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Surgical management of malignant melanotic nerve sheath tumors: an institutional experience and systematic review of the literature

Abdul Karim Ghaith, Sarah E. Johnson, Victor Gabriel El-Hajj, Oluwaseun O. Akinduro, Marc Ghanem, Gaetano De Biase, Loizos Michaelides, Antonio Bon Nieves, W. Richard Marsh, Bradford L. Currier, John L. Atkinson, Robert J. Spinner, and Mohamad Bydon

OBJECTIVE

Malignant melanotic nerve sheath tumors are rare tumors characterized by neoplastic melanin-producing Schwann cells. In this study, the authors report their institution’s experience in treating spinal and peripheral malignant melanotic nerve sheath tumors and compare their results with the literature.

METHODS

Data were collected from 8 patients who underwent surgical treatment for malignant melanotic nerve sheath tumors between 1996 and 2023 at Mayo Clinic and 63 patients from the literature. Time-to-event analyses were performed for the combined group of 71 cases to evaluate the risk of recurrence, metastasis, and death based on tumor location and type of treatment received. Unpaired 2-sample t-tests and Fisher’s exact tests were used to determine statistical significance between groups.

RESULTS

Between 1996 and 2023, 8 patients with malignant melanotic nerve sheath tumors underwent surgery at the authors’ institution, while 63 patients were identified in the literature. The authors’ patients and those in the literature had the same mean age at diagnosis (43 years). At the authors’ institution, 5 patients (63%) experienced metastasis, 6 patients (75%) experienced long-term recurrence, and 5 patients (62.5%) died. In the literature, most patients (60.3%) were males, with a peak incidence between the 4th and 5th decades of life. Nineteen patients (31.1%) were diagnosed with Carney complex. Nerve root tumors accounted for most presentations (n = 39, 61.9%). Moreover, 24 patients (38.1%) had intradural lesions, with 54.2% (n = 13) being intramedullary and 45.8% (n = 11) extramedullary. Most patients underwent gross-total resection (GTR) (n = 41, 66.1%), followed by subtotal resection (STR) (n = 12, 19.4%), STR with radiation therapy (9.7%), and GTR with radiation therapy (4.8%). Sixteen patients (27.6%) experienced metastasis, 23 (39.7%) experienced recurrence, and 13 (22%) died. Kaplan-Meier analyses showed no significant differences among treatment approaches in terms of recurrence-free, metastasis-free, and overall survival (p > 0.05). Similar results were obtained when looking at the differences with respect to intradural versus nerve root location of the tumor (p > 0.05).

CONCLUSIONS

Malignant melanotic nerve sheath tumors are rare tumors with a high potential for malignancy. They carry a dismal prognosis, with a pooled local recurrence rate of 42%, distant metastasis rate of 27%, and mortality rate of 26%. The findings from this study suggest a trend favoring the use of GTR alone or STR with radiation therapy over STR alone. Mortality was similar regardless, which highlights the need for the development of effective treatment options to improve survival in patients with melanotic schwannomas.

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Letter to the Editor. C5 nerve sheath tumors and new postoperative weakness

Lei Zhao, Liwei Peng, Peng Wang, and Weixin Li

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Perineural spread of peripheral neurolymphomatosis to the cauda equina

Nikhil K. Murthy, Kimberly K. Amrami, Stephen M. Broski, Patrick B. Johnston, and Robert J. Spinner

OBJECTIVE

Neurolymphomatosis (NL) is a rare manifestation of lymphoma confined to the peripheral nervous system that is poorly understood. It can be found in the cauda equina, but extraspinal disease can be underappreciated. The authors describe how extraspinal NL progresses to the cauda equina by perineural spread and the implications of this on timely and safe diagnostic options.

METHODS

The authors used the Mayo Clinic medical records database to find cases of cauda equina NL with sufficient imaging to characterize the lumbosacral plexus diagnosed from tissue biopsy. Demographics (sex, age), clinical data (initial symptoms, cerebrospinal fluid, evidence of CNS involvement, biopsy location, primary or secondary disease), and imaging findings were reviewed.

RESULTS

Ten patients met inclusion and exclusion criteria, and only 2 of 10 patients presented with cauda equina symptoms at the time of biopsy, with 1 patient undergoing a cauda equina biopsy. Eight patients were diagnosed with diffuse large B-cell lymphoma, 1 with low-grade B-cell lymphoma, and 1 with mantle cell lymphoma. Isolated spinal nerve involvement was identified in 5 of 10 cases, providing compelling evidence regarding the pathophysiology of NL. The conus medullaris was not radiologically involved in any case. Lumbosacral plexus MRI was able to identify extraspinal disease and offered diagnostically useful biopsy targets. FDG PET/CT was relatively insensitive for detecting disease in the cauda equina but was helpful in identifying extraspinal NL.

CONCLUSIONS

The authors propose that perineural spread of extraspinal NL to infiltrate the cauda equina occurs in two phases. 1) There is proximal and distal spread along a peripheral nerve, with eventual spread to anatomically connected nerves via junction and branch points. 2) The tumor cells enter the spinal canal through corresponding neural foramina and propagate along the spinal nerves composing the cauda equina. To diffusely infiltrate the cauda equina, a third phase occurs in which tumor cells can spread circumdurally to the opposite side of the spinal canal and enter contralateral nerve roots extending proximally and distally. This spread of disease can lead to diffuse bilateral spinal nerve disease without diffuse leptomeningeal spread. Recognition of this phasic mechanism can lead to identification of safer extraspinal biopsy targets that could allow for greater functional recovery after appropriate treatment.

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Do all outpatient spine surgeries cost the same? Comparison of economic outcomes data from a state-level database for outpatient lumbar decompression performed in an ambulatory surgery center or hospital outpatient setting

Mohammed Ali Alvi, Waseem Wahood, Shyam J. Kurian, Jad Zreik, Molly M. Jeffery, James M. Naessens, Robert J. Spinner, and Mohamad Bydon

OBJECTIVE

Spinal procedures are increasingly conducted as outpatient procedures, with a growing proportion conducted in ambulatory surgery centers (ASCs). To date, studies reporting outcomes and cost analyses for outpatient spinal procedures in the US have not distinguished the various outpatient settings from each other. In this study, the authors used a state-level administrative database to compare rates of overnight stays and nonroutine discharges as well as index admission charges and cumulative 7-, 30-, and 90-day charges for patients undergoing outpatient lumbar decompression in freestanding ASCs and hospital outpatient (HO) settings.

METHODS

For this project, the authors used the Florida State Ambulatory Surgery Database (SASD), offered by the Healthcare Cost and Utilization Project (HCUP), for the years 2013 and 2014. Patients undergoing outpatient lumbar decompression for degenerative diseases were identified using CPT (Current Procedural Terminology) and ICD-9 codes. Outcomes of interest included rates of overnight stays, rate of nonroutine discharges, index admission charges, and subsequent admission cumulative charges at 7, 30, and 90 days. Multivariable analysis was performed to assess the impact of outpatient type on index admission charges. Marginal effect analysis was employed to study the difference in predicted dollar margins between ASCs and HOs for each insurance type.

RESULTS

A total of 25,486 patients were identified; of these, 7067 patients (27.7%) underwent lumbar decompression in a freestanding ASC and 18,419 (72.3%) in an HO. No patient in the ASC group required an overnight stay compared to 9.2% (n = 1691) in the HO group (p < 0.001). No clinically significant difference in the rate of nonroutine discharge was observed between the two groups. The mean index admission charge for the ASC group was found to be significantly higher than that for the HO group ($35,017.28 ± $14,335.60 vs $33,881.50 ± $15,023.70; p < 0.001). Patients in ASCs were also found to have higher mean 7-day (p < 0.001), 30-day (p < 0.001), and 90-day (p = 0.001) readmission charges. ASC procedures were associated with increased charges compared to HO procedures for patients on Medicare or Medicaid (mean index admission charge increase $4049.27, 95% CI $2577.87–$5520.67, p < 0.001) and for patients on private insurance ($4775.72, 95% CI $4171.06–$5380.38, p < 0.001). For patients on self-pay or no charge, a lumbar decompression procedure at an ASC was associated with a decrease in index admission charge of −$10,995.38 (95% CI −$12124.76 to −$9866.01, p < 0.001) compared to a lumbar decompression procedure at an HO.

CONCLUSIONS

These “real-world” results from an all-payer statewide database indicate that for outpatient spine surgery, ASCs may be associated with higher index admission and subsequent 7-, 30-, and 90-day charges. Given that ASCs are touted to have lower overall costs for patients and better profit margins for physicians, these analyses warrant further investigation into whether this cost benefit is applicable to outpatient spine procedures.

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Incidence and risk factors for prolonged postoperative opioid use following lumbar spine surgery: a cohort study

Anshit Goyal, Stephanie Payne, Lindsey R. Sangaralingham, Molly Moore Jeffery, James M. Naessens, Halena M. Gazelka, Elizabeth B. Habermann, William Krauss, Robert J. Spinner, and Mohamad Bydon

OBJECTIVE

Sustained postoperative opioid use after elective surgery is a matter of growing concern. Herein, the authors investigated incidence and predictors of long-term opioid use among patients undergoing elective lumbar spine surgery, especially as a function of opioid prescribing practices at postoperative discharge (dose in morphine milligram equivalents [MMEs] and type of opioid).

METHODS

The OptumLabs Data Warehouse (OLDW) was queried for postdischarge opioid prescriptions for patients undergoing elective lumbar decompression and discectomy (LDD) or posterior lumbar fusion (PLF) for degenerative spine disease. Only patients who received an opioid prescription at postoperative discharge and those who had a minimum of 180 days of insurance coverage prior to surgery and 180 days after surgery were included. Opioid-naive patients were defined as those who had no opioid fills in 180 days prior to surgery. The following patterns of long-term postoperative use were investigated: additional fills (at least one opioid fill 90–180 days after surgery), persistent fills (any span of opioid use starting in the 180 days after surgery and lasting at least 90 days), and Consortium to Study Opioid Risks and Trends (CONSORT) criteria for persistent use (episodes of opioid prescribing lasting longer than 90 days and 120 or more total days’ supply or 10 or more prescriptions in 180 days after the index fill). Multivariable logistic regression was performed to identify predictors of long-term use.

RESULTS

A total of 25,587 patients were included, of whom 52.7% underwent PLF (n = 13,486) and 32.5% (n = 8312) were opioid-naive prior to surgery. The rates of additional fills, persistent fills, and CONSORT use were 47%, 30%, and 23%, respectively, after PLF and 35.4%, 19%, and 14.2%, respectively, after LDD. The rates among opioid-naive patients were 18.9%, 5.6%, and 2.5% respectively, after PLF and 13.3%, 2.0%, and 0.8%, respectively, after LDD. Using multivariable logistic regression, the following were identified to be significantly associated with higher risk of long-term opioid use following PLF: discharge opioid prescription ≥ 500 MMEs, prescription of a long-acting opioid, female sex, multilevel surgery, and comorbidities such as depression and drug abuse (all p < 0.05). Elderly (age ≥ 65 years) and opioid-naive patients were found to be at lower risk (all p < 0.05). Similar results were obtained on analysis for LDD with the following significant additional risk factors identified: discharge opioid prescription ≥ 400 MMEs, prescription of tramadol alone at discharge, and inpatient surgery (all p < 0.05).

CONCLUSIONS

In an analysis of pharmacy claims from a national insurance database, the authors identified incidence and predictors of long-term opioid use after elective lumbar spine surgery.

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A significant association between C5 nerve sheath tumors and new postoperative weakness

Anthony L. Mikula, Brandon W. Smith, Nikita Lakomkin, Matthew K. Doan, Megan M. Jack, Mohamad Bydon, and Robert J. Spinner

OBJECTIVE

The objective of this study was to determine if patients with nerve sheath tumors affecting the C5 spinal nerve are at greater risk for postoperative weakness than those with similar tumors affecting other spinal nerves contributing to the brachial plexus.

METHODS

A retrospective chart review (1998–2020)identified patients with pathologically confirmed schwannomas or neurofibromas from the C5 to T1 nerves. Patients with plexiform nerve sheath tumors, tumors involving more than 1 nerve, and malignant peripheral nerve sheath tumors were excluded. Collected variables included basic demographics, tumor dimensions, its location relative to the dura, involved nerve level, surgical approach, extent of resection, presenting symptoms, postoperative neurological deficits, and recurrence rate.

RESULTS

Forty-six patients (23 men, 23 women) were identified for inclusion in the study with an average age of 47 ± 17 years, BMI of 28 ± 5 kg/m , and follow-up of 32 ± 45 months. Thirty-nine patients (85%) had schwannomas and 7 (15%) had neurofibromas. Tumors involved the C5 (n = 12), C6 (n = 11), C7 (n = 14), C8 (n = 6), and T1 (n = 3) nerves. Multivariable logistic regression analysis with an area under the curve of 0.85 demonstrated C5 tumor level as an independent predictor of new postoperative weakness (odds ratio 7.4, p = 0.028). Of those patients with new postoperative weakness, 75% improved and 50% experienced complete resolution of their motor deficits.

CONCLUSIONS

Patients with C5 nerve sheath tumor resections are at higher odds of new postoperative weakness. This may be due to the predominant single innervation of shoulder muscle targets in contrast to other upper extremity muscles that receive input from 2 or more spinal nerves. These findings are important for clinical decision-making and preoperative patient counseling.

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A significant association between C5 nerve sheath tumors and new postoperative weakness

Anthony L. Mikula, Brandon W. Smith, Nikita Lakomkin, Matthew K. Doan, Megan M. Jack, Mohamad Bydon, and Robert J. Spinner

OBJECTIVE

The objective of this study was to determine if patients with nerve sheath tumors affecting the C5 spinal nerve are at greater risk for postoperative weakness than those with similar tumors affecting other spinal nerves contributing to the brachial plexus.

METHODS

A retrospective chart review (1998–2020)identified patients with pathologically confirmed schwannomas or neurofibromas from the C5 to T1 nerves. Patients with plexiform nerve sheath tumors, tumors involving more than 1 nerve, and malignant peripheral nerve sheath tumors were excluded. Collected variables included basic demographics, tumor dimensions, its location relative to the dura, involved nerve level, surgical approach, extent of resection, presenting symptoms, postoperative neurological deficits, and recurrence rate.

RESULTS

Forty-six patients (23 men, 23 women) were identified for inclusion in the study with an average age of 47 ± 17 years, BMI of 28 ± 5 kg/m , and follow-up of 32 ± 45 months. Thirty-nine patients (85%) had schwannomas and 7 (15%) had neurofibromas. Tumors involved the C5 (n = 12), C6 (n = 11), C7 (n = 14), C8 (n = 6), and T1 (n = 3) nerves. Multivariable logistic regression analysis with an area under the curve of 0.85 demonstrated C5 tumor level as an independent predictor of new postoperative weakness (odds ratio 7.4, p = 0.028). Of those patients with new postoperative weakness, 75% improved and 50% experienced complete resolution of their motor deficits.

CONCLUSIONS

Patients with C5 nerve sheath tumor resections are at higher odds of new postoperative weakness. This may be due to the predominant single innervation of shoulder muscle targets in contrast to other upper extremity muscles that receive input from 2 or more spinal nerves. These findings are important for clinical decision-making and preoperative patient counseling.

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Need for arthrodesis following facetectomy for spinal peripheral nerve sheath tumors: an institutional experience and review of the current literature

Mohammed Adeeb Sebai, Panagiotis Kerezoudis, Mohammed Ali Alvi, Jang Won Yoon, Robert J. Spinner, and Mohamad Bydon

OBJECTIVE

Spinal peripheral nerve sheath tumors (PNSTs) are a group of rare tumors originating from the nerve and its supporting structures. Standard surgical management typically entails laminectomy with or without facetectomy to gain adequate tumor exposure. Arthrodesis is occasionally performed to maintain spinal stability and mitigate the risk of postoperative deformity, pain, or neurological deficit. However, the factors associated with the need for instrumentation in addition to PNST resection in the same setting remain unclear.

METHODS

An institutional tumor registry at a tertiary care center was queried for patients treated surgically for a primary diagnosis of spinal PNST between 2002 and 2016. An analysis focused on patients in whom a facetectomy was performed during the resection. The addition of arthrodesis at the index procedure comprised the primary outcome. The authors also recorded baseline demographics, tumor characteristics, and surgery-related variables. Logistic regression was used to identify factors associated with increased risk of fusion surgery.

RESULTS

A total of 163 patients were identified, of which 56 (32 had facetectomy with fusion, 24 had facetectomy alone) were analyzed. The median age was 48 years, and 50% of the cohort was female. Age, sex, and race, as well as tumor histology and size, were evenly distributed between patients who received facetectomy alone and those who had facetectomy and fusion. On univariate analysis, total versus subtotal facetectomy (OR 9.0, 95% CI 2.01–64.2; p = 0.009) and cervicothoracic versus other spinal region (OR 9.0, 95% CI 1.51–172.9; p = 0.048) were significantly associated with increased odds of performing immediate fusion. On multivariable analysis, only the effect of total facetectomy remained statistically significant (OR 6.75, 95% CI 1.47–48.8; p = 0.025).

CONCLUSIONS

The authors found that total facetectomy and cervicothoracic involvement may be highly associated with the need for concomitant arthrodesis at the time of index surgery. These findings may help surgeons to determine the best surgical planning for patients with PNST.

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The implications of intradural extension in paraspinal malignant peripheral nerve sheath tumors: effects on central nervous system metastases and overall survival

Hannah E. Gilder, Ross C. Puffer, Mohamad Bydon, and Robert J. Spinner

OBJECTIVE

In this study, the authors sought to compare tumors with intradural extension to those remaining in the epidural or paraspinal space with the hypothesis that intradural extension may be a mechanism for seeding of the CSF with malignant cells, thereby resulting in higher rates of CNS metastases and shorter overall survival.

METHODS

The authors searched the medical record for cases of malignant peripheral nerve sheath tumors (MPNSTs) identified from 1994 to 2017. The charts of the identified patients were then reviewed for tumor location to identify patients with paraspinal malignancy. All patients included in the study had tumor specimens that were reviewed in the surgical pathology department. Paraspinal tumors with intradural extension were identified in the lumbar, sacral, and spinal accessory nerves, and attempts were made to match this cohort to another cohort of patients who had paraspinal tumors of the cranial nerves and lumbar and sacral spinal regions without intradural extension. Further information was collected on all patients with and without intradural extension, including date of diagnosis by pathology specimen review; nerve or nerves of tumor origin; presence, location, and diagnostic date of any CNS metastases; and either the date of death or date of last follow-up.

RESULTS

The authors identified 6 of 179 (3.4%) patients who had intradural tumor extension and compared these patients with 12 patients who harbored paraspinal tumors that did not have intradural extension. All tumors were diagnosed as high-grade MPNSTs according to the surgical pathology findings. Four of 6 (66.7%) patients with intradural extension had documented CNS metastases. The presence of CNS metastases was significantly higher in the intradural group than in the paraspinal group (intradural, 66.7% vs paraspinal, 0%; p < 0.01). Time from diagnosis until death was 11.2 months in the intradural group and approximately 72 months in the paraspinal, extradural cohort.

CONCLUSIONS

In patients with intradural extension of paraspinal MPNSTs, significantly higher rates of CNS metastases are seen with a reduced interval of time from diagnosis to metastatic lesion detection. Intradural tumor extension is also a poor prognostic factor for survival, with these patients showing a reduced mean time from diagnosis to death.

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Lateral pectoral nerve transfer for spinal accessory nerve injury

Andrés A. Maldonado and Robert J. Spinner

Spinal accessory nerve (SAN) injury results in loss of motor function of the trapezius muscle and leads to severe shoulder problems. Primary end-to-end or graft repair is usually the standard treatment. The authors present 2 patients who presented late (8 and 10 months) after their SAN injuries, in whom a lateral pectoral nerve transfer to the SAN was performed successfully using a supraclavicular approach.