Choroid plexus hemorrhage mimicking an intraventricular neoplasm in a newborn

Imaging yielded a differential diagnosis of embryonal tumor, ependymoma, and hemorrhagic choroid plexus papilloma. Histomorphology shows acute hemorrhage and hemosiderin-stained choroid plexus with a rounded, hobnail-shaped epithelial surface. The rounded surface distinguishes this normal choroid plexus from the epithelium of a choroid plexus papilloma, which has a flat surface.

Floating neurons in specific glioneuronal elements of a dysembrioplastic neuroepithelial tumor

Uveal melanoma at iris root

Neoplasm is extending into and blocking anterior chamber angle

Summary of the Major Changes in the 2016 WHO Classification of CNS Tumors

Major restructuring of medulloblastomas, with incorporation of genetically defined entities

Addition of brain invasion as a criterion for atypical meningioma

Restructuring of solitary fibrous tumor and hemangiopericytoma (SFT/HPC) as one entity and adapting a grading system to accommodate this change

Expansion and clarification of entities included in nerve sheath tumors, with addition of hybrid nerve sheath tumors and separation of melanotic schwannoma from other schwannomas

Expansion of entities included in hematopoietic/lymphoid tumors of the CNS (lymphomas and histiocytic tumors)

Addition of the following newly recognized entities, variants and patterns:

- IDH-wildtype and IDH-mutant glioblastoma (entities)

- Diffuse midline glioma, H3 K27M–mutant (entity)

- Embryonal tumour with multilayered rosettes, C19MC-altered (entity)

- Ependymoma, RELA fusion–positive (entity)

- Diffuse leptomeningeal glioneuronal tumor (entity)

- Anaplastic PXA (entity)

- Epithelioid glioblastoma (variant)

- Glioblastoma with primitive neuronal component (pattern)

- Multinodular and vacuolated pattern of ganglion cell tumor (pattern)

Deletion of the following entities, variants and terms:

- Gliomatosis cerebri

- Protoplasmic and fibrillary astrocytoma variants

- Cellular ependymoma variant

- “Primitive neuroectodermal tumour” terminology

(Adapted from table 2 in Louis DN et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol (2016) 131:803–820.

Orbital rhabdomyosarcoma

Orbital rhabdomyosarcoma with cross striations and rhabdomyoblasts. Arrow points to eosinophilic strap cell with cross striations. Rhabdomyosarcoma is the most common malignant orbital tumor of childhood.

(Adapted from Eye Pathology: An Atlas and Text [2nd edition] by Ralph C. Eagle)

Xanthic cell in a pleomorphic xanthoastrocytoma

AANP Meeting Presidential Symposium Speaker: Neil Cashman, MD

From the American Association of Neuropathologists front office:

Neil Cashman, MD

AANP is very excited to have Dr. Neil Cashman present at this year’s Presidential Symposium on Sunday, June 19. His talk will be on Seeding and Propagation of SOD1 Misfolding in Amyotrophic Lateral Sclerosis.

Dr. Neil Cashman is a neurologist-neuroscientist working in neurodegeneration and neuroimmunology.  His special areas of work are the motor neuron diseases, particularly amyotrophic lateral sclerosis, and the amyloid encephalopathies, including prion illnesses and Alzheimer’s disease. He is Professor of Medicine at the University of British Columbia, where he holds the Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases. He is the Founder and Chief Scientific Officer of ProMIS Neurosciences in Toronto.

Special honors include the Jonas Salk Prize (2000), his Tier 1 Canada Research Chair in at the UBC (2005-2018), election to the Canadian Academy of Health Sciences (2008), and Genome BC award for Scientific Excellence (2012).

We look forward to Dr. Cashman’s discussion on ALS at the 92^nd Annual Meeting!

Finally!!! The new WHO CNS tumor classification book has been published

After months of anticipation, the new brain tumor WHO classification book is here! You can order it at this web address.

Thanks to Dr. Mark Cohen for alerting me to this development.

MYB-QKI fusion: A novel alteration that may define and drive pediatric angiocentric glioma

Angiiocentric glioma

Angiocentric glioma is a rare form of pediatric low-grade gliomas (PLGG), first described in 2005, that arises in the cerebral cortex and shares histological features of astrocytomas and ependymomas. Until now, nothing was known of the genetic events underlying this tumor type. In a recent study published in Nature Genetics, Bhandopadhayay et al (see reference below) used whole genome sequencing and/or RNAseq to show that all seven angiocentric gliomas in their sample set harbored rearrangements in MYB, the most common being intrachromosomal deletions resulting in MYB-QKI gene fusions. QKI encodes the RNA-binding protein Quaking, which has been previously established as a tumor suppressor in glioblastoma. Analysis of 12 additional FFPE angiocentric glioma specimens revealed that all of these had alterations in MYB, with the MYB-QKI alteration being confirmed in six cases. The MYB-QKI gene fusion was not observed in any other PLGGs in the panel and therefore may specifically define angiocentric glioma. The MYB-QKI fusion protein was shown by mechanistic studies to drive expression of pro-oncogenic target genes. These data strongly support the concepts that MYB-QKI fusions define angiogentric glioma and act as the oncogenic driver mutation in this tumor.

This post is adapted from "Highlights from the Literature", edited by Kenneth Aldape in the journal Neuro-Oncology 18(6), 761–763, 2016

Reference:
Bhandopadhayay P, Ramkissoon LA, Jain P, et al. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat Genet 2016;48(3):273–282.

Absence of Lymphatic Vessels in PCNSL May Contribute to Confinement of Tumor Cells to the Central Nervous System

Did you ever wonder why primary CNS lymphoma stays restricted to the CNS? Over the years, I have been asked that by several students and trainees, but I could never give a good answer. An article published online in the Journal of Neuropathology and Experimental Neurology on May 3rd points toward an answer. The phenomenon may be related to the unique lymphatic drainage system of the CNS. The brief report, entitled Absence of Lymphatic Vessels in PCNSL May Contribute to Confinement of Tumor Cells to the Central Nervous System, is authored by Martina Deckert and colleagues from the Department of Neuropathology at the University Hospital of Cologne (Germany) and the Institute of Human Genetics at Christian-Albrechts-University Kiel (Germany).

Deckert and colleagues investigated PCNSL for the presence of lymphatic vessels using immunohistochemistry for Lyve-1, podoplanin, and Prox-1 expression in a series of 20 intraparenchymal PCNSL biopsies in comparison with 8 dural/meningeal-based foci of systemic diffuse large B-cell lymphoma (DLBCL) as well as 20 glioblastomas lacking any contact with the meninges.

Absence of lymphatic vessels in PCNSL demonstrated by
negative Prox-1 staining
(inset: human tonsils serve as positive control) 

All PCNSLs and glioblastomas investigated lacked lymphatic vessels as evidenced by absence of immunohistochmemical lymphatic vessel markers. However, dural/meningeal DLBCL foci harbored lymphatic vessels that expressed Lyve-1 (3/8 tumors), podoplanin (5/8 tumors), and Prox-1 (5/8
tumors) in areas where the tumors had invaded the fibrous tissue of the dura. Taken together, the immunohistochemical panel demonstrated lymphatic vessels in 7 out of 8 (87.5%) of the DLBCLs investigated.

The authors note that although cerebrospinal fluid drains to lymph nodes through a variety of routes, these passages are presumably too small to allow passage of large neoplastic lymphocytes.

This report leaves one glaring question unanswered: If one investigated glioblastomas that did have contact with the dura/meninges, would those show evidence of lymphatic vessels? If so, why do those glioblastomas not metastatize to areas outside the CNS?

Best Post of March 2016: A list of neuropathologists who are departmental chairs

The next in our "Best of the Month" series is from March 25, 2016. After the initial post, several readers wrote in to add to the original collection of names. 

There is a disproportionate number of neuropathologists who are chairs of their departments. Some readers thought it would be interesting if a list of these chairs could be compiled. With the help of Mark Cohen, Bette Kleinschmidt-DeMasters, and Robert Mrak, a pretty comprehensive list has been assembled:

Douglas Anthony at Brown

Steven Carroll at Medical University of South Carolina

Robert Corona at SUNY Upstate

Jeffrey Golden at Brigham and Women's Hospital

Eyas Hattab at University of Louisville

Alex Judkins at Children's Hospital Los Angeles

David Louis at Massachusetts General Hospital

Jenny Libien at SUNY Downstate

Thomas Montine currently at University of Washington and soon to be at Stanford

Edwin Monuki at the University of California Irvine

Robert Mrak at the University of Toledo

Amyn Rojiani at Augusta University

Kevin Roth at Columbia

John Schweitzer at East Tennessee State University

Also of note:

William Hickey at Dartmouth (acting chair of pharmacology and toxicology, former pathology chair)