History
3-day-old boy born with a mass in the left calf. A biopsy of
the mass is performed on day 7.
According to the clinician, the mass measures about 4 cm, is
firm and relatively well demarcated.
Pathology
The biopsy measures 0.5 x 0.2cm and is made of a whitish soft
tissue. On histology, it consists of a fragment
of striated muscle and fibrous tissue. The muscle fibres are
disorganized by a proliferation of small oval or fusiform cells
within a myxoid background that is strongly Alcian Blue positive.
Mitotic figures are scarce. The non involved striated muscle
fibres show variable sizes and atrophic changes, some cells
are isolated or replaced by adipocytes.
On immunohistochemistry, the clusters of small
fusiform cells show a strong positivity for
vimentin and smooth muscle actin. Desmin reaction is positive
only in preserved or regenerating striated muscle fibres.
On electron microscopy study, 3 different types
of cells are seen: 1) many well differentiated
adipocytes filled with fatty vacuoles; 2) small fusiform cells
centred by elongated, partly
convoluted nuclei with small nucleoli and relatively abundant
cytoplasm containing many
organelles, well developed dilated rough endoplasmic reticulum,
mitochondria and microfilaments with dense bodies, compatible
with actin filaments of smooth muscle; 3) other cells of fibroblastic
nature have an elongated cytoplasm, bordered by basal lamina
with numerous pinocytic vesicles in their cytoplasmic border
and intermediate size filaments in their cytoplasm.
Discussion
Infantile fibromatosis is one of the most common fibrous tumours
of infancy, although it was previously considered rare. It
usually presents in the first decade, with 60% at, or shortly
after birth and 90% diagnosed in the first 2 years of life.
Stout was one of the first investigators to document some of
the unique features of these neoplasms in infants and children,
now referred as «fibromatoses» and following his
report, only a small number of cases have been added to the
literature. The myofibroblast plays an important role in these
lesions. Some fibromatoses are sporadic, whereas others are
a manifestation of a familial condition, such as Gardner syndrome.
The biochemical and molecular genetic basis of fibromatoses
are incompletely understood. The typical appearance of the
fibromatoses is that of a firm, circumscribed, uncapsulated
mass with an irregular and coarsely fibrous tan cut surface.
The infantile fibromatosis represents the childhood counterpart
of musculoaponeurotic
fibromatosis. It usually arises as a solitary mass in skeletal
muscle or in the adjacent fascia, aponeurosis or periosteum.
It chiefly affects children from birth to 8 years of age and
is slightly more common in boys than girls. There are considerable
variations in its morphological appearance ranging from primitive
mesenchymal forms to lesions that closely resemble adult desmoid
lesions except perhaps for a less uniform pattern and a greater
degree of cellularity. In most cases, the mass originates in
skeletal muscle, especially in the muscles of the head and neck,
the shoulder, upper arm and the lower extremities. As the lesion
progresses, it may infiltrate adjacent muscles and may grow around
vessels and nerves. This may result in tenderness, pain or functional
disturbances. In some cases, the lesions may involve bone and
render difficult to identify the primary site of involvement.
Grossly, the tumour is firm, ill-defined,
grey to white in colour and measures from 1 to 10
cm. The lesion is never encapsulated and usually
has to be excised together with portions of the involved
muscle and subcutaneous fat.
Microscopically, infantile fibromatosis
has a wide morphological range reflecting progressive
stages in the differentiation of fibroblasts. 1)
The least mature, most common type of lesion is
described as the diffuse or mesenchymal type of infantile fibromatosis.
It is found chiefly in
infants during the first few months of life and is characterized
by small haphazardly arranged round or oval cells within a myxoid
background. The cells are intermediate in appearance between
primitive mesenchymal cells and fibroblasts and are often intimately
associated with residual muscle fibres and lipocytes. The interspersed
lipocytes are probably the result of ex vacuo fatty proliferation
secondary to muscular atrophy of the infiltrated and immobilized
muscle tissue. 2) The diffuse type often blends with another
and more cellular presentation, the fibroblastic type, which
is chiefly composed of plump spindle-shaped fibroblasts arranged
in distinct bundles and fascicles. It may be very cellular and
difficult to distinguish from infantile fibrosarcoma (aggressive
type). 3) The desmoid type is less cellular and more collagenous
and may be virtually indistinguishable from the adult forms of
fibromatosis or desmoid tumour. It usually occurs in children
older than 5 years of age and its behaviour is similar to that
of the adult form of fibromatosis.
On ultrastructure, the proliferation is made of a mixture of
fibroblasts and myofibroblasts with prominent and often dilated
rough endoplasmic reticulum with bundles of peripherally placed
microfilaments in the cytoplasm.
The differential diagnosis is different according
to the type of proliferation. In the diffuse or mesenchymal type,
it may be confused with 1) a myxoid or lipomatous tumour because
of the large amount of lipocytes, which can be quite immature,
especially if the tumour occurs during the first year of life.
The myxoid liposarcoma is rare in children under 5 years of age
and usually is marked by lipoblasts and a plexiform capillary
pattern. 2) Botryoid rhabdomyosarcoma occurs
at the same age, but is uncommon in the musculature, it occurs
in the wall of mucosa-lined cavities like urinary bladder or
vagina. 3) Lipoblastomatosis can be distinguished
by its distinct lobular pattern and the uniform appearance of
the constituent lipoblasts without the mesenchymal primitive
looking cells. 4) It may be confused with early stages of
calcifying aponeurotic fibroma and fibrodysplasia
ossificans progressiva, but the lack of association
with extremities malformations, particularly in fingers and toes
and the absence of plantar or palmar lesions are helpful to exclude
these particular presentations. The most difficult problem in
differential diagnosis is the separation of the more cellular
variant of fibromatosis from infantile fibrosarcoma.
The clue would be the variation in cellularity within a mixed
pattern of collagenous areas, residual muscle tissue and fat.
A tumour with a high cellularity and mitotic activity as well
as a rapid growth with destruction would be considered an infantile
fibrosarcoma. According to Enzinger, transition from fibromatosis
to fibrosarcoma is not well established so far.
The infantile fibromatosis is a lesion that does not metastasize,
but it may reach a large size and should be excised with ample
margins to avoid progressive and infiltrative extension. However,
neither the location nor the morphological picture seems to permit
an accurate prediction of the outcome. The cause of the lesion
is not clear. There is no proof that trauma plays a role, particularly
in congenital presentation. There is no familial incidence observed.
