- Email: [email protected]
Thymus
6 Thymus
6
25
Thymus LISA C. ZUCKERWISE | LING LI | JOSHUA A. COPEL
Introduction
ULTRASOUND
The thymus is a lymphoepithelial organ with key adaptive immune functions during both intrauterine and extrauterine life.1,2 The thymus develops from the third pharyngeal pouch, which gives rise to endodermal-derived thymic cortical epithelium, and the third pharyngeal cleft, which is thought to give rise to ectodermalderived medullary thymic epithelium.3,4 The thymus enlarges in the ninth gestational week when lymphocytes and hematopoietic cells migrate from embryonal blood vessels to spaces between thymus epithelial cells. After the 12th gestational week, the thymus descends into the anterior mediastinum and becomes an encapsulated, lobulated organ with a cortex that is densely populated with lymphocytes and a medulla that appears more epithelial because of a relative paucity of lymphoid cells.5 The thymus continues to grow throughout fetal life.6
The fetal thymus is visualized on ultrasound (US) as a homogeneous quadrangular structure in the anterior superior mediastinum, ventral to the pericardium and great vessels of the heart, and between both lungs. It is well visualized in the three-vessel view or the three-vessel–trachea view, lying anterior to the vessels (pulmonary artery, aorta, and superior vena cava, with the trachea to the right of the vessels) (Figs. 6.2–6.5).8,9 It is most often identified between the sternum and great vessels of the heart in the axial view of the fetal chest. From the sagittal view, the thymus appears triangular or teardrop-shaped (Fig. 6.6). Compared with the lungs, it is similar in echogenicity or
Normal Anatomy GENERAL ANATOMIC DESCRIPTIONS
Thymus L-Lung
R-Lung
The thymus consists of two lateral lobes placed in close contact along the midline, situated partly in the thorax and partly in the neck, and extending from the fourth costal cartilage upward, approaching the lower border of the thyroid gland (Fig. 6.1). It is covered by the sternum and by the origins of the sternohyoid and sternothyroid muscles.7 Below, it rests on the pericardium, and is separated from the aortic arch and great vessels by a layer of fascia. In the neck, it lies on the anterior surface of the trachea, behind the sternohyoid and sternothyroid muscles.7
Heart
Fig. 6.1 Normal fetal thymus in a 26-week, 2-day gestation.
26
PART 2 Thorax R
R
Thymus
SP
SVC
SVC
Tr
Ao
Thymus
Ao
PA
PA
L
L Fig. 6.2 Ultrasound (US) image (three-vessel view) in a 20-week fetus showing the thymus as a quadrangular structure in front of the three vessels (aorta [Ao], pulmonary artery [PA], superior vena cava [SVC]). The thymus is slightly more echogenic than the lungs. L, Left; R, right.
R
Fig. 6.4 Ultrasound (US) image (three-vessel–trachea view) in an 18-week, 3-day fetus showing the thymus as a quadrangular structure in front of the three vessels (aorta [Ao], pulmonary artery [PA], superior vena cava [SVC], thymus [Th]). The thymus is slightly more echogenic than the lungs. L, Left; R, right; SP, spine; Tr, trachea.
Thymus
L
PA
Lung Ao
Thymus
SVC
SVC Ao
SP
PA
R Lung
L
Fig. 6.5 Ultrasound (US) image (three-vessel view) in a 24-week, 6-day fetus showing the thymus as a quadrangular structure in front of the three vessels (aorta [Ao], pulmonary artery [PA], superior vena cava [SVC]). The thymus is less echogenic than the lungs. L, Left; R, right; SP, spine.
Fig. 6.3 Ultrasound (US) image (three-vessel view) in a 28-week fetus showing the thymus as a quadrangular structure in front of the three vessels (aorta [Ao], pulmonary artery [PA], superior vena cava [SVC]). The thymus is less echogenic than the lungs. L, Left; R, right.
slightly more echogenic in the early second trimester, between 17 weeks’ and 22 weeks’ gestation (see Figs. 6.2 and 6.4), and less echogenic in later pregnancy (see Figs. 6.3 and 6.5).10 With the development and application of three-dimensional (3D) US and four-dimensional (4D) US, the entire fetal thymus can be reconstructed and measured using a 3D model derived from multiple two-dimensional (2D) planes, which conquers the limitation of single-plane information from 2D US. Using off-line virtual organ computer-aided analysis (VOCAL) software, the 3D morphology of the fetal thymus can be evaluated from any orientation (Figs. 6.7–6.9).11 There are several studies of ultrasonic measurement data for normal fetal thymic size in the English literature: anteriorposterior thickness by Felker et al.,9 perimeter by Zalel et al.,8
ST
Heart
Thymus
Fig. 6.6 Ultrasound (US) image (sagittal view) in a 21-week, 6-day fetus showing the thymus. ST, Stomach.
6 Thymus
27
Volume B Area A
Fig. 6.7 Virtual organ computer-aided analysis (VOCAL) calculation of fetal thymus volume in 22-week gestation (QLAB software). Four images are shown: Right three images are three orthogonal planes; left image is reconstruction thymus volume. Upper right shows thymus volume = 2.05 mL.
Differential Considerations
Fig. 6.8 Virtual organ computer-aided analysis (VOCAL) calculation of fetal thymus volume in 26-week gestation (4D view software). Four images are shown: Left two images and upper right are three orthogonal planes; lower right image is reconstruction thymus volume. Lower right shows thymus volume = 3.17 mL.
transverse diameter by Jeppesen et al.6 and Cho et al.,10 and 3D volume by Li et al.11 The thy-box technique, which uses vascular boundaries with Doppler (internal mammary arteries laterally, three vessels posteriorly, and sternum anteriorly) to identify the thymus and produce measurements, was described by Paladini in 2011 and has demonstrated favorable feasibility and reproducibility for use into the early third trimester.12,13 DETAILED DESCRIPTION OF SPECIFIC AREAS Normal Variants The two lobes of the thymus generally differ in size. They are occasionally united to form a single mass and sometimes separated by an intermediate lobe.7
Thymic hypoplasia is a condition in which the thymus is underdeveloped or involuted. Thymic aplasia is congenital absence of the thymus. Thymic hypoplasia and thymic aplasia have been reported as an associated finding in various diseases, such as 22q11.2 deletion (DiGeorge syndrome),14 Ellis-van Creveld syndrome,15 severe combined immunodeficiency,16 human immunodeficiency virus (HIV) infection,17 fetal growth restriction (FGR), 18 acute illness, 19 exposure to ethanol, 20 and chorioamnionitis.21 Chaoui et al.22 and Barrea et al.23 investigated the fetal thymus and found that absent or hypoplastic thymus on US is a marker for deletion 22q11.2 in fetal cardiac defects, with a sensitivity of at least 90% and specificity of 98.5% in a group of fetuses with prenatally diagnosed cardiac defects. A larger study of 74 fetuses with confirmed 22q11.2 deletion by fluorescence in situ hybridization (FISH) analysis found that 86% of these fetuses had a thymic abnormality at autopsy, with 53.3% having complete thymic agenesis and 46.7% demonstrating thymic hypoplasia.24 Taken together, these studies suggest that thymic evaluation by ultrasound can be useful to identify patients at risk for 22q11.2 deletion in the presence of small or absent thymus. Cromi et al.25 assessed fetal thymus size in growth-restricted fetuses and found that the vast majority of growth-restricted fetuses (58/60, 97%) demonstrated thymic size smaller than fifth percentile, compared with only 7/60 (11%) controls having small thymus. The authors postulated that a small fetal thymus is a marker of the fetal immune-endocrine response to malnutrition. A clinically relevant study by Ekin et al.26 assessed the implication of small thymus in cases of growth-restricted fetuses and confirmed significantly smaller thymuses than in normally grown controls. Importantly, they also found that smaller thymus size within the growth-restricted fetuses was associated with significantly higher risk of perinatal morbidity including preterm delivery, respiratory distress syndrome, early neonatal sepsis, and longer intensive care unit stays.
28
PART 2 Thorax
A
B
D
E
C
F
Fig. 6.9 Virtual organ computer-aided analysis (VOCAL) calculation of fetal thymus volume in 22-week gestation (different views). (A) Transverse view of fetal thymus (QLAB from Philips, Bothell, Washington). (B) Transverse view of fetal thymus (4D view from GE , Milwaukee, Wisconsin). (C) Sagittal view of fetal thymus (QLAB from Philips). (D) Sagittal view of fetal thymus (4D view from GE). (E) Coronal view of fetal thymus (QLAB from Philips). (F) Coronal view of fetal thymus (4D view from GE).
Yinon et al.,27 Di Naro et al.,28 and El-Haieg et al.29 demonstrated that fetal thymic involution (as demonstrated by size smaller than fifth percentile) is a predictor of the fetal inflammatory response syndrome both in women with preterm labor and intact membranes and in women with preterm premature rupture of membranes. In fact, Cetin et al.30 found reduced fetal thymus diameter below the fifth percentile to be a promising prenatal marker for predicting early neonatal sepsis in patients admitted for preterm premature rupture of membranes, with a sensitivity of 100% and specificity of 73% in their series of 40 consecutive cases.
of membranes, a small thymus may indicate thymic involution, representing a worse fetal prognosis.26–30
Pertinent Imaging Considerations Assessment of the fetal thymus may be indicated when DiGeorge syndrome (22q11.2 deletion), Ellis-van Creveld syndrome, severe combined immunodeficiency, HIV infection, FGR, acute illness, exposure to ethanol, or chorioamnionitis is suspected. If the fetal thymus is significantly decreased in size or absent on the anatomic survey US scan, careful assessment of fetal anatomy, including cardiac anatomy, is necessary, as is consideration of genetic counseling and testing. When fetal congenital heart disease is suspected, especially conotruncal anomalies, assessment of the fetal thymus may be helpful in stratifying risk for associated fetal conditions and counseling on diagnostic genetic testing.11 In cases of FGR, preterm labor or preterm premature rupture
SUGGESTED READING
KEY POINTS • On 2D US, the fetal thymus is visualized as a homogeneous structure in the anterior superior mediastinum. • The thymus grows throughout fetal life. • Thymic hypoplasia and thymic aplasia are associated findings in various diseases.
Hata T, Deter RL. A review of fetal organ measurements obtained with ultrasound: normal growth. J Clin Ultrasound. 1992;20:155-174. Munoz-Chapuli M, Gamez F, Bravo C, et al. The thy-box for sonographic assessment of the fetal thymus: nomogram and review of the literature. J Ultrasound Med. 2015;34:853-858. Haynes BF, Hale LP. The human thymus: a chimeric organ comprised of central and peripheral lymphoid components. Immunol Res. 1998;18:175-192. Mastrolia SA, Erez O, Loverro G, et al. Ultrasonographic approach to diagnosis of Fetal Inflammatory Response Syndrome: a tool for at risk fetuses? Am J Obstet Gynecol. 2016;215:9-20.
All references are available online at www.expertconsult.com.
REFERENCES 1. Schwartz R. Acquisition of immunologic self-tolerance. Cell. 1989;57:1073-1081. 2. Haynes B, Hale L. The human thymus: a chimeric organ comprised of central and peripheral lymphoid components. Immunol Res. 1998;18:175-192. 3. Haynes B, Denning S, Le P, et al. Human intrathymic T cell differentiation. Semin Immunol. 1990;2:67-77. 4. Haynes B. Human thymic epithelium and T cell development: current issues and future directions. Thymus. 1990;16:143-157. 5. Von Gaudecker B. The development of the human thymus microenvironment. Curr Top Pathol. 1986;75:1-42. 6. Jeppesen DL, Hasselbalch H, Nielsen SD, et al. Thymic size in preterm neonates: a sonographic study. Acta Paediatr. 2003;92:817-822. 7. Gray H. The thymus. In: Anatomy of the Human Body. Philadelphia: Lea & Febiger; 1985. 8. Zalel Y, Gamzu R, Mashiach S, et al. The development of the fetal thymus: an in utero sonographic evaluation. Prenat Diagn. 2002;22:114-117. 9. Felker RE, Cartier MS, Emerson DS, et al. Ultrasound of the fetal thymus. J Ultrasound Med. 1989;8:669-673. 10. Cho JY, Min JY, Lee YH, et al. Diameter of the normal fetal thymus on ultrasound. Ultrasound Obstet Gynecol. 2007;29:634-638. 11. Li L, Bahtiyar M, Buhimschi C, et al. Assessment of the fetal thymus by 2D and 3D ultrasound during normal human gestation and in fetuses with congenital heart defects. Ultrasound Obstet Gynecol. 2011;37:404-409. 12. Paladini D. How to identify the thymus in the fetus: the thy-box. Ultrasound Obstet Gynecol. 2011;37:488-492. 13. Munoz-Chapuli M, Gamez F, Bravo C, et al. The thy-box for sonographic assessment of the fetal thymus: nomogram and review of the literature. J Ultrasound Med. 2015;34:853-858. 14. Dodson WE, Alexander D, Al-Aish M, et al. The DiGeorge syndrome. Lancet. 1969;1:574-575. 15. Ichijima K, Yamabe H, Kobashi Y, et al. An unusual case of metaphyseal chondrodysplasia with an abnormal perilacunar matrix associated with agranulocytosis and hypoplasia of the thymus. Virchows Arch A Pathol Anat Histol. 1981;391:275-289. 16. Martin JP, Aguilar FT. Thymic hypoplasia with severe combined immunodeficiency. Ann Allergy. 1977;39:196-200.
6 Thymus 28.e1 17. Zalel Y, Gamzu R, Mashiach S, et al. The development of the fetal thymus: an in utero sonographic evaluation. Prenat Diagn. 2002;22:114-117. 18. Hartge R, Jenkins DM, Kohler HG. Low thymic weight in small-for-dates babies. Eur J Obstet Gynecol Reprod Biol. 1978;8:153-155. 19. Van-Baarlen SJ, Achuurman HJ, Huber J. Acute thymic involution in infancy and childhood: a reliable marker for duration of acute illness. Hum Pathol. 1988;19:1155-1160. 20. Ewald SJ, Frost WW. Effect of prenatal exposure to ethanol on development of the thymus. Thymus. 1987;9:211-215. 21. Toti P, De Felice C, Stumpo M, et al. Acute thymic involution in fetuses and neonates with chorioamnionitis. Hum Pathol. 2000;31:1121-1128. 22. Chaoui R, Kalache KD, Heling KS, et al. Absent or hypoplastic thymus on ultrasound: a marker for deletion 22q11.2 in fetal cardiac defects. Ultrasound Obstet Gynecol. 2002;20:546-552. 23. Barrea C, Yoo SJ, Chitayat D, et al. Assessment of the thymus at echocardiography in fetuses at risk for 22q11.2 deletion. Prenat Diagn. 2003;23:9-15. 24. Noel A, Pelluard F, Delezoid A, et al. Fetal phenotype associated with 22q11 deletion. Am J Med Genet A. 2014;164:2724-2731. 25. Cromi A, Ghezzi F, Raffaelli R, et al. Ultrasonographic measurement of thymus size in IUGR fetuses: a marker of the fetal immunoendocrine response to malnutrition. Ultrasound Obstet Gynecol. 2009;33:421-426. 26. Ekin A, Gezer C, Taner CE, et al. Prognostic value of fetal thymus size in intrauterine growth restriction. J Ultrasound Med. 2016;35:511-517. 27. Yinon Y, Zalel Y, Weisz B, et al. Fetal thymus size as a predictor of chorioamnionitis in women with preterm premature rupture of membranes. Ultrasound Obstet Gynecol. 2007;29:639-643. 28. Di Naro E, Cromi A, Ghezzi F, et al. Fetal thymic involution: a sonographic marker of the fetal inflammatory response syndrome. Am J Obstet Gynecol. 2006;194:153-159. 29. El-Haieg DO, Zidan AA, El-Nemr MM. The relationship between sonographic fetal thymus size and the components of the systemic fetal inflammatory response syndrome in women with preterm prelabour rupture of membranes. Br J Obstet Gynaecol. 2008;115:836-841. 30. Cetin O, Dokurel Cetin I, Uludag S, et al. Serial ultrasonographic examination of the fetal thymus in the prediction of early neonatal sepsis in preterm premature rupture of membranes. Gy necol O bstet Invest. 2014;78:201-207.
6
25
Thymus LISA C. ZUCKERWISE | LING LI | JOSHUA A. COPEL
Introduction
ULTRASOUND
The thymus is a lymphoepithelial organ with key adaptive immune functions during both intrauterine and extrauterine life.1,2 The thymus develops from the third pharyngeal pouch, which gives rise to endodermal-derived thymic cortical epithelium, and the third pharyngeal cleft, which is thought to give rise to ectodermalderived medullary thymic epithelium.3,4 The thymus enlarges in the ninth gestational week when lymphocytes and hematopoietic cells migrate from embryonal blood vessels to spaces between thymus epithelial cells. After the 12th gestational week, the thymus descends into the anterior mediastinum and becomes an encapsulated, lobulated organ with a cortex that is densely populated with lymphocytes and a medulla that appears more epithelial because of a relative paucity of lymphoid cells.5 The thymus continues to grow throughout fetal life.6
The fetal thymus is visualized on ultrasound (US) as a homogeneous quadrangular structure in the anterior superior mediastinum, ventral to the pericardium and great vessels of the heart, and between both lungs. It is well visualized in the three-vessel view or the three-vessel–trachea view, lying anterior to the vessels (pulmonary artery, aorta, and superior vena cava, with the trachea to the right of the vessels) (Figs. 6.2–6.5).8,9 It is most often identified between the sternum and great vessels of the heart in the axial view of the fetal chest. From the sagittal view, the thymus appears triangular or teardrop-shaped (Fig. 6.6). Compared with the lungs, it is similar in echogenicity or
Normal Anatomy GENERAL ANATOMIC DESCRIPTIONS
Thymus L-Lung
R-Lung
The thymus consists of two lateral lobes placed in close contact along the midline, situated partly in the thorax and partly in the neck, and extending from the fourth costal cartilage upward, approaching the lower border of the thyroid gland (Fig. 6.1). It is covered by the sternum and by the origins of the sternohyoid and sternothyroid muscles.7 Below, it rests on the pericardium, and is separated from the aortic arch and great vessels by a layer of fascia. In the neck, it lies on the anterior surface of the trachea, behind the sternohyoid and sternothyroid muscles.7
Heart
Fig. 6.1 Normal fetal thymus in a 26-week, 2-day gestation.
26
PART 2 Thorax R
R
Thymus
SP
SVC
SVC
Tr
Ao
Thymus
Ao
PA
PA
L
L Fig. 6.2 Ultrasound (US) image (three-vessel view) in a 20-week fetus showing the thymus as a quadrangular structure in front of the three vessels (aorta [Ao], pulmonary artery [PA], superior vena cava [SVC]). The thymus is slightly more echogenic than the lungs. L, Left; R, right.
R
Fig. 6.4 Ultrasound (US) image (three-vessel–trachea view) in an 18-week, 3-day fetus showing the thymus as a quadrangular structure in front of the three vessels (aorta [Ao], pulmonary artery [PA], superior vena cava [SVC], thymus [Th]). The thymus is slightly more echogenic than the lungs. L, Left; R, right; SP, spine; Tr, trachea.
Thymus
L
PA
Lung Ao
Thymus
SVC
SVC Ao
SP
PA
R Lung
L
Fig. 6.5 Ultrasound (US) image (three-vessel view) in a 24-week, 6-day fetus showing the thymus as a quadrangular structure in front of the three vessels (aorta [Ao], pulmonary artery [PA], superior vena cava [SVC]). The thymus is less echogenic than the lungs. L, Left; R, right; SP, spine.
Fig. 6.3 Ultrasound (US) image (three-vessel view) in a 28-week fetus showing the thymus as a quadrangular structure in front of the three vessels (aorta [Ao], pulmonary artery [PA], superior vena cava [SVC]). The thymus is less echogenic than the lungs. L, Left; R, right.
slightly more echogenic in the early second trimester, between 17 weeks’ and 22 weeks’ gestation (see Figs. 6.2 and 6.4), and less echogenic in later pregnancy (see Figs. 6.3 and 6.5).10 With the development and application of three-dimensional (3D) US and four-dimensional (4D) US, the entire fetal thymus can be reconstructed and measured using a 3D model derived from multiple two-dimensional (2D) planes, which conquers the limitation of single-plane information from 2D US. Using off-line virtual organ computer-aided analysis (VOCAL) software, the 3D morphology of the fetal thymus can be evaluated from any orientation (Figs. 6.7–6.9).11 There are several studies of ultrasonic measurement data for normal fetal thymic size in the English literature: anteriorposterior thickness by Felker et al.,9 perimeter by Zalel et al.,8
ST
Heart
Thymus
Fig. 6.6 Ultrasound (US) image (sagittal view) in a 21-week, 6-day fetus showing the thymus. ST, Stomach.
6 Thymus
27
Volume B Area A
Fig. 6.7 Virtual organ computer-aided analysis (VOCAL) calculation of fetal thymus volume in 22-week gestation (QLAB software). Four images are shown: Right three images are three orthogonal planes; left image is reconstruction thymus volume. Upper right shows thymus volume = 2.05 mL.
Differential Considerations
Fig. 6.8 Virtual organ computer-aided analysis (VOCAL) calculation of fetal thymus volume in 26-week gestation (4D view software). Four images are shown: Left two images and upper right are three orthogonal planes; lower right image is reconstruction thymus volume. Lower right shows thymus volume = 3.17 mL.
transverse diameter by Jeppesen et al.6 and Cho et al.,10 and 3D volume by Li et al.11 The thy-box technique, which uses vascular boundaries with Doppler (internal mammary arteries laterally, three vessels posteriorly, and sternum anteriorly) to identify the thymus and produce measurements, was described by Paladini in 2011 and has demonstrated favorable feasibility and reproducibility for use into the early third trimester.12,13 DETAILED DESCRIPTION OF SPECIFIC AREAS Normal Variants The two lobes of the thymus generally differ in size. They are occasionally united to form a single mass and sometimes separated by an intermediate lobe.7
Thymic hypoplasia is a condition in which the thymus is underdeveloped or involuted. Thymic aplasia is congenital absence of the thymus. Thymic hypoplasia and thymic aplasia have been reported as an associated finding in various diseases, such as 22q11.2 deletion (DiGeorge syndrome),14 Ellis-van Creveld syndrome,15 severe combined immunodeficiency,16 human immunodeficiency virus (HIV) infection,17 fetal growth restriction (FGR), 18 acute illness, 19 exposure to ethanol, 20 and chorioamnionitis.21 Chaoui et al.22 and Barrea et al.23 investigated the fetal thymus and found that absent or hypoplastic thymus on US is a marker for deletion 22q11.2 in fetal cardiac defects, with a sensitivity of at least 90% and specificity of 98.5% in a group of fetuses with prenatally diagnosed cardiac defects. A larger study of 74 fetuses with confirmed 22q11.2 deletion by fluorescence in situ hybridization (FISH) analysis found that 86% of these fetuses had a thymic abnormality at autopsy, with 53.3% having complete thymic agenesis and 46.7% demonstrating thymic hypoplasia.24 Taken together, these studies suggest that thymic evaluation by ultrasound can be useful to identify patients at risk for 22q11.2 deletion in the presence of small or absent thymus. Cromi et al.25 assessed fetal thymus size in growth-restricted fetuses and found that the vast majority of growth-restricted fetuses (58/60, 97%) demonstrated thymic size smaller than fifth percentile, compared with only 7/60 (11%) controls having small thymus. The authors postulated that a small fetal thymus is a marker of the fetal immune-endocrine response to malnutrition. A clinically relevant study by Ekin et al.26 assessed the implication of small thymus in cases of growth-restricted fetuses and confirmed significantly smaller thymuses than in normally grown controls. Importantly, they also found that smaller thymus size within the growth-restricted fetuses was associated with significantly higher risk of perinatal morbidity including preterm delivery, respiratory distress syndrome, early neonatal sepsis, and longer intensive care unit stays.
28
PART 2 Thorax
A
B
D
E
C
F
Fig. 6.9 Virtual organ computer-aided analysis (VOCAL) calculation of fetal thymus volume in 22-week gestation (different views). (A) Transverse view of fetal thymus (QLAB from Philips, Bothell, Washington). (B) Transverse view of fetal thymus (4D view from GE , Milwaukee, Wisconsin). (C) Sagittal view of fetal thymus (QLAB from Philips). (D) Sagittal view of fetal thymus (4D view from GE). (E) Coronal view of fetal thymus (QLAB from Philips). (F) Coronal view of fetal thymus (4D view from GE).
Yinon et al.,27 Di Naro et al.,28 and El-Haieg et al.29 demonstrated that fetal thymic involution (as demonstrated by size smaller than fifth percentile) is a predictor of the fetal inflammatory response syndrome both in women with preterm labor and intact membranes and in women with preterm premature rupture of membranes. In fact, Cetin et al.30 found reduced fetal thymus diameter below the fifth percentile to be a promising prenatal marker for predicting early neonatal sepsis in patients admitted for preterm premature rupture of membranes, with a sensitivity of 100% and specificity of 73% in their series of 40 consecutive cases.
of membranes, a small thymus may indicate thymic involution, representing a worse fetal prognosis.26–30
Pertinent Imaging Considerations Assessment of the fetal thymus may be indicated when DiGeorge syndrome (22q11.2 deletion), Ellis-van Creveld syndrome, severe combined immunodeficiency, HIV infection, FGR, acute illness, exposure to ethanol, or chorioamnionitis is suspected. If the fetal thymus is significantly decreased in size or absent on the anatomic survey US scan, careful assessment of fetal anatomy, including cardiac anatomy, is necessary, as is consideration of genetic counseling and testing. When fetal congenital heart disease is suspected, especially conotruncal anomalies, assessment of the fetal thymus may be helpful in stratifying risk for associated fetal conditions and counseling on diagnostic genetic testing.11 In cases of FGR, preterm labor or preterm premature rupture
SUGGESTED READING
KEY POINTS • On 2D US, the fetal thymus is visualized as a homogeneous structure in the anterior superior mediastinum. • The thymus grows throughout fetal life. • Thymic hypoplasia and thymic aplasia are associated findings in various diseases.
Hata T, Deter RL. A review of fetal organ measurements obtained with ultrasound: normal growth. J Clin Ultrasound. 1992;20:155-174. Munoz-Chapuli M, Gamez F, Bravo C, et al. The thy-box for sonographic assessment of the fetal thymus: nomogram and review of the literature. J Ultrasound Med. 2015;34:853-858. Haynes BF, Hale LP. The human thymus: a chimeric organ comprised of central and peripheral lymphoid components. Immunol Res. 1998;18:175-192. Mastrolia SA, Erez O, Loverro G, et al. Ultrasonographic approach to diagnosis of Fetal Inflammatory Response Syndrome: a tool for at risk fetuses? Am J Obstet Gynecol. 2016;215:9-20.
All references are available online at www.expertconsult.com.
REFERENCES 1. Schwartz R. Acquisition of immunologic self-tolerance. Cell. 1989;57:1073-1081. 2. Haynes B, Hale L. The human thymus: a chimeric organ comprised of central and peripheral lymphoid components. Immunol Res. 1998;18:175-192. 3. Haynes B, Denning S, Le P, et al. Human intrathymic T cell differentiation. Semin Immunol. 1990;2:67-77. 4. Haynes B. Human thymic epithelium and T cell development: current issues and future directions. Thymus. 1990;16:143-157. 5. Von Gaudecker B. The development of the human thymus microenvironment. Curr Top Pathol. 1986;75:1-42. 6. Jeppesen DL, Hasselbalch H, Nielsen SD, et al. Thymic size in preterm neonates: a sonographic study. Acta Paediatr. 2003;92:817-822. 7. Gray H. The thymus. In: Anatomy of the Human Body. Philadelphia: Lea & Febiger; 1985. 8. Zalel Y, Gamzu R, Mashiach S, et al. The development of the fetal thymus: an in utero sonographic evaluation. Prenat Diagn. 2002;22:114-117. 9. Felker RE, Cartier MS, Emerson DS, et al. Ultrasound of the fetal thymus. J Ultrasound Med. 1989;8:669-673. 10. Cho JY, Min JY, Lee YH, et al. Diameter of the normal fetal thymus on ultrasound. Ultrasound Obstet Gynecol. 2007;29:634-638. 11. Li L, Bahtiyar M, Buhimschi C, et al. Assessment of the fetal thymus by 2D and 3D ultrasound during normal human gestation and in fetuses with congenital heart defects. Ultrasound Obstet Gynecol. 2011;37:404-409. 12. Paladini D. How to identify the thymus in the fetus: the thy-box. Ultrasound Obstet Gynecol. 2011;37:488-492. 13. Munoz-Chapuli M, Gamez F, Bravo C, et al. The thy-box for sonographic assessment of the fetal thymus: nomogram and review of the literature. J Ultrasound Med. 2015;34:853-858. 14. Dodson WE, Alexander D, Al-Aish M, et al. The DiGeorge syndrome. Lancet. 1969;1:574-575. 15. Ichijima K, Yamabe H, Kobashi Y, et al. An unusual case of metaphyseal chondrodysplasia with an abnormal perilacunar matrix associated with agranulocytosis and hypoplasia of the thymus. Virchows Arch A Pathol Anat Histol. 1981;391:275-289. 16. Martin JP, Aguilar FT. Thymic hypoplasia with severe combined immunodeficiency. Ann Allergy. 1977;39:196-200.
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