Gliomatosis cerebri overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]
Overview
Gliomatosis cerebri is a rare primary brain tumor. According to WHO, gliomatosis cerebri is classified as a distinct nosological entity among other glial tumors of the central nervous system. Gliomatosis cerebri is defined as a diffusely infiltrating neuroepithelial tumor, which involves at least three cerebral lobes and occasionally infratentorial structures or the spinal cord. The brain architecture is commonly preserved, with neurons being spared, and the mass effect is minimal. Gliomatosis cerebri was first reported by Landau in 1910. Since then, several physicians published isolated cases of gliomatosis cerebri and only later in 1938, it was completely studied and described by Nevin. On gross pathology, gliomatosis cerebri is characterized by a diffuse astrocytic growth pattern involving at least three cerebral lobes and bilateral involvement of the cerebral hemispheres, deep gray matter, brainstem, or cerebellum. On microscopic histopathological examination, gliomatosis cerebri is characterized by diffuse proliferation of immature glial elements resembling astrocytes, oligodendroglia, or undifferentiated cells with cytologic and nuclear atypia, calcifications, microcysts, and mitotic figures without the presence of any necrosis or microvascular proliferation. Gliomatosis cerebri is a rare brain tumor. The incidence of gliomatosis cerebri is estimated to be less than 100 cases per year in the United States. Gliomatosis cerebri is a disease that tends to affect the middle-aged population. The peak incidence for gliomatosis cerebri is 20-40 years. The median age at diagnosis is 34 years.Males are more commonly affected with gliomatosis cerebri than females. The male to female ratio is approximately 1.5 to 1.If left untreated, patients with gliomatosis cerebri may progress to develop focal neurological deficits, altered mental status, hydrocephalus, brain herniation, and ultimately death. Transformation into glioblastoma (grade 4) may occur a few years later. Common complications of gliomatosis cerebri include brain herniation, hydrocephalus, coma, metastasis, recurrence, benign intracranial hypertension, and side effects of radiotherapy and chemotherapy. Prognosis of gliomatosis cerebri is generally poor, and the 5-year survival rate of patients with treatment is approximately 17.7%. Symptoms of gliomatosis cerebri include headache, nausea, vomiting, seizure, loss of balance, memory loss, personality changes, cognitive problems, confusion, diplopia, difficulty in swallowing, difficulty in speech, motor weakness, and facial numbness.On head CT scan, gliomatosis cerebri is characterized by an isodense and hypoattenuated mass with ill-defined asymmetry and lack of mass effect. On brain MRI, gliomatosis cerebri is characterized by bilateral and diffuse infiltrative tumor which is isointense or hypointense on T1-weighted images and hyperintense on T2-weighted and FLAIR images. Other imaging studies for gliomatosis cerebri include MR spectroscopy, MR perfusion, PET scan, and bone scan. Radiotherapy and chemotherapy are recommended among all patients who develop gliomatosis cerebri. Temozolomide and PCV 3 combination chemotherapy are the preferred drugs for the treatment of high-grade and low-grade gliomatosis cerebri, respectively. Supportive therapy for gliomatosis cerebri includes anticonvulsants and corticosteroids. Surgery is not the first-line treatment option for patients with gliomatosis cerebri.
Historical Perspective
Gliomatosis cerebri was first reported by Landau in 1910. Since then, several physicians published isolated cases of gliomatosis cerebri and only later in 1938, it was completely studied and described by Nevin.
Classification
Gliomatosis cerebri may be classified into several subtypes based on the origin (primary and secondary) and the type of tumor cell (astrocytic, oligodendroglial, and mixed).
Pathophysiology
Genes involved in pathogenesis of gliomatosis cerebri include p53, OLIG-2, Ki-67, EGFR, PTEN, VCAM1, VEGF, and gene on chromosomes 7q, 10q, and 13q. Gliomatosis cerebri may be associated with neurofibromatosis type 1 and pilomatricoma. On gross pathology, gliomatosis cerebri is characterized by a diffuse astrocytic growth pattern involving at least three cerebral lobes and bilateral involvement of the cerebral hemispheres, deep gray matter, brainstem, or cerebellum. On microscopic histopathological examination, gliomatosis cerebri is characterized by diffuse proliferation of immature glial elements resembling astrocytes, oligodendroglia, or undifferentiated cells with cytologic and nuclear atypia, calcifications, microcysts, and mitotic figures without the presence of any necrosis or microvascular proliferation. Gliomatosis cerebri is demonstrated by positivity to tumor markers such as GFAP, S-100, and Ki-67.
Causes
Common causes of gliomatosis cerebri include genetic mutations. The genes associated with the etiology of gliomatosis cerebri include p53,OLIG2, Ki-67, EGFR, PTEN, VCAM1, VEGF, and genes on chromosome 7q, 10q, and 13q.
Differentiating brain tumors from other diseases
Gliomatosis cerebri must be differentiated from progressive multifocal leukoencephalopathy, multiple sclerosis, Marburg disease, multicentric glioblastoma, primary CNS lymphoma, viral encephalitis, acute disseminated encephalomyelitis, CNS vasculitis, Behçet's disease, venous sinus thrombosis, stroke, Gerstmann syndrome, leptomeningeal gliomatosis, Alzheimer's disease, Lewy body dementia, and parkinsonism.
Epidemiology and Demographics
Gliomatosis cerebri is a rare brain tumor. The incidence of gliomatosis cerebri is estimated to be less than 100 cases per year in the United States. Gliomatosis cerebri is a disease that tends to affect the middle-aged population. The peak incidence for gliomatosis cerebri is 20-40 years. The median age at diagnosis is 34 years. Males are more commonly affected with gliomatosis cerebri than females. The male to female ratio is approximately 1.5 to 1.
Risk factors
The most potent risk factor associated with the development of gliomatosis cerebri is neurofibromatosis type 1.
Screening
There is insufficient evidence to recommend routine screening for gliomatosis cerebri.
Natural History, Complications and Prognosis
If left untreated, patients with gliomatosis cerebri may progress to develop focal neurological deficits, altered mental status, hydrocephalus, brain herniation, and ultimately death. Transformation into glioblastoma (grade 4) may occur a few years later. Common complications of gliomatosis cerebri include brain herniation, hydrocephalus, coma, metastasis, recurrence, benign intracranial hypertension, and side effects of radiotherapy and chemotherapy. Prognosis of gliomatosis cerebri is generally poor, and the 5-year survival rate of patients with treatment is approximately 17.7%. Median survival of patients who are treated with whole brain radiotherapy alone is 13.7 months (range 1–35), whereas those who are treated with combined whole brain radiation therapy and chemotherapy have a median survival of 26.14 months (range 6–42).
Staging
There is no established system for the staging of gliomatosis cerebri.
History and Symptoms
When evaluating a patient for gliomatosis cerebri, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus when obtaining the history include review of common associated conditions such as neurofibromatosis type 1. Symptoms of gliomatosis cerebri include headache, nausea, vomiting, seizure, loss of balance, memory loss, personality changes, cognitive problems, confusion, diplopia, difficulty in swallowing, difficulty in speech, motor weakness, and facial numbness.
Physical examination
Common physical examination findings of gliomatosis cerebri include dysphagia, dysarthria, nystagmus, papilledema, hemiparesis, facial paresthesia, vision loss, ataxia, mental status changes, aphasia, and focal neurological defects (corticospinal tract defects, spinocerebellar tract defects, and cranioneuropathies).
Laboratory Findings
There are no diagnostic lab findings associated with gliomatosis cerebri.
Chest X Ray
Chest x-ray may be performed to detect metastases of gliomatosis cerebri to the lungs.
CT
Head CT scan is helpful in the diagnosis of gliomatosis cerebri. On head CT scan, gliomatosis cerebri is characterized by an isodense and hypoattenuated mass with ill-defined asymmetry and lack of mass effect.
MRI
Brain MRI is helpful in the diagnosis of gliomatosis cerebri. On brain MRI, gliomatosis cerebri is characterized by bilateral and diffuse infiltrative tumor which is isointense or hypointense on T1-weighted images and hyperintense on T2-weighted and FLAIR images.
Ultrasound
There are no ultrasound findings associated with gliomatosis cerebri.
Other Imaging Findings
Other imaging studies for gliomatosis cerebri include MR spectroscopy (decreased NAA/creatine ratio and elevated choline/creatine ratio, choline/NAA ratio, and myoinositol), MR perfusion (low/normal relative cerebral blood flow), PET scan (markedly decreased accumulation of [18F]-fluorodeoxyglucose on F-18 FDG PET, hypermetabolism on C-11 methionine PET, and marked increase in cerebral blood flow on 15(O)-water PET), and bone scan (metastasis to bones).
Other Diagnostic Studies
Other diagnostic studies for gliomatosis cerebri include biopsy, which demonstrates glial cells resembling astrocytes, oligodendrocytes, or undifferentiated cells with atypia and mitoses.
Medical Therapy
Radiotherapy and chemotherapy are recommended among all patients who develop gliomatosis cerebri. Temozolomide and PCV 3 combination chemotherapy are the preferred drugs for the treatment of high-grade and low-grade gliomatosis cerebri, respectively. Supportive therapy for gliomatosis cerebri includes anticonvulsants and corticosteroids.
Surgery
Surgery is not the first-line treatment option for patients with gliomatosis cerebri. CSF shunting is usually reserved for patients with hydrocephalus.
Primary Prevention
There is no established method for prevention of gliomatosis cerebri.
Secondary Prevention
There are no secondary preventive measures available for gliomatosis cerebri.