Fibrosarcoma



Fibrosarcoma







Key Points



  • Fibrosarcoma (FS) is a highly malignant tumor of fibrous tissue


  • These tumors predominantly arise from tendons and fascia of deep soft tissues, most often in the extremities, trunk, head, and neck


  • The infantile type is classified as a tumor of intermediate malignancy that rarely metastasizes


  • The adults type is a very malignant tumor with a high metastatic potential


  • The etiology has not been identified, but genetic mutations and predisposing factors, such as scar tissues, former burns, foreign material, and radiotherapy, may be influential


  • It usually presents as a painless, firm, spherical, sharply demarcated mass


  • Treatment is with wide surgical resection, and for larger deep tumors radiation therapy after surgical resection


  • The prognosis is poor with an overall 5-year survival rate of 40% to 60%, and the 10-year survival rate is 60% for low-grade and 30% for high-grade tumors, respectively


Fibrosarcoma (FS) is a highly malignant tumor of fibrous tissue. These tumors predominantly arise from tendons and fascia of deep soft tissues and most often involve soft tissues of the extremities, trunk, head, and neck. There have been reports of FS in visceral organs and retroperitoneum, but these have been questioned and it has been suggested that they represent other malignant lesions.1 FS can occur inside bones as a primary tumor, and the periosteum also can be a site of origin.2 Areas of preexisting bone injury or radiotherapy may give rise to secondary FS tumors.3

Two types of FS have been distinguished, an infantile/congenital type (IFS), and an adult type. FS in adults is classified as a highly malignant tumor with high metastatic potential. While this was previously believed to be the most common malignant soft-tissue sarcoma in adults,1 more recent data show that FS accounts for only 3.6% of all adult sarcomas.4 Adult FSs mainly arise in middle-aged and older individuals between the ages of 25 and 80 years, with a median of 50 years,1 and may be slightly more common in males.5

Several clinically, morphologically, and genetically distinct subtypes of adult FS have been recognized.1 Low-grade fibromyxoid sarcoma occurs most often in young adults but can affect children in about 20% of cases.6,7,8,9 It most commonly involves the deep soft tissues of the extremities and has a low risk of metastasis of approximately 15%. Sclerosing epithelioid FS has been considered to represent a distinct variant of FS, but some data suggest a link between this variant and low-grade fibromyxoid sarcoma.10,11,12,13 It may exhibit aggressive behavior, metastatic spread, and a mortality rate of 25% to 57%.12

The infantile type of FS is classified by the World Health Organization as a tumor of intermediate malignancy that rarely metastasizes. It represents about 5% to 10% of all sarcomas in infants younger than 1 year.14,15,16,17,18,19 The incidence in the United States is estimated to be five new cases per million infants. Infantile fibrosarcoma (IFS) is similar to adult FS histologically, but these two tumors differ in that ETV6-NTRK3 gene fusion expression is present in IFS but absent in adult FS.20

FS can develop in the eyelid and orbit either as a primary lesion or as a secondary malignancy in children with retinoblastoma, with or without a history of radiotherapy.21


Etiology and Pathogenesis

A definitive etiology for FS has not been identified, but some genetic mutations and other predisposing factors, such as scar tissues, former burns, foreign material, and radiotherapy, may be influential.22,23,24 Adult FS has been reported to show multiple nonspecific numerical and structural chromosomal abnormalities, including complex karyotypes, unbalanced translocations, deletions, and inversion.25,26 However, there do not appear to be any characteristic chromosomal changes.

IFS is associated with the characteristic t(12;15) (p13;q26) translocation encoding a novel fusion protein (ETV6-NTRK3) containing the protein-protein interaction domain of ETV6 and the tyrosine kinase domain of NTRK3. This results in an active fusion oncoprotein that is capable of transforming cultured fibroblasts.20 This translocation does not occur in adult-type FS. Trisomy of chromosomes 8, 11, 17, and 20 are also frequent findings in IFS.27


Clinical Presentation

FS mainly arises in regions of deep connective tissue rich in collagen. The adult type is seen predominantly in the lower extremities, particularly around the thighs, knees, arms, and trunk.28 Occurrence in the head or neck is less common. The tumor usually presents as a painless, firm, spherical, sharply demarcated mass (Figures 131.1 and 131.2).29 Deep-seated
lesions become symptomatic when surrounding tissues are compressed.