly after presentation, she underwent laminoplasty and subtotal resection for decompression of the spinal cord, but proceeded with a reoperation a few days later in order to achieve a greater extent of resection once histological diagnosis was finalized and consistent with ATRT (Table 2). She was started on chemotherapy with Cytoxan, Adriamycin, cisplatin, and etoposide, along with intrathecal methotrexate and cytarabine. This was then transitioned to a regimen of carboplatin, thiotepa, etoposide, myeloablative chemotherapy, and autologous stem cell rescue (ASCR). She completed this chemotherapeutic regimen 1 year after her initial surgery. Radiotherapy was avoided because of her good response to chemotherapy.

The patient did well clinically and was followed closely by oncology and neurosurgery with serial imaging. However, almost a decade after her initial surgery, she began having progressive urinary urgency, leg weakness, and spasticity. Repeat MRI did not show any evidence of recurrent disease, but she was diagnosed with hydromyelia and a tethered cord for which she underwent T1–6 laminectomies for cord detethering and syringotomy. Four years later, the patient required surgery again for resection of meningeal scarring and cyst fenestration after she began having weakness in the muscles of the ulnar nerve distribution and decreased sensation in her thoracic dermatomes. Six months later, she required cyst fenestration and placement of a syringopleural shunt because of a progressive loss of function of her hands. Seven months after this, we together with orthopedic surgery took the patient for a thoracolumbar fusion and Ponte osteotomies for reduction of her postlaminectomy kyphosis and concurrent exploration of a dorsal cervicothoracic pseudomeningocele with repair of a dural defect. The patient did well after this last procedure and was last seen in the clinic at our institution 19 years after her initial diagnosis without evidence of recurrent disease.

Discussion

A review of the English-language literature revealed 48 additional cases of primary spinal pediatric ATRT, with the first case reported by Robson et al. in 1987 (Table 3).48 Two articles reporting on three cases of pediatric spinal ATRT were excluded because they focused on the genetic and/or histological analysis of specimens obtained from tumor banks, and we could not determine if these specimens were the patients’ primary lesions.8,11 Age at presentation for the included cases ranged from 2 months to 19 years. Our four-case series had a similar distribution of ages, with two patients presenting at the age of 2 years, one at the age of 5, and one at the age of 11. The cases reported in the literature had a male preponderance, which was not reflected in our series.

TABLE 3.

Summary of cases of primary spinal pediatric ATRT reported in the English-language literature

Authors & YearSexAge at DxSymptoms at DxID Tumor Location (n = 23*)InterventionChemoRTRecurrence/MetastasisOther Subsequent InterventionsOutcome
Rosemberg et al., 1994F2 yrsIDEMNS
Rorke et al., 1996NAInfantCervical IDEMNSNANA
Tamiya et al., 2000F7 mosProgressive paraplegia & BLE hypesthesiaT7–L3 IDIMT12–L3 laminectomies for STRYY3 mos, DOD
Bambakidis et al., 2002M22 mosParaplegia ×2 wksT11–L3 IDIMSTRY & ASCRY10 mos, DOD
M17 yrsDiffuse IDIMBiopsyNY1 mo, DOD
Cheng et al., 2005F2 yrsLow-back pain & BLE weaknessT12–S1 ID spine (IDEM?)Multimodal intensive therapy (NS)NSNS2 mos, DOD
Chen et al., 2005M15 yrsMid-back painIDEM w/ invasion of rootletsSTRY & ASCRY, CS34 mos, NED
Tanizaki et al., 2006F10 mosProgressive paraplegiaT10–conus IDIMDecompressive laminectomy for biopsyYY3 mos, DOD
Moeller et al., 2007M9 yrsRt LE numbness, weakness, urinary incontinence ×3 mosT11–L2 IDEMGTRDeclinedYNone at 3-mo postop imaging3 mos, NED
Yang et al., 2007M7 yrsBack pain & unstable gait ×3 wksL2–4 IDEML2–4 laminectomies (NS)YYAt 5 mos: local recurrenceNA7 mos, DOD
Tinsa et al., 2008F4 yrsUnstable gait ×1 mo, fever, weakness, anorexiaC1–T1 IDIMC1 laminectomy, C2–7 laminoplasties & biopsyNNLeptomeningeal dissemination at Dx0.5 mo, DOD
Yano et al., 2008F1.75 yrsAcute, progressive tetraparesisCervical spine IDEMGTRY & ASCRY, CSRemission at 27 mos postop27 mos, NED
Mohapatra et al., 2010M4.5 yrsNSC1–2 IDEMEOR NSNNUnknownUnknownUnknown
Imagama et al., 2012F2 yrsRecent fever, 1 wk BLE paralysis & painT12–S1 IDEMEmergency T10–S1 laminectomy for GTRY, ITNAt 6 mos: local recurrenceRT9 mos, DOD
At 9 mos: ICH s/p craniotomy
Kelley et al., 2012M4 yrs2 wks constipation & several days of BLE paraplegiaT10–L1 IDEM massT9–L3 laminectomies for STRY, ITYNone at 5 yrsCorrection of post-laminectomy kyphosis5 yrs, NED
Yang et al., 2014F8 mosProgressive limb weaknessC2–T2 IDIMSTRNN1 mo, DOD
Dhir et al., 2015M30 mosInability to ambulate, encopresis, urinary dribbling since 2 wks of age, decreased rectal tone, bilat foot dropL3 & below IDEML3–S2 laminoplasty NSYNNone at 8 mos8 mos, NED
Mankotia et al., 2016M5 yrsRapidly ascending quadriparesis ×1 wk, respiratory distress, sensory loss below T4, myelopathic featuresT5–10 IDEMT4–10 laminoplasty for STRYNNone at 1 mo1 mo, NED
Buccoliero et al., 2019F44 mosDifficulty walking, pain in pelvis & legsT11–L2 IDIMSTRYN4 mos, DOD
Chao et al., 2017M16 mosUrinary retention, change in bowel habits, unable to walk w/ decreased sitting balance ×1 wk, BLE loss of muscle toneT11–L3 IDEMT10–L3 laminectomies w/ neuroendoscopic resection (NS)Y, ITY, CSAt 3 mos: local recurrenceRedo STR & chemo & RT7 mos, NED
Shiflett et al., 2018F17 mosSuddenly stopped walking → weight loss, decreased movement BLE → paraplegia, areflexia, decreased rectal toneT11–L5 IDIMMidthoracic to L5 laminoplasties GTR w/ resection of lumbar nerve roots, meninges, & conus medullarisNNAt 1 wk: extensive leptomeningeal dissemination0.75 mo, DOD
Hale et al., 2018F4 yrsFroin’s syndrome, MCA infarct, weight loss, HCPSpinal (reported EDIM)NNNNALumbar puncture, EVD
Babgi et al., 2018M6 yrsNSThoracolumbar junction (IM & EM)Resection ×2YYNSNS16 mos, DOD
Tantana et al., 1988NANASymptomatic spinal cord compressionED bony destructionY (NS)
Horie et al., 1992F4 mosDorsal soft-tissue massLt thoracic ED space & paravertebral regionLaminectomy for STRYNAt 4 mos: lt thoracic cavity, lung, liver, cerebellum4 mos, DOD
Mahmood et al., 2003M11 yrsBilat neck swelling, dysphagia, anorexia, rt shoulder pain ×3 mosPst oropharynx & cervical chain LAD w/ invasion of clivus, lt petrous apex, occipital bone & C1–2 vertebral bodiesLymph node biopsyNSNSNSNSNS
Robbens et al., 2007M19 yrsNeck & lt UE pain w/ lt thumb sensory disturbancesED C5/6 lumbar neural foramen w/ osteolysis of C5Ant approach for STRYNAt 6 mos: local recurrence, ED lesion at T1–3, C7–T2 prevertebral mass, lung metastases, mediastinal LADBiopsy8 mos, DOD
Agrawal et al., 2009F18 mosIncreasingly painful swelling in low back w/ firm lumpLumbar spine paraspinal mass w/ erosion of lt L2 transverse processNear-total resectionYNAt 2 mos: extensive recurrenceNSNS
Heuer et al., 2010M7 yrsPain w/ head turning ×11 mos, photophobia ×4 mosClival–C2 EDTransoral GTR & occiput–C5 fusionY, ITYAt 27 mos: L1 IDEM metastasis; several mos later: leptomeningeal disseminationT12–L1 laminectomy & chemo, ASCR42 mos, DOD
Dobbs et al., 2011F17 yrsLt S1 pain & paresthesias ×3 mosLt presacral space & S2 neural foramenBiopsy of lt S2 lamina → marginal resection of presacral mass (STR)YNNSNSNS
Xin et al., 2014F10 yrsNeck pain ×2 mosC2–5 ED w/ C3 osteolysisSTR (90%)NNAt 2 mos: lung metastases & LADChemo & RT8 mos, DOD
Tang et al., 2015F13 yrsNeck pain & lt neck massC4 vertebraPercutaneous needle biopsyYYAt 6 mos: local progressionChemo & radioactive 125I seed implant40 mos, NED
At 9 mos: local recurrenceRedo resection, chemo
Singla et al., 2016M3 mosRt LE flaccid paralysesT12–S1 EDGTRNNAt 1 mo: local recurrenceNNS
Nishimoto et al., 2018M3 yrs2 wks of tetraparesis & dysphagiaC1–2 ED & osteolysis lower clivusEmergent C1 laminectomy & delayed lat approach for STR & occiput–C2 fusionNY, SRSAt 8 mos: rib metastasesGTR & chemo29 mos, DOD
At 24 mos: nasopharynx & oropharynx metastasesChemo
Bannykh et al., 2006M4 yrsProgressive BLE flaccid paralysis × few days, pain in low back & rt hip, areflexic BLE, sensory loss below L1, constipationT9–L1 IDEM & ED extensionT9–L1 laminectomies for resection of ED component; STRY, ITYNone at 18 mos postop18 mos, NED
Kodama et al., 2007M9 mosTetraparesis, severe loss of muscle tone, increased knee jerkC4–T6 IDEM w/ ED extension to rt C6/7 neural foramenSTRYYAt 15 mos: leptomeningeal dissemination20 mos, DOD
Athale et al., 2009M4.25 yrs2 days of mild fever, progressive generalized weakness, back pain & BLE pain, difficulty walking, rt UE weaknessC5–T2 IDEM w/ predominant ED extension into neckCervicothoracic laminectomies for STRYY1 mo after chemo: IC & spinal metastases11 mos, DOD
Niwa et al., 2009M6 yrsLt neck pain & UE ×3 mosC4–6 IDEM w/ ED extension into lt neural foramenEmergent C3–6 laminectomy & resection of IDEM component (STR)NANANSNS
Stabouli et al., 2010M2 mosProgressive tetraparesis ×4 days, respiratory failure, BLE hyperreflexia, & BabinskiC1–5 IDEM w/ ED extension into brachial plexusOpen biopsyYNEVD placement for HCP6 mos, DOD
Makis et al., 2011M8 mosBLE weakness, hyporeflexia, loss of motor milestonesL4–SC IDEM w/ ED extensionBiopsyYNNone at 3-wk imaging0.75 mo, NED
Buccoliero et al., 2019M18 mosPain & weakness lt LEL1–5 IDEM w/ ED extensionSTRYN3 mos, DOD
Song et al., 2018M16 mosBLE weakness ×2 wks, areflexicL1–3 IDEM w/ ED extensionL1–4 laminoplasty for resection (EOR NS)NY
Garling et al., 2018F15 yrs3 mos of BLE weakness, decreased sensation, weight loss, back pain, & progressive B/B incontinenceL3–S2 IDEM w/ ED extension into sacral plexusL3–5 laminectomies for STR (50%)NSNSNSNS
Hong et al., 2018M3 yrsRt UE weakness → quadriparesis, B/B incontinenceC3–5 IDEM w/ ED extensionGTRYY
Robson et al., 1987Thoracic spine
Fridley et al., 200913 mosSymptomatic spinal cord compressionCervical spineResected twiceYLeptomeningeal disseminationCSF diversion4 mos, DOD
Huddleston et al., 2010M6 mosCervical spineNS
Amit et al., 2018MTeenCervical spine

— = not applicable or not reported; ant = anterior; B/B = bowel and bladder; BLE = bilateral lower extremity; CS = craniospinal; EDIM = extradural intramedullary; EM = extramedullary; EOR = extent of resection; ICH = intracranial hemorrhage; ID = intradural; IM = intramedullary; LAD = lymphadenopathy; LE = lower extremity; MCA = middle cerebral artery; N = no; n = number of cases; NED = no evidence of recurrent/progressive disease; NS = not specified; SC = sacrococcygeal region; SRS = stereotactic radiosurgery; UE = upper extremity; Y = yes.

Fourteen EM, 8 IM, and 1 IM and EM.

Postmortem diagnosis.

Our patients presented with symptoms of pain and neurological deficits referable to the level of spinal cord or nerve root compression. This is similar to the presentation of patients in the literature, who experienced neck or back pain, extremity pain, regression of motor functions/milestones, and bowel or bladder dysfunction. The majority of cases (n = 23) were intradural tumors: 14 extramedullary,14–16,18,25,31,32,37–39,49,50,68,70 8 intramedullary,6,12,53,58,60,63,69 and 1 that was both intra- and extramedullary.4 A minority of historical reports documented cases of pediatric primary spinal ATRT involving the extradural spine, with only 11 cases reporting solely extradural involvement,1,19,26,28,35,41,46,54,59,61,67 and 10 cases3,7,12,23,27,33,36,42,55,56 reporting both intradural and extradural components. Four cases did not specify the location of the spinal tumor.1,21,30,48 In addition, these tumors were most likely to be found in the cervical or cervicothoracic region of the spine, as was seen in 43% (18 of 42 cases) of cases that specified the tumor location in relation to the spinal column level.2,3,21,26,27,30,33,35,39,41,42,46,49,56,63,67,69,70 This is similar to other, more common pediatric spinal cord tumors that favor the cervical and cervicothoracic spine.51

Diagnosis

Radiographically, these tumors have a heterogeneous appearance and look similar to their intracranial counterparts. They can appear hyperdense on CT because of their hypercellularity.9 On MRI, ATRTs appear hypo- to isointense on T1- and T2-weighted imaging given their necrotic and hemorrhagic components, may have cystic components, and are heterogeneously enhancing.9,51 Because these tumors are so rare, especially in the extracranial CNS, and given their heterogeneous appearance on imaging, they may be easily mistaken for other, more common tumors of the spine. In addition, lesions with a significant extradural component extending through neural foramina, as in the patient in case 3, may have a radiographic appearance mimicking that of a schwannoma or malignant peripheral nerve sheath tumor.3,12,19,27,55 In fact, authors of one report have described initially monitoring their patient with serial imaging because the tumor’s appearance resembled a nerve sheath tumor and the preliminary clinical diagnosis was neurofibromatosis.19 It was only after the lesion showed significant enlargement on imaging, 7 months later, that a biopsy was attempted for diagnostic purposes.

Imaging of the entire neuraxis should also be performed on initial presentation, as these tumors have a high propensity for metastasis and may have already disseminated when the spinal lesion is detected. Three cases of pediatric spinal ATRT were excluded from our literature review given the evidence of intracranial disease at the time of presentation.29,52,65 None of our patients had intracranial disease at the time of presentation, but two patients (cases 1 and 3) did end up having intracranial disease and/or leptomeningeal dissemination on follow-up imaging, after receiving therapy. Because of this propensity for leptomeningeal spread, it has been suggested that cytological analysis of CSF should be included as part of the initial diagnosis and routine staging.3,9

Histological analysis of the tumors is not always straightforward since “rhabdoid” or “teratoid” histological features can be infrequent, while primitive neuroectodermal features can dominate.9,49 In addition, these tumors can also have mesenchymal and epithelial features. And because of their high grade, mitotic figures, necrotic regions, and hemorrhage are often present. Immunohistochemical analysis helps to diagnose these heterogeneously appearing tumor specimens on staining for BAF-47 (a gene product of INI-1), which shows a loss of normal nuclear expression in ATRT. This correlates with cytogenetic findings of deletion or mutation of the SMARCB1 locus on chromosome 22q11.2, which is a hallmark of this disease.8,9

Management

Given the rarity of these tumors, no universal approach has been established for the treatment of pediatric CNS ATRTs, let alone spinal ATRTs.3,9,24 Generally, management involves some combination of aggressive multimodal therapy, including surgery, radiation, and chemotherapy. Prompt surgical decompression is important for patients demonstrating progressive symptomatic spinal cord compression. Resection allows for rapid relief of symptoms, as well as the ability to obtain tissue specimens for histopathological diagnosis. Intraoperative frozen section (Table 2) can be used to guide intraoperative extent of resection but can also be misleading. Neuromonitoring with SSEPs and MEPs aids in safe dissection of tumor away from intimately involved nerve roots or safe spinal cord myelotomy. For cases in which adequate spinal cord decompression cannot be achieved, due to either swelling or incomplete resection, expansile duraplasty can be considered in addition to bony decompression. Expansile duraplasty was not deemed necessary for the resections performed in the above illustrative cases. Certain studies have demonstrated that GTR confers a significant improvement in PFS and/or overall survival (OS) compared to subtotal resection,9,17 but other studies have shown no significant difference.3,13 In light of these results, maximal safe resection should be attempted.

All of our patients underwent systemic chemotherapy with intrathecal chemotherapy. Three of our patients were treated using the DFCI ATRT protocol.17 This consisted of induction chemotherapy within 50 days of surgery using a modified Intergroup Rhabdomyosarcoma III (IRS-III) regimen consisting of vincristine, dactinomycin, cyclophosphamide, cisplatin, doxorubicin, and temozolomide. Since our patients did not have evidence of CSF dissemination (M0 disease) at initial diagnosis, they received intrathecal chemotherapy consisting of methotrexate, cytarabine, and hydrocortisone administered via Ommaya reservoir or lumbar puncture, coinciding with a cycle of chemotherapy. In addition, per the DFCI ATRT protocol, radiation therapy was administered focally in two patients (cases 2 and 3) using 1.8-Gy fractions for a total of 54 Gy. Radiation therapy was deferred in the patient in case 1 because of her young age. Although this did not apply to our patients, per the DFCI ATRT protocol, patients with initially positive CSF cytology receive intrathecal chemotherapy weekly until two negative specimens are obtained. Patients with M+ disease at diagnosis also received craniospinal radiation, as opposed to focal radiation therapy.

After the patient in case 3 progressed despite aggressive multiagent chemotherapy, he was transitioned to the PED-MA-2010 protocol, consisting of a multidrug antiangiogenic regimen of bevacizumab, fenofibrate, Celebrex, thalidomide, cyclophosphamide, and etoposide, and additional intrathecal chemotherapy with etoposide and cytarabine.44 Antiangiogenic regimens employ continuous administration of lower doses of chemotherapeutic agents, which is thought to be better tolerated than higher-dose conventional therapy.47 Antiangiogenic regimens aim to achieve cancer control through sustained chemotherapeutic drug levels that target the more vulnerable tumor endothelial cells, altering tumor blood supply, enhancing the proapoptotic effects of cytotoxic agents, and producing an immunostimulatory response.5 There has also been some evidence that tumors that have developed resistance to high-dose cytotoxic therapy may be responsive to metronomic antiangiogenic regimens.10

The patient in case 4 was treated using an aggressive multiagent chemotherapeutic regimen with alkylating agents and intrathecal chemotherapy. In addition, she underwent consolidative myeloablative chemotherapy and ASCR. Although she did not receive radiation therapy, because of both her young age at diagnosis and her excellent response to chemotherapy, she has a known PFS of 19 years. Her case supports some evidence in the literature indicating that alkylator-based chemotherapy regimens, high-dose methotrexate, and regimens with high-dose myeloablative chemotherapy and ASCR may be more effective.9,24,62

Radiation therapy also plays an important role in influencing OS for ATRT patients. Those who received a combination of chemotherapy and radiation therapy had a longer OS than those who received chemotherapy alone (18.4 vs 8.5 months, p = 0.097), and this effect was statistically significant for the patients in the age group of 3 years or younger (15.8 vs 7.9 months, p = 0.005).3 These effects were corroborated by an examination of the Surveillance, Epidemiology, and End Results (SEER) database, with radiation therapy found to be an independent predictor of improved OS, especially in patients younger than 3 years of age.13

Still, given worries about the effects of radiation on children during a critical period in their neurodevelopment, radiation is often reserved for patients who have evidence of recurrence. High-dose chemotherapy with ASCR has been used as a method of salvage therapy in patients with relapsed disease or as a method of delaying radiation therapy in young patients.24 A meta-analysis by Athale et al. showed that even without GTR or radiation, patients who received intrathecal chemotherapy had a significantly improved OS (2-year OS 64% vs 17.3% without intrathecal chemotherapy).3 Therefore, high-dose myeloablative chemotherapy with ASCR and/or intrathecal chemotherapy can also be considered in some patients for whom radiation therapy would rather be avoided.

Documented outcomes in our review of the literature ranged from death after 2 weeks63 to ongoing PFS at 5 years after initial diagnosis (Fig. 5).32 One of our patients (case 4) has the longest ongoing PFS documented in pediatric primary spinal ATRT, at about 19 years (229 months) after her initial diagnosis. This is longer than most documented OSs for any CNS ATRT, with the majority of these cases occurring in adults.57 Although the treatment regimens are not consistently detailed in the cases in the literature review, the patients with PFSs over 1 year all received multimodal therapy with aggressive chemotherapy and radiation therapy—three received intrathecal chemotherapy,7,26,32 two received myeloablative chemotherapy with ASCR,15,70 four received focal radiation,7,26,32,33 and two received craniospinal radiation.15,70 Unfortunately, regardless of treatment, the majority of patients still have a recurrence or show progression of their disease within 6 months.9

FIG. 5.
FIG. 5.

A: Kaplan-Meier curve demonstrating OS data available from 24 of 48 cases in the literature review with extended follow-up. B: Kaplan-Meier curve demonstrating PFS data available from 16 of 48 cases in the literature review with extended follow-up. Respective time points for patients in our case series are indicated (asterisks). The patient in case 4 is not represented in these curves because she was last seen 19 years after diagnosis, alive and well without progressive disease. Figure is available in color online only.

Given the retrospective nature of this case series and the literature available for review, only limited recommendations regarding diagnosis and management can be made. Inconsistent detailing of treatment regimens and the lack of randomized clinical trials make it difficult to draw direct conclusions on ideal management or multimodal treatment regimens. However, that is largely attributable to the overall rarity of this pathology. Moreover, the retrospective review of patient data, some of which predate the adoption of electronic medical records, makes inferring perioperative plans and histological reanalysis difficult. Despite these limitations, we believe that this literature review and case series allow for a reevaluation of the potential varied presentations of this rare pathology and a critical summary of multimodal management options available to minimize morbidity and maximize survival for these patients.

Conclusions

Pediatric primary spinal ATRT is a rare presentation of an aggressive CNS malignancy. We report the largest single-center series of pediatric primary spinal ATRT. Two of our patients’ tumors are notable for their rare presentation, one with extensive extradural and IDEM involvement and one with a mixed intradural tumor location (both intra- and extramedullary). Finally, one other case in our series has the longest documented PFS of any pediatric primary spinal ATRT patient. We aim to contribute our experience to the growing fund of knowledge surrounding this challenging disease. Awareness of this pathology and its various presentations is crucial in order to facilitate timely diagnosis and initiation of intensive multimodal treatment.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Li, Heiferman, Syed, Santos. Acquisition of data: Li, Wadhwani. Analysis and interpretation of data: Li, Heiferman, Alden. Drafting the article: Li, Alden. Critically revising the article: Li, Heiferman, DiPatri. Reviewed submitted version of manuscript: all authors. Study supervision: Bowman, DiPatri, Tomita, Alden. Care of patients in case series: Syed, Santos, Bowman, DiPatri, Tomita, Alden.

Supplemental Information

Previous Presentations

Portions of this work were presented in e-poster form at the American Association of Neurological Surgeons Annual Scientific Meeting held in San Diego, California, on April 13–17, 2019.

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  • PRISMA flowchart depicting citations identified and evaluated for the purposes of the literature review.

  • Case 1. Preoperative sagittal T2-weighted (A), T1-weighted noncontrast FLAIR (B), and T1-weighted postcontrast (C) MRI demonstrated a heterogeneously enhancing IDIM expansile mass extending from C2 to C6 with surrounding cervical cord edema and intratumoral hemorrhage. Sagittal T2-weighted (D) and postcontrast T1-weighted FLAIR (E) imaging demonstrated postoperative changes without definite residual enhancing tumor. Interval imaging with evidence of a recurrent C6 enhancing lesion on sagittal T2-weighted (F) and sagittal and axial T1-weighted postcontrast (arrows, G and H) MRI, with restricted diffusion on a diffusion-weighted sequence (I). Interval postcontrast T1-weighted MRI (J) demonstrated new enhancement along the thoracic spinal cord, conus medullaris, and cauda equina. Interval postcontrast T1-weighted MRI (K) demonstrated a 4-mm enhancing nodule (arrow) along the right cauda equina nerve roots at approximately the L4 level. Histological examination of tumor tissue with the loss of normal nuclear INI-1 demonstrated on BAF-47 immunohistochemical staining (L) and eosinophilic cells with a rhabdoid appearance on routine H & E preparation (M). Original magnification ×40. Figure is available in color online only.

  • Case 2. Preoperative MRI of the entire spine was performed on initial presentation to an outside institution, demonstrating an IDEM lesion in the right lateral aspect of the spinal canal at the level of L1–2. The lesion demonstrated predominantly T2 hypointensity with small internal cystic areas on sagittal (A) and axial (F) T2-weighted MRI sequences. There was associated restricted diffusion on diffusion-weighted (D) and apparent diffusion coefficient (E) sequences. The lesion demonstrated mild heterogeneous contrast enhancement on sagittal precontrast T1-weighted (B) and sagittal (C) and axial (G) postcontrast T1-weighted FLAIR imaging. Axial T2-weighted (F) and T1-weighted postcontrast (G) MRI showed significant stenosis of the spinal canal at this level and displacement of the conus medullaris (arrows) to the left. Postoperative MRI of the lumbar spine demonstrated no definite residual enhancing lesion on sagittal (H) and axial (I) T2-weighted imaging and sagittal (J) and axial (K) T1-weighted postcontrast imaging. Sagittal postcontrast T1-weighted MRI of the entire spine was performed 20 months after her initial diagnosis, demonstrating several thoracic enhancing foci, with a dominant lesion along the left aspect of the spinal cord at the T6–7 level (arrow, L). A new nodularity and increased enhancement along the margins of the resection site, as well as diffusely throughout the cauda equina nerve roots, was also seen (M). Coronal (N), axial (O), and sagittal (P) postcontrast T1-weighted imaging of the brain was performed 35 months from initial diagnosis, demonstrating a prominent midline lesion likely arising from the parasagittal meninges along the cingulate gyrus distorting the corpus callosum (arrow, P). A dominant lesion involving the right cerebellopontine angle (arrow, N) is visible, as are several areas of additional leptomeningeal thickening consistent with metastatic disease (arrow, O). Figure is available in color online only.

  • Case 3. Preoperative MRI of the cervical spine with sagittal T2-weighted (A), precontrast T1-weighted (B), and postcontrast T1-weighted (C) sequences, as well as axial T2-weighted (D) and T1-weighted postcontrast (E) sequences and coronal postcontrast T1-weighted sequences through the intradural (F) and extradural (G) components. There was a heterogeneous and multilobulated mass with solid components of varying enhancement characteristics in both the spinal canal and the left paraspinal tissues, contiguous through an expanded left C7–T1 intervertebral foramen. The intraspinal component of the mass caused severe compression of the spinal cord at the cervicothoracic junction, and the extraspinal component caused mass effect upon many adjacent structures including the left vertebral artery origin, the esophagus, and the left lung apex. Two-year post-diagnosis MRI of the entire spine showed no evidence of local recurrence on sagittal T2-weighted (H) and T1-weighted postcontrast (I) sequences of the cervical spine but did show evidence of new cauda equina metastases, the largest at L3 (arrow) on sagittal (J) and axial (K) T1-weighted postcontrast sequences. Repeat MRI 2 months after GTR of the L3 lesion revealed postsurgical changes, no recurrent lesion, but a new S2 enhancing lesion (arrow) on sagittal T2-weighted (L), T1-weighted precontrast (M), and T1-weighted postcontrast (N) sequences. Brain MRI 6 months later with axial postcontrast T1-weighted sequences demonstrated a new right cerebellopontine angle mass (arrow, O) and new left internal auditory canal nodule (arrow, P). Repeat sagittal postcontrast T1-weighted MRI demonstrated a new T3 lesion (arrow, Q) and enlarging right cerebellopontine angle mass (arrow, R) despite radiation therapy. Figure is available in color online only.

  • A: Kaplan-Meier curve demonstrating OS data available from 24 of 48 cases in the literature review with extended follow-up. B: Kaplan-Meier curve demonstrating PFS data available from 16 of 48 cases in the literature review with extended follow-up. Respective time points for patients in our case series are indicated (asterisks). The patient in case 4 is not represented in these curves because she was last seen 19 years after diagnosis, alive and well without progressive disease. Figure is available in color online only.

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