Clinical Radiology xxx (2014) e1ee16
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Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Pictorial Review
Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor A.M. Priola*, S.M. Priola Department of Diagnostic Imaging, San Luigi Gonzaga University Hospital, Orbassano, Torino, Italy
art icl e i nformat ion Article history: Received 28 October 2013 Received in revised form 7 January 2014 Accepted 8 January 2014
Myasthenia gravis (MG) is an autoimmune disorder often associated with thymic abnormalities. At onset, thymic lymphoid hyperplasia (TLH) and thymoma can be found in up to 65% and 15% of patients, respectively. Diagnostic imaging is crucial in this setting in order to detect the presence and type of the thymic abnormality and in the preoperative planning, when indicated. Chest radiography has a minor role due to its low accuracy. Computed tomography is the imaging modality of choice, although the differentiation between a small thymoma and TLH that appears as a focal soft-tissue mass may be not possible. Magnetic resonance imaging (MRI) is not usually employed, but it is useful in equivocal cases, especially in differentiating focal TLH from thymoma by using chemical-shift sequences for defining the proper management. In addition, diffusion-weighted (DW)-MRI can differentiate lipid-poor normal/hyperplastic thymus from thymoma and could be useful in differentiating non-advanced from advanced thymomas. Positron emission tomography (PET)-CT is not helpful in distinguishing early from advanced thymoma but can be used to differentiate thymic carcinoma from thymoma. Hereby, we discuss the imaging features of thymic abnormalities in MG, even focusing on novel aspects of chemical-shift and DW-MRI. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction characterized by muscle weakness, often initially involving the extrinsic ocular muscles and subsequently resulting in generalized MG in two-thirds of patients.1e5 There is a bimodal age of onset, with a female predominance below 40 years (female/male ratio, 3/1), a male predominance over 50 years (female/ male ratio, 1/2), and a fairly even gender distribution in the fifth decade and puberty.2,3 Overall, a female
* Guarantor and correspondent: A.M. Priola, Department of Diagnostic Imaging, San Luigi Gonzaga University Hospital, Regione Gonzole 10, 10043 Orbassano, Torino, Italy. Tel.: þ39 011 9026406; fax: þ39 011 6705463. E-mail address: [email protected] (A.M. Priola).
preponderance is reported in European and U.S. studies, which show a female/male ratio that varies from 1.4/1 to 2/1.1e3 The thymus plays an important role in MG as many patients have thymic abnormalities, namely thymic lymphoid hyperplasia (TLH) and thymic epithelial tumours (TETs, mostly thymomas and rarely thymic carcinomas).6 TLH refers to the presence of thymic tissue with lymphoid germinal centres in the thymic medulla. It is observed in a number of autoimmune diseases, most commonly MG, being seen in up to 65% of MG patients.3,7e9 Thymomas are benign or low-grade malignant tumours arising from the thymic epithelium and approximately 30e50% of patients with thymoma develop MG; otherwise, 15% of patients presenting with MG are found to have thymoma.10,11 Hence, diagnostic imaging is crucial in all patients with recent onset of MG to evaluate the presence of an underlying TLH
0009-9260/$ e see front matter Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.crad.2014.01.005
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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A.M. Priola, S.M. Priola / Clinical Radiology xxx (2014) e1ee16
or thymoma.12e14 Furthermore, diagnostic imaging is useful in preoperative planning of MG patients, as thymectomy is strongly recommended in all patients with thymoma and the radiological assessment can aid in differentiating nonadvanced from advanced disease in order to select patients for induction chemotherapy before surgery.5,15 For non-thymomatous patients, the clinical efficacy of thymectomy has been questioned because the evidence supporting its use is not clear and has largely been based on single-institution retrospective, observational studies.1e5 Although no uniformly accepted guidelines are available, thymectomy is believed to be suitable for patients with generalized MG under 50 years with antibodies to the acetylcholine receptor and TLH, for achieve clinical improvement and complete stable remission.15,16 Conversely, effectiveness of extended thymectomy is still under discussion in cases of generalized MG with atrophic thymus because the results of different studies are controversial. As a rule, thymectomy is not routinely performed when imaging demonstrates completely fatty involution of the thymus.15,16 Therefore, the role of radiological assessment in MG patients is primarily the detection of thymoma and its differentiation from TLH. Diagnostic imaging is able to define the presence and location of TLH, even in cases of ectopic thymic tissue, and aids the surgeon in complete removal, because persistence of lymphoid thymic tissue has been considered one of the main reasons of relapse after thymectomy.17e19 The aim of this review is to highlight the role of diagnostic imaging in patients with MG and to discuss the radiological features of TLH and TETs using conventional radiography, computed tomography (CT), magnetic resonance imaging (MRI), and combined positron-emission tomography and CT (PET-CT). In addition, as TLH may appear indistinguishable from a normal thymus, a brief reference to the CT, MRI, and PET-CT appearance of the normal thymus at different age ranges is also discussed.
Conventional radiography Chest radiography (CR) represents the basic imaging method in the evaluation of patients with MG.20 Even in young patients, frontal and lateral projections must be performed as small lesions of the anterior mediastinum that do not distort the mediastinal contours may go undetected on the unique frontal view.21
Thymic lymphoid hyperplasia CR has no role in the evaluation of TLH in patients with MG.21 Indeed, as for the normal thymus of children >3 years and adults, TLH rarely produces evident radiographic findings due to its usual small size and low attenuation.
Thymic epithelial tumors CR may help detect relatively large thymomas and as many as 80% of thymomas are identified on frontal CR, although smaller lesions may go undetected.22 When
thymic lesions are detectable on CR, it can demonstrate location, size, density, and presence of calcifications. On frontal view, small TETs usually appear as focal or diffuse thickening of the anterior junction line and/or as an abnormal mediastinal contour (Fig 1).20,24 When large, thymomas typically appear as roughly spherical or ovoid, well-marginated, smooth masses that extend to one or the other side of the midline (Fig 2), whereas bilateral tumour growth occurs less frequently.20,23 On lateral radiography, thymomas usually manifest as sharply marginated retrosternal areas of increased opacity with smooth or lobulate borders (Figs 1 and 2) or as subtle increased soft-tissue density in the retrosternal clear space.6,20 Occasionally, CR may help detect advanced disease by demonstrating pulmonary invasion (through an irregular border against the adjacent lung parenchyma), phrenic nerve involvement (as elevation of the ipsilateral hemidiaphragm), or pleural involvement (as multifocal soft tissue nodules usually ipsilateral to the mediastinal mass).23 Pleural effusion, lung metastases, or hilar prominence secondary to lymphadenopathies are not typical of thymomas, whereas these may be found in thymic carcinomas that are more aggressive and clearly malignant tumours, and usually occur as large anterior mediastinal masses at CR.6,25,26
Computed tomography CT is able to characterize abnormalities previously identified on CR and may demonstrate small thymomas in patients with MG who have normal CR.27e29 Unenhanced chest CT is initially performed and needs no further investigations when findings are suggestive of normal thymus, TLH, or fat involution of the thymus (Fig 3). When unenhanced chest CT detects a mass with soft-tissue attenuation, intravenous contrast medium injection is usually employed to assess the enhancement characteristics of the lesion and the invasion of adjacent structures, and to better show small pleural/pericardial implants (Figs 3f, 5 and 6).24,30e34 Moreover, as invasive thymoma can cross the diaphragm into the abdomen and retroperitoneum, contrast-enhanced CT of the upper abdomen should be performed to assess the extent of transdiaphragmatic spread.24,35 When histological diagnosis is required because imaging techniques are equivocal for a diagnosis of TET, non-surgical needle core biopsy may be obtained under CT-guidance obviating the need for surgical biopsy.21 Indeed, the diagnostic role of core biopsy in patients with suspected TET is mainly to exclude other types of non-surgical lesions, especially to differentiate thymoma from thymic carcinoma and TETs from lymphomas, which is crucial for the correct management of patients.36e38 In addition, histology is required for suspected advanced thymomas at imaging in order to confirm the diagnosis of TET before administration of induction chemotherapy.4,5 Core biopsy must be always preferred over fine-needle aspiration cytology, as previous studies have obtained higher rates of specific diagnoses using core biopsy, with reported values of sensitivity, specificity, and diagnostic accuracy of >83%.36,37
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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Figure 1 Chest radiograph of a 34-year-old woman with recent onset of MG and small thymoma (MasaokaeKoga stage I, WHO type AB). Posteroanterior radiograph (left image) shows a slight hilar prominence on the right side (white arrows) and an abnormally thickened anterior junction line (black arrows) secondary to an anterior mediastinal mass. Lateral radiograph (right image) clearly demonstrates a sharply wellmarginated retrosternal area of increased opacity with thin linear peripheral calcifications (arrows).
Figure 2 Chest radiograph of a 57-year-old man with a large thymoma who presented with chest pain and MG (MasaokaeKoga stage IIb, WHO type B1). Frontal view (left image) detects a large left anterior mediastinal mass that produces an abnormal mediastinal contour (arrows) and obscure the upper part of the heart border. Lateral view (right image) shows a well-defined, lobulate soft-tissue opacity in the retrosternal clear space that projects over the anterior mediastinum (arrows).
Conversely, no preoperative histological diagnosis is required when CT findings strongly suggest non-advanced thymoma (small, resectable, capsulated lesion with no signs of invasion), although in these cases further characterization with chemical-shift MRI before surgical resection is useful for differentiating non-advanced thymoma from TLH that appears as a focal mass with soft-tissue attenuation.20,30 Non-advanced thymoma should not be biopsied because the crossing and breaking of the capsule caused by the needle could make staging difficult according to the MasaokaeKoga system after complete resection. In addition, another practical problem of CT-guided biopsy for non-advanced disease is the potential increased risk of tumour spread along the needle tract, a condition that has
been reported for thymic cancer in a single case of chest wall implantation following fine needle-aspiration cytology, although there have been more reports of needle-tract seeding following lung cancer biopsies.39
Normal thymus and thymic lymphoid hyperplasia The normal thymus usually fills the anterior superior mediastinum and varies widely in size and shape depending on age. AT CT, it shows soft-tissue attenuation similar to muscle in infants and young adults. In children 25 years, the thymus may no longer be recognizable as a soft-tissue organ, but may appear as islands of soft-tissue attenuation that exhibit linear, ovoid, or rounded shapes within a network of more abundant fat tissue.6,20,23,30 Although the thymus may still be recognized as a discrete structure until the age of 40 years, it commonly
appears to be entirely replaced by fat in half of subjects >40 years.30 In patients with MG, TLH is usually appreciable in the anatomical location of the thymus, but can occur anywhere from the thoracic inlet to the cardiophrenic angle (Fig 3e).8,40 At CT, TLH can exhibit variable morphologies and sizes as it may appear normal (45% of cases), diffusely
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
A.M. Priola, S.M. Priola / Clinical Radiology xxx (2014) e1ee16
Figure 4 Unenhanced chest CT (soft tissue window) obtained at the level of the left brachiocephalic vein in a 48-year-old woman with MG demonstrates a small thymoma (arrow; MasaokaeKoga stage I, WHO type A) in the anterior mediastinum, with smooth and wellcircumscribed borders, homogeneous soft tissue attenuation (mean densitometric value, 35 H.U.), and a maintained fat plain surrounding the lesion (magnification in the left box, asterisks). Note that the appearance of the soft tissue mass is similar to that of Fig 3f.
enlarged (35%, mostly with triangular shape and smooth margins but even quadrilateral shape and/or lobulate contours), or as a focal thymic mass (20%) (Fig. 3bef).31,32 As CT attenuation features of TLH are similar to those of the normal thymus, TLH is indistinguishable from the normal thymus when it is of normal size with a triangular or arrowhead morphology (Fig 3c).41 Differentiation between TLH and thymoma is essential for proper management, as thymectomy is indicated in all patients who have thymoma and some surgeons advocate thymectomy without biopsy for anterior mediastinal masses suggestive of thymoma at CT. This differentiation is mostly based on morphological assessment and attenuation features.6,21,29 Indeed, a normal CT appearance of the thymus or a diffuse symmetric enlargement of the gland with areas of fat attenuation represent the key morphological features of hyperplasia, whereas a diagnosis of thymoma is suggested if a solid focal mass is identified.6,20,30 However, in adults, as TLH can also occur as a focal mass with homogeneous soft-tissue attenuation and no clear fatty infiltration, it may be indistinguishable from a small thymoma.9,31e34 In fact, in a cohort of 45 patients with MG who underwent CT, a previous study reported that histological examination revealed TLH in five out of 12 focal masses that resembled thymomas in the anterior mediastinum.31 Furthermore, thymoma may produce diffuse thymic enlargement, mimicking diffusely enlarged TLH.6,20,32
Thymic epithelial tumors CT is currently considered the cross-sectional imaging technique of choice in the identification, staging, and follow-up of patients with TETs.28,42 Indeed, CT is useful for their characterization, for defining local invasive features, and for assessing pleural seeding and metastatic disease.29
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TETs arise from the thymic epithelium and demonstrate various histological features and biological behaviour.30 Histopathological and surgical classifications are essential to determine prognosis and proper management. The World Health Organization (WHO) histological classification divides TETs according to the degree of differentiation based on cellular morphology and relative proportions of epithelial cells and lymphocytes within the tumour (Table 1), whereas the MasaokaeKoga staging system is based on gross operative findings with evaluation of microscopic extension of disease in the capsule and surrounding organs (Table 2).43,44 CT has limited value in differentiating among the various WHO histological subtypes and in detecting residual or recurrent disease after treatment.45e50 Thymoma represents 20% of all mediastinal tumours in adults and is commonly located in the upper anterior mediastinum, although uncommon locations have been reported from the submandibular region to the cardiophrenic angle.11,41 It consists of an encapsulated noninvasive type and invasive type (15e40%) that has spread beyond the capsule. Although it may be difficult to distinguish invasive from encapsulated thymoma, CT can aid in differentiating MasaokaeKoga stage IeII from stage IIIeIV, as large tumour size, infiltration of the fat surrounding the tumour, and lobulate contours are significantly associated with advanced disease (stage IIIeIV) (Fig 5a).45 This distinction is essential to plan the proper treatment, because patients with advanced disease receive neoadjuvant chemotherapy before surgery.51 At CT, stage IeII thymomas manifest as round or oval and sharply demarcated masses completely or partially enclosed by a fibrous capsule and outlined by adjacent mediastinal fat, with homogeneous soft-tissue attenuation, smooth margins, no lobulations, and mild-to-moderate contrast enhancement (Fig 4). Conversely, stage IIIeIV thymomas may present lobulate and/or irregular margins, calcifications, focal low attenuation areas (that reflect haemorrhage, necrosis, or cystic change), heterogeneous enhancement, local tumour invasion through obliteration of the adjacent fat planes with encasement of mediastinal structures, and pleural or pericardial seeding (Fig 5).45 At CT, pleural seeding may appear as discrete soft-tissue nodules or as circumferential diffuse pleural thickening (Fig 6). Lymphadenopathies and haematogenous metastases are rare, but have been described in approximately 5% of patients.11 Thymic carcinomas are rare epithelial neoplasms, accounting for about 20% of TETs that exhibit histological features of malignancy. They are more aggressive tumours than invasive thymomas and typically present with local and/or metastatic spread (lung, liver, lymph nodes, and bone) in 50e65% of cases at presentation.23,24,28 At CT, they usually appear as large masses with irregular or lobular margins, areas of necrosis and calcification, heterogeneous enhancement, and lack a well-defined capsule.20,23,51 Although it may be difficult to distinguish thymic carcinomas from advanced thymomas due to considerable overlap of imaging findings, thymic carcinomas are more commonly associated with vessel invasion, mediastinal
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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Figure 5 CT image of a 62-year-old man with MG and advanced thymoma (MasaokaeKoga stage IVa, WHO type B2). (a) Unenhanced and enhanced chest CT image obtained at the level of the arch of the azygos vein (mediastinal window) demonstrate an oval right anterior mediastinal mass (thin arrows) with irregular contours that suggest invasion into the surrounding mediastinal fatty tissue, and a slight heterogeneous enhancement. Note the loss of the fat plane between the lesion and the neighbouring structures (black asterisks) and the complete encasement of the superior vena cava consistent with vascular invasion (thick arrow) with an irregular border against the contrast mediumfilled azygos vein. (b) Contrast-enhanced chest CT image (mediastinal window) shows an enhancing right pleural-based soft-tissue nodule ipsilateral to the anterior mediastinal mass along the cardiophrenic border, closely attached to the pericardium (thin arrow), and two nodular thickenings of the left side of pericardium (thick arrows) that represent pleural and pericardial implants, respectively. Note that the pericardial fat plane is maintained nearby the pleural implant (black asterisks), whereas it is not appreciable in the site of pericardial nodules (L ¼ liver).
lymphadenopathies, pleural/pericardial effusion, and extrathoracic metastases, but less commonly associated with pleural/pericardial implants (Figs. 5e7).20,26 CT is routinely employed for the imaging follow-up of TETs after surgical resection (for exclusion of residual disease, local recurrence, pleural/pericardial implants, or distant metastases), and in cases of non-resectable disease to assess response to chemotherapy and radiation therapy.20,21 In 81% of cases, recurrence occurs in the thorax (pleura, pericardium, lung, and mediastinum), whereas it is extra-thoracic (liver, bone) in the remaining cases.49 PET-CT is advantageous over CT in postoperative and follow-up
assessment, especially in patients with higher stages and/ or incompletely resected thymoma in which recurrence is more frequent, because diseased tissue may be subtle at CT.20,24 When local recurrence and/or pleural seeding are detected, recurrence and pleural implants should be surgically removed when complete resection is feasible.42 If complete resection is achieved at recurrence, the survival rate is similar to that of patients without tumour recurrence after initial resection (5 year survival rates of 65e80%), although the mean time to recurrence is longer in patients with MasaokaeKoga stage I thymoma compared to stage IIeIV thymoma (10 years versus 3 years).50
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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Table 1 World Health Organization (WHO) histological classification of thymic epithelial tumours (2004).a Type
Definition
A
Spindle cells: bland spindle/oval epithelial tumour cells with few or no lymphocytes Mixed spindle cells and lymphocytes: mixture of a lymphocyte-poor type A thymoma component and a more lymphocyte-rich type B-like component Lymphocytes > epithelial cells, predominantly cortical: areas resembling cortex of the normal thymus with epithelial cells scattered in a prominent population of immature lymphocytes and areas of medullary differentiation with or without Hassall’s corpuscles, similar to the normal thymic medulla. Some epithelial tumour cells present large nuclei of pale chromatin and small nucleoli Mixed lymphocytes and epithelial cells, cortical: large, polygonal tumour cells arranged in a loose network with large vascular nuclei and prominent large nucleoli, closely resembling the predominant epithelial cells of the normal thymic cortex. A background population of immature T-cells is always detectable and lymphocytes are less abundant than in type B1 Predominance of epithelial cells: prominent population of medium-sized round or polygonal epithelial cells with slight nuclear atypia and some prominent nucleoli mixed with a minor component of lymphocytes
AB
B1
B2
B3
Type A, AB, B1: low-risk thymomas; type B2, B3: high-risk thymomas. Thymic carcinoma: type C in 1999 WHO classification. a € ller-Hermelink et al.43 Modified from Mu
Figure 6 Different appearances of pleural implants in patients with MG and thymoma. Contrast-enhanced CT obtained at the level of the diaphragm detects nodular (a) and diffuse band-like (b) thickening of the right pleura (arrows).
Magnetic resonance imaging Currently, MRI is not routinely employed in the assessment of patients with MG, although it can provide more specific characterization compared to CT, especially in differentiating TLH from thymoma. Conversely, in most centres, MRI is generally reserved for further evaluation of equivocal CT findings of local invasion because of its better contrast resolution.20,52,53 Furthermore, MRI may be particularly useful for those cases with suspected vascular invasion in which iodinated contrast medium cannot be administered. Chemical-shift MRI is helpful in differentiating TLH from thymic neoplasms, especially in equivocal cases at CT. It is able to detect microscopic fatty infiltration within the normal/hyperplastic thymus, which would be indistinct at CT, by showing homogeneous signal decrease on opposedphase images relative to in-phase images, whereas signal loss is absent in thymoma that does not include fat (Figs 8 and 9a).54e58
Diffusion-weighted (DW)-MRI is another useful tool for characterizing thymic abnormalities in MG. It reflects tumour cell density and cellular architecture.59e61 The intra- and extracellular molecular diffusion of water detected by DW-MRI that is sensitive to thermally driven molecular water motion, can be measured as signal loss and expressed with the apparent diffusion coefficient (ADC). The ADC depends largely on the presence of barriers to diffusion within the water microenvironment, namely cell membranes and macromolecules, that alter the diffusion characteristics of the tissue.59e61 On this basis, DW-MRI has been used in different organs to differentiate benign from malignant lesions. Benign lesions (as TLH) usually present high ADC values and unrestricted diffusion, whereas
Table 2 MasaokaeKoga staging system for thymoma.a Stage
Definition
I
Macroscopically completely encapsulated tumour, with no microscopically detectable capsular invasion Macroscopic invasion into surrounding mediastinal fatty tissue or mediastinal pleura Microscopic invasion into the capsule Macroscopic invasion into neighbouring organs, such as pericardium, great vessels, and lung Pleural or pericardial dissemination through direct extension or drop metastasis Lymphogenous or haematogenous metastases
IIa IIb III IVa IVb
Stage I: non-invasive thymoma; stages IIeIV: invasive thymoma. a Modified from Masaoka et al.44
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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Figure 7 CT of a 55-year-old man with MG and thymic carcinoma, who presented with chest pain. Unenhanced (left image) and contrastenhanced (right image) chest-CT (mediastinal window) obtained at the level of the aortic arch demonstrate a slightly heterogeneous softtissue mass (thin arrow) with a right lobulate border (thick arrow) that invades the superior vena cava (asterisk). Note the loss of the fat plane between the mass and the mediastinal great vessels, the left pleural effusion (arrowhead), and a mildly enlarged ipsilateral mediastinal lymph node adjacent the arch of the azygos vein (dotted arrow).
Figure 8 Chemical-shift MRI image of a 47-year old man with MG and TLH surgically removed (same patient as Fig 3f). The round-shaped softtissue mass of the anterior mediastinum that mimics a small thymoma presents a remarkable homogeneous decrease in signal intensity on transverse opposed-phase dual-echo T1-weighted MRI image compared to in-phase image (arrows), consistent with the presence of fatty component within the tissue that suggests the diagnosis of focal TLH.
malignant lesions (as TETs) have low ADC values and restricted diffusion (Figs 9b,10bec).62e65
Normal thymus and thymic lymphoid hyperplasia The MRI signal characteristics of the normal thymus change over time reflecting the gradual fatty replacement. On T1- and T2-weighted sequences, the normal thymus in infants and young children shows homogeneous and low signal intensity on both sequences, similar to that of muscle. In older children and adolescents, the thymus typically
reveals homogeneous and increased signal intensity, intermediate between muscle and fat. Subsequently, the signal intensity of the gland gradually increases with age due to the progressive fatty infiltration, becoming similar to that of fat on T2-weighted images.41,52 When the thymus has almost completely replaced by fat, reticulonodular strands of thymic tissue and occasionally small rounded islands of residual thymus can be observed on fat-suppressed T2weighted images.52 The appearance of TLH is similar to that of the normal thymus on T1- and T2-weighted sequences.41,66 In TLH, as in
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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Figure 9 MRI of the same patient as Fig 4. (a) Transverse chemical-shift dual-echo T1-weighted MRI images demonstrate no change in signal intensity of the mass (arrows) on in-phase image relative to opposed-phase image, consistent with the absence of fatty component that suggests the diagnosis of small thymoma. (b) DW-MRI was obtained at different b-values of 0, 150, 500, and 800 s/mm2. The transverse image obtained at a b-value of 0 s/mm2 that results in conventional anatomical T2-weighted images with no vessel signal attenuation, demonstrates a high signal intensity within the lesion (arrow). At higher b-values, where vessels signal attenuation is seen, the lesion presents a progressive slight attenuation of the signal intensity (arrows) that is not completely suppressed, even at the b800 gradient image. This appearance suggests a restricted diffusion within the tissue, with a low ADC value of 1.03 103 mm2/s that strengthens the hypothesis of small thymoma.
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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the normal thymus, chemical-shift MRI shows a decrease in signal intensity on opposed-phase images in contrast to inphase images, although it can depict physiological fatty infiltration of the normal thymus in all subjects 16 years, but in none
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Pictorial Review
Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor A.M. Priola*, S.M. Priola Department of Diagnostic Imaging, San Luigi Gonzaga University Hospital, Orbassano, Torino, Italy
art icl e i nformat ion Article history: Received 28 October 2013 Received in revised form 7 January 2014 Accepted 8 January 2014
Myasthenia gravis (MG) is an autoimmune disorder often associated with thymic abnormalities. At onset, thymic lymphoid hyperplasia (TLH) and thymoma can be found in up to 65% and 15% of patients, respectively. Diagnostic imaging is crucial in this setting in order to detect the presence and type of the thymic abnormality and in the preoperative planning, when indicated. Chest radiography has a minor role due to its low accuracy. Computed tomography is the imaging modality of choice, although the differentiation between a small thymoma and TLH that appears as a focal soft-tissue mass may be not possible. Magnetic resonance imaging (MRI) is not usually employed, but it is useful in equivocal cases, especially in differentiating focal TLH from thymoma by using chemical-shift sequences for defining the proper management. In addition, diffusion-weighted (DW)-MRI can differentiate lipid-poor normal/hyperplastic thymus from thymoma and could be useful in differentiating non-advanced from advanced thymomas. Positron emission tomography (PET)-CT is not helpful in distinguishing early from advanced thymoma but can be used to differentiate thymic carcinoma from thymoma. Hereby, we discuss the imaging features of thymic abnormalities in MG, even focusing on novel aspects of chemical-shift and DW-MRI. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction characterized by muscle weakness, often initially involving the extrinsic ocular muscles and subsequently resulting in generalized MG in two-thirds of patients.1e5 There is a bimodal age of onset, with a female predominance below 40 years (female/male ratio, 3/1), a male predominance over 50 years (female/ male ratio, 1/2), and a fairly even gender distribution in the fifth decade and puberty.2,3 Overall, a female
* Guarantor and correspondent: A.M. Priola, Department of Diagnostic Imaging, San Luigi Gonzaga University Hospital, Regione Gonzole 10, 10043 Orbassano, Torino, Italy. Tel.: þ39 011 9026406; fax: þ39 011 6705463. E-mail address: [email protected] (A.M. Priola).
preponderance is reported in European and U.S. studies, which show a female/male ratio that varies from 1.4/1 to 2/1.1e3 The thymus plays an important role in MG as many patients have thymic abnormalities, namely thymic lymphoid hyperplasia (TLH) and thymic epithelial tumours (TETs, mostly thymomas and rarely thymic carcinomas).6 TLH refers to the presence of thymic tissue with lymphoid germinal centres in the thymic medulla. It is observed in a number of autoimmune diseases, most commonly MG, being seen in up to 65% of MG patients.3,7e9 Thymomas are benign or low-grade malignant tumours arising from the thymic epithelium and approximately 30e50% of patients with thymoma develop MG; otherwise, 15% of patients presenting with MG are found to have thymoma.10,11 Hence, diagnostic imaging is crucial in all patients with recent onset of MG to evaluate the presence of an underlying TLH
0009-9260/$ e see front matter Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.crad.2014.01.005
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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or thymoma.12e14 Furthermore, diagnostic imaging is useful in preoperative planning of MG patients, as thymectomy is strongly recommended in all patients with thymoma and the radiological assessment can aid in differentiating nonadvanced from advanced disease in order to select patients for induction chemotherapy before surgery.5,15 For non-thymomatous patients, the clinical efficacy of thymectomy has been questioned because the evidence supporting its use is not clear and has largely been based on single-institution retrospective, observational studies.1e5 Although no uniformly accepted guidelines are available, thymectomy is believed to be suitable for patients with generalized MG under 50 years with antibodies to the acetylcholine receptor and TLH, for achieve clinical improvement and complete stable remission.15,16 Conversely, effectiveness of extended thymectomy is still under discussion in cases of generalized MG with atrophic thymus because the results of different studies are controversial. As a rule, thymectomy is not routinely performed when imaging demonstrates completely fatty involution of the thymus.15,16 Therefore, the role of radiological assessment in MG patients is primarily the detection of thymoma and its differentiation from TLH. Diagnostic imaging is able to define the presence and location of TLH, even in cases of ectopic thymic tissue, and aids the surgeon in complete removal, because persistence of lymphoid thymic tissue has been considered one of the main reasons of relapse after thymectomy.17e19 The aim of this review is to highlight the role of diagnostic imaging in patients with MG and to discuss the radiological features of TLH and TETs using conventional radiography, computed tomography (CT), magnetic resonance imaging (MRI), and combined positron-emission tomography and CT (PET-CT). In addition, as TLH may appear indistinguishable from a normal thymus, a brief reference to the CT, MRI, and PET-CT appearance of the normal thymus at different age ranges is also discussed.
Conventional radiography Chest radiography (CR) represents the basic imaging method in the evaluation of patients with MG.20 Even in young patients, frontal and lateral projections must be performed as small lesions of the anterior mediastinum that do not distort the mediastinal contours may go undetected on the unique frontal view.21
Thymic lymphoid hyperplasia CR has no role in the evaluation of TLH in patients with MG.21 Indeed, as for the normal thymus of children >3 years and adults, TLH rarely produces evident radiographic findings due to its usual small size and low attenuation.
Thymic epithelial tumors CR may help detect relatively large thymomas and as many as 80% of thymomas are identified on frontal CR, although smaller lesions may go undetected.22 When
thymic lesions are detectable on CR, it can demonstrate location, size, density, and presence of calcifications. On frontal view, small TETs usually appear as focal or diffuse thickening of the anterior junction line and/or as an abnormal mediastinal contour (Fig 1).20,24 When large, thymomas typically appear as roughly spherical or ovoid, well-marginated, smooth masses that extend to one or the other side of the midline (Fig 2), whereas bilateral tumour growth occurs less frequently.20,23 On lateral radiography, thymomas usually manifest as sharply marginated retrosternal areas of increased opacity with smooth or lobulate borders (Figs 1 and 2) or as subtle increased soft-tissue density in the retrosternal clear space.6,20 Occasionally, CR may help detect advanced disease by demonstrating pulmonary invasion (through an irregular border against the adjacent lung parenchyma), phrenic nerve involvement (as elevation of the ipsilateral hemidiaphragm), or pleural involvement (as multifocal soft tissue nodules usually ipsilateral to the mediastinal mass).23 Pleural effusion, lung metastases, or hilar prominence secondary to lymphadenopathies are not typical of thymomas, whereas these may be found in thymic carcinomas that are more aggressive and clearly malignant tumours, and usually occur as large anterior mediastinal masses at CR.6,25,26
Computed tomography CT is able to characterize abnormalities previously identified on CR and may demonstrate small thymomas in patients with MG who have normal CR.27e29 Unenhanced chest CT is initially performed and needs no further investigations when findings are suggestive of normal thymus, TLH, or fat involution of the thymus (Fig 3). When unenhanced chest CT detects a mass with soft-tissue attenuation, intravenous contrast medium injection is usually employed to assess the enhancement characteristics of the lesion and the invasion of adjacent structures, and to better show small pleural/pericardial implants (Figs 3f, 5 and 6).24,30e34 Moreover, as invasive thymoma can cross the diaphragm into the abdomen and retroperitoneum, contrast-enhanced CT of the upper abdomen should be performed to assess the extent of transdiaphragmatic spread.24,35 When histological diagnosis is required because imaging techniques are equivocal for a diagnosis of TET, non-surgical needle core biopsy may be obtained under CT-guidance obviating the need for surgical biopsy.21 Indeed, the diagnostic role of core biopsy in patients with suspected TET is mainly to exclude other types of non-surgical lesions, especially to differentiate thymoma from thymic carcinoma and TETs from lymphomas, which is crucial for the correct management of patients.36e38 In addition, histology is required for suspected advanced thymomas at imaging in order to confirm the diagnosis of TET before administration of induction chemotherapy.4,5 Core biopsy must be always preferred over fine-needle aspiration cytology, as previous studies have obtained higher rates of specific diagnoses using core biopsy, with reported values of sensitivity, specificity, and diagnostic accuracy of >83%.36,37
Please cite this article in press as: Priola AM, Priola SM, Imaging of thymus in myasthenia gravis: From thymic hyperplasia to thymic tumor, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.01.005
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Figure 1 Chest radiograph of a 34-year-old woman with recent onset of MG and small thymoma (MasaokaeKoga stage I, WHO type AB). Posteroanterior radiograph (left image) shows a slight hilar prominence on the right side (white arrows) and an abnormally thickened anterior junction line (black arrows) secondary to an anterior mediastinal mass. Lateral radiograph (right image) clearly demonstrates a sharply wellmarginated retrosternal area of increased opacity with thin linear peripheral calcifications (arrows).
Figure 2 Chest radiograph of a 57-year-old man with a large thymoma who presented with chest pain and MG (MasaokaeKoga stage IIb, WHO type B1). Frontal view (left image) detects a large left anterior mediastinal mass that produces an abnormal mediastinal contour (arrows) and obscure the upper part of the heart border. Lateral view (right image) shows a well-defined, lobulate soft-tissue opacity in the retrosternal clear space that projects over the anterior mediastinum (arrows).
Conversely, no preoperative histological diagnosis is required when CT findings strongly suggest non-advanced thymoma (small, resectable, capsulated lesion with no signs of invasion), although in these cases further characterization with chemical-shift MRI before surgical resection is useful for differentiating non-advanced thymoma from TLH that appears as a focal mass with soft-tissue attenuation.20,30 Non-advanced thymoma should not be biopsied because the crossing and breaking of the capsule caused by the needle could make staging difficult according to the MasaokaeKoga system after complete resection. In addition, another practical problem of CT-guided biopsy for non-advanced disease is the potential increased risk of tumour spread along the needle tract, a condition that has
been reported for thymic cancer in a single case of chest wall implantation following fine needle-aspiration cytology, although there have been more reports of needle-tract seeding following lung cancer biopsies.39
Normal thymus and thymic lymphoid hyperplasia The normal thymus usually fills the anterior superior mediastinum and varies widely in size and shape depending on age. AT CT, it shows soft-tissue attenuation similar to muscle in infants and young adults. In children 25 years, the thymus may no longer be recognizable as a soft-tissue organ, but may appear as islands of soft-tissue attenuation that exhibit linear, ovoid, or rounded shapes within a network of more abundant fat tissue.6,20,23,30 Although the thymus may still be recognized as a discrete structure until the age of 40 years, it commonly
appears to be entirely replaced by fat in half of subjects >40 years.30 In patients with MG, TLH is usually appreciable in the anatomical location of the thymus, but can occur anywhere from the thoracic inlet to the cardiophrenic angle (Fig 3e).8,40 At CT, TLH can exhibit variable morphologies and sizes as it may appear normal (45% of cases), diffusely
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Figure 4 Unenhanced chest CT (soft tissue window) obtained at the level of the left brachiocephalic vein in a 48-year-old woman with MG demonstrates a small thymoma (arrow; MasaokaeKoga stage I, WHO type A) in the anterior mediastinum, with smooth and wellcircumscribed borders, homogeneous soft tissue attenuation (mean densitometric value, 35 H.U.), and a maintained fat plain surrounding the lesion (magnification in the left box, asterisks). Note that the appearance of the soft tissue mass is similar to that of Fig 3f.
enlarged (35%, mostly with triangular shape and smooth margins but even quadrilateral shape and/or lobulate contours), or as a focal thymic mass (20%) (Fig. 3bef).31,32 As CT attenuation features of TLH are similar to those of the normal thymus, TLH is indistinguishable from the normal thymus when it is of normal size with a triangular or arrowhead morphology (Fig 3c).41 Differentiation between TLH and thymoma is essential for proper management, as thymectomy is indicated in all patients who have thymoma and some surgeons advocate thymectomy without biopsy for anterior mediastinal masses suggestive of thymoma at CT. This differentiation is mostly based on morphological assessment and attenuation features.6,21,29 Indeed, a normal CT appearance of the thymus or a diffuse symmetric enlargement of the gland with areas of fat attenuation represent the key morphological features of hyperplasia, whereas a diagnosis of thymoma is suggested if a solid focal mass is identified.6,20,30 However, in adults, as TLH can also occur as a focal mass with homogeneous soft-tissue attenuation and no clear fatty infiltration, it may be indistinguishable from a small thymoma.9,31e34 In fact, in a cohort of 45 patients with MG who underwent CT, a previous study reported that histological examination revealed TLH in five out of 12 focal masses that resembled thymomas in the anterior mediastinum.31 Furthermore, thymoma may produce diffuse thymic enlargement, mimicking diffusely enlarged TLH.6,20,32
Thymic epithelial tumors CT is currently considered the cross-sectional imaging technique of choice in the identification, staging, and follow-up of patients with TETs.28,42 Indeed, CT is useful for their characterization, for defining local invasive features, and for assessing pleural seeding and metastatic disease.29
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TETs arise from the thymic epithelium and demonstrate various histological features and biological behaviour.30 Histopathological and surgical classifications are essential to determine prognosis and proper management. The World Health Organization (WHO) histological classification divides TETs according to the degree of differentiation based on cellular morphology and relative proportions of epithelial cells and lymphocytes within the tumour (Table 1), whereas the MasaokaeKoga staging system is based on gross operative findings with evaluation of microscopic extension of disease in the capsule and surrounding organs (Table 2).43,44 CT has limited value in differentiating among the various WHO histological subtypes and in detecting residual or recurrent disease after treatment.45e50 Thymoma represents 20% of all mediastinal tumours in adults and is commonly located in the upper anterior mediastinum, although uncommon locations have been reported from the submandibular region to the cardiophrenic angle.11,41 It consists of an encapsulated noninvasive type and invasive type (15e40%) that has spread beyond the capsule. Although it may be difficult to distinguish invasive from encapsulated thymoma, CT can aid in differentiating MasaokaeKoga stage IeII from stage IIIeIV, as large tumour size, infiltration of the fat surrounding the tumour, and lobulate contours are significantly associated with advanced disease (stage IIIeIV) (Fig 5a).45 This distinction is essential to plan the proper treatment, because patients with advanced disease receive neoadjuvant chemotherapy before surgery.51 At CT, stage IeII thymomas manifest as round or oval and sharply demarcated masses completely or partially enclosed by a fibrous capsule and outlined by adjacent mediastinal fat, with homogeneous soft-tissue attenuation, smooth margins, no lobulations, and mild-to-moderate contrast enhancement (Fig 4). Conversely, stage IIIeIV thymomas may present lobulate and/or irregular margins, calcifications, focal low attenuation areas (that reflect haemorrhage, necrosis, or cystic change), heterogeneous enhancement, local tumour invasion through obliteration of the adjacent fat planes with encasement of mediastinal structures, and pleural or pericardial seeding (Fig 5).45 At CT, pleural seeding may appear as discrete soft-tissue nodules or as circumferential diffuse pleural thickening (Fig 6). Lymphadenopathies and haematogenous metastases are rare, but have been described in approximately 5% of patients.11 Thymic carcinomas are rare epithelial neoplasms, accounting for about 20% of TETs that exhibit histological features of malignancy. They are more aggressive tumours than invasive thymomas and typically present with local and/or metastatic spread (lung, liver, lymph nodes, and bone) in 50e65% of cases at presentation.23,24,28 At CT, they usually appear as large masses with irregular or lobular margins, areas of necrosis and calcification, heterogeneous enhancement, and lack a well-defined capsule.20,23,51 Although it may be difficult to distinguish thymic carcinomas from advanced thymomas due to considerable overlap of imaging findings, thymic carcinomas are more commonly associated with vessel invasion, mediastinal
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Figure 5 CT image of a 62-year-old man with MG and advanced thymoma (MasaokaeKoga stage IVa, WHO type B2). (a) Unenhanced and enhanced chest CT image obtained at the level of the arch of the azygos vein (mediastinal window) demonstrate an oval right anterior mediastinal mass (thin arrows) with irregular contours that suggest invasion into the surrounding mediastinal fatty tissue, and a slight heterogeneous enhancement. Note the loss of the fat plane between the lesion and the neighbouring structures (black asterisks) and the complete encasement of the superior vena cava consistent with vascular invasion (thick arrow) with an irregular border against the contrast mediumfilled azygos vein. (b) Contrast-enhanced chest CT image (mediastinal window) shows an enhancing right pleural-based soft-tissue nodule ipsilateral to the anterior mediastinal mass along the cardiophrenic border, closely attached to the pericardium (thin arrow), and two nodular thickenings of the left side of pericardium (thick arrows) that represent pleural and pericardial implants, respectively. Note that the pericardial fat plane is maintained nearby the pleural implant (black asterisks), whereas it is not appreciable in the site of pericardial nodules (L ¼ liver).
lymphadenopathies, pleural/pericardial effusion, and extrathoracic metastases, but less commonly associated with pleural/pericardial implants (Figs. 5e7).20,26 CT is routinely employed for the imaging follow-up of TETs after surgical resection (for exclusion of residual disease, local recurrence, pleural/pericardial implants, or distant metastases), and in cases of non-resectable disease to assess response to chemotherapy and radiation therapy.20,21 In 81% of cases, recurrence occurs in the thorax (pleura, pericardium, lung, and mediastinum), whereas it is extra-thoracic (liver, bone) in the remaining cases.49 PET-CT is advantageous over CT in postoperative and follow-up
assessment, especially in patients with higher stages and/ or incompletely resected thymoma in which recurrence is more frequent, because diseased tissue may be subtle at CT.20,24 When local recurrence and/or pleural seeding are detected, recurrence and pleural implants should be surgically removed when complete resection is feasible.42 If complete resection is achieved at recurrence, the survival rate is similar to that of patients without tumour recurrence after initial resection (5 year survival rates of 65e80%), although the mean time to recurrence is longer in patients with MasaokaeKoga stage I thymoma compared to stage IIeIV thymoma (10 years versus 3 years).50
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Table 1 World Health Organization (WHO) histological classification of thymic epithelial tumours (2004).a Type
Definition
A
Spindle cells: bland spindle/oval epithelial tumour cells with few or no lymphocytes Mixed spindle cells and lymphocytes: mixture of a lymphocyte-poor type A thymoma component and a more lymphocyte-rich type B-like component Lymphocytes > epithelial cells, predominantly cortical: areas resembling cortex of the normal thymus with epithelial cells scattered in a prominent population of immature lymphocytes and areas of medullary differentiation with or without Hassall’s corpuscles, similar to the normal thymic medulla. Some epithelial tumour cells present large nuclei of pale chromatin and small nucleoli Mixed lymphocytes and epithelial cells, cortical: large, polygonal tumour cells arranged in a loose network with large vascular nuclei and prominent large nucleoli, closely resembling the predominant epithelial cells of the normal thymic cortex. A background population of immature T-cells is always detectable and lymphocytes are less abundant than in type B1 Predominance of epithelial cells: prominent population of medium-sized round or polygonal epithelial cells with slight nuclear atypia and some prominent nucleoli mixed with a minor component of lymphocytes
AB
B1
B2
B3
Type A, AB, B1: low-risk thymomas; type B2, B3: high-risk thymomas. Thymic carcinoma: type C in 1999 WHO classification. a € ller-Hermelink et al.43 Modified from Mu
Figure 6 Different appearances of pleural implants in patients with MG and thymoma. Contrast-enhanced CT obtained at the level of the diaphragm detects nodular (a) and diffuse band-like (b) thickening of the right pleura (arrows).
Magnetic resonance imaging Currently, MRI is not routinely employed in the assessment of patients with MG, although it can provide more specific characterization compared to CT, especially in differentiating TLH from thymoma. Conversely, in most centres, MRI is generally reserved for further evaluation of equivocal CT findings of local invasion because of its better contrast resolution.20,52,53 Furthermore, MRI may be particularly useful for those cases with suspected vascular invasion in which iodinated contrast medium cannot be administered. Chemical-shift MRI is helpful in differentiating TLH from thymic neoplasms, especially in equivocal cases at CT. It is able to detect microscopic fatty infiltration within the normal/hyperplastic thymus, which would be indistinct at CT, by showing homogeneous signal decrease on opposedphase images relative to in-phase images, whereas signal loss is absent in thymoma that does not include fat (Figs 8 and 9a).54e58
Diffusion-weighted (DW)-MRI is another useful tool for characterizing thymic abnormalities in MG. It reflects tumour cell density and cellular architecture.59e61 The intra- and extracellular molecular diffusion of water detected by DW-MRI that is sensitive to thermally driven molecular water motion, can be measured as signal loss and expressed with the apparent diffusion coefficient (ADC). The ADC depends largely on the presence of barriers to diffusion within the water microenvironment, namely cell membranes and macromolecules, that alter the diffusion characteristics of the tissue.59e61 On this basis, DW-MRI has been used in different organs to differentiate benign from malignant lesions. Benign lesions (as TLH) usually present high ADC values and unrestricted diffusion, whereas
Table 2 MasaokaeKoga staging system for thymoma.a Stage
Definition
I
Macroscopically completely encapsulated tumour, with no microscopically detectable capsular invasion Macroscopic invasion into surrounding mediastinal fatty tissue or mediastinal pleura Microscopic invasion into the capsule Macroscopic invasion into neighbouring organs, such as pericardium, great vessels, and lung Pleural or pericardial dissemination through direct extension or drop metastasis Lymphogenous or haematogenous metastases
IIa IIb III IVa IVb
Stage I: non-invasive thymoma; stages IIeIV: invasive thymoma. a Modified from Masaoka et al.44
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Figure 7 CT of a 55-year-old man with MG and thymic carcinoma, who presented with chest pain. Unenhanced (left image) and contrastenhanced (right image) chest-CT (mediastinal window) obtained at the level of the aortic arch demonstrate a slightly heterogeneous softtissue mass (thin arrow) with a right lobulate border (thick arrow) that invades the superior vena cava (asterisk). Note the loss of the fat plane between the mass and the mediastinal great vessels, the left pleural effusion (arrowhead), and a mildly enlarged ipsilateral mediastinal lymph node adjacent the arch of the azygos vein (dotted arrow).
Figure 8 Chemical-shift MRI image of a 47-year old man with MG and TLH surgically removed (same patient as Fig 3f). The round-shaped softtissue mass of the anterior mediastinum that mimics a small thymoma presents a remarkable homogeneous decrease in signal intensity on transverse opposed-phase dual-echo T1-weighted MRI image compared to in-phase image (arrows), consistent with the presence of fatty component within the tissue that suggests the diagnosis of focal TLH.
malignant lesions (as TETs) have low ADC values and restricted diffusion (Figs 9b,10bec).62e65
Normal thymus and thymic lymphoid hyperplasia The MRI signal characteristics of the normal thymus change over time reflecting the gradual fatty replacement. On T1- and T2-weighted sequences, the normal thymus in infants and young children shows homogeneous and low signal intensity on both sequences, similar to that of muscle. In older children and adolescents, the thymus typically
reveals homogeneous and increased signal intensity, intermediate between muscle and fat. Subsequently, the signal intensity of the gland gradually increases with age due to the progressive fatty infiltration, becoming similar to that of fat on T2-weighted images.41,52 When the thymus has almost completely replaced by fat, reticulonodular strands of thymic tissue and occasionally small rounded islands of residual thymus can be observed on fat-suppressed T2weighted images.52 The appearance of TLH is similar to that of the normal thymus on T1- and T2-weighted sequences.41,66 In TLH, as in
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Figure 9 MRI of the same patient as Fig 4. (a) Transverse chemical-shift dual-echo T1-weighted MRI images demonstrate no change in signal intensity of the mass (arrows) on in-phase image relative to opposed-phase image, consistent with the absence of fatty component that suggests the diagnosis of small thymoma. (b) DW-MRI was obtained at different b-values of 0, 150, 500, and 800 s/mm2. The transverse image obtained at a b-value of 0 s/mm2 that results in conventional anatomical T2-weighted images with no vessel signal attenuation, demonstrates a high signal intensity within the lesion (arrow). At higher b-values, where vessels signal attenuation is seen, the lesion presents a progressive slight attenuation of the signal intensity (arrows) that is not completely suppressed, even at the b800 gradient image. This appearance suggests a restricted diffusion within the tissue, with a low ADC value of 1.03 103 mm2/s that strengthens the hypothesis of small thymoma.
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the normal thymus, chemical-shift MRI shows a decrease in signal intensity on opposed-phase images in contrast to inphase images, although it can depict physiological fatty infiltration of the normal thymus in all subjects 16 years, but in none
