Canine Gliomatosis Cerebri: Morphologic and Immunohistochemical Characterization Is Supportive of Glial Histogenesis

Abstract

Gliomatosis cerebri (GC) is a glioma subtype with diffuse neuroparenchymal infiltration without architectural distortion. GC was first used in human neuropathology and remained controversial until its elimination from the diagnostic lexicon in 2016. GC is currently defined as a diffuse growth pattern of glioma rather than a distinct entity. In this article, we characterize 24 cases of canine GC and classify these neoplasms as diffuse gliomas. Selected cases of canine GC were reviewed and immunolabeled for oligodendrocyte lineage transcription factor 2 (Olig2), glial fibrillary acidic protein (GFAP), and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase). The mean age of affected dogs was 7 years, and 9 were brachycephalic. Gross lesions (8 cases) consisted mainly of parenchymal swelling. Histologically, of the 24 cases, there was widespread infiltration of neoplastic cells with astrocytic (12 cases), oligodendroglial (8 cases), or mixed morphology (4 cases) in the brain (18 cases), spinal cord (4 cases), or both (2 cases). Secondary structures occurred across different tumor grades and were not restricted to high-grade neoplasms. Astrocytic neoplasms had moderate nuclear immunolabeling for Olig2 and robust cytoplasmic immunolabeling for GFAP. Oligodendroglial neoplasms had robust nuclear immunolabeling for Olig2, moderate or absent cytoplasmic immunolabeling for GFAP, and moderate cytoplasmic immunolabeling for CNPase. Tumors with mixed morphology had robust nuclear immunolabeling for Olig2 and variable cytoplasmic immunolabeling for GFAP and CNPase. Morphologic and immunohistochemical features confirmed a glial histogenesis for all tumors and allowed for their classification as diffuse, low- or high-grade astrocytoma; oligodendroglioma; or undefined glioma. Further research is needed to confirm or refute the hypothesis that canine GC represents an infiltrative growth pattern of canine glioma.

Cranial Spinal Spreading of Canine Brain Gliomas after Hypofractionated Volumetric-Modulated Arc Radiotherapy and Concomitant Temozolomide Chemotherapy: A Four-Case Report

“…As a differential diagnosis, another form of glioma, gliomatosis cerebri (GC), was considered. Cerebral gliomatosis is a rare type of neoplasm that has been described to infiltrate the spinal cord in dogs [ 39 , 40 ], but, differently from our cases, MRI examination showed that cerebral gliomatosis tended to be widespread, with relative conservation of neuronal architecture [ 40 , 41 , 42 , 43 ], predominantly astrocytic, and without neovascularization [ 44 , 45 ]. In the dogs reported in the present paper, the primary lesions were well circumscribed, did not occupy three continuous lobes, were not present in the thalamus, and the area of the caudal fossa was not affected.…”

Doublecortin immunolabeling in canine gliomas with distinct degrees of tumor infiltration

“…9 However, rare subsets of gliomas (referred to as diffusely infiltrating gliomas or gliomatosis cerebri) infiltrate widely into the neuroparenchyma without causing distortion to its overall architecture. 12 Although highly invasive, diffusely infiltrating gliomas are morphologically and immunohistochemically identical to the more commonly diagnosed nodular gliomas. 12 In fact, it is likely that diffusely infiltrating gliomas represent a growth pattern of canine glioma rather than a separate entity (gliomatosis cerebri), as has been the case in human neuropathology.…”

“…12 Although highly invasive, diffusely infiltrating gliomas are morphologically and immunohistochemically identical to the more commonly diagnosed nodular gliomas. 12 In fact, it is likely that diffusely infiltrating gliomas represent a growth pattern of canine glioma rather than a separate entity (gliomatosis cerebri), as has been the case in human neuropathology. 12,14 Doublecortin (DCX) is a microtubule-associated protein that plays an essential role in neuroblast migration in cerebrocortical development during embryonal life, but its expression has been also detected in subsets of adult subependymal and hippocampal neurons.…”

“…12 In fact, it is likely that diffusely infiltrating gliomas represent a growth pattern of canine glioma rather than a separate entity (gliomatosis cerebri), as has been the case in human neuropathology. 12,14 Doublecortin (DCX) is a microtubule-associated protein that plays an essential role in neuroblast migration in cerebrocortical development during embryonal life, but its expression has been also detected in subsets of adult subependymal and hippocampal neurons. 1,4 Thus, DCX immunohistochemistry (IHC) has been utilized to detect neuronal progenitor cells and neuronal differentiation in human, canine, and feline gliomas.…”

“…12 Although highly invasive, diffusely infiltrating gliomas are morphologically and immunohistochemically identical to the more commonly diagnosed nodular gliomas. 12 In fact, it is likely that diffusely infiltrating gliomas represent a growth pattern of canine glioma rather than a separate entity (gliomatosis cerebri), as has been the case in human neuropathology. 12,14…”