infantile myofibromatosis

Definition: Infantile myofibromatosisis is defined by the presence of multiple infantile myofibromas. Infantile myofibromatosis is a term coined by Chung and Enzinger.

It exclusively affects infants and young children, with 60% of cases noted at birth or shortly thereafter and more than 80% occurring before the age of 2 years.

Infantile myofibromatosis is one of the most commonly occurring tumors of the neonatal period, presenting in both solitary and multicentric forms.

Most solitary forms occur in the head and neck region; the upper extremity is the next most common site. Solitary lesions are usually cutaneous, involving the dermis and extending to subcutaneous tissue, muscle, and bone.

The visceral type is associated with significant morbidity, sometimes even mortality, and its presence requires clinical evaluation for other potential multicentric tumors.

Spontaneous regression is generally the natural history of those infantile myofibromatosis lesions without visceral involvement.

A histologic zoning phenomenon is present in infantile myofibromatosis lesions. Peripheral spindle-shaped cells arranged in bundles blend centrally into less differentiated round or polygonal cells arranged in sheets.

The spindle cells have the ultrastructural and immunohistochemical characteristics of myofibroblasts, staining positive for vimentin and alpha-smooth-muscle actin but negative for desmin.

The cells are also negative for s-100 protein, differentiating them from more immature histiocytes. Progressive cell differentiation is a possible explanation for the spontaneous regression of the solitary lesions.

Epidemiology

 sporadic cases
 familial cases (8600777, 16581573)

• autosomal dominant inheritance (12894106, 1739928, 6742314)
• autosomal-recessive inheritance (11260217)

Localization

 orbital region (11410140)
 central nervous system (12720031), spinal canal (9703012)
 oral region (10792791), gingiva (12472999)
 bone
 muscle
 viscera (heart, lungs, liver, gastrointestinal tract (2672792), bile ducts and pancreas (3185365), endocrine organs)
 subcutaneous tissue, soft tissues
 digestive tract

• intestinal infantile myofibromatosis

 infantile generalized myofibromatosis

Microscopical synopsis

Biphasic pattern
 zonation effect : smooth-muscle-appearing cells on the periphery of the lesion with central fibromatosis cells
 fascicles of spindle cells with abundant eosinophilic cytoplasm that resembled smooth muscle
 more primitive spindled cells associated with a hemangiopericytoma-like vascular pattern
 interlacing fascicles of myofibroblasts with abundant eosinophilic cytoplasm
 variable necrosis
  calcifications in some sites
 hemangiopericytoma-like features
 angiocentric and perivascular growth of myofibroblasts (+/-) (8597844)

Immunochemistry

 vimentin+
 smooth muscle actin+

Subtypes

 solitary myofibromatosis
 systemic myofibromatosis, multicentric myofibromatosis

• congenital generalized myofibromatosis (CGMF) (8597844)
• aggressive infantile myofibromatosis (3784986)

Two types can be distinguished; the solitary type, defined by the presence of one nodule in the skin, muscle, bone or subcutaneous tissue; and the multicentric type which can be divided into two sub-types.

In the first sub-type the lesions are multicentric but without visceral involvement, while in the second, visceral involvement is present.

 adult-type myofibroma
 infantile generalized myofibromatosis

Associations (sporadic)

 neonatal hemochromatosis (11196755)
 Turner syndrome (9821432)
 arterial fibromuscular dysplasia (15455480)
 verrucous epidermal nevus (15459537)
 neurofibromatosis type 1 (NF1) (15459537)
 multiple congenital anomalies (2303073, 15916589)

• oesophageal atresia (2303073)
• annular pancreas (2303073)
• additional sacral vertebra (2303073)
• hypoplatic right kidney (2303073)

Cytogenetics

 del(6)(q12q15) (10425309)
 monosomy 9q (15365831)
 trisomy 16q (15365831)

Prognosis

The prognosis of the disease depends on whether visceral involvement is present. Solitary and multicentric nodules without visceral involvement usually have excellent prognosis with spontaneous regression of lesions within 1 to 2 years of diagnosis.

Visceral lesions are associated with a significant morbidity and mortality, resulting from vital organ obstruction, failure to thrive, or infection. Death in these cases often occurs at birth, or soon after, and is usually due to cardio-pulmonary or gastrointestinal complications. However, multicentic type of infantile myofibromatosis with visceral involvement can spontaneously regress. (11510506)

Differential diagnosis

 low-grade myofibroblastic neoplasms

• low-grade myofibroblastic sarcoma (9777985)

 fibromatoses

• composite fibromatoses

 congenital fibrosarcoma (infantile fibrosarcoma)
 inflammatory myofibroblastic tumor
 fibrous fibrohistiocytic tumors
 solitary fibrous tumor
 nodular fasciitis
 desmoplastic fibroblastoma (collagenous fibroma)
 smooth muscle tumors

• leiomyoma
• leiomyosarcoma

 neurogenic tumors

• schwannoma and neurofibroma
• low-grade MPNST

 juvenile xanthogranuloma

See also

 hemaniopericytomatous pattern
 fibrosing tumors (sclerosing tumors)
 fibrous tumors
 myofibroblastic tumors
 fibroblastic/myofibroblastic tumors

References

 Granter SR, Badizadegan K, Fletcher CD. Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation. Am J Surg Pathol. 1998 May;22(5):513-25. PMID: 9591720

 Mentzel T, Calonje E, Nascimento AG, Fletcher CD. Infantile hemangiopericytoma versus infantile myofibromatosis. Study of a series suggesting a continuous spectrum of infantile myofibroblastic lesions. Am J Surg Pathol. 1994 Sep;18(9):922-30. PMID: 8067513

 Dictor M, Elner A, Andersson T, Ferno M. Myofibromatosis-like hemangiopericytoma metastasizing as differentiated vascular smooth-muscle and myosarcoma. Myopericytes as a subset of "myofibroblasts". Am J Surg Pathol. 1992 Dec;16(12):1239-47. PMID: 1463097