ARTICLE
Auteur(s) : Fabio Arcangeli, Donato Calista
Department of Dermatology, M. Bufalini Hospital, Viale Ghirotti,
286, 47023 Cesena, Italy
accepté le 13 Decembre 2005
Infantile myofibromatosis (IM) is a rare mesenchymal disorder
characterized by the onset of nodules in the skin, striated
muscles, bones and, more rarely, visceral organs [1]. Despite being
an infrequent entity, IM is the most frequent fibrous tumour in
children. The condition is almost twice as common in males as in
females. IM may occur in solitary or multicentric lesions, may be
present at birth or become apparent in early infancy or
occasionally in adult life [1-3]. A familial pattern of inheritance
has rarely been described [4-16]. We present a new family in which
2 siblings were affected by congenital IM.
Case one
A 1-month-old male infant was first seen in 1997 because of the
presence, since birth, and progressive enlargement of 3
subcutaneous masses on the vertex, the left hand-side of the
forehead and the dorsal aspect of the trunk. On clinical
examination, about 30 hard, dermal, subcutaneous and muscular
nodules, 5-30 mm in size, were detected on the patient’s head,
trunk and limbs (( figure 1A )). All but one
lesion on the midback, which had an angiomatous aspect, were
covered with normal skin. A cranial X-ray showed, beneath the
vertex lesion, an oval osteolytic area with marginal sclerosis ((
figure 1B )). A
cranial CT scan excluded penetration of the cortex. Chest X-ray,
abdomen echotomography, and a computed tomography (CT) scan ruled
out any other visceral involvement or abnormalities. Complete blood
and urine tests were within normal values, as were cardiac and
neurological examinations. Because of their continuous growth, the
head lesions were surgically excised under general anaesthesia.
Histopathologic findings were compatible with the diagnosis of IM.
During the following 24 months all the lesions involved
spontaneously. Now five years old, the patient is well, although
two small subcutaneous nodules have recently appeared on his head
and trunk.
Case two
In October 2002 the parents of the aforementioned patient requested
dermatological evaluation of their second child, a 6-month-old
female. On clinical examination there were 15, tender, subcutaneous
and soft tissue lesions, 10-40 mm in size, located on her head
and trunk (( figure
2A )). Cranial CT scans showed 2 round osteolytic areas in
the frontal and left parietal regions (( figure 2B )). Magnetic
resonance imaging revealed isointense lesions on T1, T2 and proton
density-weighted images adjacent to the dura mater in the frontal
and left parietal areas. A whole body CT showed additional nodules
in the VII hepatic segment and in the right erector muscle of the
trunk. There were no other abnormalities nor malformations. A
biopsy of a subcutaneous abdominal mass was taken for
histopathologic examination.
Histology showed similar findings in both cases. Circumscribed
non-encapsulated nodules, separated from one another by fibrous
tissue, infiltrated the reticular dermis. Spindle-shaped cells
arranged in interlacing bundles formed the nodules (( figure 3 )). No mitotic
figures were noted. Immunohistochemical studies showed cytoplasmic
vimentin and muscle-specific actin positive stains, while desmin
and S-100 protein were negative. Six months later all the lesions
had regressed in size.
On clinical examination both the parents were healthy. They
reported that they were non-consanguineous, and that no member of
either of their families had ever had similar lesions. Kariotype
examination of family members failed to reveal any macroscopic
abnormality.
Comment
Infantile myofibromatosis is a rare tumour of infants and young
children. It presents as subcutaneous or soft tissue nodules,
commonly involving the skin of the head, neck and trunk [1-3].
Skeletal and muscular lesions occur in 50% of patients. Internal
organs such as the lungs, liver, gastrointestinal tract and spleen
have occasionally been involved, while the pancreas, heart, and
central nervous system are exceptional [17-19]. Based on the
location and extent of the lesions, IM has been classified as
follows: solitary myofibromatosis, congenital multiple
myofibromatosis with multicentric lesions but without visceral
involvement, and congenital generalized myofibromatosis with both
cutaneous and visceral involvement [3, 18].
The pathogenesis of the disease is still unknown. A link between
IM and estrogenic hormones was postulated in the early 1950s, on
account of the onset of similar lesions in guinea pigs after
prolonged administration of estrogens [20]. This hypothesis has not
been verified in humans as IM develops in subjects with neither
estrogenic stimulation nor hormonal dysfunction, nor augmented
estrogens receptor proteins [4]. Iijima studied the histological
aspect of a single myofibroma in a Japanese patient, through
biopsies taken during the 2 years from its onset, and raised the
possibility of immature histiocytes as the precursors of the
myofibroblastic spindle cells [21]. Large areas of tissue necrosis
induced by apoptosis in the central area of some IM masses may
account for the spontaneous involution of the tumors [20-22].
Hemosiderosis has been found to be associated in 3 cases and
Turner’s syndrome in one, but the ultimate significance of this
relationship has yet to be understood [2, 23].
In most cases, the diagnosis of IM is not difficult, and is made
on histopathological grounds. Well-circumscribed nodules, formed by
a central haemangiopericytoma-like vascular proliferation, are
surrounded by sweeping fascicles of fibroblastic and
myofibroblastic cells [24, 25].
Differential diagnosis includes: the groups of paediatric
sarcomas, neurofibromatosis, desmoid tumours, fibrous hamartoma of
infancy, nodular fasciitis, and hyaline juvenile fibromatosis,
juvenile haemangioma, tufted haemangioma, haemangiopericitoma
[24-28]. The prognosis for IM depends on the degree of visceral
involvement. Since IM tumors have a spontaneous propensity to
regress, the prognosis is excellent in cases with cutaneous
involvement, or in restricted skeletal, muscular or visceral
localizations, when the mass does not compress vital organs. In
these patients therapeutic abstention and observation are
recommended. Surgery, chemotherapy, interferon alfa, or
radiotherapy should be reserved for progressive lesions involving
vital organs associated with a high mortality rate [28, 29].
A review of international literature showed that, although most
of the reported cases are sporadic, almost 15 families, including
ours, have been reported in which more than one family member was
affected by IM. It is likely that familial IM may be more frequent
than is known, because in the majority of the sporadic patients
described family history is not reported and symptoms could pass
unnoticed or even be misdiagnosed, especially in cases with mild
clinical expression. From the available data, no ethnic group seems
to be more involved than others. No candidate gene has been
identified at present. Consanguinity in parents was confirmed in
only 3 families [4, 13]. A horizontal pattern of inheritance, which
suggests an autosomal recessive inheritance, was found in 11 out of
19 families, including ours. A vertical mode of transmission, which
suggests an autosomal dominant inheritance, occurred in 5 families.
In these cases, the possibility of parents with the same autosomal
recessive pattern should not be excluded. An uncertain family
history was found in the remaining 2 families. In order to detect
even the subtlest symptoms of IM, it is crucial to have access to a
patient’s detailed family history, and examine as many relatives as
possible.
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