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DOI:10.2214/AJR.04.1717
AJR 2006; 186:805-811
© American Roentgen Ray Society

Clinical Observations

Lipofibromatous Hamartoma of the Upper Extremity: A Review of the Radiologic Findings for 15 Patients

Andoni P. Toms1, Dimitri Anastakis2, Robert R. Bleakney3 and Thomas J. Marshall

1 Department of Radiology, Norfolk and Norwich University Hospital, Colney Ln., Norwich, Norfolk NR4 7UY, England.
2 Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
3 Mount Sinai Hospital, University Health Network, Toronto, ON, Canada.

Received November 7, 2004; accepted after revision January 31, 2005.

 
Address correspondence to A. P. Toms (andoni.toms{at}nnuh.nhs.uk).


Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The purpose of this study was to analyze the radiologic characteristics of lipofibromatous hamartomas affecting upper limb peripheral nerves.

CONCLUSION. Although there are pathognomonic features that characterize lipofibromatous hamartoma on MRI, the range of appearances is broad. Sonography appears to show equally characteristic features and may be a useful tool for assessing this condition.

Keywords: lipofibromatous hamartoma • MRI • soft-tissue neoplasms • sonography


Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The term "lipofibromatous hamartoma" is most commonly used to describe the proliferation of mature adipocytes within peripheral nerves resulting in a palpable yellow neurogenic mass (Fig. 1). Mature fat infiltrates the nerve, separating axonal bundles sheathed in perineurium, which normally lie adjacent to each other. Perineural and endoneural fibrosis thickens the axonal bundles, which are interspersed through the proliferative fat, to produce the characteristic histologic appearances.


Figure 1
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  		Fig. 1 —52-year-old man with lipofibromatous hamartoma. Intraoperative photograph illustrates typical gross appearance of lipofibromatous hamartoma. Multiple soft, gray-yellow lobulated masses (arrows) are present within epineural sheath of radial digital nerve of this right index finger. Epineurium of digital nerve had extensive perineural fibrosis.

 

The World Health Organization tumor classification describes this entity as lipomatosis of the nerve [1]. Although this description simplifies the numerous descriptions in the literature, such as neural lipoma and fibrolipoma, it does not do justice to the fibrous element within the lesion.

Lipofibromatous hamartomas are rare. Patients typically present in their third or fourth decade of life with a long history of painless swelling in the distal forearm that often was first noted in childhood [2-8]. The median nerve is the most commonly involved peripheral nerve [2, 3, 5, 6, 8-16], with involvement of other peripheral nerves of the upper extremity reported less frequently [2, 7, 17-21].

Involvement of peripheral nerves outside the upper extremity has been reported only as isolated cases [22-26]. Patients with median nerve involvement commonly present with carpal tunnel syndrome [6, 8, 11]. Before the widespread availability of MRI, the diagnosis of lipofibromatous hamartoma was confirmed after exploratory surgery and biopsy of the lesion [2]. In the largest reported series on lipofibromatous hamartoma, approximately one quarter of patients had macrodystrophia lipomatosa—gigantism produced by mesenchymal overgrowth confined to the affected nerve territory [2]. Similar findings have been reported for a smaller radiologic series [20] and a number of case reports [27-29].

The appearance of lipofibromatous hamartoma on MRI has been well described in numerous isolated case reports [5-12]. The MRI features common to all cases of lipofibromatous hamartoma have been analyzed and are considered to be pathognomonic [20, 30]. However, the range of morphologic features of lipofibromatous hamartoma on MRI has not been analyzed systematically. The sonographic findings for lipofibromatous hamartoma have been described in a single case report [6] and appear to correlate with the MRI appearances. But, to date, the sonographic findings for lipofibromatous hamartoma have not been analyzed systematically. The purpose of this study was to analyze the radiologic characteristics of lipofibromatous hamartoma affecting upper limb peripheral nerves, paying particular attention to the range of morphologic features on MRI, and to correlate these appearances with sonographic findings.


Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
This study included 15 patients who underwent sonography, CT, or MRI. The patients came from two centers: 12 from Toronto Western Hospital in Toronto, Canada, and three from the Norfolk and Norwich University Hospital in Norwich, England. The patients were identified from hospital and personal databases.

The radiologic examinations took place between 1998 and 2003. Ten sonographic examinations, 15 MRI examinations, and one CT examination were performed. Sonography was performed on an ATL 5000 HDI machine (Wave Imaging) with a 5- to 12-MHz linear-array probe. CT was performed on a LightSpeed machine (GE Healthcare) with 5-mm axial slices acquired with a pitch ratio of 1.5 and reconstructed every 5 mm. MRI studies were performed on a 1.5-T Signa machine (GE Healthcare). Axial T1-weighted and fat-saturated T2-weighted sequences were performed on all patients, with at least two additional sequences performed in at least one other plane. All radiologic studies were archived on a PACS (Centricity, GE Healthcare). Data for all studies were recalled and reviewed retrospectively by two musculoskeletal radiologists using a DICOM viewer (eFilm Workstation, Merge Healthcare) on a high-resolution 2K monitor.

The shape, length, cross-sectional area, and number of neural bundles of each lesion were recorded along with sonographic, CT, and MRI characteristics. Any associated hypertrophy of local osseous and soft tissues was also noted. Any reporting discrepancies were resolved by consensus.


Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The results are summarized in Table 1. Of the 15 patients reviewed, seven were men and eight were women (age range, 22-55 years; average, 37.4 years). Six patients had isolated median nerve lesions, six had isolated ulnar nerve lesions, and three had lipofibromatous hamartoma involving multiple upper limb nerves (of which two had brachial plexus involvement). Four patients had macrodystrophia lipomatosa; two of these had isolated lipofibromatous hamartoma of the median nerve, whereas one had extensive involvement of the median, ulnar, and radial nerves along with the proximal brachial plexus. Seven of the 15 patients had histologic confirmation of the radiologic diagnosis. Tissue samples were obtained as part of a carpal tunnel release in two patients, after debulking in four, and after amputation in one.


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  		TABLE 1: Summary of Results

 


Figure 2
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  		Fig. 2A —52-year-old man with lipofibromatous hamartoma of median nerve and macrodystrophia lipomatosa. Photograph of volar aspect of right hand and forearm shows local gigantism of thumb and radial half of index finger (arrowheads), with associated peripheral cyanosis. Scar (arrow) extending from thenar eminence proximally into forearm bears witness to previous surgical exploration and decompression of "fatty mass."

 


Figure 3
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  		Fig. 2B —52-year-old man with lipofibromatous hamartoma of median nerve and macrodystrophia lipomatosa. Conventional radiograph of same patient shows regional osseous gigantism in median nerve distribution. Premature osteoarthrosis of interphalangeal joints (arrowheads) has been treated by arthrodesis and internally fixed with cerclage wires.

 
Isolated Median Nerve Lipofibromatous Hamartoma
Six patients had isolated median nerve lesions that measured between 2.4 and 20 cm in length (mean, 11.3 cm) and had maximal cross-sectional areas ranging from 0.6 to 2.4 cm2 (mean, 1.35 cm2). In five of the six patients, the proximal margins were found at the level of the pronator quadratus whereas the distal position was more variable. In one patient, the proximal end of the lesion, which extended into the forearm, was not included in the field of view of the MRI study. Within these isolated lesions, between 15 and 20 neural bundles measuring 1-3 mm in diameter were identified, with evenly interspersed fat.

Isolated Ulnar Nerve Lipofibromatous Hamartoma
Six patients had isolated ulnar nerve lesions. Five patients had diffuse ulnar nerve involvement whereby three or four thickened neural bundles were evenly interspersed with fat. Lesions measured between 2 and at least 8 cm in length (mean, 6.25 cm). Cross-sectional areas ranged from 0.3 to 0.7 cm2 (mean, 0.37 cm2). In four patients, the proximal margins of the lesions were included in the MRI study and were identified within Guyon's canal. In the other two patients, the proximal edge of the lesion was not included in the field of view. One of the three ulnar nerve lesions had a homogeneous fatty component (with a cross-sectional area of 17 cm2) that extended eccentrically from Guyon's canal through the palm and into the web spaces.

Multiple Nerve Lipofibromatous Hamartoma
Two patients presented with involvement of the brachial plexus and its branches, including the axillary, musculocutaneous, radial, median, and ulnar nerves. The total length of these lesions was 80 cm, and the maximal cross-sectional areas were 2.2 and 4.5 cm2. The neural bundles numbered 15-16 and were approximately 2 mm in diameter. Unlike the isolated median nerve lesions, the fatty component was typically unevenly distributed through the nerve, with multiple eccentric, lobulated areas.

Four patients with lipofibromatous hamartoma of the median nerve underwent a sonographic examination that revealed 15-16 nearly anechoic bundles encased in echogenic soft tissue with no detectable Doppler signal. CT of the wrist in one patient showed neural bundles of soft-tissue attenuation encased in fat within the carpal tunnel. MRI studies in all but one patient showed a characteristic signal: Neural bundles were of low signal intensity on all sequences and, on T1- and T2-weighted images, were encased in soft tissue of fatty signal intensity that was completely saturated on spectral fat suppression or inversion recovery sequences. In one patient with isolated median nerve involvement and macrodystrophia lipomatosa, the neural bundles were of intermediate signal intensity and surrounded by fat of relatively low signal intensity on T1-weighted images. Soft-tissue edema was not noted on any sequences.


Discussion
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The average age and range of this series of patients were similar to the two previously reported series of patients with lipofibromatous hamartoma [2, 20]; the incidence of macrodystrophia lipomatosa (four of 15 patients) was also nearly the same as the 25% reported by the same authors (Figs. 2A and 2B). The near-equal numbers of men and women were typical.

Consistent with previous reports, the median nerve was the most common anatomic location for lipofibromatous hamartoma in this series (nine of 15 patients). However, the incidence of ulnar nerve involvement was much higher, at nearly 50% (eight of 15 patients), than the approximately 10% previously reported [2, 20]. Two of the patients with ulnar nerve involvement had this as part of a generalized involvement of all upper extremity nerves, resulting in a 40% incidence (six of 15 patients) of isolated ulnar nerve involvement. On cross-sectional imaging, lipofibromatous hamartoma of the ulnar nerve can be more difficult to appreciate than is lipofibromatous hamartoma involving the median nerve. Ulnar nerve lesions typically have a cross-sectional area of 0.3 cm2 in the cubital tunnel, range from 2 to 8 cm in length, and contain three or four neural bundles of low signal intensity measuring 1 mm in diameter (Fig. 3). Continued growth of the lesion must proceed in less restricted surroundings proximal or distal to the cubital tunnel (Fig. 4).


Figure 4
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  		Fig. 3 —31-year-old woman who presented with paresthesia in ulnar nerve distribution. Axial T1-weighted MR image through wrist at level of distal carpal row shows Guyon's canal distended with fat (arrowhead) and thickened fascicles of ulnar nerve. Conductive delay was confirmed with electromyelography.

 

Figure 5
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  		Fig. 4 —41-year-old man with lipofibromatous hamartoma of median nerve. Coronal T1-weighted MR image of hand shows that tumor (arrow) is predominantly lipomatous and extends from Guyon's canal. Palmar mass had first been noticed at age of 6 years and grew slowly for 35 years until presentation.

 


Figure 6
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  		Fig. 5 —40-year-old woman with lipofibromatous hamartoma of median nerve. Axial T1-weighted MR image of wrist at level of proximal carpal row shows that median nerve is enlarged, as are individual neural bundles, but that signal characteristics are those of normal nerve. Neural bundles have higher T1 signal (arrow) than does normal muscle, and no discrete lipomatous component is present at this level.

 
The radiologic characteristics of lipofibromatous hamartoma of the median nerve are consistent with previously reported descriptions (Figs. 5, 6A, and 6B). The pathognomonic pattern of an enlarged nerve containing 15 or 16 coaxial "cables" or bundles of axons encased in epineural fibrous tissue was the norm. The bundles were characteristically larger than in the ulnar nerve, measuring 2 mm and occasionally 3 mm in diameter. In the region of the carpal tunnel, the neural bundles were evenly interspersed with fat in all patients, such that the cross-sectional area of the median nerve was increased to 0.6-1.6 cm2. Even in the two patients with extensive lipofibromatous hamartoma of the upper extremity nerves, where the distribution of fat in the lesion was, in most places, wildly eccentric (Figs. 7A and 7B), the components within the carpal and cubital tunnels conformed to this description of evenly interspersed fat and neural bundles. The fibroosseous tunnels appear to restrict the distribution of fat in the nerve because of their inability to expand; above and below these restrictions the fatty component has room to proliferate more freely and erratically.


Figure 7
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  		Fig. 6A —31-year-old woman with extensive lipofibromatous hamartoma of upper limb nerves. Sonograms of enlarged median nerve acquired in sagittal (A) and axial (B) planes show hypoechoic cablelike neural bundles (arrows) separated by hyperechoic fat.

 

Figure 8
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  		Fig. 6B —31-year-old woman with extensive lipofibromatous hamartoma of upper limb nerves. Sonograms of enlarged median nerve acquired in sagittal (A) and axial (B) planes show hypoechoic cablelike neural bundles (arrows) separated by hyperechoic fat.

 

Figure 9
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  		Fig. 7A —55-year-old man with lipofibromatous hamartoma of median nerve. Coronal T1-weighted MR image shows lipofibromatous hamartoma of brachial plexus (arrow) at level of formation of terminal branches.

 

Figure 10
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  		Fig. 7B —55-year-old man with lipofibromatous hamartoma of median nerve. Axial T1-weighted image through arm shows lipofibromatous hamartoma of radial and median nerves (arrows).

 
Sonography showed the characteristic hypoechoic coaxial cabling encased by an echogenic substratum (Figs. 6A and 6B). In all but one patient, the MRI findings were characteristic, with low-signal-intensity axonal bundles surrounded by fat (Fig. 5). One patient showed less typical signal characteristics but a morphologic arrangement typical of lipofibromatous hamartoma of the median nerve. Throughout the lesion, the neural bundles were hyperintense to muscle and the surrounding substratum was isointense to muscle on T1-weighted images (Fig. 8). These signal characteristics may represent an unusual developmental distribution of the fibrous and fatty elements within this lesion. Although not the pathognomonic appearances of lipofibromatous hamartoma on MRI, these appearances previously have been attributed to lipofibromatous hamartoma [31]. The lack of high signal intensity on the fat-saturated T2-weighted sequences excludes hereditary hypertrophic interstitial neuritis [20]. The patient did not have a biopsy of this lesion, and therefore histologic correlation was not possible. This case therefore must be considered a potential atypical variant based solely on imaging characteristics that are similar to the classic description of lipofibromatous hamartoma, illustrating a limitation of this study. Only seven of the 15 patients had histologic confirmation of the diagnosis, as is consistent with the view that the MRI appearances of lipofibromatous hamartoma preclude the need for histologic confirmation [20]. This view therefore is used to justify the diagnosis of lipofibromatous hamartoma in this series.


Figure 11
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  		Fig. 8 —31-year-old man. Axial T1-weighted MR image through wrist shows enlarged median nerve and divided flexor retinaculum. Signal intensities of nerve are reversed from typical pattern seen in lipofibromatous hamartoma, with neural fascicles of high fat intensity (arrow) and intervening substratum of intermediate soft-tissue intensity.

 

Of the six patients with isolated lipofibromatous hamartoma of the median nerve, the proximal end of the lesion was identified in the distal forearm at the level of the pronator quadratus for five patients, in all of whom a normal-caliber median nerve was identified proximal to the pronator quadratus. The proximal end of the lesion in the sixth patient was not included in the MR images.

Two patients had an extensive lipofibromatous hamartoma affecting the brachial plexus and all major upper extremity nerves. Maximal axial diameters were 2.2 and 4.5 cm2 and occurred in the proximal median nerve in both patients. The distribution of fat within the nerve was typically eccentric, with lipomatous masses bulging from the nerve at multiple sites and extending into adjacent muscles (Figs. 7A and 7B). The lesions extended proximally into the brachial plexus to the level of the clavicle. The proximal margin was not defined because imaging of the cervical spine was not performed.

The sonographic data from this study illustrate, for what is to our knowledge the first time, consistent echo patterns in a series of patients with lipofibromatous hamartoma, and we suggest that these patterns are characteristic. The sonographic features of a thickened hyperechoic nerve containing discrete hypoechoic cablelike fascicles corresponded, in all patients, to the MRI signal patterns. In theory, sonography should be quicker and easier to perform than MRI for both diagnosis and delimitation of lipofibromatous hamartoma, particularly in patients with extensive disease. These patients require MRI studies with multiple, time-consuming fields of view, whereas sonography can cover the lesion in a matter of minutes. Our anecdotal experience suggests that sonography is the more convenient technique. However, in all but one patient, the sonography was performed with full knowledge of the diagnosis made on MRI, precluding any direct comparison of the utility of the two techniques in this retrospective study.

In conclusion, lipofibromatous hamartoma is a rare disorder that most commonly manifests in the nerves of the upper extremity and increasingly is being recognized and reported. The MRI features are considered pathognomonic, but this series shows the morphologic variability; sonographic and CT features have been described less frequently but are also characteristic of the lesion. The sonographic findings consistently corresponded to the MRI findings and may be characteristic of this condition. Sonography may be useful for extensive lesions, on which complete assessment of the affected nerve can be obtained more easily than with MRI. The histologic features are the same for all lipofibromatous hamartomas, but the gross morphologic appearances may vary widely from small, simple lesions of the ulnar nerve to extensive, complex lipomatosis involving all upper extremity nerves. For lipofibromatous hamartoma, knowledge of characteristic radiologic findings—both sonographic and MRI—may obviate diagnostic biopsy in centers with extensive peripheral-nerve experience.


References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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