Abstract
BACKGROUND
Intraneural perineuriomas (INPs) are rare benign peripheral nerve sheath tumors with characteristic clinical and MRI features. Their 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) appearance has not been characterized in a patient series. The authors evaluated FDG uptake patterns in INP.
OBSERVATIONS
The authors retrospectively reviewed that data of patients with confirmed INP who had MRI and FDG PET studies that included the affected nerve. Eight patients were included (5 male and 3 female; mean age 30.8 years, range 16–61 years). All lesions showed mildly increased FDG uptake relative to the contralateral nerve (lesion maximum standardized uptake value [SUVmax]: mean 1.5, median 1.2, range 1.1–3.5; contralateral nerve SUVmax: mean 0.9, median 0.9, range 0.8–1.0) and skeletal muscle background (SUVmean: mean 0.8, range 0.5–0.9). Six patients had denervation edema and/or fatty atrophy, without appreciably increased FDG uptake in the affected musculature. No additional abnormal hypermetabolic foci were identified.
LESSONS
INPs generally demonstrate low-level FDG uptake. PET is best regarded as a complementary test when already available or when metabolic characterization may refine the differential diagnosis; unexpectedly high uptake should prompt reconsideration of the diagnosis or additional evaluation.
Keywords: intraneural perineurioma, nerve tumor, nerve imaging, FDG PET, fluorodeoxyglucose, positron emission tomography, peripheral nerve
ABBREVIATIONS: CIDP = chronic inflammatory demyelinating polyradiculoneuropathy, FDG = 18F-fluorodeoxyglucose, INP = intraneural perineurioma, PET = positron emission tomography, SUV = standardized uptake value
Perineuriomas are rare benign tumors arising from epithelial myofibroblasts that form the perineurium. They are classified as extraneural (soft tissue) or intraneural perineuriomas (INPs).1–3 Historical terms for INP include pseudo-onion bulb neuropathy, localized hypertrophic neuropathy, and intraneural neurofibroma.4,5 INPs show characteristic pseudo-onion bulb formation and an immunophenotype that typically includes epithelial membrane antigen positivity and limited S100 reactivity.6,7 They most often occur in children and young adults and cause slowly progressive motor-predominant neuropathy; undergrowth in the affected nerve territory may also occur.1
Typical MRI findings include fusiform fascicular enlargement, T2 hyperintensity, and postcontrast enhancement.4 When the clinical and MRI features are classic, a diagnosis can often be made without biopsy; targeted nerve biopsy may be reserved for diagnostically uncertain cases.1,8 To our knowledge, no prior study has characterized the 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) appearance of INP in a patient series. The purpose of this retrospective study was therefore to describe the FDG PET characteristics of INP.
Study Description
Patient Selection and Clinical Data
The institutional review board approved this retrospective study and waived the requirement for informed consent. The inclusion criteria were 1) confirmed INP based on characteristic imaging findings and/or pathology and 2) available MRI and FDG PET studies that included the affected nerve. Cases were identified through an institutional electronic medical record search covering the preceding 20 years. Patients were excluded when the affected nerve segment was outside the PET field of view or MRI was unavailable for anatomical correlation.
Recorded clinical variables included age, sex, presenting symptoms, affected nerve, undergrowth in the involved nerve territory, biopsy status, treatment or intervention, and available clinical follow-up.
Imaging Review and Statistical Analysis
All available MRI and PET examinations were reviewed. Measurements included the maximum standardized uptake value (SUVmax) of the INP and contralateral normal nerve and the SUVmean of adjacent skeletal muscle as a regional background reference. The examinations were also assessed for denervation edema and fatty atrophy in the affected nerve territory.
Measurements were performed with Visage PACS software (version 7.1.19, Visage Imaging). PET regions of interest were localized by direct correlation with MRI. Imaging data were abstracted independently by two readers, and discrepancies were adjudicated by a fellowship-trained radiologist with expertise in musculoskeletal and nuclear radiology. Formal interreader agreement was not calculated because the final descriptive analysis used consensus or adjudicated measurements. Only descriptive statistics were calculated. Continuous variables are reported as mean, standard deviation, median, and/or range, as appropriate; categorical variables are reported as counts and proportions.
Results
Patient Cohort
The initial search identified 11 patients with confirmed INP and available PET imaging. Three were excluded because the affected nerve segment was outside the PET field of view, leaving 8 patients (5 male and 3 female) in the final series. The mean age at diagnosis was 30.8 ± 12.3 years (range 16–61 years). Involved nerves were the sciatic nerve (n = 2), femoral nerve (n = 2), lumbosacral plexus (n = 2), ulnar nerve (n = 1), and brachial plexus (n = 1). Two patients had undergrowth in the affected limb.
All patients reported weakness, 5 reported sensory abnormalities, and 3 reported pain. Three patients underwent fascicular biopsy; 1 of these patients also had a reported prior partial resection at an outside institution. All biopsies were performed after PET. The remaining 5 cases were diagnosed on the basis of characteristic clinical and MRI findings. Follow-up at the study institution was limited: 3 patients had more than 1 month of follow-up, at 2, 12, and 32 months.
Imaging Findings
Three patients had fatty atrophy on the CT component of PET/CT. Three additional patients had mild denervation edema on MRI without fatty atrophy on CT, and 2 had neither denervation edema nor fatty atrophy. The denervated musculature did not show appreciably increased FDG uptake.
All INPs showed mildly increased FDG uptake relative to the contralateral normal nerve (lesion SUVmax: mean 1.5, median 1.2, range 1.1–3.5; contralateral nerve SUVmax: mean 0.9, median 0.9, range 0.8–1.0) (Figs. 1 and 2). Adjacent skeletal muscle showed a mean SUVmean of 0.8 (median 0.8, range 0.5–0.9). No additional abnormal hypermetabolic foci were identified. Clinical and imaging findings are summarized in Table 1.
FIG. 1.
Case 6. A: T2-weighted axial image obtained at the level of L5 showing thickening and T2 hyperintensity of the right L5 nerve (arrow). B: Postcontrast axial MR image obtained at the same level demonstrating avid postcontrast enhancement of the L5 nerve (arrow). C and D:Corresponding fused axial PET/CT scan (C) and maximum intensity projection image (D) from an FDG PET/CT study demonstrating mild FDG avidity of the lesion (arrow and dashed ellipse, respectively).
FIG. 2.
Case 4. A: Axial T2-weighted image obtained at the level of the mid-thigh showing thickening and slight T2 hyperintensity of the right sciatic nerve (arrow). B: Postcontrast axial image obtained at the same level demonstrating avid enhancement of the perineurioma (arrow). The contralateral normal sciatic nerve is labeled with arrowheads for comparison. C: Maximum intensity projection image from an FDG PET/CT study demonstrating slight FDG avidity of the proximal right sciatic nerve (dashed ellipse) and the craniocaudal extent of the lesion.
TABLE 1.
Summary of demographic and PET data
| Case No. | Demographic & Clinical Information | PET Data | |||||
|---|---|---|---|---|---|---|---|
| Sex | Age at Dx, yrs | Nerve | Side | SUVmax of Lesion | SUVmax of Contralat Nerve | SUVmean of Muscle | |
| 1 | M | 61 | Femoral | Rt | 1.16 | 1.04 | 0.84 |
| 2 | M | 37 | Femoral | Lt | 1.24 | 0.83 | 0.76 |
| 3 | F | 38 | Sciatic | Rt | 1.65 | 0.87 | 0.78 |
| 4 | M | 17 | Sciatic | Rt | 1.23 | 0.86 | 0.54 |
| 5 | F | 37 | Ulnar | Rt | 1.2 | 0.89 | 0.71 |
| 6 | F | 24 | Lumbosacral plexus | Rt | 3.49 | 0.89 | 0.59 |
| 7 | M | 16 | Brachial plexus | Rt | 1.28 | 1.04 | 0.92 |
| 8 | M | 16 | Lumbosacral plexus | Lt | 1.1 | 0.9 | 0.88 |
Dx = diagnosis.
Informed Consent
The necessary informed consent was obtained in this study.
Discussion
Observations
This patient series indicates that INPs generally have low FDG avidity, with uptake only mildly above that of the contralateral normal nerve and regional skeletal muscle. This metabolic profile may be useful when PET was performed for another indication or when the differential diagnosis includes more FDG-avid infiltrative or neoplastic nerve processes.
Reported FDG uptake is generally higher in malignant peripheral nerve sheath tumors and neurolymphomatosis than in the present INP series. In one PET/MRI study, malignant peripheral nerve sheath tumors had a mean SUVmax of 10.1 ± 1.0, compared with 4.2 ± 0.4 for benign peripheral nerve sheath tumors. B-cell neurolymphomatosis has shown a mean SUVmax of 7.1 ± 4.5 (range 1.5–17.0).9,10 By comparison, the mean SUVmax in our series was 1.5 and the maximum was 3.5. These values should not be treated as diagnostic thresholds, but the marked difference in typical uptake may help prioritize the differential diagnosis when interpreted with clinical and MRI findings.
One lesion had an SUVmax of 3.5, higher than the values of the remaining INPs. This lesion was slightly larger, which may have reduced partial-volume averaging. Because most INPs are small and elongated, MRI correlation is essential to ensure accurate PET localization and avoid overinterpretation of subtle uptake differences. Six of 8 patients had denervation edema and/or fatty atrophy, but no appreciable increase in FDG uptake was identified in the affected musculature. Increased muscular FDG uptake can occur after denervation, although its presence depends on timing and other technical and biological factors.11
Other nerve-related conditions can overlap with INP on anatomical imaging. Neuromuscular choristoma has a muscle-like signal on all MRI sequences and usually only mild enhancement; associated or developing desmoid-type fibromatosis may show greater FDG activity.12–14 Neurolymphomatosis and perineural tumor spread are often more FDG avid and usually occur in a different clinical context, although overlap is possible.9,15 Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) can be confused with INP; however, CIDP typically lacks postcontrast enhancement and has a different clinical presentation, natural history, and treatment.16,17 Peripheral nerve amyloidosis may also produce fascicular enlargement, T2 hyperintensity, variable enhancement, denervation changes, and low-level FDG uptake; amyloid-specific tracers such as 18F-florbetapir may provide greater specificity in selected patients.18,19
PET should therefore not replace MRI as the primary imaging examination for suspected INP and should not be a part of routine INP evaluation if pathognomonic imaging features of INP are present. However, in cases in which MRI features of INP are equivocal, multifocal disease is suspected, or malignancy is part of the differential diagnosis, FDG PET should be considered. Minimal or mild uptake concordant with characteristic MRI findings may provide supportive information, whereas unexpectedly high uptake or discordance between PET and MRI findings should prompt reconsideration of the diagnosis, closer surveillance, or tissue sampling when clinically appropriate. Our institution does not include FDG PET study as a routine test for the evaluation of an INP. Cases in our series happened to have FDG PET studies on file; however, none were obtained for evaluation of INP showing pathognomonic features on MRI.
This study is limited by its retrospective design, small sample size, tertiary-referral selection bias, and limited clinical follow-up. PET quantification in small peripheral nerves is also susceptible to partial-volume effects and variation in scanner and acquisition protocols. The findings are descriptive and require validation in additional series.
Lessons
INPs generally demonstrate low-level FDG uptake, only mildly above that of the contralateral nerve and skeletal muscle background. FDG PET is a complementary rather than primary diagnostic examination: concordant low uptake may support a characteristic MRI diagnosis, whereas unexpectedly high uptake should raise concern for an alternative process or justify additional evaluation.
Disclosures
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Author Contributions
Conception and design: all authors. Acquisition of data: all authors. Analysis and interpretation of data: all authors. Drafting the article: all authors. Critically revising the article: Spinner, Marek, Broski. Reviewed submitted version of manuscript: Spinner, Marek, Broski. Approved the final version of the manuscript on behalf of all authors: Spinner. Administrative/technical/material support: Spinner. Study supervision: Spinner.
Correspondence
Robert J. Spinner: Mayo Clinic, Rochester, MN. spinner.robert@mayo.edu.
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