Published online before print April 26, 2007, 10.1148/radiol.2433060797
(Radiology 2007;243:869-876.)
© RSNA, 2007
Thymic Hyperplasia and Thymus Gland Tumors: Differentiation with Chemical Shift MR Imaging1
Tsutomu Inaoka, MD,
Koji Takahashi, MD, PhD,
Masayuki Mineta, MD, PhD,
Tomonori Yamada, MD,
Noriyuki Shuke, MD, PhD,
Atsutaka Okizaki, MD,
Kenichi Nagasawa, MD,
Hiroyuki Sugimori, RT, and
Tamio Aburano, MD, PhD
1 From the Department of Radiology, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan. From the 2005 RSNA Annual Meeting. Received May 6, 2006; revision requested June 27; revision received July 29; final version accepted September 18.
Address correspondence to T.I. (e-mail: tinaoka{at}asahikawa-med.ac.jp).
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ABSTRACT
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Purpose: To prospectively evaluate chemical shift magnetic resonance (MR) imaging for differentiating thymic hyperplasia from tumors of the thymus gland.
Materials and Methods: The institutional review board approved this study; informed consent was obtained and patient confidentiality was protected. The authors assessed 41 patients (17 male, 24 female; age range, 16–78 years) in whom thymic lesions were seen at chest computed tomography. Patients were assigned to a hyperplasia group (n = 23) (18 patients with hyperplastic thymus associated with Graves disease and five with rebound thymic hyperplasia) and a tumor group (n = 18) (seven patients with thymomas, four with invasive thymomas, five with thymic cancers, and two with malignant lymphomas). T2-weighted fast spin-echo and T1-weighted in-phase and opposed-phase MR images were obtained in all patients and visually assessed. A chemical shift ratio (CSR), determined by comparing the signal intensity of the thymus gland with that of the paraspinal muscle, was calculated for quantitative analysis. Mean CSRs for the patient groups and subgroups were analyzed by using Welch t and Newman-Keuls tests. P < .05 indicated a significant difference.
Results: The thymus gland had homogeneous signal intensity in all 23 patients in the hyperplasia group and in 12 of the 18 patients in the tumor group. The mean CSR (± standard deviation) was 0.614 ± 0.130 in the hyperplasia group and 1.026 ± 0.039 in the tumor group. Mean CSRs in the patients with a hyperplastic thymus and Graves disease, rebound thymic hyperplasia, thymoma, invasive thymoma, thymic cancer, and malignant lymphoma were 0.594 ± 0.120, 0.688 ± 0.154, 1.033 ± 0.043, 1.036 ± 0.040, 1.020 ± 0.044, and 0.997 ± 0.010, respectively. The difference in CSR between the hyperplasia and tumor groups was significant (P < .001). Mean CSRs in the hyperplasia subgroups were lower than those in the tumor subgroups (P < .001). All hyperplasia group patients had an apparent decrease in thymus gland signal intensity at chemical shift MR imaging; no tumor group patients had a decrease in thymus gland signal intensity.
Conclusion: Chemical shift MR imaging can be used to differentiate thymic hyperplasia from thymic tumors.
© RSNA, 2007
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INTRODUCTION
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Currently, the thymus gland can be assessed with computed tomography (CT) and/or magnetic resonance (MR) imaging for various imaging features. Because of overlapping imaging features, however, it can be difficult to make a specific diagnosis, particularly in patients with diffuse thymic enlargement (1–6). Moreover, age-related and reactive alterations of the thymus gland also present diagnostic challenges (7–10). Although scintigraphic evaluations have been performed for various thymic lesions, the diagnostic criteria overlap considerably (11–13).
Minimally invasive surgical techniques, including transcervical incision and video-assisted thoracoscopic surgery, are now more popular than conventional open techniques, mainly in patients with myasthenia gravis (12,14,15). Robot-assisted thymectomy has been reported (16). These methods, however, are not recommended for patients with neoplastic lesions such as thymoma because of the risk of local recurrence. Therefore, the importance of preoperative evaluation of thymic abnormalities has increased as more therapeutic techniques have been developed.
It has recently been reported that chemical shift MR imaging is useful for identifying normal and hyperplastic thymus by proving that normal fat infiltration is present within the tissues (17). Although it is reasonable to assume that chemical shift MR imaging will reveal no decrease in the signal intensity of tumors of the thymus gland because these organs usually do not include fat, to our knowledge, in no study have investigators systematically assessed various thymic lesions with chemical shift MR imaging. Thus, the aim of our study was to prospectively evaluate chemical shift MR imaging in the differentiation of thymic hyperplasia and tumors of the thymus gland.
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MATERIALS AND METHODS
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Patients
Our institutional review board approved this study. We obtained informed consent from all patients and protected patient confidentiality. From May 2000 to October 2005, 46 patients suspected of having thymic abnormalities at CT were prospectively examined with MR imaging. Patients 15 years or younger were excluded from this study because chemical shift MR imaging may not depict physiologic fat infiltration of the thymus gland in this age group (18). In addition, the patients with thymic cyst were excluded from this study. Our study included 41 patients (17 male, 24 female) with a mean age (± standard deviation) of 47.1 years ± 18.8 (age range, 16–78 years). The patients were assigned to two groups: a hyperplasia group (n = 23) consisting of 18 patients with hyperplastic thymus associated with Graves disease and five patients with rebound thymic hyperplasia and a tumor group (n = 18) consisting of seven patients with thymoma, four with invasive thymoma, five with thymic cancer, and two with malignant lymphoma. The mean ages of the patients in the hyperplasia and tumor groups were 41.1 years ± 17.1 and 54.7 years ± 18.6, respectively. Patients in the hyperplasia group were significantly younger than those in the tumor group (P < .001).
All 18 patients with a hyperplastic thymus associated with Graves disease, who were admitted to our hospital to undergo radioiodine therapy for Graves hyperthyroidism, underwent neck CT to estimate the thyroid volume before treatment. Volumetric CT was routinely performed through the angle of the mandible and the tracheal carina because the thyroid gland occasionally extended to the superior and anterior mediastinum. In the five patients with rebound thymic hyperplasia, underlying diseases included breast cancer (n = 2), soft-tissue sarcoma (n = 2), and ovarian cancer (n = 1). In the tumor group, two patients each in the thymoma and invasive thymoma subgroups had myasthenia gravis.
Proof of Diagnosis
In the hyperplasia group (n = 23), pathologic proof could be obtained in only one of the five patients with rebound thymic hyperplasia. In the remaining four patients, the diagnosis was made by identifying an increase in the size of the thymus gland at CT after chemotherapy, surgery, and/or radiation therapy with no further increase in size detected at follow-up CT performed at 1 and 6 months. These patients did not undergo any treatment during 6-month follow-up because no biochemical sign of recurrence or metastasis was found at monthly checkups.
For the other 18 patients in the hyperplasia group, the diagnosis was made on the basis of clinical and CT findings. The thymus gland appeared at initial CT as a soft-tissue structure with a biconvex margin in the anterior mediastinum. No fat infiltration was seen within the thymus gland. In addition, a maximal thymus thickness of 14 mm at CT was used as the threshold for differentiating hyperplasia from a normal thymus (1,2). The diagnosis of hyperplastic thymus was made on the basis of accompanying Graves disease, in which either a decrease in the size of the thymus gland was identified at follow-up CT performed 6 months after the treatment for Graves disease (n = 3) or stability in the size of the thymus gland was confirmed at follow-up CT and no clinical symptom was found during the follow-up period (mean follow-up, 21.9 months; range, 6–39 months) (n = 15). It is well known that hyperplastic thymus may be associated with Graves disease (19).
For the 18 patients in the tumor group, the diagnosis was pathologically established with core biopsy (n = 3) or surgical excision (n = 15).
MR Imaging
MR imaging was performed with 1.5-T units (Signa, GE Medical Systems, Milwaukee, Wis [n = 23]; Magnetom Sonata, Siemens Medical Systems, Erlangen, Germany [n = 18]) to evaluate thymic lesions. Patients were assigned to the MR units on the basis of the availability of the machines. A dedicated phased-array surface coil was used. In all patients, imaging was performed in the transverse plane with T2-weighted fast spin-echo and T1-weighted gradient-echo in-phase and opposed-phase MR sequences. T2-weighted fast spin-echo images were obtained with the following parameters: 3000–5217/73.0–92.0 (repetition time msec/echo time msec), 275–400-mm field of view, 256 x 256 matrix, 5-mm-thick sections, 0–0.5-mm gap between sections, and two signals acquired. Respiratory gating was used; cardiac gating was not used.
T1-weighted gradient-echo images were obtained with the following parameters: 240–400-mm field of view, 256 x 256 matrix, 6–8-mm-thick sections, 0–0.5-mm gap between sections, one signal acquired, and one 20–28-second breath hold. Fast multiplanar spoiled two-dimensional gradient-echo MR sequences (Signa) were performed with a 90° flip angle and 150/4.5 for in-phase images and 150/2.3 for opposed-phase images. Two-dimensional fast gradient-recalled-echo MR sequences (Magnetom Sonata) were performed with a 90° flip angle and 154/4.6 for in-phase images and 154/2.3 for opposed-phase images. The in-phase and opposed-phase images were obtained in separate breath holds. In general, we used an anterior-to-posterior phase-encoding direction. In seven of the 41 patients, however, we switched to a left-to-right phase-encoding direction to avoid flow artifacts within the thymus gland. The phase-encoding direction was always the same on the in-phase and opposed-phase images.
MR Image Analysis
All MR images were assessed for the shape, size, signal intensity, and heterogeneity of the thymus gland by two radiologists (T.Y. and T.I., with 13 and 8 years of experience in clinical MR imaging, respectively). The readers evaluated the images independently and were blinded to the patients' identification and clinical information. Final decisions were made by consensus. The shape of the thymus gland was classified as diffuse enlargement (biconvex margin) with or without lobulation, round, or irregular. The thymus glands with diffuse enlargement were further classified as those with and those without lobulation because the former classification may indicate the presence of an associated mass lesion within the thymus gland. To determine the size, the maximal thickness of the thymus gland was measured on transverse images when it showed diffuse enlargement; the maximal diameter of the thymus gland was measured on transverse images when it was round or irregularly shaped.
The signal intensity of the thymus gland was compared with that of the paraspinal muscle. The lesion was classified as homogeneous if it was composed of one signal intensity. If the lesion had heterogeneous signal intensity, the signal intensity was determined by using the dominant signal intensity. In addition, the readers determined whether the decrease in signal intensity of the thymus gland was seen on the opposed-phase image relative to the in-phase image. For quantitative assessment, two authors (T.I. and H.S., with 5 years experience in clinical MR imaging) measured the signal intensities of the thymus gland and paraspinal muscle on both in-phase and opposed-phase images by consensus agreement. They manually positioned one circular region of interest (area, 0.76–1.55 cm2) each at the center of the thymus gland and at the center of the paraspinal muscle on the standard MR console. The chemical shift ratio (CSR), which was determined by comparing the signal intensity of the thymus gland (tSI) with that of the paraspinal muscle (mSI) on both in-phase (in) and opposed-phase (op) images, was calculated (T.I.) with computer software (Excel for Windows 2000; Microsoft, Redmond, Wash) by using the following equation: CSR = (tSIop/mSIop)/(tSIin/mSIin). Because the in-phase and opposed-phase images were separately obtained at chemical shift MR imaging, we compared the signal intensity of the thymus gland with that of the paraspinal muscle by using the CSR calculations to assess any dropout in signal intensity of the thymus gland between the two images.
Statistical Analyses
The CSR values are expressed as means ± standard deviations for the groups and subgroups. To test between-group differences, the t test for equal or unequal variance (Welch t test) was performed after the equality of variance was tested with the F test. To test between-subgroup differences, one-way analysis of variance was performed following the Newman-Keuls multiple-comparisons test after confirming the equality of variance with the Levene test. All statistical analyses were performed with software (Statistica for Windows 1999; StatSoft, Tulsa, Okla) by T.I. and N.S. The thymic lymphoma subgroup was excluded from statistical analysis of the between-subgroup difference because of the limited number of patients in this subgroup. P values of less than .05 were considered indicative of a statistically significant difference.
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RESULTS
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MR Image Assessment
In the 23 patients in the hyperplasia group, the thymus gland showed diffuse enlargement with lobulation in six patients and diffuse enlargement without lobulation in 17. In all patients, the thymus gland had homogeneous intermediate signal intensity at T1-weighted imaging and homogeneous, slightly high or high signal intensity relative to that of muscle at T2-weighted imaging. The maximal thickness of the thymus gland ranged from 14 to 26 mm (mean, 17.2 mm). In the subgroup of patients with a hyperplastic thymus associated with Graves disease, the maximal thickness of the thymus gland ranged from 14 to 26 mm (mean, 17.5 mm). In the subgroup of patients with rebound thymic hyperplasia, the maximal thickness of the thymus gland ranged from 14 to 18 mm (mean, 16.2 mm).
In the tumor group, the thymus gland was round in 15 patients, had diffuse enlargement without lobulation in two patients, and had an irregular shape in one patient. On transverse images, the maximal diameter of the round and irregularly shaped thymus gland ranged from 18 to 50 mm (mean, 32.6 mm). In the two patients with diffuse thymic enlargement, the maximal thicknesses were 14 and 22 mm. The thymus gland of all patients in the tumor group had homogeneous intermediate signal intensity at T1-weighted imaging. At T2-weighted imaging, the thymus gland had homogeneous, slightly high or high signal intensity in 12 patients, heterogeneous high signal intensity in five patients, and low signal intensity in one patient. Therefore, all 23 patients (100%) in the hyperplasia group and 12 of the 18 patients (67%) in the tumor group had a homogeneous signal intensity pattern in the thymus.
In the qualitative analysis of chemical shift MR imaging, a homogeneous decrease in the signal intensity of the thymus gland was identified on the opposed-phase image relative to the in-phase image in all patients in the hyperplasia group. No signal intensity loss in the thymus gland was identified on the opposed-phase image relative to the in-phase image in any patients in the tumor group (Table 1; Figs 1, 2).
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Figure 1a: Hyperplastic thymus in a 28-year-old woman with Graves disease. Chest CT depicted an enlarged thymus with lobulation. No fat attenuation was seen. (a) Transverse T2-weighted fast spin-echo MR image (5217/83.7) shows diffuse thymic enlargement (long arrows) with mild lobulation (short arrows). The thymus gland has homogeneous high signal intensity that is slightly higher than that of muscle. The maximal thickness of the thymus gland is 22 mm. Transverse (b) in-phase (150/4.5) and (c) opposed-phase (150/2.3) gradient-echo T1-weighted MR images demonstrate an apparent decrease in the signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 0.670. The left-to-right phase-encoding direction was used to avoid flow artifacts within the thymus gland.
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Figure 1b: Hyperplastic thymus in a 28-year-old woman with Graves disease. Chest CT depicted an enlarged thymus with lobulation. No fat attenuation was seen. (a) Transverse T2-weighted fast spin-echo MR image (5217/83.7) shows diffuse thymic enlargement (long arrows) with mild lobulation (short arrows). The thymus gland has homogeneous high signal intensity that is slightly higher than that of muscle. The maximal thickness of the thymus gland is 22 mm. Transverse (b) in-phase (150/4.5) and (c) opposed-phase (150/2.3) gradient-echo T1-weighted MR images demonstrate an apparent decrease in the signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 0.670. The left-to-right phase-encoding direction was used to avoid flow artifacts within the thymus gland.
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Figure 1c: Hyperplastic thymus in a 28-year-old woman with Graves disease. Chest CT depicted an enlarged thymus with lobulation. No fat attenuation was seen. (a) Transverse T2-weighted fast spin-echo MR image (5217/83.7) shows diffuse thymic enlargement (long arrows) with mild lobulation (short arrows). The thymus gland has homogeneous high signal intensity that is slightly higher than that of muscle. The maximal thickness of the thymus gland is 22 mm. Transverse (b) in-phase (150/4.5) and (c) opposed-phase (150/2.3) gradient-echo T1-weighted MR images demonstrate an apparent decrease in the signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 0.670. The left-to-right phase-encoding direction was used to avoid flow artifacts within the thymus gland.
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Figure 2a: Thymoma in a 48-year-old woman with myasthenia gravis. Chest CT depicted a homogeneous soft-tissue structure with a biconvex margin in the anterior mediastinum. No lobulation was seen. Therefore, this case was misdiagnosed as hyperplastic thymus at chest CT. (a) Transverse T2-weighted fast spin-echo MR image (3660/73.0) shows diffuse thymic enlargement (arrows) with high signal intensity relative to that of muscle. The maximal thickness of the thymus gland is 22 mm. Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate no apparent decrease in signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 1.080.
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Figure 2b: Thymoma in a 48-year-old woman with myasthenia gravis. Chest CT depicted a homogeneous soft-tissue structure with a biconvex margin in the anterior mediastinum. No lobulation was seen. Therefore, this case was misdiagnosed as hyperplastic thymus at chest CT. (a) Transverse T2-weighted fast spin-echo MR image (3660/73.0) shows diffuse thymic enlargement (arrows) with high signal intensity relative to that of muscle. The maximal thickness of the thymus gland is 22 mm. Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate no apparent decrease in signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 1.080.
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Figure 2c: Thymoma in a 48-year-old woman with myasthenia gravis. Chest CT depicted a homogeneous soft-tissue structure with a biconvex margin in the anterior mediastinum. No lobulation was seen. Therefore, this case was misdiagnosed as hyperplastic thymus at chest CT. (a) Transverse T2-weighted fast spin-echo MR image (3660/73.0) shows diffuse thymic enlargement (arrows) with high signal intensity relative to that of muscle. The maximal thickness of the thymus gland is 22 mm. Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate no apparent decrease in signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 1.080.
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CSR Calculation
The mean CSR was 0.614 ± 0.130 in the hyperplasia group and 1.026 ± 0.039 in the tumor group. The mean CSRs in the patients with hyperplastic thymus, rebound thymic hyperplasia, thymoma, invasive thymoma, thymic cancer, and malignant lymphoma were 0.594 ± 0.120, 0.688 ± 0.154, 1.033 ± 0.043, 1.036 ± 0.040, 1.020 ± 0.044, and 0.997 ± 0.010, respectively. The Welch t test was performed for group comparison because a statistically significant F value was found (P < .001). Statistically significant differences were seen between the hyperplasia and tumor groups (P < .001); there was no overlap in range. The CSRs in the hyperplasia subgroups were significantly lower than those in the tumor subgroups (P < .001) (Table 2, Figs 3–5).
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Figure 3a: Box plots demonstrate CSRs for (a) the hyperplasia and tumor groups and (b) the five subgroups. Subgroups include patients with hyperplastic thymus associated with Graves disease (HT-GD), rebound thymic hyperplasia (RTH), thymoma (T), invasive thymoma (IT), and thymic cancer (TC). The box plot is a graphic representation of summary values for CSR. The boxes stretch from the 25th to the 75th percentiles. The horizontal line across each box is the median. The vertical lines with whiskers extending below and above the boxes indicate the minimal and maximal values, respectively, in the tolerance. The values outside this range are displayed in individual points ( ). Note that the data in the hyperplasia and tumor groups do not overlap.
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Figure 3b: Box plots demonstrate CSRs for (a) the hyperplasia and tumor groups and (b) the five subgroups. Subgroups include patients with hyperplastic thymus associated with Graves disease (HT-GD), rebound thymic hyperplasia (RTH), thymoma (T), invasive thymoma (IT), and thymic cancer (TC). The box plot is a graphic representation of summary values for CSR. The boxes stretch from the 25th to the 75th percentiles. The horizontal line across each box is the median. The vertical lines with whiskers extending below and above the boxes indicate the minimal and maximal values, respectively, in the tolerance. The values outside this range are displayed in individual points (). Note that the data in the hyperplasia and tumor groups do not overlap.
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Figure 4a: Rebound thymic hyperplasia in a 41-year-old woman with left breast cancer. The thymus gland increased in size at chest CT after postoperative radiation therapy. (a) Transverse T2-weighted fast spin-echo MR image (3660/73.0) shows diffuse thymic enlargement (arrows) with homogeneous high signal intensity relative to that of the muscle. Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate an apparent decrease in signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 0.613. The maximal thickness of the thymus gland is 15 mm.
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Figure 4b: Rebound thymic hyperplasia in a 41-year-old woman with left breast cancer. The thymus gland increased in size at chest CT after postoperative radiation therapy. (a) Transverse T2-weighted fast spin-echo MR image (3660/73.0) shows diffuse thymic enlargement (arrows) with homogeneous high signal intensity relative to that of the muscle. Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate an apparent decrease in signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 0.613. The maximal thickness of the thymus gland is 15 mm.
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Figure 4c: Rebound thymic hyperplasia in a 41-year-old woman with left breast cancer. The thymus gland increased in size at chest CT after postoperative radiation therapy. (a) Transverse T2-weighted fast spin-echo MR image (3660/73.0) shows diffuse thymic enlargement (arrows) with homogeneous high signal intensity relative to that of the muscle. Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate an apparent decrease in signal intensity of the thymus gland (arrows) on c relative to b. The CSR is 0.613. The maximal thickness of the thymus gland is 15 mm.
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Figure 5a: Malignant lymphoma of the thymus gland in a 49-year-old woman. Chest CT depicted an irregularly shaped lesion with soft-tissue attenuation in the anterior mediastinum. Contrast material–enhanced CT revealed homogeneous enhancement within the lesion. (a) Transverse T2-weighted fast spin-echo MR image (3000/92.0) shows that a lesion with relatively homogeneous high signal intensity involves the thymus gland (arrows). Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate no change in signal intensity of the lesion (arrows) on c relative to b. The CSR is 0.989.
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Figure 5b: Malignant lymphoma of the thymus gland in a 49-year-old woman. Chest CT depicted an irregularly shaped lesion with soft-tissue attenuation in the anterior mediastinum. Contrast material–enhanced CT revealed homogeneous enhancement within the lesion. (a) Transverse T2-weighted fast spin-echo MR image (3000/92.0) shows that a lesion with relatively homogeneous high signal intensity involves the thymus gland (arrows). Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate no change in signal intensity of the lesion (arrows) on c relative to b. The CSR is 0.989.
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Figure 5c: Malignant lymphoma of the thymus gland in a 49-year-old woman. Chest CT depicted an irregularly shaped lesion with soft-tissue attenuation in the anterior mediastinum. Contrast material–enhanced CT revealed homogeneous enhancement within the lesion. (a) Transverse T2-weighted fast spin-echo MR image (3000/92.0) shows that a lesion with relatively homogeneous high signal intensity involves the thymus gland (arrows). Transverse (b) in-phase (154/4.6) and (c) opposed-phase (154/2.3) gradient-echo T1-weighted MR images demonstrate no change in signal intensity of the lesion (arrows) on c relative to b. The CSR is 0.989.
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DISCUSSION
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Chemical shift MR imaging is much more sensitive than other fat-suppressed MR sequences for detecting microscopic fat within tissue because it relies on the unique difference in resonance frequency between protons in water and those in triglyceride molecules (20,21). Chemical shift MR imaging enables one to effectively prove the presence of an intravoxel mixture of fat and water in tissues, which would be indistinct at CT, by showing a loss of signal intensity on the opposed-phase image relative to the in-phase image. In clinical MR examinations, this technique is widely used to diagnose fat-containing adrenal adenoma and fatty liver (20,21).
It can be challenging to differentiate hyperplastic thymus from thymoma on the basis of morphologic assessment alone, especially in patients with myasthenia gravis (22,23). Thymoma may show diffuse thymic enlargement at CT, and this can be incorrectly diagnosed as a hyperplastic thymus. In addition, hyperplastic thymus may appear at CT as a soft-tissue mass mimicking thymoma. The results of our study show that chemical shift MR imaging can help differentiate between hyperplastic thymus and thymoma.
Malignant lymphoma may involve the thymus gland. When the thymus gland increases in size after chemotherapy and/or radiation therapy, it may be difficult to differentiate rebound thymic hyperplasia from recurrence of lymphoma (24–26). A biopsy may be necessary in some patients. Rebound thymic hyperplasia has normal histologic features (9). Our results show that rebound thymic hyperplasia lost signal intensity on the opposed-phase images relative to the in-phase images, whereas thymic lymphoma did not. Although we excluded patients with malignant lymphoma from statistical analysis of the between-subgroup differences owing to their limited number, chemical shift MR imaging may be useful for the differentiation.
Thallium 201 (201Tl) scintigraphy—which mainly depicts cellular metabolic activity, regional blood flow, and the number of viable cells—is used to evaluate thymic lesions (12). The detection of hyperplastic thymus and thymoma with this method is equal or superior to that with CT. Furthermore, assessment of 201Tl uptake on both early and delayed images—obtained 15 and 180 minutes after the injection, respectively—is useful for differentiating among normal thymus, hyperplastic thymus, and thymoma in patients with myasthenia gravis (12). However, in addition to the disadvantages of low spatial resolution, high cost, low throughput, and irradiation with 201Tl scintigraphy, there is considerable overlap in the criteria used to make a diagnosis. Furthermore, this method is not recommended for patients with symptoms of pulmonary disease or heart failure, both of which may cause 201Tl uptake in the lungs and thereby result in an underestimation of the uptake ratio (12,27).
Positron emission tomography (PET) with fluorine 18 fluorodeoxyglucose (FDG) reveals a substantial accumulation of FDG in the normal thymus, hyperplastic thymus, rebound thymic hyperplasia, thymoma, thymic cancer, and metastasis (13,28). In general, however, FDG uptake in malignant tumors is higher than that in benign lesions. Although the standard uptake value may be effective for differentiating thymic cancer from other thymic diseases, it may not enable reliable differentiation of normal from abnormal thymic uptake because there is considerable overlap in the ranges of standard uptake values (13,29). In addition, PET is not suitable for differentiating among normal thymus, rebound thymic hyperplasia, and thymic lymphoma because FDG may accumulate in the normal thymus and in rebound thymic hyperplasia (30,31).
There were limitations to our study. First, we did not obtain pathologic proof of the diagnosis for most patients in the hyperplasia group. Second, the sample sizes were small and were determined without a power analysis owing to the relatively rare incidences of thymic hyperplasia and tumors. In particular, the number of patients with malignant lymphoma was very limited, even though it is important to differentiate this disease from thymic hyperplasia. Moreover, we did not evaluate thymic lymphoma after treatment. Therefore, further experience with a large number of patients is warranted to clarify the usefulness of chemical shift MR imaging in the diagnosis of thymic lymphoma. Third, only four subjects with myasthenia gravis were enrolled in this study. Further evaluation is needed for these patients as well. Last, the CSR occasionally exceeds 1.000. For this reason, we thought that the region of interest may have microscopically included the boundary or fat of the paraspinal muscles. Therefore, the region of interest should be properly positioned within the muscles, and the presence of intramuscular fat should be given particular consideration in elderly subjects.
In conclusion, all patients in the hyperplasia group showed an apparent decrease in the signal intensity of the thymus gland at chemical shift MR imaging; none of the patients in the tumor group showed a decrease in signal intensity. In addition, the mean CSR in the hyperplasia group was considerably lower than that in the tumor group, and there was no overlap in range. In particular, when the thymus gland appeared as a homogeneous soft-tissue structure at CT and/or MR imaging, chemical shift MR imaging was very useful for depicting the hyperplastic thymus. Therefore, we believe that evaluation with chemical shift MR imaging may help differentiate thymic hyperplasia from tumors of the thymus gland and that our results, if confirmed in larger studies, may justify the routine use of this method in the evaluation of thymic abnormalities.
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ADVANCES IN KNOWLEDGE
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- Chemical shift MR imaging helps differentiate thymic hyperplasia and thymus gland tumors in patients 16 years of age or older.
- Chemical shift MR imaging depicts no decrease in signal intensity of thymic tumors, unlike the decreased signal intensity of thymic hyperplasia.
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FOOTNOTES
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Abbreviations: CSR = chemical shift ratio
Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, all authors; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, T.I., K.N.; clinical studies, T.I., M.M., T.Y., H.S.; statistical analysis, T.I., N.S., A.O.; and manuscript editing, T.I., K.T., T.A.
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INTRODUCTION
