Infantile myofibromatosis

Infantile myofibromatosis is a benign myofibroblastic neoplasm classified among pericytic/perivascular tumors by the WHO.[1][2] It is the most common fibrous tumor of infancy, with an estimated incidence of 1 in 150,000–400,000 live births.[1][3] The tumor arises from myofibroblasts and may present as a solitary nodule, multicentric soft-tissue and osseous lesions, or, rarely, generalized disease with visceral involvement.[4][5] In the jaws, it characteristically appears as a well-defined radiolucent lesion, most often in the mandible, and is managed by conservative surgical excision with an excellent prognosis in the absence of visceral disease.[6][7]

The WHO classification of soft tissue tumors places myofibroma and myofibromatosis within the family of benign pericytic (perivascular) tumors, reflecting a morphologic continuum with myopericytoma.[1][2] Current accepted terminology:

• Myofibroma — solitary lesion (preferred term for a single tumor regardless of patient age)
• Infantile myofibromatosis — multicentric disease presenting in infancy or early childhood
• Myofibromatosis — multicentric disease at any age

Obsolete or superseded terms include congenital generalized fibromatosis, congenital fibromatosis, multiple vascular leiomyomas of the newborn, and infantile hemangiopericytoma.[5][8] The designation "infantile hemangiopericytoma" is now subsumed within the myofibroma spectrum.[9]

• Age: Most lesions present before age 2 years; up to 74% are present at birth, and 89% are diagnosed within the first 2 years of life. Solitary jaw myofibromas have a somewhat later median age of presentation (approximately 6–7 years in jaw-specific series).[4][6][7]
• Sex: The solitary form shows a male predominance; the multicentric form is more common in females.[5]
• Jaw involvement: The mandible is the most frequently affected jaw, followed by the maxilla; rare cases involve both jaws simultaneously. Within the oral cavity, the mandible is the single most common site of myofibroma occurrence.[7][10]
• Disease distribution: Solitary lesions account for approximately 50–74% of all cases; multicentric forms without visceral involvement represent most of the remainder; generalized disease with visceral involvement occurs in a minority of cases.[4][11]

Jaw myofibromas present in two distinct clinical patterns:[6]

Exophytic (dentoalveolar) type

• Rapidly growing, firm, painless or mildly tender mass in the alveolar or gingival region
• Tooth displacement, mobility, and premature tooth loss are common
• Bony expansion with cortical thinning or perforation may be clinically palpable
• Overlying mucosa is typically intact but may appear purple or erythematous[6][12]

Intraosseous type

• Often asymptomatic and discovered incidentally on dental radiographs
• Slow growth; painless swelling of the jaw may develop over time[6][13]
• Occasionally associated with impacted or displaced developing teeth[14]

General features

• Firm, well-demarcated mass; gray-white on cut section[13][14]
• Multicentric disease should be suspected when jaw lesions are accompanied by cutaneous, subcutaneous, or osseous nodules elsewhere[11][15]
• Visceral involvement (lung, heart, gastrointestinal tract) is a red flag for life-threatening complications and carries significant morbidity and mortality[4][12]

Location and distribution

Intraosseous jaw myofibromas occur most commonly in the posterior mandible, including the body and ramus.[6][7] The maxilla is the second most frequent site, with the anterior region occasionally affected.[7] Lesions are typically solitary within the jaw; bilateral jaw involvement is rare.[7] In multicentric disease, additional lytic lesions may be identified in the skull, ribs, spine, or long bones.[16]

Periphery and shape

The characteristic appearance is a well-defined, unilocular radiolucency with a corticated (sclerotic) border.[17][18] The lesion is typically round to ovoid. A sclerotic rim is a common finding in osseous myofibromas and may be visible on both panoramic radiographs and cross-sectional imaging.[17][19] Occasionally, the margins may appear less well defined, particularly in exophytic lesions with cortical perforation.[6]

Internal architecture

The internal structure is purely radiolucent without intrinsic mineralization, consistent with the fibrous nature of the tumor.[17][20] Calcification within the lesion is not a typical feature on dental radiographs. The lesion is solid on cross-sectional imaging despite its cyst-like radiographic appearance.[13][21]

Effects on teeth and adjacent structures

• Tooth displacement: Developing tooth buds and erupted teeth may be displaced away from the lesion, a common finding in the exophytic type[6][14]
• Tooth impaction: Association with impacted teeth has been reported, mimicking a dentigerous cyst or ameloblastoma[14]
• Root resorption: External root resorption of adjacent teeth may occur but is not a consistent feature[6][18]
• Tooth mobility and premature loss: Particularly associated with the exophytic dentoalveolar presentation[6]

Cortical involvement and expansion

• Bony expansion is characteristic, particularly in the exophytic type[6][13]
• Cortical thinning is common; cortical perforation with extension into adjacent soft tissues occurs in more aggressive-appearing exophytic lesions[6]
• Cross-sectional imaging is superior to panoramic radiography for evaluating the extent of cortical thinning, perforation, and buccal-lingual expansion[22][23]
• Despite cortical disruption, the lesion maintains a well-demarcated interface with surrounding bone intraoperatively[13][14]

Growth pattern

Intraosseous lesions tend to grow slowly and may remain stable for extended periods.[6] Exophytic dentoalveolar lesions may demonstrate more rapid growth with progressive bony destruction.[6][24] Periosteal reaction is not a typical feature.

Recognized variants and mimicry

The radiographic appearance is nonspecific and frequently mimics odontogenic lesions, including dentigerous cysts, ameloblastoma, odontogenic keratocyst, and central odontogenic fibroma.[13][14][21] In the multicentric form, multiple well-defined lytic lesions throughout the skeleton may simulate Langerhans cell histiocytosis or metastatic disease.[15][16]

MRI

On MRI, jaw myofibromas demonstrate low signal intensity on T1-weighted images and variable signal on T2-weighted images, with the center showing either low or high signal intensity.[25][26] Marked peripheral enhancement after gadolinium administration is characteristic and reflects the biphasic histologic architecture, with the enhancing periphery corresponding to the myofibroblastic component and the non-enhancing center corresponding to the hemangiopericytoma-like vascular zone.[19][25] This enhancement pattern, when present, can help distinguish myofibroma from cystic odontogenic lesions.

CT (medical)

On contrast-enhanced CT, the mass shows attenuation similar to or lower than adjacent muscle, with peripheral enhancement and occasional calcifications.[25][26] Erosion of adjacent bone is well demonstrated.[25] CT is useful for delineating the extent of cortical destruction and soft-tissue extension in larger lesions.

FDG-PET

Myofibromas may show strong FDG uptake, which can raise concern for malignancy.[27] This finding is important to recognize to avoid misinterpretation as a sarcoma or metastatic disease.

The radiographic differential diagnosis of a well-defined radiolucent jaw lesion in a child is broad. Patient age, location, and the relationship to developing teeth are the most useful narrowing features.

The highest-risk diagnostic pitfall is misidentification of myofibroma as a malignant spindle cell neoplasm (infantile fibrosarcoma or rhabdomyosarcoma), which may lead to unnecessarily aggressive treatment. Biopsy with immunohistochemistry is essential for definitive diagnosis before surgical planning.[13][32]

Microscopic features

The hallmark is a biphasic growth pattern:[5][10]

• Peripheral zone: Interlacing fascicles of plump, spindle-shaped myofibroblasts with pale eosinophilic cytoplasm arranged in short bundles, separated by collagen
• Central zone: Smaller, rounded cells with hyperchromatic nuclei arranged around thin-walled branching vessels in a hemangiopericytoma-like (staghorn) pattern
• Necrosis and calcification may be present centrally[5][8]
• Intravascular growth is occasionally seen but does not affect clinical behavior[5]

Immunohistochemistry

• Positive: Smooth muscle actin (SMA), vimentin; muscle-specific actin[9][10]
• Negative: S100, CD34, desmin (usually)[9][14]
• A low Ki-67 proliferative index supports the benign nature[14]
• β-catenin positivity has been observed more frequently in recurrent cases in some series[33]

Morphologic spectrum and pitfalls

Highly cellular, primitive variants with scant myoid differentiation may closely resemble congenital infantile fibrosarcoma.[9][32] Molecular testing for the ETV6-NTRK3 fusion transcript (present in infantile fibrosarcoma, absent in myofibroma) is an important diagnostic adjunct in ambiguous cases.[32] Regressive lesions with myxoid change and inflammation may mimic nodular fasciitis.[9]

Radiologic-pathologic correlation

The well-defined radiolucent appearance with a sclerotic rim corresponds to the circumscribed, nodular growth pattern. The solid nature of the lesion on cross-sectional imaging correlates with the densely cellular myofibroblastic proliferation, distinguishing it from true cystic lesions despite a cyst-like appearance on panoramic radiographs.[13][21]

Workup

• Incisional biopsy before definitive surgery is recommended to exclude malignant spindle cell neoplasms[13][33]
• In pediatric patients, evaluation for multicentric disease should include clinical examination for cutaneous and subcutaneous nodules; skeletal survey or whole-body imaging may be warranted when multiple lesions are suspected[34][35]
• Visceral screening (chest radiograph, abdominal ultrasound) should be considered in infants with multicentric disease[4][34]

Surgical treatment

• Intraosseous jaw lesions: Enucleation and curettage is the standard approach, with excellent outcomes and low recurrence[6][7]
• Exophytic dentoalveolar lesions: Resection with free margins is preferred given the more aggressive local behavior[6][7]
• Complete excision is the treatment of choice once the diagnosis is confirmed[7][14]

Recurrence

• Recurrence after complete excision of jaw myofibromas is uncommon[6][7]
• Incompletely resected lesions have a higher risk of local recurrence[36]
• Positive surgical margins in solitary myofibromas do not uniformly lead to recurrence; some residual tumors remain stable or regress spontaneously[26][37]

Prognosis

• Solitary and multicentric forms without visceral involvement carry an excellent prognosis[4][12]
• Spontaneous regression has been documented in both solitary and multicentric forms, likely mediated by apoptosis[5][26]
• Generalized disease with visceral involvement (lung, heart, gastrointestinal tract) is associated with significant morbidity and mortality[4][35]
• Chemotherapy (vinblastine/methotrexate or vincristine/dactinomycin/cyclophosphamide) is reserved for life-threatening, progressive, or unresectable visceral disease[4][26]

Surveillance

• Clinical and radiographic follow-up is recommended, as late recurrence and progression from solitary to multicentric disease have been reported in rare cases[3][35]

Molecular genetics and familial disease

• Somatic gain-of-function mutations in PDGFRB are identified in the majority of multicentric cases and a minority of solitary tumors[2][38]
• Germline PDGFRB variants underlie familial infantile myofibromatosis, which follows autosomal dominant inheritance with variable expressivity[8][38]
• NOTCH3 variants and novel gene fusions (e.g., SAMD5–SASH1) have also been reported[1][34]
• Mutant PDGFRB receptors are sensitive to tyrosine kinase inhibitors (imatinib, dasatinib, ponatinib) in preclinical models, offering a potential targeted therapy for severe or refractory disease[2][38]

Pediatric considerations

• Given the predilection for infants and young children, treatment planning must account for developing dentition and jaw growth
• Solitary cutaneous myofibroma in an infant may precede the development of multicentric disease; surveillance imaging has been recommended even for apparently solitary presentations[34][35]
• Genetic counseling and PDGFRB testing should be considered in familial cases or when multicentric disease is identified[2][4]