A Classification System for Neuroma Morphology: Does Size and Shape Matter?
Floris V. Raasveld, MD1, Daniel T. Weigel, MD1, Maximilian Mayrhofer-Schmid, NA2, Barbara Gomez-Eslava, MD, MS1, Wen-Chih Liu, MD1, Ian L Valerio, MD, MS, MBA1 and Kyle R. Eberlin, MD1, 1Massachusetts General Hospital/Harvard Medical School, Boston, MA, 2Heidelberg Medical School, Heidelberg, Germany
Introduction: Anatomic and morphological features of neuromas have been evaluated via imaging, but have not been investigated in ex-vivo, resected neuroma specimens. Moreover, little is known about neuroma growth over time following nerve injury, and whether differences in size and shape are associated with differences in pain severity. In this study, we analyze the influence of time on neuroma size and shape, and characterize the significance of morphological features.
Methods: Patients undergoing neuroma excision were prospectively included between January 2022 through May 2023. Neuroma specimens were obtained intra-operatively and standardized measurements of morphology and size, expressed as the neuroma-to-nerve-ratio (NNR), were conducted with image analysis software ImageJ (Fig. 1). Pain data (Numeric rating scale, 0-10) was prospectively collected during pre-operative interview, and patient factors were collected from chart review. A morphological classification is proposed and the inter-rater reliability (IRR) was assessed.
Results: Forty-five terminal neuroma specimens from 27 patients were included in this study. Amputees comprised 93% of the population, of which 2 were upper (8%) and 23 were lower extremity (89%) amputees. The median neuroma diameter was 9.53mm (IQR 6.80-14.31) with a median proximal “normal” nerve diameter of 3.78mm (IQR 2.10-7.59), resulting in a median NNR of 2.48 (IQR 1.70-3.44). Time-to-neuroma excision was significantly associated with a larger NNR (p=0.008) (Fig 2). A smaller proximal nerve diameter was associated with a larger NNR (p<0.001) (Fig. 3). NNR and preoperative pain were not associated (p=0.110) (Fig. 4). The proposed morphological classification, consisting of three groups (bulbous, fusiform and atypical), demonstrated a strong IRR (Cohen’s kappa=0.8). Atypical neuromas were associated with higher preoperative pain, compared to bulbous (p=0.018) and fusiform (p=0.003) (Fig. 5). Atypical morphology was significantly more prevalent in patients with diabetes (p=0.011) and peripheral vascular disease (PVD) (p=0.018).
Conclusion: In this study we observed that neuroma size, expressed as NNR, is negatively associated with the proximal nerve diameter, suggesting that larger caliber nerves develop smaller neuromas relative to the normal nerve caliber. The time-to-neuroma-excision was significantly associated with NNR, suggesting continued growth and development of neuromas over time. A validated morphological classification of neuroma is introduced, indicating that atypically shaped neuromas were associated with diabetes, PVD and higher preoperative pain, reflecting the potential relationship with the vascular and metabolic microenvironment. These findings may assist surgeons and researchers in better understanding of symptomatic neuroma development.
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