Case 1. A four-month-old girl presented to the clinic with
enlarged second and third toes on the left foot. The condition had been
present at birth. The mother's pregnancy had been full term and unremarkable.
There was no family history of limb malformations or neurofibromatosis. The
patient was otherwise healthy and had a normal examination except for very
enlarged second and third toes. Radiographs revealed increased soft-tissue
density and enlargement of the second and third phalanges and metatarsals
(Fig. 1-A). Resection of the
second and third rays was performed when the patient was six months of age.
Histologically, the resected specimens were enlarged but were otherwise normal
in structure and had excessive amounts of normal-appearing adipose tissue.
Postoperatively, the foot was noted to be similar in width and height to the
contralateral, uninvolved foot.
By three months after the operation, the mother noted enlargement of the
plantar aspect of the child's foot. The patient, who was then nine months of
age, underwent repeat excision of the redundant fatty tissue. Histological
specimens again showed excessive adipose tissue and fibrosis.
By the time the patient was five years of age, the soft-tissue hypertrophy
had returned and involved the entire left foot as well as the calf. Because of
the large size of the foot, the patient was only able to wear custom-made
shoes. The forefoot was stiff, but there was no loss of ankle or subtalar
motion. At that time, she underwent resection of the hypertrophied fatty
tissue and skin of the central portion of the foot. Following this procedure,
there was progressive enlargement of the leg and foot, and the enlargement
gradually involved the thigh. A liposuction procedure was performed, with
removal of a large amount of fatty tissue. Within a few weeks of the
procedure, the leg appeared to be as large as it was prior to the
intervention. The patient also tried a regimen with a Jobst pump (Beiersdorf
AG, Hamburg, Germany) and compressive stockings, but no change was noted in
the limb. At ten years of age, the patient was unable to find shoes to fit her
left foot (Fig. 1-B) and she
was noted to have a mild inequality in limb length, mainly due to the
excessive fatty tissue in the sole of the foot. At this time, the remaining
left toes were excised in order to facilitate footwear. The pathology report
at that time noted only an excess of normal tissue, especially the fatty
component. When the patient was twelve years old, clinical examination
revealed a limb-length discrepancy of 3 cm. Radiographs revealed a bone age of
between eleven and twelve years. Scanograms revealed that the left tibia was
1.1-cm longer than the right tibia. A left distal femoral epiphysiodesis was
performed.
At thirteen years of age, the patient was very unhappy with the cosmetic
appearance of the limb. She was functionally able to perform all activities,
including running, roller-skating, and cheerleading, but she continued to have
difficulty with footwear. She did not have any pain. A magnetic resonance
imaging scan was performed to delineate the extent of the soft-tissue
hypertrophy, and the adipose tissue was noted to infiltrate the gastrocnemius
muscle as well as the posterior compartment of the thigh
(Fig. 1-C). There was no
enlargement of the sciatic nerve. A two-stage operation was performed to treat
the soft-tissue lesion. A Syme amputation was performed first and included
debulking of the left calf. The entire fatty lesion was excised in continuity,
with removal of a 30-lb (13.6-kg) mass of fatty tissue. A few weeks later,
during the second stage of the operation, another 30-lb (13.6-kg) mass of
fatty tissue was removed from the left buttock and thigh. To facilitate
prosthetic fitting, the tibia was shortened by 4 cm through a proximal
osteotomy. Histological examination again failed to reveal any abnormal
tissue. There was fatty infiltration throughout the muscle planes.
Following the procedures, the patient was able to walk in the prosthesis
without difficulty. Over the subsequent five years of follow-up, there was
moderate further enlargement of the thigh and buttock, but no change in the
lower leg (Fig. 1-D). The
sparing of the calf may have been due to the compressive effect of the
prosthesis. The patient was last seen during her mid-twenties, at which time
she was training to become a prosthetist.
Case 2. A six-year-old boy presented with macrodactyly of the
index and long fingers of the left hand. The condition had been present at
birth and appeared to be static. A previous syndactyly release as well as
debulking had been performed in the home country of the patient, with
disproportionate growth recurring in the two digits after that operation. The
mother's pregnancy had been full term and unremarkable. There was no family
history of limb malformations or neurofibromatosis. The patient was otherwise
healthy. Physical examination revealed enlargement at the radial aspect of the
hand, including the thumb. There was full motion of all the joints except
those in the index and middle fingers. Radiographs revealed hypertrophic
phalanges and metacarpals of the index and long fingers as well as the thumb,
to a lesser degree (Fig. 2-A).
The patient underwent ray resection of the index and middle digits with
shortening of the radial digital nerve to the ring finger and reconstruction
of the ulnar digital nerve to the thumb with use of the dorsal radial sensory
branch. Intraoperatively, the median nerve as well as the surrounding
fibrofatty tissue was noted to be massively hypertrophied, as were the thenar
motor branch and the sensory branch to the thumb. Fibrofatty tissue was noted
to have infiltrated the first dorsal interosseous muscle as well as the
adductor pollicis muscle. The patient did well postoperatively with normal
sensation as well as good use of the remaining digits.
At almost nine years of age (three years after the ray resection), the
patient returned for follow-up. The parents had noted a progressive increase
in the girth of the left forearm and arm. The lesion was quite soft and fatty
in consistency, and the circumference of the left arm was 10 cm greater than
that of the unaffected arm (Fig.
2-B). Radiographs revealed soft-tissue enlargement without
concomitant osseous involvement. The patient reported that he still had normal
sensation in the hand and that he did not wish to undergo additional surgery.
At the time of writing, he was being followed in his home country by another
physician.
True macrodactyly can be classified into two types: static and
progressive1. With
static macrodactyly, the affected enlarged digits grow proportionally to the
rest of the limb. With progressive macrodactyly, which includes
macrodystrophia lipomatosa, the affected enlarged digits grow
disproportionally faster than the rest of the limb. The term macrodystrophia
lipomatosa was initially created by Feriz in 1925 to describe cases of
lower-extremity osseous overgrowth that was associated with massive overgrowth
of the associated adipose
tissue7. Golding and
then Ranawat et al. expanded the term to include the same findings in the
upper
extremity8,9.
The terms macrodactyly, gigantism, megalodactyly, acromegaly, clubbed finger,
and elephantiasis have all been used to describe this condition or variations
of it. Currently, the term macrodystrophia lipomatosa refers to a form of
progressive macrodactyly with osseous involvement associated with diffuse
overgrowth of adipose
tissue4,6,10.
The condition has been described in all reported cases as a unilateral,
progressive, disproportionate overgrowth that often necessitates multiple
operations for aesthetic as well as functional reasons. The deformity is
present at birth, characterized by enlarged digits. The soft-tissue
enlargement is caused by an increase in adipose and connective tissue and
predominates on the plantar or palmar aspect of the extremity.
Radiographs reveal soft-tissue and osseous overgrowth, often with
elongated, broadened, and splayed
phalanges11.
Magnetic resonance images show fatty soft-tissue masses, often distributed in
the territory of either the median nerve or the medial plantar nerve, that are
hyperintense on T1-weighted images and have lower signal intensity on
T2-weighted images. Sagittal short tau inversion recovery (STIR) images
confirm the fatty lesions by signal
suppression12.
Magnetic resonance imaging may also reveal fatty tissue surrounding neural
fascicle within the nerve
sheath2.
While macrodystrophia lipomatosa is not a hereditary disorder, its etiology
is unknown. Vascular abnormalities have been reported in a number of
enlargement
conditions13. A
disturbed lymphatic system, a defici6ent muscular layer in the arteries, or
abnormal fetal
circulation10 have
been implicated as etiologies for macrodystrophia lipomatosa. However, the
histological analyses that have been reported in the literature have not
provided evidence to support these
theories6.
Histological examination of the tissue in one of our patients did not
demonstrate any enlarged blood or lymphatic vessels or angiomas.
Neurological abnormalities have also been reported to cause tissue
overgrowth14. There
is a relationship between the nervous system and growth, as evidenced by the
smaller affected limbs of patients with hemiplegia as a result of cerebral
palsy15. An
abnormal nervous system, whether peripheral or central, may result in
disturbed growth10,
and fibrolipomatous hamartomata of nerves are associated with macrodystrophia
lipomatosa3.
However, cases of fibrolipomatous hamartoma have been reported to occur
without associated macrodystrophia lipomatosa. In the patient in Case 1,
although the involvement of the left limb seemed to be in the distribution of
the sciatic nerve as it divided into the posterior tibial nerve and the medial
plantar nerve, the actual nerve was not found to be intimately involved in the
lesion. In the patient in Case 2, there was marked involvement of the median
nerve and the branches of that nerve were intimately associated with the
lipomatous tissue.
Fibrolipomatous hamartoma of nerve is a rare tumor-like lipomatous process
that usually involves a peripheral nerve and its
branches16.
Histological analysis reveals abnormal fatty tissue interspersed with nerve
bundles and also shows endoneural and perineural
fibrosis2,3.
The enlarged nerve may cause pain, numbness, and diminished sensation and
strength, and carpal tunnel syndrome may occur if the median nerve is enlarged
beneath the flexor
retinaculum16.
Silverman and Enzinger reviewed the cases of twenty-six patients with
fibrolipomatous hamartoma of nerve, all of which occurred in the upper
extremity except for one, and found that only seven patients demonstrated
macrodactyly3.
However, Tsuge and Ikuta studied thirty-two patients with macrodactyly of the
fingers or toes and, in all patients, found underlying nerve abnormalities
that were shown to be histologically identical to fibrolipomatous hamartoma of
nerve17. Yet,
although there appears to be a relationship between fibrolipomatous hamartoma
of nerve and macrodystrophia lipomatosa and even though it may be impossible
to distinguish between the two entities once nerve involvement is present,
fibrolipomatous hamartoma of nerve has been shown to occur without the
presence of
macrodactyly2,3.
Silverman and Enzinger have suggested that, rather than macrodystrophia
lipomatosa, the term to properly describe these lesions should be
fibrolipomatous hamartoma of nerve with or without
macrodactyly3.
At our institution, investigators who have performed research on tissue
samples from patients with macrodactyly have uncovered a specific abnormality
in the
perineurium18.
Normal perineurium surrounds the nerve fascicles and forms a diffusion barrier
that separates the axons and Schwann cells in the fascicle from the externally
located adipocytes. This perineural myofibrotic layer demonstrated abnormal
thickening in macrodactyly tissue compared with control tissue obtained from
patients with polydactyly. Although further investigation is needed to
characterize the specific abnormalities of this neural tissue, this recent
finding may indicate a possible relationship between nerve tissue and
macrodactylous tissue.
Various theories regarding deranged embryonal development have been
proposed, including disturbed mesenchymal
proliferation6,
errors in segmentation, and in utero disturbance of a growth-limiting
factor19. Viola et
al. reported a case in which the macrodystrophia lipomatosa affected only the
areas in a limb that had developed from the preaxial hind-limb
bud6. They theorized
that the alteration occurs in the apical zone of mesenchymal proliferation,
which accounts for the variable clinical presentation of macrodystrophia
lipomatosa. While the patient in Case 2 seemed to have involvement of the
preaxial limb, the distribution of the lesion followed the median nerve and
did not involve the dorsum of the limb. The patient in Case 1 did not exhibit
preaxial and/or postaxial distribution of the macrodystrophia lipomatosa, and
the posterior distribution of the lesion is difficult to explain through the
embryonal theory.
Postzygotic germline mutations have been found to be associated with the
overgrowth syndromes of Beckwith-Wiedemann syndrome and Proteus
syndrome20-23.
There are multiple phenotypically overlapping overgrowth syndromes, and it may
be that multiple causative molecular genetic and epigenetic mechanisms are the
cause of the heterogeneous clinical characteristics of each syndrome.
Treatment of progressive macrodystrophia lipomatosa often requires surgical
intervention, particularly to facilitate footwear and decrease deformity. The
authors of several case reports have noted successful results with repeated
debulking and partial
amputation4,5,24,25,
but midfoot or even more proximal amputations, such as the Syme amputation
that was necessary for our patient in Case 1, are often
required19.
However, amputation may not preclude recurrence of the lesion proximal to the
site of amputation. Although the macrodystrophia lipomatosa appears to regress
to a static lesion on completion of the child's
growth24, there
have been reported cases of the lesions continuing to slowly enlarge in
adulthood19.
Therefore, patients and their families should be counseled that recurrence of
the lesions may necessitate multiple operations.
The cases of our two patients are noteworthy for two reasons: (1) The
macrodactyly initially appeared to be static in nature, staying proportional
to the rest of the limb, until the hand and foot were debulked with ray
resections. After this intervention, the nature of the lesions became
progressive and advanced proximally in the limb at an alarming rate. With
regard to the patient in Case 1, we were unable to control or arrest the
progression of the disease with further surgical intervention; in fact, each
operation seemed to cause the macrodystrophia lipomatosa to increase robustly
and behave even more aggressively. (2) The distribution of the progressive
macrodystrophia lipomatosa in the patient in Case 1 was limited to the
posterior aspect of the leg and thigh, ascending as proximal as the buttock,
and this particular distribution, to our knowledge, has not been reported
previously. ?