Clinical History: An 80 year-old male presents with a one year history of a left forearm mass and left hand numbness. Axial T1-weighted (1a) and coronal STIR (1b) images of the forearm are presented. What are the findings? What is your diagnosis?
Schwannoma of the median nerve.
Neurogenic tumors are relatively common and account for approximately 12 per cent of all benign and 7 to 8 per cent of all malignant soft tissue neoplasms.1,2 In contrast to many other soft tissue tumors, certain imaging features suggest a neurogenic origin. These characteristic imaging findings include a specific clinical presentation or location, relationship to a nerve, and certain lesion shape and signal intensity patterns. This article reviews the MR imaging appearance of the most common tumors and tumor-like lesions of neurogenic origin.
Anatomy of Peripheral Nerves
A good knowledge of both the histologic architecture and the anatomic location of the peripheral nerves is essential for their study by MR imaging. The three components of the peripheral nerves are axons, Schwann cells, and connective tissue sheaths that support and protect the nerve fibers (C). Axons and Schwann cells form the nerve fibers. A myelinated fiber results if only one axon is encased by a single Schwann cell. Unmyelinated fibers result if a Schwann cell encases multiple axons. The endoneurium is the innermost connective tissue sheath. It consists of loose vascular tissue and extracellular fluid surrounding the nerve fibers. Nerve fibers and endoneurium are bundled together into nerve fascicles, which are surrounded by a sheath of dense connective tissue called the perineurium. A peripheral nerve consists of one or more nerve fascicles held together by the epineurium, which is the outermost connective tissue sheath.3 There are two distinct layers within the epineurium.4 The outer epineurium is a thick layer of dense connective tissue that surrounds the entire peripheral nerve. The inner part of the epineurium, the interfascicular epineurium, is composed of dense connective tissue containing longitudinally arranged collagen fibrils, elastic fibers, small vessels, and variable amounts of fat. The interfascicular epineurium surrounds the nerve fascicles.
Nerves are supplied by small intra- and interfascicular blood vessels. Microvascular plexi are found in the epineurium, perineurium, and endoneurium.5 As in the blood-brain barrier of the central nervous system, the endoneurial blood vessels prevent the passage of certain micromolecules through their walls. This property is known as the blood-nerve barrier.
The MR appearance of peripheral nerves corresponds to the fascicular pattern seen histologically. The nerve fascicle is the smallest unit that can be visualized with conventional MR imaging.6 On cross-sectional T1-weighted or proton density-weighted images, peripheral nerves contain numerous small rounded hypointense dots which correspond to the nerve fascicles. The fascicles are surrounded by high signal intensity connective tissue which corresponds to the fat within the epineurium (4a). On cross-sectional fluid sensitive images, peripheral nerves appear isointense to slightly hyperintense compared with normal skeletal muscle (E). Nerve fascicles, which contain endoneurial fluid, may have a slightly higher signal intensity than surrounding connective tissue.6 The major disadvantage of T2-weighted images acquired without fat suppression is that the high signal intensity of the fat found in the epineurium makes it difficult to identify the nerve fascicles and can obscure pathologic changes in the nerves, which usually exhibit high signal intensity. Normal peripheral nerves show no enhancement after intravenous administration of gadolinium-containing contrast material due to the integrity of the blood-nerve barrier (5a).7
It is important to realize that the signal intensity of peripheral nerves is dependent upon their orientation relative to the static magnetic field. When the nerve fibers are oriented at an angle of approximately 55 degrees to the main magnetic field on T2-weighted images, the signal intensity is increased.8 This artifact is called the ‘magic angle effect’ and is well known in highly ordered, linearly oriented collagen-rich tissues such as tendons and ligaments. Because the epineurium contains collagen, the signal intensity of peripheral nerves may also show the magic angle effect. However, in contrast to tendons, in which the magic angle effect is typically seen in sequences with a short TE, nerves may show this effect on images with longer values of TE.8 This artifact must be understood as it may simulate pathology within the nerve.
Schwannoma and Localized Neurofibroma
Solitary benign peripheral nerve sheath tumors have classically been divided into two major categories: Schwannoma and localized neurofibroma. Although these lesions are similar and contain cellular elements closely related to normal Schwann cells, several clinical and pathologic features will often allow distinction.
Schwannoma (neurilemmoma, neurinoma) is a slow-growing tumor that is believed to arise from the Schwann cells of a peripheral nerve. Therefore, the lesion usually develops eccentrically to the nerve fibers and is encapsulated by the perineurium. Schwannoma most frequently affects patients 20 – 50 years of age and accounts for approximately 5% of all benign soft tissue neoplasms.1 Men and women are affected equally. Although the head and neck, the flexor surfaces of the extremities (particularly the ulnar and peroneal nerves), and the mediastinum and retroperitoneum represent the most common sites of involvement, schwannomas can occur almost anywhere. Pain and neurologic symptoms are uncommon unless the lesion is large.9,10 Long-standing tumors that are relatively large can undergo degenerative changes such as cyst formation, calcification, hemorrhage, and fibrosis and are described as ancient schwannomas.11
Localized or solitary neurofibromas are slowly-growing fusiform lesions with a centrally entering and exiting nerve. These lesions often lack a capsule and the tumor tissue cannot be separated from normal nerve fibers. Neurofibromas account for approximately 5% of all benign soft tissue tumors and are usually observed in younger individuals between the ages of 20 and 30 years with no sex predilection.1
Schwannomas and neurofibromas share many, if not all, morphological features on MR imaging. Both lesions present as fusiform, well-defined masses that rarely exceed 5 cm in diameter. A dumbbell shape is typical for paraspinal lesions, which may enlarge a neural foramen. Continuity with a nerve is usually best seen in lesions arising from larger nerves and is virtually diagnostic (7a). The distinction of Schwannomas and neurofibromas by the position of the tumor relative to the nerve (eccentric versus central) is often difficult. This is best appreciated on axial MR images when a large peripheral nerve is involved.
With an intramuscular location, the lesions may be surrounded by fat, a feature that can create the ‘split fat sign’ on T1-weighted MR images oriented along the long axis of the extremity (8a,9a). Most benign nerve sheath tumors are isointense or slightly hyperintense to muscle on T1-weighted images and are markedly hyperintense to fat with a variable degree of heterogeneity on T2-weighted MR images. On fluid-sensitive sequences the lesions may exhibit high signal intensity in the periphery and low to intermediate signal intensity centrally. This appearance has been termed the ‘target sign’ (10a) and is caused by the zonal architecture of the lesion with more myxoid material peripherally and more fibrous tissue centrally.12 Although the target sign was initially believed to be pathognomonic of neurofibroma, it has been observed in both neurofibromas and schwannomas and has even been reported in malignant peripheral nerve sheath tumors (MPNST).13
The ‘fascicular sign’ is another finding that has been reported with neurogenic tumors (11a). It describes multiple ring-like structures within the lesion, possibly reflecting the fascicular bundles seen histologically. A thin, low signal intensity capsule might be identified on T2-weighted images, particularly if the tumor is surrounded by fat. This is slightly more common in schwannomas than in neurofibromas. On contrast-enhanced images, small nerve sheath tumors often show intense and relatively homogeneous enhancement. Large lesions may demonstrate predominantly peripheral, central, or heterogeneous nodular enhancement. Atrophy of innervated muscles is an imaging finding that suggests a neurogenic tumor and should be specifically searched for.13
Schwannomas are typically treated by surgical excision. As the nerve is typically displaced rather than infiltrated, these lesions can usually be resected with sparing of the associated nerve (12a,13a). Neurofibromas are also usually treated with surgical resection. However, unlike with Schwannomas, this requires excision of the involved nerve because it cannot be separated from the neoplasm. With either lesion, recurrence is unusual and malignant transformation is rare.
Plexiform neurofibroma is a subtype of neurofibroma that is essentially pathognomonic of Neurofibromatosis type 1. Plexiform neurofibromas usually develop during childhood and can precede the appearance of cutaneous neurofibromas. Estimates of the lifetime risk for malignant transformation vary from 2% to 29% with an average of approximately 5%.13
Plexiform neurofibromas diffusely involve a long segment of nerve, often extending into its branches and creating a “bag of worms” appearance on gross inspection. At early stages, smaller lesions may be contained within the epineurium. Later, the lesions typically extend beyond the epineurium into surrounding soft tissues. MR imaging demonstrates a tortuous mass of irregularly expanded nerve branches that may invade adjacent muscles and connective tissues (14a). In general, plexiform neurofibromas exhibit the same signal characteristics and contrast enhancement pattern as a solitary lesion.13
Neural Fibrolipoma (Fibrolipomatous Hamartoma)
Neural fibrolipoma (lipomatosis of nerve, fibrolipomatous hamartoma) refers to a tumor-like process with epineural and perineural infiltration of adipose and fibrous tissue. The disease typically presents before 30 years of age, often at birth or in early childhood, and most commonly affects the median or ulnar nerve. The lesion is associated with macrodactyly in the hand or foot in about a third of cases.14 The slow-growing mass can cause increasing pain, diminished sensation or paraesthesia, and loss of strength.
MR imaging is virtually pathognomonic of the disease (15a,16a). Transverse images demonstrate diffuse enlargement of the involved nerve with a cable-like appearance that is created by the fibrolipomatous tissue surrounding the thickened nerve fascicles. The signal intensity of the tissue surrounding the nerve fibers varies from isointense to fat to relatively hypointense on all pulse sequences, based on the relative amounts of fat and fibrous tissue that are present.13
A Morton neuroma is a non-neoplastic lesion of a plantar digital nerve that results from perineural fibrosis and degeneration. This lesion has been discussed in a previous Web Clinic.
Traumatic neuromas have been divided into two major categories based on the anatomic location of the disorganized proliferation of axonal tissue. Spindle neuromas are internal, localized, fusiform swellings that occur as a fibroinflammatory response to chronic friction or irritation of an intact nerve.15 Terminal neuromas result from tangled regenerating axons in response to an injury or surgery (amputation) and represent an abortive attempt of the severed or injured proximal nerve ending to reestablish continuity. Most traumatic neuromas are seen in the lower extremity following amputation. They can develop within 1 to 12 months of the traumatic event and can present as a painful mass.13
MR images show fusiform (spindle neuroma) or bulbous (terminal neuroma) masses in continuity with the injured or transected nerve (17a,18a). Most traumatic neuromas are of intermediate signal intensity on T1-weighted images and of intermediate to high signal intensity on T2-weighted images, possibly with a peripheral rim of low signal intensity. The signal intensity is often heterogeneous with a fascicular pattern that correlates with the histology of nerve fascicles. Contrast enhancement is variable.13
Initial non-operative treatment may include physical therapy, steroid injection, and nerve stimulation and has been successful in up to 50% of patients. Surgical techniques attempt to remove the proximal nerve stump from the area of fibrosis, limiting the potential for lesion recurrence. Surgical resection is undertaken in patients who are not responsive to non-operative measures.16
Malignant peripheral nerve sheath tumors
MPNST (malignant schwannoma, neurogenic sarcoma, neurofibrosarcoma) defines a spindle cell sarcoma that arises from a nerve or neurofibroma and/or demonstrates neural differentiation. These account for approximately 7 to 8% of all soft tissue neoplasms.2 Twenty-five to fifty percent of MPNST’s occur in patients with NF-1, making neurofibromatosis the most important risk factor for developing MPNST.10 Clinical features that strongly suggest a malignant histology are pain at rest, often severe enough to require analgesics, and neurologic deficits such as severe muscle weakness.9 The duration of symptoms in malignant tumors also tends to be shorter than in benign tumors.
In many cases, MR imaging does not allow confident distinction of MPNST from benign nerve sheath tumors. Although less frequent than in benign lesions, the split fat sign, target sign, and fascicular sign may also be seen with MPNST.13 However, several MR imaging characteristics have been found significant in the distinction of benign from malignant lesions. The four features on MR imaging that favor a malignant diagnosis are – mass over 5cm in size, peripheral pattern of contrast enhancement, perilesional edemalike signal, and an intratumoral cystic lesion.10 The presence of two or more of the listed features is highly suggestive of malignancy.
Numerous neurogenic tumors can affect the musculoskeletal system as described above. The diagnosis of neurogenic tumors can be suggested from their MR imaging appearance, including lesion shape and signal characteristics. It is also important to establish lesion location along the course of a peripheral nerve. Although the differentiation of schwannoma from neurofibroma and of benign from malignant peripheral nerve sheath tumor can be difficult, recognition of the MR appearance of neurogenic tumors often allows a proper pre-operative diagnosis and improves patient management.
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