Segmental Schwannomatosis of the Upper Extremity

Abstract

Schwannomatosis is characterized by the development of multiple schwannomas without evidence of vestibular tumors. Segmental schwannomatosis is defined as being limited to 1 limb or 5 or fewer contiguous segments of the spine. We report a case of a 38-year-old male with multiple, painful masses of the right upper extremity with associated numbness and paresthesia in the ulnar and radial nerve distribution. An open, microsurgical approach provided definitive diagnosis and treatment. Twenty-one cases of segmental schwannomatosis of the upper extremity have been reported in the literature, making this case the 22nd. It is 1 of 5 cases of segmental schwannomatosis to have simultaneous tumors in the forearm and hand. We are the first to report multiple schwannomas of the ulnar and ulnar sensory nerve and the second to report multiple schwannomas of the radial sensory nerve. We additionally review the literature regarding pathogenesis, diagnosis, and treatment of this uncommon tumor.

Introduction

A schwannoma (neurilemmoma) is the most common peripheral nerve tumor yet constitutes only 5% of all soft tissue tumors. ¹ Schwannomatosis, defined by the development of multiple schwannomas without evidence of vestibular tumors, represents one of the 3 major forms of NF. ² A rare variant of schwannomatosis is segmental schwannomatosis, characterized as being limited to 1 limb or 5 or fewer contiguous segments of the spine. ³

Twenty-one cases of segmental schwannomatosis of the upper extremity have been reported to date in the English literature, ^{1 –9} making this case the 22nd. To add to the rarity of this report, it is 1 of 5 cases of segmental schwannomatosis to have simultaneous tumors in the forearm and hand. ^4,7,9 Additionally, to the extent of our knowledge, we are the first to report a case of multiple schwannomas of the ulnar and ulnar sensory nerve and the second to report a case of multiple schwannomas of the radial sensory nerve. ²

Case Report

A 38-year-old Caucasian male ballroom dance instructor presented with complaints in the right hand, wrist, and forearm soft tissue masses of 15 years duration. The masses were progressively painful and incapacitating with associated numbness and paresthesia in the ulnar and radial nerve distributions. Physical examination revealed multiple, firm, nodular, fixed masses of varying sizes of the right upper extremity (RUE) extending along the volar forearm and dorsal wrist and hand. Positive Tinel’s sign was demonstrated at each lesion with distal sensation diminished. Motor function was intact with strength +4/5 due to inability to grasp strenuously secondary to pain. He had no symptoms of vestibular dysfunction. Magnetic resonance imaging (MRI) of the RUE revealed multiple nodular masses with evidence of high lipid content. (Figure 1)

Figure 1.

Magnetic resonance imaging of the right upper extremity with nerve cell lesions following the ulnar, ulnar sensory, and radial sensory nerve distribution.

Due to the patient’s progressive pain and neurological symptoms, an open, microsurgical technique was indicated for approach, dissection, and removal of tumors. Surgical exploration and excision of 5 separate intraneural tumors from the dorsal ulnar sensory nerve sheath of the RUE were performed with the use of nerve wrap (NeuraGen—Stryker Medical, Bloomington, Indiana) for nerve reconstruction. Four months after the initial surgery, surgical exploration and excision of 9 separate intraneural tumors from the ulnar nerve, dorsal ulnar sensory nerve, and radial sensory nerve of the RUE were performed (Figure 2). The ulnar nerve was found to be frayed but intact; therefore, nerve wrap (NeuraGen—Stryker Medical, Bloomington, Indiana) was placed along the ulnar nerve in areas of greatest dissection (Figure 3). All tumors histopathologically diagnosed as schwannomas (Figure 4).

Figure 2.

The right upper extremity segmental schwannomatosis of the distal ulnar nerve (A) before excision (B) after excision.

Figure 3.

Collagen nerve wrap of the ulnar nerve.

Figure 4.

(A) Low magnification of a section of one of the schwannomas. It is composed of areas with increased and decreased cellularity (so-called Antoni A and B areas) and is surrounded by a thin capsule. B, Higher magnification showing nerve fibers within the capsule surrounding the schwannoma. C, Higher magnification with rows of nuclei adjacent to areas of fibrillar stroma, representing a Verocay body. This finding is essentially diagnostic of a schwannoma.

At 3-year follow-up, the patient had developed new masses in areas of prior excision. The masses were painful and interfered with function. The right upper extremity surgical revision was performed with excision of 4 intraneural tumors of the radial sensory nerve at the wrist and ulnar sensory branches in the hypothenar eminence. Again, nerve wrap (Axoguard—Axogen Medical, Alachua, Florida) was utilized, and all tumors histopathologically diagnosed as schwannomas. By postoperative day 10, patient had complete resolution of pain with intact neural function. Follow-up at 3 years revealed no recurrence of tumors or clinical symptoms.

Discussion

Pathogenesis

Schwannomatosis can broadly be divided into 2 classes, sporadic—80% to 85% and familial—15% to 20%. ¹⁰ Presentation of schwannomatosis is usually multiple, palpable, well-circumscribed masses of the flexor surfaces. ¹ Race and gender are affected equally with occurrence between 30 and 60 years of age. ⁴ The most common symptoms are pain, sensory deficits, or paresthesia. ^1,4 Neurological examination does not demonstrate vestibular or optic nerve involvement, and family history is negative for central nervous system disease processes and cutaneous tumors. ²

There are several types of soft tissue masses in the extremities that must be carefully differentiated from schwannomatosis. Differential diagnosis should include lipoma, lymph node, epidermoid inclusion cyst, malignant peripheral nerve sheath tumor, benign/malignant schwannoma, ganglion cyst, neurofibroma, and perineuriomas. ⁴ The evaluation of schwannomas involves careful clinical assessment of the patient in conjunction with imaging, histopathological analysis, and potentially molecular testing. ¹⁰

It is important to distinguish between neurofibroma and schwannoma because the natural history, treatment, and genetic risks are markedly different. ¹ Neurofibromatosis type II (NF2) is due to a germline mutation on chromosome 22q12, characterized by bilateral vestibular schwannomas, and symptomatic at a relatively young age with dysfunction. ⁴ Neurofibromas are not encapsulated, and there is potential for malignant degeneration. ¹⁰

The etiology of schwannomatosis is unclear, but there has been notable advancement in research involving molecular and genetic origin of schwannomatosis. Molecular investigation of the NF2 gene in patients with schwannomatosis phenotype has not shown germline mutations but has confirmed frameshift, nonsense, and truncating mutations. ¹⁰ The SMARCB1, a tumor suppressor gene, is thought to be closely related to schwannomatosis and occurs in 40% to 50% of familial cases and 8% to 10% of sporadic cases. ^4,10 The CABINI gene has been recognized in the pathogenesis of NF2 and schwannomatosis. ⁴ The future molecular and genetic research goals of schwannomatosis are to detect additional genes that predispose to schwannomatosis and further understanding of chromosome 22 in schwannoma development. ¹⁰

Imaging and Histopathology

The imaging and histopathological characteristics of schwannomatosis are parallel to those of solitary schwannomas. ⁴ Diagnostic tools include ultrasonography, computed tomography, MRI, and nerve conduction studies. ¹ Magnetic resonance imaging being the most valuable in assistance with diagnosis of schwannoma—isointense to muscles on T1-weighted images, hyperintense to high lipid content tissue on T2-weighted images, and homogeneous enhancement with gadolinium. ³ Schwannomas appear as well-defined, rounded lesions distributed along the course of the peripheral nerve in the extremities (Figure 1). ² A cranial MRI additionally may be performed to assess the evidence of vestibular schwannomas. ⁴ Schwannomas are encapsulated, well-circumscribed, spindle cell tumors with diffuse expression of S100 protein on immunochemistry. The histopathological appearance is characterized by the pattern of cellular elements—Antoni A, Antoni B, and Verocay bodies (Figure 4). ³

Surgical Strategy

Managing patients with schwannomatosis is an evolving course with surgical intervention reserved to prevent progressive neurological deficit. ³ Additionally, patients should be counseled regarding the potential for surgical iatrogenic nerve injury and the relatively high possibility of local recurrence or formation of new lesions. ⁹ Currently, there are no drug therapies recommended for the treatment of schwannomatosis as a surgical alternative. ¹⁰

Schwannomas typically can be completely enucleated during excision; however, if there is fascicular distention, removal of the tumor may result in neuropraxia of the fascicles and can cause functional deficit. ¹¹ When planning the surgical approach, one must take into consideration history and physical examination, type of nerve involved, and extent of nerve damage. Nerve conduits have never been documented as part of the surgical treatment in schwannomas. Since 1990, nerve conduit has been used in digital nerve repair with comparable long-term autograft results. ¹² In addition, nerve wrap used in recurrent compression neuropathies has been reported as being successful. ^13,14 We combined these concepts and performed a nerve wrap of the ulnar and radial nerve trunk when found to be frayed but intact during our operative procedure. Wrap techniques are theorized to provide a contained conduit that allows nerves to glide, protection from perineural scar formation, and creation of a favorable microenvironment. ¹⁴ The collagen conduit may also be advantageous if there is need to resect a small neural segment with the tumor and to avoid morbidity associated with harvesting of autograft. ^11,12 Overall, nerve conduit provides a practical and effective technique for the treatment of local nerve damage during excision of the upper extremity schwannomatosis.

Conclusion

An awareness of segmental schwannomatosis should provide the ability to make the diagnosis clinically in conjunction with imaging, histopathology, and molecular testing. ² Surgical intervention is reserved for prevention of progressive neurological deficit and patients should be counseled as to the possibility for recurrence or formation of new lesions. ⁹ Schwannomas typically can be completely enucleated; however, if there is fascicular distention, removal of the tumor may result in neuropraxia of the fascicles with residual functional deficit. ⁹ Nerve wrap can aid surgical excision and theoretically provide a contained conduit which allows nerves to glide, protection from perineural scar formation, and creation of a favorable microenvironment. ¹⁴