—  SPECIALTY CONFERENCE  —

BONE AND SOFT TISSUE PATHOLOGY

Case 2 - Infantile fibrosarcoma (IFS)

Cheryl M. Coffin
Primary Children's Medical Center
Salt Lake City, Utah


Click on each slide thumbnail image for an enlarged view
Clinical History:
A two-day-old boy underwent resection of a congenital tumor from the left thigh. The tumor was 4.5 cm in diameter, and the overlying skin was erythematous.

Discussion/Differential Diagnosis:
Infantile fibrosarcoma is histologically identical to classic adult fibrosarcoma but has an entirely different clinical course. IFS occurs in infants and young children, seldom metastasizes, and shares a natural history similar to the fibromatoses. Synonyms include congenital fibrosarcoma,7  congenital-infantile fibrosarcoma,13  juvenile fibrosarcoma,47  and other less commonly encountered terms 2.

36 to 80% of cases are congenital, and nearly all cases occur in the first year of life.11, 13, 22, 37, 44, 47  IFS is seldom encountered after two years of age 13, and in that context, would require supporting cytogenetic data.

The solitary enlarging non-tender mass or swelling grows rapidly in soft tissues and may reach a diameter in excess of 30 cm.11, 13, 19, 47  The tumor is often grotesquely large in proportion to the size of the infant. The overlying skin is tense, erythematous, and may become ulcerated. IFS affects the superficial and deep soft tissues of the extremities, especially distally. The trunk and head and neck are other major sites, and rare cases occur in the mesentery and retroperitoneum.

Macroscopically, IFS is a poorly circumscribed lobulated mass that infiltrates adjacent tissues. Compression of adjacent tissue simulates a pseudocapsule, but the actual margins are irregular. The cut surface is soft and firm, fleshy and grey to tan with variable areas of myxoid change, cystic degeneration, hemorrhage, and necrosis.6, 11, 14, 35, 46, 47 


Case 2 - Figure 1 - IFS displays a cellular spindled proliferation with focal necrosis and dilated blood vessels.
Case 2 - Figure 2 - IFS forms interlacing fascicles of spindle cells with a sparse mononuclear infiltrate.
Case 2 - Figure 3 - IFS consists of primitive, mitotically active spindle cells.

Morphologically, the densely cellular neoplasm is composed of intersecting fascicles of primitive ovoid and spindle cells with a herringbone pattern or forming interlacing cords, sinuous bands, or sheets of cells. Zonal necrosis and hemorrhage are frequent and may be associated with dystrophic calcification. The tumor cells show little pleomorphism, and giant cells are seldom found. Collagen formation is variable, and mitotic activity is prominent. Most IFS contains scattered chronic inflammatory cells and may display focal extramedullary hematopoiesis. Histologic variations include a focally prominent hemangiopericytoma-like pattern of irregular, cavernous, or clefted blood vessels, dilated blood vessels with fibrin thrombi, myxoid foci, or a predominant round or ovoid primitive cellular proliferation with minimal collagen. Entrapped adipose tissue, skeletal muscle, and other structures are identified as a result of infiltrative growth. Composite tumors with overlapping features of infantile myofibromatosis, infantile hemangiopericytoma, and infantile fibrosarcoma are occasionally encountered.48 

The immunohistochemical features are heterogeneous, although vimentin immunoreactivity is found in virtually 100%.13, 26, 42, 48, 49  Neuron-specific enolase, alpha smooth muscle actin, HHF35 actin, muscle specific actin, desmin, and other markers are variable. While TRKC or NTRK3 immunoreactivity with cytoplasmic paranuclear staining is detectable in nearly all IFS, the nonspecific staining is observed in many other fibroblastic-myofibroblastic lesions.16, 42  Apoptosis and cell proliferation are distinctive.24  Ultrastructurally, the tumor displays characteristics of fibroblasts and myofibroblasts with a variable histiocytic-macrophagic component.5, 17, 26 

Cytogenetic abnormalities in IFS are well defined. Numerical abnormalities of chromosomes 8, 11, 17, and 20 detectable by conventional cytogenetics and FISH.30, 39, 40  Many infantile fibrosarcomas harbor a chromosomal translocation involving 12p and 15q, which results in oncogenic activation of the NTRK3 receptor tyrosine kinase gene.1, 4, 9, 25, 33  A genetic profile similar to that of IFS is also seen in mixed histology and cellular congenital mesoblastic nephroma, and the pathogenesis of these two tumors is likely closely related.3, 8, 25, 36, 38, 41  Like IFS, rare examples of congenital mesoblastic nephroma pursue an aggressive clinical course and may metastasize.20, 21, 23 

IFS has a favorable outcome when compared with adult fibrosarcoma. The mortality ranges from 4 to 25% and the recurrence rate is 5 to 50%.11, 13, 22, 37, 44, 47  Metastases are extremely rare, especially in more recently reports. Hemorrhage and involvement of vital structures by locally aggressive tumors may cause death. Spontaneous regression and nonrecurrence of incompletely excised IFS have been reported.15, 29, 32, 45, 49  Although surgery is the treatment of choice, low-dose chemotherapy is effective.10, 12, 18, 27, 28, 31, 34, 43 

The differential diagnosis includes other spindle cell tumors such as fibromatoses, infantile myofibromatosis, infantile hemangiopericytoma, other types of fibrosarcoma, synovial sarcoma, spindle cell rhabdomyosarcoma, smooth muscle tumors, and fibrohistiocytic tumors.

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