|ECR 2018 / C-2762|
|Imaging findings of abdominal neurogenic tumors: what every radiologist should know|
Findings and procedure details
1. TUMORS OF GANGLION CELL ORIGIN
Ganglioneuromas are rare, benign neurogenic tumors, that originates from sympathetic ganglia, and are composed of mature Schwann cells, ganglion cells, and nerve fibers. Although benign, poorly differentiated components, such as ganglioneuroblastoma, neuroblastoma, or pheochromocytoma, can appear in up to 25% of them.
The tumor affects more frequently children and young adults (42-60%), but can occur in all ages, and is slightly more often in female. The most common locations are the retroperitoneum (32-52%) and posterior mediastinum (39-43%), but the tumor may arise anywhere along the paravertebral sympathetic plexus, and also the adrenal gland, usually in patients older than 40 years.
Even with large volumes, the tumor is usually asymptomatic, although may appear with abdominal mass, and sometimes pain. They have an excellent prognosis, with low rates of recurrence after surgical resection.
The imaging findings of retroperitoneal or adrenal ganglioneuromas are characterized by homogeneous, well-defined tumors, with oval, crescentic, or lobulated shape, calcification in about 20% of cases, and gradually increasing enhancement post-contrast. The mass can surround major blood vessels, with almost no compromise of the lumen. In MRI, the tumor is seen with a low signal intensity on T1-weighted images, and variable T2 signal intensity, depending on the proportion of myxoid stroma, cellular components, and collagen fibers. A characteristic finding is the whorled appearance, given by curvilinear low-signal-intensity bands on T2-weighted images.
Ganglioneuroblastomas are rare tumors, more commonly arising in the abdomen of children from 2 to 4 years old. It is important to recall that these neoplasms are almost exclusively pediatric and very rarely found in patients older than 10 years.
Imaging appearance is highly variable, resembling a lot the aforementioned neuroblastoma imaging findings.
These tumors are transitional tumors composed by elements of both ganglioneuromas and neuroblastomas. Histologic distinction is of major importance since the prognosis is much better when compared to neuroblastomas.
Neuroblastomas are malignant tumors that consists of primitive nerve cells and arises in sympathetic neural ganglia and adrenal medulla. It is the most common extracranial tumor diagnosed in infancy, affecting mainly children between 0 and 4 years of age (median age 19 months), with a mal-to-female ratio of 1,2:1. In North America and Europe the incidence is estimated at 10.5 per million children under 14 years of age. The adult-type neuroblastoma is extremely rare.
The clinical features depend on the tumor location and extension, with the majority located in the abdomen (65%), usually the adrenal gland. Other sites include paravertebral sympathetic chain or presacral area, and more rarely the celiac axis or organ of Zuckerkandl. The symptoms can result from the expansive effect on organs, vessels or nerves, causing abdominal pain, distension and constipation.
Approximately 70% of patients present with metastatic disease, through both lymphatic and hematogenous routes, with predilection mainly for bone, bone marrow, and liver.
The prognosis varies from spontaneous regression to aggressive metastatic tumors and patients can be categorized as low, intermediate, and high risk for recurrence.
In the imaging exams, they are seen more commonly as irregularly shaped, lobulated, and unencapsulated lesions, with heterogeneous enhancement, due to necrosis and hemorrhage. Calcifications are often present, showing a coarse, amorphous, and mottled appearance. It is important to determine the tumor invasion of adjacent organs, the involvement of adjacent vessels, and the extension to the retroperitoneal lymph nodes or into the vertebral canal.
The metaiodobenzylguanidine (MIBG) is an analogue of norepinephrine that selectively concentrates in sympathetic nervous tissue, being an ideal tumor-specific agent for imaging, and is used in scintigraphy to detect primary tumors and metastatic sites.
2. TUMORS OF THE PARAGANGLIONIC SYSTEM
Pheochromocytoma, also called extraadrenal paraganglioma, is a rare catecholamine secreting tumors derived from chromaffin cells. Any physical contact with these neoplasms can precipitate cardiac arrhythmias and malignant hypertension. Demonstrate a nesting (Zellballen) microscopic pattern, composed of well-defined clusters of tumors cells containing eosinophilic cytoplasm separated by fibrovascular stroma. May occur cystic degeneration, necrosis, lipidic, calcification and fibrosis.
More than 90% are located in adrenal glands and 98% occurs within the abdomen. Extradrenal tumors develop, usually in paraganglionic chromaffin tissue of the sympathetic nervous system. The extraadrenal locations are zuckerkandl organ, bladder wall, retroperitoneum, heart, mediastinum, carotid glomus jugular bodies. Occurs 0,1 – 0,9% of hypertensive individuals. 10% of cases are asymptomatic and tend to be larger than hyperfunctioning tumors.
Hypertension or cardiac arrhythmias because of excessive cathecholamine secretion. 10% malignant and hereditary and related with syndrome (MEN II and III, SVHL, Sturg-Weber and others). The diagnosis of pheochromocytoma is dependent on the imaging identification of an appropriately located mass with accompanying clinical and biochemical confirmation. Biochemical confirmation should be obtained before imaging (plasma metanephrine levels and of 24 hour urinary catecholamine levels).
Usually unilateral and benign manifestation. On computed tomography pheochromocytomas may be homogeneous or heterogeneous, solid or cystic complex masses or may show calcification. The attenuation provides valuable information. Adenomas can often be differentiated from others masses owing to intracellular fat that causes decrease of attenuation and tend to be less than 10 HU. Most pheochromocytomas have higher attenuation, more than 10 HU. Sometimes it cannot be used because they can contain fat or necrosis and may contain very high attenuation with hemorrhage. Typically enhance avidly but can be heterogeneous or show no enhancement due cystic changes. Washout patterns is inconsistent and variable.
Magnetic resonance imaging appearance is typically a mass with low signal intensity at T1-weighted imaging and with high signal intensity at T2-weighed imaging. However the appearance can vary with low signal pheochromocytomas encountered at T2-weighted imaging. Pheochromocytomas cannot be excluded on the basis of a lack of high signal intensity at T2 weight MR imaging. Conversely, nonpheochromocytomas, including some metastases, may be wrongly classified as pheochromocytomas. Metaiodobenzylguanidine (MIBG) has almost 100% of specificity but limited sensivity.
Pheochromocytoma and paragangliomas can have any imaging appearance. Also adenomas and angiomyolipomas.
Paraganglioma is a peculiar neuroendocrine tumor derived from chromaffin cells, can be observed at various locations such as the skull base, neck, thorax, and abdomen. It is a rare clinical issue with incidence of 0,2-0,5 cases/100.000 per population/year and they usually occur from head-and-neck through the retroperitoneal periaotic, but can be found in adrenal (pheochromocytomas) and extra adrenal locations. One of the major location is the region located at the site of distal aortic bifurcation associated with the sympathetic chain (Zuckerkandl organ). About 90% is located at adrenal gland and 10% extra adrenal. It has been reported that 97% of paragangliomas were considered benign and occurs more frequently in women between 30 to 40 years of age. There are two types: functional and nonfunctional. The functional is associated with clinical symptoms and occurs in 77% of all cases and the 23% nonfunctional is usually asymptomatic, but may present with pain and palpable abdominal mass.
The clinical symptom of most paraganglioma includes headache, hypertension, heart palpitation and pain due to excessive secretion of catecholamine. Most tumors are sporadic, come cases may be associated with hereditary tumor syndromes such as neurofibromatosis, von Hippel-Lindau syndrome Sturge-Weber syndrome, and tuberous sclerosis. Endocrine examination including catecholamine and noradrenaline en serum and 24-hour urine should be performed if paraganglioma or pheochromocytoma is suspected.
The tumor consist in tumor cells surrounded by sustentacular cells and separated into polygonal nest by fibrovascular stroma. Immunohistochemistry is also critical for diagnosis with positivity for CgA, PCK, CD56 and S-100 protein.
Computed tomography shows a well-circumscribed, solid, with avid and rapid wash-out, lobulated mass may be identified. If small tumors may have homogeneusly enhancing and heterogeneous in large tumors. The presence of ring-like calcification in the periphery of the mass may occur. On MRI, the tumors are homogeneously hyperintense on T1-Weightd images and iso-to-mildly hyperintense on T2-Weithcet imagens and demonstrate intense enhancement after contrast administration. Paragangliomas have been reported to show a salt-and-pepper appearance, reflecting foci of hemorrhage (“salt”) and vessel flow voids (“peppers). May have higher ADC values and indicates water diffusion is not restricted, which can be related to low cellularity, hypervascularity, rich stroma and low nuclear/cytoplasmic ratio. Iodina-123 metaiodobenzylguanidina (MIBG) snca is hygly specifc (96%) for diagnosis of paragangliomas and is also useful for detection of metastatic disease. Surgical excision of the tumor following adrenergic blockade is the treatment of choice for localize disease. Approximately 5-20% cases show malignat behavior, evidenced by metastases, and extensive local disease.
3. TUMORS OF NERVE SHEATH ORIGIN
3.1 SCHWANNOMA OR NEURILEMMOMAS
Schwannomas or neurilemmomas are encapsulated benign peripheral nerve tumors that arise from the Schwann cells.
They more commonly arise sporadically in the fifth and sixth decades. When multiple schwannomas occur in the same patient neurofibromatosis type 2, or rarely schwannomatosis, should be suspected.
Clinical presentation varies greatly, but patients usually present with a painless growing mass and symptoms related to local mass effect.
Tumors are most commonly situated in the posterior fossa or the spine, but also relatively common in the flexor surface of the upper and lower extremities. Abdominal schwannomas are tipically situated in the retroperitoneum, in the paravertebral regions. Gastrointestinal schwannomas are extremely rare and usually gastric, representing an important differential diagnosis to gastrointestinal stromal tumors (GISTs).
Histologically, these tumors can be indentified by alternating areas of the classic Antoni classification.
Antoni A: more cellular with spindle cells and palisades.
Antoni B: edematous fluid between the cells, hypocellular losse myxoid component.
Neurilemmomas are tipically small, measuring less than 5 cm. Their appearance in CT and MRI is classically that of a fusiform well-demarcated tumor. Density and signal intensity are higly dependent on the predominance of Antoni A or Antoni B regions, with correlation to cellularity and fluid content. Also, the more fluid within the tumor, less enhancement is expected. Calcification, hemorrhagic and cystic changes can also be found.
The “target sign”, which represents the typical low signal intensity in the central part of the tumor, and the “fascicular sign”, characterized by the multiple ring-like structures within the tumor, are classical radiologic signs have been associated to schwannomas.
Differential diagnosis is usually made with neurofibromas, synovial sarcomas, malignant peripheral nerve sheath tumors (MPNST) and hematomas. Other neurogenic tumors should be in the differential diagnosis of retroperitoneal schwannomas and adnexial lesions and lymphoma should also be included when the lesion is pelvic.
First-line treatment of neurilemmomas is surgical resection. Unlike neufibromas, these tumors can be separated from the nerve during the procedure, because they do not infiltrate it. Prognosis is very good. Only rare cases of malignant transformation hvave been reported.
3.2 NEUROFIBROMAS AND NEUROFIBROMATOSIS
Neurofibromas can manifest as a solitary tumor or as a component of neurofibromatosis type-1 (NF1). Neurofibromas originate from the nerve sheath, and are histologically characterized by proliferation of nerve sheath cells interspersed with thick, wavy collagen bundles and may show variable degrees of myxoid degeneration.
Although, about 90% of neurofibromas were of the solitary type, when found, should support the hypothesis of NF1. Approximately 30% of patients with solitary neurofibroma have NF1, and virtually all patients with multiple neurofibromas or plexiform neurofibromas have NF1.
NF1, also known as von Recklinghausen disease, is a common autosomal dominant condition with an approximate incidence of one per 3000 births. Abdominopelvic involvement in NF1 is primarily extraperitoneal, lesions are mostly detected in the abdominopelvic wall and lumbosacral plexus.
CT may shows solid fusiform masses along the distribution of nerves, with central areas of low attenuation and occasional calcification. The masses usually are well defined and have homogeneous low attenuation. Asymmetry in the size or attenuation of the mass may suggest malignant transformation. They may also show mild to moderate heterogeneous post-contrast enhancement.
T1-weighted MR images show the central portion with higher signal intensity than the periphery, whereas on T2- weighted images the periphery has higher signal intensity.
Although both neurilemmomas and neurofibromas are of nerve sheath origin pure neurofibromas are solid tumors and areas of cystic degeneration are uncommon in neurofibromas. Neurofibromas often undergo malignant degeneration, particularly in cases of neurofibromatosis, whereas neurilemmomas rarely if ever undergo malignant degeneration.
3.3 MALIGNANT PERIPHERAL NERVE SHEATH TUMORS
Malignant peripheral nerve sheath tumors (MPNST) are described as highly aggressive tumors that arise from a peripheral nerve, a pre-existing peripheral nerve sheath tumor, or associated with neurofibromatosis type 1 (NF1) syndrome. They may also arise from a plexiform neurofibroma, a benign tumor derived from Schwann cells, de novo, or secondary to previous radiotherapy. MPNSTs commonly occur in deep soft tissues, usually next to a nerve trunk. The common sites are sciatic nerve, brachial and sacral plexus. The World Health Organization uses the term MPNST to replace less former well-defined terms of malignant schwannoma, neurogenic sarcoma and neurofibrossarcoma.
MPNST comprise about 2%-10% of all sarcomas, at any age and with no gender predilection, 40%-60% of MPNST arise from cases with NF1, with an overall 4% chance of malignant transformation from NF1. They tend to present earlier in life than other complex genomic sarcomas, with median age for sporadic MPNST in between 4th and 7th decades, and for NF1-associated MPNST in between 3rd and 5th.
Histologic features of MPNST are rather nonspecific, with monotous spindle cells arranged in intersecting fascicles, often with hypercellular areas localized close to blood vessels, with either hemorrhage, necrosis or degenerative changes. The distinction between MPNST and typical neurofibromas can be made with the marked tumor cellularity, pleomorphism and presence of mitotic figures, with less extracellular matrix material.
Clinically, pain is the most common symptom, and other findings include a large mass, usually 5 cm or more, with irregular borders and rapid growth. Neurologic deficits can occur secondary to neural impingement or mass effect along the involved nerves.
Radiologically, MPNST are indistinctive to typical neurofibromas, usually presenting low-attenuation level on CT, due to fat content of myelin from Schwann cells and high water-content of water myxoid tissue.
MR imaging is the best diagnostic imaging modality because of its multiplanar capability and superior soft-tissue contrast. Both benign and malignant nerve sheath tumors may have heterogenous low signal on T1WI, intermediate to high signal intensity on T2WI and demonstrate avid enhancement with gadolinium-based contrast media administration. Although benign and MPNST have some overlapping imaging features, there are some characteristics that can help distinguish them. The radiologist should be alert to some imaging findings that should prompt further evaluation as intratumoral lobulation, ill-defined margins, and marked heterogeneity on T1WI, both before and after the intravenous administration of gadolinium-based contrast agent. Also, as mention before, rapid growth and a more infiltrative appearance is commonly seen in malignant tumors.
In general, MPNST is known to have high metastatic potential and poor prognosis. Several large series report significantly worse outcomes for MPNST arising in the setting of NF1 compared with sporadic disease. Genetic counseling of family members suspected to have NF1 should be performed.
For differential diagnosis considerations, all tumors that involve the nerve sheath should be remembered, both benign and malignant.