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Fibrosarcoma
Authors

Donald D. Davis1; Steven M. Kane2.

Affiliations
1 Wellstar Atlanta Medical Center
2 Wellstar Atlanta Medical Center

Last Update: December 2, 2020.

Continuing Education Activity

Fibrosarcoma is defined as a neoplasm composed of fibroblasts with variable collagen production. This activity serves
to provide a high-level overview of the topic of fibrosarcomas to allow medical practitioners to better understand the
basic diagnosis and management. Furthermore, the activity serves to highlight the role of an interprofessional team
member's management of this neoplasm, to optimize patient care.

Objectives:

Identify the etiology of fibrosarcomas.

Describe the evaluation of fibrosarcomas.

Review the management options available for fibrosarcomas.

Earn continuing education credits (CME/CE) on this topic.

Introduction
Fibrosarcomas are defined as a malignant neoplasm composed of fibroblasts that may have varying amounts of
collagen production and a "herringbone" architecture. Adult fibrosarcomas have displayed a declining incidence over
the past several decades as the classification of fibrosarcoma continually narrows, and other mesenchymal and non-
mesenchymal tumors that mimic fibrosarcomas are more accurately diagnosed.[1][2] Fibrosarcomas can be sub-
divided into two types: infantile or congenital fibrosarcomas, or adult-type fibrosarcomas. Infantile fibrosarcomas
rarely metastasize, while adult-type fibrosarcomas are highly malignant.[3]

Etiology
Fibrosarcomas typically originate from fascia and tendons of soft tissue but can also occur in bones as a primary or
secondary tumor within the medullary canal or the periosteum. Prior bone damage, whether from trauma or
radiotherapy, may give rise to fibrosarcomas of the bone.[4][3]

Epidemiology
Adult fibrosarcoma is most common in middle-aged and older adults, and rarely occur in children. There is a slight
predominance in male patients, and most commonly involves the deep soft tissues of the extremities, trunk, head, and
neck.[5][2]

In a survey of adult fibrosarcomas, 80% were classified as "high-grade" (Grade 2 or 3), with 25% of the remaining
low-grade lesions progressing to a high-grade sarcoma locally over time.

Pathophysiology
Fibrosarcomas derive from a mesenchymal cell origin, composed of spindle-cell fibroblasts with uncontrolled
proliferation. Most frequently, fibrosarcomas originate from tendons and fascias of deep tissues, but may also occur
within the medullary canal or the periosteum of bones. Pre-existing bone lesions or irradiated tissues may also give
rise to secondary fibrosarcomas of the bone.[3]

Histopathology
Fibrosarcomas are a spindle cell type of soft tissue sarcoma, characterized by its fusiform oval nuclei, lance-shaped
tapered cells, and unipolar or bipolar cytoplasm. Adult fibrosarcomas show a mild to moderate degree of
pleomorphism. Neoplastic cells are arranged in long sweeping fascicles that form a classic "herringbone" pattern.
Note that a high degree of pleomorphism should classify any tumor as an undifferentiated pleomorphic sarcoma.
Fibrosarcomas display varying degrees of mitotic activity and have darkly staining nuclei with prominent nucleoli and
scant cytoplasm. There is a variable amount of stromal collagen present within fibrosarcomas and may mimic
fibromatosis in some tumors.

While histopathology is not sufficient to distinguish fibrosarcomas from other spindle-cell sarcomas, appropriate
immunohistochemistry can greatly assist in diagnosis by identifying characteristic tumor markers. Furthermore,
measurement of these markers on the cell surface or within the tumor environment is often critical in monitoring for
treatment efficacy and tumor recurrence.

Vimentin is a marker that is indicative of a mesenchymal cell origin and is often the only positively stained marker in
the diagnosis of fibrosarcomas. One might also find alpha smooth muscle actin, muscle-specific actin, and desmin to
be common myogenic markers, which often serve to represent myofibroblastic differentiation.

In contrast, a positive S-100 protein marker would be indicative of a nerve sheath tumor, while CD31, CD34,
and Factor VIII non-von Willebrand factor would suggest a vascular tumor rather than a true fibrosarcoma.[3][5][6]

History and Physical

Practitioners should inquire about the location, size, shape, and consistency of any soft tissue mass. Furthermore,
providers should inquire about any local scar tissue, especially as a consequence of prior burn injuries. Similarly, the
presence of prior vascular grafts, joint prosthetics, or other surgically implanted foreign materials should be noted.
Previously irradiated tissues may be a risk factor for the development of a fibrosarcoma as are pre-existing
dermatofibrosarcoma or well-differentiated liposarcoma.[3][7]

Additionally, the regional lymph node examination should be accompanied by a complete neurovascular examination.
Fibrosarcomas typically arise in deep connective tissue rich with collagen, and thus, it is less common in the
retroperitoneum, mediastinum, head, and neck. Fibrosarcomas generally are spherical with sharp demarcation from
surrounding tissue and have a firm consistency on palpation. Fibrosarcoma tumors typically range from 3-8 cm in
size.[3][8]

Fibrous tumors often have a very delayed diagnosis, as they arise from deep tissue and cause painless soft-tissue
swelling. It is often not until symptoms arise from the local mass effect of a deep tumor that the lesion is identified
and diagnosed. Impeded blood circulation, nerve compressions, or movement restriction is often present when
diagnosing a fibrosarcoma.[3]

Late presentations of fibrosarcomas may be accompanied by weight loss and anorexia. Furthermore, pain associated
with a deep soft tissue mass greater than 5 cm in size increases suspicion of malignancy, and warrants referral for
further specialist evaluation.[3]

Evaluation
Radiographic imaging is the first diagnostic step when history and physical examination suggests a diagnosis of a
malignant soft tissue tumor. Contrast-enhanced MRI is the preferred procedure to evaluate tumors of the extremities
or pelvis and will provide information pertaining to a tumor's size, margins, signal density, degree of necrosis, and
vascularization. CT Scans may also be employed to assess for tumors of the retroperitoneum or to identify any
possible bony involvement. Fibrosarcomas appear as localized, nonspecific ovoid lesions with slightly irregular
margins. One will see the displacement of surrounding tissue.[3]

If imaging suggests the presence of a soft tissue malignancy, a biopsy in the form of a core needle biopsy is
warranted, as a fine needle aspiration (FNA) has been criticized as being unsuitable for providing an accurate initial
diagnosis. FNA does, however, have utility in monitoring progression, as well as identifying tumor recurrence or
metastasis if previous cytological studies are available for comparison. Finally, in tumors where minimally invasive
biopsy techniques have failed or are untenable, more invasive surgical biopsies may be warranted. Excisional biopsy
is generally recommended when you suspect a soft tissue sarcoma of 3 to 5 cm in size, whereas partial incisional
biopsies are appropriate when tumor size exceeds 5 cm.[9][8][3]

Treatment / Management
Surgical excision is the mainstay of treatment for localized soft tissue sarcomas. Intramuscular tumors should have a
compartmental en-bloc excision, and in this scenario, no additional radiation therapy would be indicated. If there is
extracompartmental growth, or if the tumor does not reach the origin or insertion of the muscle, a wide-surgical
resection would be appropriate, with the goal of obtaining tumor-free margins. Two centimeters of margin is generally
recommended; however, there is a paucity of definitive evidence for the best safety margin. Surrounding structures
such as nerves and vascular structures must always be taken into account.

For tumors that are high grade and larger than 5 cm, adjuvant radiation therapy is highly recommended. If clear
margins are not obtained, reoperation is the most appropriate next step in management.

The utility of chemotherapy in the management of soft tissue sarcomas is unclear and, therefore, not generally
recommended in standard treatment. Additionally, fibrosarcomas tend to form a co-resistance to drugs such as
vincristine, vinblastine, and etoposide after the use of the first-line agent doxorubicin. Therefore, only patients with
high stage fibrosarcomas that require chemotherapy should be treated with anthracyclines as the first-line treatment.
The addition of actinomycin D and ifosfamide may increase the response to treatment. That being said, and
improvement of survival has only been demonstrated in 4-11% of sarcoma patients treated with standard
chemotherapy.

Finally, intra-tumoral injections of matrix metalloproteinase inhibitors such as TIMP-1-GPI fusion protein has been
shown to lead to a decreased tumor mass and growth. Furthermore, injection shows inhibition of cell migration as
well as increased tumor cell apoptosis.[3][10]

Differential Diagnosis
By definition, a diagnosis for fibrosarcoma is a diagnosis of exclusion. Low-grade fibromyxoid sarcomas, sclerosing
epithelioid fibrosarcomas, fibrosarcomatous dermatofibrosarcoma protuberans, and synovial sarcomas are all
clinically distinct diagnoses that may be mistaken for a true adult fibrosarcoma.

While storiform areas may be present on histology in association with adult fibrosarcomas, storiform growth suggests
the tumor arose from dermatofibrosarcoma protuberans. Furthermore, CD34 positive tumors likely represent
fibrosarcomas arising from dermatofibrosarcoma protuberans or a fibrosarcoma progression from a single malignant
fibrous tumor.

It is unlikely to find a fibrosarcoma within visceral organs, and these tumors likely represent cytokeratin-negative
carcinomas. In the retroperitoneum, initially reported fibrosarcoma-like lesions frequently prove to be dedifferentiated
liposarcomas.[5][2]

Prognosis
As discussed above, 80% of adult fibrosarcomas were determined to be high-grade (Grades 2 or 3). Furthermore, 25%
of the remaining low-grade lesions progressed to a local recurrence of high-grade sarcoma. These tumors were
aggressive with many local recurrences as well as lymph and parenchymal metastases. The survival of adult
fibrosarcomas is < 70% at two years, and < 55% at five years.[5][11][12]

Complications
As the mainstay of treatment for fibrosarcoma is surgical, complications are the same as any other surgery and include
infection, bleeding, damage to surrounding tissues or structures, and even death. Adjuvant radiation therapy can
further increase potential complications such as local fibrosis or increased risk of wound infection. In cases of high
stage fibrosarcomas, chemotherapy may be used. Each chemotherapy agent carries its own risk profile, but
doxorubicin, which is the mainstay of treatment, is classically associated with an increased risk of dilated
cardiomyopathy.

Deterrence and Patient Education

Fibrosarcoma has a poor prognosis due to its aggressive disease course. To maximize outcomes, patients must seek
medical treatment from trained specialists with an understanding of musculoskeletal tumors.

Optimal outcomes are seen when there is complete surgical tumor resection with histologically tumor-free margins,
appropriate adjuvant treatment to surgical intervention to maximize treatment benefit, and minimize recurrence. There
is the prevention of tumor invasion and metastasis. All patients should undergo routine medical screenings and should
inquire with their primary care physician regarding any soft tissue masses they may have noticed on self-examination.
[3]

Enhancing Healthcare Team Outcomes

The appropriate management of sarcomas, such as fibrosarcoma, is dependent on an interprofessional team of primary
care physicians and specialists. As surgical excision is the mainstay of treatment for fibrosarcomas, a surgical team
with experience in musculoskeletal oncology is important to optimize patient outcomes while minimizing risks and
complications of surgery. A pathologist is required to assist in forming an accurate diagnosis of any sarcomatous
lesion and help guide appropriate treatment. But most importantly, nurses and other medical staff must work in
conjunction with the patient to ensure a patient-centered approach to care that meets all physical, psychological, and
emotional needs of the patient. [Level 5]

Continuing Education / Review Questions

Access free multiple choice questions on this topic.

Earn continuing education credits (CME/CE) on this topic.

Comment on this article.

References
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