The adrenal cortex is of mesodermal origin, whereas the medulla forms from ectodermal elements. The primitive adrenal cortex arises from coelomic mesoderm around the fifth week of gestation. Additional cells migrate to join this initial aggregation at approximately 7 weeks. This early adrenal cortex separates from the peritoneal mesothelium by the end of the eighth week. Adrenocortical differentiation continues after birth, resulting in completed formation of the zona glomerulosa, zona fasciculi, and zona reticularis by about the age of 3 years.
The adrenal medulla forms from neural crest cells that migrate from the embryonic ectoderm to form the primitive sympathetic ganglia. Some of these differentiate into endocrine cells (chromaffin cells) and migrate to the medial aspect of the developing adrenal cortex at about the 10th week of gestation. There is prominent paraganglionic chromaffin tissue during fetal development. After birth, the majority of the extraadrenal chromaffin tissue atrophies, but small collections of these cells persist adjacent to the origins of the celiac and superior mesenteric arteries and in the organ of Zuckerkandl adjacent to the inferior mesenteric artery.
Early in fetal development, the adrenal gland is larger than the adjacent kidney. At the time of birth, the adrenal gland of most neonates is approximately one-third the size of the ipsilateral kidney. The cortical portions of the glands rapidly atrophy during the first few weeks of life to assume their mature morphology. In the normal neonate, the adrenal medulla is hyperechoic on sonography, and the cortex is relatively hypoechoic. The entire gland is hypoechoic after the first year of life.
Development of the adrenal glands is independent to that of the kidneys. Therefore, adrenal gland location is usually normal despite renal ectopia or aplasia. In this situation, the adrenal gland may assume an elongated, flattened, or elliptical shape.1,2 When elliptical, care must be exercised to avoid mistaking the normal adrenal gland for a hypoplastic kidney on diagnostic imaging studies. The abnormally shaped adrenal gland in an infant with renal aplasia or ectopia maintains a normal pattern of echogenicity, with a central echogenic stripe and a peripheral hypoechoic zone.
The medulla of the adrenal gland synthesizes and secretes the catecholamines epinephrine and norepinephrine. The surrounding cortex consists of 3 zones. The outer zone, the zona glomerulosa, secretes aldosterone, which regulates renal tubular sodium retention and potassium excretion. The inner 2 zones, the zona fasciculata and the zona reticularis, secrete cortisol as well as small amounts of androgenic steroids.
The hypothalamus and anterior pituitary gland control adrenal steroid secretion. Corticotropin-releasing hormone secreted by the hypothalamus stimulates the release of corticotropin (adrenocorticotropic hormone [ACTH]) in the anterior lobe of the pituitary gland. Circulating corticotropin evokes the release of cortisol and androgens from the adrenal cortex. Prolonged elevation of corticotropin causes enlargement of the adrenal gland.
Corticotropin plays a minor role in controlling aldosterone secretion. This adrenal steroid is predominantly regulated by the renin-angiotensin-aldosterone system. Stimuli such as diminished intrarenal blood pressure or increased sympathetic tone cause secretion of renin by the juxtaglomerular cells of the kidney. Within the plasma, renin cleaves angiotensinogen to form angiotensin I. Angiotensin-converting enzyme removes 2 amino acids from angiotensin I to form angiotensin II. Angiotensin II stimulates aldosterone secretion by the adrenal cortex and also directly causes peripheral blood vessel vasoconstriction. Both of these mechanisms serve to increase blood volume and blood pressure.
The adrenal medulla is part of the sympathetic nervous system. The major mechanism by which secretion of adrenal catecholamines occurs is in response to impulses carried into the medulla by preganglionic neurons of the sympathetic nervous system. To some extent, glucocorticoids synthesized in the adrenal cortex regulate the synthesis of adrenal catecholamines as well. Various stresses, such as exercise, heat, cold, and trauma, stimulate catecholamine release by the adrenal medulla.
Adrenal agenesis is a rare developmental abnormality. Unilateral adrenal agenesis is accompanied by compensatory enlargement of the contralateral gland. Bilateral adrenal gland agenesis is incompatible with life.
Adrenal hypoplasia congenita is distinct from acquired hypoadrenalism (Addison disease). Patients with true congenital hypoplasia exhibit no response to exogenous ACTH. Because the adrenal insufficiency is not related to a defect in steroidogenesis, there is no abnormal excretion of metabolites of androgens or progesterone in the urine. In many instances, congenital adrenal hypoplasia is familial. Some patients with congenital adrenal hypoplasia have a mutation of the nuclear receptor DAX1 (encoded by the gene NR0B1). Adrenal hypoplasia congenita is a component of the IMAGe syndrome (i.e., intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital abnormalities).3
The potential clinical manifestations of congenital adrenal hypoplasia are similar to those of acquired adrenal insufficiency, for example, increased pigmentation, abdominal pain, and weakness. Although a congenital lesion, the clinical presentation sometimes does not occur until several years of age. Imaging studies may show normal or small adrenal glands.4
Congenital fusion of the adrenal glands is termed horseshoe adrenal gland. This anomaly most often occurs in association with asplenia syndrome (horseshoe adrenal gland has not been reported with polysplenia syndrome). Other reported associations include neural tube defects and renal anomalies. The mechanism may involve deficiency of the layers of the coelomic epithelium that normally separate the embryonic adrenal glands. The event occurs at approximately the sixth week of gestation.5
Sonography of horseshoe adrenal shows the fused adrenal glands to form a band across the upper portion of the abdomen at the midline (Figure 56-1). The tissue maintains the characteristics of the normal adrenal gland, with a thin central echogenic stripe. In patients with asplenia, the isthmus of the horseshoe adrenal usually passes anterior to the aorta, whereas it passes posterior to the aorta in most other patients.6
Accessory adrenal tissue can be located nearly anywhere in the retroperitoneum, although most of these accessory glands are near the parent gland. These apparently represent fragments separated from the primary anlage during fetal development. Accessory adrenal rests are usually too small to be detected with imaging studies. The tissue may increase in size in response to exogenous administration of ACTH, as in patients following adrenalectomy.
A testicular adrenal rest is a rare form of adrenal ectopia that can cause a scrotal mass. This anomaly is due to trapping of adrenal tissue in the developing embryonic gonad. Microscopic rests are present within or adjacent to the testis in up to 15% of newborns.7 These cells can enlarge and produce a symptomatic intrascrotal mass when exposed to elevated ACTH. The most common stimulating condition is congenital adrenal hyperplasia. Other potential causes of ACTH elevation include Addison disease, Cushing syndrome, and adrenogenital syndrome. Glucocorticoid replacement therapy results in stabilization or regression of the lesion.
Imaging studies of testicular adrenal rests usually show multiple, bilateral, and eccentrically located nodules. The sonographic appearance is variable, ranging from multiple hypoechoic lesions to heterogeneous hyperechoic foci with shadowing. Testicular adrenal rests are hypointense on both T1- and T2-weighted MR images. Testicular vein sampling demonstrates elevated cortisol levels.8–14
Adrenal-renal heterotopia refers to an anomalous connection between the adrenal gland and the adjacent kidney, due to a capsular defect. Extension of renal tissue into the adrenal gland is sometimes present on histologic examination. There may be shared vasculature. Most often, imaging studies show the involved adrenal gland to have a normal configuration and to be in a normal location.
The retroperitoneal space is the zone between the dorsal layer of the parietal peritoneum and the muscles of the posterior wall of the abdominal cavity. It is bounded superiorly by the diaphragm and inferiorly by the peritoneal attachments within the pelvis. Structures located within the retroperitoneal space include the kidneys, adrenal glands, ureters, pancreas, portal vein, abdominal aorta, inferior vena cava, and a portion of the duodenum. The sympathetic trunk, celiac plexus, and peripheral nerves (including branches of the sacral plexus) are also retroperitoneal.
Most primary retroperitoneal neoplasms arise in the adrenal glands, kidneys, or pancreas. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma can arise within the adrenal medulla or from neural crest cells in other retroperitoneal locations, such as the sympathetic ganglia and organ of Zuckerkandl. The paraspinal portion of the retroperitoneum is a common site of neurofibromas in patients with neurofibromatosis type 1. Retroperitoneal lymph nodes are common sites of metastasis and are frequently involved in patients with lymphoma. Table 56-1 summarizes the differential diagnosis of an adrenal mass in an infant or child.15–19
Cushing syndrome refers to the clinical manifestations of excess circulating glucocorticoids, regardless of the cause. Clinical manifestations of Cushing syndrome include central obesity, osteoporosis, glucose intolerance, and diminished immune resistance. There are 2 types of intrinsic Cushing syndrome: ACTH-dependent and ACTH-independent. The ACTH-dependent form is most common. Most patients with this form have excess ACTH production by a basophil pituitary adenoma; this is termed Cushing disease. There are rare instances of ectopic ACTH secretion from a nonpituitary source. ACTH-independent Cushing syndrome is most often due to an adrenal adenoma, nodular adrenal hyperplasia, or an adrenocortical carcinoma.
In patients with ACTH-independent Cushing syndrome, imaging of the adrenal gland serves to detect and characterize the responsible lesion. As a rule, an adrenal mass in a patient with Cushing syndrome should be considered to be malignant when it is greater than 4 cm in diameter. A symptomatic adenoma is usually at least 2 cm in diameter. A unilateral cortisol-secreting adrenal adenoma causes suppression of ACTH secretion; therefore, normal ipsilateral and contralateral adrenal tissue is atrophic in these patients. Adrenal adenomas are sometimes multifocal.
Adrenal cortical hyperplasia in patients with Cushing syndrome is usually bilateral, and may be diffuse (most common) or nodular in character. Imaging studies show enlargement of the gland(s). On MR, the signal intensity of the hyperplastic adrenal gland is usually normal. Decrease in signal intensity on out-of-phase gradient-recalled echo chemical shift images may occur when there are adenomatous cortical nodules.20
Primary hyperaldosteronism (Conn syndrome) is characterized by hypertension, hypokalemia, and metabolic alkalosis. The most common cause is an aldosterone-producing adenoma. Bilateral adrenal hyperplasia accounts for most of the remaining cases; rarely, there is an underlying adrenocortical carcinoma. The most important role for diagnostic imaging in these patients is to differentiate an adenoma (surgical therapy) from bilateral hyperplasia (medical therapy).21
Patients with suspected primary hyperaldosteronism can be evaluated with CT or MR. An aldosterone-producing adenoma is usually relatively small; the typical range is between 1 and 4 cm. These lesions typically contain intracellular lipid. Adrenal hyperplasia is characterized by enlarged adrenal glands, which can have nodular or smooth contours. When the imaging findings are equivocal, transcatheter venous sampling is an option. The accuracy of venous sampling is increased when adrenocorticotropic hormone stimulation is carried out as part of the procedure.22
Adrenal insufficiency can be divided into primary, secondary, and tertiary forms (Table 56-2). Primary adrenal insufficiency, or Addison disease, is the most common. A frequent cause of Addison disease is primary idiopathic atrophy of the adrenal glands; this is apparently an autoimmune process. As described earlier in this chapter, congenital adrenal hypoplasia is a rare developmental form of primary adrenal insufficiency. Other potential causes of acquired adrenal insufficiency include hemorrhage, surgery, trauma, infection, hemochromatosis, and antiphospholipid syndrome. Approximately 90% of the adrenal cortex must be destroyed in order to produce clinical manifestations of adrenal insufficiency. Potential clinical features of adrenal insufficiency include weakness, hypoglycemia, dehydration, increased pigmentation, abdominal pain, nausea, developmental delay, intellectual impairment, and adrenal crisis. In patients with primary idiopathic adrenal insufficiency, imaging studies show markedly atrophic adrenal glands.23
| Primary | Congenital adrenal hypoplasia | |
| Idiopathic | ||
| Infection | Tuberculosis | |
| HIV infection | ||
| Adrenoleukodystrophy | ||
| IMAGe syndrome | ||
| Adrenal hemorrhage | ||
| Hemochromatosis | ||
| Antiphospholipid syndrome | ||
| Secondary | Pituitary or hypothalamus impairment | Tumor |
| Trauma | ||
| Tertiary | Hypothalamic disease (deficient corticotropin-releasing factor) | |
Neuroblastoma is a neoplasm that arises from embryonal neural crest tissue in the adrenal medulla or extraadrenal sympathetic nervous system. It accounts for 8% to 10% of all childhood cancers, and is the most common extracranial solid malignancy of childhood.24 The median patient age at presentation is 22 months. Approximately 80% of patients are less than 4 years old, and nearly all are less than 10.25 This tumor can arise in the fetus; neuroblastoma accounts for approximately 30% of all fetal tumors.26 The 5-year survival rate for neuroblastoma is 70% to 80%. Long-term survival is inversely related to the age at diagnosis.27–31
The normal fetal adrenal gland contains neuroblastic nodules that are histologically indistinguishable from neuroblastoma in situ. The number of these nodules peaks at 17 to 20 weeks gestation. These foci subsequently mature or regress. Pathological examination demonstrates neuroblastic nodules in 100% of second-trimester fetuses, but only 0.5% to 2.5% of neonates. The pathogenesis of adrenal neuroblastoma presumably involves failure of this normal maturation and regression process.32
Most neuroblastomas arise in the adrenal gland or in any portion of the sympathetic chain, from the neck to the pelvis. In children 65% of neuroblastomas are retroperitoneal and 40% originate in the adrenal glands.33 Sympathetic chain sites of origin include the abdomen (25%), thorax (15%), pelvis (5%), and neck (5%). More than 90% of neuroblastomas detected in the fetus are located in the adrenal gland. In infants, about one-third arise in the adrenal gland and one-third arise in the thorax. In children over the age of 1 year, approximately 55% of neuroblastomas arise in the adrenal gland, 20% elsewhere in the abdomen, and 15% in the thorax.
Metastasis, either local or distant, is present in approximately 80% of children with neuroblastoma at the time of diagnosis. This is somewhat more common in older children (85%) than infants (70%). Approximately 70% of neuroblastomas discovered in the fetus are confined to the site of origin. The pattern of spread varies somewhat with patient age. Metastatic spread in infants tends to involve the liver, bone marrow, skin, and lymph nodes. The most common sites of metastasis in children over 1 year of age are lymph nodes, cortical bone, bone marrow, and liver.
The clinical presentation of neuroblastoma is often related to metastatic disease rather than direct effects of the primary tumor. Children with this neoplasm frequently appear systemically ill. Malaise and/or pain due to metastatic disease are the presenting complaints in up to 60% of children over the age of 1 year with neuroblastoma; anemia from bone marrow involvement is also common (50% of patients). Neuroblastoma often produces an increase in the serum and urinary levels of catecholamines.
Paraneoplastic syndromes occur in fewer than 5% of neuroblastoma patients. Intractable watery diarrhea and hypokalemia in these children result from the secretion of vasoactive intestinal peptide.34 This clinical presentation, which can mimic that of malabsorption syndrome, is more often associated with ganglioneuroblastoma than neuroblastoma. Symptoms of paraneoplastic syndrome resolve following removal of the tumor. Another unusual symptom complex that can occur with neuroblastoma is cerebellar ataxia and opsomyoclonus (“dancing feet, dancing eyes syndrome” or “myoclonic encephalopathy of infancy”); this is most often associated with thoracic primaries.33 Hypertension in children with neuroblastoma can occur due to encasement or stretching of a renal artery or activation of the renin-angiotensin system.
Cervical neuroblastoma can produce Horner syndrome, a palpable mass, dysphagia, or stridor. A mediastinal primary may cause respiratory distress or Horner syndrome. A paraspinal lesion can lead to back pain, scoliosis, and manifestations of spinal cord or nerve root compression. A pelvic neuroblastoma may cause urinary tract obstruction or symptoms due to bowel compression.
Fetal neuroblastoma is most often clinically silent, with the lesion detected incidentally on prenatal sonography. Uncommonly, the lesion secretes sufficient catecholamine to produce maternal hypertension and preeclampsia. This complication increases the likelihood of placental metastasis and is associated with substantial neonatal mortality. Sonography or MR of fetal neuroblastoma demonstrates a cystic, solid, or complex suprarenal mass. There is a predilection for the right side. About half of fetal neuroblastomas are cystic. Echogenic foci due to calcifications are occasionally present. Images should be inspected for evidence of metastasis (e.g., liver, lymph nodes); rarely, this neoplasm metastasizes to the chorionic villi of the placenta. Sequential imaging studies of fetal neuroblastoma sometimes show spontaneous involution.35
Diagnostic imaging plays an important role in the staging and preoperative assessment of neuroblastoma in infants and children. The terminology used in describing the imaging findings is important for proper staging. The definition of midline extension is protrusion beyond the pedicle contralateral to the tumor. Vascular encasement is defined as tumor surrounding at least three-quarters of the circumference of at least 1 major abdominal artery or vein. Intraspinal extension refers to tumor within the spinal canal that is contiguous with the primary lesion. Involvement of a regional lymph node is suggested if a mass separate from the main lesion is identified.
The International Neuroblastoma Staging System is based on the imaging findings, surgical resectability, lymph node involvement, and bone marrow involvement: Stage 1—localized tumor with complete resection; Stage 2A—localized tumor with incomplete gross resection (ipsilateral nonadherent nodes are negative); Stage 2B—localized tumor (ipsilateral nodes positive, contralateral nodes negative); Stage 3—unresectable unilateral tumor infiltrating across the midline, or localized tumor with positive contralateral nodes, or midline tumor with bilateral extension; Stage 4—distant metastasis, except as defined in stage 4S; Stage 4S—infant less than 1 year old, with dissemination limited to skin, liver, and/or bone marrow (<10% of nucleated marrow cells malignant) (Figure 56-2).36
Important prognostic factors that indicate a greater likelihood of an adverse outcome in children with neuroblastoma include high-stage disease, patients who are greater than or equal to 1 year of age, deletion of chromosome arm 1p, amplification of the N-myc oncogene, and gain of chromosome segment 17q21-qter. The most widely reported genetic marker for neuroblastoma is amplification of the MYCN proto-oncogene.37,38 There is an association between MYCN amplification and high-grade lesions that have an advanced stage at presentation, rapid progression, and a poor prognosis.39 MYCN gene amplification is present in approximately 40% of patients with stage III or IV disease, compared with less than 10% of patients with lower stage disease. Gain of genetic material from chromosome arm 17q (gain of segment 17q21-qter) is the most common cytogenetic abnormality of neuroblastoma cells. This finding is an important prognostic factor that is associated with an adverse outcome.40 Expression of members of the tropomyosin-receptor-kinase (TRK) family of neurotrophin receptors in neuroblastoma cells is associated with a more favorable outcome.4
Children diagnosed with neuroblastoma prior to their first birthday have substantially better survival outcomes than older children, even when there is advanced disease at presentation. Survival also stratifies dramatically with respect to disease stage: the 5-year survival for stage 1, 2, and 4S patients is 75% to 90%, compared with a 10% to 30% 2-year survival for stage 3 or 4 disease. The survival rate for fetal neuroblastoma is 90% to 95%.4,41–43
Cross-sectional imaging studies of infants and children with neuroblastoma typically demonstrate a large, irregular, retroperitoneal mass. The retroperitoneal origin of the lesion is indicated by anterior displacement of other retroperitoneal structures (e.g., the aorta, vena cava, duodenum, and pancreas), lateral displacement of the posterior fat stripe along the right lobe of the liver, and obliteration of ipsilateral perinephric fat. Evidence of encasement of retroperitoneal vessels is an imaging feature that is characteristic of this neoplasm (Figure 56-3). CT frequently shows punctate or amorphous calcifications within the mass (Figure 56-4). Cystic and necrotic components are common. On sonography, the solid components of neuroblastoma are hyperechoic relative to the kidney (Figure 56-5). Occasionally, a paraspinal neuroblastoma extends into the extradural space of the spinal canal through 1 or more neural foramina; this is most common with lesions that arise in the thorax or neck. If detected when small (and usually asymptomatic), an adrenal neuroblastoma may appear as a circumscribed suprarenal mass that is indistinguishable from an adrenocortical tumor on standard cross-sectional imaging studies. Unlike adrenocortical neoplasms, however, neuroblastoma accumulates iodine-labeled metaiodobenzylguanidine (MIBG).44
Figure 56–3
Neuroblastoma.
Contrast-enhanced CT demonstrates a large right adrenal mass that contains small hypoattenuating cysts. A portion of the enhancing right kidney is displaced along the lateral margin of the tumor. There is encasement of the aorta, venal cava, and celiac vessels. The tumor displaces the pancreas.
Neuroblastoma typically has a heterogeneous appearance on MR. The majority of the tumor produces low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-weighted images. A variable degree of enhancement occurs with gadolinium. Areas of necrosis or cyst formation produce low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, and do not enhance. Calcifications, when present, tend to be irregular, and produce low signal intensity on all sequences. Metastatic lymphadenopathy has intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. MR demonstrates bone marrow involvement as abnormally high signal intensity on STIR and fat-suppressed T2-weighted sequences. Prominent gadolinium enhancement may be present. MR has been shown to be of greater sensitivity than CT for the characterization of stage 4 neuroblastoma.45,46
| Pathology | Radiology |
|---|---|
| Malignant neural crest tumor | Large mass |
| Infiltrative margins | |
| Vascular encasement | |
| MIBG uptake | |
| Necrosis, cysts | Heterogeneous |
| Nonenhancing regions | |
| Calcification | Punctate or amorphous calcifications |
Accumulation of bone-seeking radiopharmaceutical (99mTc-MDP) occurs in 40% to 85% of neuroblastomas (Figure 56-6). Appreciable uptake is more common in large tumors. This finding does not correlate with the presence or absence of tumor calcification, and has no known prognostic implication. Cortical metastases are detectable earlier with bone scintigraphy than with standard radiography. These lesions typically appear as foci of avid uptake (Figure 56-7). However, highly aggressive bone destruction or ischemia can occasionally result in decreased uptake.
Figure 56–7
Stage IV neuroblastoma.
A. Anterior (A) and posterior (P) bone scintigraphy images of a 16-month-old child show multiple foci of abnormal uptake, including the right facial bones, left acetabulum, and left femur (arrows). Faint uptake is present in the primary left adrenal tumor (arrow on posterior image). B. 123I MIBG scintigraphy also demonstrates uptake in the primary tumor (arrow), mediastinal metastatic lymphadenopathy, and multiple sites of skeletal metastasis (arrows). C. A contrast-enhanced CT image shows the primary tumor in the left suprarenal region. There is encasement of the aorta and superior mesenteric artery.
Accumulation of 123Iodine metaiodobenzylguanidine (MIBG) occurs in cells of the adrenal medulla and the sympathetic nervous system. MIBG scintigraphy is useful for the assessment of neuroectodermally derived neoplasms such as neuroblastoma, pheochromocytoma, and ganglioneuroma. At least 95% of neuroblastomas are MIBG-avid. Imaging with this agent provides a sensitivity of 92% and a specificity of 99% for the diagnosis of neuroblastoma in children. Uptake occurs in neuroblastomas that arise in the adrenal gland, as well as in extraadrenal primaries (Figure 56-8). Metastatic deposits of sufficient size can also be detected.
In the extremities, there is slight uptake of MIBG in muscles. Because there is no substantial accumulation of MIBG in normal bone or bone marrow, this agent is quite sensitive and specific for the demonstration of skeletal metastasis (Figure 56-9). In addition, MIBG does not accumulate at sites of bone repair, such as healing metastases, trauma, or biopsy. MIBG is also useful for whole-body surveillance. MIBG, however, is of limited sensitivity for the detection of small tumor deposits. Positron emission tomography (PET) imaging provides greater tumor-to-background ratios than MIBG scintigraphy and does not require multiday imaging. PET imaging with 2-fluorine-18-fluoro-2-deoxy-dglucose (FDG) may serve a role for evaluating children with neuroblastomas that do not accumulate MIBG. PET imaging with 11C-hydroxyephedrine targets sympathetic nervous system tissue, thereby providing similar information as MIBG scintigraphy.4
Most neuroblastoma metastases to cortical bone are radiographically lytic. The most common sites are the long bones, spine, pelvis, ribs, calvaria, and facial bones. Calvarial metastases usually are permeative, often associated with sclerosis. In some instances, thin vertical osseous striations extend from the cortical surface into the soft tissue component of the metastatic lesion (i.e., “hair-on-end” pattern). Sutural diastasis suggests elevated intracranial pressure due to intracranial (usually epidural) metastasis.
The most important retroperitoneal neoplasm in the differential diagnosis of a suspected neuroblastoma is Wilms tumor. The renal origin of a large Wilms tumor is sometimes inconclusive on imaging studies, and neuroblastoma can invade the kidney (Figure 56-10). Both of these tumors can be calcified and necrotic, and often extend across the midline. Because neuroblastoma more rapidly invades adjacent tissues than does Wilms tumor, typical imaging findings include vascular encasement, anterior displacement of the aorta and vena cava, and intraspinal extension (Figure 56-11). Wilms tumor tends to displace vessels without substantial encasement; intraspinal extension of Wilms tumor is rare. Renal parenchyma encases at least a portion of a Wilms tumor (i.e., the “claw sign”) (see Chapter 49).47
Figure 56–10
Neuroblastoma.
A, B. Axial and coronal contrast-enhanced images of a 12-month-old child show a large left retroperitoneal mass. There is renal invasion; enhancing renal parenchyma is draped around the lesion. There is encasement of the aorta and inferior vena cava. Tumor extends into the thoracic paraspinal regions.
Figure 56–11
Neuroblastoma versus Wilms tumor.
A. An axial CT image of a child with neuroblastoma shows displacement of the left kidney by a large retroperitoneal mass. There is extensive vascular encasement. B. CT of a child with a right-sided Wilms tumor shows enhancing renal parenchyma surrounding much of the mass. There is no vascular encasement.
As with neuroblastoma and ganglioneuroma, ganglioneuroblastoma arises from neural crest cells. Ganglioneuroblastoma can arise from the sympathetic chain and plexuses, the adrenal glands (medulla), and the organ of Zuckerkandl. This lesion is more frequently located in the thorax than is neuroblastoma. Ganglioneuroblastoma most often presents as a palpable or incidentally discovered retroperitoneal, abdominal, or thoracic mass. As with other neural crest tumors, secretion of vasoactive peptides by this lesion can produce chronic diarrhea.48
The malignant potential of ganglioneuroblastoma is intermediate between that of neuroblastoma and ganglioneuroma. Ganglioneuroblastoma has mixed histological features, with malignant neuroblasts as well as benign ganglioneuromatous elements. Assignment of patients to clinically favorable and unfavorable groups is based on the histological findings. Some ganglioneuroblastomas apparently represent neuroblastomas that have undergone spontaneous maturation.49–52
Imaging studies do not allow accurate differentiation between ganglioneuroblastoma and neuroblastoma. Ganglioneuroblastoma tends to be smaller and more well defined than neuroblastoma at the time of diagnosis. A variable degree of vascular encasement or displacement can occur with those that arise in the retroperitoneum (Figure 56-12). MR typically shows intermediate signal intensity on T1-weighted images and heterogeneous high signal intensity on T2-weighted images. There is moderate heterogeneous contrast enhancement. As with neuroblastoma, ganglioneuroblastoma avidly accumulates bone-seeking radiopharmaceutical (99mTc-MDP) and sometimes contains sufficient adrenergic activity to produce detectable uptake of 131I-MIBG.53–57
Figure 56–12
Retroperitoneal ganglioneuroblastoma.
A. A coronal T2 fast imaging with steady-state precession (FISP) image of a 16-year-old girl shows a lobulated retroperitoneal mass (arrows). B. The lesion is moderately hyperintense on this T2 fat-suppressed image. There is encasement of the abdominal aorta (arrow) and anterolateral displacement of the vena cava (arrow). There is displacement of the left kidney. C. The mass (arrows) undergoes mild to moderate contrast enhancement. The margins of the lesion are well defined.
Ganglioneuroma is the most differentiated of the adrenal neoplasms of neural crest cell origin. This benign tumor most often presents in older children and adults. In addition to the adrenal glands, ganglioneuroma can arise elsewhere in the retroperitoneum, in the mediastinum, and in the peritoneal cavity. Overall, approximately half of ganglioneuromas arise in the abdomen or retroperitoneum. Less than one-fourth of all ganglioneuromas arise in the adrenal gland.
Ganglioneuroma is a slowly growing benign neoplasm. This lesion is occasionally first identified on a diagnostic imaging study performed for an unrelated indication. Symptoms occur in some patients due to mass effect. Neurological findings can occur when there is intraspinal extension through 1 or more neural foramina. In other patients, the presentation is due to a palpable mass. Occasional children with ganglioneuroma have sufficient elevation of circulating catecholamines to produce systemic manifestations such as hypertension, sweating, and diarrhea.58,59
On gross pathology, ganglioneuroma is a well-marginated soft mass that tends to conform to adjacent confining structures. The tumor contains sympathetic ganglion cells, which sometimes produce a vasoactive intestinal polypeptide. Occasionally, there are intermixed elements of pheochromocytoma, ganglioneuroblastoma, or neuroblastoma. There are rare instances in which a malignant peripheral nerve sheath tumor arises within a long-standing benign ganglioneuroma.
On diagnostic imaging evaluation, ganglioneuroma usually appears as a soft tissue mass with well-defined borders. A somewhat lobulated contour is common. Most often, adjacent structures are mildly displaced by the tumor, but not invaded. There are unusual instances in which the findings mimic those of neuroblastoma, with encasement of retroperitoneal vascular structures. The lesion is usually relatively homogeneous and shares some of the imaging characteristics of peripheral nerve sheath tumors.
Ganglioneuroma is often moderately hypoechoic on sonography. CT imaging shows attenuation values less than those of muscle. There is only minimal contrast enhancement. Punctate calcifications are present in about half of these tumors, resulting in echogenic foci on sonography and high-attenuation areas on CT. Ganglioneuroma tends to have a whorled appearance on MR. On T1-weighted images, the lesion is hypointense compared with the liver. The lesion is hyperintense to liver on T2-weighted images; the composition often appears somewhat heterogeneous on this sequence. A delayed enhancement pattern is often present on dynamic contrast-enhanced CT or MR images. An enhancing capsule is sometimes visible on gadolinium-enhanced T1-weighted images.60–62
Pheochromocytoma is a rare catecholamine-secreting tumor that is derived from chromaffin cells in neural crest tissue of the autonomic nervous system. The most common (80% to 90%) site of origin is the adrenal medulla. Extraadrenal pheochromocytomas (also termed paragangliomas) arise in paraganglionic chromaffin tissue of the sympathetic nervous system, anywhere from the base of the brain to the bladder. The most common extraadrenal sites include chromaffin cell-bearing tissue adjacent to the lower portion of the abdominal aorta, the organ of Zuckerkandl, and the bladder wall. In approximately 90% of patients with an adrenal lesion, the mass is unilateral.
In the pediatric age group, pheochromocytoma usually occurs in older children; the typical pediatric age range for this tumor is 6 to 14 years. A family history is present in a minority of patients. Approximately 25% of patients with sporadic pheochromocytoma have identifiable germline mutations. Functioning adrenal medullary hyperplasia may be a precursor of pheochromocytoma, with diffuse medullary hyperplasia representing the initial pathological change in the adrenal gland that leads to the development of nodular hyperplasia and an adrenal medullary tumor. Pheochromocytoma can arise in patients with neurofibromatosis type 1, von Hippel-Lindau disease, Sturge Weber syndrome, tuberous sclerosis, and multiple endocrine neoplasia types IIA, IIB, and III. Approximately 90% of pheochromocytomas in children are benign. Pheochromocytoma is a lesion of “ten percents”: 10% bilateral, 10% in children, 10% extraadrenal, 10% familial, and 10% malignant.63,64
Pheochromocytomas are endocrinologically active and secrete catecholamines. This tumor can precipitate life-threatening hypertension or cardiac arrhythmias because of excessive catecholamine secretion. The most common presenting symptom of pheochromocytoma is constant or paroxysmal headache due to hypertension. Patients with pheochromocytoma are chronically vasoconstricted because of the high levels of circulating catecholamines; therefore, there is diminished overall blood volume. Catecholamine secretion from a pheochromocytoma is independent of neurogenic control. The size of the tumor does not correlate with the severity of symptoms. Labile hypertension and tremors are common. Phentolamine is the medication of choice for a pheochromocytoma-related hypertensive crisis. Approximately 10% of patients with this tumor are asymptomatic, presumably due to minimal catecholamine secretion.
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