The schwannomas, also known as neurilemmomas or neurinomas, are the most common benign soft tissue neoplasms that originate from the peripheral nerve sheath.^[1] The most common localizations are head and neck, while the incidence of cases involving upper and lower limbs is significantly lower.^{[1, 2]} These tumors often present as slow growing lone masses, and malignant degeneration into neurofibrosarcomas or malignant schwannomas is sporadic, occurring in less than 1% of all schwannomas.‌^[2] Although neurinomas can stay clinically silent, symptoms may appear and worsen as the tumor volume increases, compressing the native nerve and of the adjacent structures. Eventual clinical manifestations may consist of various combinations of pain, swelling, and alteration of neuromotor or sensitive neurological functionality.^[2–4] The Hoffman-Tinel sign, consisting in an induced pain or paresthesia through percussion, is also typically associated with schwannomas.^[2–6]

Once anamnestic and clinical findings suggest schwannoma, imaging evidence is necessary to investigate the lesion further. Although ultrasound evaluations can be useful and easy to perform, MRI remains the radiological investigation of choice to identify its nerve of origin and further orient toward the presumptive diagnosis of schwannoma that usually appears as a well-circumscribed and encapsulated mass, a heterogeneous signal.^[7]

Once the presumptive diagnosis has been established, surgical treatment is the only available approach to remove the neoplastic mass. Surgeons are called to remove schwannomas as a whole to minimize the risk of local recurrence and preserve the continuity of the involved nerve, especially in the case of major nervous structures. For this reason, the operative treatment of choice is the enucleation of the neoplastic mass when it involves a major nerve or complete resection when the nerve is too thin to be preserved. The enucleation consists of a linear cut of the perineurium and a smooth dissection of the neoplastic mass from the nearby nervous bundles, that should be spared in order to preserve the nerve’s post-operative functionality.^[8]

Due to the rarity of schwannomas arising from the upper limb, only a few studies available at the moment focus on clinical presentation and prognostic factors.^[2-6,8-18] and evaluate the impact of schwannomas and their treatment on patient’s upper limb functionality.^[19]

This study evaluates the clinical impact of upper limb schwannomas, focusing on patients’ functionality. We also assessed the effectiveness of the surgical approach in reducing patients’ symptoms, restoring patients’ upper limbs’ performance, and increasing their quality of life.

This single-center retrospective study was conducted according to the ethical standards in the 1964 Declaration of Helsinki and its later amendments.

Our study consisted of a review of all schwannomas arising from the major nerves of the upper limb and treated with surgery in our institution between January 2016 and January 2024.

For each patient, we collected data regarding their age, gender, first symptom associated with the disease, and its date, alongside the date on which schwannoma was diagnosed. We reviewed the tumor’s localization in terms of the anatomical segment involved (shoulder, arm, elbow, forearm, wrist, or hand) and the nerve from which the neoplasm originated. The diagnostic interval, corresponding to the time between the onset of the first symptom and the definitive histological diagnosis, was recorded for each patient.

Our patients’ pre-operative functional status was evaluated using the Disability of Arm, Shoulder, and Hand (DASH) score and the Musculoskeletal Tumor Society (MSTS) score at the moment of hospitalization. Before surgery, the Medical Research Council (MRC) scale was used to assess the contractile strength of the muscular segments of the treated area, paying particular attention to those innervated by the involved nerve. In parallel, a Tinel-Hoffmann test and a careful examination of the deep and cutaneous sensitivity were practiced on every patient suspected of neurinoma before their intervention.

Each patient underwent a pre-operative MRI (Fig. 1), which was used to orientate the diagnosis, guide the surgical planning, and estimate the tumor size.

In the surgical theater, before the surgical incision, lesions were localized under ultrasound guidance, in order to orientate the surgical approach to the tumor. Intra-operatively, the involved nerves were identified and isolated, and schwannomas were carefully enucleated, preserving the continuity of the involved nerves (Fig. 2).

Surgical specimens (Fig. 3) were examined by our pathologists to confirm the diagnosis of schwannoma using routine histology, histochemistry, and immunohistochemistry techniques.

All of our patients were treated with oral integration of lipoic acid, citicoline and vitamins B for 30 days after surgery in order to obtain an antioxidant, neurotrophic and neuroprotective effect.

Postoperative follow-up consisted of serial office visits, clinical evaluations, and postoperative MRIs performed within one month (clinical evaluation only) and later 6 and 12 months after surgery. Further evaluations were scheduled depending on the necessities of each single case.

Each complication with a grade II or higher, according to the Clavien-Dindo classification, was reported. Local recurrences and their eventual treatments were also recorded.

At each patient’s latest follow-up, we evaluated the presence of sensitive deficits, repeated the Tinel test, and assessed muscular strength according to the MRC scoring scale. We also recalculated the overall functional status of the treated upper limbs using the MSTS and the DASH score.

Twenty-two consecutive cases of schwannomas of the upper limbs were treated in our institution between January 2016 and December 2023. Our cohort included 11 females and as many males, with a mean age of 54.0 (38–78) at surgery.

Two cases (9%) had their lesion localized in the shoulder girdles, 6 (27%) in their arms and 5 (23%) in their elbows. The forearm was the location of 7 (32%) schwannomas, whereas the remaining two cases were diagnosed with schwannomas in their wrist and hand (9%). The most common nerve of origin for treated schwannomas was the radial nerve (10; 45%), followed by the ulnar (4; 18%) and the median nerve (3; 14%). In the remaining cases, schwannomas arose from the brachial plexus (2; 9%), the musculocutaneous nerve (2; 9%), and the anterior interosseous nerve (1; 5%). A summary of schwannomas’ localization is provided in Fig. 4.

Only one of our cases (4%) had an incidental diagnosis without any sign attributable to the disease. The remaining 21 cases (96%) were brought to medical attention by the onset of symptoms attributable to the disease. The first symptom was palpable swelling in 19 cases (86%) and pain in the remaining 2 cases (10%). On average, the diagnosis was established 16.7 months after the onset of the first symptom. Eleven cases (50%) had a positive Tinel sign at the moment of patients’ hospitalization. According to a two-tailed T Student test, presence or absence of the Tinel sign did not represent a factor that influenced the diagnostic interval. The mean pre-operative MRC score was 4.8 (4-5), as five patients (23%) experienced a mild reduction in their muscular strength. Before surgery, 13 cases (59%) had developed dysesthesia or paresthesia; symptoms were mild in 10 (45%) and moderate in 3 cases (14%). The remaining nine patients (41%) did not complain of any sensitive deficit.

The overall functionality of our patients’ upper limbs was calculated using the MSTS and DASH scores before surgery. The mean pre-operative MSTS score was 27.9 (21-30), and the mean pre-operative DASH score was 5.7 (0-25).

The size of the neoplasms was assessed using the MRI scans and later confirmed on surgical specimens: the mean larger diameter was 3.8 cm (1.5–11.0). A Pearson correlation test stated that the larger the schwannomas were, the lower the MSTS score and the higher the DASH score was before surgery (p=0.0001).

Intra-operatively, surgeons could successfully enucleate all the treated schwannomas, preserving the continuity of all nerves. Histological evaluations confirmed the diagnosis of Schwannoma in each case.

None of our cases had major intra-operative or peri-operative complications.

The mean post-operative follow-up was 43.1 (6-92). Only one patient (Case 14) complained of increased sensitive deficits after surgery, passing from mild to moderate paresthesia and experiencing hand tingling that was not present before surgery. The sensitivity deficits of all the remaining cases with pre-operative deficits were reduced after surgical treatment, and only two patients (9%) had dysesthesia at their latest follow-up. According to a Fisher Exact test, the rate of sensitive deficits was significantly lower after surgery compared to the pre-operative records (p=0.0011).

No Tinel sign was recorded after surgery. Case 14 was also the only one to maintain a slight muscular strength impairment (MRC 4); the MRC score of the remaining cases was as high as 5.

The mean post-operative MSTS score was 29.7 (24-30). The difference between this value and the pre-operative one was statistically significant, as testified by a Pearson correlation test (p=0.0022).

The mean post-operative DASH score was 0.7 (0-16). According to a Pearson correlation test (p=0.0029), this value was significantly lower than the one recorded before surgery.

None of our cases was diagnosed with a local recurrence through their post-operative intercourse.

The characteristics of our cohort are summarized in Table 1.

The clinical presentation of the schwannomas of the upper limb can include a large variety of signs and symptoms. Correctly evaluating signs and symptoms attributable to the disease is crucial to starting a proper diagnostic pathway and minimizing the risk of misdiagnosis. Although the number of studies in the literature on this topic is slowly but progressively increasing^[2-6,8-19], the distance between the onset of the first symptom and the establishment of a histological diagnosis still represents one of the main issues in clinical practice. The diagnostic interval in our population amounted to 16.6 months, aligning with the most recent studies published in the third decade of the 21st century (12-30) (Table 2).^[4,8-11,19] Several other studies dating back to the dawn of the new millennium reported diagnostic delays even longer than 40 months^[6,12,13], testifying to the difficulty of obtaining an early diagnosis in upper limb schwannomas. Although the improvements in imaging technologies and an ever more profound knowledge of soft tissue tumors show promise of more straightforward and earlier diagnoses in the future, a better comprehension of signs and symptoms is still crucial in today’s approach to upper limb schwannomas. As other authors had already experienced, the most frequent outbreak symptom in our cases was localized swelling.^[2,12,14,15] This tendency differs from peripheral lower limb schwannomas, where paresthesia and neurological deficits often anticipate a palpable swelling.^{[20, 21]} This difference could be attributable to the fewer subcutis and muscular masses in the upper limb that unveil the schwannomas before it would have happened in the more muscular and hypoderma-rich lower limb. Although not prominent outbreak symptoms, sensitive deficits were documented in most of our cases (59%) during their hospitalization. Our data fall in between a highly heterogeneous and broad spectrum in literature. Some authors, such as Takase et al.^[6], Sawada et al.^[12], and Knight et al.^[2], reported a prevalence of sensitive symptoms or muscular weakness lower than 30%. In particular, Knight et al.^[2] carefully evaluated the pre-operative clinical picture in 170 upper limb schwannomas, highlighting a rate of sensory alterations of 4.5% and a rate of muscular weakness as low as 1.6%.

On the other hand, Gosk et al.^[5], El Sayed et al.^[10], and Istefan et al.^[11] had neurological deficit rates higher than 80% in their cohorts. Beyond the variations in prevalence, most authors agreed that neurological symptoms generally present as mild or moderate.^[3,4,11,16] Our casuistry confirms this tendency, as none of our cases complained of sensitive or motor deficits of significant entities.

The Tinel sign still represents one of the most iconic and broadly used tests for the clinical assessment of neurinomas. Although our prevalence of 50% ranks among the lowest reported in modern literature for relatively large cohorts (33-100%).^{[2–6,8–10,12,14–18]}, it still corroborates the use of the test in everyday clinical practice, considering it is quick, easy to perform, and does not require specific instrumentation.

While several authors described the frequency of single symptoms, modern literature severely lacks evidence about the global impact of schwannomas on upper limb functionality. Few studies have provided evidence based on widely used scoring systems, such as the DASH or MSTS scores. Raj et al.^[19] used the DASH score to assess the functional performances of 24 upper limbs treated with surgical resection, obtaining a mean DASH score of 6.1. Our mean DASH score of 5.7 confirms that, although present, the functional impairment attributable to upper limb schwannomas is often limited and generally causes only minor limitations to the ordinary activities of daily living. The same conclusions come from a fair pre-operative MSTS score of 27.9. The lack of overwhelming symptoms and the often-well-preserved functionality could be partially responsible for the relatively long diagnostic interval in upper limb schwannomas.

Surgical resection of the neoplastic mass, performed with careful enucleation from the involved nerve, is a safe procedure, as confirmed by the absence of major intra-operative or peri-operative complications in our cohort.

Its effectiveness, already confirmed by previous studies, was also evidenced in our population by the significant reduction in sensitive symptoms after surgery (p=0.0011). Furthermore, both the MSTS (29.7) and the DASH score (0.7) got significantly better after surgery, marking an almost complete remission of the limitations caused by the disease. This result differs from the findings of Raj et al.^[19], who did not experience a significant improvement in patients’ functionality after surgery. Our experience suggests that a careful diagnostic and treatment can lead to a total or subtotal remission of most symptoms and signs attributable to schwannomas and successfully restore the functionality of the involved upper limbs.

We acknowledge that our study had some limitations. The rarity of these tumors did not allow us to operate on broader populations, which partially limited the statistical significance of some of the data associations we wanted to investigate at the beginning of our research. Another limitation is represented by the retrospective nature of our study, which did not allow the complete standardization of the post-operative follow-up procedures for each patient.

Despite these limitations, our study provides significant information on the clinical presentation of upper limb schwannomas and the clinical and functional outcomes that follow their treatment with surgical enucleation. To this date, diagnosing the schwannomas of the upper limb may still represent a challenge, especially for those who lack direct experience in this field. However, once a correct diagnosis has been established, surgical resection represents a reliable and effective surgical treatment both to remove the neoplasm and provide symptom relief.

The enucleation, performed to preserve the continuity of the nerve, can substantially reduce pre-operative symptoms and restore the upper limb’s functionality, allowing patients to return to their previous activities of daily living, thereby increasing their quality of life.

The authors have no support to report.

The authors have no funding to report.