Extracranial Glioblastoma Metastasis: A Neuropathological Case Report

Abstract

Glioblastoma (GBM) is a central nervous system (CNS) high-grade glioma with a dismal patient prognosis. Classical concepts surrounding GBM development and progression indicate its ability to produce metastasis within the CNS, one of the few primary tumors with such capabilities. While classical concepts state that no primary CNS tumor produces extracranial metastasis, there have been multiple reports of such occurrences over the previous two decades. Here, we report a case of a male in his forties who presented to our institution with complaints of progressive headache and a history of right temporal craniotomy one month prior with a histologically verified GBM performed at another institution. Neuroradiology confirmed a residual tumor in the areas of the previous craniotomy, and gross total excision confirmed the diagnosis of GBM, although based on the presence of connective tissue amidst the tumor stroma, gliosarcoma could not be ruled out. The patient initiated treatment, and his condition remained stable for four calendar years until he again presented to our institution with a rapidly growing tumor mass in the right lateral neck region. Excision of the neck mass showed histopathological features of a tumor comprised of atypical cells with pronounced polymorphism, some with spindle cell morphology and a tendency for fascicular growth and focal palisade necrosis. Immunohistochemistry with a broad set of markers disproved epithelial, mesenchymal, melanocytic, and lymphoid genesis, with some markers of glial genesis present; hence, metastatic GBM was established. The patient reinitiated treatment and is currently stable. The steadily increasing amount of similar reported cases, together with the steady, albeit small, increase in GBM patient survival and improvement of neurooncological healthcare distribution and follow-up, challenge the classical concepts of GBM and other primary CNS tumors being unable to produce metastasis and swaying this perception towards the biological capabilities of these tumors to produce metastasis, while such rarely develop due to the short patient survival.

Postoperative Extracranial Glioblastoma

“…In both our two cases, GFAP staining shows strong diffuse positivity. However, GFAP negative metastatic GBM has been reported 31 . In this case, a careful interpretation of histological, immunohistochemical, and clinical data is warranted.…”

Letter to the editor regarding “unusual extraneural metastasis of glioblastoma”

“…GBM has classically been considered incapable of extracranial metastasis since Cushing and Bailey’s famous 1926 report. [ 7 , 9 , 20 ] However, as described by Achi et al ., extracranial GBM metastases have been well-reported in the literature. [ 1 ] In fact, 0.2–2.7% of GBMs are accompanied by extracranial metastases,[ 3 ] and up to 20% of GBM patients have circulating tumor cells present in their bloodstream.…”

“…Several metastatic pathways have been described, including leptomeningeal extension,[ 7 , 9 , 21 ] cerebrospinal fluid (CSF) bulk flow,[ 15 ] direct invasion through surrounding tissues, along cranial nerves or spinal nerves,[ 11 , 21 ] hematogenous dissemination,[ 5 ] and through the recently described “glymphatic” drainage pathway. [ 20 ] We wish to specifically highlight the roles of iatrogenic spread and glymphatic drainage in GBM metastasis.…”

“…These perivenous spaces drain into the dural lymphatics, which ultimately exit the skull and drain into the deep cervical lymph nodes and the systemic circulation. [ 4 , 12 , 19 , 20 ] It has been postulated that GBM metastases may occur through this drainage system, as GBM metastases appear to have a predilection for the deep cervical lymph nodes; in fact, 51% of reported extracranial GBM metastases occur in the cervical lymph nodes. [ 17 , 26 ] Furthermore, there have also been several reports of GBM metastases to the parotid gland, which is imbued with a rich lymphatic network during embryological development.…”

“…The low reported rate of GBM metastasis is due to the rate of mortality before the development of a recognizable extracranial tumor: [ 16 ] The median time between GBM diagnosis and verified GBM metastasis is 2 years,[ 26 ] while the medial survival of GBM following initial diagnosis is 13 months. [ 9 ] We hypothesize that extracranial GBM metastases may begin to present clinically significant problems as GBM survival increases;[ 18 , 20 , 21 , 22 , 25 ] furthermore, extracranial GBM management protocols do not currently exist. [ 5 , 9 , 21 , 22 , 25 ] Until protocols are developed, we recommend attempting to limit the impact of iatrogenic tumor spread during surgery.…”