Macrodystrophia Lipomatosa: A Single Large Radiological Study of a Rare Entity

INTRODUCTION

Macrodystrophia lipomatosa is a rare disorder of localized gigantism characterized by overgrowth of all the mesenchymal elements, predominantly involving the fibroadipose tissue. It is a congenital and nonhereditary condition. The term “macrodystrophia lipomatosa”was originally used to describe localized gigantism involving the lower limb by Feriz in 1925.[1] Golding later extended the term to describe localized gigantism affecting the upper limb.[2] The term macrodactyly is often interchangeably used to describe macrodystrophia lipomatosa.[3] The etiology of macrodystrophia lipomatosa is poorly understood, and several hypotheses exist. Recent studies have shown an association with PIK3CA gene mutation.[4] Pathologically, there is an increase in adipose tissue in the subcutaneous plane with a fine lattice of fibrous tissue and can occasionally involve bone marrow, periosteum, muscles, and nerve sheath in a sclerotomal distribution.[2,5] The disease is usually present since birth and the affected region/digit increases in length and girth until puberty when growth ceases. The affected individuals are usually asymptomatic except for the cosmetic disfigurement. Some of them manifest with hindered function, premature degenerative changes or very rarely due to symptoms of neurovascular compression.

Macrodystrophia lipomatosa is often associated with fibrolipomatous hamartoma (FLH) of the median nerve.[6,7] The other associated conditions are clinodactyly, syndactyly, polydactyly, and symphalangism. The rarity of this condition and the variety of terms that have been used to describe it has resulted in confusion. The purpose of this study was to report one of the largest case series, elaborate its associated findings, radiographic features and to suggest the use of the term macrodystrophia lipomatosa exclusively for isolated congenital localized gigantism with or without nerve involvement.

MATERIALS AND METHODS

It is a retrospective study. After obtaining Institutional Review Board approval, a case search was conducted in our PACS server from April 2000 to April 2018 to identify the cases of macrodystrophia lipomatosa. The search terms used were “macrodactyly,”“fibrolipohamartoma,”“macrodystrophia lipomatosa,”and “localized gigantism.”The inclusion criteria were cases with an isolated enlarged limb or digit/digits, with or without nerve involvement. Exclusion criteria were cases with a diagnosis of localized gigantism due to other causes such as neurofibromatosis, vascular malformations, cutaneous hemangiomas, and overgrowth syndromes such as Proteus syndrome and Klippel-Trenaunay syndrome.

The plain radiographs in anteroposterior and lateral views were assessed. Ultrasound was performed on Philips EPIQ 5G with L18-5 high-resolution linear probe and Siemens Acusons 2000 with 14 L5 high-resolution linear probe.

RESULTS

Initial search fetched a total of 38 cases, of which seven cases were excluded. Three cases were incompletely evaluated, and the available radiological features were not specific for macrodystrophia. One case had discolored skin with a small arteriovenous malformation at the distal phalanx level (which was confirmed by digital subtraction angiography). Two cases had slow flow venous malformation which was confirmed with ultrasound. One case had isolated fibrolipohamartoma of the median nerve without localized gigantism. A total of 31 cases was included for the final analysis. Twenty-five patients had radiographs of the affected region, out of which, 20 patients were further investigated with MRI, four patients had both MRI plus ultrasound and one patient had only ultrasound. A total of six patients had only MRI.

DISCUSSION

Macrodystrophia lipomatosa was first described by Feriz[1] in 1925 and is a disorder of localized gigantism characterized by abnormal proliferation of the fibroadipose tissue. It is a congenital and nonhereditary disorder. There is overgrowth that usually occurs in a specific sclerotomal distribution.[2] Barsky classified macrodystrophia lipomatosa as static or progressive based on the growth pattern and former being the most common type.[3] In static type, the growth of the enlarged digit is at the same rate as the other digits. In the progressive type, the growth of the affected digit is more rapid than the rest of the extremity. The etiology of macrodystrophia lipomatosa is poorly understood, and several hypotheses exist, none of which are conclusive. Recent studies have shown an association with PIK3CA gene mutation.[4]

In our study, males were more commonly affected than females. Unilateral involvement is the norm and was the most common pattern in our study group. Bilateral involvement is rare, and as noted in previous studies,[8] we also had only one case. There were case reports of abdominal wall involvement.[9] None of our cases had abdominal wall lipomatosis.

Clinically, macrodystrophia is present since birth with swelling of the affected digit or limb leading to cosmetic disfigurement [Figure 1a and b]. Some may present with hindered/loss of function, pain due to neurovascular compression or degenerative changes.

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Figure 1

A 2-year-old child with localized gigantism. (a and b) Clinical images show gross enlargement of the third and fourth digits of the left hand with syndactyly. Abnormal soft-tissue hypertrophy predominantly involving the volar aspect. (c and d) Anteroposterior and lateral radiographs show grossly enlarged left middle and index fingers, abnormal soft tissue along the volar aspect with resultant dorsal bending of the digits, syndactyly, and symphalangism.

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According to the pattern of distribution, the macrodystrophia lipomatosa was divided into “nerve territory oriented type”and “diffuse or pure lipomatous type.” [10] In the “nerve territory oriented type,”there are hypertrophied soft tissues especially that of fat, with or without fatty infiltration of the nerves. In the pure lipomatous type, there was a marked hypertrophy of adipose tissue without the involvement of the nerves. We also observed a “mixed pattern type”where there was an overlap of “nerve territory oriented type”and “diffuse lipomatous type”in two cases. In our study, the most common pattern identified was the “nerve territory-oriented type.”The most common nerve territory distribution was along the median nerve in the upper limb and along the medial plantar nerve in the lower limb. In the hands and feet, the involvement of the 2^nd and 3^rd digit is common corresponds to the median and the medial plantar nerve supply respectively. Our results are in concordance with the literature.[11-14] Prasetyono et al., and Gupta et al., had similar observations in their study.

The presence of nerve involvement was confirmed on either ultrasound or MRI when there was enlargement of the nerve with interfascicular adipose tissue proliferation splaying the nerve fascicles giving a coaxial cable appearance. The term “fibrolipohamartoma”or “lipomatosis of nerve”is most commonly used to describe the proliferation of mature adipocytes within peripheral nerves.[14] The circumferential proliferation of fat around the epineurium of the nerve has also been reported.[15] Earlier studies have suggested FLH of the nerve and macrodystrophia lipomatosa as separate entities.[5,16] However, neural involvement in macrodystrophia and FLH of the nerve are interchangeably used as they define the same pathological and radiological finding. In our study, there was 100% of upper limb cases, and 66% of lower limb cases had neural involvement.

Imaging in cases with localized gigantism, using radiographs and ultrasonography (USG), is required for confirming the diagnosis and assessing the accurate distribution of the disease for further management.

Plain radiographs are first and most commonly used imaging modality.[17] The common findings are soft tissue overgrowth with osseous hypertrophy of the affected digit or limb. The osseous changes are increased length, width, and cortical thickening. In digits, these changes are seen along the volar aspect leading to dorsal bending [Figure 1c and d]. Bony outgrowths with or without degenerative changes in the adjacent joints can be ascertained [Figure 2]. In long-standing cases, there may be ankylosis. Other associated findings such as syndactyly and polydactyly [Figure 3] and symphalangism[18] [Figure 1c and d] can be readily appreciated on the plain radiographs.

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Figure 2

(a and b) Radiograph of the foot shows isolated enlargement of the 2^nd digit with soft tissue and osseous hypertrophy of the phalanges along with bony excrescences of the proximal interphalangeal joint.

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Figure 3

Anteroposterior radiograph of the hand shows, postaxial hexadactyly, proximal phalanx of the 6^th digit articulates with the 5^th metacarpal phalangeal joint. Syndactyly of left 3^rd and 4^th digits.

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High-resolution ultrasound reveals soft-tissue hypertrophy and extremely helpful in assessing the involvement of the nerves. Fat hypertrophy can be subcutaneous, inter- or intra-muscular in distribution. Fibrolipohamartoma of the nerve appears as an enlarged nerve with prominent fascicles and interfascicular fat hypertrophy [Figure 4]. Focused USG is also very helpful in excluding the clinical mimics of the localized overgrowth such as vascular malformation which can be missed on plain radiographs.

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Figure 4

(a and b) Ultrasound images of two different patients, showing an enlarged median nerve with prominent hypoechoic nerve fascicles and hyperechoic interfascicular fat (large arrows). Figure on the right in 4a shows normal left median nerve (small arrow).

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Computed tomography is not indicated, as it does not provide additional information. MRI is helpful, especially in assessing “diffuse lipomatous”and “mixed pattern”types.[19,20] MRI demonstrates the nonencapsulated fibrofatty proliferation of the soft tissues which follows the subcutaneous fat in all sequences and the osseous hypertrophy. MRI is useful in assessing the FLH of the nerve [Figures 5 and 6] and also in assessing the neurovascular bundle in other associations such as syndactyly [Figure 7]. It is the investigation of choice in cases of diffuse lipomatous and mixed type, where ultrasound is suboptimal [Figure 8].

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Figure 5

Typical appearance of the fibrolipohamartoma of median nerve on magnetic resonance imaging. (a) Coaxial cable appearance (arrow) in the axial images with interfascicular fat, (b) suppressing on fat suppressed sequence. (c) Spaghetti like appearance in the coronal images (arrow). There is associated intermuscular fat hypertrophy in the thenar muscles.

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Figure 6

Fibrolipohamartoma of tibial nerve on magnetic resonance imaging, non fat suppressed images. (a) Coaxial cable appearance (red arrow) in the axial images with interfascicular fat. (b) Spaghetti-like appearance in the coronal images (red arrow). (c) Fibrolipomatous hamartoma of the medial plantar nerve. There is associated intramuscular fat hypertrophy of the gastrocnemius and soleus muscle and in the subcutaneous plane.

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Figure 7

(a) Magnetic resonance imaging of the hand, non fat suppressed images showing syndactyly, spaghetti-like median nerve and the common artery which is bifurcating into the digital arteries (red arrow). (b) Shows fusion of the distal phalanges - symphalangism (red arrow).

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Figure 8

(a) Radiograph of the lower limbs shows an elongated right lower limb with limb length discrepancy, hypertrophied soft tissue, and postepiphysiodesis fixation screws. (b) Radiograph of the foot anteroposterior view in the same patient, shows elongated 1–4 digits with associated soft tissue hypertrophy. (c) T2 axial image at the level of the mid-third of leg shows hypertrophy of fat in the subcutaneous and intermuscular fascial planes.

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Macrodystrophia lipomatosa can be associated commonly with syndactyly, symphalangism, polydactyly, brachydactyly, or clinodactyly and rarely with lipomatous growths in subcutaneous plane and intestines, pulmonary cysts, and calvarial abnormalities.[2,5] In our study, we had three cases with syndactyly and one case with symphalangism and one case with polydactyly.

Localized gigantism associated with cutaneous hemangiomas/varicose veins or cutaneous discoloration or palmar and plantar cerebroid thickening or cafe au lait spots should indicate an alternate diagnosis.

Treatment options include serial follow-up or surgical intervention in the form of debulking with staged reconstruction or epiphysiodesis or ray amputation. The choice of treatment offered and the treatment taken by our study group is beyond the scope of this study.

CONCLUSION

The most commonly used terminologies for congenital isolated limb or digit enlargement are macrodystrophia lipomatosa and macrodactyly. However, the usage of the term “macrodactyly”for the diffuse involvement of an entire limb with or without digital enlargement as seen in three of our cases, may not be appropriate. In conclusion, we have reserved the term “macrodystrophia lipomatosa”for congenital isolated limb or digit/digits enlargement with or without fibrolipohamartoma of nerve. The presence of cutaneous hemangiomas/varicose veins, cutaneous discoloration, palmar, and plantar cerebroid thickening or cafe au lait spots should indicate an alternate diagnosis. The term “isolated fibrolipohamartoma of nerve”can be used in cases when there is only nerve enlargement without subcutaneous, inter-muscular and intra-muscular fibrofatty hypertrophy, as seen in one of our cases. Plain radiographs and high-resolution ultrasound are sufficient for the diagnosis of macrodystrophia lipomatosa with or without fibrolipohamartoma. MRI is indicated to assess the status of the neurovascular bundle in case of complex cases with syndactyly for operative planning.