CHAPTER 244 Benign Tumors of the Peripheral Nerve
History
From the time of Hippocrates through the 18th century, the common belief was that an injured nerve could not be repaired and that manipulation of an injured nerve could lead to pain, convulsions, or even death. Most reports of nerve tumors in the 17th century concerned the swellings found at the ends of transected nerves. Odier of Geneva coined the term neuroma for enlargement of peripheral nerves.1 The first recognizable description of what was probably a peripheral nerve sheath tumor was reported by Cheselden in 1741. In the text of The Anatomy of the Human Body, Cheselden described a tumor that occupied the center of the “cubital” nerve, displacing the nerve fibers to the periphery.2 Wood, in his extensive 1829 review of nerve tumors, noted that “a number of nervous fasciculi, sometimes a good deal flattened, can be traced in a perfect state of continuity running over the surface to be connected below to the trunk of the nerve.”3 Although it appears obvious today that the tumor can be removed sparing the nerve’s fascicles, the dogma of the day was that it was dangerous to manipulate a peripheral nerve. In 1800, Hunter performed an en bloc resection of a length of a patient’s musculocutaneous nerve containing a tumor. His assistant, Home, took the specimen to the laboratory and was able to dissect the nerve fascicles from the tumor. Home went on to enucleate a tumor from the axillary nerve preserving the underlying fascicles.4 Unfortunately, the patient died on the seventh postoperative day, and an autopsy failed to reveal a cause of death. Subsequently, both Swan and Wood discouraged dissecting tumors from nerves, speculating that the inflammation of the nerve led to Home’s patient’s death.3,5
In the Lancet, Mr. James Syme reported treating a 43-year-old farm laborer who had “a swelling of the forearm on the palmer side, a little above the wrist about as large as a hen’s egg.”6 Mr. Syme assessed the patient as having a neuroma of the median nerve and wrote, “I think before resorting to removal of the hand, an attempt should be made to dissect out the tumor, but the chances of success in accomplishing this being very small.” At the time of operation, he found the tumor intimately connected to the nerve and amputated the hand. On examining the specimen, he found “the tumor itself was of roundish form, of yellow-white color, and pretty firm consistency. The fibers of the nerve were beautifully expanded over its surface.”
Through the early 1800s, there was confusion in distinguishing between traumatic neuromas and nerve tumors. In 1849, R. W. Smith articulated the difference among traumatic, saltatory, and multiple neuromas.7 Nevertheless, Smith continued to advocate en bloc resection over enucleation for fear of causing inflammation of the nerve and death of the patient. Virchow divided peripheral nerve tumors into true tumors, which contained both nerve fibers and elements of the nerve sheath, and fake tumors, which contained only the elements of the nerve sheath.8 By the mid-1800s, surgeons became interested in reestablishing nerve continuity. As noted by Walker, Michon in 1889 and Nelaton in 1863 described management of the sciatic and median nerves, respectively, with en bloc resection followed by reapproximation of the nerve ends.9 Amputation as a primary treatment for peripheral nerve tumors became increasingly less popular, and in 1887, Krause advocated simple excision for well-encapsulated nerve tumors, reserving amputation for recurrent nerve tumors.10
Introduction
Peripheral neural sheath tumors (PNSTs) originate and grow within the nerve.11,12 PNSTs include the schwannoma and neurofibroma, whose differentiation has been clarified using electron microscopy and immunohistochemistry. These same techniques have resulted in a wide acceptance that the principle cell of origin of these tumors is the Schwann cell.13 Benign peripheral non–neural sheath tumors (PNNSTs) can behave aggressively and include ganglions, lipomas, desmoids, ganglioneuromas, hemangiomas, myoblastomas or granular cell tumors, lymphangiomas, and the rare hemangioblastoma or meningioma.
Benign Tumors of Neural Sheath Origin
Schwannoma
Schwannomas are the most common benign tumor of peripheral nerves, yet they account for fewer than 8% of all soft tissue tumors.14 The incidence of benign schwannomas involving peripheral nerve tends to be higher in females than in males. These tumors can occur in patients with NF1; however, neurofibromas are much more common in this population.15
A benign schwannoma of peripheral nerve characteristically presents as a painless, eccentric, oval mass present for some time in a deep location in the course of a nerve or plexal element.16 On palpation, it can be moved laterally, but not longitudinally in the direction that the tumor runs. Percussion over the mass may produce Tinel’s sign, that is, paresthesias in the distribution of the involved nerve.17
Because the growth of peripheral nerve schwannomas usually occurs over many years, large lesions slowly stretch and elongate the fascicles.18,19 Thus, neurological function tends to be intact in these tumors. Loss of function from smaller benign schwannomas is also rare unless a prior biopsy had injured the involved nerve or an unsuccessful attempt at tumor removal had been performed. Under these circumstances, the residual mass may be quite painful, motor loss in the distribution of the involved nerve can be severe, and sensation is markedly impaired or absent. A six-point grade system, based on the level of contraction or movement that can be attained in the affected limb, is used to evaluate the symptoms of neural peripheral nerve tumors (Table 244-1).
TABLE 244-1 Louisiana State University Medical Center Criteria for Grading Muscle Function After Tumor
| GRADE | EVALUATION | DESCRIPTION |
|---|---|---|
| 0 | Absent | No muscle contraction, absent sensation |
| 1 | Poor | Proximal muscles contract but not against gravity; sensory grade 1 or 0 |
| 2 | Fair | Proximal muscles contract against gravity; distal muscles do not contract; sensory grade, if applicable, is usually 2 or lower |
| 3 | Moderate | Proximal muscles contract against gravity and some resistance; some distal muscles contract against at least gravity; sensory grade is usually 3 |
| 4 | Good | All proximal and some distal muscles contract against gravity and some resistance; sensory grade is 3 or better |
| 5 | Excellent | All muscles contract against moderate resistance; sensory grade is 4 or better |
Adapted from Kim DH, Midha R, Murovic J, et al: Kline & Hudsons Nerve Injuries. 2nd ed. Philadelphia: Saunders; 2008.
The cell of origin of the schwannoma is the Schwann cell, which has a basement lamella and is more differentiated than, for example, the perineurial fibroblast. The cells of the tumor are arranged in varying proportions of arrays of cells called Antoni type A and Antoni type B tissues. The Antoni type A tissue of the schwannoma is very cellular with a compact array of spindle-shaped cells. Some of these cells may palisade to form Verocay bodies. The Antoni type B pattern seen in some schwannomas, on the other hand, is less compact and has a loose-textured matrix (Fig. 244-1A). When schwannoma tissue is stained with Alcian blue, a mucopolysaccharide stain, or with reticular stains, the results are less positive than those seen with a neurofibroma. In neurofibromas, connective tissue fibers, especially collagen, are conspicuous elements. In addition, nerve fibers within a neurofibroma are more numerous and more obvious under the microscope than in a schwannoma.
Surgical Approach
The removal of a schwannoma is straightforward; however, serious complications can occur if care is not taken with the dissection and preservation of involved plexal elements or nerves.20–22 Exposure of the nerve of origin well proximal and distal to the lesion is necessary. Other nerves or plexal elements and vessels are dissected away and spared. An area in the circumference of the capsule with few or no fascicles is then opened in a longitudinal fashion. The encapsulated tumor spreads or “baskets” the nerve fascicles apart, displacing them to its periphery.23 These fascicles may be adherent to the outer capsular surface of the tumor, although they are seldom incorporated into the capsule.24
One or sometimes two small fascicles are seen entering and leaving the tumor, and these are exposed and encircled with vasoloops (Fig. 244-1B to D). Stimulation and recording across the fascicles entering and the fascicles leaving each pole of the encapsulated tumor are then performed (Fig. 244-2A and B). Stimulation of the entering fascicles usually does not produce distal muscle function, nor do these fascicles conduct a nerve action potential (NAP) through the tumor to distal elements or nerves. These mostly nonfunctional proximal or distal fascicles are sectioned, and the tumor is removed as a single mass. One way to do this is to section one nonfunctional entering or leaving fascicle, lift the tumor at that pole, and dissect it away from underlying and laterally reflected but retained fascicles. The opposite pole’s nonfunctional fascicle is then sectioned to complete the removal.
An alternative approach sometimes used on large tumors is to open the capsule longitudinally and enucleate the homogenous or sometimes cystic tumoral contents using suction, forceps and scissors, or a Cavitron ultrasonic surgical aspirator (CUSA).25,26 The spared fascicles are teased away from the tumor capsule, which is then resected. The capsule is totally removed to reduce the chance of recurrence, although some surgeons disagree with this concept and leave the capsule.
Some schwannomas become quite large and extend beyond the immediate region of the nerve. These lesions are more difficult to remove, which increases the possibility of recurrence from the remaining tumor or capsule.27
Surgical Outcome
In the recent review of our 30 years of experience treating neural sheath tumors, we found that schwannomas were less common than neurofibromas in both the brachial plexus and the pelvic plexus and that most schwannomas of the brachial plexus region were located supraclavicularly. See Table 244-2 for a summary of this case review.28
We also found that in a representative sample of 76 patients with schwannomas, baseline function was preserved or improved 89% of the time.28 The preoperative and postoperative grades (0 to 6) were compared to determine the effectiveness of surgical treatment (Table 244-3).29
Neurofibroma
There are two groups of neurofibromas. The first group includes the solitary tumor or non-NF1 neurofibroma, which is unassociated with other such tumors.30 This tumor is most likely to be fusiform in appearance.31 The second group of neurofibromas, the plexiform neurofibromas, are seen almost exclusively in conjunction with NF1. Plexiform neurofibromas exhibit multiple nodular growths along a long segment of a major nerve trunk, and these growths extend into the nerve branches. They result in the “bag of worms” appearance on gross inspection and cross-sectional imaging. Fusiform lesions are, however, more likely to be seen in patients with NF1 than are plexiform neurofibromas.
Neurofibromas are intraneural masses, which are more likely to be more painful than schwannomas. Percussion over a neurofibroma usually produces a dramatic Tinel sign.32 Like schwannomas, these tumors, along with their nerve of origin, can be displaced from side to side, but not longitudinally. Pain can become a very severe problem if there has been prior biopsy or attempted removal.33
NF1-associated neurofibromas are found in patients with other stigmata of that disease including café au lait spots, multiple small spots of skin discoloration, skin tags or smaller subcutaneous tumors, Lisch nodules of the iris, and central nervous system tumors such as acoustic neurilemoma or tumors arising from the nerve roots of the spine.34
The neurofibroma has a myxomatous matrix and exhibits a prominent mucopolysaccharide staining (Fig. 244-3A). The intense reticulum staining of the neurofibroma is due to the numerous collagen fibrils in its myxocollagenous background, whereas the schwannoma has a paucity of these collagen fibrils and, hence, stains poorly.
Surgical Approach
The neurofibroma usually has two or more entering and exiting fascicles, which are larger than those seen in a schwannoma, and a capsule that is more adherent to the central mass of the tumor than that of a schwannoma (Fig. 244-3B). A large neurofibroma can sometimes be approached from above the inferiorly located fascicles or below fascicles located superiorly at the tumor’s proximal or distal ends. The entering or exiting fascicles are then dissected free, sectioned, and used to elevate the tumor. This maneuver allows the dissection of fascicular structures away from the tumor, beginning at one end until the opposite pole is reached.
Fascicles entering and exiting the tumor are tested by stimulating the proximal fascicles and recording NAPs from the distal ones. As with the schwannoma, if traces are flat, the entering and exiting fascicles can be sacrificed, and the tumor can be removed as a solitary mass (Fig. 244-3C and D). If NAPs are positive across these fascicles, the fascicles need to be traced into and out of the tumor and spared. At times, even these fascicles need to be sacrificed to achieve resection of the tumor. In these cases, fascicular defects can be replaced by grafts or, on occasion, partial fascicular graft repairs. Even a large fusiform lesion can be associated with multiple smaller neurofibromas or neurofibromatous change in nerve both above and below the lesion, necessitating similar graft repair.
Surgical Outcome
Most of the benign tumors of the brachial plexus treated by us in a 30-year period at LSUHSC were neurofibromas (62%); 63% of these were sporadic solitary neurofibromas, and 37% were neurofibromas removed from patients with NF1. The tumors associated with NF1 were completely removed in 56% of cases and partially resected in 44%. See Table 244-2 for a complete listing of the results of this series.
In the LSUHSC review, the NF1-associated neurofibromas were excised in most cases without producing a serious deficit even when they involved a major nerve. Owing to the more difficult dissection of neurofibromas in patients with NF1, resolution of symptoms was often not as good as that in patients without NF1. Nonetheless, in patients with NF1 in whom neurofibromas were resected, 83% had stable or improved motor function. Because neurofibromas in patients with NF1 are more likely to be plexiform, the incidence of total resection was 76%, compared with all tumors in patients harboring solitary neurofibromas.28
A series of 99 solitary neurofibromas and 48 NF1-associated neurofibromas was studied by comparing the symptomatic grade before and after surgical treatment. See Table 244-3 for a summary of the results of this case series.29
Surgical treatment of plexiform neurofibromas (Fig. 244-4A) tends to be difficult, but it is possible when there are good indications such as symptomatic tumors involving sensory nerves or branches. In our experience, complete removal generally was not possible without a loss of neurological function. In some cases, even subtotal removal of a plexiform tumor led to some loss of function. Nerve sections proximal and distal to the lesion, followed by repair of the often lengthy gap, did not usually restore function. For large tumors or in cases in which severe pain was a dominant symptom, decompression with removal of a portion of the tumor bulk provided benefit (Fig. 244-4B
