Infantile myofibromatosis

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Infantile Myofibromatosis

Infantile myofibromatosis, previously known as congenital generalized fibromatosis, is the most prevalent fibrous tumor of infancy. It is characterized by the formation of tumors, either in a solitary or in a multicentric fashion, in the skin, muscle, viscera, bone, and subcutaneous tissue.

GENETICS/BASIC DEFECTS

1. Etiology: unknown but appears to originate in utero. Fetal estrogenic hormone stimulation or hamartomas of myofibroblasts have been considered

a. Sporadic in most cases

b. Several reports of familial cases i. Autosomal dominant ii. Autosomal recessive 2. Types

a. Solitary myofibroma

i. More common in males (69%)

ii. Affects chiefly the soft tissues of the head-neck region and the trunk

b. Multicentric myofibromatosis (more common in females, 63%)

i. Without visceral involvement (bones)

ii. With visceral involvement (bones and viscera) 3. Spontaneous regression of tumors: possibly due to apop-

totic cell death

CLINICAL FEATURES

1. Affects almost exclusively infants and young children a. 60% noted at birth or shortly thereafter

b. 80% occurred before the age of two years 2. Characteristics of tumors

a. Superficial

i. Palpable, rubbery, firm, and freely moveable nodules

ii. Fibrotic, plaquelike, indurated, and crusted lesions

b. Deeper lesions: generally immovable c. Nontender and painless

3. Overlying skin

a. Erythema or a purple discoloration resembling a hemangioma

b. Ulceration and atrophic scar 4. Affected bones

a. Radiolucent lytic lesions (cystic defects) b. Most commonly involved locations

i. Cranium ii. Femurs iii. Tibias

iv. Spine v. Ribs

c. Circumscribed lytic tumors not present at birth but develop quickly over the first few days or weeks of life

5. Solitary form (myofibroma) a. About 80% of the cases b. Boys more commonly affected

c. Mostly involves the skin and bones, and rarely the CNS and viscera

d. A good outcome provided there is no visceral involvement

e. Natural history of myofibromas of the CNS without visceral involvement: frequently characterized by a period of initial rapid growth, subsequent stabiliza- tion, and spontaneous regression in many cases 6. Multicentric form (myofibromatosis)

a. Without visceral involvement i. Girls more commonly affected

ii. Typically undergoing spontaneous regression within the first 1 or 2 years of life when limited to the skin or bone

iii. A good outcome b. With visceral involvement

i. One fourth of cases of multicentric cases ii. Multiple nodules distributed throughout the body

a) Soft tissues b) Bone

c) Skeletal muscle

d) Viscera (kidney, pancreas, retroperitoneum, lungs, gastrointestinal tract, peritoneum, diaphragm, heart, tongue, lymph nodes, peripheral nerves, liver)

iii. Fatal outcome with visceral involvement usually within 4 months of life

a) Localized mass effect on the lung, gastrointestinal tract, or within the conduction system of the heart

b) Mortality rate approaches 75%

iv. Possible survival: spontaneous resolution of visceral lesions within the first year of life

v. Disseminated pathologic process including proliferation of multiple nodules of collagen- forming fusiform cells

vi. Likely origin of proliferating cells: myofibrob- last (displaying both smooth muscle and fibrob- last features)

7. Differential diagnosis a. Neurofibromatosis b. Leiomyomas

c. Hyaline fibromatoses d. Hemangiomas e. Soft tissue sarcomas

f. Metastatic neuroblastomas

8. Prognosis depending on the extent of involvement and location of the lesions

a. Solitary forms usually cause little morbidity and virtually no mortality. However, a solitary nodule 545

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546 INFANTILE MYOFIBROMATOSIS

involving the central nervous system (CNS) may be fatal

b. Lesions confined to soft tissue and bone: usually self- limited with good prognosis

c. Good prognosis with frequent spontaneous regression when viscera are not involved

d. Poor prognosis with infantile myofibromatosis with multiple visceral involvement

i. Progression to death: usual outcome

ii. Death resulting from complications due to car- diopulmonary or gastrointestinal involvement

DIAGNOSTIC INVESTIGATIONS

1. Radiography, U/S, CT, and MRI

a. Soft tissue lesions: round and well defined on U/S and MRI

b. Invaluable in assessing the extent and progression or regression of the disease

i. Soft tissue lesions (multiple subcutaneous and intramuscular tumors)

ii. Bone lesions iii. Visceral lesions

c. Radiography: lesions appearing as multiple areas of osteolysis with a sclerotic margin

d. Ultrasonography: hyperechoic nodules with peripheral hyperperfusion on color Doppler

e. CT scan of the brain

i. Partially calcific masses or isodense cystic lesions with intense peripheral contrast enhance- ment and smoothly marginated bone erosion ii. Typical absence of sclerosis of the margins f. MRI: intramuscular, subcutaneous and visceral (liver,

lungs) lesions

i. Iso- or hypointense on T1-W images ii. Iso- or hypointense on T2-W images 2. Histology (biopsy of tumors)

a. Gross appearance of tumors: well demarcated b. Lesion consisting of bundles of elongated cells with

features of both fibroblasts and smooth-muscle cells c. Staining characteristics: intermediate between fibrob-

lasts and smooth muscle

d. Central part of the tumors often necrotic 3. Electron microscopy

a. Characteristic intracytoplasmic myofilaments b. Dense bodies

c. Focal basal lamina and macula adherens

GENETIC COUNSELING

1. Recurrence risk a. Patient’s sib

i. Sporadic form: not increased ii. Autosomal recessive form: 25% risk

iii. Autosomal dominant form: not increased unless a parent is affected

b. Patient’s offspring

i. Sporadic form: not increased

ii. Autosomal recessive form: not increased unless the spouse is a carrier

iii. Autosomal dominant form: 50% risk

2. Prenatal diagnosis by ultrasonography for detecting solitary or multicentric tumors in soft tissue, bones, or viscera 3. Management

a. Observation

i. Spontaneous regression

ii. Possible sequelae (tissue loss or damage) resulting from spontaneous regression

b. Surgical excision

i. To prevent complications and improve prognosis ii. Reserved for symptomatic lesions or if vital organs are compromised, in view of the tendency to spontaneous regression

iii. Radical resection reserved for those lesions pos- ing an immediate threat due to their locations or massive size and those showing obvious progression

iv. 7–10% of lesions recurred after excision c. Chemotherapy with or without radiotherapy

i. Necessary for recurrent or unresectable lesions ii. A combination of vincristine, adriamycin-D and

cyclophosphamide iii. Interferon

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Fig. 1. An infant with multicentric myofibromatosis showing subcu- taneous nodules in the back, arm (pointed by a finger), cystic lytic lesions in the humeri and femori (radiographs), and multicentric nodules (identified by dark lines) in the chest wall by MRI.