Review of the Recent Changes in the WHO Classification for Pediatric Brain and Spinal Cord Tumors.

BACKGROUND: Periodic updates to the World Health Organization (WHO) classification system for central nervous system (CNS) tumors reflect advances in the pathological diagnosis, categorization, and molecular underpinnings of primary brain, spinal cord, and peripheral nerve tumors. The 5th edition of the WHO Classification of CNS Tumors was published in 2021. This review discusses the guiding principles of the revision, introduces the more common new diagnostic entities, and describes tumor classification and nomenclature changes that are relevant for pediatric neurological surgeons. SUMMARY: Revisions to the WHO CNS tumor classification system introduced new diagnostic entities, restructured and renamed other entities with particular impact in the diffuse gliomas and CNS embryonal tumors, and expanded the requirements for incorporating both molecular and histological features of CNS tumors into a unified integrated diagnosis. Many of the new diagnostic entities occur at least occasionally in pediatric patients and will thus be encountered by pediatric neurosurgeons. New nomenclature impacts the terminology that is applied in communication between pathologists, surgeons, clinicians, and patients. Requirements for molecular information in tumor diagnosis are expected to refine diagnostic categories while also introducing practical considerations for intraoperative consultation, preliminary histological evaluation, and triaging of neurosurgical tissue samples for histology, molecular testing, and clinical trial requirements. KEY MESSAGES: Pediatric brain tumor diagnosis and clinical management are a multidisciplinary effort that is rapidly advancing in the molecular era. Interdisciplinary collaboration is critical for providing the best care for pediatric CNS tumor patients. Pediatric neurosurgeons and their local neuropathologists and neuro-oncologists must work collaboratively to put the most current CNS tumor diagnostic guidelines into standard practice.

Neurological emergency from rare spinal metalloma: Case report and literature review.

Metallosis is a rare and poorly understood long-term complication of instrumented surgery that can result in an inflammatory pseudotumor termed metalloma. We describe a particularly unique case and compare it to 6 analogous cases identified by PubMed and/or Medline search through July 2020. A 79-year-old male with multiple prior spinal lumbar fusion procedures presented with progressive weakness and pain. Imaging revealed a large mass surrounding the right-sided paraspinal rod with extension into the spinal canal, neural foramina, extraforaminal spaces, psoas muscle, marrow spaces, and right sided pedicles. The case presented is a unique example of a unilateral metalloma with mixed-metal instrumentation that created a progressive neurologic deficit without infection, pseudoarthrosis, or hardware failure. This case highlights the lack of understanding regarding the pathophysiology of metallosis and metalloma in spinal instrumentation. We highlight the imaging findings of metalloma to encourage early identification for removal and decompression.

A case of recurrent epilepsy-associated rosette-forming glioneuronal tumor with anaplastic transformation in the absence of therapy.

Rosette-forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy-associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment. We present the case of a 5-year-old girl with seizures, who underwent near total resection of a cystic temporal lobe lesion. Pathology showed morphologic and immunohistochemical features of RGNT, albeit with focally overlapping DNET-like patterns. Resections of residual or recurrent tumor were performed 1 year and 5 years after the initial resection, but no adjuvant radiation or chemotherapy was given. Ten years after the initial resection, surveillance imaging identified new and enhancing nodules, leading to another gross total resection. This specimen showed areas similar to the original tumor, but also high-grade foci with oligodendroglial morphology, increased cellularity, palisading necrosis, microvascular proliferation, and up to 13 mitotic figures per 10 high power fields. Ancillary studies the status by sequencing showed wild-type of the isocitrate dehydrogenase 1 (IDH1), IDH2, and human histone 3.3 (H3F3A) genes, and BRAF studies were negative for mutation or rearrangement. Fluorescence in situ hybridization (FISH) showed codeletion of 1p and 19q limited to the high-grade regions. By immunohistochemistry there was loss of nuclear alpha-thalassemia mental retardation syndrome, X-linked (ATRX) expression only in the high-grade region. Next-generation sequencing showed an fibroblast growth factor receptor receptor 1 (FGFR1) kinase domain internal tandem duplication in three resection specimens. ATRX mutation in the high-grade tumor was confirmed by sequencing which showed a frameshift mutation (p.R1427fs), while the apparent 1p/19q-codeletion by FISH was due to loss of chromosome arm 1p and only partial loss of 19q. Exceptional features of this case include the temporal lobe location, 1p/19q loss by FISH without true whole-arm codeletion, and anaplastic transformation associated with ATRX mutation without radiation or chemotherapy.

Applications of molecular neuro-oncology - a review of diffuse glioma integrated diagnosis and emerging molecular entities.

Insights into the molecular underpinnings of primary central nervous system tumors have radically changed the approach to tumor diagnosis and classification. Diagnostic emphasis has shifted from the morphology of a tumor under the microscope to an integrated approach based on morphologic and molecular features, including gene mutations, chromosomal copy number alterations, and gene rearrangements. In 2016, the World Health Organization provided guidelines for making an integrated diagnosis that incorporates both morphologic and molecular features in a subset of brain tumors. The integrated diagnosis now applies to infiltrating gliomas, a category that includes diffusely infiltrating astrocytoma grades II, III, and IV, and oligodendroglioma, grades II and III, thereby encompassing the most common primary intra-axial central nervous system tumors. Other neoplasms such as medulloblastoma, embryonal tumor with multilayered rosettes, certain supratentorial ependymomas, and atypical teratoid/rhabdoid tumor are also eligible for integrated diagnosis, which can sometimes be aided by characteristic immunohistochemical markers. Since 2016, advances in molecular neuro-oncology have resulted in periodic updates and clarifications to the integrated diagnostic approach. These advances reflect expanding knowledge on the molecular pathology of brain tumors, but raise a challenge in rapidly incorporating new molecular findings into diagnostic practice. This review provides a background on the molecular characteristics of primary brain tumors, emphasizing the molecular basis for classification of infiltrating gliomas, the most common entities that are eligible for an integrated diagnosis. We then discuss entities within the diffuse gliomas that do not receive an integrated diagnosis by WHO 2016 criteria, but have distinctive molecular features that are important to recognize because their clinical behavior can influence clinical management and prognosis. Particular attention is given to the histone H3 G34R/G34V mutant astrocytomas, an entity to consider when faced with an infiltrating glioma in the cerebral hemisphere of children and young adults, and to the group of histologically lower grade diffuse astrocytic gliomas with molecular features of glioblastoma, an important category of tumors to recognize due to their aggressive clinical behavior.

Seeding of Abdomen with Primary Intracranial Hemangiopericytoma by Ventriculoperitoneal Shunt: Case Report.

BACKGROUND: Ventriculoperitoneal shunt (VPS) placement has been implicated in extraneural metastasis of many primary central nervous system tumors. Reported cases include, but are not limited to, medulloblastoma, germ cell tumor, astrocytoma, oligodendroglioma, lymphoma, ependymoma, melanoma, and choroid plexus tumors. However, a literature review reveals no reported cases of extraneural metastasis of solitary fibrous tumor/hemangiopericytoma (SFT/HPC). CASE DESCRIPTION: Here we report the case of a 34-year-old man with recurrent intracranial malignant SFT/HPC who had undergone surgical tumor resection and subsequent placement of a VPS for obstructive hydrocephalus in 2004. Subsequently, the patient presented in 2011 and again in 2013 with abdominal SFT/HPC metastasis likely caused by the presence of the VPS. CONCLUSION: The case raises concern regarding placement of a VPS in patients with obstructive hydrocephalus caused by SFT/HPC. To avoid spread of SFT/HPC to the abdomen, we propose that patients with intracranial SFT/HPC and obstructive hydrocephalus be treated primarily by endoscopic third ventriculostomy.