The 2021 fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System formally recognizes four spinal entities: spinal ependymoma, spinal ependymoma with MYCN amplification, spinal subependymoma, and spinal myxopapillary ependymoma. Diagnosis is no longer a matter of histology alone. Instead, clinicians must integrate the anatomical compartment, the microscopic appearance of the tumor, and its molecular signature, most often assessed through DNA methylation profiling. That shift matters because the subtypes behave very differently. Myxopapillary ependymomas, for example, were upgraded from grade 1 to grade 2 after clinicians realized that incompletely removed tumors, once watched passively, could recur with spread through the subarachnoid space, a complication that typically forces craniospinal irradiation and carries substantial morbidity.

Pediatric-specific molecular data are beginning to sharpen this picture. In the HIT-MED spinal cohort of 83 patients aged 22 or younger, methylation classes broke down as 63 percent myxopapillary, 33 percent conventional spinal ependymoma, and 4 percent MYCN-amplified. Strikingly, within this pediatric population the molecular class did not clearly separate risk levels between the two most common groups; instead, the extent of surgical resection and the WHO grade remained the dominant determinants of progression-free survival. Molecular profiling, in other words, refines biological classification, but for most children the scalpel and the microscope still tell the most important part of the story.

The exception is the MYCN-amplified subtype, which the review describes as one of the most aggressive entities in the entire ependymoma family. These tumors tend to relapse early, typically within about 2.3 years, and can prove fatal despite aggressive multimodal treatment regardless of the age at diagnosis. Identifying MYCN amplification therefore has immediate clinical consequences: high-risk counseling, intensified craniospinal surveillance, and consideration of clinical trials or novel therapeutics. The authors argue that every spinal ependymoma specimen should undergo reflex testing for MYCN amplification alongside formal WHO 2021 grading and, where available, methylation profiling. Even the ostensibly indolent myxopapillary tumors carry sobering long-term statistics, with a 10-year progression-free survival of roughly 59 percent in mixed-age datasets, and within pediatric myxopapillary disease, methylation subtype B showed a trend toward better five-year progression-free survival than subtype A, 86 percent versus 56 percent, though the difference has not reached statistical significance.

Clinically, these tumors announce themselves quietly. Adults and older children typically report progressive sensory disturbance, gait imbalance, weakness, axial back pain, or radicular pain, and most patients are still ambulatory at diagnosis. The insidious tempo, however, often means the tumor has extended over multiple spinal segments by the time imaging is obtained. In preverbal children the presentation can be maddeningly nonspecific: torticollis, regression of motor milestones, refusal to walk or crawl, or simple irritability, signs easily misattributed to musculoskeletal or developmental causes. The review stresses that any suspicion demands gadolinium-enhanced MRI of the entire neuraxis, including the brain, because drop metastases occur in a minority of patients and missing them leads to under-staging and inadequate adjuvant planning.

On imaging, the intramedullary subtypes typically show symmetric cord expansion, well-demarcated margins, contrast enhancement, polar cysts, and syringomyelia in 40 to 70 percent of cases. A rim of hemosiderin at the tumor poles, the so-called cap sign, hints at a distinct gliotic plane that surgeons can exploit for dissection. MYCN amplification itself cannot be seen radiographically, but irregular margins, infiltrative extension, multifocal nodularity, or leptomeningeal enhancement should raise suspicion for high-risk molecular disease. Myxopapillary tumors behave differently, arising extramedullary at the filum terminale with a lobulated, avidly enhancing morphology that displaces rather than infiltrates neighboring nerve roots.

Surgery sits at the center of management, and the review frames every operative decision along three fronts: whether gross total resection is anatomically feasible, what functional neurological risks it carries, and what the biological risk of recurrence or dissemination happens to be. Gross total resection is the most consistent modifiable predictor of progression-free survival, with contemporary series reporting rates of roughly 72 to 83 percent. Continuous multimodal intraoperative neuromonitoring, combining somatosensory evoked potentials, transcranial motor evoked potentials, and D-wave recording, allows real-time assessment of the dorsal columns and corticospinal tract, and a sustained deterioration in motor potentials or a significant D-wave drop strongly predicts permanent motor deficit. When signals fail irreversibly, a deliberate subtotal resection may be the wiser course, and early postoperative MRI within 24 to 48 hours guides whether a second-look operation should precede any adjuvant therapy. For myxopapillary lesions, meticulous capsule preservation is paramount, because capsular violation is associated with local recurrence, cerebrospinal fluid dissemination, and the need for radiotherapy; en bloc resection is preferred when technically feasible.

In children, the spine itself becomes a battleground. Postoperative deformity is arguably the most important surgical morbidity in this population, and the data are stark: in one series of 161 children, 27 percent eventually required fusion, with risk rising sharply in those under 13, those with preoperative scoliosis, tumor-associated syrinx, thoracolumbar junction involvement, or each additional resection. Another study found deformity in 38 percent of children before surgery and 69 percent afterward, even when laminoplasty was used throughout, underscoring that tumor biology and preoperative status drive much of the risk. Neither laminoplasty nor laminectomy reliably prevents kyphosis, and instrumented fusion, while stabilizing, permanently sacrifices motion and growth potential and can degrade the quality of the lifelong surveillance MRI these patients need. Radiation adds its own age-dependent hazard: a comprehensive PENTEC review found clinically significant scoliosis at vertebral doses as low as 15 Gy in infants under two, with rates exceeding 30 percent above 20 Gy in children aged two to six, thresholds substantially below the 45 to 59.4 Gy focal doses typically prescribed.

Adjuvant therapy follows a risk-adapted logic. After gross total resection of a grade 2 spinal ependymoma, most contemporary evidence supports surveillance without routine radiotherapy, since a clear benefit has not been consistently demonstrated. After subtotal resection or biopsy, focal conformal radiotherapy is recommended because incomplete resection consistently predicts inferior progression-free survival. Grade 3 tumors receive focal radiotherapy regardless of resection extent, and craniospinal irradiation is considered when dissemination is present or suspected. For myxopapillary tumors the role of postoperative radiotherapy remains genuinely contested, with some retrospective series, including pediatric cohorts, suggesting improved control even after complete resection, particularly with dose escalation above 50.4 Gy or when high-risk features exist, while other adult-dominant datasets support observation alone. A recent multi-institutional pediatric and young adult series of high-risk myxopapillary disease reported five-year overall survival of 100 percent and progression-free survival of 60.8 percent, but patients still relapsed outside the treated field and intracranially, arguing for vigilance beyond the radiation volume rather than dose escalation alone. Chemotherapy, meanwhile, has no established frontline role; it is reserved for recurrent or disseminated disease, clinical trials, or as a deliberate strategy to defer radiotherapy in infants, an approach validated for intracranial ependymoma but never formally studied in the spine.

The review’s most candid contribution may be its systematic accounting of what medicine does not know. Nearly every management domain, from radiotherapy dosing and timing to the value of molecular stratification beyond MYCN, rests on adult or mixed-age retrospective cohorts, and no prospective pediatric-specific data address whether current thresholds should differ for a growing child. Local recurrence remains the dominant failure pattern even after complete resection, and craniospinal dissemination can appear years later, which is why the authors recommend lifelong MRI surveillance for every patient, with intensified brain and full-neuraxis imaging for those with dissemination or high-risk subtypes. For isolated recurrences, repeat maximal safe resection remains the mainstay, followed by focal radiotherapy in radiation-naive patients, though cumulative dose tolerance to the spinal cord and the specter of radiation-induced deformity weigh heavily in children who face a far longer horizon of potential exposure. The path forward, the authors conclude, requires prospective multicenter studies, validated molecular risk models, and novel systemic therapies for the aggressive subtypes, so that the next generation of children with spinal ependymoma can be treated on evidence of their own rather than borrowed from adults.

Subject of Research: Molecular classification and management of pediatric spinal ependymoma

Article Title: Spinal ependymoma: a comprehensive review of molecular classification, management guidelines, and clinical outcomes with a focus on the pediatric population (Part III of ependymomas across compartments)

Article References: Price, A. M., Fredricks, N. S., Koutsouras, G., Vallejo, F. A., Bonfield, C., Pastakia, D. J., Luo, L. Y., Boop, F., Ramaswamy, V., & Dewan, M. C. (2026). Spinal ependymoma: a comprehensive review of molecular classification, management guidelines, and clinical outcomes with a focus on the pediatric population (Part III of ependymomas across compartments). Journal of Neuro-Oncology, 180(1), Article 6. https://doi.org/10.1007/s11060-026-05816-9

Image Credits: AI Generated

DOI: 10.1007/s11060-026-05816-9

Keywords: spinal ependymoma, pediatric neuro-oncology, MYCN amplification, myxopapillary ependymoma, WHO CNS5 classification, gross total resection, intraoperative neuromonitoring, adjuvant radiotherapy, spinal deformity, DNA methylation profiling, craniospinal irradiation, lifelong surveillance

Neuroblastoma is a cancer of the sympathetic nervous system that arises most often in the adrenal glands or along the spine, and it accounts for a disproportionate share of childhood cancer deaths. The girl at the center of this report carried one of the worst prognostic markers in the disease: amplification of the MYCN gene, a genetic signature associated with aggressive, treatment-resistant tumors. Her initial treatment followed the standard European induction protocol known as COJEC, a rapid cycle of cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide, followed by two courses of topotecan, vincristine, and doxorubicin. When doctors re-evaluated her disease, the news was grim. The primary tumor in her abdomen remained large and active, it pressed on critical blood vessels, and scans revealed widespread involvement of her bones and bone marrow, yielding a skeletal disease score of 45 on the SIOPEN scale used across European pediatric oncology centers.

What followed was a relentless escalation of therapy. Second-line chemotherapy with temozolomide and irinotecan, later combined with the anti-GD2 antibody dinutuximab beta, succeeded in clearing the metastatic disease from her bones and marrow. She then underwent consolidation with two rounds of radiometabolic therapy using iodine-131 labeled MIBG—a radioactive form of the same tracer molecule used to image neuroblastoma—each followed by reinfusion of her own stem cells, and finally high-dose chemotherapy with busulfan and melphalan supported by another stem-cell rescue. Yet when the dust settled, one enemy remained entrenched: a residual mass in her retroperitoneum, the space behind the abdominal organs, measuring 13.3 by 9.8 by 6.9 centimeters. The mass continued to light up on MIBG scans, proof that living neuroblastoma cells persisted within it, and it wrapped around the celiac artery and the right renal artery while compressing the inferior vena cava, the largest vein in the body.

This anatomical situation presented surgeons with an impossible calculus. Any attempt at resection risked catastrophic hemorrhage from vessels that the tumor had encased, and there was no guarantee that a complete removal could be achieved even at that price. A biopsy taken through the skin confirmed that the mass contained viable neuroblastoma tissue showing differentiating features, meaning the cells were still alive and capable of regrowth. It was at this impasse that a multidisciplinary tumor board—bringing together pediatric oncologists, surgeons, interventional radiologists, pathologists, and radiation therapists at Bambino Gesù Children’s Hospital in Rome—turned to a technique that had never before been applied to a child with this disease: percutaneous electrochemotherapy.

The principle behind electrochemotherapy is elegantly physical. Cell membranes, though thin, are formidable barriers that normally prevent many chemotherapy drugs from entering cells efficiently. When short, high-voltage electric pulses are applied across a tissue, they transiently reorganize the lipid bilayer of those membranes, opening nanoscale pores in a process called reversible electroporation. The pores allow drug molecules to flood into the cell interior, and because the pulses are calibrated carefully, the membranes reseal afterward and the cells survive—only to be killed by the chemotherapy they have now absorbed in quantities far beyond what ordinary exposure could achieve. The drugs most commonly paired with electroporation are bleomycin and cisplatin, both of which become dramatically more cytotoxic inside electroporated cells. In adults, the technique has earned validated roles against melanoma, sarcoma, and head and neck tumors, but pediatric experience has been almost nonexistent.

The Roman team tailored the procedure to the unique biology of neuroblastoma. Rather than administering cisplatin intravenously, they injected it directly into the tumor, a strategy designed to maximize drug concentration within the lesion while minimizing systemic side effects—a rational choice given that platinum compounds are among the drugs to which neuroblastoma is classically sensitive. Under general anesthesia, with the child positioned prone, three variable-geometry needle electrodes with an active length of three centimeters were inserted intercostally, between the ribs, using computed tomography and ultrasound guidance. The target was the most metabolically active portion of the mass, precisely the region where MIBG single-photon emission imaging had shown the greatest tracer uptake and where the tumor pressed hardest against the inferior vena cava. Once the electrodes bracketed the target, an 18-gauge coaxial biopsy was taken through the field, and four milligrams of cisplatin at a concentration of two milligrams per milliliter were injected through a Chiba needle. The Cliniporator VITAE device then delivered voltage pulses ranging from 900 to 1,700 volts, completing the session.

The technical choreography matters because electroporation is unforgiving of sloppy planning. The electric field must cover the entire tumor volume homogeneously; any region that falls between electrodes may receive sub-lethal exposure and survive as a seed of recurrence. This is why careful pre-treatment planning and meticulous electrode placement are considered the linchpins of the technique, particularly for large or irregularly shaped lesions like the one in this case. Encouragingly, the procedure itself was uneventful. No immediate or delayed complications occurred, post-procedure monitoring revealed nothing concerning, and the child was discharged in stable condition. The team notes that the approach is also repeatable, an important attribute for a disease where residual lesions sometimes require more than one local intervention.

The follow-up imaging tells the story in two snapshots. One month after the procedure, magnetic resonance imaging revealed a necrotic, liquefied area of 20 by 20 millimeters within the treated field—direct evidence that the electroporated cells had died on schedule, consistent with the six-to-eight-week window in which electrochemotherapy’s radiological effects typically become apparent. The child then completed her maintenance phase of treatment with cis-retinoic acid and dinutuximab beta without any complications. Twelve months after the procedure, computed tomography and MIBG imaging delivered the decisive verdict: the mass had shrunk to 9.2 by 8.9 by 9.4 centimeters, and, critically, no residual MIBG uptake could be detected anywhere in the treated area. The metabolically active component that had survived everything modern pediatric oncology could throw at it had been silenced.

Why does the disappearance of MIBG avidity matter so much? MIBG is a norepinephrine analog that is taken up specifically by neuroblastoma cells, so persistent tracer uptake is a molecular signature of living tumor. In neuroblastoma, residual primary disease that remains MIBG-avid after multimodal treatment is a well-established negative prognostic factor, strongly correlated with relapse and poor survival. The ability to selectively target and neutralize these metabolically active foci—without opening the abdomen, without thermal energy that could damage vessels and adjacent organs, and without adding systemic toxicity—addresses one of the most frustrating gaps in current therapy. Thermal ablation techniques such as radiofrequency ablation and cryoablation have been used in selected pediatric tumors, but they are hazardous near major vessels, which act as heat sinks and limit ablation margins, and near structures like the celiac artery that cannot tolerate thermal injury. Electrochemotherapy’s non-thermal mechanism sidesteps that constraint, and the authors note that its effects are applicable across tumor histologies, including tumors resistant to other modalities.

The caveats are as important as the promise. This is a single case, reported by the team of Giulia Cassanelli, Maria Antonietta De Ioris, and Gian Luigi Natali, and pediatric oncology is littered with promising one-patient results that failed to generalize. The authors themselves are careful, framing electrochemotherapy as a feasible local option for selected patients and calling for further evaluation within a multidisciplinary framework rather than declaring a new standard of care. Yet the signals here are hard to dismiss: a first-in-child application performed safely in one of the most anatomically hostile locations imaginable, durable local control of the exact tumor component that predicts relapse, and a treatment that can be repeated if needed. If larger studies confirm these findings, children with refractory neuroblastoma whose tumors are deemed inoperable may one day have an option that today they lack entirely—a minimally invasive, precisely targeted way to finish what chemotherapy, antibodies, and radiation started.

Subject of Research: Electrochemotherapy for residual MIBG-avid disease in refractory pediatric neuroblastoma

Article Title: Electrochemotherapy as a potential local treatment for residual MIBG-avid disease in refractory pediatric neuroblastoma: a case report

Article References: Cassanelli, G., De Ioris, M. A., & Natali, G. L. (2026). Electrochemotherapy as a potential local treatment for residual MIBG-avid disease in refractory pediatric neuroblastoma: a case report. CVIR Oncology, 2(1), Article 3. https://doi.org/10.1007/s44343-026-00032-8

Image Credits: AI Generated

DOI: 10.1007/s44343-026-00032-8

Keywords: neuroblastoma, electrochemotherapy, electroporation, cisplatin, pediatric oncology, interventional radiology, MIBG imaging, tumor ablation, MYCN amplification, residual disease, case report, local therapy