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Research ArticleClinical Studies

Schwannoma of Foot and Ankle: Seven Case Reports and Literature Review

XINGPEI HAO, DAVID LEVINE, JOON YIM, CHENFENG QI, LEE FIRESTONE, IAN BEISER, ENZO LEONE, KIRK WOELFFER and GENE MIRKIN
Anticancer Research September 2019, 39 (9) 5185-5194; DOI: https://doi.org/10.21873/anticanres.13715
XINGPEI HAO
1Foot and Ankle Specialists of the Mid-Atlantic, LLC., Rockville, MD, U.S.A.
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  • For correspondence: xhao@footandankle-usa.com gmirkin@footandankle-usa.com
DAVID LEVINE
1Foot and Ankle Specialists of the Mid-Atlantic, LLC., Rockville, MD, U.S.A.
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JOON YIM
1Foot and Ankle Specialists of the Mid-Atlantic, LLC., Rockville, MD, U.S.A.
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CHENFENG QI
2Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, U.S.A.
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LEE FIRESTONE
1Foot and Ankle Specialists of the Mid-Atlantic, LLC., Rockville, MD, U.S.A.
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IAN BEISER
1Foot and Ankle Specialists of the Mid-Atlantic, LLC., Rockville, MD, U.S.A.
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ENZO LEONE
1Foot and Ankle Specialists of the Mid-Atlantic, LLC., Rockville, MD, U.S.A.
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KIRK WOELFFER
1Foot and Ankle Specialists of the Mid-Atlantic, LLC., Rockville, MD, U.S.A.
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GENE MIRKIN
1Foot and Ankle Specialists of the Mid-Atlantic, LLC., Rockville, MD, U.S.A.
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  • For correspondence: xhao@footandankle-usa.com gmirkin@footandankle-usa.com
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Abstract

Background: Schwannoma is most often grown on the trunk, upper and lower extremities, and head and neck, but rarely on the foot. This study aimed to reveal clinical presentations, histopathology and treatment options for schwannoma of the foot. Materials and Methods: Seven schwannomas out of 174 soft-tissue tumors on the foot and ankle were retrieved from our Institute in a 3-year period, and 42 schwannomas on the foot and ankle in the literature in a 30-year period were reviewed. Results: The incidence of schwannoma of foot was found to be 4.0%. The patient age ranged from 8 to 84 years, with a mean of 47.4 years. More than 80% of tumors were located on the ankle, heel and plantar aspect. Overall, 77.6% of patients complained about a painful mass. Magnetic resonance imaging revealed a well-circumscribed, round or ovoid mass with iso-intensity signal compared with surrounding neuromuscular tissues on T1-weighted images and hyper-intensity signal on T2. Forty-eight out of 49 patients were treated with surgical excision or enucleation without recurrence in follow-up from 2 months to 4 years. Histologically, schwannoma was composed of hypercellular Antoni A zone with palisaded spindle cells with strong immunostaining for S-100 and hypocellular Antoni B zone with vascularization in myxoid stroma. Conclusion: Schwannoma of the foot and ankle is a rare, painful, indurated tumor. Magnetic resonance imaging reveals the location, size, texture and relationships with surrounding neuromuscular structures. Surgical excision is the primary treatment option with excellent outcome.

  • Ankle
  • excision
  • foot
  • MRI
  • pathology
  • schwannoma

Schwannoma, also called neurilemoma, derived from Schwann cells in the peripheral nerves, is a solid, slow-growing tumor. It was first reported by Verocay in 1910 (1), and was named ‘schwannoma’ by Masson in 1932 (2). Schwannoma accounts for about 5% benign tumors as revealed by an analysis of 18,677 benign soft-tissue tumors by Kransdorf (3) and others (4). It frequently occurs in the trunk, flexor side of upper and lower extremities, head and neck (3, 5, 6), especially in the eighth cranial vestibular nerves (7-9), but is uncommon on the foot and ankle (10-12). Toepfer et al. observed 11 (10.5%) neurinomas, including both schwannoma and neurofibroma, out of 104 benign soft-tissue tumors of the foot and ankle at a university tumor institute between 1997 and 2015 (13). Kehoe et al. recorded 12 out of 104 (11.5%) peripheral nerve tumors on the foot in a 32-year period (7), and Carvajal et al. reported eight out of 87 (9.2%) schwannomas were located on the foot in a 16-year period observation (14). In 1969, Das Gupta et al. analyzed 303 schwannomas with none of them being on the foot (5), whereas in 1998 with Chaudhuri, they reported four out of 104 schwannomas to be found on the foot (15). Odom et al. reviewed 557 schwannomas and noted 19 (2.93%) involving the foot (16). Most published results were reports of single case or small case series. Here, we report seven cases of schwannoma on the foot and ankle from our Institute in a 3-year period, and further review 42 cases in the literature from 1988 to date in a 30-year period, with the aim of describing its clinical manifestations, diagnosis, differential diagnosis and treatment options.

Patients and Methods

All tumors on the foot and ankle were retrospectively analyzed from Foot and Ankle Specialists of Mid-Atlantic (FASMA) in a 3-year period from Sept 1st 2015 to Aug 30th, 2018. FASMA comprises 63 podiatrists located in Washington DC, Maryland, Virginia, North Carolina and Pennsylvania who treat various foot and ankle conditions. All pathology slides of schwannomas were reviewed with confirmation of the original diagnoses (XPH). Clinicopathological features were retrieved from FASMA's database, analyzed by one observer (XPH) and were further confirmed by the referring podiatrists.

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Table I.

Clinicopathological characteristics of study patients with schwannoma on the foot and ankle.

Results

Clinicopathological characteristics of schwannoma of foot and ankle. In total, seven schwannomas out of 174 benign soft-tissue tumors were diagnosed in the foot and ankle areas in a 3-year period. The incidence of schwannoma of the foot and ankle was 4.0%. The clinicopathological characteristics of seven schwannomas are shown in Table I.

English literature of 42 schwannomas involving the foot and ankle from 1988 for a 30-year period were reviewed (Table II). Only cases with clear age, gender, size, site, MRI, histology report, treatment, follow-up etc. were included for further analysis. Other reports without detailed clinical information were not included. This brought the number to a total of 49 patients including the current seven cases, making this the most detailed analysis of schwannomas involving the foot and ankle. The clinicopathological features were analyzed based on these 49 cases.

Clinically, most of the patients (38/49, 77.6%) complained of painful mass on the foot or ankle with or without weakness or paresthesia. Three patients exhibited tarsal tunnel syndrome due to involvement of the tibial nerve in the tarsal tunnel. The duration from the symptom onset to surgery ranged from 2 months to 48 years, with a mean and median of 7.3 and 3 years, respectively. Both males and females were equally affected (males to females: 1:1). The patients' ages ranged from 8 to 84 years, with a mean and median of 47.4 and 51.5 years, respectively. The tumor size ranged from 0.38 cm to 14 cm in diameter, with an average of 3.3 cm and a median of 2.5 cm. The tumor locations of 46 patients were retrieved, with 28 (60.9%) being located on the left side. The tumors were mainly localized on the ankle (14/46, 30.3%), plantar aspect (14/46, 30.3%) and heel (9/46, 19.6%). Three tumors were found in the dorsal web of the interdigital spaces, one on the dorsum of the foot. Sub-anatomical locations on the foot were not specified in five patients. Out of the 49 patients, 29 were pre-surgically examined by magnetic resonance imaging (MRI). Typical MRI of schwannoma showed a well-circumscribed, round or oval mass with isointense or reduced signal intensity relative to surrounding skeletal muscle on T1-weighted images and significantly increased homogeneous or heterogeneous signal intensity on T2-weighted images (Figure 1). Fascicular sign (fascicular bundles in neurogenic tumors), target sign (centrally decreased with peripherally increased signal intensity) and split-fat sign (a rim of fat surrounding the tumor), reflecting different proportions of stromal tissues and tumor components (4), were described. Forty-eight out of 49 patients were selected to undergo surgical excision or enucleation, whereas one patient from our series opted for observation after biopsy due to the small size. No recurrences were reported, with a period of follow-up from 2 months to four years.

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Table II.

Review of clinicopathological features of patients with schwannoma on the foot and ankle reported in literature.

Grossly, schwannomas were usually round, ovoid, well-circumscribed, solid masses. The cut surface was often gray to yellow, solid, glistening and well-encapsulated. Degenerative changes including cystic formation and hemorrhage were observed in some cases. Histopathologically, the majority of schwannomas exhibited typical biphasic morphology, composed of hypercellular Antoni A and hypocellular Antoni B zones. Antoni A zone consisted of elongated spindle cells with indistinct borders palisaded together, forming a Verocay body, while Antoni B presented reduced cellularity in a myxoid matrix with increased vascularization (Figure 2). Other variants, including plexiform and ancient types, were reported. One variant of schwannoma with ‘ancient’ changes in our series showed atypical nuclei with increased size and chromatin density. Immunostain showed strong positive cytoplasmic staining for S-100 but negative staining for alpha smooth actin (αSMA) and CD34 in spindle cells (Figure 2). One of our patients showed coexistence of compound melanocytic nevus with underlying schwannoma, both neval cells of the nevus and spindle cells of the schwannoma exhibited positive staining for both S-100 and HMB-45.

Figure 1.
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Figure 1.

Magnetic resonance imaging of patient 1 showing a well-circumscribed, solid mass along the posteromedial aspect of the right ankle with iso-intensity signal relative to surrounding muscles on T1-weighted images (A, coronal view; C, sagittal view) and hyperintensity signal on T2-weighted images (B: coronal view, D: sagittal view).

Figure 2.
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Figure 2.

Microphotographs of hematoxylin and eosin and immunostained schwannoma on the heel of patient 2. A: A full view of the slide showing a well-circumscribed subcutaneous mass with hypercellular and hypocellular regions (×2). Inset shows areas described in B and C. B: The Antoni A zone, characterized by spindle Schwann cells arranged in palisading pattern (Verocay body) (×200). C: The left third of the image shows the Verocay body in (A), while the right two-thirds shows Antoni B zone featuring hypocellularity in myxoid stroma (×200). D: Microphotograph showing strong S-100 immunoexpression in tumor whereas surrounding stromal tissues were negative (×5). E: Higher magnification of D showing S-100 cytoplasmic expression in spindle tumor cells where the encapsulated fibroblasts were negative (×200). F: Microphotograph of immunostaining showing negative alpha-smooth muscle actin expression in spindle tumor cells but strong positive expression in vascular smooth muscle cells among tumor cells and surrounding stromal tissues, which served as an internal positive control (×100).

Discussion

We presented seven cases of schwannoma of foot and ankle with its clinical manifestation, histopathology and treatment. Schwannoma accounted for 4.0% among 174 benign soft-tissue tumors involving the foot and ankle diagnosed in a 3-year period at our Institute with 63 podiatrists. Ruggieri et al. reported that 14 schwannomas out of 189 benign soft-tissue tumors of the foot (7.5%) were diagnosed at the Rizzoli Institute in an 18-year period between 1990 and 2007 (12). These data further support the observation that schwannoma on the foot and ankle is rare.

Clinically, schwannoma on the foot and ankle usually presents as a painful, movable, well-defined mass; weakness and paresthesia can be observed when associated nerves are affected. The symptoms are mainly related to the tumor location, especially on the sites of weight bearing or easily compressed regions including the plantar aspect and inter-digital spaces. Tinel sign and tarsal tunnel syndrome can be elicited when the tibial nerve is evoked. Even though tumor can occur on any part of the foot, the most frequent locations were found to be the ankle, heel and plantar aspect of the foot (78.3%). Occurrences in interdigital spaces and on dorsum of foot were uncommon. Both males and females were found to be equally affected. Interestingly, 60.9% of tumors occurred on the left foot. The modalities of pre-surgical diagnosis include X-ray radiography, ultrasound and MRI. Radiography usually does not reveal remarkable changes unless calcification noticed inside tumor tissue or bone tissues are involved. Ultrasound examination of schwannoma usually exhibits a round or ovoid, solid, well-delineated, hypoechoic homogenous mass and is useful for distinguishing between cystic and solid lesions. MRI is the most valuable tool for evaluating schwannoma, not only for location, size and texture, but also for relationships with nerves and other surrounding anatomical structures. Typical MRI of schwannomas show isointense or reduced signal intensity relative to surrounding skeletal muscle on T1-weighted images and significantly increased signal intensity on T2-weighted images.

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Table III.

Differential diagnosis of schwannoma from other tumor types.

Surgical excision or enucleation is the primary treatment option, even though for a smaller tumor observation can be opted for. Extreme care needs to be taken to dissect the tumor from associated nerves in order to preserve or restore nerve functions to a maximal level. Recurrence is extremely rare (less than 1%) unless tumor tissue is incompletely excised (4, 17, 18).

Morphologically, schwannoma of the foot and ankle is similar to that at other sites of the body. It is composed of an Antoni A zone with hypercellularity with palisaded spindle cells arranged in short bundles or fascicles, and an Antoni B zone with hypocellularity with vascu-larization in myxoid matrix. Immunostaining for S-100 is positive, whereas that for αSMA and CD34 is negative, which is useful for diagnosis and differential diagnosis. One of our patients had coexistence of compound melanocytic nevus and underlying schwannoma. It is not clear if there is any etiological relationship between these two lesions.

Schwannoma on the foot and ankle needs to be differentiated from other lesions, including ganglion cyst, neuroma, spindle-cell lipoma, neurofibroma, solitary fibrous tumor, fibroma, leiomyoma. Careful clinical and histopathological evaluation with immunohistochemistry can lead to an accurate diagnosis (Table III).

Trauma, Carney's complex, and neurofibromatosis type 1 or 2 may be associated with the development of schwannoma (19). One of our patients related frequently hitting the inside of his ankle against his chair at work as the probable cause of his tumor. In total, four [one of our cases plus three others (20-22)] out of 49 patients (8.0%) reported minor trauma in the related areas before development of schwannoma. In one patient, schwannoma was associated with neurofibromatosis 1 (14), whereas no clinical presentation of neurofibromatosis for any of the other patients, suggesting that the majority of schwannomas involving the foot and ankle occur spontaneously.

In conclusion, schwannoma on the foot is a rare tumor. Both males and females are equally affected. It is histologically composed of palisaded spindle cells forming Antoni A and B zones. Ultrasound and MRI are good diagnostic tools for revealing tumor location, size, texture, involved nerves and relationships with surrounding muscular structures. Surgical excision is the primary treatment option with recurrence being rare.

Footnotes

  • Authors' Contributions

    Xingpei Hao: Study conceptualization, data collection, analysis and interpretation, writing and revising the article. David Levine: Patient care, data collection, analysis and interpretation, article revision. Joon Yim: Diagnosis, data collection, analysis and interpretation, article revision. Chenfeng Qi: Diagnosis, data collection, analysis and interpretation, article revision. Lee Firestone: Patient care, data collection, analysis and interpretation, article revision. Ian Beiser: Patient care, data collection, analysis and interpretation, article revision. Enzo Leone: Patient care, data collection, analysis and interpretation, article revision. Kirk Woelffer: Patient care, data collection, analysis and interpretation, article revision. Gene Mirkin: Study conceptualization, patient care, data collection, analysis and interpretation, coordination, article revision.

  • Financial Disclosure

    None reported.

  • Conflicts of Interest

    None reported.

  • Received July 23, 2019.
  • Revision received August 8, 2019.
  • Accepted August 9, 2019.
  • Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

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Anticancer Research: 39 (9)
Anticancer Research
Vol. 39, Issue 9
September 2019
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Schwannoma of Foot and Ankle: Seven Case Reports and Literature Review
XINGPEI HAO, DAVID LEVINE, JOON YIM, CHENFENG QI, LEE FIRESTONE, IAN BEISER, ENZO LEONE, KIRK WOELFFER, GENE MIRKIN
Anticancer Research Sep 2019, 39 (9) 5185-5194; DOI: 10.21873/anticanres.13715

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Schwannoma of Foot and Ankle: Seven Case Reports and Literature Review
XINGPEI HAO, DAVID LEVINE, JOON YIM, CHENFENG QI, LEE FIRESTONE, IAN BEISER, ENZO LEONE, KIRK WOELFFER, GENE MIRKIN
Anticancer Research Sep 2019, 39 (9) 5185-5194; DOI: 10.21873/anticanres.13715
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Keywords

  • Ankle
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  • Schwannoma
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