Fibrolipomatous Hamartoma of the Median Nerve of the Hand: A Case Report and Literature Review


 Introduction: Fibrolipomatous Hamartoma (FLH) is a rare tumor-like disease, mainly occurs in benign tumors of the peripheral nerves of the upper limbs, which characterized by the overgrowth of neuronal fat and fibrous tissue.Case presentation: A patient had numbness of fingers in the left hand for more than 5 years. Three years ago, the superficial sensation at the metacarpophalangeal joint of the hypothenar of the left hand was weakened. Two years later, the distal ulnar side of the index finger and the distal radial side of the middle finger were secondary to weakened superficial sensation and megalodactyly symptoms of the middle finger and index finger of the left hand were developed. Physical examination showed a mass on the left palm side. MRI showed an abnormal subcutaneous fusiform signal at the palmar side of the left wrist: T1W1 isointensity, T2W1 inhomogeneous slightly hyperintense signal. The clinical features, radiologic presentations, treatment choice, and pathologic characteristic were illustrated. During the operation, the appearance of the nerve was hypertrophic and variant, without obvious masses, the proliferated fibrous tissues were showed a fusiform change, and the nerve fibers were degenerated and atrophied. Immunohistochemical results showed S-100 (+), NSE (focus +), EMA (portion +), GFAP (-), ERG (blood vessel +), SMA (blood vessel +), Ki-67 (1%+), NF (small region +). The patient's finger numbness symptom improved obviously and the condition was stable when paying a return visit 3 months after the operation. Conclusions：The clinical symptoms of FLH of median nerve mainly include gradually enlarged painless mass, macrodactyly, pain, numbness, paresthesia and carpal tunnel syndrome. The diagnosis mainly depends on ultrasonic examination and MRI. The pathological sections of FLH sometimes show perineurioma-like changes, which need to be identified by clinical and MRI features. The treatment methods include prophylactic carpal tunnel release (CTR) and nerve transplantation after the whole nerve resection. CTR, has been proven to be helpful for many patients suffering from carpal tunnel symptoms and can relieve most of the symptoms, is the main method. However, the pathogeny needs to be further explored.


Introduction
Fibrolipomatous hamartoma (FLH), also known as nerve brolipoma or nerve lipomatosis, is a rare tumor-like disease that mainly occurs in benign tumors of the peripheral nerves of the upper limbs. It is characterized by the overgrowth of neuronal fat and brous tissue. The cause of this disease is unknown. It is more common in young people under the age of 30, more common in men than in women, and more common in left hands than in the right hands. And asymptomatic soft tissue swelling and related nervous lesions are the main clinical manifestations 1,2 . B-scan ultrasonography and magnetic resonance inspection are the main methods for diagnosing the disease, and clinicians will also misdiagnose it as a simple lipoma because of the rarity of this disease.
This article reports a case of FLH of median nerve with left hand nger nerve entrapment symptom and a literature review.

History, Physical and Laboratory Examinations
The patient is a 46-year-old male, admitted to the hospital with the chief complaint of "numbness in the ngers of his left hand for more than 5 years". Five years ago, the patient had numbness in the ngers of his left hand with no obvious predisposing causes, and he came to the hospital. The hospital considered that the condition was caused by cervical spine disease, so he was treated with oral nutritional nerve drugs (the speci c situation is unknown), but it did not improve, and the patient did not pay attention to it. Three years ago, the super cial sensation at the metacarpophalangeal joint of the hypothenar of the left hand was weakened. One year ago, the distal ulnar side of the index nger and the distal radial side of the middle nger were secondary to weakened super cial sensation and megalodactyly symptom of the middle nger and index nger of the left hand were developed. It can be found that a mass on the left palm side, which is soft, movable when pushed, with clear borders, no tenderness, and no uctuation. Then he admitted to the hospital again.
The physical examination showed obvious swelling in the index nger and middle nger of the left hand, normal body temperature, grade V muscle strength, and no tenderness, the super cial sensations at the hypothenar of the left hand, the metacarpophalangeal joint, the distal ulnar side of the index nger and the distal radial side of the middle nger were weaker than that of the right hand, and the peripheral circulation was normal. Tinel sign(+), Phalen test (+). The upper limb electromyography report showed the electrophysiological feature of severe injury of the median nerve below the left wrist, the B-scan ultrasonography of the left wrist showed that the median nerve showed a typical hamartoma change at the outlet of carpal tunnel 5cm above the left wrist. The digital nerves on the adjacent surfaces of the index nger and middle nger were thicker than other nger nerves. The patient was recommended to undergo operative treatment and admitted to the hospital for surgical treatment. And the related inspections were improved after admission.
Laboratory studies revealed normal white blood cell count, C-reactive protein level, neutrophil count, hemoglobin level and erythrocyte sedimentation rate. Tumor makers were normal. The safety indexes such as liver and kidney function electrolyte were all normal.

Imaging Findings
Preoperative plain radiographs, X-ray examination of the left hand showed a mild ulnar deviation of the distal interphalangeal joints of the second and third ngers, hyperplasia of osteophyte on the articular surface, cystic sclerosis lesions, and swelling of surrounding soft tissues (Fig. 1). MRI examination of the left hand showed no obvious abnormality in the joint space, normal bone marrow structure signal, and no obvious abnormal signal after fat suppression, and no obvious effusion in the joint, an abnormal subcutaneous fusiform signal at the palmar side of the left wrist, T1W1 isointensity, T2W1 inhomogeneous slightly hyperintense signal (Fig. 2).The radiologic appearance suggested a hamartoma.

Surgical Treatments And Pathologic Findings
Under brachial plexus block anesthesia, the patient underwent left-hand mass incision and exploratory extraction + median nerve release in a supine position (Fig. 3). After the anesthesia was successful, the patient was routinely disinfected and draped. A longitudinal S-shaped incision was made centered on the mass. The separation to the median nerve found that the transverse carpal ligament showed hypertrophic and variant appearance of the distal nerve, the color of the outer membrane turned white, the color of the outer membrane from the distal end to the trunk along the nerve to the nerve thenar branch returned to light yellow, but still hypertrophic. After incision and separation of the outer membrane, no obvious masses were found, and proliferated brous tissues were found to grow along the epineurium and endoneurium, showing a fusiform change, and the nerve bers were degenerated and atrophied (Fig. 4). The surrounding tissues were fully released and the proliferated brous tissue was separated and sent for pathological examination.

Follow-up
At the time of hospital discharge, the patient felt that the numbness in the ngers of the left hand is improved. Three months after the operation, the patient was followed up by telephone. He complained that he had not received other treatments after discharge. At present, the condition of the disease is stable, and there is no aggravation of numbness.

Literature Retrieval And Result
We searched Pubmed and Medline comprehensively by computer, and manually searched related journals and conference papers with search keywords of "hamartoma", "FLH", "FLH of median nerve", which were included in clinical literature and excluded basic researches such as biomechanics. After rigorous screening, a total of 10 articles were included in this study 1,3−8 . (Table 1)

Discussion And Conclusion
FLH is a rare, slow-growing, and benign peripheral nerve tumor. The origin of FLH is still obscure, and it is more common in adolescents, which indicates that there may be a congenital cause, although there are a few cases reported in the elderly 9 .
This disease was rst reported by Mason in 1953 and was rst described as having a painless and rare benign slowgrowing lesion 10 . Subsequently, in 1964, Mikhail published 2 cases of diffuse brous fat overgrowth involving the median nerve fatty tissue 11 . In the same year, Yeoman reported 3 cases of patients with fatty in ltration of the median nerve and pointed out that the tight junction of the intraneural brous fatty tissues prevented the extraction of the swelling 12 .
Johnson and Bon glio reviewed the literature in 1969, and presented their cases, and gave a detailed histological description of the lesion, which was o cially named as FLH 13 .
In our research on limited literature reports, we found that the median nerve and its branches were the main involved parts, followed by the radial nerve, ulnar nerve, dorsal pedal nerve, brachial plexus, and cranial nerve; the involved parts in the median nerve were usually located in the wrist or hand, and rarely in the elbow 6 . This disease is more common in young people under the age of 30, including several cases of infants and young children reported by some scholars as a congenital disease [12][13][14] , the ratio of male to female is about 2:1 14 , with more left hands than right hands. The main symptoms of clinical manifestations were gradually enlarged painless masses, and pain, numbness, paresthesia and carpal tunnel syndrome usually appeared in the later stage 15,16 . One-third of FLH patients had related macrodactyly symptoms in the innervation area of the affected area, which is called "seborrheic lipodystrophy", which was rst described by Feriz in 1925 17 . For patients with hand hypertrophy or macrodactyly, especially if the patient has signs or symptoms of nerve entrapment, FLH should be considered in the diagnosis 18 . In the case we reported, the patient was accompanied by painless masses, macrodactyly, and paresthesia and numbness along the median nerve of the hand, which mainly affected the ulnar side of the index nger and the radial side of the middle nger.
Neural brolipoma is an orange-yellow, fusiform, sausage like or ropelike enlargement of the nerve 19,20 . As seen in the case of this study, the appearance of the nerve was hypertrophic and variant, and it showed a fusiform change, the color of the outer membrane turned white, the color of the outer membrane from the distal end to the trunk along the nerve to the nerve thenar branch returned to light yellow, but still hypertrophic.
X-ray is not sensitive to FLH detection, and the X-ray lm may show normal or thickening of soft tissue, which is not diagnosable 21 . Due to the special features of B-scan ultrasonography and magnetic resonance imaging of FLH, the B-scan ultrasonography shows that the hypoechoic sound beam is surrounded by the hyperechoic brous fat structure, showing a typical "snakeskin-like" change. MRI shows fat with high signal strength on T1-weighted and T2-weighted images, a characteristic coaxial cable appearance on axial images, and a "spaghetti-like" appearance on sagittal images 21,22 .
Transverse sections may show the 'lotus sign' that occurs due to the thin hypointense septa within the fat tissue that separates the fat bundles. This is consistent with the characteristic pathological ndings seen in FLH of the thickened perineurium due to perineural brosis with septation of nerve fascicles 5,23 . Therefore, visualization of the coronal and axial characteristics obviates the need for a biopsy to make the diagnosis of FLH [24][25][26] . However, it should be differentiated from traumatic neuroma, neuro broma, neuroma, schwannoma, ganglion cyst, lipoma, hereditary hypertrophic interstitial neuritis, vascular malformation and the like during diagnosis 27,28 .
In limited literature reports, patients with FLH of median nerve basically choose to undergo mass resection and pathological examination. Gross pathological specimens show that the involved nerve is thickened in spindle shape, with yellow brous fatty tissue in ltration, which is generally con ned to the nerve sheath. Histology shows that there is a mixed in ltration of mature fatty tissue and brous tissue in and around the involved nerve sheath, which separates the nerve bundles, one of its remarkable features is that the brous tissue around the nerve is concentric 29 .Other changes in the involved nerve include the formation of the separated micro nerve bundles and the pseudo-onion skin-like structure, similar to the intraneural peripheral nerve tumor, as shown in this case; occasionally osseous metaplasia.
Jose A. Plaza 29 once mentioned that there were 3 cases of FLH of median nerve whose pathological sections showed perineurioma-like changes, as seen in this case report. Because the pathological results cannot guide the clinic well, very few hospitals will continue to perform immunohistochemistry of pathological sections. Jenna-Lynn Senger 4  There is no clear and best treatment recommendation in the limited number of cases of FLH reported in the literature.
Therefore, the current clinical treatment is mainly based on the presence or absence of symptoms and the severity of symptoms to determine the treatment plan. It is very important to understand the degree of nerve involvement of FLH for the preoperative plan. Prophylactic CTR is the main treatment for the disease. It has been clinically proven that CTR can relieve most of the symptoms of patients with carpal tunnel symptoms. Most scholars advocate early carpal tunnel decompression and brous lipid sheath decompression, anatomical and microsurgical resection is usually reserved for those patients who have undergone carpal tunnel decompression but still have progressive and disabling median nerve damage. However, this method may lead to permanent loss of motor and sensory functions, and the effect is not obvious 3 .
Some scholars believe that the progressive worsening of neurological symptoms after decompression may be related to the direct compression of individual nerve bundles by massive brosis around the nerve rather than the compression of the median nerve in the carpal tunnel. Therefore, some scholars have achieved satisfactory functional results through largescale resection of diseased tissue and sural nerve transplantation [30][31][32][33] .
In summary, the onset age of FLH is usually under the age of 30, and often at birth. while in this case, the patient was attacked by FLH at the age of 41-year-old, showing his rarity,the clinical symptoms of FLH of median nerve mainly include gradually enlarged painless mass, macrodactyly, pain, numbness, paresthesia and carpal tunnel syndrome, and the diagnosis mainly depends on B-scan ultrasonography and magnetic resonance inspection. The pathological sections of FLH sometimes show perineurioma-like changes, which need to be identi ed with clinical and MRI features. The treatment methods include CTR and nerve transplantation after the whole nerve resection. CTR has been proven to be helpful for many patients suffering from carpal tunnel symptoms and can relieve most of the symptoms. It is the main method of treatment of the disease, and the cause of the disease needs to be further explored.

Declarations
Ethics approval and consent to participate Not applicable.