Keywords glioblastoma - brain metastasis - primary central nervous system lymphoma (PCNSL)
- predictor - differentiation
Introduction
A solitary contrast-enhancing brain lesion is a usual finding of neoplastic diseases
of the brain, including malignant brain tumors.[1 ] The common malignant lesions of the brain are glioblastoma (GBM), primary central
nervous system lymphoma (PCNSL), and metastasis.[2 ] Contrast-enhanced neuroimaging studies play a major role in the differentiation
and diagnosis of these tumors. Nevertheless, overlapping neuroradiological features
of these malignant neoplasms are occasionally seen, resulting in a difficult diagnosis.[2 ]
[3 ]
Preoperative differentiation between GBM, PCNSL, and metastasis is useful in clinical
situations, because the treatments for these tumors are different. Complete resection
is the primary therapy for GBM, whereas PCNSL requires a tissue biopsy, followed by
high-dose chemotherapy with or without radiation therapy.[4 ]
[5 ]
[6 ] In patients with a single accessible metastatic brain tumor who have a favorable
performance status and a well-controlled primary cancer, surgical removal is a good
treatment option for improving the survival and neurological condition of these patients.
The aim of this study was to identify the predictors differentiating between GBM,
PCNSL, and metastasis in patients presenting with a solitary contrast-enhancing intracranial
tumor.
Materials and Methods
Patient Population
This cross-sectional study recruited individuals who had a histopathological diagnosis
of GBM, PCNSL, or metastasis and had a solitary contrast-enhancing intracranial tumor.
The tumors had been revealed by cranial computed tomography (CT) or magnetic resonance
imaging (MRI) scanning. All patients underwent cranial CT and head MRI was performed
in some cases. The enrolled patients were operated at the Division of Neurosurgery,
Department of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. In
all cases, a craniotomy with resection or stereotactic biopsy of the tumor was performed.
The tumors of individuals with intracranial lymphoma primarily occurred in an intracranial
location with no extracranial involvement. Prior to the surgery for the intracranial
tumors, none of the included patients had ever undergone brain surgery or received
radiation therapy to the brain. Patients who underwent surgery for residual tumors
were excluded from the research to avoid confounding features in radiographic studies
of the brain. This work was approved by the Siriraj Institutional Review Board, Faculty
of Medicine Siriraj Hospital, Mahidol University, Thailand. The study has been conducted
in accordance with the principles set forth in the Helsinki Declaration.
Data Collection
The gathered data comprised demographic characteristics, clinical information, and
radiographic features. The demographic characteristics were age, gender, and histopathological
diagnosis. The clinical manifestations (increased intracranial pressure, seizure,
focal neurological deficit, and functional impairment) and their duration prior to
surgery were collected from outpatient and inpatient records. Focal neurological deficit
is defined as an impairment of the focal neurological function, such as hemiparesis,
dysphasia, or visual field deficit. Functional impairment is defined as limitations
of patients' functions due to the disease (patients may not achieve certain functions
in their daily life, and there may be limitations in social and occupational aspects).
The radiographic features consisted of the tumor size, presence and degree of perilesional
brain edema and midline shift, tumor location, characteristics of the tumor margin
and contrast enhancement, presence of cystic appearance, central necrosis, intratumoral
hemorrhage, aberrant flow void, leptomeningeal enhancement, hydrocephalus, and involvement
of the skull. The tumor size was measured by a maximum diameter in any dimension of
contrast-enhanced lesion on postcontrast neuroimaging. The degree of perilesional
brain edema was calculated by a maximum diameter in any dimension of peritumoral hypodensity
area on postcontrast cranial CT or peritumoral hyperintensity area on T2-weighted
(T2W) cranial MRI. The tumor characteristics revealed by the cranial CT and MRI scanning
and the relative cerebral blood volume (rCBV) were also analyzed. The radiographic
variables were independently interpreted by two experienced neurosurgeons (P.C. and
B.S.). The variables with discordance between the interpreters were totally collected
for decision-making of agreement by both interpreters. Eventually, concordance of
all variables was achieved. All values of the rCBV were evaluated by neuroradiologists
and the data were obtained from MRI reports. However, some information was unavailable
for some patients. Thus, the case numbers (n ) of some variables were different from most.
Statistical Analysis
All data were analyzed using the IBM SPSS Statistics for Windows (version 24.0; IBM
Corp., Armonk, New York, United States). Demographic data were analyzed using descriptive
statistics. The analyses of the associations between the variables and the types of
tumors were performed using either the Pearson's chi-squared test or the Fisher's
exact test. The strengths of association were calculated using odds ratios (OR) and
95% confidence intervals (95% CI). The Kruskal–Wallis test was used to investigate
differences in the ages, tumor sizes, degrees of peritumoral brain edema, and midline
shift of the tumor groups. A p -value of less than 0.05 was deemed statistically significant. Furthermore, sensitivity,
specificity, positive likelihood ratio (LR + ), negative likelihood ratio (LR − ),
positive predictive value (PPV), negative predictive value (NPV), and accuracy of
individual statistically significant variables were presented.
Results
In all, 138 patients were enrolled. Sixty-two cases (44.9%) were GBM, 23 (16.7%) were
PCNSL, and 53 (38.4%) were metastasis. There were 70 males (50.7%) and 68 females
(49.3%), with a median age of 57 years (range, 15–81 years). The most common clinical
manifestation was focal neurological deficit (114 patients; 82.6%), whereas increased
intracranial pressure was the second most common symptom (60 patients; 43.5%). Seizure
was a dominant clinical feature of the GBM group, whereas functional impairment was
obvious in the GBM and PCNSL groups. There were no differences in the durations of
the symptoms of the three groups.
The tumor size was significantly larger for the GBM group than the other groups (p < 0.001). In terms of the degree of perilesional brain edema and midline shift, there
was no significant difference between the groups. As to the tumor location, the infratentorial
location was the most common in cases of metastasis but exceedingly rare for the GBM
group (p < 0.001). With the PCNSL group, the supratentorial location was the most common.
Tumors with an extra-axial location were rare in all groups and were exclusively found
in the metastatic group (p = 0.035). A tumor arising in a deep-seated location was the hallmark of the PCNSL
group (p = 0.006), whereas tumors with a smooth margin were obviously found in the metastatic
group (p < 0.001). After contrast injection, the tumors of most PCNSL patients showed a homogeneous
contrast enhancement, whereas the tumors in almost all the GBM patients and the majority
of the metastatic group demonstrated a heterogeneous contrast enhancement (p < 0.001). The PCNSL group had no cystic appearance (p = 0.008) and had exceedingly rare intratumoral hemorrhage (p = 0.018). In the GBM group, the significant characteristics were the presence of
central necrosis (p < 0.001) and abnormal flow void (p < 0.001). As to the precontrast cranial MRI studies, most tumors in the GBM group
showed the presence of hypointensity component (p = 0.027) on T1-weighted (T1W) MRI. Furthermore, we found that the presence of isointensity
component of tumors on fluid-attenuated inversion recovery (FLAIR) sequence was apparently
found in metastasis (p = 0.047). There was a significant difference in the number of cases with the presence
of hypodensity component of tumor in the noncontrast-enhanced cranial CT scans (p < 0.001). In the PCNSL group, there was a predominance of tumors with isodensity
component in the noncontrast-enhanced cranial CT scans (p = 0.008). There were no significant differences in the incidences of perilesional
brain edema, midline shift, leptomeningeal enhancement, hydrocephalus, skull involvement,
characteristic of tumor flow void, and degree of rCBV of the three tumor groups. The
associations between the demographic, clinical, and radiographic variables and the
types of tumors are detailed in [Table 1 ].
Table 1
The associations between the demographic, clinical, and radiographic variables and
the tumor types
Variables
Analyzed cases (n )
Histopathology
p -Value
GBM
PCNSL
Metastasis
Total numbers (%)
138
62 (44.9%)
23 (16.7%)
53 (38.4%)
Age (y), median (range)
138
58 (15–79)
64 (35–78)
56 (30–81)
0.083
Gender, n (%)
138
0.096
Male
35 (56.5%)
7 (30.4%)
28 (52.8%)
Female
27 (43.5%)
16 (69.6%)
25 (47.2%)
Clinical manifestation, n (%)
138
Increased intracranial pressure
24 (38.7%)
8 (34.8%)
28 (52.8%)
0.205
Seizure
15 (24.2%)
1 (4.3%)
5 (9.4%)
0.025[a ]
Focal neurological deficit[b ]
52 (83.9%)
22 (95.7%)
40 (75.5%)
0.097
Functional impairment[c ]
18 (29.0%)
8 (34.8%)
4 (7.5%)
0.005[a ]
Duration of symptoms (d), median (range)
138
21 (1–240)
14 (6–120)
21 (1–90)
0.418
Tumor size (mm), median (range)
138
51 (14–76)
42 (10–61)
36 (15–90)
<0.001[a ]
Tumor location A[d ], n (%)
138
<0.001[a ]
Supratentorial
61 (98.4%)
21 (91.3%)
36 (67.9%)
Infratentorial
1 (1.6%)
2 (8.7%)
17 (32.1%)
Tumor location B[e ], n (%)
138
0.035[a ]
Intra-axial
62 (100.0%)
23 (100.0%)
49 (92.5%)
Extra-axial
0 (0.0%)
0 (0.0%)
4 (7.5%)
Tumor location C[f ], n (%)
138
0.006[a ]
Superficial
53 (85.5%)
16 (69.6%)
51 (96.2%)
Deep-seated
9 (14.5%)
7 (30.4%)
2 (3.8%)
Tumor margin, n (%)
138
<0.001[a ]
Smooth
13 (21%)
10 (43.5%)
30 (56.6%)
Irregular
49 (79%)
13 (56.5%)
23 (43.4%)
Contrast enhancement, n (%)
138
<0.001[a ]
Homogeneous
1 (1.6%)
14 (60.9%)
7 (13.2%)
Heterogeneous
61 (98.4%)
9 (39.1%)
46 (86.8%)
Cystic appearance, n (%)
138
19 (30.6%)
0 (0%)
17 (32.1%)
0.008[a ]
Central necrosis, n (%)
138
49 (79%)
9 (39.1%)
17 (32.1%)
<0.001[a ]
Intratumoral hemorrhage, n (%)
138
21 (33.9%)
1 (4.3%)
12 (22.6%)
0.018[a ]
Perilesional brain edema, n (%)
138
54 (87.1%)
22 (95.7%)
46 (86.6%)
0.493
Degree of brain edema (mm), median (range)
138
36 (15–60)
38 (17–61)
32 (13–61)
0.214
Midline shift, n (%)
138
43 (69.4%)
12 (52.2%)
28 (52.8%)
0.136
Degree of midline shift (mm), median (range)
138
8 (2–18)
9 (3–15)
7 (3–19)
0.763
Abnormal flow void, n (%)
138
36 (58.1%)
2 (8.7%)
10 (18.9%)
<0.001[a ]
Characteristic of flow void, n (%)
48
0.295
Intratumoral
8 (22.2%)
1 (50%)
5 (50%)
Peritumoral
22 (61.1%)
1 (50%)
5 (50%)
Both
6 (16.7%)
0 (0%)
0 (0%)
Leptomeningeal enhancement, n (%)
138
9 (14.5%)
1 (4.3%)
6 (11.3%)
0.428
Hydrocephalus, n (%)
138
14 (22.6%)
2 (8.7%)
15 (28.3%)
0.170
Skull involvement, n (%)
138
0 (0%)
0 (0%)
3 (5.7%)
0.127
Tumor characteristic on precontrast T1W MRI, n (%)
57
Presence of hypointensity component
29 (90.6%)
8 (72.7%)
8 (57.1%)
0.027[a ]
Presence of isointensity component
19 (59.4%)
7 (63.6%)
11 (78.6%)
0.555
Presence of hyperintensity component
0 (0.0%)
0 (0.0%)
2 (14.3%)
0.091
Tumor characteristic on T2W MRI, n (%)
57
Presence of hypointensity component
4 (12.5%)
0 (0.0%)
4 (28.6%)
0.140
Presence of isointensity component
9 (28.1%)
2 (18.2%)
7 (50.0%)
0.253
Presence of hyperintensity component
32 (100.0%)
10 (90.9%)
12 (85.7%)
0.079
Tumor characteristic on FLAIR MRI, n (%)
57
Presence of hypointensity component
1 (3.1%)
0 (0.0%)
3 (21.4%)
0.075
Presence of isointensity component
4 (12.5%)
1 (9.1%)
6 (42.9%)
0.047[a ]
Presence of hyperintensity component
31 (96.9%)
10 (90.9%)
12 (85.7%)
0.287
Tumor characteristic on NCECT, n (%)
81
Presence of hypodensity component
29 (96.7%)
6 (50.0%)
32 (82.1%)
<0.001[a ]
Presence of isodensity component
12 (40.0%)
11 (91.7%)
24 (61.5%)
0.008[a ]
Presence of hyperdensity component
8 (26.7%)
1 (8.3%)
8 (20.5%)
0.466
rCBV, n (%)
42
0.391
High
23 (95.8%)
8 (88.9%)
8 (88.9%)
Normal
0 (0%)
1 (11.1%)
1 (11.1%)
Low
1 (4.2%)
0 (0%)
0 (0%)
Abbreviations: FLAIR, fluid-attenuated inversion recovery; GBM, glioblastoma; MRI,
magnetic resonance imaging; n , number of cases; NCECT, noncontrast-enhanced computerized tomography; PCNSL, primary
central nervous system lymphoma; rCBV, relative cerebral blood volume; T1W, T1-weighted;
T2W, T2-weighted.
a Statistical significance.
b Focal neurological deficit is defined as an impairment of the focal neurological
function, such as hemiparesis, dysphasia, or visual field deficit.
c Functional impairment is defined as limitations of patients' functions due to the
disease (patients may not achieve certain functions in their daily life, and there
may be limitations in social and occupational aspects).
d Tumor location A is categorized into supratentorial and infratentorial locations.
e Tumor location B is categorized into intra-axial and extra-axial locations.
f Tumor location C is categorized into superficial locations (cortical or subcortical
region, epidural, or subdural space) and deep-seated locations (periventricular region,
basal ganglia, thalamus, corpus callosum, or brainstem).
In an analysis of the strengths of association ([Table 2 ]), the factors with a significant association with GBM were functional impairment
(OR, 5.0; 95% CI, 1.6–15.9; p = 0.004), central necrosis (OR, 8.0; 95% CI, 3.4–18.5; p < 0.001), intratumoral hemorrhage (OR, 11.3; 95% CI, 1.4–89.5; p = 0.010), abnormal flow void (OR, 14.5; 95% CI, 3.1–67.5; p < 0.001), presence of hypointensity component on cranial T1W MRI (OR, 7.3; 95% CI,
1.5–35.6; p = 0. 015), and hypodensity component on cranial noncontrast-enhanced CT (OR, 29.0; 95%
CI, 2.9–287.0; p = 0.001). In the case of PCNSL, the predicting factors for this type of tumor were
functional impairment (OR, 6.5; 95% CI, 1.7–24.8; p = 0.005), deep-seated tumor location (OR, 11.2; 95% CI, 2.1–59.2; p = 0.003), homogeneous contrast enhancement (OR, 94.9; 95% CI, 11.1–811.5; p < 0.001), and presence of isodensity component of cranial noncontrast-enhanced CT
(OR, 16.5; 95% CI, 1.9–145.0; p = 0.005). The factors indicating a high association with metastasis were infratentorial
tumor location (OR, 28.8; 95% CI; 3.7–225.7; p < 0.001), smooth tumor margin (OR, 4.9; 95% CI; 2.2–11.1; p < 0.001), and homogeneous contrast enhancement (OR, 9.3; 95% CI, 1.1–78.1; p = 0.023).
Table 2
The strengths of association between the variables and tumor types
Variables/tumor types
Odds ratio (95% CI)
p -Value
Seizure
PCNSL
1.0
Metastasis
2.3 (0.25–20.8)
0.661
GBM
7.0 (0.9–56.6)
0.058
Functional impairment[b ]
Metastasis
1.0
GBM
5.0 (1.6–15.9)
0.004[a ]
PCNSL
6.5 (1.7–24.8)
0.005[a ]
Infratentorial tumor location
GBM
1.0
PCNSL
5.8 (0.5–67.4)
0.177
Metastasis
28.8 (3.7–225.7)
<0.001[a ]
Deep-seated tumor location[c ]
Metastasis
1.0
GBM
4.3 (0.9–21.0)
0.062
PCNSL
11.2 (2.1–59.2)
0.003[a ]
Smooth tumor margin
GBM
1.0
PCNSL
2.9 (1.0–8.1)
0.054
Metastasis
4.9 (2.2–11.1)
<0.001[a ]
Homogeneous contrast enhancement
GBM
1.0
Metastasis
9.3 (1.1–78.1)
0.023[a ]
PCNSL
94.9 (11.1–811.5)
<0.001[a ]
Central necrosis
Metastasis
1.0
PCNSL
1.4 (0.5–3.8)
0.604
GBM
8.0 (3.4–18.5)
<0.001[a ]
Intratumoral hemorrhage
PCNSL
1.0
Metastasis
6.4 (0.8–52.8)
0.094
GBM
11.3 (1.4–89.5)
0.010[a ]
Abnormal flow void
PCNSL
1.0
Metastasis
2.4 (0.5–12.2)
0.327
GBM
14.5 (3.1–67.5)
<0.001[a ]
Presence of hypointensity component on precontrast T1W MRI
Metastasis
1.0
PCNSL
2.0 (0.4–10.9)
0.677
GBM
7.3 (1.5–35.6)
0.015[a ]
Presence of isointensity component on FLAIR MRI
GBM
1.0
PCNSL
1.4 (0.1–14.4)
0.762
Metastasis
5.3 (1.2–23.3)
0.029[a ]
Presence of hypodensity component on NCECT
PCNSL
1.0
Metastasis
4.6 (1.1–18.5)
0.053
GBM
29.0 (2.9–287.0)
0.001[a ]
Presence of isodensity component on NCECT
GBM
1.0
Metastasis
2.4 (0.9–6.4)
0.093
PCNSL
16.5 (1.9–145.0)
0.005[a ]
Abbreviations: CI, confidence interval; FLAIR, fluid-attenuated inversion recovery;
GBM, glioblastoma; MRI, magnetic resonance imaging; NCECT, noncontrast-enhanced computerized
tomography; PCNSL, primary central nervous system lymphoma; T1W, T1-weighted.
a Statistical significance.
b Functional impairment is defined as limitations of patients' functions due to the
disease (patients may not achieve certain functions in their daily life, and there
may be limitations in social and occupational aspects).
c Deep-seated location refers to an area located at the deep part of the brain (the
periventricular region, basal ganglia, thalamus, corpus callosum, or brainstem).
Additionally, the individual categorical variable with statistical significance in
[Table 1 ] was analyzed in terms of sensitivity, specificity, LR + , LR − , PPV, NPV, and accuracy.
Results of the analysis are demonstrated in [Table 3 ]. Numerous variables showed dominant positive (supporting) and negative (opposing)
possibilities of being GBM, PCNSL, or metastasis. For instance, in the variable of
homogeneous contrast enhancement on neuroimaging studies, PCNSL revealed high specificity,
LR + , NPV, and accuracy, whereas GBM showing low sensitivity, LR + , PPV, and accuracy.
These results supported that tumor showing homogenous contrast enhancement on neuroimaging
studies were likely to be PCNSL and unlikely to be GBM. Similarly, in the variable
of infratentorial tumor location, high specificity, LR + , PPV, and accuracy were
found in metastatic tumor but GBM exhibiting low sensitivity, LR + , PPV, and accuracy.
We could interpret that a solitary contrast-enhancing tumor located in the posterior
cranial fossa carried an outstanding possibility of being metastasis and a weak possibility
of being GBM.
Table 3
Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive
predictive value, negative predictive value, and accuracy of individual variable in
differentiation of the tumor types
Variables
Sensitivity (%)
Specificity (%)
LR+
LR−
PPV (%)
NPV (%)
Accuracy (%)
Seizure
GBM
24.2
92.1[a ]
3.1
0.8
71.4[a ]
59.9
61.6
PCNSL
4.4[b ]
82.6
0.3
1.2
4.8[b ]
81.2[b ]
69.5
Metastasis
9.4
81.2
0.5
1.1
23.8
59.0
53.6
Functional impairment
GBM
29.0
84.2
1.8
0.8
60.0
59.3
59.4
PCNSL
34.8
80.9
1.8
0.8
26.7
86.1[a ]
73.2[a ]
Metastasis
7.6
69.4
0.3
1.3
13.3
54.6
45.7
Infratentorial tumor location
GBM
1.6[b ]
75.0
0.1[b ]
1.3
5.0[b ]
48.3
42.1
PCNSL
8.7
84.4
0.6
1.1
10.0
82.2
71.7
Metastasis
32.1
96.5[a ]
9.1[a ]
0.7
85.0[a ]
69.5
71.7
Deep-seated tumor location
GBM
14.5
88.2
1.2
1.0
50.0
55.9
55.1
PCNSL
30.4
90.4[a ]
3.2
0.8
39.0
86.6[a ]
80.4[a ]
Metastasis
3.8[b ]
81.2
0.2[b ]
1.2
11.1[b ]
57.5
51.5
Smooth tumor margin
GBM
20.3
47.4
0.4
1.7
24.5
42.4
35.5
PCNSL
43.5
62.6
1.2
0.9
18.9
84.7[a ]
59.4
Metastasis
56.6
72.9[a ]
2.1
0.6
56.6
73.0
66.7
Homogeneous contrast enhancement
GBM
1.6[b ]
72.4
0.1[b ]
1.4
4.5[b ]
47.4
40.6
PCNSL
60.9
93.0[a ]
8.8[a ]
0.4
63.7
92.2[a ]
87.7[a ]
Metastasis
13.2
82.4
0.8
1.1
31.8
60.4
55.8
Cystic appearance
GBM
30.7
77.6
1.4
0.9
52.8
57.9
56.5
PCNSL
0.0[b ]
68.7
0.0[b ]
1.5
0.0[b ]
77.4[b ]
57.2
Metastasis
32.1
77.7
1.4
0.9
47.2
64.7
60.2
Central necrosis
GBM
79.0[a ]
65.8
2.3
0.3[a ]
65.3[a ]
79.4
71.4[a ]
PCNSL
39.1
42.6
0.7
1.4
12.0
77.7
42.0
Metastasis
32.0
31.8
0.5
2.1
22.7
42.9
31.9
Intratumoral hemorrhage
GBM
33.9
82.9[a ]
2.0
0.8
61.7[a ]
60.6
60.9
PCNSL
4.4[b ]
71.3
0.2
1.3
3.0[b ]
78.8[b ]
60.1
Metastasis
22.6
74.1
0.9
1.0
35.3
60.6
54.4
Abnormal flow void
GBM
58.1
84.2[a ]
3.7
0.5
75.0[a ]
71.1
72.5
PCNSL
8.7
60.0
0.2
1.5
4.2
76.6
51.4
Metastasis
18.9
55.3
0.4
1.5
20.8
52.2
41.3
Presence of hypointensity component on precontrast T1W MRI
GBM
90.6[a ]
36
1.4
0.3
53.6
82.5[a ]
60.5
PCNSL
72.7
19.6
0.9
1.4
15.4
78.2
28.4
Metastasis
72.7
19.6
0.9
1.4
36.1
53.5
40.0
Presence of isointensity component on FLAIR MRI
GBM
12.5
72
0.5
1.2
26.7
50.2
45.3
PCNSL
9.1
78.3
0.4
1.2
7.7
81.1
66.7
Metastasis
54.6
89.1[a ]
5.0[a ]
0.5
75.8[a ]
75.9
75.9
Presence of hypodensity component on NCECT
GBM
85.3[a ]
19.2
1.0
0.8
46.2
61.5
48.9
PCNSL
60.0
14.1
0.7
2.8
12.3
63.7
21.8
Metastasis
86.5[a ]
20.5
1.1
0.7
40.4
70.8
45.8
Presence of isodensity component on NCECT
GBM
35.3
25.5
0.5
2.5
27.9
32.6
29.9
PCNSL
91.7[a ]
47.8
1.8
0.2[a ]
26.1
96.6[a ]
55.2
Metastasis
64.9
47.7
1.2
0.7
43.6
68.5
54.3
Abbreviations: FLAIR, fluid-attenuated inversion recovery; GBM, glioblastoma; LR − ,
negative likelihood ratio; LR + , positive likelihood ratio; MRI, magnetic resonance
imaging; NCECT, noncontrast-enhanced computerized tomography; NPV, negative predictive
value; PCNSL, primary central nervous system lymphoma; PPV, positive predictive value;
T1W, T1-weighted.
a Value with dominant positive relationship between the individual variable and tumor.
b Value with dominant negative relationship between the individual variable and tumor.
Discussion
The most common primary malignant brain tumor is GBM.[7 ]
[8 ] Brain metastasis is a tumor that is being increasingly found in cancer survivors,
whereas PCNSL is a relatively rare entity with an aggressive course.[9 ] Patients with any of these three types of tumors can present with a solitary contrast
enhancing intracranial tumor. With some patients who have brain imaging showing this
finding, difficulty in differentiating between the three tumor types are encountered.
There are no pathognomonic findings to distinguish between each of the individual
types of tumors. The authors conducted this study to establish the predictive factors
for GBM, PCNSL, and metastasis. Our results may be useful for the preoperative decision-making
related to the neurosurgical management of these intracranial malignant lesions. In
patients with GBM and single brain metastasis arising in an accessible location, total
surgical removal remains the treatment of choice. In cases harboring lesions with
the high possibility of being intracranial lymphoma, tissue biopsy without resection
is appropriate for treatment with chemotherapy or radiation therapy. Surgical resection
of PCNSL is not helpful in improving survival outcomes.[10 ]
In our study, several predictors were found to be associated with the possibility
of being GBM. The tumor size was significantly larger in GBM because this type of
tumor usually grows rapidly and is found when it is large, resulting in rapidly progressing
symptoms of increasing intracranial pressure or neurological deficits. The tumor margin
of GBM was also irregular compared with PCNSL and metastasis ([Fig. 1A ]). GBM is an infiltrative high-grade glioma, and tumor cells can be found in the
peritumoral area. These properties of GBM may make the tumor margin more irregular
than those of the other types of tumor. After contrast injection, almost all instances
of GBM in our study (98.4%) showed heterogeneous contrast enhancement ([Fig. 1B ]). Contrast-enhanced component represents the highly vascularized portion of GBM,
whereas the area without contrast enhancement represents central necrosis ([Fig. 1C ]), which was significantly associated with GBM in the present study. As to intratumoral
hemorrhage, Ding et al found that the intratumoral hemorrhagic burden and the number
of vessels within the tumors detected by susceptibility-weighted imaging were significantly
higher in high-grade gliomas and metastasis than those in PCNSL. They also demonstrated
that there was no significant difference in these two variables of high-grade glioma
and metastasis.[11 ] Our study had similar results. Intratumoral hemorrhage ([Fig. 1D ]) and abnormal tumor flow void ([Fig. 1E ]) were significantly prominent in the GBM group. As to the aforementioned highly
vascularized properties of GBM, the prominent vascular structures are represented
as tumor flow void and may result in intratumoral hemorrhagic phenomenon. Nevertheless,
characteristics of tumor flow void were not significantly different between the tumor
groups. Furthermore, hypodensity component on noncontrast-enhanced cranial CT associated
with GBM may indicate some parts of central necrosis and cystic component within the
tumor ([Fig. 1F ]).
Fig. 1 Cranial images of patients with GBM. (A ) GBM with irregular margin (arrowheads) on contrast-enhanced T1W MRI; (B ) contrast-enhanced T1W MRI showing heterogeneous enhancement, including solid (arrow)
and cystic (arrowhead) components; (C ) central necrosis (arrowhead) on contrast-enhanced CT; (D ) intratumoral hemorrhage (arrowhead) on noncontrast-enhanced CT; (E ) abnormal flow void (arrowhead) on T2W MRI; (F ) hypodensity component (arrow) on noncontrast-enhanced CT. CT, computed tomography;
GBM, glioblastoma; MRI, magnetic resonance imaging; T1W, T1-weighted; T2W, T2-weighted.
Turning to the analysis of the peritumoral area, Maurer et al showed that the ratio
of the maximum diameter of the peritumoral area on T2W MRI (d T2) to the maximum diameter
of the enhancing mass area on postcontrast T1W MRI (d T1 postcontrast) was useful
in differentiating between GBM and metastasis. A lower d T2/d T1 postcontrast ratio
with a cutoff point of 2.35 favored the possibility of the tumor being GBM.[12 ] However, the usefulness of the degree of peritumoral brain edema, measured by our
method, in differentiating between the three tumor types could not be confirmed by
our study.
PCNSL, a relatively rare intracranial malignant neoplasm, is found in 5% of all primary
brain tumors.[13 ] It may masquerade as other diseases, or it may have atypical imaging characteristics.[14 ] In our study, the most common location of PCNSL was the supratentorial region. A
deep-seated location—particularly the periventricular areas, basal ganglia, or corpus
callosum ([Fig. 2A–D ])—was more common with PCNSL than GBM or metastasis. The involvement of the cerebellum
and brainstem was uncommon in our PCNSL group. Our results corresponded with those
of other studies.[15 ]
[16 ]
[17 ] Because of the high nuclear-to-cytoplasmic ratio, PCNSL typically showed hyperdensity
or isodensity in the CT scans ([Fig. 2E ]), hypointensity on precontrast T1W MRI, and homogeneous enhancement following contrast
injection ([Fig. 2F ]).[16 ] Necrotic areas and intratumoral hemorrhage are rare in PCNSL.[14 ] We also found these findings in our PCNSL group.
Fig. 2 Cranial images of patients with PCNSL. (A ) Contrast-enhanced CT and (B ) contrast-enhanced T1W MRI showing the periventricular location of a tumor (arrowhead);
(C ) contrast-enhanced T1W MRI showing basal ganglial involvement (arrowhead); (D ) lymphoma involving the splenium of the corpus callosum (arrowhead) on T1W MRI after
contrast injection; (E ) tumor with isodensity appearance (arrowhead) on noncontrast-enhanced CT; (F ) contrast-enhanced CT showing homogeneous enhancement of a tumor (arrowhead). CT
computed tomography; MRI, magnetic resonance imaging; PCNSL, primary central nervous
system lymphoma; T1W, T1-weighted.
A few predictors of metastasis were found by our study. Of them, the predictors with
a high strength of association included an infratentorial tumor location ([Fig. 3A ]) and a smooth tumor margin ([Fig. 3B, C ]). GBM and PCNSL are uncommon tumors arising in the posterior cranial fossa. Therefore,
if a solitary enhancing tumor is found at the cerebellum, it has a greater possibility
of being a metastatic lesion than GBM or PCNSL. Additionally, most metastatic tumors
have well-defined borders, so circumferential complete tumor resection without resection
of the surrounding brain can be performed in such cases.
Fig. 3 Cranial images of patients with brain metastasis. (A ) Contrast-enhanced CT revealing a tumor arising in the posterior cranial fossa (arrowhead);
(B ) contrast-enhanced CT, and (C ) FLAIR MRI showing smooth margin of a tumor (arrowhead). CT, computed tomography;
FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging.
Many studies have demonstrated that the rCBV in GBM and metastasis was greater than
the rCBV in PCNSL.[18 ]
[19 ]
[20 ] Nevertheless, our study did not find a significant difference in the rCBVs of the
three tumor groups. Almost all patients in the three groups had a high rCBV. This
may be a result of having too small analyzed cases of rCBV, particularly in the PCNSL
and metastatic groups; this is acknowledged as being a limitation of our study.
The role of advanced imaging studies has been steadily increasing. Various MRI sequences
are helpful in differentiating between GBM, PCNSL, and metastasis, for instance, apparent
diffusion coefficient,[21 ]
[22 ] dynamic contrast-enhanced MRI,[23 ]
[24 ]
[25 ] perfusion MRI,[26 ]
[27 ] diffusion tensor imaging,[23 ]
[28 ] diffusion-weighted imaging,[29 ] a whole-tumor histogram analysis of normalized cerebral blood volume,[3 ]
[22 ] and arterial spin labeling.[25 ]
[29 ] Additionally, fluorodeoxyglucose positron emission tomography (18 F-FDG PET)/CT is a helpful radiographic tool for the detection of an extracranial
involvement of lymphoma and the differentiation of lymphoma from GBM and metastasis.
Lymphoma has shown a significantly high metabolic uptake compared with GBM and metastasis.[2 ]
[29 ]
[30 ] Recently, machine learning models have been used for differentiating GBM, PCNSL,
and metastasis. Several studies showed useful of the models in preoperative prediction
of the tumor types.[31 ]
[32 ]
[33 ] In current clinical practice, it would be practical to interpret the difference
between these tumors using these advanced imaging techniques. Even though these advanced
tools are useful in differentiating between these tumors with overlapping features,
they are not generally available and require skilled interpreters. By comparison,
our predictors are easily feasible because they are based on common clinical characteristics
and radiographic features on imaging studies. Regarding the analyzed data obtained
from [Tables 1 ], [2 ], and [3 ], variables either supporting or opposing possibility of being GBM, PCNSL, and metastasis
are summarized in [Table 4 ]. These variables are helpful and can be used as strong predictors for distinguishing
between the three types of malignant brain tumor. Furthermore, the literature review
regarding predictors of being GBM, PCNSL, and metastasis are summarized in [Table 5 ].
Table 4
Variables supporting or opposing possibility of being glioblastoma, primary central
nervous system lymphoma, and metastasis
Variables
GBM
PCNSL
Metastasis
Seizure
+
−
Functional impairment
+
Infratentorial tumor location
−−
+ +
Deep-seated tumor location
+ +
−
Smooth tumor margin
+
+ +
Homogeneous contrast enhancement
−−
+ +
Cystic appearance
−−
Central necrosis
+
Intratumoral hemorrhage
+
−
Abnormal flow void
+
Presence of hypointensity component on precontrast T1W MRI
+
Presence of isointensity component on FLAIR MRI
+
Presence of hypodensity component on NCECT
+
+
Presence of isodensity component on NCECT
+
Abbreviations: FLAIR, fluid-attenuated inversion recovery; GBM, glioblastoma; MRI,
magnetic resonance imaging; NCECT, noncontrast-enhanced computerized tomography; PCNSL,
primary central nervous system lymphoma; T1W, T1-weighted.
+ Variable supporting possibility of being the tumor.
++ Variable greatly supporting possibility of being the tumor.
− Variable opposing possibility of being the tumor.
−− Variable greatly opposing possibility of being the tumor.
Table 5
The literature review regarding predictors of being glioblastoma, primary central
nervous system lymphoma, and metastasis
Authors,
year
Population, n
Used method
Compared parameter
Predictor
GBM/HGG
PCNSL/lymphoma
Metastasis
Calli et al[18 ] 2002
Total 48 cases (GBM 17, AA 4, 8 PCNSL, 9 metastasis)
C-MRI, DWI, PWI
ADCmin , rCBVmax
[a ]Higher ADCmin
[a ]Higher rCBVmax
[a ]Lower ADCmin
[a ]Lower rCBVmax
Not different from GBM for ADCmin and rCBVmax
Wang et al[23 ] 2011
Total 67 cases (GBM 26, PCNSL 16, metastasis 25)
DTI, DSC-MRI
ADC, FA, CL, CP, CS, rCBV, rCBVmax
[a ]Higher ADC in ER
[a ]Higher FA in ER, IPR, DPR
[a ]Higher CL in ER, IPR
[a ]Higher CP in ER, IPR, DPR
[a ]Lower CS in ER, IPR
[a ]Higher rCBV in ER, IPR
[a ]Higher rCBVmax in ER, IPR
[a ]Lower ADC in ER
[a ]Lower FA in ER, IPR, DPR
[a ]Lower CL in ER, IPR
[a ]Lower CP in ER, IPR, DPR
[a ]Higher CS in ER, IPR
[a ]Lower rCBV in ER, IPR
[a ]Lower rCBVmax in ER, IPR
[a ]High ADC in ER
[a ]Lower FA in ER, IPR
[a ]Lower CL in ER, IPR
[a ]Lower CP in ER, IPR, DPR
[a ]Higher CS in ER, IPR
[a ]Lower rCBV in IPR
[a ]Lower rCBVmax in IPR
Not difference from GBM for FA in DPR; rCBV in ER, DPR; rCBVmax in ER, DPR
Neska-Matuszewska et al[20 ] 2018
Total 74 cases (GBM 27, PCNSL 17, metastasis 30)
DWI, PWI
ADC, rCBV, rPH, rPSR
[a ]Higher ADCmean
[a ]Higher ADCmin
[a ]Higher rCBVmean
[a ]Higher rCBVmax
[a ]Higher rPHmean
[a ]Higher rPHmax
[a ]Lower rPSRmean
[a ]Lower rPSRmax
[a ]Lower ADCmean
[a ]Lower ADCmin
[a ]Lower rCBVmean
[a ]Lower rCBVmax
[a ]Lower rPHmean
[a ]Lower rPHmax
[a ]Higher rPSRmean
[a ]Higher rPSRmax
Not different from GBM for ADCmean , ADCmin , rCBVmean , rCBVmax , rPHmean , rPHmax , rPSRmean , rPSRmax
Lee et al[34 ] 2019
Total 54 cases (GBM 14, PCNSL 7, metastasis 20, meningioma 13)
DSC-MRI
rCBV, PSR, normalized baseline signal intensity
rCBV was better than PSR in differentiating GBM from PCNSL, and meningioma from GBM
rCBV and PSR were poor in differentiating GBM from metastasis
Normalized baseline signal intensity was better than rCBV and PSR differentiating
GBM from metastasis
PSR was better than rCBV in differentiating PCNSL from metastasis
rCBV and PSR were similar in differentiating PCNSL from GBM or meningioma
rCBV was better than PSR in differentiating metastasis from meningioma
Eyüboğlu et al[35 ] 2021
Total 125 cases (HGG 55, LGG 22, lymphoma 16, metastasis 32)
DWI
ADCt , ADCt ratio,
ADCtch , ADCtch ratio
HGG showing
[a ]Lower ADCtch
[a ]Lower ADCtch ratio
Not different from lymphoma and metastasis for ADCt and ADCt ratio
[a ]Higher ADCtch
[a ]Higher ADCtch ratio
[a ]Higher ADCtch
[a ]Higher ADCtch ratio
Bilgin and Ünal[36 ] 2023
Total 39 cases (GBM 13, PCNSL 13, metastasis 13)
C-MRI, DWI
Edema–mass ratio, ADC in lesion and perilesional area
[a ]Lower edema–mass ratio
[a ]Higher ADC in lesion
Not different from PCNSL and metastasis for ADC in perilesional area
[a ]Higher edema–mass ratio
[a ]Lower ADC in lesion
[a ]Higher edema–mass ratio
Not different from GBM for ADC in lesion
Ma et al[3 ] 2010
Total 59 cases (GBM 28, lymphoma 12, metastasis 22)
C-MRI, DSC-MRI
HW, PHP, and MV of CBV
For contrast-enhancing lesion
[a ]Higher HW
[a ]Higher PHP
[a ]Higher MV
For perienhancing lesion
[a ]Higher HW
[a ]Higher PHP
[a ]Higher MV
For contrast-enhancing lesion
[a ]Lower HW
[a ]Lower PHP
[a ]Lower MV
For perienhancing lesion
[a ]Lower HW
[a ]Lower PHP
[a ]Lower MV
For contrast-enhancing lesion, not different from GBM for higher HW, PHP, and MV
For perienhancing lesion
[a ]Lower HW
[a ]Lower PHP
[a ]Lower MV
Goyal et al[37 ] 2017
Total 56 cases (GBM 18, lymphoma 15, metastasis 13, AEG 10)
DSC-MRPI
CBVmean , CBVmax
[a ]Higher CBVmean
[a ]Higher CBVmax
[a ]Lower CBVmean
[a ]Lower CBVmax
[a ]Higher CBVmean
[a ]Higher CBVmax
Not compared with GBM for CBVmean , CBVmax
Xi et al[25 ] 2019
Total 35 cases (HGG 21, PCNSL 8, metastasis 6)
C-MRI, ASL, DCE-MRI
CBF, rCBF, Ktrans , Ve
HGG showing
[a ]Higher CBF
[a ]Higher rCBF
[a ]Lower Ktrans
[a ]Lower Ve
[a ]Lower CBF
[a ]Lower rCBF
[a ]Higher Ktrans
[a ]Higher Ve
[a ]Higher CBF
[a ]Higher rCBF
[a ]Lower Ktrans
[a ]Lower Ve
Onishi et al[19 ] 2018
Total 39 cases (GBM 22, PCNSL 6, metastasis 11)
Perfusion CT
rCBFt, rCBVt, rCBFp, rCBVp, rMTTt
[a ]Higher rCBFt
[a ]Higher rCBVt
[a ]Higher rCBFp
[a ]Higher rCBVp
[a ]Lower rMTTt
[a ]Lower rCBFt
[a ]Lower rCBVt
Higher rCBFp
Higher rCBVp
[a ]Lower rMTTt
[a ]Lower rCBFt
[a ]Lower rCBVt
[a ]Lower rCBFp
[a ]Lower rCBVp
[a ]Higher rMTTt
Ding et al[11 ] 2014
Total 104 lesions (HGG 35, PCNSL 23, metastasis 46)
C-MRI, SWI
Intralesional hemorrhagic burden, number of intralesional vessel
[a ]Higher intralesional hemorrhagic burden and number of intralesional vessel for HGG
[a ]Lower intralesional hemorrhagic burden and number of intralesional vessel
Not different from HGG for intralesional hemorrhagic burden and number of intralesional
vessel
Lu et al[24 ] 2016
Total 75 cases (GBM 38, PCNSL 16, metastasis 21)
DCE-MRI
Ktrans , Ve
[a ]Lower Ktrans
[a ]Lower Ve
[a ]Higher Ktrans
[a ]Higher Ve
[a ]Lower Ktrans
[a ]Lower Ve
Das et al[38 ] 2011
Total 20 cases (GBM 8, LGG 7, PCNSL 1, metastasis 4)
18 F-FDG PET/CT
SUVavg , SUVmax
[a ]Lower SUVavg
[a ]Lower SUVmax
[a ]Higher SUVavg
[a ]Higher SUVmax
SUVmax of 15.0 was cutoff for diagnosis of PCNSL
Metastasis showing higher SUVavg and SUVmax than GBM
Meric et al[39 ] 2015
Total 76 cases (HGG 18, PCNSL 6, metastasis 52)
18 F-FDG PET/CT
SUVavg , SUVmax , Tmax :Cimax , Tmax :Ccmax ,
Tmax :WMimax ,
Tmax :WMcmax , Tavg :Ciavg , Tavg :Ccavg ,
Tavg :WMiavg ,
Tavg :WMcavg
[a ]Lower for all parameters than PCNSL
[a ]Lower for Tmax :Cimax , Tmax :Ccmax , Tmax :WMimax , Tavg :Ciavg , Tavg :Ccavg , Tavg :WMiavg , Tavg :WMcavg than metastasis
[a ]Higher for all parameters than HGG
[a ]Higher for SUVavg , SUVmax , Tmax :Cimax , Tmax :Ccmax , Tmax :WMimax , Tavg :Ciavg than metastasis
[a ]Higher for Tmax :Cimax , Tmax :Ccmax , Tmax :WMimax , Tavg :Ciavg , Tavg :Ccavg , Tavg :WMiavg , Tavg :WMcavg than HGG
a Lower for SUVavg , SUVmax , Tmax :Cimax , Tmax :Ccmax , Tmax :WMimax , Tavg :Ciavg than PCNSL
Purandare et al[2 ] 2017
Total 101 cases (GBM 30, lymphoma 25, metastasis 46)
18 F-FDG PET/CT
SUVmax , tumor to background activity ratio
[a ]Lower SUVmax
[a ]Lower tumor to background activity ratio
[a ]Higher SUVmax
[a ]Higher tumor to background activity ratio
[a ]Lower SUVmax
[a ]Lower tumor to background activity ratio
Wang et al[40 ] 2022
Total 192 cases (GBM 70, PCNSL 41, metastasis 81)
Age, blood test
Age, platelet count in CBC, LDH, β2-MG, α2-G, INR, TT, FDP
[a ]Lower INR and higher TT than for PCNSL and metastasis
Accuracy of diagnostic model was 76.1%
Accuracy of diagnostic model was 22%
[a ]Older age and lower platelet count than for GBM
Accuracy of diagnostic model was 88.2%
The present study
Total 138 (GBM 62, PCNSL 23, metastasis 53)
Clinical variables, NCECT, CECT, C-MRI
Clinical variables, tumor location, and characteristics on neuroimaging
[a ]Presence of seizure
[a ]Central necrosis
[a ]Intratumoral hemorrhage
[a ]Abnormal flow void
[a ]Presence of hypointensity component on precontrast T1W MRI
[a ]Functional impairment
[a ]Deep-seated tumor location
[a ]Smooth tumor margin
[a ]Homogeneous contrast enhancement
[a ]Presence of isodensity component on NCECT
[a ]Infratentorial tumor location
[a ]Smooth tumor margin
[a ]Presence of isointensity component on FLAIR
[a ]Presence of hypodensity component on NCECT
Abbreviations: AA, anaplastic astrocytoma; ADC, apparent diffusion coefficient; ADCmean , mean apparent diffusion coefficient; ADCmin , minimum apparent diffusion coefficient; ADCt , apparent diffusion coefficient from tumor; ADCtch , apparent diffusion coefficient from tumor circumferential hyperintensity; AEG, anaplastic
enhancing glioma; ASL, arterial spin labeling; CBC, complete blood count; CBV, cerebral
blood volume; CBVmax , maximum cerebral blood volume; CBVmean , mean cerebral blood volume; CECT, contrast-enhanced computerized tomography; CEMRI,
contrast-enhanced magnetic resonance imaging; CL, linear anisotropy coefficient; C-MRI,
conventional magnetic resonance imaging; CP, planar anisotropy coefficient; CS, spheric
anisotropy coefficient; CT, computed tomography; DCE-MRI, dynamic contrast-enhanced
magnetic resonance imaging; DPR, distant peritumoral region; DSC-MRI, dynamic susceptibility
contrast-enhanced magnetic resonance imaging; DSC-MRPI, dynamic susceptibility-weighted
magnetic resonance perfusion imaging; DTI, diffusion tensor imaging; DWI, diffusion-weighted
imaging; ER, enhancing region; FA, fractional anisotropy; FDG PET, fluorodeoxyglucose
positron emission tomography; FDP, fibrin degradation product; FLAIR, fluid-attenuated
inversion recovery; GBM, glioblastoma; HGG, high grade glioma; HW, histogram width;
INR, international normalized ratio; IPR, immediate peritumoral region; Ktrans , volume transfer constant; LDH, lactate dehydrogenase; LGG, low-grade glioma; MV,
maximum value; NCECT, noncontrast-enhanced computerized tomography; PCNSL, primary
central nervous system lymphoma; PHP, peak height position; PSR, percentage signal
recovery; PWI, perfusion-weighted imaging; rCBFp, relative cerebral blood flow in
peritumoral region; rCBFt, relative cerebral blood flow in tumor; rCBV, relative cerebral
blood volume; rCBVmax , maximum relative cerebral blood volume; rCBVmean , mean relative cerebral blood volume; rCBVp, relative cerebral blood volume in peritumoral
region; rCBVt, relative cerebral blood volume in tumor; rMTTt, relative mean transit
time in tumor; rPH, relative peak height; rPHmax , maximum relative peak height; rPHmean , mean relative peak height; rPSR, relative percentage of signal recovery; rPSRmax , maximum relative percentage of signal recovery; rPSRmean , mean relative percentage of signal recovery; SUVavg , average standardized uptake value; SUVmax , maximum standardized uptake value; SWI, susceptibility-weighted imaging; T1W, T1-weighted;
Tavg :Ccavg , the tumor SUVavg to contralateral cortex SUVavg ratio; Tavg :Ciavg , the tumor SUVavg to ipsilateral cortex SUVavg ratio; Tavg :WMcavg , the tumor SUVavg to contralateral white matter SUVavg ratio; Tavg :WMiavg , the tumor SUVavg to ipsilateral white matter SUVavg ratio; Tmax :Ccmax , the tumor SUVmax to contralateral cortex SUVmax ratio; Tmax :Cimax , the tumor SUVmax to ipsilateral cortex SUVmax ratio; Tmax :WMcmax , the tumor SUVmax to contralateral white matter SUVmax ratio; Tmax :WMimax , the tumor SUVmax to ipsilateral white matter SUVmax ratio; TT, thrombin time; Ve , extravascular extracellular volume; α2-G, α2-globulin; β2-MG, β2-macroglobulin.
a Statistically significant difference when compared with other type(s) of tumor in
the same study.
A major limitation of the study should be mentioned. Some neuroimaging modalities,
including cranial MRI, cranial CT, and measurement of the rCBV, were available in
not all cases. Therefore, analyzed population numbers were different between these
modalities. The heterogeneity in population numbers may affect results of data analysis
of some variables. In the future, research in homogeneous study group should be conducted.
Conclusion
Our study established useful predictors to differentiate between GBM, PCNSL, and metastasis.
The predictors of being GBM are functional impairment, large tumor size, irregular
tumor margin, heterogeneous contrast enhancement, central necrosis, intratumoral hemorrhage,
abnormal flow void, presence of hypointensity component on precontrast cranial T1W
MRI, and hypodensity component on noncontrast cranial CT. The predictors of being
PCNSL comprise functional impairment, deep-seated tumor location, homogeneous contrast
enhancement, absence of cystic appearance, and presence of isodensity component on
noncontrast cranial CT. Finally, the predictors of being metastasis are an infratentorial
or extra-axial tumor location, smooth tumor margin, and presence of isointensity component
on cranial FLAIR MRI.
