- Email: [email protected]
Lipofibromatous Hamartoma of the Median Nerve
IN BRIEF
Lipofibromatous Hamartoma of the Median Nerve Shailesh Agarwal, MD, Steven C. Haase, MD CME INFORMATION AND DISCLOSURES The Review Section of JHS will contain at least 3 clinically relevant articles selected by the editor to be offered for CME in each issue. For CME credit, the participant must read the articles in print or online and correctly answer all related questions through an online examination. The questions on the test are designed to make the reader think and will occasionally require the reader to go back and scrutinize the article for details. The JHS CME Activity fee of $20.00 includes the exam questions/answers only and does not include access to the JHS articles referenced. Statement of Need: This CME activity was developed by the JHS review section editors and review article authors as a convenient education tool to help increase or affirm reader’s knowledge. The overall goal of the activity is for participants to evaluate the appropriateness of clinical data and apply it to their practice and the provision of patient care. Accreditation: The ASSH is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. AMA PRA Credit Designation: The American Society for Surgery of the Hand designates this Journal-Based CME activity for a maximum of 2.00 “AMA PRA Category 1 Credits™”. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
In Brief
ASSH Disclaimer: The material presented in this CME activity is made available by the ASSH for educational purposes only. This material is not intended to represent the only methods or the best procedures appropriate for the medical situation(s) discussed, but rather it is intended to present an approach, view, statement, or opinion of the authors that may be helpful, or of interest, to other practitioners. Examinees agree to participate in this medical education activity, sponsored by the ASSH, with full knowledge and awareness that they waive any claim they may have against the ASSH for reliance on any information presented. The approval of the US Food and Drug Administration is required for procedures and drugs that are considered experimental. Instrumentation systems discussed or reviewed during this educational activity may not yet have received FDA approval. Provider Information can be found at http://www.assh.org/Pages/ContactUs.aspx. Technical Requirements for the Online Examination can be found at http://jhandsurg. org/cme/home. Privacy Policy can be found at http://www.assh.org/pages/ASSHPrivacyPolicy.aspx.
EPIDEMIOLOGY AND CHARACTERISTICS Lipofibromatous hamartoma (LFH) is a rarely occurring, benign neoplasm consisting of fibroadipose tissue that affects peripheral nerves. This entity was first described by
ASSH Disclosure Policy: As a provider accredited by the ACCME, the ASSH must ensure balance, independence, objectivity, and scientific rigor in all its activities. All authors participating in the activity are required to disclose to the audience any relevant financial relationships with any commercial interest to the provider. The intent of this disclosure is not to prevent authors with relevant financial relationships from serving as authors, but rather to provide members of the audience with information on which they can make their own judgments. The ASSH must resolve any conflicts of interest prior to the commencement of the educational activity. It remains for the audience to determine if the audience’s relationships may influence the educational content with regard to exposition or conclusion. When unlabeled or unapproved uses of drugs or devices are discussed, these will also be indicated. Disclosures for this Article Editors The editors involved with this CME activity and all content validation/peer reviewers of this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). Authors All authors of this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). Planners The planners involved with this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). The editorial and education staff involved with this journal-based CME activity has reported no relevant financial relationships with commercial interest(s). Learning Objectives • Discuss the sites of occurrence for lipofibromatous hamartoma. • Describe the macrodactyly associated with lipofibromatous hamartoma. • State the advanced imaging studies employed to diagnose a lipofibromatous hamartoma. • List the magnetic resonance imaging findings typical for a lipofibromatous hamartoma. • Summarize the treatment options for a lipofibromatous hamartoma. • Compare and contrast the various adjuvant treatments with respect to recurrence rates after resection of giant cell tumors of the tendon sheath. Deadline: Each exam purchased in 2012 must be completed by January 31, 2013, to be eligible for CME. A certificate will be issued upon completion of the activity. Estimated time to complete each month’s JHS CME activity is 2 hours. Copyright © 2013 by the American Society for Surgery of the Hand. All rights reserved.
Dr. Michael L. Mason1 at the seventh meeting of the American Society for Surgery of the Hand in 1952. He reported on 2 patients with diffuse, fusiform enlargements of the median nerve, in which no normal-appearing nerve
From the Department of Surgery, Section of Plastic Surgery, University of Michigan Health System, Ann Arbor, MI.
Corresponding author: Steven C. Haase, MD, University of Michigan Health System, 2130 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0340; e-mail: [email protected].
Received for publication May 11, 2012; accepted in revised form October 13, 2012.
0363-5023/13/38A02-0030$36.00/0 http://dx.doi.org/10.1016/j.jhsa.2012.10.042
No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.
392 䉬 © ASSH 䉬 Published by Elsevier, Inc. All rights reserved.
LIPOFIBROMATOUS HAMARTOMA
393
Fatty infiltration of nerve Fatty or fibrous neoplasm of nerve Fibrofatty proliferation of nerve Fibrolipoma Fibrolipomatous hamartoma Fibroneurolipoma Intraneural lipoma Lipofibroma Lipomatosis of nerve
fibers could be identified. Since that initial report, this entity has gone by several names (Table 1).2,3 Ultimately, the term lipofibromatous hamartoma was introduced by Johnson and Bonfiglio4 in 1969, and this is the preferred nomenclature for this lesion at this time. A recent review of the literature notes that only 88 cases have been reported for this rare condition.5 Lipofibromatous hamartoma is more often found in the upper extremity than in other regions of the body, and within the upper extremity, the median nerve is the most common nerve affected.6 Other, less common upper extremity sites have included the radial nerve, ulnar nerve, digital nerve, and brachial plexus.3,7–10 In the lower extremity, it has been found affecting the sciatic nerve11 and branches of the medial plantar nerve.2 It is probably congenital in nature, but it grows slowly, usually presenting with symptoms in the third or fourth decade of life, although rapid growth can lead to earlier discovery.12–14 This tumor is often associated with macrodactyly, which is present in approximately 30% of cases.2,5,6,9,13,15 In fact, LFH is the most common condition associated with macrodactyly of the upper extremity.2 The macrodactyly is typically noted in the distal distribution of the nerve involved with the LFH lesion proximally. Although this arrangement is also found in neurofibromatosis patients, LFH is easily distinguished from neurofibromatosis by the large quantities of fat found in the LFH nerve lesions.9 The exact relationship between these conditions is the subject of some debate. Lipofibromatous hamartoma occurring with macrodactyly can be thought of as a proximal extension of the distal growth disturbance.9 Despite histologic similarities, it is possible that LFH occurring in isolation is a separate pathologic entity or simply a form of the disease with less penetrance. Because both forms are rare, existing data are insuf-
DIAGNOSIS, IMAGING, AND HISTOPATHOLOGY Lipofibromatous hamartoma presents most commonly as a painless, slowly enlarging mass. If associated with macrodactyly, enlargement of the digit(s) and/or palm can be the first manifestation of this condition.2 Due to the abnormal enlargement of the nerve(s) associated with this tumor, signs and symptoms of nerve compression are often noted. For example, median nerve lesions at the wrist often present with signs and symptoms of carpal tunnel syndrome. Both sensory and motor disturbances have been reported with these tumors.2,3,8,16 Nerve conduction and EMG studies are abnormal in these cases, as expected. The differential diagnosis for this type of lesion includes neurofibroma, neurilemoma, neuroma, ganglion, lipoma, or vascular malformation, among others. When macrodactyly is present, radiographs should be obtained to evaluate the bony structures. Lipofibromatous hamartoma can be evaluated by ultrasound; the affected nerve will appear grossly enlarged, usually in a fusiform shape. As described by Toms,17 these tumors will have “characteristic hypoechoic coaxial cabling encased by an echogenic substratum” (Fig. 1). Magnetic resonance imaging (MRI) is generally the imaging modality of choice to assist with diagnosis and surgical planning. On MRI, the appearance of these tumors is pathognomonic: the nerve is enlarged, containing 15 or 16 coaxial “cables” that correspond to 2to 3-mm diameter bundles of axons encased in epineural fibrous tissue (Fig. 2). These bundles are typically interspersed evenly with fat at the carpal tunnel, increasing the overall cross-sectional area of the nerve (up to 1.6 cm2) without changing the innate MRI signal of the nerve.17 The appearance of this tumor on MRI is so distinct that it can effectively make the diagnosis without the need for biopsy in most patients.18 On gross pathologic inspection, median nerve LFH appears as an intrinsically enlarged nerve, sometimes with surrounding extrinsic fibrofatty tissue. As expected, this tissue can be yellow or tan in color, consistent with its fatty and/or fibrous nature. On histopathologic evaluation, the epineurium is found to be expanded by the increased fibroadipose tissue that surrounds and separates the individual nerve bundles.6 TREATMENT OPTIONS AND PROGNOSIS Treatment options for median nerve LFH described in the literature include a wide range of options, from
JHS 䉬 Vol A, February
In Brief
ficient to draw conclusions about the differences between the 2.
TABLE 1. Synonyms for Lipofibromatous Hamartoma
394
LIPOFIBROMATOUS HAMARTOMA
FIGURE 1: Ultrasound appearance of lipofibromatous hamartoma of the median nerve at the wrist. A The median nerve is outlined in this axial view, which demonstrates the “coaxial cable-like” appearance. B Sagittal view demonstrates the bundle of multiple longitudinal cables (between the arrows).
In Brief FIGURE 2: The MRI appearance of lipofibromatous hamartoma of the median nerve at the wrist (marked with an arrow in each image). A T1- and B T2-weighted axial images showing the cable-like appearance of the enlarged median nerve. C Coronal and D sagittal T1-weighted images show the longitudinal appearance of the tumor as it passes through the carpal tunnel. This has been described as “serpiginous” due to the snake-like, wavy appearance of some LFH lesions.
close observation to complete nerve resection. Each of the options has advantages and disadvantages, which are outlined later. Of course, when macrodactyly is
present, debulking of the overgrown tissue and epiphysiodesis are often required in addition to surgery to address the LFH tumor itself.2
JHS 䉬 Vol A, February
LIPOFIBROMATOUS HAMARTOMA
395
In the absence of any notable neurologic symptoms, observation has been advocated in a couple of case reports.18,19 No long-term follow-up on these patients is provided in these publications. Most authors advocate carpal tunnel release (CTR) to decompress the median nerve in symptomatic patients, combined with biopsy of the tumor to confirm a pathologic diagnosis. Case reports with follow-up between 6 months and 5 years show that this can result in complete resolution of symptoms in some patients.5,16,20 However, not all results from simple decompression are this encouraging. Louis reported on a series of 4 patients with median nerve LFH that were initially managed by CTR with or without epineurotomy.21 All subjects required repeat surgery between 4 and 13 years later for recurrence of the mass and/or progression of symptoms. Despite more aggressive resection and debulking of the tumor at the time of repeat surgery, 2 patients ultimately lost all median nerve function; one patient had progressive, permanent loss of sensation; and the final patient’s outcome was not conclusively better after a repeat surgery. Frykman reports a mixed experience in 2 cases of median nerve LFH. One patient seemed to get good relief from CTR alone, and another had early resection (at age 4) leading to motor dysfunction, requiring opposition transfer at age 5. This patient ultimately had median nerve excision due to intractable pain.9 Similarly, Johnson reported on a patient whose first LFH tumor resection in infancy resulted in loss of thumb opposition and greatly diminished sensation in the radial digits. Despite this aggressive primary surgery, the mass continued to grow and ultimately required a second debulking procedure years later.4
The literature regarding early, aggressive resection of these tumors shows mixed results. Occasionally, resection of large portions of fibrofatty tissue can be accomplished without removal of substantial portions of the median nerve and without the need for invasive intraneural dissection.12 However, many of these tumors present as fusiform lesions that permeate the entire nerve, without any portion of the tumor that is easily accessible (Fig. 3). For these lesions, some authors have recommended epineurotomy and intraneural dissection, resecting the tumor tissue from around individual groups of fascicles when possible. Bains reports on a case in which this type of limited intraneural excision left a patient with normal nerve function at 10 months’ follow-up.14 Al-Qattan performed debulking in 7 cases of LFH but does not report on the patient’s neurologic function after surgery.15 Ulrich reported on 2 patients who had intraneural dissection with partial tumor excision, with no neurologic deficits 6 – 8 years after surgery.22 These reports would indicate that good results can be obtained with intraneural dissection in some cases. However, not all reports are as promising. Clafijo-Alvarez treated a patient with median nerve LFH with intraneural fascicular dissection for tumor excision, with preserved motor and sensory function at 6 months. Unfortunately, the tumor recurred, and a repeat excision and nerve grafting were performed 2 years later. He reported no postoperative motor deficit (possibly due to ulnar nerve contributions to the thenar muscles) and return of protective sensation by 6 months; the patient was tumor free at 3 years.23
JHS 䉬 Vol A, February
In Brief
FIGURE 3: Intraoperative photographs of carpal tunnel decompression in a patient with lipofibromatous hamartoma of the median nerve. A Extended carpal tunnel incision, with the diffusely enlarged median nerve visible at the radial edge of the wound (between the arrows). B The retractor is gently lifting the median nerve, which is remarkable for a diffuse, yellowish fibrofatty infiltrate.
396
LIPOFIBROMATOUS HAMARTOMA
Hsu describes performing epineurotomy and microsurgical dissection of the motor branch through the tumor in a retrograde fashion, so that the motor function could be preserved when the remainder of the nerve was excised and grafted. Three years after surgery, there was no sign of tumor recurrence. Opposition and grip strength were intact, but sensory recovery was incomplete (2-point discrimination ⬎ 15 mm).24 Warhold reports on a series of LFH patients treated with a variety of different procedures, from CTR alone to nerve excision with and without grafting. He points out that in one 14-year-old girl, complete excision of 8 cm of the median nerve was performed, with “no loss of sensation” after surgery. He suggests that this could be due to the presence of ulnar nerve contributions to the median-innervated structures, as well as the ability of the central nervous system to adapt in children.13
In Brief
RECOMMENDATIONS Because LFH remains a rare tumor, there is little highlevel evidence to guide treatment. However, based on the literature available, we agree with a conservative approach whenever possible for this nonmalignant neoplasm.25 Patients without symptoms might require only close observation. Those patients presenting with symptoms of carpal tunnel syndrome should have decompression with biopsy to confirm the pathologic diagnosis. This biopsy can be obtained by excising a small, noncritical nerve branch or by making a limited epineurotomy on the ulnar/dorsal portion of the nerve to extract intraneural tumor for analysis. Because more aggressive, intraneural resections have not been shown to conclusively lower recurrence rates, and can actually worsen median nerve function, we do not recommend this for patients with normal or near-normal median nerve function. For patients with worsening nerve function despite decompression, intraneural dissection or nerve excision with grafting might be indicated. When possible, the motor branch should be preserved in these cases. If the motor branch is not functional, or if a long nerve graft is required, consideration should be given to early opposition transfer to improve function. Although there are occasional reports of patients who have done well after nerve excision without grafting, we consider this approach to be unwise, even in children, in whom the deficit might be more easily overcome with adaptation. Recurrence of LFH in nerve grafts has not been described. Lipofibromatous hamartoma is a rare tumor of fibroadipose tissue that commonly affects the nerves of the upper extremity, particularly the median nerve. Despite its benign nature, LFH can cause symptoms of nerve compression and can lead to a dramatic decline in nerve function in some patients. A conservative approach is re-
commended, consisting of carpal tunnel release for decompression, as well as cautious biopsy of the lesion to confirm the diagnosis. More invasive, intraneural tumor resection or median nerve excision and grafting can lead to permanent nerve dysfunction. Therefore, these options should be reserved for cases in which conservative management has failed or when nerve function deteriorates to the point at which the morbidity of these surgical procedures is outweighed by some potential benefit. REFERENCES 1. Mason ML. American Society for Surgery of the Hand. J Bone Joint Surg. 1953;35A(1):257–275. 2. Amadio PC, Reiman HM, Dobyns JH. Lipofibromatous hamartoma of nerve. J Hand Surg Am. 1988;13(1):67–75. 3. Herrick RT, Godsil RD Jr, Widener JH. Lipofibromatous hamartoma of the radial nerve: a case report. J Hand Surg Am. 1980;5(3):211–213. 4. Johnson RJ, Bonfiglio M. Lipofibromatous hamartoma of the median nerve. J Bone Joint Surg Am. 1969;51 (5):984 –990. 5. Patil VS, Nagle S. Lipofibromatous hamartoma of the median nerve: A case report and review of the literature. Indian J Plast Surg. 2009;42(1):122–125. 6. Silverman TA, Enzinger FM. Fibrolipomatous hamartoma of nerve. A clinicopathologic analysis of 26 cases. Am J Surg Pathol. 1985;9(1):7–14. 7. Price AJ, Compson JP, Calonje E. Fibrolipomatous hamartoma of nerve arising in the brachial plexus. J Hand Surg Br. 1995;20(1):16–18. 8. Gouldesbrough DR, Kinny SJ. Lipofibromatous hamartoma of the ulnar nerve at the elbow: brief report. J Bone Joint Surg Br. 1989;71(2):331–332. 9. Frykman GK, Wood VE. Peripheral nerve hamartoma with macrodactyly in the hand: Report of three cases and review of the literature. J Hand Surg. 1978;3(4):307–312. 10. Jacob RA, Buchino JJ. Lipofibroma of the superficial branch of the radial nerve. J Hand Surg Am. 1989;14(4):704 –706. 11. Wong BZ, Amrami KK, Wenger DE, Dyck PJ, Scheithauer BW, Spinner RJ. Lipomatosis of the sciatic nerve: typical and atypical MRI features. Skeletal Radiol. 2006;35(3):180 –184. 12. Sirinoglu H, Sonmez A, Sav A, Numanoglu A. Lipofibromatous hamartoma of the median nerve. Ann Plast Surg. 2010;65(2):174–176. 13. Warhold LG, Urban MA, Bora FW Jr, Brooks JS, Peters SB. Lipofibromatous hamartomas of the median nerve. J Hand Surg Am. 1993;18(6):1032–1037. 14. Bains R, Kotwal A, Saeed W. Recurrent carpal tunnel syndrome in a child due to fibrolipomatous hamartoma of the median nerve successfully treated by limited excision and decompression. J Plast Reconstr Aesthet Surg. 2006;59(12):1394 –1397. 15. Al-Qattan MM. Lipofibromatous hamartoma of the median nerve and its associated conditions. J Hand Surg Br. 2001;26(4):368 –372. 16. Afshar A. Carpal tunnel syndrome due to lipofibromatous hamartoma of the median nerve. Arch Iran Med. 2010;13(1):45– 47. 17. Toms AP, Anastakis D, Bleakney RR, Marshall TJ. Lipofibromatous hamartoma of the upper extremity: a review of the radiologic findings for 15 patients. AJR Am J Roentgenol. 2006;186(3):805– 811. 18. Nardella D, Sohawon S, Carlier A. Lipofibromatous hamartoma of the median nerve. Three case reports. J Plast Reconstr Aesthet Surg. 2009;62(9):e314 –317. 19. Nouira K, Belhiba H, Baccar S, et al. Fibrolipoma of the median nerve. Joint Bone Spine. 2007;74(1):98 –99. 20. Al-Jabri T, Garg S, Mani GV. Lipofibromatous hamartoma of the median nerve. J Orthop Surg Res. 2010;5:71. 21. Louis DS, Hankin FM, Greene TL, Dick HM. Lipofibromas of the median nerve: long-term follow-up of four cases. J Hand Surg Am. 1985;10(3):403– 408. 22. Ulrich D, Ulrich F, Schroeder M, Pallua N. Lipofibromatous hamartoma of the median nerve in patients with macrodactyly: diagnosis and treatment of a rare disease causing carpal tunnel syndrome. Arch Orthop Trauma Surg. 2009;129(9):1219 –1224.
JHS 䉬 Vol A, February
LIPOFIBROMATOUS HAMARTOMA
23. Clavijo-Alvarez JA, Price M, Stofman GM. Preserved neurologic function following intraneural fascicular dissection and nerve graft for digital and median nerve lipofibromatous hamartoma. Plast Reconstr Surg. 2010;125(3):120e–122e.
397
24. Hsu CC, Chen DJ, Chen HC. Lipofibromatous hamartoma of the median nerve with long-term follow-up. Chang Gung Med J. 2005;28(2):111–116. 25. Razzaghi A, Anastakis DJ. Lipofibromatous hamartoma: review of early diagnosis and treatment. Can J Surg. 2005;48(5):394 –399.
JOURNAL CME QUESTIONS Lipofibromatous Hamartoma of the Median Nerve What condition is associated with lipofibromatous hamartoma? a. Macrodactyly b. Wilms tumor c. Maffucci syndrome d. Neurofibromatosis e. Fibrosarcoma
What is the treatment for a 30-year-old man with presumed lipofibromatous hamartoma of the median nerve with minimal symptoms? a. Observation b. Biopsy for confirmation c. Carpal tunnel release and biopsy d. Intraneural resection e. Resection and cable grafting
In Brief
To take the online test and receive CME credit, go to http://www.jhandsurg.org/CME/home.
JHS 䉬 Vol A, February
Lipofibromatous Hamartoma of the Median Nerve Shailesh Agarwal, MD, Steven C. Haase, MD CME INFORMATION AND DISCLOSURES The Review Section of JHS will contain at least 3 clinically relevant articles selected by the editor to be offered for CME in each issue. For CME credit, the participant must read the articles in print or online and correctly answer all related questions through an online examination. The questions on the test are designed to make the reader think and will occasionally require the reader to go back and scrutinize the article for details. The JHS CME Activity fee of $20.00 includes the exam questions/answers only and does not include access to the JHS articles referenced. Statement of Need: This CME activity was developed by the JHS review section editors and review article authors as a convenient education tool to help increase or affirm reader’s knowledge. The overall goal of the activity is for participants to evaluate the appropriateness of clinical data and apply it to their practice and the provision of patient care. Accreditation: The ASSH is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. AMA PRA Credit Designation: The American Society for Surgery of the Hand designates this Journal-Based CME activity for a maximum of 2.00 “AMA PRA Category 1 Credits™”. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
In Brief
ASSH Disclaimer: The material presented in this CME activity is made available by the ASSH for educational purposes only. This material is not intended to represent the only methods or the best procedures appropriate for the medical situation(s) discussed, but rather it is intended to present an approach, view, statement, or opinion of the authors that may be helpful, or of interest, to other practitioners. Examinees agree to participate in this medical education activity, sponsored by the ASSH, with full knowledge and awareness that they waive any claim they may have against the ASSH for reliance on any information presented. The approval of the US Food and Drug Administration is required for procedures and drugs that are considered experimental. Instrumentation systems discussed or reviewed during this educational activity may not yet have received FDA approval. Provider Information can be found at http://www.assh.org/Pages/ContactUs.aspx. Technical Requirements for the Online Examination can be found at http://jhandsurg. org/cme/home. Privacy Policy can be found at http://www.assh.org/pages/ASSHPrivacyPolicy.aspx.
EPIDEMIOLOGY AND CHARACTERISTICS Lipofibromatous hamartoma (LFH) is a rarely occurring, benign neoplasm consisting of fibroadipose tissue that affects peripheral nerves. This entity was first described by
ASSH Disclosure Policy: As a provider accredited by the ACCME, the ASSH must ensure balance, independence, objectivity, and scientific rigor in all its activities. All authors participating in the activity are required to disclose to the audience any relevant financial relationships with any commercial interest to the provider. The intent of this disclosure is not to prevent authors with relevant financial relationships from serving as authors, but rather to provide members of the audience with information on which they can make their own judgments. The ASSH must resolve any conflicts of interest prior to the commencement of the educational activity. It remains for the audience to determine if the audience’s relationships may influence the educational content with regard to exposition or conclusion. When unlabeled or unapproved uses of drugs or devices are discussed, these will also be indicated. Disclosures for this Article Editors The editors involved with this CME activity and all content validation/peer reviewers of this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). Authors All authors of this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). Planners The planners involved with this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). The editorial and education staff involved with this journal-based CME activity has reported no relevant financial relationships with commercial interest(s). Learning Objectives • Discuss the sites of occurrence for lipofibromatous hamartoma. • Describe the macrodactyly associated with lipofibromatous hamartoma. • State the advanced imaging studies employed to diagnose a lipofibromatous hamartoma. • List the magnetic resonance imaging findings typical for a lipofibromatous hamartoma. • Summarize the treatment options for a lipofibromatous hamartoma. • Compare and contrast the various adjuvant treatments with respect to recurrence rates after resection of giant cell tumors of the tendon sheath. Deadline: Each exam purchased in 2012 must be completed by January 31, 2013, to be eligible for CME. A certificate will be issued upon completion of the activity. Estimated time to complete each month’s JHS CME activity is 2 hours. Copyright © 2013 by the American Society for Surgery of the Hand. All rights reserved.
Dr. Michael L. Mason1 at the seventh meeting of the American Society for Surgery of the Hand in 1952. He reported on 2 patients with diffuse, fusiform enlargements of the median nerve, in which no normal-appearing nerve
From the Department of Surgery, Section of Plastic Surgery, University of Michigan Health System, Ann Arbor, MI.
Corresponding author: Steven C. Haase, MD, University of Michigan Health System, 2130 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0340; e-mail: [email protected].
Received for publication May 11, 2012; accepted in revised form October 13, 2012.
0363-5023/13/38A02-0030$36.00/0 http://dx.doi.org/10.1016/j.jhsa.2012.10.042
No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.
392 䉬 © ASSH 䉬 Published by Elsevier, Inc. All rights reserved.
LIPOFIBROMATOUS HAMARTOMA
393
Fatty infiltration of nerve Fatty or fibrous neoplasm of nerve Fibrofatty proliferation of nerve Fibrolipoma Fibrolipomatous hamartoma Fibroneurolipoma Intraneural lipoma Lipofibroma Lipomatosis of nerve
fibers could be identified. Since that initial report, this entity has gone by several names (Table 1).2,3 Ultimately, the term lipofibromatous hamartoma was introduced by Johnson and Bonfiglio4 in 1969, and this is the preferred nomenclature for this lesion at this time. A recent review of the literature notes that only 88 cases have been reported for this rare condition.5 Lipofibromatous hamartoma is more often found in the upper extremity than in other regions of the body, and within the upper extremity, the median nerve is the most common nerve affected.6 Other, less common upper extremity sites have included the radial nerve, ulnar nerve, digital nerve, and brachial plexus.3,7–10 In the lower extremity, it has been found affecting the sciatic nerve11 and branches of the medial plantar nerve.2 It is probably congenital in nature, but it grows slowly, usually presenting with symptoms in the third or fourth decade of life, although rapid growth can lead to earlier discovery.12–14 This tumor is often associated with macrodactyly, which is present in approximately 30% of cases.2,5,6,9,13,15 In fact, LFH is the most common condition associated with macrodactyly of the upper extremity.2 The macrodactyly is typically noted in the distal distribution of the nerve involved with the LFH lesion proximally. Although this arrangement is also found in neurofibromatosis patients, LFH is easily distinguished from neurofibromatosis by the large quantities of fat found in the LFH nerve lesions.9 The exact relationship between these conditions is the subject of some debate. Lipofibromatous hamartoma occurring with macrodactyly can be thought of as a proximal extension of the distal growth disturbance.9 Despite histologic similarities, it is possible that LFH occurring in isolation is a separate pathologic entity or simply a form of the disease with less penetrance. Because both forms are rare, existing data are insuf-
DIAGNOSIS, IMAGING, AND HISTOPATHOLOGY Lipofibromatous hamartoma presents most commonly as a painless, slowly enlarging mass. If associated with macrodactyly, enlargement of the digit(s) and/or palm can be the first manifestation of this condition.2 Due to the abnormal enlargement of the nerve(s) associated with this tumor, signs and symptoms of nerve compression are often noted. For example, median nerve lesions at the wrist often present with signs and symptoms of carpal tunnel syndrome. Both sensory and motor disturbances have been reported with these tumors.2,3,8,16 Nerve conduction and EMG studies are abnormal in these cases, as expected. The differential diagnosis for this type of lesion includes neurofibroma, neurilemoma, neuroma, ganglion, lipoma, or vascular malformation, among others. When macrodactyly is present, radiographs should be obtained to evaluate the bony structures. Lipofibromatous hamartoma can be evaluated by ultrasound; the affected nerve will appear grossly enlarged, usually in a fusiform shape. As described by Toms,17 these tumors will have “characteristic hypoechoic coaxial cabling encased by an echogenic substratum” (Fig. 1). Magnetic resonance imaging (MRI) is generally the imaging modality of choice to assist with diagnosis and surgical planning. On MRI, the appearance of these tumors is pathognomonic: the nerve is enlarged, containing 15 or 16 coaxial “cables” that correspond to 2to 3-mm diameter bundles of axons encased in epineural fibrous tissue (Fig. 2). These bundles are typically interspersed evenly with fat at the carpal tunnel, increasing the overall cross-sectional area of the nerve (up to 1.6 cm2) without changing the innate MRI signal of the nerve.17 The appearance of this tumor on MRI is so distinct that it can effectively make the diagnosis without the need for biopsy in most patients.18 On gross pathologic inspection, median nerve LFH appears as an intrinsically enlarged nerve, sometimes with surrounding extrinsic fibrofatty tissue. As expected, this tissue can be yellow or tan in color, consistent with its fatty and/or fibrous nature. On histopathologic evaluation, the epineurium is found to be expanded by the increased fibroadipose tissue that surrounds and separates the individual nerve bundles.6 TREATMENT OPTIONS AND PROGNOSIS Treatment options for median nerve LFH described in the literature include a wide range of options, from
JHS 䉬 Vol A, February
In Brief
ficient to draw conclusions about the differences between the 2.
TABLE 1. Synonyms for Lipofibromatous Hamartoma
394
LIPOFIBROMATOUS HAMARTOMA
FIGURE 1: Ultrasound appearance of lipofibromatous hamartoma of the median nerve at the wrist. A The median nerve is outlined in this axial view, which demonstrates the “coaxial cable-like” appearance. B Sagittal view demonstrates the bundle of multiple longitudinal cables (between the arrows).
In Brief FIGURE 2: The MRI appearance of lipofibromatous hamartoma of the median nerve at the wrist (marked with an arrow in each image). A T1- and B T2-weighted axial images showing the cable-like appearance of the enlarged median nerve. C Coronal and D sagittal T1-weighted images show the longitudinal appearance of the tumor as it passes through the carpal tunnel. This has been described as “serpiginous” due to the snake-like, wavy appearance of some LFH lesions.
close observation to complete nerve resection. Each of the options has advantages and disadvantages, which are outlined later. Of course, when macrodactyly is
present, debulking of the overgrown tissue and epiphysiodesis are often required in addition to surgery to address the LFH tumor itself.2
JHS 䉬 Vol A, February
LIPOFIBROMATOUS HAMARTOMA
395
In the absence of any notable neurologic symptoms, observation has been advocated in a couple of case reports.18,19 No long-term follow-up on these patients is provided in these publications. Most authors advocate carpal tunnel release (CTR) to decompress the median nerve in symptomatic patients, combined with biopsy of the tumor to confirm a pathologic diagnosis. Case reports with follow-up between 6 months and 5 years show that this can result in complete resolution of symptoms in some patients.5,16,20 However, not all results from simple decompression are this encouraging. Louis reported on a series of 4 patients with median nerve LFH that were initially managed by CTR with or without epineurotomy.21 All subjects required repeat surgery between 4 and 13 years later for recurrence of the mass and/or progression of symptoms. Despite more aggressive resection and debulking of the tumor at the time of repeat surgery, 2 patients ultimately lost all median nerve function; one patient had progressive, permanent loss of sensation; and the final patient’s outcome was not conclusively better after a repeat surgery. Frykman reports a mixed experience in 2 cases of median nerve LFH. One patient seemed to get good relief from CTR alone, and another had early resection (at age 4) leading to motor dysfunction, requiring opposition transfer at age 5. This patient ultimately had median nerve excision due to intractable pain.9 Similarly, Johnson reported on a patient whose first LFH tumor resection in infancy resulted in loss of thumb opposition and greatly diminished sensation in the radial digits. Despite this aggressive primary surgery, the mass continued to grow and ultimately required a second debulking procedure years later.4
The literature regarding early, aggressive resection of these tumors shows mixed results. Occasionally, resection of large portions of fibrofatty tissue can be accomplished without removal of substantial portions of the median nerve and without the need for invasive intraneural dissection.12 However, many of these tumors present as fusiform lesions that permeate the entire nerve, without any portion of the tumor that is easily accessible (Fig. 3). For these lesions, some authors have recommended epineurotomy and intraneural dissection, resecting the tumor tissue from around individual groups of fascicles when possible. Bains reports on a case in which this type of limited intraneural excision left a patient with normal nerve function at 10 months’ follow-up.14 Al-Qattan performed debulking in 7 cases of LFH but does not report on the patient’s neurologic function after surgery.15 Ulrich reported on 2 patients who had intraneural dissection with partial tumor excision, with no neurologic deficits 6 – 8 years after surgery.22 These reports would indicate that good results can be obtained with intraneural dissection in some cases. However, not all reports are as promising. Clafijo-Alvarez treated a patient with median nerve LFH with intraneural fascicular dissection for tumor excision, with preserved motor and sensory function at 6 months. Unfortunately, the tumor recurred, and a repeat excision and nerve grafting were performed 2 years later. He reported no postoperative motor deficit (possibly due to ulnar nerve contributions to the thenar muscles) and return of protective sensation by 6 months; the patient was tumor free at 3 years.23
JHS 䉬 Vol A, February
In Brief
FIGURE 3: Intraoperative photographs of carpal tunnel decompression in a patient with lipofibromatous hamartoma of the median nerve. A Extended carpal tunnel incision, with the diffusely enlarged median nerve visible at the radial edge of the wound (between the arrows). B The retractor is gently lifting the median nerve, which is remarkable for a diffuse, yellowish fibrofatty infiltrate.
396
LIPOFIBROMATOUS HAMARTOMA
Hsu describes performing epineurotomy and microsurgical dissection of the motor branch through the tumor in a retrograde fashion, so that the motor function could be preserved when the remainder of the nerve was excised and grafted. Three years after surgery, there was no sign of tumor recurrence. Opposition and grip strength were intact, but sensory recovery was incomplete (2-point discrimination ⬎ 15 mm).24 Warhold reports on a series of LFH patients treated with a variety of different procedures, from CTR alone to nerve excision with and without grafting. He points out that in one 14-year-old girl, complete excision of 8 cm of the median nerve was performed, with “no loss of sensation” after surgery. He suggests that this could be due to the presence of ulnar nerve contributions to the median-innervated structures, as well as the ability of the central nervous system to adapt in children.13
In Brief
RECOMMENDATIONS Because LFH remains a rare tumor, there is little highlevel evidence to guide treatment. However, based on the literature available, we agree with a conservative approach whenever possible for this nonmalignant neoplasm.25 Patients without symptoms might require only close observation. Those patients presenting with symptoms of carpal tunnel syndrome should have decompression with biopsy to confirm the pathologic diagnosis. This biopsy can be obtained by excising a small, noncritical nerve branch or by making a limited epineurotomy on the ulnar/dorsal portion of the nerve to extract intraneural tumor for analysis. Because more aggressive, intraneural resections have not been shown to conclusively lower recurrence rates, and can actually worsen median nerve function, we do not recommend this for patients with normal or near-normal median nerve function. For patients with worsening nerve function despite decompression, intraneural dissection or nerve excision with grafting might be indicated. When possible, the motor branch should be preserved in these cases. If the motor branch is not functional, or if a long nerve graft is required, consideration should be given to early opposition transfer to improve function. Although there are occasional reports of patients who have done well after nerve excision without grafting, we consider this approach to be unwise, even in children, in whom the deficit might be more easily overcome with adaptation. Recurrence of LFH in nerve grafts has not been described. Lipofibromatous hamartoma is a rare tumor of fibroadipose tissue that commonly affects the nerves of the upper extremity, particularly the median nerve. Despite its benign nature, LFH can cause symptoms of nerve compression and can lead to a dramatic decline in nerve function in some patients. A conservative approach is re-
commended, consisting of carpal tunnel release for decompression, as well as cautious biopsy of the lesion to confirm the diagnosis. More invasive, intraneural tumor resection or median nerve excision and grafting can lead to permanent nerve dysfunction. Therefore, these options should be reserved for cases in which conservative management has failed or when nerve function deteriorates to the point at which the morbidity of these surgical procedures is outweighed by some potential benefit. REFERENCES 1. Mason ML. American Society for Surgery of the Hand. J Bone Joint Surg. 1953;35A(1):257–275. 2. Amadio PC, Reiman HM, Dobyns JH. Lipofibromatous hamartoma of nerve. J Hand Surg Am. 1988;13(1):67–75. 3. Herrick RT, Godsil RD Jr, Widener JH. Lipofibromatous hamartoma of the radial nerve: a case report. J Hand Surg Am. 1980;5(3):211–213. 4. Johnson RJ, Bonfiglio M. Lipofibromatous hamartoma of the median nerve. J Bone Joint Surg Am. 1969;51 (5):984 –990. 5. Patil VS, Nagle S. Lipofibromatous hamartoma of the median nerve: A case report and review of the literature. Indian J Plast Surg. 2009;42(1):122–125. 6. Silverman TA, Enzinger FM. Fibrolipomatous hamartoma of nerve. A clinicopathologic analysis of 26 cases. Am J Surg Pathol. 1985;9(1):7–14. 7. Price AJ, Compson JP, Calonje E. Fibrolipomatous hamartoma of nerve arising in the brachial plexus. J Hand Surg Br. 1995;20(1):16–18. 8. Gouldesbrough DR, Kinny SJ. Lipofibromatous hamartoma of the ulnar nerve at the elbow: brief report. J Bone Joint Surg Br. 1989;71(2):331–332. 9. Frykman GK, Wood VE. Peripheral nerve hamartoma with macrodactyly in the hand: Report of three cases and review of the literature. J Hand Surg. 1978;3(4):307–312. 10. Jacob RA, Buchino JJ. Lipofibroma of the superficial branch of the radial nerve. J Hand Surg Am. 1989;14(4):704 –706. 11. Wong BZ, Amrami KK, Wenger DE, Dyck PJ, Scheithauer BW, Spinner RJ. Lipomatosis of the sciatic nerve: typical and atypical MRI features. Skeletal Radiol. 2006;35(3):180 –184. 12. Sirinoglu H, Sonmez A, Sav A, Numanoglu A. Lipofibromatous hamartoma of the median nerve. Ann Plast Surg. 2010;65(2):174–176. 13. Warhold LG, Urban MA, Bora FW Jr, Brooks JS, Peters SB. Lipofibromatous hamartomas of the median nerve. J Hand Surg Am. 1993;18(6):1032–1037. 14. Bains R, Kotwal A, Saeed W. Recurrent carpal tunnel syndrome in a child due to fibrolipomatous hamartoma of the median nerve successfully treated by limited excision and decompression. J Plast Reconstr Aesthet Surg. 2006;59(12):1394 –1397. 15. Al-Qattan MM. Lipofibromatous hamartoma of the median nerve and its associated conditions. J Hand Surg Br. 2001;26(4):368 –372. 16. Afshar A. Carpal tunnel syndrome due to lipofibromatous hamartoma of the median nerve. Arch Iran Med. 2010;13(1):45– 47. 17. Toms AP, Anastakis D, Bleakney RR, Marshall TJ. Lipofibromatous hamartoma of the upper extremity: a review of the radiologic findings for 15 patients. AJR Am J Roentgenol. 2006;186(3):805– 811. 18. Nardella D, Sohawon S, Carlier A. Lipofibromatous hamartoma of the median nerve. Three case reports. J Plast Reconstr Aesthet Surg. 2009;62(9):e314 –317. 19. Nouira K, Belhiba H, Baccar S, et al. Fibrolipoma of the median nerve. Joint Bone Spine. 2007;74(1):98 –99. 20. Al-Jabri T, Garg S, Mani GV. Lipofibromatous hamartoma of the median nerve. J Orthop Surg Res. 2010;5:71. 21. Louis DS, Hankin FM, Greene TL, Dick HM. Lipofibromas of the median nerve: long-term follow-up of four cases. J Hand Surg Am. 1985;10(3):403– 408. 22. Ulrich D, Ulrich F, Schroeder M, Pallua N. Lipofibromatous hamartoma of the median nerve in patients with macrodactyly: diagnosis and treatment of a rare disease causing carpal tunnel syndrome. Arch Orthop Trauma Surg. 2009;129(9):1219 –1224.
JHS 䉬 Vol A, February
LIPOFIBROMATOUS HAMARTOMA
23. Clavijo-Alvarez JA, Price M, Stofman GM. Preserved neurologic function following intraneural fascicular dissection and nerve graft for digital and median nerve lipofibromatous hamartoma. Plast Reconstr Surg. 2010;125(3):120e–122e.
397
24. Hsu CC, Chen DJ, Chen HC. Lipofibromatous hamartoma of the median nerve with long-term follow-up. Chang Gung Med J. 2005;28(2):111–116. 25. Razzaghi A, Anastakis DJ. Lipofibromatous hamartoma: review of early diagnosis and treatment. Can J Surg. 2005;48(5):394 –399.
JOURNAL CME QUESTIONS Lipofibromatous Hamartoma of the Median Nerve What condition is associated with lipofibromatous hamartoma? a. Macrodactyly b. Wilms tumor c. Maffucci syndrome d. Neurofibromatosis e. Fibrosarcoma
What is the treatment for a 30-year-old man with presumed lipofibromatous hamartoma of the median nerve with minimal symptoms? a. Observation b. Biopsy for confirmation c. Carpal tunnel release and biopsy d. Intraneural resection e. Resection and cable grafting
In Brief
To take the online test and receive CME credit, go to http://www.jhandsurg.org/CME/home.
JHS 䉬 Vol A, February