History
4-week-old girl with a nodule in the left axilla. It is excised
because lymphoma is
suspected; the clinical differential diagnosis includes teratoma,
tuberculosis or
«BCG-itis».
Pathology
Gross examination reveals a multinodular lesion with a smooth
surface. On cut
section it consists of solid firm whitish tissue with necrotic
areas. Microscopically, in the section circulated, there is prominent
central necrosis with focal calcification and cell shadows arranged
in a hemangiopericytoma-like fashion. The periphery consists
of a vital zone of more mature-appearing myofibroblastic cells
in rim bundles and whirls, focally adjacent to skeletal muscle,
with some degree of skeletal muscle infiltration. There are some
cellular foci of more immature, small round cells surrounding
vascular lumina in a hemangiopericytoma-like pattern.
Discussion
Myofibromatosis was initially described in 1951 by
Williams and Schrum as ‘congenital fibrosarcoma’,
and reclassified as ‘congenital generalized fibromatosis’
by Stout in 1954. A variety of terms were applied to the disorder
in the years to follow, including ‘benign mesenchymoma’,
generalized hamartomatosis’ and multiple mesenchymal hamartomas’.
In 1965, Kauffmann and Stout separated a form with multiple lesions
and a good prognosis from a generalized form with visceral lesions
and a poor prognosis. In 1981, Chung and Enzinger introduced
the term ‘infantile myofibromatosis’, after recognition
of the myofibroblastic nature of the lesion. Since some reports
describe myofibromatosis in adults, the term ‘infantile’
has been dropped.
Myofibromatosis is one of the most
common fibrous soft tissue proliferations in infancy.
54% are present at birth and thus congenital, 89%
are diagnosed during the first 2 years of life. It
most frequently occurs in the solitary form (70-80%),
less frequently in the multiple, and rarely in the
generalized form.
In solitary myofibromatosis, skin, subcutaneous tissue and skeletal
muscle are affected most frequently, usually in the head, neck
and trunk. Solitary lesions involving the viscera are rare. Solitary
myofibromatosis has been reported in the skeleton. The most frequently
affected bones are the skull, vertebrae, ribs, femur and tibia.
Multicentric lesions composed 26% of the AFIP cases. These lesions
occur in the neonatal period and involve the underlying soft
tissues, bone and / or viscera, as well as the skin. They may
be divided into the multiple and generalized forms, the latter
having visceral involvement. In the generalized form, the most
common locations are the lung, heart, gastrointestinal tract
and pancreas, as well as rarely the central nervous system. Solitary
and rarely multiple myofibromatosis have both been described
in adults as well, sometimes with a less well developed zonal
pattern.
The presence of familial occurrence in some instances suggests
the possibility of autosomal recessive or autosomal dominant
inheritance.
Macroscopically, these lesions present
as firm, scar-like, nodular and lobulated tumours.
More superficial lesions, like the present one, tend
to be more circumscribed, while deeper tumours are
more often diffuse or infiltrative.
The microscopic appearance is characteristically biphasic, with
a central cellular
hemangiopericytoma-like zone, surrounded by a nodular and fascicular
peripheral zone with fewer fibroblastic and myofibroblastic cells.
The cells in the center appear less well differentiated and have
scant cytoplasm, indistinct cell borders, and distinctly basophilic
oval nuclei. The peripheral myofibroblasts are rich in eosinophilic
or clear cytoplasm, with more distinct cell margins and uniform,
mostly vesicular nuclei.
Hemangiopericytomatous and myofibroblastic components occur in
variable proportions. Sometimes, hemangiopericytomatous areas
with the more primitive-appearing cells are scarce or absent.
Mild to moderate nuclear pleomorphism can be found in most lesions.
Normal mitotic figures may be quite common. Abnormal mitotic
figures should not be present. Peripheral intravascular growth
is common, but does not affect the prognosis. Necrosis can be
present and extensive as in the present case. Similarly, calcification
is not an uncommon feature. There may be central cystic degeneration.
Immunohistochemically, the cells display the features of myofibroblasts
with expression of Alpha Smooth Muscle Actin and inconstant expression
of Desmin. S-100 and Cytokeratin are negative. It has been suggested,
that myofibromatosis is derived from pluripotent periendothelial
cells.
Cytogenetic investigation in a single case of solitary myofibromatosis
showed a deletion del(6)(q12q15) as the sole cytogenetic abnormality.
Connective tissue growth factor expression has been shown to
be increased in pediatric myofibroblastic tumours.
The differential diagnosis essentially depends upon the predominant
component:
myofibroblasts or the more primitive small cells. It includes
nodular fasciitis, neurofibroma, fibrous histiocytoma, infantile
fibromatosis, leiomyoma, infantile hemangiopericytoma, hyaline
fibromatosis, fibroma of tendon sheath.
Nodular fasciitis is a rare lesion in newborns and infants, but
should be considered in the differential diagnosis in adults.
It has a more prominent myxoid matrix and occasional inflammatory
cells, but no hemangiopericytoma-like pattern.
Neurofibroma shows S100 expression. Neurofibromatosis presents
in older children with evidence of café-au-lait spots
and a family history in half of the patients.
Fibrous histiocytoma has a more pronounced storiform pattern
and expression of Factor XIIIa.
Infantile fibromatosis tends to
be less well circumscribed, arises in muscle and
consists of a more uniform spindle cell proliferation.
There is no central necrosis or hemangiopericytomalike
vascular pattern.
Juvenile hyalin fibromatosis bears a superficial resemblance
to myofibromatosis, but differs in its cutaneous distribution
and histologic picture. Most patients with juvenile hyalin fibromatosis
suffer from gingival hypertrophy and painful joint contractures,
which may precede the development of skin lesions. In contrast,
gums or joints have never been found involved in myofibromatosis.
Histology of juvenile hyalin fibromatosis is characterized by
a paucity of cells, a fibrillary matrix and complete absence
of mature collagen. Pathogenetically, aberrant glycosaminoglycan
synthesis results in a predominance of dermatan sulfate, in contrast
to a predominance of hyaluronan in normal skin. Spontaneous regression
of the lesions has been reported only rarely. Usually more than
one sibling in the same family is affected. Inheritance is autosomal
recessive.
Infantile hemangiopericytoma similarly shows a pattern of primitive
cells surrounding
vascular spaces, and may in some examples also contain an admixture
of myofibroblastic cells. Also, infantile hemangiopericytoma
and myofibromatosis share a number of clinical similarities.
Therefore, Fletcher and Mentzel and other authors have concluded,
that the two lesions are closely related and represent different
stages in maturation of the same entity.
Biopsies from the central cellular portion may have features
resembling small round cell sarcomas with a hemangiopericytoma-like
vasculature: PNET, mesenchymal
chondrosarcoma, poorly differentiated synovial sarcoma. Immunohistochemical
panels
including cytokeratins, CD99 and S100 can assist in this differential
diagnosis.
Treatment and Prognosis
The clinical outcome for young patients depends on whether the
process is solitary or multicentric, and upon the site affected.
Clinicians should be made aware of the possibility of multicentricity
and of the presence of deeper nodules. Solitary or multicentric
lesions confined to skin, soft tissues or bone carry an excellent
prognosis and rarely require more than a simple excision. Spontaneous
resolution of these lesions is common. Local recurrence has
been observed in only 9-11% of patients, in part after incomplete
excision. Clinicians should be reassured of the benign nature
of this entity, even when causing pathological fracture.
On the other hand, infants with generalized visceral lesions
have the worst prognosis. As many as 75% die of their disease,
depending on extent and location of the tumours. The visceral
lesions are responsible for severe respiratory distress, vomiting
and diarrhea, which often fail to respond to therapy and prove
fatal within days or weeks after birth. Yet, if the patients
survive the initial growth phase of the disseminated lesions,
spontaneous resolution has also been reported in some such patients
with generalized myofibromatosis.
Adult lesions are most often solitary, superficial, and usually
cured by simple excision, although rare non-aggressive recurrences
have been described.
