Clinical, Radiological, and Histological Characteristics of Intraosseous Schwannoma: Case Series of a Rare Benign Neoplasm of Bone

Abstract

Background and Objective

Schwannomas of intraosseous location represent an extremely rare clinical presentation of a benign bone neoplasm originating from Schwann cells. Its rarity and the broad spectrum of possible differential diagnoses render intraosseous schwannoma diagnostically challenging. Currently, only scattered evidence is available in the literature. We aimed, therefore, to summarize our clinical experience with this rare histological entity.

Materials and Methods

A retrospective clinical chart review was performed, and seven patients with an intraosseous schwannoma were identified, including six female and one male patient. The mean age of included cases was 42 years (range: 17–58). In four patients (57%), the axial skeleton was affected, of which three cases involved the spine and one case involved the acetabulum.

Results

The other three cases of intraosseous schwannomas were located in the lower extremity, with one case in the distal femur, one case in the distal tibia, and another case in the distal fibula, respectively. Spinal presentation was invariably associated with large extraosseous components. In all cases, a biopsy was performed. All included patients were symptomatic and underwent surgical removal of the tumor. Histology from biopsy and surgery matched in all cases and confirmed the diagnosis of an intraosseous schwannoma.

Conclusion

Intraosseous schwannomas show a considerable heterogeneity in clinical presentation, patients' age, and tumor location. Combined with its rarity, diagnosis can be challenging and warrants a multidisciplinary approach with orthopaedic surgeons, radiologists, and pathologists. The diagnosis is incumbent on the combined radiological and histological appearance. Indication for surgical removal is guided by the patients' symptoms and the risk of impending fracture.

Keywords

pathologists - orthopaedic surgeons - retrospective studies - bone neoplasms lower extremity - radiologists

Introduction

Schwannomas are commonly encountered benign neoplasms arising from Schwann cells in peripheral nerve sheaths.[1] Intraosseous involvement, however, is extremely rare. Estimates suggest a ratio of 1 to 2 per 1,000 primary bone tumors, in itself an already very rare entity.[2] Three distinct mechanisms involved in the development of intraosseous schwannomas were postulated, including primary extraosseous schwannomas causing secondary bone erosion, schwannomas originating in the nutrient canal, and primary central intraosseous schwannomas.[2] [3] [4] Various locations of intraosseous schwannomas were described, while the most commonly reported sites include the mandible and the sacrum.[5] [6] Epi-, meta-, and diaphyseal location with involvement of various bones of the appendicular skeleton were reported.[2] [3] [4] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] Also, a case with multiple sites of intraosseous schwannomas in the foot was published.[29] Clinical presentation was reported to include unspecific pain in the area of the affected bone and also two cases of pathological fractures of the humerus.[3] [7] [8] [10] [30] [31] There are also cases of intraosseous schwannoma of the spine at various levels available in literature.[32] Unspecific back pain and also neurological complications and fractures of involved or adjacent vertebral bodies can be associated with spinal intraosseous schwannomas.[33]

Diagnostic workup includes plain radiographs, which demonstrate lytic and geocentric bone lesion, and magnetic resonance imaging (MRI) showing benign features but characteristics of local aggressive growth with bone erosion and endosteal scalloping are commonly encountered.[16] These uncharacteristic radiological appearance warrants a biopsy in every case in view of numerous possible differential diagnoses. The spectrum of these is broad and includes bone sarcomas, soft tissue sarcomas with osseous infiltration, chordoma, malignant nerve sheath tumor, giant cell tumor, aneurysmal bone cyst, osteomyelitis, metastatic bone deposits, brown tumor, and hematological disease among others.[13] Histologically, intraosseous schwannomas are comparable to their soft tissue counterparts with both cellular and myxoid components.[2] [3] [31]

Treatment of intraosseous schwannomas comprises surgical removal and defect reconstruction based on the tumor location.[8] [10] [30] Local recurrence was described in isolated cases, particularly in cases of incomplete excision, but surgical removal was reported to be generally associated with satisfactory outcomes.[5] [20] [34]

The aim of this paper was to review the experience of intraosseous schwannoma from a single institution, looking particularly at the histological and radiological appearances as well as the outcomes following surgery.

Materials and Methods

The study was performed at a single tertiary referral center for orthopaedic oncology. The institutional review board approved the study protocol and waived the need for patients' informed consent as this study was of retrospective nature. A retrospective clinical chart review was performed using a prospectively maintained database capturing details in over 61,000 patients treated between 1983 and 2022 to identify patients diagnosed with intraosseous schwannoma. All included cases were reviewed by orthopaedic surgeons, radiologists, and pathologists trained in musculoskeletal oncology and discussed in the local sarcoma multidisciplinary team meeting to confirm the diagnosis.

Results

Clinical Characteristics

Patients' details are listed in [Table 1]. A total of seven patients were identified, which represents 0.01% of cases available in our database. The first patient diagnosed with intraosseous schwannoma in our database was treated in 2008, whereas the last included patient was treated in 2022, respectively. All patients but one were female and the mean age was 42 years (range: 17–58). None of the included cases had a known history of neurofibromatosis. One case (#1) was referred to our center for a recurrent intraosseous schwannoma and had undergone two previous excisions prior to referral. The remaining six cases were treatment-naïve. All patients underwent investigation in the form of plain radiographs, MRI, and biopsy. Five patients (71%) underwent computed tomography (CT) guided biopsy, whereas two patients had a percutaneous needle biopsy. Tumor dimensions were available in six cases and ranged from 17.39 cm² in a distal fibula (case #3) to 1,000 cm² in a sacrum (case #2) (median: 54.33 cm²).

Table 1 Demographics and clinical details of included patients

Patient number	Sex	Age	Previous surgery	Location	Soft tissue mass	Symptoms	Type of procedure	Complications
1	Female	56	Intralesional curettage × 2	Acetabulum	No	Mechanical hip pain	Curettage	No
2	Female	50	–	Sacrum	Yes	Sciatica, incontinence	N/A	N/A
3	Female	17	–	Fibula/DTFJ	No	Pain after trauma	Curettage/bone grafting	No
4	Female	21	–	Vertebral body L4	Yes	Lower back pain, stenotic symptoms	Excision and spinal reconstruction	Infection
5	Female	58	–	Vertebral body L4	Yes	Lower back pain, stenotic symptoms	Excision and spinal reconstruction	No
6	Female	38	–	Distal femur	No	Unspecific knee pain	Curettage/bone grafting	No
7	Male	54	–	Distal tibia	Yes	Pain, swelling	Curettage/bone grafting + cementation	No

Abbreviations: DTFJ, distal tibiofibular joint; N/A, not applicable.

The clinical and radiological presentations for the seven patients included in the study are shown in [Table 1]. The location of the tumor varied. In our series, spinal involvement was the most common site (n = 3), of which one case involved the sacrum and the remaining two cases involved the fourth lumbar vertebral body. The remaining cases involved the acetabulum, the distal femur, the distal tibia, and the distal fibula, involving the distal tibiofibular joint [Fig. 1]–[4]. In five cases, long-standing nonspecific symptoms led to further investigation. Spinal involvement was associated with an unspecific lower back pain in all cases. One case of spinal involvement was associated with stenotic symptoms. In one case (patient 2), the patient presented with a 1-year history of worsening sciatic radiculopathy complicated by a sudden onset of urinary and fecal incontinence. MRI demonstrated a large lytic sacral lesion with an extensive extraosseous intra- and extrapelvic soft tissue component. Patient 1 presented with a recurrent intraosseous schwannoma of the acetabulum with mechanical hip pain. Patient 3 presented with an ankle sprain and suspected fracture. Imaging demonstrated an intraosseous schwannoma of the distal fibula with involvement of the distal tibiofibular joint. Patient 6 presented with 2 years of knee pain with no benefit from conservative management, including physiotherapy and pain medication. Patient 7 presented with more than 10 years of ankle pain and swelling.

Details of surgical management were available for six patients. In two patients with spinal involvement, this included marginal excision and reconstruction. Involvement of the acetabulum, femur, and distal fibula was treated with intralesional curettage and bone grafting in the latter two cases. In Case 7, a combination of bone grafting and cementation was used following detailed intralesional curettage.

Clinical follow-up was available for three patients. Patient 1 presented with significant neuropathic pain around the right hip at final available follow-up at 51 months, most likely related to nerve damage caused by three previous curettages. There was no clear evidence of recurrent or residual disease on repeated MRI over the course of the follow-up. The patient died of an unrelated cause shortly thereafter. Curettage of the distal fibula and distal femur in patients 3 and 6, respectively, was associated with complete remission of symptoms shortly after the surgical intervention and discharged from follow-up consultations four months after surgery. There was one surgery-related complication in patient 4 with a superficial wound infection, which was successfully treated with a short course of oral antibiotics.

Radiological Findings

Findings on plain radiographs were nonspecific in all cases. Common features included a lytic appearance with an intraosseous well-defined zone of transition with a narrow sclerotic rim ([Fig. 1A]). Tumors arising from the spine, in general, were larger and more often associated with an extraosseous component when compared with tumors arising from the appendicular skeleton. Tumors arising from the spine were often associated with canal compromise and neurological symptoms due to extraosseous extension. In general, intraosseous schwannomas were seen as well-defined lesions on MRI with low signal on T1 sequences and high signal on fluid-sensitive sequences. Cystic change with fluid–fluid level was observed in larger intraosseous schwannomas ([Fig. 3B]). Endosteal scalloping was encountered in both cases of appendicular intraosseous schwannoma. Intraosseous schwannoma of the distal fibula (case 3) was associated with extension into the distal tibiofibular joint, causing scalloping of the fibular notch of the distal tibia. No perilesional soft tissue or osseous oedema was seen in our series. There were no imaging features of denervation with no edema or fatty atrophy of adjacent muscles.

Fig. 1 Intraosseous schwannoma in the medial condyle of the distal femur (patient #6) on plain radiographs (A: anteroposterior, B: lateral) and fat-suppressed fast-spin echo proton density weighted sequences on magnetic resonance imaging (C: axial, D: sagittal).

Fig. 2 Intraosseous schwannoma with large soft tissue mass arising from the fourth lumbar vertebra (patient #4) on magnetic resonance imaging (A: coronal short inversion time inversion recovery (STIR), B: coronal T1, C: axial STIR, D: axial computed tomography).

Fig. 3 Large intraosseous schwannoma arising from the sacrum on magnetic resonance imaging (patient #2, A: axial T1, B: sagittal T2).

Fig. 4 Case #7 presenting with a relatively large intraosseous schwannoma in the distal tibia with soft tissue mass (A–C: intraoperative images, D–E: preoperative T2 fat suppressed sagittal (D) and axial (E), F: postoperative X-ray).

Histological Presentation

These tumors presented as large expansile lytic lesions. The morphological presentation featured an unencapsulated and firm mass with a pale tan colored cut surface. We also noted cystic degeneration in some cases. Similar to its soft tissue counterpart, intraosseous schwannoma shows variable cellularity and nuclear palisades known as Verocay bodies. These tumors strongly expressed S100 ([Fig. 5B]) and SOX10 in all cases.

Fig. 5 Representative histological appearance of an intraosseous schwannoma in the hematoxylin and eosin staining (A). High expression of S-100 in areas of high cellularity (B).

Discussion

Intraosseous schwannoma are an extremely rare form of a benign bone tumor. Histological findings in our series are in agreement with previously published reports and include characteristic Verocay bodies found in cellular-rich areas with concomitant high expression of S-100 and SOX10.[3] [9] Negative staining for desmin and smooth muscle cell actin is an important hallmark for distinction from potential differential diagnoses.[3] [9] Compared with soft tissue schwannomas, intraosseous schwannomas are associated with slightly increased cellularity with less organized nuclear palisading and Verocay bodies.[3] [9] In general, different subtypes of schwannomas are distinguished based on cellular differentiation.[8] There are reports of cases of melanotic, plexiform, and epithelioid intraosseous schwannomas.[35] [36] [37] [38] None of these subtypes was identified in our series.

An association with neurofibromatosis and intraosseous schwannoma was reported; however, these cases usually represent primary extraosseous schwannomas with secondary bone erosion (e.g., schwannoma arising from sacral nerve roots with secondary bone erosion) and exhibit a distinct histopathological appearance and microarchitecture.[1] [2] [9] Furthermore, intraosseous schwannomas were reported in cases of schwannomatosis.[39] Malignant transformation of a recurrent intraosseous schwannoma not associated with neurofibromatosis has also been reported.[34] While none of the included cases in this series involved these variants, these must be considered as part of the diagnostic workup.

As intraosseous schwannoma is a nonmalignant diagnosis, the difficulty in surgical treatment is to find the balance between ensuring effective treatment to improve symptoms while minimizing the risk of recurrence and avoiding unnecessary surgical morbidity. While the best surgical approach for the management of intraosseous schwannoma remains dictated largely by the anatomical location, intralesional procedures are known to be associated with an increased risk of local recurrence, although the available evidence is poor at defining the exact risk of recurrence.[5] [20] [34] Complete removal was associated with satisfactory outcomes in our series in concordance with the available literature.[8] [10] [30]

In 2002, our group published a case of bifocal subperiosteal schwannomas of the femur, which was not included in this report due to the extraosseous location.[40]

The question remains whether all intraosseous schwannomas are symptomatic. If not, then the actual prevalence may be higher due to unreported cases. There are no reports available regarding incidental findings with subsequent observation, as invariably, patients included in any series have presented with symptoms. Therefore, we can only assume that for this rare histological entity, patients invariably have symptoms. Lesion-related symptoms and/or an impending fracture risk are the main indications for surgical intervention in intraosseous schwannoma.

The majority of patients in our series was female, but the literature provides numerous case reports for both sexes without predilection for neither females nor males.[2] [3] [4] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] Interestingly, patients in a recent case series were all female and tumors were exclusively located in the lumbosacral region.[41]

Given its rarity and unspecific appearance on imaging, we strongly recommend discussion of every suspected case of intraosseous schwannoma in a dedicated sarcoma multidisciplinary team meeting to guide further diagnostic and therapeutic management. The surgical management is entirely dependent on the location of the tumor, as the risk of collateral damage at the time of surgical intervention must be offset by the potential reduction in local recurrence by en bloc excision. In some cases, such as in the sacrum or in craniofacial locations, this may simply not be possible, and intralesional surgery may be more appropriately balanced by the risk of recurrence. In all cases, malignant entities must be excluded prior to surgery to prevent inadvertent and inappropriate intervention of a malignant neoplasm.

Limitations

As this study was a retrospective chart review, several limitations are inherent. As intraosseous schwannomas represent an extremely rare clinical entity, we were able to only include a small number of patients in this case series. Also, clinical follow-up was only partially available.

Conflict of Interest

None declared.

Authors' Contributions

Conceptualization: T.H., M.C.P., V.S.; methodology: T.H., V.S., R.B.; validation: M.C.P., V.S.; data curation: T.H.; writing—original draft: T.H., V.S.; writing—review and editing: M.C.P., R.B.

• References

• 1 Helbing DL, Schulz A, Morrison H. Pathomechanisms in schwannoma development and progression. Oncogene 2020; 39 (32) 5421-5429
• 2 Fawcett KJ, Dahlin DC. Neurilemmoma of bone. Am J Clin Pathol 1967; 47 (06) 759-766
• 3 McAleese T, Clesham K, Moloney D, Hughes A, Faheem N, Merghani K. Intraosseous schwannoma of the femur in a patient with monoclonal gammopathy of undetermined significance. Int J Surg Case Rep 2020; 72: 494-498
• 4 Suzuki K, Yasuda T, Watanabe K, Kanamori M, Kimura T. Association between intraosseous schwannoma occurrence and the position of the intraosseous nutrient vessel: a case report. Oncol Lett 2016; 11 (05) 3185-3188
• 5 Handa K, Ozawa H, Aizawa T. et al. Surgical management of giant sacral schwannoma: a case series and literature review. World Neurosurg 2019; 129: e216-e223
• 6 Kardouni Khoozestani N, Motiee-Langroudi M, Salehi A, Ranji P. Intraosseous ancient schwannoma: a rare case in the mandible and a literature review. Rare Tumors 2021 ;13:20363613211026480
• 7 Kamath J, Shetty HB, Madegowda A, Bhatt AS. Intraosseous schwannoma of the humerus: a rarity yet warrants consideration. BMJ Case Rep 2021; 14 (09) e240007
• 8 Lim KX, Wu K. First-ever intraosseous ancient schwannoma of the proximal ulna successfully treated using the cement technique. J Int Med Res 2021; 49 (02) 300060520987732
• 9 de la Monte SM, Dorfman HD, Chandra R, Malawer M. Intraosseous schwannoma: histologic features, ultrastructure, and review of the literature. Hum Pathol 1984; 15 (06) 551-558
• 10 Haberal B, Turkbey Simsek D, Simsek EK. Intraosseous schwannoma of the calcaneus: a rare tumor of the bone. Case Rep Orthop 2018; 2018: 9824025
• 11 Al-Lhedan F. Schwannoma of the femur: a rare case report. J Bone Oncol 2017; 8: 1-3
• 12 Kito M, Yoshimura Y, Isobe K, Aoki K, Momose T, Kato H. Intraosseous neurilemmoma of the proximal ulna. Int J Surg Case Rep 2014; 5 (12) 914-918
• 13 Igai H, Kamiyoshihara M, Kawatani N, Ibe T, Shimizu K. Sternal intraosseous schwannoma mimicking breast cancer metastasis. J Cardiothorac Surg 2014; 9: 116
• 14 Flores Santos F, Pinheiro M, Felicíssimo P. Large foot schwannoma with bone invasion - a case report. Foot Ankle Surg 2014; 20 (02) e23-e26
• 15 Tian YW, Zhang LY, Liu ZQ. Giant intraosseous schwannoma of scapula: a rare case report and review of the literature. Diagn Pathol 2014; 9: 31
• 16 Wang T, Giugale JM, Ding M, Goodman MA, Schoedel K, Rao UN. Primary intraosseous schwannoma in tibial epiphysis with unique immunohistochemical phenotype: a case report. Int J Surg Pathol 2014; 22 (06) 574-578
• 17 Wang XJ, Hartley K, Holt GE, Fadare O, Cates JM. Intracortical schwannoma of the femur. Skeletal Radiol 2014; 43 (05) 687-691
• 18 Hoshi M, Takada J, Oebisu N, Nakamura H. Intraosseous schwannoma of the proximal femur. Asia Pac J Clin Oncol 2012; 8 (03) e29-e33
• 19 Afshar A, Afaghi F. Intraosseous schwannoma of the second metacarpal: case report. J Hand Surg Am 2010; 35 (05) 776-779
• 20 Ang WM, Yates P, Robbins P, Wood D. Recurrent benign solitary intraosseous schwannoma of the tibia. Orthopedics 2008; 31 (02) 176
• 21 Meyer A, Sailhan F, Coulomb A. et al. Proximal tibial epiphyseal intraosseous schwannoma: a rare entity. J Pediatr Orthop 2008; 28 (07) 786-790
• 22 Meek RM, Sharma H, Jane MJ, Raby N, Macduff E, Reid R. Solitary intraosseous schwannoma of the metatarsal bone: a case report. Foot Ankle Int 2007; 28 (07) 845-848
• 23 Kujala S, Kallioinen M, Forsman M, Ryhänen J. Intraosseous schwannoma of the middle phalanx. Scand J Plast Reconstr Surg Hand Surg 2006; 40 (05) 318-320
• 24 Ilgenfritz RM, Jones KB, Lueck N, Buckwalter JA. Intraosseous neurilemmoma involving the distal tibia and fibula: a case report. Iowa Orthop J 2006; 26: 138-143
• 25 Mutema GK, Sorger J. Intraosseous schwannoma of the humerus. Skeletal Radiol 2002; 31 (07) 419-421
• 26 Vora RA, Mintz DN, Athanasian EA. Intraosseous schwannoma of the metacarpal. Skeletal Radiol 2000; 29 (04) 224-226
• 27 Aoki J, Tanikawa H, Fujioka F. et al. Intraosseous neurilemmoma of the fibula. Skeletal Radiol 1997; 26 (01) 60-63
• 28 Sanado L, Ruiz JL, Laidler L, Polo M. Femoral intraosseous neurilemoma. Arch Orthop Trauma Surg 1991; 110 (04) 212-213
• 29 Wang G, Wen X, Qu L, Qi X, Yang C. Intraosseous schwannoma involving multiple bones of the foot: a case report. J Foot Ankle Surg 2016; 55 (01) 201-206
• 30 Reyniers P, Wafa H, Sinnaeve F, Debeer P, Sciot R. Intraosseous schwannoma of the glenoid: case report and literature review. SICOT J 2021; 7: 2
• 31 Huajun J, Wei Q, Yuxuan W, Jingjing Y. Intraosseous schwannoma of the proximal humerus with pathologic fracture. Eur J Med Res 2021; 26 (01) 72
• 32 Naidu MR, Dinakar I, Rao KS, Ratnakar KS. Intraosseous schwannoma of the cervical spine associated with skeletal fluorosis. Clin Neurol Neurosurg 1988; 90 (03) 257-260
• 33 Nooraie H, Taghipour M, Arasteh MM, Daneshbod K, Erfanie MA. Intraosseous schwannoma of T12 with burst fracture of L1. Arch Orthop Trauma Surg 1997; 116 (6-7): 440-442
• 34 Peng X, Chen L, Du H, Lai Y, Li F, Zou X. Malignant transformation of benign intraosseous schwannoma in the cervical spine: a case report with an immunohistochemical study. Int Surg 2011; 96 (04) 337-344
• 35 Kim MJ, Choi J, Khang SK, Kim JS, Lee JS, Cho KJ. Primary intraosseous melanotic schwannoma of the fibula associated with the Carney complex. Pathol Int 2006; 56 (09) 538-542
• 36 Bhandarkar GP, Shetty KV, Desai D. Intramandibular plexiform schwannoma presenting as a nonspecific benign lesion: how specific can we be? A case report with a review of the literature. J Cancer Res Ther 2020; 16 (03) 641-646
• 37 Nagashima Y, Nishimura Y, Eguchi K. et al. Intraosseous melanotic schwannoma in the sacrum mimicking primary bone tumor. NMC Case Rep J 2020; 7 (03) 107-111
• 38 Lang Y, Liu D, Xiang P, Wang J, Li Y. Primary intraosseous hybrid epithelioid schwannoma/perineurioma in the proximal tibia: a case report of benign hybrid neoplasm with local hypercellularity. Diagn Pathol 2019; 14 (01) 51
• 39 Kashima TG, Gibbons MR, Whitwell D. et al. Intraosseous schwannoma in schwannomatosis. Skeletal Radiol 2013; 42 (12) 1665-1671
• 40 Verma RR, Khan MT, Davies AM, Mangham DC, Grimer RJ. Subperiosteal schwannomas of the femur. Skeletal Radiol 2002; 31 (07) 422-425
• 41 Shomal Zadeh F, Azhideh A, Mantilla JG. et al. Imaging features of intraosseous schwannoma: a case series and review of the literature. Diagnostics (Basel) 2023; 13 (09) 1610

Publication History

Article published online:
29 January 2026