CLINICALLY SPEAKING
Schwannoma of the Left Foot A Brief Overview with Focus on Associated Clinical Syndromes Joseph R. Kallini, MD*† Amor Khachemoune, MD† In this article, we present a 25-year-old man who developed an asymptomatic schwannoma on his left lateral heel and review the salient features of this cutaneous condition. A schwannoma is a slowly growing neoplasm of Schwann cell origin. Histology shows high cellularity (Antoni A regions), nuclear palisades (Verocay bodies), and alternating myxoid regions (Antoni B regions). Very few cases have been reported on the foot or ankle. As with this patient, most schwannomas do not cause symptoms, but some result in dysesthesia and nerve dysfunction. Multiple schwannomas may indicate an underlying syndrome such as neurofibromatosis type 1, type 2, and schwannomatosis. The differential diagnosis for schwannoma includes fibrosarcoma, leiomyosarcoma, and neurofibroma. The definitive treatment is surgical excision. This usually results in complete resolution with minimal recurrence, as was the case for this patient. (J Am Podiatr Med Assoc 104(5): 535-538, 2014)
A schwannoma is a solitary, slow-growing neoplasm. These lesions were first described as neuromas in 1910 by Verocay1 and later given the name ‘‘schwannoma’’ by Masson2 in 1932. Some may reach a diameter of 17 cm.3 Schwannomas originate from Schwann cells that sheathe peripheral nerves. However, these tumors can occur in the superficial dermis.4 A variety of histologic variants exist and include cellular, ancient, and plexiform.5 Schwannomas mainly occur in the fifth decade of life, but any age group may be affected, as was the case here.6 Benign lesions are usually solitary and most commonly affect the acoustic nerve; they also occur in other cranial and peripheral nerves. Schwannomas have been noted to preferentially appear along the flexor tendons, as well as along specific nerves.7 Although a solitary benign schwannoma is reassuring, the discovery of one schwannoma should trigger a careful search for others. This is especially important considering that multiple benign lesions *Baylor College of Medicine, Houston, TX. Dr. Kallini is now with the Department of Dermatology, Saint Louis University, Saint Louis, MO. †SUNY Downstate and Veterans Affairs Hospital, Dermatology Service, Mohs Micrographic Surgery and Dermatopathology, Brooklyn, NY. Corresponding author: Amor Khachemoune, MD, SUNY Downstate and Veterans Affairs Hospital, Dermatology Service, Mohs Micrographic Surgery and Dermatopathology, 800 Poly Place, Brooklyn, New York 11209. (E-mail: [email protected])
or a malignant schwannoma may be indicative of other syndromes or pathologies. For example, more than 5% of patients with a malignant schwannoma have been found to have another primary tumor elsewhere. In addition, these lesions can be the first clinical sign of neurofibromatosis syndromes.8 Most commonly discussed in the literature are neurofibromatosis type 1, type 2, and schwannomatosis.9-11 These syndromes may be present even if the schwannomas are isolated to only a single extremity. Allelic studies for a series of mutations are particularly useful in such patients with multiple cutaneous schwannomas. We report a 25-year-old man with no relevant past medical history who presented with a solitary, biopsyconfirmed schwannoma on his lateral left heel.
Case Presentation A 25-year-old man presented to the dermatology service at SUNY Downstate (Brooklyn, New York) with a painless, asymptomatic growth on his lateral left heel that had appeared at least 1 year earlier. The patient denied any recent trauma or physical exertion. He does not have a personal or family history of skin cancer or skin disease. He denied nausea, vomiting, fever, chills, and weight loss. Cutaneous examination revealed a 3 3 3-cm fleshcolored nodule on the lateral aspect of the left heel (Fig. 1). The nodule was soft and indurated. Mild annular hyperpigmentation was also noted on the
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Figure 1. A 25-year-old man presented with this
painless, asymptomatic nodule on his lateral left heel. skin surrounding the nodule. No neurologic deficits were noted. The rest of the physical examination and laboratory results were all within normal limits. Histologic studies of the excised lesion were notable for high cellularity (Antoni A regions), nuclear palisades (Verocay bodies), and alternating myxoid regions (Antoni B regions) (Fig. 2), all of which were consistent with the diagnosis of schwannoma. No mitoses were visualized. Further immunohistochemical studies confirmed the benign nature of the tumor. The neoplasm did not recur after complete surgical excision.
Discussion This patient presented with a painless, sporadic, benign schwannoma. Half of all reported cases in the literature present asymptomatically. Otherwise, these lesions can be tender and may cause shooting pain, dysesthesia after trauma, or peripheral nerve dysfunction. The etiology of sporadic benign schwannomas is unknown but has been proposed to be secondary to trauma. Schwannomas of the lower extremity are rare. Our patient was unique in that the lesion presented in an atypical location; superficial benign schwannomas are commonly reported on the upper extremities, with less than 10% found on the foot or ankle.12 One group found a plexiform schwannoma of the left forefoot of a 65-year-old man; this was one of only 11 cases in the literature.13 Interestingly, schwannoma is the most common peripheral nerve sheath tumor of the foot and ankle. However, the overall incidence of peripheral nerve sheath tumor in this location is only 10.2%.14
536
Figure 2. A high-power view of histopathologic
staining of the nodule on the lateral left heel of a 25-year-old man shows highly cellular Antoni A tissue mixed with loosely organized Antoni B tissue and nuclear palisades (Verocay bodies). (H&E, x10). Although rare, schwannomas in the lower extremity can result in unique difficulties and sequelae. The most common presenting symptom of schwannomas of the foot and ankle is pain. They are usually smaller than their upper-extremity counterparts.13 Some have reported tarsal tunnel syndrome as a result of tibial nerve sheath impingement.15-17 One 20-year-old woman with a cellular schwannoma (a rare variant) of the right lateral great toe developed a painful, nonhealing ulcer in the region. Both the ulcer and the underlying lesion were completely resolved after surgical resection.18 Another 42-year-old man also developed ulceration of his left great toe in association with a schwannoma – also cured by blunt dissection.19 Overall, surgical excision of lower-extremity schwannomas is curative and usually does not result in postoperative neurological dysfunction.14 A unique obstacle caused by schwannomas of the lower extremity is delayed diagnosis. One group studied 25 patients with a schwannoma of the posterior tibial nerve. The mean duration of symptoms before diagnosis was 86.5 months, with a median of 48 months. Two reasons suggested for the delay in diagnosis were 1) deep-seated schwannomas of the thigh impalpable on physical exam and 2) neurological symptoms being misdiagnosed for other conditions. Twenty-four percent had been diagnosed as having lumbosacral radiculopathy, 16% as chronic regional pain syndrome, 12% with tarsal tunnel syndrome, 12% with other entrapment
September/October 2014 Vol 104 No 5 Journal of the American Podiatric Medical Association
neuropathies, and one patient with diabetic neuropathy.20 Although a solitary benign schwannoma is reassuring, multiple benign schwannomas or a malignant schwannoma may be indicative of neurofibromatosis type 1, type 2, and schwannomatosis (Table 1). According to the ‘‘Baser’’ criteria, at least two of the following clinical features must be present if neurofibromatosis type 1 is suspected: 1) six or more cafe´-au-lait spots that are greater than 5 mm in diameter in prepubertal or greater than 15 mm in diameter in postpubertal individuals; 2) two or more neurofibromas of any type or one plexiform neurofibroma; 3) freckling in the axillary or inguinal regions; 4) optic glioma; 5) two or more Lisch nodules (iris hamartomas); 6) a distinctive bony lesion such as sphenoid dysplasia or thinning of the long bone cortex with or without pseudoarthrosis; and 7) a first-degree relative (parent, sibling, or offspring) with neurofibromatosis type 1.21 If neurofibromatosis type 2 is suspected, one of the following criteria must be present: 1) bilateral vestibular schwannomas; 2) a first-degree relative with neurofibromatosis type 2 and either a) a unilateral vestibular schwannoma or b) any two of the following: meningioma, schwannoma, glioma, neurofibroma, and posterior subcapsular lenticular opacities; 3) unilateral vestibular schwannoma and any two of the following: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities; 4) multiple meningiomas and either a) a unilateral vestibular schwannoma or b) any two of the following: schwannoma, glioma, neurofibroma, and cataract.22 The following criteria are diagnostic of schwannomatosis: 1) presence of two or more noncutaneous schwannomas; 2) absence of vestibular tumor; and 3) absence of an NF-2 mutation. If a first-degree relative has confirmed schwanno-
matosis, then only one nonvestibular schwannoma is necessary for diagnosis of schwannomatosis.23 The differential diagnosis of schwannoma is listed in Table 2.24-26 It is also important to differentiate schwannomas from neurofibromas, as the latter would indicate neurofibromatosis type 2 and the need for alternate work-up. Also, neurofibromas are more likely to undergo malignant transformation. The definitive treatment of a schwannoma is surgical excision. This is usually followed by histopathologic analysis to rule out malignancy and the possible existence of another pathology. Excision results in good prognosis with rare recurrence.27
Patient Follow-Up Our 25-year-old patient presented with a single painless schwannoma of his left heel, the lower extremities being an uncommon location. The patient did not develop associated neuropathy or ulceration. Meticulous total body skin examination did not reveal multiple similar lesions, thus ruling out concerning pathologies such as neurofibromatosis type 1, type 2, and schwannomatosis. The lesion of this patient was completely excised without recurrence.
Conclusions A schwannoma is a slow-growing neoplasm that originates from Schwann cells that sheathe peripheral nerves. A variety of histologic variants exist: cellular, ancient, and plexiform. Histologic studies show Antoni A and B regions and Verocay bodies. Less than 10% of schwannomas occur on the foot or ankle. Schwannomas of the lower extremity pose unique problems that include delayed diagnosis, neuropathies, and ulceration. Half of all cases are
Table 1. Syndromes Associated with Multiple Schwannomas. Syndrome
Clinical Features
References
NF-1
Neurofibromas, iris hamartomas, osseous lesions, freckling, CNS tumors, pheochromocytoma, neurofibrosarcoma, malignant schwannoma, Wilm’s tumor
Kluwe, et al11
NF-2
Neurofibroma, meningioma, glioma, schwannoma (most commonly affecting acoustic nerve), juvenile posterior subcapsular lenticular opacities
Jacobson et al12
Schwannomatosis
Multiple schwannomas on cranial, peripheral, and spinal nerves as well as other locations. Sometimes limited to certain extremities (known as segmental schwannomatosis)
Izumi10 and Milnes15
Abbreviations: CNS, central nervous system; NF, neurofibromatosis
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Table 2. Differential Diagnosis for Schwannoma Neurofibromas. While neurofibromas contain heterogeneous mixtures of cells such as fibroblasts and Schwann cells, a key distinguishing feature is that schwannomas are solely composed of Schwann cells.16 Fibrosarcoma and leiomyosarcoma. These may be difficult to differentiate from cutaneous schwannomas and require immunohistochemistry to confirm diagnosis. Leiomyosarcoma stains positive for muscle cell markers such as actin and vimentin, while a fibrosarcoma stains positive for vimentin and negative for actin.17,18
asymptomatic, although some cause dysesthesia and nerve dysfunction. Multiple schwannomas may indicate an underlying syndrome such as neurofibromatosis type 1, type 2, and schwannomatosis. The differential diagnosis for schwannoma includes neurofibroma, fibrosarcoma, and leiomyosarcoma. The definitive treatment is surgical excision, which results in minimal recurrence. A 25-year-old man with no relevant past medical history presented with a solitary, biopsy-confirmed schwannoma on his lateral left heel; standard excision was curative. Financial Disclosure: None reported. Conflict of Interest: None reported.
References 1. VEROCAY J: Zur Kenntnis der ‘‘Neurofibrome.’’ Beitr Pathol Anat 48: 60, 1910. 2. MASSON P: Recklinghausen’s Neurofibromatosis, Sensory Neuromas and Motor Neuromas, Vol 2, p 793, International Press, New York, 1932. 3. PASTERNACK WA, WINTER-REIKEN DJ: Unusually large cellular schwannoma of the foot. JAPMA 95: 157, 2005. 4. RITTER SE, ELSTON DM: Cutaneous schwannoma of the foot. Cutis 67: 127, 2001. 5. REQUENA L, SANGUEZA OP: Benign neoplasms with neural differentiation: a review. Am J Dermatopathol 17: 75, 1995. 6. KRANSDORF MJ: Benign soft-tissue tumors in a large referral population: distribution of specific diagnoses by age, sex, and location. AJR Am J Roentgenol 164: 395, 1995. 7. LIEBAU C, BALTZER AW, SCHNEPPENHEIM M, ET AL: Isolated peripheral neurilemoma attached to the tendon of the flexor digitorum longus muscle. Arch Orthop Trauma Surg 123: 98, 2003. 8. RUGGIERI M: The different forms of neurofibromatosis. Childs Nerv Syst 15: 295, 1999. 9. MURRAY AJ, HUGHES TA, NEAL JW, ET AL: A case of multiple cutaneous schwannomas: schwannomatosis or neurofibromatosis type 2? J Neurol Neurosurg Psychiatry 77: 269, 2006.
538
10. IZUMI AK, ROSATO FE, WOOD MG: Von Recklinghausen’s disease associated with multiple neurolemomas. Arch Dermatol 104: 172, 1971. 11. KLUWE L, FRIEDRICH RE, HAGEL C, ET AL: Mutations and allelic loss of the NF2 gene in neurofibromatosis 2associated skin tumors. J Invest Dermatol 114: 1017, 2000. 12. JACOBSON GF, EDWARDS MC JR: Neurilemoma presenting as a painless mass on the dorsum of the foot. JAPMA 83: 228, 1993. 13. JACOBSON JM, FELDER JM 3RD, PEDROSO F, ET AL: Plexiform schwannoma of the foot: a review of the literature and case report. J Foot Ankle Surg 50: 68, 2011. 14. CARVAJAL JA, CUARTAS E, QADIR R, ET AL: Peripheral nerve sheath tumors of the foot and ankle. Foot Ankle Int 32: 163, 2011. 15. MILNES HL, PAVIER JC: Schwannoma of the tibial nerve sheath as a cause of tarsal tunnel syndrome: a case study. Foot (Edinb) 22: 243, 2012. 16. KWOK KB, LUI TH, Lo WN: Neurilemmoma of the first branch of the lateral plantar nerve causing tarsal tunnel syndrome. Foot Ankle Spec 2: 287, 2009. 17. MANGRULKAR VH, BRUNETTI VA, GOULD ES, ET AL: Unusually large pedal schwannoma. J Foot Ankle Surg 46: 398, 2007. 18. NATH AK, SANMARKAN AD, D’SOUZA M, ET AL: Non-healing ulcer on the great toe due to cellular schwannoma. Clin Exp Dermatol 34: e904, 2009. 19. OC¸GU¨DER A, UG˘URLU M, TECIMEL O, ET AL: [A case of ancient schwannoma of the great toe]. Acta Orthop Traumatol Turc 42: 382, 2008. 20. NAWABI DH, SINISI M: Schwannoma of the posterior tibial nerve: the problem of delay in diagnosis. J Bone Joint Surg Br 89: 814, 2007. 21. DEBELLA K, SZUDEK J, FRIEDMAN JM: Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics 105: 608, 2000. 22. BASER ME, FRIEDMAN JM, JOE H, ET AL: Empirical development of improved diagnostic criteria for neurofibromatosis 2. Genet Med 13: 576, 2011. 23. WESTHOUT FD, MATHEWS M, PARE´ LS, ET AL: Recognizing schwannomatosis and distinguishing it from neurofibromatosis type 1 or 2. J Spinal Disord Tech 20: 329, 2007. 24. SHARMA S, SARKAR C, MATHUR M, ET AL: Benign nerve sheath tumors: a light microscopic, electron microscopic and immunohistochemical study of 102 cases. Pathology 22: 191, 1990. 25. SACHDEV R, SINGHAL N, MANDAL AK: Congenital fibrosarcoma of the upper extremity: a case report and review of literature. Indian J Pathol Microbiol 48: 474, 2005. 26. YAMAMOTO T, MINAMI R: Epithelioid leiomyosarcoma of the external deep soft tissue. Arch Pathol Lab Med 126: 468, 2002. 27. MOTT RC, DELLON AL: Multiple schwannomas of the foot. Case report and strategy for treatment. JAPMA 93: 51, 2003.
September/October 2014 Vol 104 No 5 Journal of the American Podiatric Medical Association
Schwannoma of the Left Foot A Brief Overview with Focus on Associated Clinical Syndromes Joseph R. Kallini, MD*† Amor Khachemoune, MD† In this article, we present a 25-year-old man who developed an asymptomatic schwannoma on his left lateral heel and review the salient features of this cutaneous condition. A schwannoma is a slowly growing neoplasm of Schwann cell origin. Histology shows high cellularity (Antoni A regions), nuclear palisades (Verocay bodies), and alternating myxoid regions (Antoni B regions). Very few cases have been reported on the foot or ankle. As with this patient, most schwannomas do not cause symptoms, but some result in dysesthesia and nerve dysfunction. Multiple schwannomas may indicate an underlying syndrome such as neurofibromatosis type 1, type 2, and schwannomatosis. The differential diagnosis for schwannoma includes fibrosarcoma, leiomyosarcoma, and neurofibroma. The definitive treatment is surgical excision. This usually results in complete resolution with minimal recurrence, as was the case for this patient. (J Am Podiatr Med Assoc 104(5): 535-538, 2014)
A schwannoma is a solitary, slow-growing neoplasm. These lesions were first described as neuromas in 1910 by Verocay1 and later given the name ‘‘schwannoma’’ by Masson2 in 1932. Some may reach a diameter of 17 cm.3 Schwannomas originate from Schwann cells that sheathe peripheral nerves. However, these tumors can occur in the superficial dermis.4 A variety of histologic variants exist and include cellular, ancient, and plexiform.5 Schwannomas mainly occur in the fifth decade of life, but any age group may be affected, as was the case here.6 Benign lesions are usually solitary and most commonly affect the acoustic nerve; they also occur in other cranial and peripheral nerves. Schwannomas have been noted to preferentially appear along the flexor tendons, as well as along specific nerves.7 Although a solitary benign schwannoma is reassuring, the discovery of one schwannoma should trigger a careful search for others. This is especially important considering that multiple benign lesions *Baylor College of Medicine, Houston, TX. Dr. Kallini is now with the Department of Dermatology, Saint Louis University, Saint Louis, MO. †SUNY Downstate and Veterans Affairs Hospital, Dermatology Service, Mohs Micrographic Surgery and Dermatopathology, Brooklyn, NY. Corresponding author: Amor Khachemoune, MD, SUNY Downstate and Veterans Affairs Hospital, Dermatology Service, Mohs Micrographic Surgery and Dermatopathology, 800 Poly Place, Brooklyn, New York 11209. (E-mail: [email protected])
or a malignant schwannoma may be indicative of other syndromes or pathologies. For example, more than 5% of patients with a malignant schwannoma have been found to have another primary tumor elsewhere. In addition, these lesions can be the first clinical sign of neurofibromatosis syndromes.8 Most commonly discussed in the literature are neurofibromatosis type 1, type 2, and schwannomatosis.9-11 These syndromes may be present even if the schwannomas are isolated to only a single extremity. Allelic studies for a series of mutations are particularly useful in such patients with multiple cutaneous schwannomas. We report a 25-year-old man with no relevant past medical history who presented with a solitary, biopsyconfirmed schwannoma on his lateral left heel.
Case Presentation A 25-year-old man presented to the dermatology service at SUNY Downstate (Brooklyn, New York) with a painless, asymptomatic growth on his lateral left heel that had appeared at least 1 year earlier. The patient denied any recent trauma or physical exertion. He does not have a personal or family history of skin cancer or skin disease. He denied nausea, vomiting, fever, chills, and weight loss. Cutaneous examination revealed a 3 3 3-cm fleshcolored nodule on the lateral aspect of the left heel (Fig. 1). The nodule was soft and indurated. Mild annular hyperpigmentation was also noted on the
Journal of the American Podiatric Medical Association Vol 104 No 5 September/October 2014
535
Figure 1. A 25-year-old man presented with this
painless, asymptomatic nodule on his lateral left heel. skin surrounding the nodule. No neurologic deficits were noted. The rest of the physical examination and laboratory results were all within normal limits. Histologic studies of the excised lesion were notable for high cellularity (Antoni A regions), nuclear palisades (Verocay bodies), and alternating myxoid regions (Antoni B regions) (Fig. 2), all of which were consistent with the diagnosis of schwannoma. No mitoses were visualized. Further immunohistochemical studies confirmed the benign nature of the tumor. The neoplasm did not recur after complete surgical excision.
Discussion This patient presented with a painless, sporadic, benign schwannoma. Half of all reported cases in the literature present asymptomatically. Otherwise, these lesions can be tender and may cause shooting pain, dysesthesia after trauma, or peripheral nerve dysfunction. The etiology of sporadic benign schwannomas is unknown but has been proposed to be secondary to trauma. Schwannomas of the lower extremity are rare. Our patient was unique in that the lesion presented in an atypical location; superficial benign schwannomas are commonly reported on the upper extremities, with less than 10% found on the foot or ankle.12 One group found a plexiform schwannoma of the left forefoot of a 65-year-old man; this was one of only 11 cases in the literature.13 Interestingly, schwannoma is the most common peripheral nerve sheath tumor of the foot and ankle. However, the overall incidence of peripheral nerve sheath tumor in this location is only 10.2%.14
536
Figure 2. A high-power view of histopathologic
staining of the nodule on the lateral left heel of a 25-year-old man shows highly cellular Antoni A tissue mixed with loosely organized Antoni B tissue and nuclear palisades (Verocay bodies). (H&E, x10). Although rare, schwannomas in the lower extremity can result in unique difficulties and sequelae. The most common presenting symptom of schwannomas of the foot and ankle is pain. They are usually smaller than their upper-extremity counterparts.13 Some have reported tarsal tunnel syndrome as a result of tibial nerve sheath impingement.15-17 One 20-year-old woman with a cellular schwannoma (a rare variant) of the right lateral great toe developed a painful, nonhealing ulcer in the region. Both the ulcer and the underlying lesion were completely resolved after surgical resection.18 Another 42-year-old man also developed ulceration of his left great toe in association with a schwannoma – also cured by blunt dissection.19 Overall, surgical excision of lower-extremity schwannomas is curative and usually does not result in postoperative neurological dysfunction.14 A unique obstacle caused by schwannomas of the lower extremity is delayed diagnosis. One group studied 25 patients with a schwannoma of the posterior tibial nerve. The mean duration of symptoms before diagnosis was 86.5 months, with a median of 48 months. Two reasons suggested for the delay in diagnosis were 1) deep-seated schwannomas of the thigh impalpable on physical exam and 2) neurological symptoms being misdiagnosed for other conditions. Twenty-four percent had been diagnosed as having lumbosacral radiculopathy, 16% as chronic regional pain syndrome, 12% with tarsal tunnel syndrome, 12% with other entrapment
September/October 2014 Vol 104 No 5 Journal of the American Podiatric Medical Association
neuropathies, and one patient with diabetic neuropathy.20 Although a solitary benign schwannoma is reassuring, multiple benign schwannomas or a malignant schwannoma may be indicative of neurofibromatosis type 1, type 2, and schwannomatosis (Table 1). According to the ‘‘Baser’’ criteria, at least two of the following clinical features must be present if neurofibromatosis type 1 is suspected: 1) six or more cafe´-au-lait spots that are greater than 5 mm in diameter in prepubertal or greater than 15 mm in diameter in postpubertal individuals; 2) two or more neurofibromas of any type or one plexiform neurofibroma; 3) freckling in the axillary or inguinal regions; 4) optic glioma; 5) two or more Lisch nodules (iris hamartomas); 6) a distinctive bony lesion such as sphenoid dysplasia or thinning of the long bone cortex with or without pseudoarthrosis; and 7) a first-degree relative (parent, sibling, or offspring) with neurofibromatosis type 1.21 If neurofibromatosis type 2 is suspected, one of the following criteria must be present: 1) bilateral vestibular schwannomas; 2) a first-degree relative with neurofibromatosis type 2 and either a) a unilateral vestibular schwannoma or b) any two of the following: meningioma, schwannoma, glioma, neurofibroma, and posterior subcapsular lenticular opacities; 3) unilateral vestibular schwannoma and any two of the following: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities; 4) multiple meningiomas and either a) a unilateral vestibular schwannoma or b) any two of the following: schwannoma, glioma, neurofibroma, and cataract.22 The following criteria are diagnostic of schwannomatosis: 1) presence of two or more noncutaneous schwannomas; 2) absence of vestibular tumor; and 3) absence of an NF-2 mutation. If a first-degree relative has confirmed schwanno-
matosis, then only one nonvestibular schwannoma is necessary for diagnosis of schwannomatosis.23 The differential diagnosis of schwannoma is listed in Table 2.24-26 It is also important to differentiate schwannomas from neurofibromas, as the latter would indicate neurofibromatosis type 2 and the need for alternate work-up. Also, neurofibromas are more likely to undergo malignant transformation. The definitive treatment of a schwannoma is surgical excision. This is usually followed by histopathologic analysis to rule out malignancy and the possible existence of another pathology. Excision results in good prognosis with rare recurrence.27
Patient Follow-Up Our 25-year-old patient presented with a single painless schwannoma of his left heel, the lower extremities being an uncommon location. The patient did not develop associated neuropathy or ulceration. Meticulous total body skin examination did not reveal multiple similar lesions, thus ruling out concerning pathologies such as neurofibromatosis type 1, type 2, and schwannomatosis. The lesion of this patient was completely excised without recurrence.
Conclusions A schwannoma is a slow-growing neoplasm that originates from Schwann cells that sheathe peripheral nerves. A variety of histologic variants exist: cellular, ancient, and plexiform. Histologic studies show Antoni A and B regions and Verocay bodies. Less than 10% of schwannomas occur on the foot or ankle. Schwannomas of the lower extremity pose unique problems that include delayed diagnosis, neuropathies, and ulceration. Half of all cases are
Table 1. Syndromes Associated with Multiple Schwannomas. Syndrome
Clinical Features
References
NF-1
Neurofibromas, iris hamartomas, osseous lesions, freckling, CNS tumors, pheochromocytoma, neurofibrosarcoma, malignant schwannoma, Wilm’s tumor
Kluwe, et al11
NF-2
Neurofibroma, meningioma, glioma, schwannoma (most commonly affecting acoustic nerve), juvenile posterior subcapsular lenticular opacities
Jacobson et al12
Schwannomatosis
Multiple schwannomas on cranial, peripheral, and spinal nerves as well as other locations. Sometimes limited to certain extremities (known as segmental schwannomatosis)
Izumi10 and Milnes15
Abbreviations: CNS, central nervous system; NF, neurofibromatosis
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Table 2. Differential Diagnosis for Schwannoma Neurofibromas. While neurofibromas contain heterogeneous mixtures of cells such as fibroblasts and Schwann cells, a key distinguishing feature is that schwannomas are solely composed of Schwann cells.16 Fibrosarcoma and leiomyosarcoma. These may be difficult to differentiate from cutaneous schwannomas and require immunohistochemistry to confirm diagnosis. Leiomyosarcoma stains positive for muscle cell markers such as actin and vimentin, while a fibrosarcoma stains positive for vimentin and negative for actin.17,18
asymptomatic, although some cause dysesthesia and nerve dysfunction. Multiple schwannomas may indicate an underlying syndrome such as neurofibromatosis type 1, type 2, and schwannomatosis. The differential diagnosis for schwannoma includes neurofibroma, fibrosarcoma, and leiomyosarcoma. The definitive treatment is surgical excision, which results in minimal recurrence. A 25-year-old man with no relevant past medical history presented with a solitary, biopsy-confirmed schwannoma on his lateral left heel; standard excision was curative. Financial Disclosure: None reported. Conflict of Interest: None reported.
References 1. VEROCAY J: Zur Kenntnis der ‘‘Neurofibrome.’’ Beitr Pathol Anat 48: 60, 1910. 2. MASSON P: Recklinghausen’s Neurofibromatosis, Sensory Neuromas and Motor Neuromas, Vol 2, p 793, International Press, New York, 1932. 3. PASTERNACK WA, WINTER-REIKEN DJ: Unusually large cellular schwannoma of the foot. JAPMA 95: 157, 2005. 4. RITTER SE, ELSTON DM: Cutaneous schwannoma of the foot. Cutis 67: 127, 2001. 5. REQUENA L, SANGUEZA OP: Benign neoplasms with neural differentiation: a review. Am J Dermatopathol 17: 75, 1995. 6. KRANSDORF MJ: Benign soft-tissue tumors in a large referral population: distribution of specific diagnoses by age, sex, and location. AJR Am J Roentgenol 164: 395, 1995. 7. LIEBAU C, BALTZER AW, SCHNEPPENHEIM M, ET AL: Isolated peripheral neurilemoma attached to the tendon of the flexor digitorum longus muscle. Arch Orthop Trauma Surg 123: 98, 2003. 8. RUGGIERI M: The different forms of neurofibromatosis. Childs Nerv Syst 15: 295, 1999. 9. MURRAY AJ, HUGHES TA, NEAL JW, ET AL: A case of multiple cutaneous schwannomas: schwannomatosis or neurofibromatosis type 2? J Neurol Neurosurg Psychiatry 77: 269, 2006.
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September/October 2014 Vol 104 No 5 Journal of the American Podiatric Medical Association
