Fibrosarcoma: Symptoms, Diagnosis, and Treatment of Soft Tissue Sarcoma — Overview, Diagnosis & Treatment Options | MyMedicPlus

Fibrosarcoma is a malignant mesenchymal tumor of fibroblastic differentiation, subdivided into adult-type (rare, high-grade, affects adults aged 30-70) and infantile or congenital fibrosarcoma (affects children under 2 years, ETV6-NTRK3 fusion-positive, much better prognosis). Adult fibrosarcoma represents less than 1% of all soft tissue sarcomas. Common sites include the thigh, knee area, and trunk. Prompt diagnosis and treatment at a sarcoma specialist center are essential.

Adult fibrosarcoma risk factors include prior therapeutic radiation (post-irradiation fibrosarcoma arising 5-30 years after radiotherapy), Paget's disease of bone, chronic lymphedema (Stewart-Treves syndrome), Li-Fraumeni syndrome (TP53 germline mutation), and neurofibromatosis type 1. Industrial carcinogens (vinyl chloride, asbestos, phenoxyacetic acid, chlorophenol) have been implicated in some cases. Infantile fibrosarcoma arises from chromosomal translocation t(12;15) creating the ETV6-NTRK3 fusion, without established environmental risk factors.

Fibrosarcoma typically presents as a progressively enlarging painless or mildly painful soft tissue mass, most commonly in the deep soft tissues of the thigh, knee, or upper extremity. Skin changes overlying the tumor (erythema, dilated veins) occur with very large tumors. Restricted joint motion occurs if the tumor is adjacent to a joint. Infantile fibrosarcoma often presents at birth or within the first 2 years of life as a large, rapidly growing extremity mass that may ulcerate the overlying skin.

MRI with contrast is the preferred imaging modality for assessing local tumor extent, relationship to neurovascular structures, and compartment involvement. CT of the chest evaluates for pulmonary metastases (the most common distant metastatic site). Core needle biopsy in the resection plane is performed for histological confirmation. Immunohistochemistry panels and molecular testing (FISH for ETV6-NTRK3, NTRK expression) are required. Staging follows AJCC soft tissue sarcoma TNM criteria incorporating tumor size, depth, grade, and metastasis status.

Wide surgical excision with microscopically negative margins (R0) is the primary treatment. Limb-sparing surgery combined with perioperative radiation (external beam or brachytherapy) is preferred to amputation for extremity tumors. Adjuvant chemotherapy with doxorubicin and ifosfamide is used for high-grade, large (greater than 5 cm), or margin-positive tumors. Metastatic disease: doxorubicin plus ifosfamide first-line; trabectedin, gemcitabine-docetaxel, pazopanib for subsequent lines. ETV6-NTRK3-positive infantile fibrosarcoma: larotrectinib or entrectinib achieves greater than 75% response rate.

Adult fibrosarcoma 5-year overall survival is approximately 40-60%, with outcomes strongly influenced by tumor grade (French FNCLCC grading system) and resection margin status. High-grade tumors metastasize to lung in approximately 50% of cases, usually within 2 years of diagnosis. Infantile fibrosarcoma has an excellent prognosis with 5-year OS exceeding 80% with surgery alone or with TRK inhibitor therapy, despite a high-grade histological appearance. Local recurrence occurs in 20-40% of patients after wide excision.

No established general prevention strategy exists for sporadic fibrosarcoma. Minimizing radiation dose and field when treating other cancers reduces post-irradiation sarcoma risk. Patients with Li-Fraumeni syndrome (TP53 germline mutation) should undergo annual whole-body MRI surveillance (Toronto and NCCN protocols). Individuals with NF1 should have regular soft tissue assessments for sarcoma development. Genetic counseling should be offered to patients diagnosed with fibrosarcoma at a young age or with relevant family history.