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Bilateral Plexiform Neurofibromas of the Posterior Interosseous Nerve Mimicking Dorsal Wrist Ganglions
CASE REPOSITORY
Bilateral Plexiform Neurofibromas of the Posterior Interosseous Nerve Mimicking Dorsal Wrist Ganglions Rikesh A. Gandhi, MD,* David J. Bozentka, MD*†
A 33-year-old woman presented with bilateral dorsal wrist masses associated with pain and limited range of motion. On initial presentation, the masses were believed to be ganglion cysts and the patient opted for observation. Three years later, she was found to have a chest wall mass diagnosed by biopsy to be a neurofibroma. When she later returned to seek treatment for her wrist masses, magnetic resonance imaging demonstrated posterior interosseous nerve (PIN) neurofibromas. Dorsal wrist masses situated over the scapholunate interval are commonly attributed to ganglion cysts. Neurofibromas of the PIN, although rare, should be considered in the differential diagnosis when a mass elicits pain with percussion, fails to transilluminate, fails aspiration, or if the patient has a history of neurofibromas elsewhere in the body. (J Hand Surg Am. 2019;-(-):1.e1-e4. Copyright Ó 2019 by the American Society for Surgery of the Hand. All rights reserved.) Key words Dorsal wrist mass, intraneural, neurofibroma, posterior interosseous nerve.
D
is frequently encountered by hand surgeons. Although commonly attributed to a ganglion cyst, hand surgeons should be aware of other potential causes of a painful, persistent dorsal wrist mass. Intrinsic lesions of the posterior interosseous nerve (PIN) such as peripheral nerve sheath tumors (PNSTs) have rarely been described in the literature.1 Their incidence is unknown. Distal PIN PNSTs, where the nerve courses through the fourth extensor compartment, may present as an isolated dorsal wrist mass. ORSAL WRIST PAIN AND SWELLING
From the *Department of Orthopaedic Surgery, University of Pennsylvania; and the †Department of Orthopaedic Surgery, Penn Presbyterian Medical Center, Philadelphia, PA Received for publication February 26, 2019; accepted in revised form October 7, 2019. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article. Corresponding author: Rikesh A. Gandhi, MD, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA; e-mail: [email protected]. 0363-5023/19/---0001$36.00/0 https://doi.org/10.1016/j.jhsa.2019.10.016
Benign PNSTs include schwannomas and neurofibromas. Each can occur either sporadically or in association with neurofibromatosis (NF).2 Schwannomas are the most common benign tumors of peripheral nerves originating from Schwann cells of the nerve sheath.2 These tumors are typically encapsulated and easily surgically excised while preserving nerve continuity. In contrast, neurofibromas infiltrate between nerve fascicles and do not have a discrete capsule, making simple excision impossible. Overall, solitary neurofibromas carry a very low risk of malignant transformation, but in the setting of NF, eventual transformation into a neurofibrosarcoma is more common.3 This article describes the case of a young woman who presented with symptomatic bilateral dorsal wrist masses initially diagnosed to be ganglion cysts. Years later, she was found to have a neurofibroma on her chest wall and further work-up of her dorsal wrist masses revealed PIN neurofibromas. We discuss diagnostic findings that may alert the hand surgeon to the possibility of a neurofibroma and aid the surgeon in making a timely diagnosis.
Ó 2019 ASSH
r
Published by Elsevier, Inc. All rights reserved.
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1.e1
1.e2
BILATERAL PLEXIFORM NEUROFIBROMAS OF THE PIN
FIGURE 1: MRI of the wrist mass. A Fat-suppressed T1 and B T2 MRI demonstrate a mass emerging between the third and the fourth dorsal compartments. C Sagittal MRI illustrates the dumbbell-shaped appearance of the intraneural neurofibroma of the PIN.
CASE REPORT A 33-year-old right-handed woman noted cystic prominences on the dorsal wrists bilaterally for over 10 years previously. Over the last 2 years prior to presentation, she reported increased pain and size. Her left wrist was more symptomatic than her right. Pain was elicited with direct pressure over the masses and worsened with wrist movement. She wore night orthoses to avoid accidental direct contact when sleeping. She denied fevers, night sweats, or weight loss. On examination, there were well-circumscribed prominences at the dorsal scapholunate interval on both wrists, each measuring 1.5 x 1 cm in size. The overlying skin was normal in appearance and texture. The masses were firm and immobile. She had full range of motion of the wrists with pain at terminal flexion. Sensation to light touch was normal throughout the hand. Tinel sign over the mass elicited severe pain but no radiating paresthesias. With an examination thought to be consistent with ganglion cysts, she was given the options of observation, needle aspiration with or without ultrasound guidance, or excision. At the time, she deferred treatment and opted for observation. Three years later, the patient returned to the office with persistent dorsal wrist masses and pain. In the interim, she had noted a painless, small mass on her right chest wall for which she underwent an ultrasound-guided biopsy. Pathology was consistent with a benign neurofibroma. She was referred to a neurologist who evaluated her and found no other J Hand Surg Am.
findings of NF. The neurologist believed she did not meet criteria for a diagnosis of NF. The patient also denied a personal or family history of NF. When she presented for reevaluation of her wrist masses, the probability of the lesions representing neurofibromas was higher. Magnetic resonance imaging (MRI) demonstrated an oval, elongated enhancing mass located between the third and the fourth extensor compartments that was consistent with a PNST (Fig. 1). The mass measured approximately 1 x 1 x 3.5 cm (anteroposterior, transverse, craniocaudal) and had a dumbbell appearance with a waist at the level of the radiocarpal joint. There was no underlying osseous invasion; however, there was remodeling of the dorsal aspect of the radius adjacent to the mass. Radiographs of the wrist were not obtained. The patient underwent surgical excision of the left wrist PIN mass. Immunostaining of the resected specimen revealed neural cells positive for S-100, negative for smooth muscle actin, and negative for desmin, consistent with a plexiform neurofibroma. After excision, she had complete resolution of her pain and no functional limitations in her left wrist. At 2-year follow-up and 5 years after the initial presentation, she had full left wrist range of motion with no evidence of recurrence. Her right wrist mass was becoming more symptomatic with severe pain. It was presumed to be a neurofibroma and confirmed by MRI. She elected to undergo surgical excision. The mass was excised in a similar fashion to the left side (Fig. 2). We confirmed that the mass was originating
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BILATERAL PLEXIFORM NEUROFIBROMAS OF THE PIN
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FIGURE 2: Neurofibroma of the PIN. A Intraoperative image of the PIN neurofibroma. B The mass was found to be emerging in between the third and the fourth dorsal extensor compartments. C The resected 5.5-cm segment of the PIN demonstrates an intraneural neurofibroma.
from the PIN. The mass with the involved segment of the PIN was excised. At 6-week follow-up, she had full range of motion of the wrist and no residual dorsal wrist pain or sensory deficit. Pathology was consistent with a plexiform neurofibroma.
It is important to highlight that non-NF patients may have solitary neurofibromas and to consider this diagnosis if the patient has a history of a neurofibroma elsewhere in the body. Transillumination and aspiration are 2 methods accessible in the clinic for evaluation of masses. Although transillumination has demonstrated a high accuracy and high inter-/intraobserver reliability in distinguishing solid from cystic masses, the test can result in a false positive because solid PNSTs can appear to transilluminate from having a cystic component.8 Therefore, needle aspiration can rule out the diagnosis of a ganglion cyst if no mucin is aspirated. If either test is abnormal, an MRI or ultrasound should be obtained to further evaluate the mass. There are several features on initial presentation of this case that may have suggested these masses were not classic ganglion cysts. First, the masses were apparent to the patient more than 10 years prior to presentation, suggesting that they had been present and enlarging for years. This is in contrast to ganglion cysts, which may spontaneously fluctuate in size over time. Ganglion cysts also typically present in the third or fourth decade of life,2 and these masses were present well before then. Second, the nerve lesions demonstrated a mass effect on the dorsal cortex of the distal radius with remodeling suggesting a longstanding process (Fig. 1C). Lastly, the bilateral nature of the masses should also raise the possibility of an alternative diagnosis because ganglion cysts typically do not occur bilaterally. The presenting symptoms of a neurofibroma typically involve a combination of a palpable mass, loss of nerve function, and/or pain. The pain is typically
DISCUSSION Ganglion cysts are common on the dorsal wrist and represent 50% to 70% of benign upper extremity tumors.4 Nerve tumors are not often considered in the differential diagnosis, because they comprise only 5% of upper extremity tumors in adults.5 Solitary neurofibromas of the PIN are extremely rare. Most cases of neurofibromas are associated with NF type 1 (NF1), an autosomal dominant multisystem disease due to a mutation of a tumorsuppressor gene.6 Patients with this condition can present with cutaneous, spinal, or plexiform neurofibromas. Cutaneous neurofibromas originate from nerve fibers from the skin. Multiple cutaneous neurofibromas are the hallmark of NF1. In contrast, plexiform neurofibromas originate from subcutaneous or visceral peripheral nerves and involve multiple fascicles extending the length of the nerve. Plexiform neurofibromas develop in approximately 30% of NF1 patients.7 Whereas cutaneous neurofibromas also occur in non-NF1 patients, plexiform neurofibromas are known to be almost exclusively associated with NF1. Our patient did not meet criteria for a diagnosis of NF when evaluated by a neurologist. Two of 7 criteria must be met for a diagnosis of NF1,7 and although she met the criteria of at least 1 (plexiform neurofibroma), she had no other stigmata of disease. J Hand Surg Am.
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BILATERAL PLEXIFORM NEUROFIBROMAS OF THE PIN
REFERENCES
severe and greater than that seen with a ganglion cyst. The mass may have pain with percussion and hypersensitivity to light touch. It is not clear why bilateral neurofibromas would arise at this particular segment of the PIN in a patient with no other manifestations of NF1. One theory behind neurofibroma formation that links the etiologies of fibrosis and neurofibroma formation is that they may develop secondary to trauma.9 The histology in this case did not resemble that of a traumatic neuroma, but rather an intrinsic nerve lesion, and the patient denied a specific traumatic event. Finally, we believe the report of a chest wall neurofibroma suggests this patient may have had a mild form of NF that did not necessarily meet diagnostic criteria when evaluated by her neurologist.7 Therefore, we recommend that a history of a solitary neurofibroma in addition to the clinical finding of severe pain with percussion/light touch, a failure to transilluminate, and a failure to aspirate mucin should prompt the clinician to consider this diagnosis.
J Hand Surg Am.
1. Ichikawa J, Sato E, Haro H, Anayama S, Ando T, Hamada Y. Posterior interosseous nerve palsy due to schwannoma: case report. J Hand Surg Am. 2008;33(9):1525e1528. 2. Forthman CL, Blazar PE. Nerve tumors of the hand and upper extremity. Hand Clin. 2004;20(3):233e242. 3. Mautner VF, Friedrich RE, von Deimling A, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis type 1: MRI supports the diagnosis of malignant plexiform neurofibroma. Neuroradiology. 2003;45(9):618e625. 4. Angelides AC, Wallace PF. The dorsal ganglion of the wrist: its pathogenesis, gross and microscopic anatomy, and surgical treatment. J Hand Surg Am. 1976;1(3):228e235. 5. Strickland JW, Steichen JB. Nerve tumors of the hand and forearm. J Hand Surg Am. 1977;2(4):285e291. 6. Gosein M, Ameeral A, Banfield R, Mosodeen M. Plexiform neurofibroma of the wrist: imaging features and when to suspect malignancy. Case Rep Radiol. 2013;2013:493752. 7. Ferner RE, Gutmann DH. Neurofibromatosis type 1 (NF1): diagnosis and management. Handb Clin Neurol. 2013;115:939e955. 8. Erne HC, Gardner TR, Strauch RJ. Transillumination of hand tumors: a cadaver study to evaluate accuracy and intraobserver reliability. Hand (N Y). 2011;6(4):390e393. 9. Brosseau JP, Pichard DC, Legius EH, et al. The biology of cutaneous neurofibromas: consensus recommendations for setting research priorities. Neurology. 2018;91(2 Suppl 1):S14eS20.
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Vol. -, - 2019
Bilateral Plexiform Neurofibromas of the Posterior Interosseous Nerve Mimicking Dorsal Wrist Ganglions Rikesh A. Gandhi, MD,* David J. Bozentka, MD*†
A 33-year-old woman presented with bilateral dorsal wrist masses associated with pain and limited range of motion. On initial presentation, the masses were believed to be ganglion cysts and the patient opted for observation. Three years later, she was found to have a chest wall mass diagnosed by biopsy to be a neurofibroma. When she later returned to seek treatment for her wrist masses, magnetic resonance imaging demonstrated posterior interosseous nerve (PIN) neurofibromas. Dorsal wrist masses situated over the scapholunate interval are commonly attributed to ganglion cysts. Neurofibromas of the PIN, although rare, should be considered in the differential diagnosis when a mass elicits pain with percussion, fails to transilluminate, fails aspiration, or if the patient has a history of neurofibromas elsewhere in the body. (J Hand Surg Am. 2019;-(-):1.e1-e4. Copyright Ó 2019 by the American Society for Surgery of the Hand. All rights reserved.) Key words Dorsal wrist mass, intraneural, neurofibroma, posterior interosseous nerve.
D
is frequently encountered by hand surgeons. Although commonly attributed to a ganglion cyst, hand surgeons should be aware of other potential causes of a painful, persistent dorsal wrist mass. Intrinsic lesions of the posterior interosseous nerve (PIN) such as peripheral nerve sheath tumors (PNSTs) have rarely been described in the literature.1 Their incidence is unknown. Distal PIN PNSTs, where the nerve courses through the fourth extensor compartment, may present as an isolated dorsal wrist mass. ORSAL WRIST PAIN AND SWELLING
From the *Department of Orthopaedic Surgery, University of Pennsylvania; and the †Department of Orthopaedic Surgery, Penn Presbyterian Medical Center, Philadelphia, PA Received for publication February 26, 2019; accepted in revised form October 7, 2019. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article. Corresponding author: Rikesh A. Gandhi, MD, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA; e-mail: [email protected]. 0363-5023/19/---0001$36.00/0 https://doi.org/10.1016/j.jhsa.2019.10.016
Benign PNSTs include schwannomas and neurofibromas. Each can occur either sporadically or in association with neurofibromatosis (NF).2 Schwannomas are the most common benign tumors of peripheral nerves originating from Schwann cells of the nerve sheath.2 These tumors are typically encapsulated and easily surgically excised while preserving nerve continuity. In contrast, neurofibromas infiltrate between nerve fascicles and do not have a discrete capsule, making simple excision impossible. Overall, solitary neurofibromas carry a very low risk of malignant transformation, but in the setting of NF, eventual transformation into a neurofibrosarcoma is more common.3 This article describes the case of a young woman who presented with symptomatic bilateral dorsal wrist masses initially diagnosed to be ganglion cysts. Years later, she was found to have a neurofibroma on her chest wall and further work-up of her dorsal wrist masses revealed PIN neurofibromas. We discuss diagnostic findings that may alert the hand surgeon to the possibility of a neurofibroma and aid the surgeon in making a timely diagnosis.
Ó 2019 ASSH
r
Published by Elsevier, Inc. All rights reserved.
r
1.e1
1.e2
BILATERAL PLEXIFORM NEUROFIBROMAS OF THE PIN
FIGURE 1: MRI of the wrist mass. A Fat-suppressed T1 and B T2 MRI demonstrate a mass emerging between the third and the fourth dorsal compartments. C Sagittal MRI illustrates the dumbbell-shaped appearance of the intraneural neurofibroma of the PIN.
CASE REPORT A 33-year-old right-handed woman noted cystic prominences on the dorsal wrists bilaterally for over 10 years previously. Over the last 2 years prior to presentation, she reported increased pain and size. Her left wrist was more symptomatic than her right. Pain was elicited with direct pressure over the masses and worsened with wrist movement. She wore night orthoses to avoid accidental direct contact when sleeping. She denied fevers, night sweats, or weight loss. On examination, there were well-circumscribed prominences at the dorsal scapholunate interval on both wrists, each measuring 1.5 x 1 cm in size. The overlying skin was normal in appearance and texture. The masses were firm and immobile. She had full range of motion of the wrists with pain at terminal flexion. Sensation to light touch was normal throughout the hand. Tinel sign over the mass elicited severe pain but no radiating paresthesias. With an examination thought to be consistent with ganglion cysts, she was given the options of observation, needle aspiration with or without ultrasound guidance, or excision. At the time, she deferred treatment and opted for observation. Three years later, the patient returned to the office with persistent dorsal wrist masses and pain. In the interim, she had noted a painless, small mass on her right chest wall for which she underwent an ultrasound-guided biopsy. Pathology was consistent with a benign neurofibroma. She was referred to a neurologist who evaluated her and found no other J Hand Surg Am.
findings of NF. The neurologist believed she did not meet criteria for a diagnosis of NF. The patient also denied a personal or family history of NF. When she presented for reevaluation of her wrist masses, the probability of the lesions representing neurofibromas was higher. Magnetic resonance imaging (MRI) demonstrated an oval, elongated enhancing mass located between the third and the fourth extensor compartments that was consistent with a PNST (Fig. 1). The mass measured approximately 1 x 1 x 3.5 cm (anteroposterior, transverse, craniocaudal) and had a dumbbell appearance with a waist at the level of the radiocarpal joint. There was no underlying osseous invasion; however, there was remodeling of the dorsal aspect of the radius adjacent to the mass. Radiographs of the wrist were not obtained. The patient underwent surgical excision of the left wrist PIN mass. Immunostaining of the resected specimen revealed neural cells positive for S-100, negative for smooth muscle actin, and negative for desmin, consistent with a plexiform neurofibroma. After excision, she had complete resolution of her pain and no functional limitations in her left wrist. At 2-year follow-up and 5 years after the initial presentation, she had full left wrist range of motion with no evidence of recurrence. Her right wrist mass was becoming more symptomatic with severe pain. It was presumed to be a neurofibroma and confirmed by MRI. She elected to undergo surgical excision. The mass was excised in a similar fashion to the left side (Fig. 2). We confirmed that the mass was originating
r
Vol. -, - 2019
BILATERAL PLEXIFORM NEUROFIBROMAS OF THE PIN
1.e3
FIGURE 2: Neurofibroma of the PIN. A Intraoperative image of the PIN neurofibroma. B The mass was found to be emerging in between the third and the fourth dorsal extensor compartments. C The resected 5.5-cm segment of the PIN demonstrates an intraneural neurofibroma.
from the PIN. The mass with the involved segment of the PIN was excised. At 6-week follow-up, she had full range of motion of the wrist and no residual dorsal wrist pain or sensory deficit. Pathology was consistent with a plexiform neurofibroma.
It is important to highlight that non-NF patients may have solitary neurofibromas and to consider this diagnosis if the patient has a history of a neurofibroma elsewhere in the body. Transillumination and aspiration are 2 methods accessible in the clinic for evaluation of masses. Although transillumination has demonstrated a high accuracy and high inter-/intraobserver reliability in distinguishing solid from cystic masses, the test can result in a false positive because solid PNSTs can appear to transilluminate from having a cystic component.8 Therefore, needle aspiration can rule out the diagnosis of a ganglion cyst if no mucin is aspirated. If either test is abnormal, an MRI or ultrasound should be obtained to further evaluate the mass. There are several features on initial presentation of this case that may have suggested these masses were not classic ganglion cysts. First, the masses were apparent to the patient more than 10 years prior to presentation, suggesting that they had been present and enlarging for years. This is in contrast to ganglion cysts, which may spontaneously fluctuate in size over time. Ganglion cysts also typically present in the third or fourth decade of life,2 and these masses were present well before then. Second, the nerve lesions demonstrated a mass effect on the dorsal cortex of the distal radius with remodeling suggesting a longstanding process (Fig. 1C). Lastly, the bilateral nature of the masses should also raise the possibility of an alternative diagnosis because ganglion cysts typically do not occur bilaterally. The presenting symptoms of a neurofibroma typically involve a combination of a palpable mass, loss of nerve function, and/or pain. The pain is typically
DISCUSSION Ganglion cysts are common on the dorsal wrist and represent 50% to 70% of benign upper extremity tumors.4 Nerve tumors are not often considered in the differential diagnosis, because they comprise only 5% of upper extremity tumors in adults.5 Solitary neurofibromas of the PIN are extremely rare. Most cases of neurofibromas are associated with NF type 1 (NF1), an autosomal dominant multisystem disease due to a mutation of a tumorsuppressor gene.6 Patients with this condition can present with cutaneous, spinal, or plexiform neurofibromas. Cutaneous neurofibromas originate from nerve fibers from the skin. Multiple cutaneous neurofibromas are the hallmark of NF1. In contrast, plexiform neurofibromas originate from subcutaneous or visceral peripheral nerves and involve multiple fascicles extending the length of the nerve. Plexiform neurofibromas develop in approximately 30% of NF1 patients.7 Whereas cutaneous neurofibromas also occur in non-NF1 patients, plexiform neurofibromas are known to be almost exclusively associated with NF1. Our patient did not meet criteria for a diagnosis of NF when evaluated by a neurologist. Two of 7 criteria must be met for a diagnosis of NF1,7 and although she met the criteria of at least 1 (plexiform neurofibroma), she had no other stigmata of disease. J Hand Surg Am.
r
Vol. -, - 2019
1.e4
BILATERAL PLEXIFORM NEUROFIBROMAS OF THE PIN
REFERENCES
severe and greater than that seen with a ganglion cyst. The mass may have pain with percussion and hypersensitivity to light touch. It is not clear why bilateral neurofibromas would arise at this particular segment of the PIN in a patient with no other manifestations of NF1. One theory behind neurofibroma formation that links the etiologies of fibrosis and neurofibroma formation is that they may develop secondary to trauma.9 The histology in this case did not resemble that of a traumatic neuroma, but rather an intrinsic nerve lesion, and the patient denied a specific traumatic event. Finally, we believe the report of a chest wall neurofibroma suggests this patient may have had a mild form of NF that did not necessarily meet diagnostic criteria when evaluated by her neurologist.7 Therefore, we recommend that a history of a solitary neurofibroma in addition to the clinical finding of severe pain with percussion/light touch, a failure to transilluminate, and a failure to aspirate mucin should prompt the clinician to consider this diagnosis.
J Hand Surg Am.
1. Ichikawa J, Sato E, Haro H, Anayama S, Ando T, Hamada Y. Posterior interosseous nerve palsy due to schwannoma: case report. J Hand Surg Am. 2008;33(9):1525e1528. 2. Forthman CL, Blazar PE. Nerve tumors of the hand and upper extremity. Hand Clin. 2004;20(3):233e242. 3. Mautner VF, Friedrich RE, von Deimling A, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis type 1: MRI supports the diagnosis of malignant plexiform neurofibroma. Neuroradiology. 2003;45(9):618e625. 4. Angelides AC, Wallace PF. The dorsal ganglion of the wrist: its pathogenesis, gross and microscopic anatomy, and surgical treatment. J Hand Surg Am. 1976;1(3):228e235. 5. Strickland JW, Steichen JB. Nerve tumors of the hand and forearm. J Hand Surg Am. 1977;2(4):285e291. 6. Gosein M, Ameeral A, Banfield R, Mosodeen M. Plexiform neurofibroma of the wrist: imaging features and when to suspect malignancy. Case Rep Radiol. 2013;2013:493752. 7. Ferner RE, Gutmann DH. Neurofibromatosis type 1 (NF1): diagnosis and management. Handb Clin Neurol. 2013;115:939e955. 8. Erne HC, Gardner TR, Strauch RJ. Transillumination of hand tumors: a cadaver study to evaluate accuracy and intraobserver reliability. Hand (N Y). 2011;6(4):390e393. 9. Brosseau JP, Pichard DC, Legius EH, et al. The biology of cutaneous neurofibromas: consensus recommendations for setting research priorities. Neurology. 2018;91(2 Suppl 1):S14eS20.
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Vol. -, - 2019