Tumors of the Brachial Plexus

Abstract

• »Tumors of the brachial plexus are uncommon and can present as a mass, with or without neurological symptoms. At times, asymptomatic tumors are also picked up incidentally when imaging is performed for other reasons.
• »Magnetic resonance imaging is the main imaging modality used to evaluate tumors of the brachial plexus. Other imaging modalities can be used as required.
• »Benign tumors that are asymptomatic should be observed. Excision can be considered for those that are found to be growing over time.
• »Biopsies of tumors of the brachial plexus are associated with the risk of nerve injury. Despite this, they should be performed for tumors that are suspected to be malignant before starting definitive treatment.
• »For malignant tumors, treatment decisions should be discussed at multidisciplinary tumor boards, and include both the oncology and peripheral nerve surgical team, musculoskeletal radiology, neuroradiology, and general radiology.

Less than 5% of upper extremity tumors originate from the brachial plexus. The true incidence, however, is not known, since there may be many small, asymptomatic lesions that are not detected or reported. However, a significant proportion (about one-third) of peripheral nerve tumors involve the brachial plexus^1-3. This is possibly because of the large nerve volume contained in the plexus.

Within this structure, the tumors can be intrinsic, arising from nerve tissue, or they can be extrinsic, arising from the surrounding tissue. Cancers affecting the brachial plexus can also arise from adjacent organs such as the breasts, lungs, or lymph nodes. One example is the Pancoast tumor, which was first described by Hare in 1838 as “a tumor affecting certain nerves.”^4,5 The last etiology is metastatic—though this is rare, these tumors can arise from almost any primary tumor site. A variant of metastatic tumors, neurolymphomatosis, where the peripheral nerves are involved in patients with advanced lymphoma, can also arise within the brachial plexus⁶.

In a systematic review by Shekouhi and Chim⁷, 91% of brachial plexus tumors reported were benign while 9% were malignant. Among the benign tumors, the majority were schwannomas (61%) and neurofibromas (18%), with a smaller number of other types of tumors like lipomas, desmoid tumors, and hemangiomas. Most malignant tumors were malignant peripheral nerve sheath tumors (MPNSTs), comprising 7% of all tumors of the brachial plexus while other malignant tumors like synovial sarcomas and lymphomas were also described. Most of the lesions were found to originate in the supraclavicular region (70%)⁷.

Clinical Presentation

Patients with tumors of the brachial plexus tend to present in middle age, 41.7 ± 8.7 years (range, 1-92 years), with a slight female preponderance. 11.5% have a history of neurofibromatosis. The most common clinical symptom is swelling (65%), followed by neural symptoms such as paresthesias (47%), sensory deficits (48%), and motor deficits (19%).

Patients with malignant tumors tend to have bigger tumors (>5 cm) that are fast growing, and because of their invasive nature, they tend to have neurological deficits more frequently at the time of presentation. Treatment is often delayed, with the mean duration of symptoms before medical intervention of 25.2 ± 12.3 months⁷.

There are also patients who present after tumors are incidentally picked up (“incidentalomas”) on imaging performed to evaluate other conditions. These tumors are almost always asymptomatic.

Workup and Diagnosis

Imaging Studies

Magnetic resonance imaging (MRI) is the mainstay of imaging for soft-tissue tumors. Some of the findings for schwannomas include a round or fusiform shape and eccentric location in the nerve. They appear isointense or slightly hyperintense to the skeletal muscle on T1 sequences and hyperintense on T2-weighted images. By contrast, neurofibromas tend to occupy a central location within the nerve and frequently exhibit a target sign on T2 sequences, with low-signal intensity in the center and a peripheral rim of higher signal intensity (though the target sign is not unique to neurofibromas). Neurofibromas also exhibit a predominantly central enhancement pattern after contrast injection. Cystic or hemorrhagic changes are less commonly seen in neurofibromas compared with schwannomas. Additional MRI methods like diffusion-weighted imaging can also be helpful in differentiating between schwannomas and neurofibromas^8,9.

Ultrasound imaging is useful in differentiating between benign and malignant tumors of the brachial plexus. Benign tumors tend to be well defined and without associated peritumoral edema. They also exhibit either no or homogeneous enhancement after contrast injection. Malignant tumors tend to be poorly defined. Peritumoral edema is frequently seen, as well as central necrosis and hemorrhage. They also exhibit heterogeneous enhancement with contrast^8,10.

Another modality that can help in this critical diagnostic differentiation is 18-fluorodeoxyglucose positron emission tomography scans. Malignant tumors tend to have higher metabolic activity, which is reflected by a higher maximum standardized uptake value. The cutoff level between benign and malignant tumors is still a matter of debate. However, when used in conjunction with other imaging modalities like MRI scans, the diagnostic accuracy is improved¹¹.

In patients with type 1 neurofibromatosis, sequential imaging may be required, due to the higher risk of developing malignancies, need to monitor multiple nerve sheath tumors, and the poorer survival prognosis for these patients¹².

Role of Biopsy

It is not uncommon for a diagnosis to remain indeterminate after imaging¹³. Since there is a big difference between the treatment approaches for benign and malignant tumors, and also between different types of malignant tumors, it is important to establish a clear working diagnosis before initiating treatment. Biopsies of the brachial plexus are challenging as they have the dual risk of damage to a nerve, and the difficulty and unpredictability of operating in a field where there is possible malignant tissue. While there is a risk of contamination of the surgical field and compromising the outcome for the patient during all biopsies¹⁴, this is especially critical in the brachial plexus. Balancing all these factors, it may be better in some cases, especially where the suspicion of malignancy is low, to opt for close observation and early repeat imaging, rather than intervening immediately. Conversely, should the suspicion of malignancy be high, then it is better to proceed with a biopsy to get a definitive diagnosis before treatment is initiated.

It is tempting to proceed with a marginal excision of the mass, given the concerns of both avoiding progression of the tumor, and avoiding multiple procedures for the patient when performing a biopsy alone. However, a bigger morbidity can be caused when incomplete excision of a malignant tumor is performed. The resultant contamination of the surgical field will make subsequent surgical clearance very difficult, possibly converting a salvageable situation into one that is not^15,16. Hence, it is important that these cases be discussed at multidisciplinary team meetings before a decision on biopsy or surgical excision is made.

Treatment Strategy

A summary of the treatment strategy for the various tumor types is provided in Table I.

TABLE I.

Treatment of Brachial Plexus Tumors^*

Tumor Type	Considerations	Suggested Treatment
Benign
Intrinsic
Schwannoma	Marked increase in size/worsening neurological deficit	Marginal excision
	Stable size/minimal neurological deficit	Observation
Neurofibroma	Marked increase in size, severe neurological deficit	Excision possible reconstruction
	Stable size/nonprogressive neurological deficit	Observation
Perineurioma		Observation unless there is marked progression
Lipofibromatous hamartoma		Observation unless there is marked progression
Extrinsic
Lipoma		Observation unless there is marked progression/suspicion of atypical lipomatous tumor
Hemangioma		Observation unless there is marked progression
Desmoid tumor		Discussion at MTB. Observation unless there is marked progression—to consider nonsurgical options as well
Malignant
Intrinsic
MPNST		Discussion at MTB. Consider neoadjuvant radiotherapy before resection
Extrinsic
Other sarcomas		Discussion at MTB. Consider neoadjuvant radiotherapy before resection
Other malignant tumors		Discussion at MTB. Treatment dependent on symptoms and cancer type

^*MPNST = malignant peripheral nerve sheath tumor, and MTB = multidisciplinary tumor board.

Benign Tumors

Many benign tumors, especially those that are asymptomatic and/or are picked up incidentally, can be observed. Schwannomas, which are the most common tumors, may not need to be excised unless they are causing significant functional deficits or when there is a significant rate of growth.

Lubelski et al. found that solitary schwannomas tend to fall into slow or fast growing categories. Sequential imaging makes extrapolation of the rate of growth of the tumor possible, and this guides the decision for surgery. Size alone is not a definite indication for surgery³.

When required, schwannomas can be excised using techniques that lower the risk of neural morbidity. In most of the cases, with control of the proximal and distal aspects of the involved nerve, complete excision can be performed by sharp separation under magnification from the surrounding fascicles, preserving the uninvolved fascicles.

Neurofibromas, on the other hand, can only rarely be completely excised without deficits, and the balance between the morbidity of surgery and the desire for complete removal needs to be considered. Neurofibromas tend to involve more nerve fascicles, and excision is not possible without their sacrifice. Should these fascicles serve important functions, significant morbidity for the patient will result. Selective sacrifice of nerves is possible in the course of an excision when intraoperative nerve stimulation is used. Occasionally, subtotal excision of a benign tumor may need to be performed to preserve function^2,17. Hence, careful consideration needs to be taken when deciding whether to attempt excision of a neurofibroma—often, it may be better not to excise the tumor and accept the symptoms and/or nerve deficit.

Low recurrence rates are seen in patients with schwannomas and neurofibromas following gross total resection^2,17,18. Most experience improvements clinically, with decreased pain and improved sensation, even if gross total resection was not achieved. However, approximately 15% still reported persistent or significant pain^2,18, while up to 25% reported worsened motor function following surgery¹⁸.

When a deficit occurs, reconstruction with nerve transfers, tendon transfers, or nerve grafting should be part of the treatment plan communicated to the patient. It is not often that this can be anticipated; hence, reconstruction will need to be performed in a staged manner. The exact technique of reconstruction used will depend on the deficit encountered.

The treatment of benign extrinsic tumors follow similar principles and are also determined by the primary pathology. For example, lipomas and hemangiomas can also be excised without deficits.

Malignant Tumors

For malignant tumors, the aim of treatment is focused on the preservation of life followed by salvage of the limb. There are different treatment options for different malignant tumors; hence, it is recommended that a biopsy be performed, despite the risks, so that a definite diagnosis can be established, before definitive treatment.

MPNSTs are the most commonly encountered malignant tumors in the brachial plexus. The best outcomes for MPNSTs and other sarcomas are achieved with complete resection of the tumor^19,20. An example of the management of such a case is illustrated in Figures 1, 2, and 3.

Figs. 1-A, 1-B, and 1-C MRI images showing a soft-tissue mass around the brachial plexus. A core biopsy was performed, and histology showed a synovial sarcoma. MRI = magnetic resonance imaging.

Fig. 1-A.

Fig. 1-B.

Fig. 1-C.

Fig. 2.

Wide excision of the mass was performed. The surgical approach required osteotomy of the clavicle.

Fig. 3.

Complete excision with clear margins was achieved. The patient had no neurological deficits after surgery and underwent postoperative radiotherapy. He remained disease-free 6 years after treatment and was subsequently lost to follow-up.

There is conflicting data about benefit of both radiotherapy and chemotherapy^19-23, and the decision on the appropriate treatment for each patient should be discussed at a multidisciplinary tumor board.

Despite the difficulties created during surgery, our preferred option for MPNSTs (and other high grade sarcomas) is for preoperative radiotherapy, followed by complete resection of the tumor. If intraplexal reconstruction is required, then it can be performed at the same time as tumor resection, since attempting to do so in a staged manner following preoperative radiotherapy is expected to be extremely difficult.

For lymphomas, surgery is generally not required, with chemotherapy and radiotherapy being the main modalities used. For extrinsic malignancies, there may be a benefit in excising tumors arising from adjacent organs that abut and compress the brachial plexus. However, we have not found any benefit for surgery in patients where there is evidence of direct invasion causing neurological deficits. When there is interfascicular spread of the tumor, w nerve-preserving excision is not possible. In patients with advanced local disease with no evidence of distant metastases, options like forequarter amputations can be considered.

In patients with metastatic disease, resection of the tumor is not possible or required, and maximal efforts should be made to manage symptoms and pain.

A summary of the recommendations for care is presented in Table II.

TABLE II.

Recommendations for Care in Patients with Brachial Plexus Tumors^*

Recommendations	Grade of Evidence†
Imaging for brachial plexus tumors
MRI	B
Ultrasound	B
18-FDG PET scans	B
Role of biopsy in diagnosis of brachial plexus tumors	I
Conservative excision for benign brachial plexus tumors	C
Wide excision for sarcomas involving the brachial plexus	C
Adjuvant treatment (radiotherapy and chemotherapy) for MPNSTs	I

^*18-FDG PET = 18-fluorodeoxyglucose positron emission tomography, MPNST = malignant peripheral nerve sheath tumor, and MRI = magnetic resonance imaging.

^†According to Wright²⁴, grade A indicates good evidence (Level I studies with consistent findings) for or against recommending intervention; grade B, fair evidence (Level II or III studies with consistent findings) for or against recommending intervention; grade C, poor-quality evidence (Level IV or V studies with consistent findings) for or against recommending intervention; and grade I, insufficient or conflicting evidence not allowing a recommendation for or against intervention.

Conclusion

The treatment of brachial plexus tumors is dependent on the diagnosis, severity of symptoms, and rate of growth. Benign tumors that are asymptomatic and picked up incidentally should be observed while those that are growing and/or causing severe symptoms may need to be excised or debulked. In cases where the diagnosis is not clear, observation with sequential imaging can be considered before a biopsy or excision. Finally, for tumors that are more likely malignant, a biopsy and discussion at a multidisciplinary tumor board before starting definitive treatment is recommended.

Sources of Funding

No funding was provided in the investigation of this study.