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Table 1 Differential diagnoses of tumefactive demyelinated lesions, malignant glial tumours, progressive multifocal leukoencephalopathy and progressive multifocal leukoencephalopathy associated with immune reconstitution syndrome

From: Anaplastic astrocytoma mimicking progressive multifocal leucoencephalopathy: a case report and review of the overlapping syndromes

  TDL malignant GT PML PML-IRIS References
Clinical sy motor, cognitive (aphasia, apraxia, agnosia, Gerstman, coma) sensitive, cerebellar, brain stem. Visual field defects, Epileptic seizures epileptic seizures, cognitive and memory deficit, motor, sensitive. altered mental status (aphasia), motor, limb and gait ataxia, visual symptoms: homonymous hemianopia, cortical blindness, diplopia. Epileptic seizures. No optic nerve and spinal cord involvement. altered mental status (aphasia), motor, limb and gait ataxia, visual symptoms: hemianopia, cortical blindness, diplopia. Epileptic seizures. No optic nerve and spinal cord involvement [814], [52]
MRI T2w/
FLAIR
Unilateral or bilateral. Frontal, parietal. Periventricular, juxta cortical. 2 cm, large lesion with little mass effect and edema Variable rate of hyper-intensity. Central dilated vessel.
Irregular border. Supra-tentorial WM, partially GM involvement.
Unilateral. Supra-tentorial.
Hyper or hypo intense.
Irregular border. Central necrosis.
Intensive vascular edema and mass effect
Bilateral. Supra-Intra-tentorial. Cortex, deep gray matter. (Frontal, parietal, occipital. Subcortical location, U-fibers, cortex, basal ganglia). 3 cm.
Early new lesions. Hyper-intense. Ill-defined to WM, sharp to GM.
No mass effect. Punctuate perilesional lesions.
Bilateral, spreading. Cortex and subcortical WM. Edema [1118], [16, 26, 54]
MRI T1w Hypo-intense.
CT- hypo-intensity
Hypo-intense. CT-hypo-intensity Hypo-intense.
CT-hypo intensity
Hypo-intense with hyper- intense rim [1118], [26, 54]
MRI Gd + incomplete rim enhancement complete rim enhancement negative or variable, punctuate and rim like positive or variable, punctate and rim like [1118], [26, 54]
MRI - PWI, DWI decreased PWI in lesions, increased DWI in active demyelination increased PWI, increased DWI in central necrosis DWI always hyper-intense, with peripheral rim. +/− restricted DWI [918, 26]
1H- MRS increased Cho, lipids, lactate, mildly decreased NAA and NAA/Cr (differ from malignant GT)
elevation of the β,γ-Glx peaks
increased Cho and Cho/Cr, lipids, lactate, decreased NAA, lack of β,γ-Glx elevation A decrease of NAA/Cr ratio, NAA and Cr. An increase of Lac/Cr, Cho/Cr, Cho, lipids/Cr, mIns, Lac, Lip. increased Cho, decreased NAA, the presence of Lac/lipids at 1.3 ppm, and the presence of mIns, Higher Cho/Cr, mIns/Cr, Lip1/Cr, and Lip2/Cr in PML-IRIS than PML .
Lower NAA/Cr than PML.
[11], [13, 14], [28,29,30,31]
CSF native normal or mild increased proteinorhachia and white blood count.
Positive oligoclonal bands, elevated IgG index
GFAP+ cells mildly increased cellularity, normal proteinorhachia mild to moderate increase of lymphocytes and protein levels [10, 11], [14, 15]
CSF JCV DNA negative, infrequently low positivity (less than 25) negative? unknown JCV-specific IgG, DNA copies, infrequently negative JCV-specific IgG, DNA copies. Sometimes negative [1218, 31]
Response to corticoids very good only partial none good [2, 9,10,11], [15, 27]
Histology Hyper-cellularity, myelin protein-laden macrophages, variable lymphocytic inflammation, reactive gliosis and relative axonal preservation. moderate cellularity, bizarre cells with hyperchromatic nuclei, moderate pleomorphic, gemistocytes, perivascular lymphocytes, rare areas of necrosis, neo-vascularization
GFAP + cells: immature,
reactive, and neoplastic astrocytes and ependymal cells
swelling of oligodendrocyte and multi-lobular astrocytes, basophilic nuclei, eosinophilic inclusion bodies,
2/3 of number of T cells in PML-IRIS.
Positive DNA JCV staining in all types of cells. Active gene copies in high numbers of virally infected cells, as well as a low inflam- matory infiltrate.
Hyper-cellularity, CD8+ positive T cells dominate - their number the same as in active MS lesions, fewer CD4+ and CD20+ T cells in perivascular cuffs.
High plasma and B cells in PML-IRIS-lesions.
No or low number JCV-infected cells.
[2, 10], [15, 17,18,19,20, 49], [41,42,43, 46,47,48],
[54, 55]
Outcome as typical MS progressive worsening progressive worsening worsening, regression possible [6, 1020, 49], [24, 25], [47, 48], [51]
Immunological markers in peripheral blood upregulation of transcription factors of Th1 (pSTAT1 and T-bet) and Th17 (pSTAT3) in circulating CD4+, CD8 + T-cells and monocytes. CD4+ T-cells with a proinflammatory Th1 and Th17 phenotype, lower T-bet, pSTAT1, and pSTAT3 in CD4+, CD8 + T-cells, and monocytes. Lower CD4 Th1 and Th17. Increased IL-10, TGF-β, PGE2, down modulation of co-stimulation molecules by APCs. Tumor angiogenesis, expression of CD34+ progenitor cells.
Deficit of NK cells
variable data: stable CD4+ and CD8+, non-significant decrease or increased T cells but unchanged CD4/CD8 ratio. Decrease expression of CD49d, CD29 (VLA-4), CD11a, CD62L, CXCR3 on T cells. Decreased expression of VLA4 on myeloid dendritic cells, decreased count of dendritic cells. Production of CD34+ cells, increase of memory B cells. Increased IL-10. Increased IFN-γ, IL-12p70, IL-4, IL-10, IL-5, IL-13.
CD4+,T1 + PSTAT3+, CD8+, PSTAT1+,T-bet + .
Decreased CD4+, CD25+ FoxP3+
[36,37,38,39,40,41,42,43,44,45,46,47,48, 56] [54]
  1. TDL tumefactive demyelinating lesion, GT glial tumour, PML progressive multifocal leukoencephalopathy, PML-IRIS PML -immune reconstitution inflammatory syndrome, MRI T2w T2 weighted imagines of magnetic resonance imagine, MRI T1w T1 weighted imagines, DWI diffusion weighted imagines, PWI perfusion weighted imagines, GAD gadolinium enhancement, WM white matter, GM gray matter, CT computer tomography, 1H–MRS proton magnetic resonance spectroscopy, Cho cholin, NAA N-acetyl aspartate, Cr creatine, Lac lactate, mIns myoinositol, βγGlx βγ glutamate + glutamin, Lip lipids, NK natural killers, VLA4 alfa integrin 4, IL 4,10,12,13 interleukin 4,10,12,13, CD4 T helper lymphocytes, CD8 T suppressor lymphocytes, CD11 alfa component of various integrins, CD20 B-lymphocyte antigen, CD28 proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival, CD34+ hematopoietic progenitor cell antigen, CD49 an integrin alpha subunit, CD62 a cell adhesion molecule found on lymphocytes, CD25+ FoxP3+ regulatory T cells, IgG imunoglobulin G, CXCR3 a chemokine receptor that is highly expressed on effector T cells and plays an important role in T cell trafficking and function, JCV John Cunningham virus, TGF-β transforming growth factor β,PGE2 = prostaglandin E2, GFAP glial fibrillar acidic protein, STAT 1,3 Signal transducer and activator of transcription 1,3, Th1 T1 lymphocytes, Th17 T17 lymphocytes, T-bet transcription factor, APC antigen presenting cells, CSF cerebrospinal fluid, DNA deoxyribonucleic acid