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Diffusion-Weighted Imaging Characteristics of Primary Central Nervous System Germinoma with Histopathologic Correlation

Rationale and Objectives

The aim of this study was to quantify, using diffusion-weighted magnetic resonance imaging, the microscopic rate of water diffusion in pure germinoma and to determine whether or not the apparent diffusion coefficient (ADC) values correlated with the different histologic components.

Materials and Methods

A retrospective analysis of echoplanar diffusion-weighted magnetic resonance images was conducted on 10 patients with 11 germinoma lesions. All images were obtained using 1.5-T magnets with a b value of 1000 s/mm 2 . Regions of interest were drawn separately within the solid and the cystic or necrotic components of each germinoma, as well as within the normal gray and white matter of the respective cases, to calculate ADCs. The diffusion characteristics of the germinomas were assessed using mean and normalized ADC values. Histologic samples from all cases were blindly reviewed and then correlated with the ADC values.

Results

Data are expressed as mean ± standard error. Evaluation of the solid components revealed that 36% of germinomas (4 of 11) had predominantly restricted diffusion (ADC solid , 694.71 × 10 −6 ± 74.54 × 10 −6 s/mm 2 ; ADC ratio, 0.84 ± 0.07) compared to normal brain. The majority (55% [6 of 11]) had normal diffusion (ADC solid , 947.64 × 10 −6 ± 54.38 × 10 −6 s/mm 2 ; ADC ratio, 1.14 ± 0.10). Only 9% (1 of 11) had increased diffusion (ADC solid , 1172.30 × 10 −6 ± 48.52 × 10 −6 s/mm 2 ; ADC ratio, 1.67 ± 0.16). The cystic and necrotic components had a mean ADC ratio of 2.55 ± 0.25. There was no significant correlation between the histologic components and the ADC values of germinomas.

Conclusions

The vast majority of germinomas demonstrated predominantly restricted (36%) or normal (55%) diffusion. The histologic components were not correlated with the ADC values.

Primary intracranial germinomas are rare tumors of children and young adults . They make up the bulk of central nervous system (CNS) germ cell tumors and account for approximately 0.06% to 2.24% of all intracranial neoplasms . Like other germ cell tumors, germinomas are situated in the midline, with the majority of lesions occurring in the pineal and suprasellar regions. Histologically, they are characterized by variable proportions of cellular sheets or lobules of uniform germinoma cells with large round nuclei, prominent nucleoli, and clear cytoplasm interspersed by septal bands of connective tissue rich in capillaries, lymphocytes, and at times granulomas . Cystic degeneration and necrosis may be features of germinoma. Necrosis can be in the form of single cells, small microscopic foci, or in the most extreme cases, geographic zones.

Magnetic resonance (MR) imaging plays a vital role in the diagnosis of germ cell tumors . Diffusion-weighted (DW) imaging is a fairly recently developed MR sequence that has been used for the evaluation of neurologic diseases . With fast echoplanar technology, DW imaging has become widely clinically available and is part of the routine brain imaging protocol at our institution. It is highly resistant to motion, and imaging times are <30 seconds. DW imaging provides image contrast that is dependent on the molecular (Brownian) motion of water . The apparent diffusion coefficient (ADC) is a rotationally invariant measurement of the amount of total diffusion within a given tissue , and quantification of the degree of water motion requires ADC maps . The rate of molecular water diffusion as depicted on DW imaging may be altered in various diseases . Although DW imaging has had its major impact in the evaluation of hyperacute infarctions , it is assuming an increasingly important role in the evaluation of other intracranial pathologies, such as infections and neoplasms . DW imaging has been proposed as a mechanism for producing contrast in the demarcation of different brain neoplasms . Recent studies have demonstrated hyperintense DW imaging signal in certain primary CNS neoplasms, such as lymphoma, pineoblastoma, medulloblastoma, high-grade gliomas , and two germinoma cases . However, the single study that investigated germinoma included only two cases and did not report ADC signal or value. The purpose of this study was to quantify the diffusivity of germinoma as reflected by ADC values and to determine if the ADC values correlated with the various histologic components. We hypothesized that the ADC values would correlate with the different histologic components.

Materials and methods

Patients

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Imaging Protocol

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Quantitative Analysis of the ADC Maps for Each Germinoma

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Figure 1, Placement of regions of interest (ROIs) in the solid and cystic and necrotic portions of a germinoma and in normal gray and white matter. (a) Transverse apparent diffusion coefficient (ADC) maps in the pineal region demonstrating ROI placements in the solid component of a germinoma located in the pineal region. (b) Transverse ADC map from a different patient with cystic and necrotic suprasellar germinoma demonstrating the placement of ROIs in the cystic and necrotic components and (c) in normal gray and white matter.

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Analysis of Histopathology

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Statistical Analysis

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Results

Solid Components of Germinoma

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Figure 2, Magnetic resonance images from an 11-year-old male patient with a pineal-region germinoma show restricted diffusion. (a) Transverse T2-weighted image shows an isointense mass in the pineal region. (b) Transverse diffusion-weighted imaging sequence shows hyperintense signal. (c) Transverse apparent diffusion coefficient (ADC) map shows hypointense signal. The ADC value of this lesion was relatively reduced compared to uninvolved brain. The mean ADC solid value of this germinoma (656.59 × 10 −6 ± 26 × 10 −6 s/mm 2 ) was significantly lower than ADC brain (834 × 10 −6 ± 16.37 × 10 −6 s/mm 2 ) and was consistent with restricted diffusion. (d) Contrast-enhanced transverse T1-weighted image shows enhancement of the mass.

Figure 3, Magnetic resonance images from a 9-year-old female patient with an intrasellar and suprasellar germinoma show normal diffusion. Transverse T2-weighted image (a) , diffusion-weighted (DW) imaging (b) , apparent diffusion coefficient (ADC) maps (c) , and contrast-enhanced coronal T1-weighted images (d) from a germinoma in the sellar and suprasellar region shows a germinoma with normal diffusion. The solid components have isointense signal on T2-weighted imaging, DW imaging, and ADC maps. The mean ADC value of this germinoma (843.03 × 10 −6 ± 26 × 10 −6 s/mm 2 ) is not significantly different from normal brain ADC brain (844.00 × 10 −6 ± 16.37 × 10 −6 s/mm 2 ).

Figure 4, Magnetic resonance images from a 7-year-old female patient with a suprasellar germinoma show relatively increased diffusion in the solid component. (a) Axial T2-weighted image shows an isointense mass in the suprasellar cistern. (b) The axial diffusion-weighted imaging sequence shows hypointense signal, and the axial apparent diffusion coefficient (ADC) map (c) shows mixed isointense and hyperintense signal. The ADC value of this lesion was relatively increased compared to uninvolved brain, despite effort to avoid the cystic and necrotic components. The mean ADC solid value of this germinoma (1172.3 × 10 −6 ± 48.52 × 10 −6 s/mm 2 ) was significantly higher than the ADC brain value (845.66 × 10 −6 ± 10.72 × 10 −6 s/mm 2 ) and was consistent with increased diffusion.

Table 1

Summary of ADC Values (× 10 −6 s/mm 2 ) by Individual Cases

Case Germinoma Solid Component Uninvolved Brain Germinoma Cystic/Necrotic Component_P_ ∗ Diffusion Pattern † Solid/Uninvolved Brain Cystic/Necrotic/Uninvolved Brain 1 747.35 ± 26.00 809.72 ± 15.37 920.35 ± 0.66 .0473 Restricted 0.92 ± 0.04 1.14 ± 0.02 2 667.66 ± 30.56 820.18 ± 9.52 1296.88 ± 156.60 .0009 Restricted 0.81 ± 0.04 1.58 ± 0.19 3 656.89 ± 14.97 833.71 ± 18.28 1478.06 ± 46.03 <.0001 Restricted 0.79 ± 0.02 1.77 ± 0.07 4 714.34 ± 8.24 834.14 ± 16.25 NA <.0001 Restricted 0.86 ± 0.02 NA 5 984.96 ± 67.63 819.85 ± 9.83 2833.77 ± 169.80 .0705 Normal 1.20 ± 0.08 3.46 ± 0.21 6 944.69 ± 68.90 849.57 ± 22.15 2545.19 ± 264.61 .0934 Normal 1.11 ± 0.09 3.00 ± 0.32 7 849.43 ± 31.92 870.99 ± 29.27 NA .6518 Normal 0.98 ± 0.05 NA 8 843.03 ± 13.69 844.00 ± 13.33 2330.39 ± 138.98 .9599 Normal 1.00 ± 0.02 2.76 ± 0.17 9 794.16 ± 15.95 823.11 ± 12.07 2540.03 ± 32.63 .1724 Normal 0.96 ± 0.02 3.09 ± 0.06 10 850.90 ± 20.57 821.14 ± 13.34 2726.29 ± 215.22 .2289 Normal 1.04 ± 0.03 3.32 ± 0.27 11 1172.30 ± 48.52 845.66 ± 10.72 2452.06 ± 210.18 .0008 Increased 1.39 ± 0.06 2.90 ± 0.25

ADC, apparent diffusion coefficient.

Data are expressed as mean ± standard error. Standard errors in columns 7 and 8 were calculated from those in columns 2 to 4 using Tylor’s expansion method.

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Cystic and Necrotic Components of Germinomas

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Table 2

Comparison of Apparent Diffusion Coefficient Values (× 10 −6 s/mm 2 )

Quantitative Diffusion Pattern ∗ Tissue Type Restricted Normal Increased Solid germinoma 694.71 ± 74.54 aA 947.64 ± 54.38 bD 1408.44 ± 131.64 cF Uninvolved brain 828.62 ± 8.56 dB 833.74 ± 6.46 dD 845.66 ± 16.68 dF Cystic/necrotic germinoma 2574.16 ± 125.42 eC 1875.84 ± 247.16 eE 2452.06 ± 210.18 eF Solid/uninvolved brain 0.84 ± 0.09 1.14 ± 0.07 1.67 ± 0.16 Cystic/necrotic/uninvolved brain 3.11 ± 0.15 2.25 ± 0.30 2.90 ± 0.26

Data are expressed as mean ± standard error. Standard errors in rows 5 and 6 were estimated from means and standard errors in rows 2 to 4 using Tylor’s expansion method.

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Normal Gray and White Matter (Uninvolved Brain)

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Histologic Analysis of Germinoma

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Figure 5, Classic germinoma showing lobules of densely packed tumor cells interspersed by thin bands of fibrous tissue sprinkled with lymphocytes. (Hematoxylin and eosin staining; magnification, 200×.)

Table 3

Comparison of Diffusion Pattern and Histopathologic Results

Quantitative Diffusion Pattern Component of Germinoma Classification Restricted Normal Increased_P_ Cystic/necrosis Absent 3 3 0 .55 Present 1 3 1 Connective tissue Low 0 4 0 .11 High 3 2 1 Granuloma Absent 0 4 1 .10 Present 3 2 0 Lymphocytic infiltrate Mild 0 1 1 .09 Intense 3 5 0 Cellularity <25% 0 0 0 .61 25%–50% 0 0 0 50%–75% 2 3 1 >75% 1 3 0

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Discussion

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Solid Components of Germinoma

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Germinomas with Predominantly Restricted Diffusion

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Germinomas with Predominantly Normal Diffusion

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Germinomas with Predominantly Increased Diffusion

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Cystic and Necrotic Components of Germinoma

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Analysis of Normal Gray and White Matter

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Study Limitations

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Conclusions

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