Symptomatic neuroma development following en bloc resection of skeletal and soft-tissue tumors

Authors: Aslami ZV, Leland CR, Strike SA, Forsberg JA, Morris CD, Levin AS, Tuffaha SH

Affiliation: Johns Hopkins Hospital

Journal: Plastic and Reconstructive Surgery, April 2024

PMID: 37199679

Key takeaways

• Symptomatic neuromas developed after 25% of en bloc musculoskeletal tumor resections.

• Neuropathic pain was even more common, occurring after 50% of resections.

• Younger age, multiple resections, and preoperative neuromodulator use independently predicted symptomatic neuroma formation.

• Documented nerve transection occurred in 26%, but distal numbness occurred in 42%, suggesting occult nerve injury is underrecognized.

• Neuroma prevention should be considered during oncologic tumor resection, especially when nerves are sacrificed or repeatedly dissected.

Background

Wide en bloc resection of sarcoma and other musculoskeletal tumors often requires nerve manipulation, transection, or sacrifice to obtain appropriate oncologic margins. When injured nerve ends are left untreated, painful neuromas can develop and contribute to chronic postoperative neuropathic pain.

Although neuromas are well described after amputation and peripheral nerve surgery, their incidence after limb-sparing musculoskeletal tumor resection has been poorly defined.

Objective

To determine the incidence of symptomatic neuroma formation after en bloc resection of skeletal and soft-tissue tumors and identify patient or operative factors associated with postoperative neuroma-related pain.

Methods

• Design: Single-institution retrospective cohort study at a high-volume sarcoma center, 2014–2019; Level III.

• Population: 231 adult patients undergoing 331 en bloc resections for skeletal or soft-tissue tumors of the trunk or extremities.

• Exclusions: Non-en bloc resections, primary amputations, pathologic fracture fixation, irrigation/debridement, age <18 years, and insufficient institutional follow-up.

• Follow-up: Mean follow-up 3.5 years among surviving patients; 75% had at least 2 years of follow-up.

• Primary outcome: Symptomatic neuroma, defined by clinical pain/Tinel sign or confirmatory testing plus sensory neuropathy in the expected nerve distribution at least 6 months postoperatively.

• Other outcomes: Neuropathic pain, distal numbness, postoperative neuromodulator requirement, analgesia duration, and pain scores when available.

• Statistics: Bivariate analysis and multivariable logistic regression controlling for demographic, oncologic, perioperative, and nerve-injury variables.

Results

• Cohort: 331 resections; 91% sarcoma; 77% extremity tumors; mean resection size 12 cm.

• Nerve involvement/injury: Tumor nerve involvement occurred in 52%, intraoperative nerve manipulation in 51%, documented nerve injury in 34%, and nerve transection in 26%.

• Symptomatic neuroma: 81 resections met criteria, for an incidence of 25%.

• Broader neuropathic burden: Neuropathic pain occurred in 50%, distal numbness in 42%, and postoperative neuromodulator use in 40%.

• Pain burden: Among patients with documented pain scores ≥6 months postoperatively, median visual analog pain score was 6 in the neuroma group.

• Neuroma cases: Compared with no-neuroma cases, neuroma resections more often involved tumor-nerve involvement (72% vs 46%), intraoperative nerve manipulation (70% vs 44%), nerve injury (51% vs 28%), and subsequent tumor resection (43% vs 27%).

• Independent predictors of symptomatic neuroma:

  • Age 18–39 years: aOR 3.6; P < 0.01.

  • Age 40–64 years: aOR 2.2; P = 0.04.

  • Multiple resections: aOR 3.2; P < 0.001.

  • Preoperative neuromodulator use: aOR 2.7; P = 0.01.

• Protective association: Resections including deep fascia or muscle had lower neuroma risk (aOR 0.5; P = 0.045), likely because these cases injure fewer superficial sensory nerves, which are more prone to painful neuroma symptoms.

• Not independently associated: Radiotherapy, chemotherapy, resection size, and intraoperative nerve injury did not independently predict symptomatic neuroma after adjustment.

Conclusion

Symptomatic neuromas are common after en bloc musculoskeletal tumor resection and likely underdiagnosed. Younger patients, patients undergoing repeat resections, and patients already requiring neuromodulators for neuropathic pain represent a higher-risk group that may benefit from preoperative pain optimization and planned intraoperative nerve management.

Strengths

• Large series, mean follow-up of 3.5 years.

Limitations

• Retrospective design with heterogeneous documentation of pain, Tinel sign, nerve injury, and quality-of-life impact.

• Neuropathic pain in oncology patients is multifactorial; tumor recurrence, radiation, chemotherapy, scar compression, and baseline neuropathy are alternative explanations that cannot be fully excluded retrospectively.

• Only 8% of excisions with documented nerve transection received prophylactic neuroma prevention, limiting ability to assess comparative efficacy of different techniques.

Clinical relevance

A sacrificed nerve stump during tumor resection should be treated as a source of potential long-term morbidity. When a sensory or mixed nerve is transected and direct repair is not feasible, surgeons should consider a neuroma prevention strategy such as targeted muscle reinnervation, regenerative peripheral nerve interface, muscle implantation, or a vascularized denervated muscle target.

The highest-risk patients are younger, undergoing repeat resections, or already requiring neuromodulators for neuropathic pain. These patients should have pain expectations discussed preoperatively, intentional nerve management planned intraoperatively, and a low threshold for postoperative referral to a peripheral nerve surgeon if focal neuropathic pain persists.