Radiologic–pathologic discrepancy in a plexiform schwannoma of the ulnar nerve mimicking a malignant soft-tissue tumor: A case report

Abstract

Schwannomas are common benign peripheral nerve sheath tumors; however, plexiform variants may exhibit atypical imaging features and mimic malignant soft-tissue tumors. We report a 24-year-old woman presenting with a slowly enlarging mass in the proximal forearm associated with ulnar nerve paresthesia. Ultrasound showed a heterogeneous hypervascular lesion with irregular margins. MRI demonstrated a 33 × 24 × 49 mm mass with T2 hyperintensity, avid enhancement, and a pseudo-infiltrative appearance involving adjacent flexor muscles, raising suspicion for malignancy. Classical MRI signs of benign peripheral nerve sheath tumors were not clearly identified. Ultrasound-guided biopsy suggested a benign spindle-cell tumor compatible with perineurioma. Following fascicle-sparing microsurgical excision, definitive histopathology revealed a plexiform schwannoma, characterized by multinodular architecture, Antoni A and B areas, Verocay bodies, diffuse S100 positivity, and negative EMA staining. At 3-month follow-up, no recurrence was observed and functional outcome was favorable. This case highlights a significant radiologic-pathologic discrepancy and underscores the limitations of imaging and core biopsy in heterogeneous peripheral nerve sheath tumors, emphasizing the importance of integrated diagnostic correlation.

Introduction

Benign schwannomas are slow-growing peripheral nerve sheath tumors, a substantial proportion of which occur in the upper extremity [1]. In this location, they usually present as a gradually enlarging mass, sometimes associated with pain or paresthesia due to nerve compression [1,2]. Functional outcomes after surgery are generally favorable when dissection preserves the nerve fascicles [3]. From a pathologic standpoint, schwannomas belong to the spectrum of peripheral nerve sheath tumors and are distinguished from other spindle-cell neoplasms, particularly perineuriomas and neurofibromas, by their Schwann-cell differentiation and characteristic histologic architecture [4]. Large surgical series have nevertheless shown that peripheral nerve sheath tumors may pose significant preoperative diagnostic challenges, especially when their clinical or radiologic presentation is atypical [5]. Recent upper-limb series further support early management of symptomatic lesions [6].

Magnetic resonance imaging is the reference imaging modality for preoperative evaluation of peripheral nerve sheath tumors [7]. Schwannomas typically appear as well-defined masses with T2 hyperintensity and postcontrast enhancement, often demonstrating imaging features suggestive of neural origin, including the target sign, fascicular sign, split-fat sign, or entering/exiting nerve sign [7,8]. However, atypical or plexiform variants may lack these characteristic findings and instead exhibit marked heterogeneity, hypervascularity, avid enhancement, or a pseudo-infiltrative appearance, making differentiation from malignant peripheral nerve sheath tumors and soft-tissue sarcomas particularly challenging [9,10].

We report a case of a large plexiform schwannoma arising from the proximal ulnar nerve, characterized by discordance between imaging, preoperative biopsy, and definitive histopathological analysis.

Case presentation

A 24-year-old woman with no significant past medical or surgical history presented with a progressively enlarging mass located on the proximal posteromedial aspect of the left forearm. There was no history of trauma, smoking, alcohol consumption, neurofibromatosis, hereditary disorders, or family history of peripheral nerve tumors or malignancy. The lesion had first appeared approximately 6 years before presentation and had gradually increased in size. During the preceding 6 months, the patient reported increasing local discomfort associated with intermittent electric-shock-like pain and paresthesia involving the fourth and fifth digits of the left hand.

Physical examination revealed a firm oval-shaped mass measuring approximately 5 cm in greatest dimension, located on the proximal posteromedial aspect of the left forearm. The lesion was mobile relative to the overlying skin at rest but became relatively fixed to deeper structures during muscle contraction. The overlying skin was intact without ulceration, discoloration, or trophic changes. Palpation elicited local tenderness without palpable thrill. Neurological examination demonstrated a positive Tinel sign over the lesion and hypoesthesia involving the fourth and fifth digits, corresponding to the sensory territory of the ulnar nerve. No motor deficit, intrinsic hand muscle atrophy, or regional lymphadenopathy was identified (Fig. 1).

Fig. 1.

Preoperative clinical appearance showing swelling of the proximal third of the left forearm.

Preoperative laboratory investigations revealed iron-deficiency anemia with a hemoglobin level of 8.5 g/dL (reference range 12-16 g/dL), microcytosis (mean corpuscular volume 64.3 fL; reference range 80-98 fL), and hypochromia (mean corpuscular hemoglobin 18.7 pg; reference range 27-32 pg). Platelet count was elevated at 575 × 10⁹/L (reference range 150-400 ×10⁹/L), consistent with reactive thrombocytosis secondary to iron deficiency. Renal function and coagulation parameters were within normal limits. Iron supplementation was prescribed preoperatively.

Soft-tissue ultrasound demonstrated a heterogeneous hypoechoic mass with increased Doppler flow, irregular borders, and dimensions of 38 × 35 × 22 mm. The appearance was considered suspicious for malignancy.

Magnetic resonance imaging demonstrated a 33 × 24 × 49 mm soft-tissue mass located within the anteroulnar compartment of the proximal forearm. The lesion demonstrated slight T1 hyperintensity and marked T2 hyperintensity, with avid heterogeneous enhancement following gadolinium administration. MRI revealed a hypervascular lesion extending from the subcutaneous tissue to the deep muscular compartment, with apparent transgression of the superficial fascia and close contact with the ulnar nerve, which appeared flattened without a clearly identifiable cleavage plane. The lesion also demonstrated apparent extension toward the flexor carpi ulnaris and flexor digitorum profundus muscles, creating a pseudo-infiltrative appearance. No osseous involvement was identified.

Notably, classical MRI signs usually associated with benign peripheral nerve sheath tumors, including the target sign, split-fat sign, and a definite entering/exiting nerve sign, were not clearly demonstrated. The fascicular pattern was difficult to appreciate because of the lesion's heterogeneous multinodular architecture. Given these findings, a malignant soft-tissue tumor was initially considered the leading diagnostic hypothesis (Fig. 2).

Fig. 2.

Magnetic resonance imaging of the left forearm demonstrating a peripheral nerve sheath tumor with atypical features suggestive of malignancy. (A) Axial T1-weighted image showing a lobulated soft-tissue mass in the anteroulnar compartment of the proximal forearm (white arrow), closely related to the ulnar nerve. (B) Axial fat-suppressed postgadolinium T1-weighted image demonstrating avid heterogeneous enhancement and marked hypervascular appearance of the lesion (white arrow). (C) Coronal T2-weighted image showing longitudinal extension of the mass along the flexor compartment, apparent involvement of adjacent flexor muscles, and a pseudo-infiltrative appearance (white arrow), without osseous involvement.

Ultrasound-guided biopsy revealed a benign spindle-cell proliferation without cytologic atypia or significant mitotic activity, initially interpreted as compatible with a soft-tissue perineurioma.

The procedure was performed under regional anesthesia via an axillary block. Through a longitudinal approach, the ulnar nerve was identified proximal and distal to the lesion. Despite the aggressive appearance suggested by preoperative imaging, intraoperative exploration revealed a well-circumscribed lesion closely related to the ulnar nerve, displacing rather than infiltrating the adjacent nerve fascicles. Microsurgical enucleation under magnification was performed with preservation of the nerve fascicles and macroscopically complete excision (Fig. 3).

Fig. 3.

Intraoperative and macroscopic findings. (A) Intraoperative view after exposure of the ulnar nerve. (B) Macroscopic appearance of the surgical specimen after complete fascicle-sparing microsurgical excision.

Histopathological examination of the surgical specimen showed a multinodular proliferation separated by fibrous septa, forming a plexiform architecture. The nodules consisted of spindle-shaped cells arranged in intersecting bundles with alternating compact Antoni A areas and looser Antoni B areas. Focal Verocay bodies were identified. The tumor cells had elongated, wavy nuclei without significant atypia, necrosis, or notable mitotic activity.

Immunohistochemically, the lesion showed diffuse and strong S100 expression, negative EMA staining, and weak focal CD34 expression.

These findings established the diagnosis of plexiform schwannoma (Fig. 4).

Fig. 4.

Histopathological examination of the lesion. (A) Low-power view showing a multinodular plexiform architecture (Hematoxylin–Eosin–Saffron, ×2). (B) Medium-power view demonstrating a biphasic pattern with alternating Antoni A and Antoni B areas (HES, ×5). (C) High-power view revealing Verocay bodies characterized by palisading nuclei (HES, ×40). (D) Immunohistochemistry showing strong and diffuse S100 protein expression in tumor cells.

The postoperative course was uneventful. The surgical wound healed without infection, and no postoperative motor deficit was observed. At the first postoperative follow-up, the Tinel sign had become negative, while mild residual hypoesthesia involving the fourth and fifth digits persisted.

Histopathological examination confirmed the diagnosis of plexiform schwannoma. During subsequent follow-up, sensory symptoms progressively improved. At the 3-month follow-up visit, the patient was in excellent clinical condition, with preserved motor and sensory function, no significant limitation of daily activities, and no clinical evidence of local recurrence.

Discussion

Schwannomas of the upper extremity typically present as slowly enlarging masses, sometimes painful, and may be associated with paresthesia or a positive Tinel sign [[1], [2], [3]]. Large clinical series have shown a predominance of upper-extremity locations and an overall benign course when appropriate surgical management is provided [[1], [2], [3]]. Our case fits this general clinical pattern but stands out because of its size, unusual imaging appearance, and, most importantly, the discrepancy observed across the diagnostic work-up.

From a pathophysiologic and surgical perspective, schwannomas usually develop eccentrically relative to the parent nerve and displace nerve fascicles rather than infiltrating them [4,5]. This explains why enucleation or intracapsular excision with fascicular preservation is often feasible, unlike neurofibromas, which are more commonly intraneural and infiltrative [4,5]. This distinction was particularly relevant in our case, as intraoperative exploration demonstrated an encapsulated lesion arising eccentrically from the ulnar nerve without gross fascicular invasion.

The radiologic interest of this case lies in its pseudoaggressive MRI appearance. Classical MRI features of schwannoma are well described, but large lesions may lose their typical appearance and mimic a more aggressive soft-tissue neoplasm [7,8]. MRI criteria associated with suspicion for malignancy, including larger size, heterogeneity, ill-defined margins, and apparent extension into adjacent planes, are useful but not specific [9]. This overlap is clinically important because malignant peripheral nerve sheath tumors are aggressive sarcomas whose imaging distinction from certain atypical benign lesions may remain difficult [10]. In the present case, avid enhancement, hypervascularity, and pseudo-infiltrative morphology were sufficiently concerning to raise the possibility of malignancy despite the slow clinical course. Furthermore, classical MRI signs commonly associated with benign peripheral nerve sheath tumors, including the target sign, split-fat sign, and a definite entering/exiting nerve sign, were not clearly identified. The fascicular pattern was also difficult to appreciate because of the lesion's heterogeneous multinodular architecture, further contributing to the suspicion of malignancy [7,8].

A second unusual feature was the discrepancy between the biopsy and the definitive specimen. Core biopsy suggested a soft-tissue perineurioma, whereas complete excision established plexiform schwannoma. This discrepancy is plausible in a heterogeneous multinodular lesion because biopsy samples only a limited portion of the tumor and may fail to reflect its global architecture [4,11,12]. In soft-tissue perineurioma, EMA and often claudin-1 or GLUT1 are typically positive, whereas diffuse S100 positivity and Verocay bodies support schwannoma [4,12]. In our patient, only complete histopathologic assessment of the resected specimen, combined with immunohistochemistry, allowed definitive reclassification.

The plexiform nature of the lesion deserves specific emphasis. Plexiform schwannoma is an uncommon benign variant characterized by multinodular growth. Although often described in superficial soft tissues, it may also involve major peripheral nerves. Malignant transformation is exceptionally rare, but incomplete resection may increase the risk of local recurrence compared with conventional solitary schwannoma. These features support complete but function-preserving surgery whenever feasible.

Regarding treatment, the available surgical data are consistent with the strategy adopted in the present case. Large series have shown that surgery for symptomatic peripheral nerve sheath tumors yields favorable results when atraumatic fascicle-sparing dissection is prioritized [5,11]. Intracapsular micro-enucleation has also been shown to reduce the risk of iatrogenic nerve injury [13]. More recent upper-limb data confirm that preoperative MRI is sensitive but not perfectly specific and that outcomes after excision are generally favorable, although transient postoperative sensory symptoms may occur [6,14]. In our patient, absence of postoperative motor deficit and gradual sensory improvement support the appropriateness of conservative microsurgical excision. At 3-month follow-up, no clinical evidence of recurrence was observed, and the patient demonstrated an excellent functional outcome with preserved motor function and progressive sensory recovery.

Ultimately, this case is noteworthy not only because it involves a large plexiform schwannoma of the proximal ulnar nerve, but above all because it illustrates a classic diagnostic pitfall: imaging suggestive of a malignant soft-tissue tumor, biopsy interpreted as soft-tissue perineurioma, and definitive histopathology establishing plexiform schwannoma. It underscores that no single test is infallible and that management of atypical peripheral nerve sheath tumors should rely on careful integration of radiologic, pathologic, and intraoperative findings.

Conclusion

A large plexiform schwannoma of the proximal ulnar nerve may closely mimic a malignant soft-tissue tumor on imaging, particularly when classical MRI signs of benign peripheral nerve sheath tumors are absent. This case highlights the potential for discordance between MRI, core biopsy, and definitive histopathological diagnosis in heterogeneous peripheral nerve sheath tumors. Close radiologic-pathologic correlation and fascicle-sparing microsurgical excision are essential to achieve both diagnostic accuracy and functional preservation.

Author contributions

All authors contributed to the conception of the work, data collection, manuscript drafting, and critical revision of the article. All authors approved the final version of the manuscript.

Patient consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request.